tbuckley/cabot-search huggingface dataset:
Upregulating Hif‐1α by Hydrogel Nanofibrous Scaffolds for Rapidly Recruiting Angiogenesis Relative Cells in Diabetic Wound
Authors: Hao Chen, Peng Jia, Hui Kang, Hongbo Zhang, Yi Liu, Peilang Yang, Yufei Yan, Guilai Zuo, Lei Guo, Min Jiang, Jin Qi, Yuanyuan Liu, Wenguo Cui, Hélder A. Santos, Lianfu Deng
Journal: Advanced Healthcare Materials (2016)

Nonhealing chronic wounds on foot are one of the most dreaded complications of diabetes, and biomedical scaffolds remain an attractive option for repairing or regenerating tissues. Accelerating angiogenesis in the early stage after injury is critical to wound healing process; however, the scaffolds accelerate the angiogenesis in the beginning but with the acceleration of vessel network formation the scaffold network hinders the process. In this study, the water soluble drugs‐loaded hydrogel nanofibrous scaffolds are designed for rapidly recruiting angiogenesis relative cells and promoting wound healing. The sustained release profile of desferrioxamine (DFO), which continues for about 72 h, leads to significantly increase of neovascularization. The majority of the scaffold is degraded in 14 d, leaving enough space for cell proliferation and vessel formation. The in vitro results show that the scaffolds upregulate the expression of Hif‐1α and vascular endothelial growth factor, and enhance the interaction between fibroblasts and endothelial cells. The in vivo studies show a higher expression of angiogenesis related cytokines. This study demonstrates that the DFO released from hydrogel nanofibrous scaffolds of quick degradation can interfere with the required prolyl‐hydroxylases cofactors by acting as Fe 2+ chelator and upregulate the expression of Hif‐1α, leading to a significant increase of the neovascularization.
Adherence to prescribed oral medications: Understanding the barriers to optimizing hormonal therapy in breast cancer (BC)
Authors: M. Kirk, C. Hudis
Journal: Journal of Clinical Oncology (2006)

8621 Background: Several studies have demonstrated suboptimal adherence to oral anticancer agents. Understanding barriers to treatment adherence is increasingly important with the growing number of oral agents available to treat BC. Gaining insights into the attitudes and behaviors of patients (pts) with BC regarding their prescribed treatment is necessary to identify and address factors responsible for poor adherence with oral medications. Methods: To identify barriers to adherence with oral hormonal medications, a self-reported, 30-question internet survey was posted on www.y-me.org from June 30 through October 31, 2005. Results: Of the 328 survey respondents, 65.9% were diagnosed with early BC and 53.3% were postmenopausal. Of the 60% of pts with BC who had been prescribed an oral therapy, 44.6% were prescribed tamoxifen, 31.8% anastrozole, and 7.9% letrozole. 88.6% of patients indicated that their healthcare provider discussed the importance of taking oral medications as directed. Only 44.2% reported receiving instruction on the importance of taking oral medications as directed at every office visit. For 33.3%, this topic was reportedly discussed only once, prior to treatment. 83.6% of patients indicated they were taking their oral therapy as directed, but only 57.4% rated their ability to adhere to therapy (not missing a single dose) as excellent. For 35.5%, knowing that adherence may improve clinical outcome would help them take their oral medication as directed. For 24.1%, better management of treatment-related side effects would improve their adherence to therapy. Conclusions: To improve adherence, the results of this survey suggest that healthcare professionals should discuss and emphasize 1) the importance of taking oral medications as directed and 2) the impact of adherence on clinical outcomes. Greater attention to managing treatment-related side effects may further enhance adherence to therapy. [Table: see text]
Histidinol-Mediated Enhancement of the Specificity of Two Anticancer Drugs in Mice Bearing Leukemic Bone Marrow Disease<xref ref-type="fn" rid="FN2">2</xref>
Authors: R C Warrington, W D Fang
Journal: JNCI Journal of the National Cancer Institute (1985)

