tbuckley/cabot-search huggingface dataset:
Progress and trends in successful phase II clinical trials in advanced solid cancers over the past 20 years
Authors: J. K. Chan, S. M. Ueda, J. Y. Shin, C. Herrick, C. Roth, V. E. Sugiyama, C. D. Stave, K. Osann, L. Chen, D. S. Kapp
Journal: Journal of Clinical Oncology (2008)

6556 Background: To identify progress and trends in phase II studies of advanced solid tumors over the past 20 years. Methods: From 1985 to 2005, all successful phase II clinical trials that resulted in a published phase III study were identified in PubMed, Cochrane Central Register of Controlled Trials, and BIOSIS. Over three study periods, 1985–1991, 1992–1998, and 1999–2006, data were analyzed using the chi square test and logistic regression models. Results: Of the 666 phase II studies that led to phase III trials, 186, 263, and 207 trials were identified in 1985–1991, 1992–1998, and 1999–2006, respectively. Compared to cancers such as breast and colon, the percentage of phase II trials on lung cancer increased from 12.2% to 23.2% to 31.9% over the three study periods (p 25–50) increased from 35.4% to 42.4% to 44.4%, respectively (p<0.001). There was also a significant increase in the percentage of trials performed at multiple rather than single-institutions (27.5% to 39.0% to 64.9%; p<0.001). The percentage of trials involving pharmaceutical groups increased across these time periods from 0.6% to 2.3% to 12.4% (p<0.001), while the percentage of trials from academic institutions decreased from 60.0% to 50.2% to 47.0% (p<0.001). There was a trend towards an increase in the proportion of positive compared to negative or equivocal outcomes for phase II clinical trials (p=0.005). The proportion of phase II studies that resulted in “positive” phase III trials increased from 24.5% to 34.2% to 50.6% (p<0.001). The percentage of phase II studies performed in the U.S. decreased from 51.7% to 44.9% to 34.0% (p<0.001), and an increase in European-based trials, from 38.5% to 50.0% to 51.7% (p<0.001). However, other factors such as median duration of response and survival were not significant over time. Conclusions: Over time, there was an increase in the proportion of lung cancer trials and a higher number of patients enrolled per clinical trial. In addition, more clinical trials were conducted in multiple rather than single institutions, in Europe instead of the U.S., and by pharmaceutical groups rather than academic centers. Identifying the progress and trends of successful phase II clinical trials may have significant implications toward the design and outcomes of future clinical trials. No significant financial relationships to disclose.
Long-term survival in unfavourable-risk mRCC patients after intratumoral administration of a cell-based allogeneic vaccine
Authors: Alex Karlsson-Parra, Anna Laurell, Maria Lönnemark, Einar Brekkan, AnnaCarin Wallgren, Anders Magnusson
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Initial data from a Phase I/II study in patients with recently diagnosed metastatic RCC ([NCT01525017][1]) demonstrated that intratumoral administration of a cell based allogeneic vaccine adjuvant before nephrectomy was associated with a prominent intratumoral infiltration of CD8
Bim and PD-1 identify effector CD8 T cells responsive to anti-PD-1 therapy in metastatic melanoma patients
Authors: Roxana Dronca, Xin Liu, Kottschade Lisa, Rob Mcwilliams, Svetomir Markovic, Haidong Dong
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Although PD-1 blockade therapy demonstrates promising therapeutic effects in a portion of metastatic melanoma patients, clinical outcomes remain variable, with some patients achieving durable responses, others experiencing early disease worsening followed by later tumor reduction
The Value of Considering Cost, and the Cost of Not Considering Value
Authors: Leonard B. Saltz
Journal: Journal of Clinical Oncology (2015)

