tbuckley/cabot-search huggingface dataset:
Phase II study of sequential paclitaxel (P) and bryostatin-1 (Bryo) for patients with advanced pancreatic cancer (P 5624)
Authors: A. Kaubisch, V. Vinciguerra, H. Hochster, F. Camacho, Y.-H. H. Wu, S. Mani, S. Goel, S. Wadler
Journal: Journal of Clinical Oncology (2004)

4223 Background: Bryo, a macrocyclic lactone, modulates protein kinase C and enhances P's ability to induce apoptosis. Enhanced apoptosis induction is only seen when P precedes bryo (Koutcher, Clin Cancer Res. 6: 1498). In the phase I study of sequential P followed by bryo, activity in pancreas cancer was seen; myalgias were dose limiting (Kaubisch, Proc ASCO, 2000, Abstr. 900). Methods: Patients (pts) with pathologically confirmed, locally advanced or metastatic adenocarcinoma of the pancreas were eligible. Prior treatment was permitted, prior taxane exposure was not. P was given at 90 mg/m2 over 1 hour day 1, followed by bryo 25 mcg/m2 over 1 hour on day 2, weekly x 3, followed by one week rest (28 day cycles). CT's were performed every 2 cycles. Results: 20 pts (mean age 58, 21–82) received an average of 2.6 cycles (0–10, median 2). Five pts are not evaluable for response (2 early deaths: (fungal sepsis, liver abscess); one pt withdrew, one was never treated, one ineligible). One pt (6%) achieved a minor response. Five pts (28%) had stable disease lasting 6, 9, 3, 4, and 3+ months. The remaining 8 pts (44%) progressed. Criteria for enrollment of the second stage of the Simon's two- stage design were not met. Myalgias were common, most were grade 1–2; only 2 pts had grade 3 myalgias, one withdrew as a result. Hematologic side effects : leukopenia (Gr 3: 4), neutropenia (Gr 2: 2, Gr 4: 1, neutropenic fever: 1), anemia (Gr 2: 4, Gr 4: 2), thrombocytopenia (Gr 3: 1). Both bleeding (NSAID associated GI bleed, variceal bleed) and thrombosis (DVT's (2), portal vein thrombosis, fatal pulmonary embolus) were noted during the study. Other grade 3 toxicities included: dehydration with syncope, biliary stent infection, small bowel obstruction, hyperglycemia (2), and diarrhea. Grade 2 toxicities included: diarrhea (4), fatigue (2), anorexia, weight loss, constipation, dyspnea, alopecia. Conclusions: Bryo at 25 mcg/m2, in combination with paclitaxel caused moderate myalgias, and rare pts experienced prolonged stable disease. However, there was not sufficient activity to support further study in patients with pancreas cancer. Thrombotic events appeared to be rather frequent. No significant financial relationships to disclose.
Dermatofibrosarcoma protuberans: Neoadjuvant therapy with imatinib mesylate and use of plasma PDGF-B levels to monitor clinical response
Authors: M. Macapinlac, T. Elrafei, I. Cunningham, M. Horowitz, P. Fauzia, R. Mbaoma, D. Jayabalan, S. Mani
Journal: Journal of Clinical Oncology (2004)

9049 Background: Dermatofibrosarcoma protuberance (DFSP) is a rare soft tissue sarcoma; most cases show t(17:22) resulting in a COL1A1-PDGF-B fusion protein. It is believed that DFSP arises through dysregulated PDGF-B expression and autocrine PDGF-R stimulation. Imatinib mesylate, a known inhibitor of the PDGF receptor tyrosine kinase, has produced responses in some patients with chemotherapy-resistant locally advanced or metastatic DFSP. Wide surgical excision of the tumor is still the accepted treatment despite local recurrence rate of 20–50% in completely resected patients. The value of RT in the management is not clearly defined. We present a 39-year-old man with a 7 month history of gradually enlarging facial masses with biopsy consistent with DFSP. Head and neck CT showed a 14 × 15 × 14cm cheek mass, a chin mass of 4 × 5 × 4cm and 2 facial skin lesions below the lower lip measuring 1 cm. Chest and abdomen CT showed no metastasis and PET scan showed uptake in facial lesions only. Complete wide surgical excision was not possible. Preoperative Imatinib, 400 mg/d, was initiated and tolerated well. Methods: Weekly plasma PDGF-B levels was measured using ELISA Results: After 3 weeks, CT scan showed ∼50% reduction in the left cheek and chin tumors with near complete resolution of the facial skin lesions. PET scan showed markedly decreased uptake in both masses. Weekly measurements of plasma PDGF-B levels using ELISA decreased 4 fold over 3 weeks from 1050pg/ml, 690pg/ml to 270pg/ml correlating with clinical response, which has not been previously reported. Further studies are ongoing in this and other patients. Conclusions: This case shows the potential use of imatinib as neoadjuvant treatment in DFSP, and the potential value of measuring serial PDGF-B levels as a novel tumor marker not only in DFSP but perhaps in all tumors that depend on the PDGF-B pathway. No significant financial relationships to disclose.
Comparative effectiveness of screening, surgery, and chemoprevention among BRCA1/2 mutation carriers.
Authors: V. R. Grann, P. R. Patel, J. S. Jacobson, E. Warner, D. F. Heitjan, M. Ashby-Thompson, D. L. Hershman, A. I. Neugut
Journal: Journal of Clinical Oncology (2010)

