tbuckley/cabot-search huggingface dataset:
Mammary Gland Transplantation and Tumorigenesis. I. Concentration and Clearance of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene in the Graft&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Thomas L. Dao, Charles L. King, Daniel Gawlak
Journal: JNCI Journal of the National Cancer Institute (1968)

The pattern of clearance of 7,12-dimcthylbenz[a]anthracene from the grafted mammary gland appeared similar to that from the mammary gland in situ in the first 3 days, but thereafter the graft seemed to trap the carcinogenic hydrocarbon for as long as 30 days after transplantation, whereas the mammary gland in situ contained no measurable amount of carcinogen after 7 days. Although clearance of the hydrocarbon from the graft into the recipient hosts appeared inevitable, it did not seem to enter the hosts' own mammary glands, since it was below detectable amounts in them. In all our experiments, no mammary tumor has ever been found in the hosts' own mammary glands. The data suggest that high concentration of 7,12-dimethylbenz[a]anthracene in the mammary gland is detrimental to survival of the graft. Mammary graft survival was lowest in groups in which transplantations were carried out 4 hours after intravenous injection or 24 hours after oral feeding of the carcinogen. The hydrocarbon concentration in the mammary gland was at the peak levels in these 2 groups. The graft survival was greatly improved when transplantation was delayed until 5 or 10 days after the administration of the carcinogen. The tumor incidence in the surviving grafts, however, apparently was highest in groups bearing grafts containing highest concentration of the carcinogenic hydrocarbon. The tumor incidence declined as the time between carcinogen administration and grafting lengthened. It was lowest in groups in which transplantation was done 10 days after an intravenous injection of the carcinogen in the donor rats. The significance of these observations is discussed.
Multicenter phase II study of sequential chemotherapy, radiotherapy, and immunotherapy in locally advanced pancreatic (Pa) and biliary tree (Bt) adenocarcinoma (ADK)
Authors: F. Recchia, G. Sica, G. Candeloro, R. Bisegna, S. Necozione, P. Bonfili, V. Tombolini, S. Rea
Journal: Journal of Clinical Oncology (2009)

3047 Background: The aim of this study was to evaluate the activity and toxicity of a multistep, sequential treatment including induction chemotherapy (ICT), consolidation chemoradiotherapy (CXRT), and maintenance immunotherapy (MI) in untreated patients with locally advanced (LA), inoperable, or incompletely resected Pa and Bt ADK. MI with low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) was given in order to enhance the immune function, which could eradicate minimal residual disease, as previously shown (Clin Cancer Res 2001). Methods: From September 2003 to September 2007, 54 patients, 32 men, 22 women, 63% with Pa and 37% with Bt ADK, mean age of 63 years (range 36–75), were treated with an ICT consisting of 3 courses of cisplatin, 70 mg/m 2 day 1, gemcitabine 1000 mg/m 2 day 1 and 8 every 3 weeks. Patients who were progression-free (PF) after ICT received CXRT, 45 Gy in 25 fractions, using coplanar four-field technique, with concurrent capecitabine 850 mg/m 2 /day. Six weeks after completion of CXRT, patients were restaged: In the absence of disease progression, they received, as an MI, IL-2, 1.8 x 10 6 I.U. and RA, 5 mg/kg, 5 days/week, 3 weeks/month for 1 year and thereafter until progression. Results: After a median follow-up of 27.5 months, all patients were evaluable. A response rate of 26% (95% c.i. 15–40%), was observed, with 44.5% of patients achieving stable disease. Thirty-eight patients, 27 with Pa and 11 with Bt ADK, had a clinical benefit from ICT, and were treated with CXRT. Fourteen PF patients, 7 Pa and 7 Bt ADK, received an MI with IL-2 and RA. Median progression-free survival (PFS) and overall survival (OS) for all 54 patients were 6.8 and 12.1 months, respectively, while the 14 patients treated with MI had a 5-year PFS and OS rate of 36% and 58%, respectively. Grade 3–4 hematological and gastrointestinal toxicity were observed in 30% and 37% of patients, respectively, while 28% of patients had grade 1–2 autoimmune reactions. Conclusions: These results support the efficacy and safety of a multistep sequential treatment with ICT, followed by CXRT, and an MI with IL-2 and RA, in patients with LA, inoperable or incompletely resected Pa and Bt ADK. Further studies are necessary to validate this strategy. No significant financial relationships to disclose.
MMP-7 serum levels as predictor or prognostic of cetuximab benefit in the treatment of advanced colorectal cancer: Results from a HCB-05 prospective trial.
Authors: G. Carrera, X. Garcia-Albeniz, V. Alonso-Espinaco, C. Pericay, V. Alonso, M. P. Escudero, C. Fernandez-Martos, R. Gallego, S. Castellvi-Bel, J. Maurel
Journal: Journal of Clinical Oncology (2010)