During my residency, which was, alas, some time ago, an attending physician instructed me to order a large battery of tests.These seemed to me to be highly unlikely to affect patient management.I asked him if this was really the best thing to do, and noted that it didn't seem cost effective.He replied to me, with righteous indignation, that it was "…not our job to consider cost" and that "…none of my patients ever paid me to be cost effective."I thought this was wrong then; I know it is wrong now.Whether there was ever justification for our wishful societal delusion that everything we do in health care, and especially cancer care, could and should be above consideration of cost, we are now recognizing, albeit all too slowly, that we can no longer afford this luxurious fantasy.As every drug, device, and intervention we might choose, or not, to use in the care of a patient has a specific and often substantial cost attached to it, we can no longer ignore nor can we blindly accept that cost and feel that it has no place in our medical decision making.To continue to do so would inevitably bankrupt our health care system and prevent us from ever being able to provide necessary quality care for all.In this context, the terms value, value-based care, and highvalue medicine have increasingly entered into our discussions.Often missing, however, in this developing discourse is a clear understanding of what these terms actually mean.Too often an ethereal, vague concept of value is invoked to obscure or avoid a frank consideration of the real, hard cost.A drug regimen that works well is valuable, but if it costs $300,000 per patient per year, as some of our newer regimens do, then I would argue a priori that it costs too much, and a diversion of the discussion away from this hard cost to a vague concept of value can serve as a distraction from confronting this harsh reality.Also lost, or at least underappreciated in these discussions, is that we will accomplish nothing as we confront cost, define value, and embrace high-value care unless we also define and eschew low-value care.This means identifying certain practices that we now perform that we will stop performing, because they offer insufficient value to our patients to justify their continued use.
On the Verge: Immunotherapy for Colorectal Carcinoma
Authors: David Y Oh, Alan P Venook, Lawrence Fong
Journal: Journal of the National Comprehensive Cancer Network (2015)

Although overall survival from colorectal cancer (CRC) has steadily improved over the past decade, there is still work to be done. The gains associated with improved detection and treatment paradigms with chemotherapy and biologics appear to have reached their ceiling. Immune-based therapies have recently demonstrated clinical benefit in other cancers, including CRC with microsatellite instability (MSI), but patients with CRC without MSI have not yet derived benefit. This article reviews the history of CRC immunotherapy trials, the conceptual basis for why the activity of the immune system may be relevant to survival in CRC, and current efforts in CRC immunotherapy, and speculates about future efforts in this area based on experience with immunotherapy efforts in other classes of solid tumors.
Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma
Authors: R H Prabhala, M Fulciniti, D Pelluru, N Rashid, A Nigroiu, P Nanjappa, C Pai, S Lee, N S Prabhala, R L Bandi, R Smith, S B Lazo-Kallanian, S Valet, N Raje, J S Gold, P G Richardson, J F Daley, K C Anderson, S A Ettenberg, F Di Padova, N C Munshi
Journal: Leukemia (2015)
Pancreatic cancer and diabetes: Is diabetes a risk factor or the outcome?
Authors: P. Garg, R. Gupta
Journal: Journal of Clinical Oncology (2007)

15123 Background: Though pancreatic cancer ranks eighth among all major forms of cancer related deaths, it accounts for only 3% of all cancers worldwide. Diabetes mellitus type 2 and pancreatic cancer are known to be associated but this relationship decreases inversely with an increasing duration of diabetes. The aim of the present study is to assess whether new onset type 2 diabetes is a risk factor for pancreatic cancer or it results as an outcome of pancreatic cancer. Methods: We conducted a meta-analysis of all available studies to examine this association. Using PUBMED, EMBASE &amp; MEDLINE we searched the literature for studies from 1980 to present. All published studies with quantitative estimates and standard errors, or confidence limits, of the association between type 2 diabetes and pancreatic cancer were included. Studies having patients with an un-defined period of diabetes or diabetes for greater than 5 years before the development of pancreatic cancer were excluded. 14 case control and 11 cohort trials with information on 5807 individuals with pancreatic cancer met the above criteria. Each study was independently reviewed by 2 reviewers. Results: The pooled odds ratio for case control studies for patients with diabetes and pancreatic cancer was 1.98 (95% CI - 1.58–2.42) while that for cohort studies was 1.88 (95% CI - 1.72–2.16). The combined odds ratio was 1.92 (95% CI - 1.62 - 2.38). However in patients who developed pancreatic cancer with in 2 years of diagnosis of diabetes the odd’s ratio was significantly higher (OR- 3.2, 95% CI - 2.24- 4.02). Conclusions: On the basis of above data pancreatic cancer is more likely to occur in new onset diabetes mellitus type 2 than the general population. However, the evidence above is insufficient to conclude that diabetes mellitus is indeed a risk factor for pancreatic cancer. Since the relative risk of developing pancreatic cancer was higher in patients with new onset type 2 diabetes in the first two years, it further supports the hypothesis that the development of diabetes may be a manifestation of early but yet undiagnosed pancreatic cancer. Large population based studies are needed to truly determine this relationship. No significant financial relationships to disclose.
EFFECT OF INJURY PREVENTION TRAINING ON KNEE MECHANICS IN FEMALE ADOLESCENTS DURING PUBERTY
Authors: R Otsuki, R Kuramochi, T Fukubayashi
Journal: British Journal of Sports Medicine (2014)