The possibility was investigated that L-histidinol-anticancer drug combinations may provide increased tumor cell eradication and eliminate in vivo bone marrow toxicity of proliferation-dependent anticancer agents in animals bearing an established, intrafemoral bone marrow disease. It was previously demonstrated that L-histidinol, a structural analogue of the essential amino acid L-histidine, improves the specificity of cytarabine (ara-C) and 5-fluorouracil (FUra) in DBA/2J mice bearing intraperitoneal L 1210 leukemia. Accordingly, DBA/2J mice were given iv injections of 1 X 10(6) L1210 leukemia cells 3 days before histidinol-anticancer drug treatments. During the postinjection, pretreatment interval, injected tumor cells populated the femoral marrows, shown by clonogenic assays and flow cytometric analyses. Following various drug treatments, quantitative and selective survival assays were performed of normal femoral cells and of clonogenic L1210 leukemia cells isolated from the femurs of treated mice. These experiments demonstrated that L-histidinol not only protected the marrow cell population from both ara-C and FUra, but also increased significantly the toxicities of these agents for the intrafemoral tumor cells. Thus L-histidinol mediates a substantial increase in the specificities of ara-C and FUra in mice bearing an established bone marrow leukemic condition.
Prospective screening for Lynch syndrome (LS) in a cohort of colorectal cancer (CRC) surgical patients in a community hospital.
Authors: P. R. Duncan, J. T. Lin, R. Feddersen
Journal: Journal of Clinical Oncology (2010)

1535 Background: LS is the most common hereditary form of colon cancer yet it is under-diagnosed despite well-defined clinical criteria. Screening an incident U.S. population of patients with CRC placed the proportion of CRC due to LS at 2.8% (Hampel H et al, N Engl J Med 352: 1851, 2005 and J Clin Oncol 26: 5783, 2008). Immunohistochemistry (IHC) stains for the 4 mismatch repair (MMR) proteins have shown a high sensitivity for LS identification (Shia J, J Mol Diagnostics 10: 293, 2008). We hypothesized that if only CRC patients ≤ age 60 were screened for LS by IHC, only 25% of patients would undergo testing yet 75-80% of LS would be identified. Summarized here are the results of the first 24 months of the IHC screening program for LS in a community hospital. Methods: In January 2008 a pathology reflex protocol for MMR IHC staining was initiated on all CRC ≤ age 60. The protocol was reviewed and approved by the institution's clinical practice committees. Results: From 1/01/08 through 12/31/09, 302 surgical resections for CRC were performed; 73 (24%) were in patients ≤ age 60. Eighteen of 73 (25%) showed an absence of 1 or more of the MMR proteins by IHC. Nine were deficient in MLH1 and PMS2, 8 in MSH2 and MSH6 and 1 in MSH6 alone. To date, sequence proven LS mutations have been identified in 5 (2 MLH1, 2 MSH2 and 1 MSH6), and a sixth was a previously identified Lynch family patient. A seventh had a VUS in MSH6. Three showed MLH1 methylation, 8 (44%) are pending genetic counseling or testing. Only 7 (39%) of the patients with abnormal screening results were referred for a suspicious family history and of the 6 patients with LS identified only 3 had a family history consistent with LS. Conclusions: A screening protocol for detecting LS in newly diagnosed CRC patients using MMR assessment identified LS in at least 8% of screened patients and in at least of 2.0% of all CRC resected. Clinical suspicion misses a significant proportion of patients who have LS. This protocol is a significant step forward in the timely identification of LS in a community hospital setting. No significant financial relationships to disclose.
Survival of a cohort of 25 breast cancer patients with neoplastic meningitis treated with intrathecal liposomal cytarabine
Authors: E. Le Rhun, F. Zairi, M. Baranzelli, M. Faivre-Pierret, P. Devos, J. Bonneterre
Journal: Journal of Clinical Oncology (2009)