10639 Background: To prospectively explore the role of serum MMP-7 as a predictive and prognostic marker of anti-EGFR therapy and irinotecan efficacy in third-line advanced colorectal cancer therapy. Methods: One hundred patients were recruited in a prospective serum biomarker study from six Spanish hospitals. Patients were treated with biweekly irinotecan 180 mg/m2 and cetuximab 400 mg/m2 (loading dose) and weekly cetuximab 250 mg/m2 until progressive disease or unacceptable toxicity. Baseline MMP-7 was determined using a quantitative solid phase sandwich ELISA. KRAS and BRAF mutational status were also assessed. The clinical endpoints examined were overall survival (OS), progression-free survival (PFS) and response rate (RR). Multivate analysis were adjusted by age, performance status, LDH and BRAF Results: No association between serum MMP-7 and KRAS or BRAF mutational status was found. Seventy-four patients had tissue available to do the KRAS and BRAF determination. Twenty-four patients (32%) were KRAS mutant. Six patients (8%) were BRAF mutant. The multivariate analysis revealed that MMP-7 (continuous variable) had an independent prognostic role in WT KRAS patients when assessing either OS (HR 1.03, 95%CI 1.003-1.06; p=0.029) or PFS (HR 1.03, 95% CI 1-1.055; p=0.046). Mutant BRAF predicts both OS (HR 3.55, 95% CI 1.39-9.09; p=0.008) and PFS (HR 8.49, 95% CI 2.88-25.07) in KRAS WT patients in the multivariate analysis. Conclusions: Serum MMP-7 is associated with OS and PFS in WT KRAS colorectal patients treated with anti-EGFR therapy as third-line treatment after adjusting by BRAF status. No significant financial relationships to disclose.
Histochemical Studies on Distribution of Dephosphorylating and Oxidative Enzymes and Esterases in Olfactory Bulb of the Squirrel Monkey2
Authors: T. R. Shantha Veerappa, G. H. Bourne
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Histochemical Studies on Distribution of Dephosphorylating and Oxidative Enzymes and Esterases in Olfactory Bulb of the Squirrel Monkey Get access T. R. Shantha Veerappa, T. R. Shantha Veerappa Department of Anatomy, Yerkes Regional Primate Research Center, and Laboratory for Ophthalmic Research, Emory University, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar G. H. Bourne G. H. Bourne Department of Anatomy, Yerkes Regional Primate Research Center, and Laboratory for Ophthalmic Research, Emory University, Atlanta, Georgia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 153–165, https://doi.org/10.1093/jnci/35.1.153 Published: 01 July 1965 Article history Received: 12 January 1965 Published: 01 July 1965
Abstract 19118: Coronary Artery Dissection After Blunt Chest Trauma
Authors: Chee Yuan Ng, David Choe, Hammad Khan
Journal: Circulation (2013)