Background Female adolescents change their landing mechanics during puberty. It is unknown whether implementation of anterior cruciate ligament (ACL) injury prevention training reduces the loss of knee control in female athletes during puberty. Objective To evaluate the effect of injury prevention training on knee mechanics in female athletes during puberty. Design Controlled before-and-after study. Setting Youth sports. Participants 60 female junior high school basketball players participated and were divided into 2 groups: training group (n=32) and control group (n=28). Interventions The training group underwent an injury prevention program three times per week for 6 months. The focus of the program was to ensure proper movement patterns, particularly avoiding knee valgus motion and encouraging knee flexion. The program was 20 min long and was implemented as a warm-up routine. The control group maintained a regular training routine. Main outcome measurements The knee valgus motion and knee flexion range of motion during a drop vertical jump were measured before and after the training period. The probability of a high knee abduction moment (pKAM) was also evaluated using an ACL injury prediction algorithm. Results The knee valgus motion was significantly increased in the control group (P&lt;.001), whereas it did not change in the training group (P=.64). Similarly, the knee flexion range of motion was significantly decreased in the control group (P&lt;.001), whereas it was not changed in the training group (P=.55). The pKAM was significantly increased in the control group (P&lt;.001), but not in the training group (P=.06). Conclusions Implementation of injury prevention training was effective in limiting the loss of knee control in female athletes during puberty. Although a significant improvement in landing mechanics might not be possible, implementation of injury prevention training should be initiated during puberty to reduce the risk of ACL injury.
Insulin Resistance and Inflammation in Hypogonadotropic Hypogonadism and Their Reduction After Testosterone Replacement in Men With Type 2 Diabetes
Authors: Sandeep Dhindsa, Husam Ghanim, Manav Batra, Nitesh D. Kuhadiya, Sanaa Abuaysheh, Sartaj Sandhu, Kelly Green, Antoine Makdissi, Jeanne Hejna, Ajay Chaudhuri, Mark Punyanitya, Paresh Dandona
Journal: Diabetes Care (2015)

OBJECTIVE One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo-controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. RESEARCH DESIGN AND METHODS A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. RESULTS Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (−3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P &amp;lt; 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P &amp;lt; 0.05 for all). CONCLUSIONS Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.
<i>CCR</i> 20th Anniversary Commentary: Autologous T Cells—The Ultimate Personalized Drug for the Immunotherapy of Human Cancer
Authors: Steven A. Rosenberg
Journal: Clinical Cancer Research (2015)

Abstract The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. Clin Cancer Res; 21(24); 5409–11. ©2015 AACR. See related article by Rosenberg et al., Clin Cancer Res 2011;17(13) July 1, 2011;4550–7
A modified Valsalva maneuver was more effective than standard Valsalva for treating supraventricular tachycardia
Authors: E.C. Drake Coffey, Bruce D. Adams
Journal: Annals of Internal Medicine (2015)

