tbuckley/cabot-search huggingface dataset:
Combinations of the immunocytokine F16-IL2 with doxorubicin or with paclitaxel investigated in phase Ib studies in patients with advanced solid tumors.
Authors: F. G. De Braud, C. Catania, C. Masini, M. Maur, S. Cascinu, R. Berardi, L. Giovannoni, G. Spitaleri, S. Boselli, D. Neri
Journal: Journal of Clinical Oncology (2010)

e13017 Background: F16-IL2 is a recombinant fusion protein composed of the antibody fragment scFv(F16) (specific to the alternatively spliced domain A1 of tenascin-C) and of human interleukin-2 (IL-2). Extensive preclinical studies have shown that F16- IL2 is capable of selectively and efficiently localizing in the tumor stroma in vivo. Furthermore, F16-IL2 strongly potentiates the therapeutic action of many anticancer agents. We have been performing two phase Ib studies to evaluate safety, tolerability, recommended dose (RD), and early signs of activity of F16-IL2 combined with either doxorubicin or paclitaxel. Methods: Cohorts of chemotherapy-pretreated patients with progressive solid tumors received weekly administrations of 6 escalating doses of doxorubicin (up to 25 mg/m2) or 8 escalating doses of paclitaxel (up to 90 mg/m2), combined with F16-IL2 (up to 25 million International Units of IL-2) for a maximum of 6 months. Results: 14 and 20 patients were treated in the doxorubicin and paclitaxel combination study, respectively. Phase Ib studies are planned to be completed by end of March 2010. Treatment was very well tolerated, no DLTs were observed. Toxicities were mainly G1 (fever, nausea, fatigue) and only few G2 toxicities were observed (anemia). Only one reversible G3 toxicity (hand-foot syndrome) was observed (paclitaxel trial). Pharmacokinetic (PK) analyses for both the immunocytokine and the drugs showed that the F16-IL2 blood concentration drops rapidly (half-life < 1 hour), while the immunocytokine was showed in preclinical studies to remain on the lesions for several days. Importantly, F16-IL2 PK profiles did not change significantly after multiple rounds of treatment. Objective responses and long-lasting disease stabilizations were observed, including 2 PR in heavily pretreated patients with advanced NSCLC and melanoma (paclitaxel trial). Conclusions: F16-IL2 combined with full dose of either doxorubicin (25 mg/m2) or paclitaxel (90 mg/m2), can be safely administered to chemotherapy-pretreated cancer patients. Early signs of activity in heavily pretreated patients warrant future developments in randomized phase II clinical trials. No significant financial relationships to disclose.
Modification of Irradiation Injury in Mice and Guinea Pigs by Bone Marrow Injections
Authors: Egon Lorenz, Delta Uphoff, T. R. Reid, Emma Shelton
Journal: JNCI Journal of the National Cancer Institute (1951)

Modification of Irradiation Injury in Mice and Guinea Pigs by Bone Marrow Injections Egon Lorenz, Egon Lorenz National Cancer Institute2Bethesda, Md., and The Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar Delta Uphoff, Delta Uphoff National Cancer Institute2Bethesda, Md., and The Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar T. R. Reid, T. R. Reid National Cancer Institute2Bethesda, Md., and The Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar Emma Shelton Emma Shelton National Cancer Institute2Bethesda, Md., and The Division of Biological and Medical Research, Argonne National Laboratory, Chicago, Ill. Search for other works by this author on: Oxford Academic PubMed Google Scholar 1National Institutes of Health, Public Health Service, Federal Security Agency. Author Notes JNCI: Journal of the National Cancer Institute, Volume 12, Issue 1, August 1951, Pages 197–201, https://doi.org/10.1093/jnci/12.1.197 Published: 01 August 1951 Article history Received: 28 May 1951 Published: 01 August 1951
Gene expression profile for metastatic melanoma and patient survival
Authors: D. Bogunovic, D. O’Neill, S. Adams, J. Wang, F. Darvishian, A. C. Pavlick, R. L. Shapiro, J. Zavadil, I. Osman, N. Bhardwaj
Journal: Journal of Clinical Oncology (2008)