1109 Background: Neoplastic meningitis (NM) occurs in 5% of the patients with breast cancer; if untreated the median duration of survival is 5 weeks. Combination of intrathecal (IT), systemic chemotherapy, and supportive care may increase overall survival (OS) to 5 months (Chamberlain, 2005). Methods: 30 consecutive female breast cancer patients diagnosed with NM, on the basis of cerebrospinal fluid (CSF) cytology and/or cerebrospinal MRI with clinical symptoms, have been prospectively treated for 19 months. Three patients did not receive any treatment because of a poor neurological status at diagnosis; 2 patients stopped treatment because of the lack of improvement after 1.5 months. The aim was to report clinico-pathological characteristics and OS in patients treated with IT liposomal cytarabine and supportive care with or without systemic chemotherapy. Statistical analyses were performed in the 25 treated patients. Correlations between tumor characteristics and OS were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox). Results: Median age at NM diagnosis was 56 years. Median Karnofsky Performance Status (KPS) was 75. Breast cancers were invasive ductal carcinoma in 75%. Estrogen and progesterone receptors were detected in respectively 64 and 40%. HER-2 hyperexpression was observed in 33.5%. Tumors were triple negative in 17%. At the time of NM diagnosis CSF cytology and cerebrospinal MRI were positive in respectively 64% and 87.5%. Brain metastases were present in 64% of the patients, 36% had whole brain radiotherapy. Median delay between first symptoms and diagnosis was 16 days. Median delay between NM diagnosis and first IT was 17 days. Systemic chemotherapy was given in 56.5% at the discretion of the referring oncologist. All patients had supportive care. After 5 IT a clinical stabilization or improvement was observed in 56.5%. A CSF response was observed in 36%. Median OS of treated patients was 7 months. KPS at diagnosis (≥80), neurological status after 5 IT were significantly correlated with OS. A trend was also observed between association with systemic chemotherapy and OS. Conclusions: Our results confirm that the association of IT, systemic treatment and supportive care treatment may be useful in treating this cancer complication. No significant financial relationships to disclose.
Thank You<i>JAMA Oncology</i>Authors, Peer Reviewers, and Readers
Authors: Mary L. Disis
Journal: JAMA Oncology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Clinical characteristics, univariate, and multivariate Cox model analysis of long-term (&gt; 3 years) survivors of stage IV metastatic breast cancer treated on phase II or III North Central Cancer Treatment Group (NCCTG) trials.
Authors: T. A. Patel, H. Liu, D. W. Hillman, A. C. Dueck, J. N. Ingle, V. Roy, T. J. Hobday, D. W. Northfelt, E. A. Perez
Journal: Journal of Clinical Oncology (2010)

1157 Background: In the absence of curative treatment for the majority of patients with metastatic breast cancer (MBC), the goal of therapy is focused on symptom control, improved quality of life, and prolongation of survival. Past studies have demonstrated a subset of patients that can achieve long-term survival who in general tended to be young patients with good performance status, fewer sites of metastases and smaller disease burden. An update of characteristics of long-term survivors is necessary as the MBC patient population and treatment options have changed over the last decade. Methods: We reviewed phase II and III trial data for 1,747 patients from 23 NCCTG MBC trials that enrolled patients from 1996 to 2008. We defined patients with survival beyond 3 years from the initiation of systemic treatment of breast cancer as long-term survivors (3YLTS). Univariate association between 3YLTS status and baseline demographics were performed using a t test for age and tumor size and Chi- square test for categorical covariates, with p < 0.05 used to denote statistical significance. Univariate and multivariate Cox's models were used to assess the association between overall survival time and baseline patient characteristics. Results: A total of 294 of 1,747 (16.8%) patients were 3YLTS. Multivariate Cox model demonstrated that patients with first line metastases (hazard ratio (HR) 0.65), metastasis to bone (HR 0.78) and positive ER/PR status (HR 0.58) tend to live longer. Patients with ECOG performance status of 1 or 2 (HR 1.58), >4 sites of metastatic disease (HR 2.00), liver metastasis (HR 1.30), prior radiotherapy (HR 1.55), and prior chemotherapy (HR 1.43) did worse overall. All values are statistically significant. Age did not play a statistically significant role. Conclusions: Good performance status patients with fewer metastatic sites and ER-/PR-positive tumors tend to live longer. Age was not associated with overall survival. Partial support provided by NCI (CA25244) and Breast Cancer Research Foundation. No significant financial relationships to disclose.
Illness and injury of travellers abroad: Finnish nationwide data from 2010 to 2012, with incidences in various regions of the world
Authors: H Siikamäki, P Kivelä, M Fotopoulos, J Ollgren, A Kantele
Journal: Eurosurveillance (2015)