Source Citation Appelboam A, Reuben A, Mann C, et al; REVERT trial collaborators. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet. 2015 Aug 24. [Epub ahead of print] 26314489
Plaque Volume of Carotid Endarterectomy Specimens Measured by 3D Ultrasound Technology
Authors: Anirudh Kumar, Eric Y. Yang, Gerd Brunner, Tyler O. Murray, Salim S. Virani, Zsolt Garami, Christie M. Ballantyne, Joel D. Morrisett, Vijay Nambi
Journal: JACC. Cardiovascular imaging (2015)
CDK6-mediated repression of CD25 is required for induction and maintenance of Notch1-induced T-cell acute lymphoblastic leukemia
Authors: N Jena, J Sheng, J K Hu, W Li, W Zhou, G Lee, N Tsichlis, A Pathak, N Brown, A Deshpande, C Luo, G F Hu, P W Hinds, R A Van Etten, M G Hu
Journal: Leukemia (2015)
Safety assessment for the combination of docetaxel, carboplatin, and thoracic radiotherapy in unresectable stage III non-small cell lung cancer (NSCLC): A report of the first 100 patients treated with chemoradiation on D0410
Authors: J. R. Rigas, M. S. Rubin, J. M. Waples, K. H. Dragnev, D. M. Zimmerman, R. R. Reimer, R. Droder, J. Rathmann, N. B. Green, M. Carey
Journal: Journal of Clinical Oncology (2007)

7701 Background: Concurrent chemoradiotherapy (chemoRT) is the preferred treatment for patients with unresectable stage III NSCLC. Limited safety information is available on the use of concurrent docetaxel, carboplatin and thoracic RT. We report the safety information on the initial 100 patients (pts) treated with this chemoRT as part of an ongoing US randomized phase III trial (D0410) evaluating the role of erlotinib/placebo following this concurrent chemoRT treatment. The sample size is 400 pts and the primary endpoint is progression-free survival. Methods: Pts with unresectable pathologically confirmed stage III NSCLC are randomized to receive either erlotinib 150 mg or placebo orally daily for 2 years following concurrent chemoRT with docetaxel 20 mg/m 2 , carboplatin AUC=2 intravenously weekly for 6 wks with thoracic RT of at least 61 Gy in 33 fractions over 6.5 weeks. The planned total lung volume exceeding 20 Gy (V20) was less than 32%. Only the chemoradiation safety information is being reported. This data was reviewed by an independent safety and data monitoring committee. Results: Pt characteristics; 59% males, median age 69 years (range 38 to 86), 21% adenocarcinoma, 48% squamous cell, 94% ECOG PS0–1, 49% stage IIIA, 15% weight loss = 10%. Of 600 planned chemotherapy treatments, 492 were administered (93 wk 1, 85 wk 2, 82 wk 3, 81 wk 4, 77 wk 5, 74 wk 6). There were 25 chemotherapy dose reductions; most commonly for esophagitis (8), neutropenia (5), renal dysfunction (3), hypersensitivity (2). There were no treatment-related deaths. There were 25 grade 3 and 3 grade 4 treatment-related adverse events. The most common grade 3/4 events were esophagitis (6), fatigue (3), odynophagia (2), neutropenia (1), thrombocytopenia (1), dematitis (1). Conclusions: This concurrent chemoradiation regimen appears to be safe. Enrollment to the phase III trial continues. There is a planned interim efficacy evaluation at 150 events (deaths or disease progression). Funded in part by Sanofi- Aventis, Genentech, and OSI Pharmaceuticals. [Table: see text]
Varying involvement of peripheral granulocytes in the clonal abnormality - 7 in bone marrow cells in preleukemia secondary to treatment of other malignant tumors: cytogenetic results compared with results of flow cytometric DNA analysis and neutrophil chemotaxis
Authors: J Pedersen-Bjergaard, L Vindelov, P Philip, P Ruutu, J Elmgreen, H Repo, IJ Christensen, SA Killmann, G Jensen
Journal: Blood (1982)
Atrial natriuretic peptide inhibits colorectal cancer cells growth by reverting the WNT/ß-catenin pathway
Authors: Annalucia Serafino, Pasquale Pierimarchi, Federica Andreola, Luana Mercuri, Rossana Psaila, Manuela Zonfrillo, Enrico Garaci, Guido Rasi
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