Coronary artery dissection is a rare complication of blunt chest trauma. We present an unusual case of coronary artery dissection and our approach to treatment. A 28 year-old previously healthy male presented initially to Urgent Care with chest pain for 5 days after being hit on the chest with a soccer ball. Electrocardiogram (ECG) was unremarkable and he was sent home but he returned 5 days later with worsening intermittent chest pain. Physical examination was normal. ECG showed ST elevation in leads V2-V5. Prompt coronary angiography showed a dissected and heavily thrombotic proximal to mid left anterior descending artery (LAD). AngioJet thrombectomy was performed followed by placement of three drug eluting stents: 4 x 28 mm, 4 x 16 mm and 4 x 38 mm. Transient no reflow happened which was treated via intracoronary adenosine. The final angiographic result was satisfactory but the very distal LAD remained occluded though with resolution of symptoms and ECG changes. The distal LAD recanalized on a follow up angiogram done for recurrent chest pain. The patient was placed on bivalirudin periprocedure and eptifibatide for 24 hours and was loaded with prasugrel. Troponin T peaked at 1.63 ng/mL. Echocardiogram showed ejection fraction of 35% with anteroapical hypokinesis with preserved thickness. The patient was discharged home after 3 days. Trauma-related myocardial infarction can be caused by coronary artery dissection and compression due to epicardial hematoma. We present a case of coronary artery dissection that could be easily missed in a young individual and should be suspected early on so that prompt intervention could be performed.
Views from the regions
Journal: BMJ (1976)

Questionnaires were sent to all AIDS Training and Information Centers (ATICs) to learn how regional HIV/AIDS workers feel about the AIDS programs progress and problems.  Seven ATICs responded.  Their feedback is summarized and presented on the relationship between the regions and the central program whether the workers are truly free to run the centers how the budget is controlled and what is being done with funds allocated to given regions who developed the short-term plans and where they are expected to lead whether the short-term plans are appropriate for the region what are the major problems in the region whether and from where adequate support is received the power of centrally-made decisions the most frustrating situations faced and respondents positions on the Sarafina II issue.
Measles virus nucleocapsid protein increases osteoblast differentiation in Paget’s disease
Authors: Jumpei Teramachi, Yuki Nagata, Khalid Mohammad, Yuji Inagaki, Yasuhisa Ohata, Theresa Guise, Laëtitia Michou, Jacques P. Brown, Jolene J. Windle, Noriyoshi Kurihara, G. David Roodman
Journal: Journal of Clinical Investigation (2016)

Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption and formation; therefore, PD offers key insights into mechanisms that couple bone resorption and formation. Here, we evaluated OCLs from 3 patients with PD and determined that measles virus nucleocapsid protein (MVNP) was expressed in 70% of these OCLs. Moreover, transgenic mice with OCL-specific expression of MVNP (MVNP mice) developed PD-like bone lesions that required MVNP-dependent induction of high IL-6 expression levels in OCLs. In contrast, mice harboring a knockin of p62P394L (p62-KI mice), which is the most frequent PD-associated mutation, exhibited increased bone resorption, but not formation. Evaluation of OCLs from MVNP, p62-KI, and WT mice revealed increased IGF1 expression in MVNP-expressing OCLs that resulted from the high IL-6 expression levels in these cells. IL-6, in turn, increased the expression of coupling factors, specifically ephrinB2 on OCLs and EphB4 on osteoblasts (OBs). IGF1 enhanced ephrinB2 expression on OCLs and OB differentiation. Importantly, ephrinB2 and IGF1 levels were increased in MVNP-expressing OCLs from patients with PD and MVNP-transduced human OCLs compared with levels detected in controls. Further, anti-IGF1 or anti-IGF1R blocked Runx2 and osteocalcin upregulation in OBs cocultured with MVNP-expressing OCLs. These results suggest that in PD, MVNP upregulates IL-6 and IGF1 in OCLs to increase ephrinB2-EphB4 coupling and bone formation.
A Phase I Study Of Nilotinib As a c-Kit Inhibitor Combined With Re-Induction Chemotherapy For Relapsed and Refractory c-Kit Positive Acute Myeloid Leukemia
Authors: Joseph M. Brandwein, David Hedley, Sue Chow, Karen Yee, Andre C Schuh, Vikas Gupta, Aaron Schimmer, Mark D. Minden
Journal: Blood (2013)
Phase I trial of temsirolimus (TEM) plus sorafenib (SOR) in advanced hepatocellular carcinoma (HCC) with pharmacokinetic (PK) and biomarker correlates.
Authors: Robin Katie Kelley, Halla Sayed Nimeiri, Pamela N. Munster, Mary Frances Mulcahy, Maxwell Thomas Vergo, Amanda DeSon, Christi Murphy, Benjamin M. Yeh, Andrew H. Ko, Wolfgang Michael Korn, Jimmy Hwang, Madelyn Luttgen, Peter Kuhn, Yong Huang, Al Bowen Benson, Alan Paul Venook
Journal: Journal of Clinical Oncology (2012)