6011 Background: Comparative effectiveness research has become an integral part of health care planning in most developed countries. Effectiveness is determined by cost and quality-adjusted life years of survival. We conducted a comparative effectiveness analysis of preventive interventions for BRCA1/2 mutation carriers. Methods: In a simulated cohort of women, aged 30-70 who tested positive for BRCA mutation and did not have cancer at baseline, we comparedmammography with and without MRI, prophylactic oophorectomy or mastectomy or both, and chemoprevention. Using Treeage 2009 software, we developedMarkov models, with 25,000 Monte Carlo simulations and probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence and mortality rates, and costs in 2009 dollars, on published studies and data from the SEER Program and the Centers for Medicare and Medicaid Services. For quality adjusted-life years (QALYs), we used preferences based on our recent surveys. Results: For BRCA1 mutation carriers, prophylactic oophorectomy at $1,741/QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic mastectomy, at $5,062/QALY, was more cost effective than both surgeries. Without quality adjustment, both surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost-effective than screening. Screening modalities had the highest preference ratings, but were very costly. Conclusions: In a hypothetical population of BRCA mutation carriers, prophylactic surgery dominated chemoprevention and screening primarily because of the high costs associated with imaging. In our model reducing those costs by > 50% made MRI cost effective, compared to bilateral mastectomy, among BRCA1 and BRCA2 mutation carriers. No significant financial relationships to disclose.
The gene coding for secreted phosphoprotein1/osteopontin is the most overexpressed gene in cholangiocarcinoma—detected by oligonucleotide arrays and LightCycler analysis
Authors: H. G. Hass, J. Jobst, O. Nehls, A. Frilling, J. T. Hartmann, S. Kaiser
Journal: Journal of Clinical Oncology (2006)

10036 Background: Cholangiocarcinomas (CCC) are the second most common primary hepatic malignancy with a still poor prognosis and arise from biliary epithelia or cholangiocytes. Until now, less is known about the molecular pathways leeding to CCC. Methods: Oligonucleotide arrays were used to analyze gene expression profiles of 8 intrahepatic CCCs. After isolation of tRNA and transcription into cDNA, biotin-labelled cRNA probes were hybridized to GeneArrays (Affymetrix U 133A) containing probes of more than 22.000 genes/ESTs. For two-dimensional cluster analysis we used special software programs (Genexplore, GeneSpring). Dysregulated genes were determined by presence in more than 70% and a 2-fold change in relation to the corresponding non-malignant liver tissue. Lightcycler analysis were performed to validate the expression datas of dysregulated genes. Results: A total of 694 dysregulated genes (330 up-/364 down-regulated, compared with corresponding non-malignant tissue) were detected. As the gene with the highest and most consistent upregulation we were able to identify osteopontin (OPN) with an average 5-fold overexpression in all CCC tissues. OPN is an acidic phosphoprotein that is secreted by osteoblasts, macrophages and many other cell types and binds to a variety of cell surface receptors (integrins/CD44). OPN is multifunctional, with activities in cell migration, regulation of bone metabolism, immune cell function and control of tumor cell phenotype. Elevated OPN levels were seen in different tumors but until now no data exist about the expression in CCCs. As one possible interaction in human carcinogenesis, OPN has recently been shown to be a novel substrate for some MMPs, which play an importand role in tumor invasion and metastasis. Conclusions: This is the first report about an overexpression of OPN in CCC and our data indicate an important role in cholangiocarcinogenesis. Further studies are needed to illucidate the moleculargenetic mechanisms of OPN interactions in CCC. No significant financial relationships to disclose.
Role of serum erythropoietin, erythropoietin-independent erythroid colony formation, and bone marrow assessment in the diagnosis of polycythemia vera in patients with JAK2 V617F mutation
Authors: J. M. MacKenzie-Feder, C. Eaves, K. Lambie, A. Abdi-Ali, K. M. Ramadan, S. Young, D. Horsman, P. Galbraith, A. Eaves, L. Foltz
Journal: Journal of Clinical Oncology (2009)