9049 Background: Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. Here we use gene expression profiling of metastatic melanoma samples to search for a molecular basis for this observation. Methods: We analyzed gene expression profiles of 44 metastatic melanoma specimens collected from 38 patients who were followed clinically for a median of 20 months after surgery. RNA was processed using standard methods and hybridized to Affymetrix Human Genome HU133 Plus 2.0 arrays. Data were analyzed using GeneSpring and PathwayAssist software, normalizing using a PLIER algorithm and utilizing ANOVA statistical tests. Results: Unsupervised clustering yielded 4 distinct groups of subjects, 2 of which had large differences in overall survival. We then used supervised clustering to compare patients whose post-surgery survival was less then 1.5 years (11 subjects, 9.5 month median survival) to those who survived greater than 1.5 years (23 subjects, 26 month median survival, 17 alive at last follow-up). Only genes with changes in expression of > 2 with a p value of < 0.05 were accepted, resulting in a group of approximately 200 genes. Genes associated with immune response (TNFα, IRF1, Granzyme B, CD8α, CXCL11, IL27AR, GBP1, CXCL10, CCBP2, GBP2, CCR9 and IFIT4) or with cell proliferation (FGFR1, MET, MDM2, CDC25A, RFC2, SOS1, HOXA3, MCM4, MCM7, ORC5L, KIF23 and VAV3) were highly represented. Prolonged survival was associated with elevated expression of immune response genes and decreased expression of genes associated with cell proliferation. Conclusions: Gene expression profiling of metastatic melanoma samples identified a set of genes associated with patient survival, and suggests that immune surveillance is a mechanism for prolonged survival in these patients. No significant financial relationships to disclose.
Indications for BRCA1 and BRCA2 mutation testing in hereditary breast and ovarian cancer families
Authors: R. Schmutzler, U. Schwarz-Boeger, G. Bastert, None Bender, None Beckmann, None Caffier, None Crohns, J. Deininger, None Dietl, None Ditsch, None Distler, None Estevez-Schwarz, W. Hahn, None Herröder, None Hübbel, None Hüttner, None Jackisch, None Kandl, K. Kast, None Kuschel, None Luck, None Von Minckwitz, None nestle-Krämling, B. Prieshof, None Rensing, None Rhiem, None Schäffer, None Straub, None Untch, T. Volm, M. Kiechle
Journal: Journal of Clinical Oncology (2004)

9720 Background: Since characterization of BRCA1 and BRCA2 in 1994 1995 resp. genetic testing of these genes is possible. Germline mutations in these genes are the most common reason for hereditary breast and ovarian cancer. Methods: Since December 1996 testing of BRCA1 or BRCA2 mutations is implemented in twelve university hospitals all over Germany granted by the German Cancer Aid (Deutsche Krebshilfe). After detailed counseling by a gynecologist, a psycho-oncologist and a human geneticist genetic testing is offered to those family members already laid up with breast or ovarian cancer or those who are on risk for hereditary breast or ovarian cancer. Families are grouped into different risk categories: A=three or more family members suffering from breast cancer with at least two of them becoming deseased premenopausally or male breast cancer, B=families with breast and/or ovarian cancer or more family member having breast and ovarian cancer, C=two family members suffering from breast cancer with at least one of them becoming diseased premenopausally or only one woman with bilateral breast cancer first diseased in an age of ≤ 40 years, D=two and more women suffering from postmenopausal breast cancer and E=only one woman with early onset of breast cancer (≤ 35 years). By now more than 1100 persons have been tested. These are the results of an interim analysis of 2755 (hereof 1077 tested) cancer patients out of 737 families. Results: The distribution of the families in the previously described categories was A=34,5%, B=27,1%, C=27,5%, D=4,3% and E=4,0%. In 44% of all families a mutation in BRCA1 or 2 was found but 56% of all families were found BRCA1/2 negative. Looking to all detecte BRCA1-mutations the major percentage was verified in B-category (53,5%) and the A-category (37,6%) and only 6% in C, 3% E and none in D families. BRCA2-mutations are mostly find in A (57,5%) and B families (26,0%) and less in C (12,3%), D(2,7%) and E families (1,4%). On the other hand 76,8% C, 77,4% D and 82,8% E families were tested BRCA1/2 negativ. Conclusions: According to our results genetic testing is indicated in families with either breast and ovarian cancer or multiple premenopausal breast cancer. No significant financial relationships to disclose.
Ampullary cancer ESPAC-3 (v2) trial: A multicenter, international, open-label, randomized controlled phase III trial of adjuvant chemotherapy versus observation in patients with adenocarcinoma of the ampulla of vater.
Authors: J. P. Neoptolemos, M. J. Moore, T. F. Cox, J. W. Valle, D. H. Palmer, A. Mcdonald, R. Carter, N. C. Tebbutt, C. Dervenis, D. Smith, B. Glimelius, F. Y. Coxon, F. Lacaine, M. R. Middleton, P. Ghaneh, C. Bassi, C. Halloran, A. Olah, C. L. Rawcliffe, M. W. Büchler
Journal: Journal of Clinical Oncology (2011)