2323 

Background and Aim . Atrial natriuretic peptide (ANP) belongs to a family of cardiac and vascular-derived peptide hormones playing a crucial role in cardiovascular homeostasis mainly through blood volume and pressure regulation. ANP also posses antiproliferative ability on human breast, pancreatic, and prostate adenocarcinoma cells, on small cell and squamous cell lung carcinomas. A direct interaction of this peptide with some growth-stimulating hormones, owing to DNA synthesis inhibition, has been suggested, but the mechanism underlying its anti-tumor effect is not yet clarified. We aimed to verify whether ANP is able to exert an inhibitory effect on colorectal cancer cell growth. Because the role of the deregulation or constitutive activation of the Wnt/s-catenin pathway in colorectal cancer initiation and progression, we also assessed if ANP could be able to modify the expression of some crucial molecules involved in the signal transmission initiated by Wnt ligands. Methods . DHD/K12 TRB cell line, originally established from 1,2-dimethylhydrazine-induced colon adenocarcinoma in BDIX rats, was tested. The effect of ANP on cell proliferation was analyzed by confocal microscopy (CLSM), evaluating the mitotic index after nuclei fluorescent staining, and by flow cytometry, measuring bromodeoxyuridine incorporation. The intracellular distributions of E-cadherin, s-catenin, APC and GSK-3s were analyzed by CLSM. E-cadherin, s-catenin levels were also evaluated by Western blot in soluble or membrane protein extracts. Results . ANP 1µM is able to inhibit DHD/K12 TRB cells proliferation as revealed by decrease of mitotic index as well as of cell percentage in S-phase after 24h. The antiproliferative effect is preceded by a redistribution of Wnt signaling molecules, with translocation of the onco-suppressor APC to the nucleus after 2-4h and decrease of s-catenin nuclear and cytoplasmic accumulation between 6h and 24h, concomitantly with an augmented expression of E-cadherin at the cell-cell junctions. Increased co-localization of the s-catenin/APC and s-catenin/GSK-3s deriving immunofluorescent signals during ANP treatment, indicated that the decreased expression of cytosolic s-catenin might be due to an increase of its degradation. Conclusions . Our results indicate that ANP exerts an antiproliferative effect on colorectal cancer cells inducing early modifications of Wnt/s-catenin signaling pathway. The effects on E-cadherin redistribution at the cell-cell junction encourage to explore the possibility that ANP reverts colorectal cancer cells from the proliferating to the differentiated state. This opens to a new possible approach, using ANP for colorectal cancer treatment also addressing the differentiation therapy.
Adenovirus-Mediated Human Immunodeficiency Virus-1 Nef Expression in Human Monocytes/Macrophages and Effect of Nef on Downmodulation of Fcγ Receptors and Expression of Monokines
Authors: Swapan K. De, Chettemgere N.S. Venkateshan, Prem Seth, D. Carleton Gajdusek, Clarence J. Gibbs
Journal: Blood (1998)
Clinical significance of erythropoietin (Epo) and its receptor (EpoR) in non-small cell lung carcinoma
Authors: Anna Korzeniewska, Agnieszka Halon, Renata Jankowska
Journal: European Respiratory Journal (2014)

The biological function of the Epo–EpoR system may play a significant role in tumour growth. The existing research projects investigating the expression of Epo and EpoR in non-small cell lung cancer (NSCLC) are scarce. The present paper is another effort to evaluate EPO and EPOr as predictive and prognostic factors in NSCLC.  The expression of erythropoietin and its receptor has been evaluated using immunohistochemical method. Samples of tumour tissue were obtained from 103 patients undergoing surgery. The results suggest a high sensitivity of the applied method as 95.1 per cent of the tested tumours showed the expression of Epo and the EpoR was found in 100 percent of cancer specimens.  Another purpose of this paper was to examine the relationship between demographic and clinical characteristics of surgery patients and the expression of Epo and EpoR. The following characteristics were analysed statistically: age, sex, number of pack years smoked, histological type of the cancer, stage of disease, metastasis to lymph nodes and survival time.  No correlation has been proven between the expression of erythropoietin and any of the above patient characteristics. It means the Epo expression is not a predictive or prognostic factor in NSCLC.  On the other hand, the expression of EpoR was correlated with the ability to metastasize and with the number of pack years smoked. The result obtained suggests that the evaluation of EpoR expression may have a prognostic value in NSCLC.  The results presented in this paper may suggest a significant impact of the presence of Epo receptor in an NSCLC tissue on the prognosis, especially in the group of patients with a long history of pack years smoked.