7085 Background: The discovery of the JAK2 V617F mutation in over 95% of polycythemia vera (PV) patients has led to the development of the new 2008 World Health Organization diagnostic criteria for PV. These specify a requirement for an elevated hemoglobin (Hb, males: &gt;185 g/L, females: &gt;165 g/L) and either evidence of JAK2-mutant cells plus any one of the following minor criteria: a below normal level of serum erythropoietin (Epo), detectable Epo-independent erythroid colony (EEC) formation in vitro, or panmyelosis in the bone marrow, or two of the latter in the absence of detectable JAK2-mutant cells. However, in patients with an elevated Hb and JAK2V617F positivity, there are few data to determine whether any of the 3 minor criteria actually add an independent contribution to the diagnosis of PV. Methods: We performed a retrospective chart review of 77 patients who had an elevated Hb and were positive for the JAK2 V617F mutation and who also had a test for at least one of the 3 minor criteria (serum Epo level: n = 53; EEC formation: n = 66; bone marrow examination: n = 16) to determine the frequency of cases who might lack one or more of these. Results: Although the number of patients with a complete set of data was limited, the results, nevertheless, were sufficient to show that all 3 minor criteria were highly represented and all 77 of the patients analyzed (100%) were positive for at least one of them; i.e., 47 of 53 tested (89%) had a reduced serum Epo level; 65 of 66 tested (98%) had EECs and 15 of 16 tested (94%) had evidence of bone marrow panmyelosis. Conclusions: Neither the Epo level, nor the presence of EECs nor evidence of bone marrow panmyelosis provided additional diagnostic specificity in a population of 77 patients with both JAK2 V617F-positive cells and an elevated Hb. Consideration should be given to limiting serum Epo, EEC, and bone marrow assessments to JAK2 mutant-negative patients. No significant financial relationships to disclose.
Breast cancer patients treated with intra-operative radiotherapy [IORT] alone when conventional external beam radiation therapy [EBRT] was not possible
Authors: M. Keshtgar, J. S. Tobias, J. S. Vaidya, N. Williams, C. Stacey, M. Metaxas, M. Douek, C. Brew-Graves, M. Baum
Journal: Journal of Clinical Oncology (2008)