LBA4006 Background: The effect of adjuvant treatment on overall survival (OS) of resected ampullary adenocarcinoma is not known. The aim was to compare the survival effect of adjuvant chemotherapy compared to observation (OBS) after resection and within the chemotherapy group to compare 5-fluorouracil/folinic acid (5-FU/FA) against gemcitabine (GEM). Methods: Patients were stratified by R0/R1 margins, randomised into three arms: (1) 5-FU/FA (FA, 20 mg/m 2 iv bolus then 5-FU, 425 mg/m 2 , iv bolus, 1-5d every 28 days); (2) GEM (100mg/m 2 iv infusion 1d, 8d and 15d every 4 weeks); (3) observation. The primary outcome measure was OS of chemotherapy versus no chemotherapy. 300 patients (200 chemotherapy and 100 observation) would provide 80% power to detect a 15% 5y survival difference, p&lt;0.05. Results: 304 patients were randomised (July 2000 to April 2008), 199 to chemotherapy (101 5FU, 98 GEM) and 105 to observation. Median (range) age was 62 (35 – 81) years; 187 (61.5%) were men. Median (IQR) maximum tumour diameter was 20.0 (15.0 – 28.0) mm, 186 (63%) were moderately differentiated tumours, 174 (57%) had involved lymph nodes and 276 (91%) were R0 resections. Independent prognostic factors were tumour diameter and grade, lymph node status and R0/R1 status. Median (95% CI) OS for chemotherapy [57.1 (41.7 – 73.8) months] versus no chemotherapy [43.0 (27.6 - ) months] gave an HR (95% CI) of 0.85 (0.61 – 1.18), p=0.323. For R0 patients median (95% CI) OS for chemotherapy [58.4 (45.4 – 84.0) months] versus no chemotherapy [45.1 (26.7 - ) months] gave an HR (95% CI) of 0.78 (0.55 – 1.11), p=0.173. Cox proportional hazards modelling for all 304 patients p=0.161 and for 276 R0 patients p=0.057. Conclusions: This is the only large adjuvant trial ever conducted for ampullary adenocarcinoma. The results suggest a benefit for adjuvant monochemotherapy in patients with clear resection margins.
Transplantable Leydig Cell Tumors in Fischer Rats: Hormone Responsivity and Hormone Production&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B B Jacobs, R A Huseby
Journal: JNCI Journal of the National Cancer Institute (1968)

Spontaneous testicular interstitial (Leydig) cell tumors arising in our colony of inbred Fischer rats proved to be readily transplantable. The hormone production and hormone responsivity of 8 of these Leydig cell tumors are reported. The tumors showed a wide range of morphologic and functional characteristics. All produced some androgen and/or estrogen. Some grew only in castrate recipients while others grew in intact and hypophysectomized hosts. Hormone production continued in one tumor when growing in hypophysectomized hosts. Hormone production, hormone responsivity, and the morphologic appearance of the tumors appear to be characteristics manifested independently of each other. The similarity of these tumors to estrogen-induced tumors of the mouse is discussed.
Abstract 12961: Activation Imaging: A Novel Approach to Three-Dimensional Mechanical Mapping in Native Conduction Delays and Pacing Using Speckle Tracking Echocardiography
Authors: Toshinari Onishi, Tetsuari Onishi, Mohamed Ahmed, Josef Marek, Stephanie C Harberman, Samir Saba, David Schwartzman, John Gorcsan
Journal: Circulation (2012)

Background: Quantification of electro-mechanical activation is clinically important, but previous three-dimensional (3-D) mapping approaches have been technically difficult requiring catheter inter...
O018 : 2D-shear wave elastography is equivalent or superior to transient elastography for liver fibrosis assessment: Results from an individual patient data based meta-analysis
Authors: E. Herrmann, V. de Lédinghen, C. Cassinotto, W.C.-W. Chu, V.Y.-F. Leung, G. Ferraioli, C. Filice, L. Castera, V. Vilgrain, M. Ronot, J. Dumortier, A. Guibal, S. Pol, J. Trebicka, C. Jansen, C. Strassburg, R. Zheng, J. Zheng, S. Francque, T. Vanwolleghem, L. Vonghia, E.K. Manesis, P. Zoumpoulis, I. Sporea, M. Thiele, A. Krag, M. Friedrich-Rust
Journal: Journal of Hepatology (2015)
A prospective study of delinquency in 110 adolescent boys with attention deficit disorder and 88 normal adolescent boys
Authors: J H Satterfield, C M Hoppe, A M Schell
Journal: American Journal of Psychiatry (1982)