4102 Background: Mammalian target of rapamycin inhibitors added to SOR augment antitumor effect in HCC models. We developed a phase 1 trial to determine maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of TEM plus SOR in HCC patients (pts). The study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support from Pfizer, Inc., and conducted at 2 NCCN centers. Methods: Eligibility: ≥1 measurable site. No prior systemic therapy (Tx). ECOG ≤2, Child Pugh ≤7, bilirubin ≤2 mg/dL, platelets (PLT) ≥75,000/mcL. Design: 3+3 escalation. Dose-limiting toxicity (DLT) window 28 days. MTD expansion cohort of 9 pts for PK and biomarkers. Endpoints: 1°: MTD, RP2D. 2°: Safety, toxicity, PK for TEM. Exploratory: Tumor necrosis, alpha fetoprotein (AFP)-L3, des-γ-carboxyprothrombin, and circulating tumor cells (CTC) by slide-based assay. Results: 21 pts enrolled. Median age: 60 (47-77). Male/Female: 15/6. Etiology: HCV 9 (43%), HBV 4 (19%), HBV+HCV 2 (10%), ETOH 2 (10%), unknown 4 (19%). Toxicity: DL1: 1 DLT Grade (Gr) 3 PLT. All pts required reductions for adverse events (AE); de-escalated to DL-1 for intolerability. DL-1: 1 DLT Gr3 hand-foot syndrome (HFS). Most common related ≥Gr 3 AE: HypoPO4 (52%); PLT (24%); transaminitis (19%); diarrhea, fatigue, HFS (10% each). Possibly related serious AE (SAE): Gr4 tumor rupture, Gr4 urosepsis, Gr3 dental infection with Gr2 ANC, Gr2 pneumonia (1 pt, 5% each). Best response: Confirmed partial response (PR) 2/21 (10%), stable disease (SD) 11/21 (52%), progression 1/21 (5%), 7/21 (33%) not evaluable. Time on study: Range &lt;1 to 19+ months; median 3+ months for pts who completed ≥1 cycle (16/21). 16/21 (76%) had baseline elevated AFP ≥20; 8/16 (50%) had &gt;50% decline. CTC were detected in 5/5 of tested samples. Decreased tumor enhancement on Tx was seen. Conclusions: DL-1 is MTD and RP2D, lower than a prior trial in pts without HCC; tolerability may be impacted by cirrhosis. Encouraging durable radiographic and AFP responses occurred. [Table: see text]
Trabectedin (T) in metastatic Ewing's family tumors (EFT) patients (pts) progressing after standard chemotherapy
Authors: P. Dileo, F. Grosso, M. Casanova, J. Jimeno, S. Marsoni, R. Sanfilippo, M. Podda, S. Ferrari, R. Bertulli, P. G. Casali
Journal: Journal of Clinical Oncology (2007)