11517 Background: IORT with Intrabeam has been used by us in the randomised TARGIT trial since 2000. Some patients are suitable for off-trial therapy, particularly where external beam radiotherapy cannot be offered due to the risk of side effects. Methods: Patients with invasive breast cancer underwent wide local excision followed by IORT (n=14) delivered using the Intrabeam system containing a miniature electron gun and accelerator. Low energy x-rays (50kV) are emitted from the point source, delivering 20Gy to the applicator surface located in the tumour bed. Patients who were deemed unfit for surgery (n=3) received interstitial radiotherapy alone using Intrabeam under local anaesthetic without any surgical intervention and were followed up with serial contrast enhanced MRI scans. Results: The median (IQR) age of these 17 patients at the time of IORT was 68 (56–78) years with a median (IQR) follow-up of 21 (13- 43) months (see Table). To date there have been no reports of local recurrence or radiation induced complications. One patient developed a second primary and subsequently died of brain metastases. All three patients who received interstitial radiotherapy showed evidence of near complete loss of tumour on MRI scan and one patient is still alive 8 years following the procedure. Conclusions: This cohort adds to the evidence that IORT using Intrabeam offers a safe and effective method of delivering radiotherapy to breast cancer patients in whom EBRT is not an option. NLR, no local recurrence * Patients who received interstitial radiotherapy without surgery Case Age Reasons for IORT alone Follow-up (months) Outcome 1 53 EBRT refused, long distance to travel 59 NLR 2 48 Recurrent breast cancer after WLE and EBRT, refused mastectomy 42 Second primary; Died of metastatic meningeal disease 3 60 Severe Bronchiactasis 46 NLR 4 78 Severe respiratory disease with poor lung functions 8 Died; NLR 5 54 Past history of lymphoma and Mantle radiotherapy, declined mastectomy 47 NLR 6 56 Myasthenia Gravis 43 NLR; Bone mets, internal mammary involvement 7 90 Co-morbidities 22 Died; Accident 8 68 Severe Parkinson’s disease 22 NLR 9 66 Blind 20 NLR 10 56 Morbid obesity and previous problems with EBRT for contralateral breast cancer 19 NLR 11 85 Co-morbidities 14 NLR 12 68 Hodgkin’s disease, previously treated with Mantle radiotherapy 21 NLR 13 40 Metastatic breast cancer 4 Died; NLR 14 77 Second primary, refused mastectomy 0 NLR 15* 73 Motor Neurone Disease 13 Died; motor neurone disease 16* 78 Cardiac problems 82 NLR 17* 85 Cardiac problems 12 Died; ischaemic heart disease Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Carl Zeiss Carl Zeiss
Therapeutic targeting of CD70 and CD27-CD70 interactions with the monoclonal antibody SGN-70 in Waldenstrom’s Macroglobulinemia (WM)
Authors: A. W. Ho, E. Hatjiharissi, A. Branagan, Z. Hunter, J. McEarchern, C. Law, I. S. Grewal, D. Santos, Y. Tai, S. P. Treon
Journal: Journal of Clinical Oncology (2006)

2509 Background: WM represents a lymphoplasmacytic lymphoma characterized by a monoclonal IgM gammopathy and possesses a mast cell component that may contribute to its pathogenesis. The tumor necrosis factor (TNF) receptor family member, CD27, is a transmembrane co-stimulatory molecule that is also secreted in a soluble form (sCD27). Recent evidence has suggested that interactions between CD27 and its TNF-like ligand, CD70, play a critical role in regulating B-cell activation and survival, and therefore, may provide a viable therapeutic target for the treatment of WM. Methods: Patients with the consensus panel diagnosis of WM who provided written consent were evaluated. ELISA assay kits were obtained from Bender MedSystems. Flow cytometric analysis, RT-PCR, and calcein ADCC assays were performed as previously described (Santos et al, in press). Results: By ELISA, WM patients displayed dramatically higher levels of sCD27 in their sera (median 7.45, range 0–19.42 U/ml) versus healthy donors (median 0, range 0–2.78 U/ml; p = 2.5 × 10 −7 ). CD27 was expressed in 7/7 patients using RT-PCR analysis, and on the tumor cell surface of 5/12 patients. CD70, the target for CD27, was widely expressed on tumor cells (6/6) and mast cells (10/11) using flow cytometric analysis. To define the functional role of sCD27 in WM, we cultured BCWM.1 (CD27 − CD70 + ) WM cells, LAD1 (CD27 − CD70 + ) mast cells, and primary tumor and mast cells (CD70 + ) isolated from WM patients with sCD27 (0.1–50 ug/mL), and observed no effect on their proliferation or induction of apoptosis. However, culture of LAD1 and primary WM mast cells (10/10) with sCD27 resulted in marked upregulation of two TNF family ligands which support the growth and survival of WM cells: CD40L (CD154) and a proliferation induction ligand (APRIL). Importantly, the anti-CD70 mAb SGN-70 (1 ug/ml) inhibited this upregulation by sCD27, establishing the specificity of the CD27-CD70 interaction. In addition, SGN-70 demonstrated significant ADCC against BCWM.1 WM cells at dose levels up to 20 ug/ml. Conclusions: Taken together, these studies suggest a novel functional role for sCD27 in the pathogenesis of WM, and demonstrate the feasibility of targeting CD70 and sCD27-CD70 interactions with the SGN-70 monoclonal antibody. [Table: see text]
Phthalates in cow milk: possible contamination pathways at farm level
Authors: Tine Fierens, Mirja Van Holderbeke, Hanny Willems, Isabelle Sioen, Stefaan De Henauw
Journal: Environmental Health Perspectives (2011)