The number of international tourist arrivals reached 1,000 million in 2012. Assessment of travellers' health problems has relied on proportionate morbidity data.Given the lack of data on number of visitors to each region, incidences have been impossible to calculate.This study, largest yet reporting travellers' health problems, is the first to present incidence of illness and injury. Data on Finnish travellers with health problems abroad during 2010 to 2012 were retrieved from the database of an assistance organisation,SOS International, covering 95% of those requiring aid abroad. The numbers were compared with those of Finnish travellers in the database of the Official Statistics of Finland. The SOS International database included 50,710 cases: infections constituted the most common health problem (60%), followed by injuries(14%), diseases of skin (5%), musculoskeletal system and connective tissue (5%), digestive tract (3%),and vascular system (2%). Gastroenteritis (23%) and respiratory infections (21%) proved the most frequent diagnoses. Overall incidence of illness or injury was high in Africa (97.9/100,000 travel days; 95% Bayesian credible interval (BCI): 53.1–145.5), southern Europe plus the eastern Mediterranean (92.3; 95% BCI: 75.4–110.1) and Asia (65.0; 95% BCI: 41.5–87.9). The data show significant differences between geographical regions, indicating the main risks and thus providing destination-specific tools for travelers' healthcare.
Time for global action on Zika virus epidemic
Authors: Daniel R Lucey
Journal: BMJ (2016)

Our response to infectious disease epidemics must be faster and smarter 

After criticism that the World Health Organization responded slowly in 2014 to Ebola virus disease, and now to the epidemic of Zika virus disease,1 on 1 February 2016 WHO’s director general, Margaret Chan, convened a meeting of the International Health Regulations Emergency Committee. After the meeting she declared Zika a public health emergency of international concern, because of the possible association with growing clusters of microcephaly and other neurological disorders in French Polynesia and Brazil. In less than a year this virus has spread to over 25 nations in the Americas, the Pacific islands, and Cape Verde in west Africa.

Faced with rapidly evolving concern among travelers, the public (particularly pregnant women and their partners), and the media, what are healthcare providers to do? Fortunately, they can provide accurate answers from several reliable sources, including Public Health England,2 the Pan American Health Organization,3 the US Centers …
tAnGo: A randomized phase III trial of gemcitabine (gem) in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy (CT) for women with early-stage breast cancer (EBC)
Authors: C. J. Poole, L. Hiller, H. C. Howard, J. A. Dunn, P. Canney, A. M. Wardley, M. J. Kennedy, R. E. Coleman, R. C. Leonard, H. M. Earl
Journal: Journal of Clinical Oncology (2008)

506 Background: After gem showed encouraging activity in advanced BC and pre-clinical evidence of a favorable interaction with paclitaxel, tAnGo was designed to evaluate, for the first time, its potential role in anthracycline and taxane containing adjuvant CT for EBC. Methods: tAnGo, an international phase III trial, compared EC-GT (4 cycles of epirubicin 90mg/m2 IV and cyclophosphamide 600mg/m2 IV day1 every (q) 3 weeks, followed by 4 cycles of paclitaxel 175mg/m2/3hour infusion day1 and gem 1,250mg/m2 IV days1 and 8 q3 weeks) with EC-T, in respect of disease-free survival (DFS) in women with invasive higher risk EBC, with definite indication for adjuvant CT. Stratification was by country, age, radiotherapy, and nodal, estrogen (ER) & HER2 status. Toxicity, dose delivery and QoL, presented at ASCO'04 and SABCS'06, showed both regimens to be safe, feasible and tolerable. We anticipated 550 DFS events at the preplanned primary endpoint efficacy analysis at 30 months (m) minimum follow-up (FU). Results: Between Aug'01-Nov'04, 3,152 patients were randomized from UK and Ireland, by 175 consultants from 127 centers; 1,576 EC-GT, 1,576 EC-T. Characteristics were balanced across treatments: 77% node positive (+ve), 55% <50 years old, 65% of tumors grade 3, 61% >2cm, 41% ER -ve, 37% PgR -ve, 26% HER2 +ve (of 909 tumors assayed). This preplanned analysis with median FU of 35m (IQR 25–38m) identified 339 deaths and 548 DFS events. No significant difference between treatments is observed in DFS (HR=1.0 [95%CI 0.8–1.2] p=0.96) or overall survival (HR=1.1 [95%CI 0.9–1.4] p=0.35). Forest plots highlighted no subset where EC-GT was more effective, including a preplanned analysis by ER/PgR. Conclusions: The addition of gem at this dose and schedule confers no therapeutic advantage over EC-T for EBC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, Eli Lilly Bristol-Myers Squibb, Eli Lilly Eli Lilly Bristol-Myers Squibb, Eli Lilly
Combination systemic chemotherapy and precision transarterial chemoembolization of metastatic liver tumors with drug eluting beads
Authors: R. C. Martin, C. R. Scoggins, C. Tatum
Journal: Journal of Clinical Oncology (2008)