The authors studied official arrests from childhood through adolescence in two groups of boys; one group (N = 110) was diagnosed in childhood as suffering from attention deficit disorder (ADD), and the second group (N = 88) consisted of normal control adolescents. Rates of single and multiple serious offenses and of institutionalization for delinquency were significantly higher in the ADD subjects. These findings suggest a strong relationship between childhood ADD and later arrests for delinquent behavior.
Ampulla of Vater adenocarcinoma in the Veteran's Affairs population
Authors: M. M. Safa, K. Ahmed, M. S. Beg
Journal: Journal of Clinical Oncology (2008)

15521 Background: Outcome data on Ampulla of Vater (AV) cancer is lacking. Surgical resection is the only option for long term survival. We performed a retrospective study of patients with AV adenocarcinoma treated at Veterans Affairs (VA) hospitals. Methods: The VA Central Cancer Registry (VACCR) is a function of the Oncology Program Office at VA Headquarters, Washington DC. We searched VACCR for all diagnosed AV cancer cases (primary site code 241) from 1995 to 2005. Data was entered and analyzed using SPSS v.13.0. Patient and disease characteristics were compared by chi-square test. Overall survival was estimated with Kaplan-Meier method. Multivariate analysis was performed with Cox proportional hazards regression model to determine the independent association between each variable and survival. Results: A total of 367 cases of AV adenocarcinoma were identified. Overall 314 (85.6%) individuals were white, 43 (11.7%) black, and 10 (2.7%) other. Thirty-eight patients (10.4%) had metastatic disease while 180 (49%) did not. Surgery was performed in 210 (57.2%). Overall median survival was 12 months. Survival with metastatic disease was 6.57 months and 14.37 months without metastasis (p=0.0005). In nonmetastatic disease, surgery improved survival from 4.73 to 28.9 months (p<0.001). Patients who received surgery in addition to radiation and chemotherapy for nonmetastatic disease had similar survival of 27.9 months (p=NS). In multivariate analysis with race, metastatic disease, chemotherapy, radiation, and surgery, only surgery was a significant predictor of survival (table 1). Conclusion: Adenocarcinoma of the AV is a rare malignancy of poor prognosis. To our knowledge, a systematic review of a large patient population has not been reported. In the VA, surgery was shown to improve survival in nonmetastatic disease. Adjuvant chemotherapy plus radiation did not add survival advantage. Future studies are essential to determine optimal therapy. Survival in Nonmetastatic Disease Therapy Cases Months None 62 4.73 (1.77–7.7) Surgery 74 28.9 (14.2–43.6) Surgery/Chemo/Rad 22 27.93 (1.75–54.12) No significant financial relationships to disclose.
Rapid response to Groves J. Bicycle weight and commuting time... De Selby theory requires repeated weighing.
Authors: Tocc C
Journal: BMJ (2010)

Todd C. Rapid response to Groves J. Bicycle weight and commuting time: randomised trial.  BMJ 2010;341:c6801 doi:10.1136/bmj.c6801: De Selby theory requires repeated weighing. BMJ 16/12/2010 http://www.bmj.com/rapid-response/2011/11/03/de-selby-theory-requires-repeated-weighing
Outcomes of patients with malignant melanoma treated with immunotherapy prior to or after vemurafenib.
Authors: Allison Ackerman, David F. McDermott, Donald P. Lawrence, Anasuya Gunturi, Keith T. Flaherty, Anita Giobbie-Hurder, F. Stephen Hodi, Nageatte Ibrahim, Michael B. Atkins, Daniel C. Cho, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2012)