10040 Background: T is a formerly marine-derived agent which is active in human cancers, such as ovarian cancer and adult soft tissue sarcomas (STS). Efficacy of T in pts with unresectable/metastatic pretreated advanced STS was demonstrated in phase II settings. Leiomyosarcoma and liposarcoma were shown to be sensitive, with myxoid liposarcoma being exceedingly responsive. Data are lacking on “small round blue cell” sarcomas, including EFT. In 2000 a phase II study was launched by SENDO in a sarcoma population including EFT. At Istituto Nazionale Tumori, Milano, Italy, some EFT pts were treated after the completion of this study. We analyzed treatment efficacy in EFT pts treated within these two settings. Methods: Overall 15/29 of the pts were female, and age ranged from 15 to 55 years. Pts received T at a starting dose between 1,650 and 1,100 mcg/sqm every 3 weeks as 24-hour or 3-hour infusion. Each pt received at least 2 cycles of treatment, except in case of disease progression or unacceptable toxicity. Tumor response was assessed by RECIST criteria after the first 2 cycles and then every other cycle. Dose reductions were based on the worst toxicity (hematological or non-hematological) in the previous cycle. Results: As of December 2006, 20 pts were treated in the Phase II study, and 9 on a compassionate use basis. Two pts were still on therapy. A total of 79 treatment cycles (2–14 per pt) were administered. Three pts (10.3%) demonstrated a partial response, 3 had a minor response (10.3%), and 4 (13.7%) stable disease. PFS rate at 6 months was 25%. The most common all-causality AEs were acute reversible liver toxicity, fatigue, and myelosuppression. Following the introduction of steroid pre-medication, thrombocytopenia and fatigue were less frequent. Conclusions: In this cohort, T was overall well tolerated and showed antitumor activity in pts with advanced EFT. This calls for further evaluation of this compound, alone or in combination, in pts suffering from EFT. No significant financial relationships to disclose.
A Continuous In Vitro Source of Herpesvirus saimiri
Authors: H. K. Oie, D. V. Ablashi, G. R. Armstrong, G. R. Pearson, T. Orr, U. Heine
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article A Continuous In Vitro Source of Herpesvirus saimiri Get access H. K. Oie, H. K. Oie Search for other works by this author on: Oxford Academic PubMed Google Scholar D. V. Ablashi, D. V. Ablashi Search for other works by this author on: Oxford Academic PubMed Google Scholar G. R. Armstrong, G. R. Armstrong Search for other works by this author on: Oxford Academic PubMed Google Scholar G. R. Pearson, G. R. Pearson Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Orr, T. Orr Search for other works by this author on: Oxford Academic PubMed Google Scholar U. Heine U. Heine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 1077–1080, https://doi.org/10.1093/jnci/51.3.1077 Published: 01 September 1973 Article history Received: 22 May 1973 Accepted: 12 June 1973 Published: 01 September 1973
Estimation of additional MRI resources needed in British Columbia for screening high-risk women for breast cancer.
Authors: Rasika Rajapakshe, Christabelle Bitgood, Steven McAvoy, Cynthia Araujo, Paula Gordon, Andy Coldman
Journal: Journal of Clinical Oncology (2012)