15573 Background: To assess safety and efficacy of Irinotecan and Doxorubicin loaded beads (DC Bead) delivered by trans-arterial embolization for the treatment of unresectable metastatic cancer to the liver. Methods: This open-label, single center, single arm study included 18 patients with metastatic disease to the liver (Breast n=4, Lung n=4, Esophageal n=3, Kidney n=2, Thyroid n=2, Sarcoma n=1, Cholangiocarcinoma n=2) most who had failed first line therapy. Patients received repeat embolizations with either Irinotecan loaded beads (max 100mg per embolization) or Doxorubicin loaded beads (max 150mg per embolization) pre treating physician's discretion. Chemotherapy was loaded in DC Bead of 100–300μm or 300–500μm. Patients also received simultaneous systemic chemotherapy with DC Bead therapy during the off week of patient chemotherapy cycle. Results: All patients received planned dosing as either an outpatient or 23 hour observation. Bilirubin, γ-GT, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Irinotecan bead injection lead to a greater peri-procedural pain, which was effectively managed with pre-arterial lidocaine injection. There have been no adverse severe procedure- related complications. Post Embolization Syndrome (PES) was observed in only a small (5%) all patients. Combined systemic therapy with DC Bead was well tolerated, without any significant differences in peri-procedural laboratory values or tolerance to therapy. Overall, objective response using modified RECIST criteria was 95% at 3months, and 92% at 6 months. Conclusions: Chemoembolization using either Irinotecan or Doxorubicin loaded DC Bead was safe and effective in the treatment of metastatic tumors to the liver as demonstrated by a minimal complication rate and robust tumor response. Further larger studies are needed to confirm this data, and establish where hepatic arterial precision chemotherapy should be utilized in the algorithm of the metastatic tumors to the liver. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Angiodynamics Biocompatibles
Retinoid regulation of antiviral innate immunity in hepatocytes
Authors: Noell E. Cho, Bo‐Ram Bang, Purnima Gurung, Meng Li, Dahn L. Clemens, T. Michael Underhill, Laura P. James, Jenifer R. Chase, Takeshi Saito
Journal: Hepatology (2015)

Persistent infection of hepatitis C virus (HCV) is one of the leading causes of end‐stage liver disease (ESLD), such as decompensated cirrhosis and liver cancer. Of particular note, nearly half of HCV‐infected people in the United States are reported to be heavy drinkers. This particular group of patients is known to rapidly progress to the ESLD. Although accelerated disease progression among alcohol abusers infected with HCV is clinically well recognized, the molecular pathophysiology behind this manifestation has not been well elucidated. Hepatocytes metabolize ethanol (EtOH) primarily through two steps of oxidative catabolism in which alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play central roles. The ADH‐ALDH pathway also governs the metabolism of retinol (vitamin A) to its transcriptionally active metabolite, retinoic acid (RA). In this study, we defined that the ADH‐ALDH pathway serves as a potent antiviral host factor in hepatocytes, which regulates the expression of interferon (IFN)‐stimulated genes (ISGs) by biogenesis of RA. ISGs constitute over 300 antiviral effectors, which cooperatively govern intracellular antiviral innate immunity. Our study revealed that intracellular RA levels greatly influence ISG expression under basal conditions. Moreover, RA augments ISG induction in response to viral infection or exposure to IFN in a gene‐specific manner. Lastly, our results demonstrated that EtOH attenuates the antiviral function of the ADH‐ALDH pathway, which suggests the possibility that EtOH‐retinol metabolic competition is one of the molecular mechanisms for the synergism between HCV and alcohol abuse in liver disease progression. Conclusions: RA plays a critical role in the regulation of intracellular antiviral innate immunity in hepatocytes. (H epatology 2016;63:1783‐1795)