8569 Background: Treatment of patients (pts) with BRAF mutant malignant melanoma (MM) with vemurafenib (vem), a BRAF inhibitor (BRAFi), is associated with a high response rate (RR) and improvement in progression free survival (PFS) and overall survival (OS) compared to standard chemotherapy. Responses to vem are typically not durable and most pts require additional therapy. However, there is little data to guide sequencing of vem with other standard therapies such as ipilimumab (ipi) or interleukin 2 (IL-2). Methods: 43 pts treated with vem as part of clinical trials from 2009-2012 were retrospectively identified. RR of vem was calculated for all pts as well as for pts treated with immunotherapy (IT) prior to vem. The OS from first systemic and vem treatment, duration of vem therapy, OS from when pts came off vem, and PFS and OS for post-vem ipi was determined using Kaplan-Meier estimates. Results: Of the 43 pts, 11 remain on vem and 32 are off vem (19 deceased) with a median follow up of 19 mo. Pre-vem LDH was elevated in 46% (17/37 evaluable pts). The RR to vem was 52% (22/42 evaluable pts), the median duration of therapy 5.6 months (mo), and the median OS 19.3 mo, similar to results in trials. The median OS from initiation of any treatment was 27 mo. 16 pts received IT (11 IL-2, 4 ipi, 1 IL-2 then ipi) prior to vem with a median OS of 31.2 mo; the RR of vem following IT was 75% (12/16). At time of vem discontinuation 50% of pts (12/24 evaluable) had an elevated LDH, and the median OS of the 32 pts who stopped vem was 4 mo from last vem dose. 10 of these pts then received single-agent ipi; six of whom had an elevated LDH. Five pts died within 3 mo of last vem dose, and all 10 pts had disease progression (PD) at 6 months with a median PFS of 0.7 mo and OS of 2.2 mo. The 3 pts who lived beyond 1 year following vem and then ipi were subsequently treated with a BRAFi following PD on ipi. Conclusions: Response to vem following IT appears similar to that seen in previously untreated pts. Median PFS and OS for pts receiving ipi after discontinuation of vem are poor, possibly due to rapid PD at the time of vem discontinuation. Prolonged OS is primarily seen with resumption of BRAF inhibition. Our data suggests that in appropriately selected pts, IT should be considered prior to BRAFi.
Assisted reproductive techniques after fertility-sparing treatments in gynaecological cancers
Authors: Ignacio Zapardiel, Maria Cruz, Maria D. Diestro, Antonio Requena, Juan A. Garcia-Velasco
Journal: Human Reproduction Update (2016)

BACKGROUNDThe trend toward late childbearing has made fertility preservation a major issue for women who face gynecological cancer. New techniques in assisted reproductive medicine enable conception after primary treatment of these cancers. Here, we aimed to review the efficacy and safety of assisted reproductive techniques (ART) after fertility-preserving treatment of gynaecological cancers.
Congenital Malformations
Authors: Lewis B. Holmes
Journal: New England Journal of Medicine (1976)

Congenital malformations are a common cause of illness, handicapping conditions and death. The incidence varies with the age of the person being evaluated. It is highest among spontaneous abortions, with many of the abnormalities incompatible with survival. About 2 per cent of newborns have a major malformation. Additional malformations not detected at birth, such as renal anomalies and cardiac defects, become apparent in succeeding years.TerminologySeveral terms have been adapted for use in describing the nature of malformation. Anomaly and malformation are considered synonymous for a structural abnormality. A major malformation has either surgical or cosmetic consequences; a minor . . .
Four biomechanical and anthropometric measures predict tibial stress fracture: a prospective study of 1065 Royal Marines
Authors: Michael Nunns, Carol House, Hannah Rice, Mohammod Mostazir, Trish Davey, Victoria Stiles, Joanne Fallowfield, Adrian Allsopp, Sharon Dixon
Journal: British Journal of Sports Medicine (2016)

Tibial stress fractures (TSFs) cause a significant burden to Royal Marines recruits. No prospective running gait analyses have previously been performed in military settings.We aimed to identify biomechanical gait factors and anthropometric variables associated with increased risk of TSF.1065 Royal Marines recruits were assessed in week 2 of training. Bilateral plantar pressure and three-dimensional lower limb kinematics were obtained for barefoot running at 3.6 m/s, providing dynamic arch index, peak heel pressure and lower limb joint angles. Age, bimalleolar breadth, calf girth, passive hip internal/external range of motion and body mass index (BMI) were also recorded. 10 recruits who sustained a TSF during training were compared with 120 recruits who completed training injury-free using a binary logistic regression model to identify injury risk factors.4 variables significantly (p<0.05) predicted increased risk of TSF (ORs and 95% CI): smaller bimalleolar width (0.73, 0.58 to 0.93), lower BMI (0.56, 0.33 to 0.95), greater peak heel pressure (1.25, 1.07 to 1.46) and lower range of tibial rotation (0.78, 0.63 to 0.96).Reduced impact attenuation and ability to withstand load were implicated in tibial stress fracture risk.