51 Background: Screening women at high risk with MRI has been shown to detect breast cancer at an early stage. Therefore, MRI screening has been recommended in the UK and USA for women who are at a high risk of developing breast cancer. However, there is no information available in the province of British Columbia (BC) about the number of women who have a high risk of developing breast cancer. Therefore, we carried out a study to estimate the breast cancer risk distribution in three sample populations in BC using Tyrer-Cuzick (TC) risk prediction model so that additional resource requirement for MRI breast screening can be calculated. Methods: A survey questionnaire was designed based on the TC model, which includes family history, hormonal factors, and benign breast disease. Additional questions also include factors that are used in other models (Gail, Claus, and BCRAPRO) as well as factors that may be included in the future. Women were recruited by staff and volunteers at three screening mammography clinics: Kelowna, Victoria General Hospital, and BC Women’s Health Centre in Vancouver. The survey was available to women to complete on the web, by phone, or on paper. An online database was constructed to store and query the data. The 10-year risk of developing breast cancer for each woman was calculated using the Tyrer-Cuzick IBIS Risk Evaluator software and the risk distribution of the survey population was analyzed. Results: Data from 3,200 women recruited from three sites, gives a risk distribution showing 2.6% are at high risk of developing breast cancer, 31.2% are at moderate risk, and 66.2% are at low risk. Based on NICE guidelines (UK), high risk is defined as having a 10-year risk of greater than 8%, moderate risk as 3-8%, and low risk as less than 3%. Extrapolating this to the approximately 500,000 women who are eligible to attend for screening mammography in BC, 13,000 women are considered at high risk. Conclusions: Our results indicate that 2.6% of women ages 40-79 attending screening mammography in BC may have a very high risk of developing breast cancer based on personal and family history. Based on a 14-hour work day, three additional MRI scanners would be required to implement MRI screening for these high-risk women in BC.
A quantitative image analysis model of prostate biopsies for predicting clinical risk in men enrolled in an active surveillance program.
Authors: Faisal M Khan, Gerardo Fernandez, Richard Scott, Raymond S. Lance, Carlos Cordon-Cardo, Laurence Klotz, Michael J. Donovan
Journal: Journal of Clinical Oncology (2014)

111 Background: Quantitative image analysis of the prostate needle biopsy (PNB) has proven to be a robust and predictive platform for prostate cancer (PCa) prognosis. We sought to determine the performance of quantitative metrics in identifying which patients enrolled in an active surveillance (AS) program are most likely to present with significant clinical risk, including subsequent biopsy Gleason grade (GG) upgrading and/or a short (less than 24 month) prostate-specific antigen (PSA) doubling time (PSADT). Methods: One hundred sixty two AS patients (median age 70, 94% cT1-T2a, 85% &lt;=GS6, median PSA 5.9 ng/mL) with overall 8 year median follow up and available diagnostic PNB specimens were analyzed. Computerized image analysis derived quantitative biometric features representing PCa morphology and immunofluorescent (IF) biomarkers from the PNB. Multivariate models predicting either GG upgrading on a subsequent PNB or a PSADT less than 24 months were evaluated. The AUC/concordance index (CI), sensitivity, specificity and hazard ratio (HR) were used to assess performance. Results: Univariate distribution of selective features, notably expression levels of AR and Ki67, were reflective of a low risk cohort.A multivariate model with three quantitative imaging metrics was trained with a CI of 0.77. Men at high risk within 24 months of the PNB were identified with 80% sensitivity and 73% specificity, HR of 5.7. The most important feature measured the relative proportion of tumor epithelial nuclei that were both Androgen Receptor and alpha-methylacyl-CoA racemase positive. The other two features were morphological assessments of epithelial cellular area compared to luminal area. Of note, clinical features such as age, GG and PSA were not selected in competition with the imaging metrics. Conclusions: Quantitative image analysis of morphology and IF biomarker expression in the PNB outperformed standard clinical features in a multivariate model to accurately predict which AS patients are at risk for Gleason upgrading and/or a shortened PSADT. Identifying such patients may prove beneficial in the primary treatment decision process.
Reliability of such instruments needs to be proved
Authors: D. Ruta, A. Garratt
Journal: BMJ (1996)

EDITOR,—Charlotte Paterson should be commended for piloting her patient generated outcome measure in a primary care setting.1 The “measure yourself medical outcome profile” (MYMOP) has potential for routine use, not least because it is simple to use. Also, the authors' tests of validity and responsiveness indicate that it correlates with health status and perceived improvements in health. Three important questions remain unanswered, however. Firstly, does the MYMOP really measure outcomes that matter to patients—that is, that have meaning and …