Phthalates are organic lipophilic compounds which are mainly used as plasticizer in plastic polymers. Human exposure occurs mainly via food intake and can cause a wide range of negative health effects. Phthalates are not only present in food because of environmental contamination, but also as a result of migration from contact materials. This study investigated phthalates in cow milk in order to determine the contamination pathways at farm level.
The levels of eight phthalates were determined in raw milk samples collected during summer and winter at five farms located in ‘The Kempen’ (Belgium). Both manually obtained milk samples as milk samples milked by machine were collected. Analysis was performed by gas chromatography-mass spectrometry.
The analysis of the milk samples milked by machine revealed a difference in average total phthalate level between the summer and the winter sampling period (572 versus 379 µg/kg fat). While the total phthalate levels of the different farms during winter were nearly of similar magnitude (291-587 µg/kg fat), a wide range could be observed during summer (95-1550 µg/kg fat). Comparing milk samples within a farm, lower total phthalate levels were found in the milk samples milked by hand than those by machine (100 versus 179 µg/kg fat). Di(2-ethylhexyl) phthalate which is the most commonly used plasticizer worldwide, was the most dominating one (79 % of the total concentration in milk from the central collecting tank).
The results indicate that the contamination pathways for phthalates in cow milk vary across seasons. An explanation therefore is that the feed composition is different during summer than during winter. In summer, cows are grazing in the fields where an extra phthalate contamination can occur via soil ingestion. Comparing the milk samples milked by hand with those by machine reveals that the milking equipment is another important contamination pathway.
Analyzing the patterns of treatment failure.
Authors: J H Goldie, A J Coldman
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.6.825 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3711958 Analyzing the patterns of treatment failure. J H GoldiexJ H GoldieSearch for articles by this author , A J ColdmanxA J ColdmanSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.6.825 PDF "Analyzing the patterns of treatment failure.." Journal of Clinical Oncology, 4(6), pp. 825–826© 1986 by American Society of Clinical Oncology
Erythropoietin Induces the Tyrosine Phosphorylation of GAB1 and Its Association With SHC, SHP2, SHIP, and Phosphatidylinositol 3-Kinase
Authors: Carinne Lecoq-Lafon, Frédérique Verdier, Serge Fichelson, Stany Chrétien, Sylvie Gisselbrecht, Catherine Lacombe, Patrick Mayeux
Journal: Blood (1999)
Screening in the high-risk populations: Stage of breast cancer when detected by combination imaging with MRI and mammogram.
Authors: Kendall W. Carpenter, Mindy L. Merritt, Matthew Gromet, Karinn Marie Chambers, Terry Sarantou, Teresa Flippo, Julie Gottlieb Fisher, Richard L. White
Journal: Journal of Clinical Oncology (2013)

44 Background: Screening patients at high-risk for the development of breast cancer consists of MRI and mammography. This retrospective review of screening MRIs in patients designated as high-risk for the development of breast cancer--based on family history alone or a calculated lifetime risk of ≥ 20%--seeks to determine the utility of MRI screening in the detection of early-stage breast cancer. The primary outcome evaluated was stage of malignancy detected through screening imaging. Methods: Results of screening imaging performed between 1/1/08 and 12/31/11 were retrospectively reviewed. Patients who had a personal history of breast cancer were excluded. Remaining screens were categorized based on the following criteria: family history, BRCA mutation or high-risk as calculated by risk assessment tools. Screens with corresponding core biopsies were evaluated for the following: previous imaging obtained, core biopsy pathology and pathologic staging. Results: 118 patients met inclusion criteria and had a subsequent biopsy as a result of screening. Resultant pathology was 75 (64%; 75/118) benign lesions, 19 (16%; 19/118) atypical lesions, and 24 (20%; 24/118) malignant lesions. Of the 24 malignant lesions, 1 (4%; 1/24) were found to be node-positive at the time of surgical staging, and, 23 (96%; 23/24) were node-negative. Conclusions: Four percent (1/24) of patients undergoing high-risk screening had nodal disease at surgical staging, which compares favorably to historical rates of approximately 30% node-positive disease at diagnosis (Krag DN et al., NSABP B-32). Therefore, this study shows that screening high-risk patients can decrease the nodal-positivity rate.