tbuckley/cabot-search huggingface dataset:
Periodontal Pathogens, Serum Lipids, and Lipid Peroxidation in a Population-Based Sample
Authors: Tiejian Wu, Maurizio Trevisan, Karen L Falkner, Sara G Grossi, Alex Ho, Robert J Genco
Journal: Circulation (2001)

P33 Epidemiological studies have demonstrated a significant link between periodontal disease (PD) and increased risk of cardiovascular disease (CVD). This study was conducted to evaluate if lipid metabolism and peroxidation may represent potential pathways linking PD to CVD. The study sample included 747 randomly selected residents of Erie and Niagara counties of New York who had 6 or more teeth and no history of heart attack. Periodontal assessments included pocket depth (POD) and attachment loss (ATL). Periodontitis was defined by 2+ teeth with ATL≥6mm and 1+ teeth with POD≥5mm. Subgingival plaque was sampled and tested using immunofluorescence microscopic technique for the presence of four putative periodontal pathogens: Bacteriodes forsythus (BF), Porphyromouas gingivilis (PG), Prevotella intermedia (PI), and Campyglobacter recta (CR). Fasting blood sample was obtained and determinations of total and LDL cholesterol, triglycerides, and plasma thiobarbituric acid reacting substance (TBARS) were performed. In the sample as a whole, prevalence of specific bacteria in the subgingival plaque were 29.6% for BF, 8.3% for PG, 31.6% for PI, and 4.4% for CR. As expected, prevalence was much higher in participants with periodontitis. Presence of BF and CR (but not PI and PG) was associated significantly with higher levels of LDL cholesterol (Mean LDL cholesterol (mg/dl), 151.3 for BF + and 142.8 for BF -, p&lt;0.05; and 158.4 for CR + and 144.7 for CR -, p&lt;0.05). Presence of PG and CR (but not BF and PI) was significantly associated with higher TBARS (Mean TBARS (nmol/ml), 1.51 for PG + and 1.38 for PG -, p&lt;0.05; and 1.57 for CR + and 1.38 for CR -, p&lt;0.05). These associations remained statistically significant after adjustment by sex, age, education, body mass index, diabetes status, smoking and alcohol use. No significant association with bacteria was found for total cholesterol and triglycerides. In conclusion, subgingival presence of specific periodontal bacteria (bf, pg, and cr) was associated with higher serum LDL cholesterol and/or plasma TBARS. This suggests that lipid alteration and peroxidation may represent potential pathways in the link between PD and CVD.
Confidence in knowledge discussing fertility changes with cancer treatment
Authors: C. M. Duffy, S. M. Allen
Journal: Journal of Clinical Oncology (2009)

e20540 Purpose: Infertility can be a devastating side effect of cancer treatment in younger women, but approximately one third of young women fail to recall a discussion of such issues with their oncologist prior to cancer treatment. Oncologists may not discuss these issues because they lack confidence in their knowledge of treatment-associated fertility issues and fertility preserving options. We sought to determine oncologists’ confidence in their knowledge of fertility issues and the factors associated with greater confidence. Methods: A national sample of MedOnc, HemOnc, RadOnc, and GynOnc physicians was randomly drawn from the AMA Master File. Mailed recruitment letters provided a link to an on-line survey of fertility issues in cancer treatment. Only practicing oncologists who reported treating &gt; 5 women/yr aged 21–45 were eligible to participate. Physicians were asked 8 questions regarding their confidence in knowledge of fertility changes with cancer treatments and fertility-sparing options. Responses on a 5pt likert scale ranged from 1=not at all confident to 5= very confident and a summary scale was created from participants’ answers. Multiple linear regression was conducted to determine the socio-demographic characteristics, practice settings and attitudes regarding discussing fertility issues that were associated with confidence in knowledge scores. Results: 336/1702 eligible participants responded (20%). Avg years in practice was 15.7, mean age was 48.5 and 75.2% were male. A majority were community-based (60%). Average score on confidence in knowledge scale was 2.9 (SD 0.80) with Cronbach α= 0.84. Higher confidence in knowledge scores were associated with Gyn-Onc sub-specialty, access to educational resources regarding fertility and cancer, and greater sense of responsibility to discuss fertility preservation options (p&lt;.001). Age, sex, and practice setting were not associated with confidence in knowledge. Conclusions: This is the first nationally representative survey regarding confidence in knowledge among oncologists regarding fertility and female cancer treatments. Whether confidence in knowledge is a cause or result of resource access and sense of responsibility to discuss fertility issues should be explored in future research. No significant financial relationships to disclose.
Fabrication of 3D scaffolds reproducing intestinal epithelium topography by high-resolution 3D stereolithography
Authors: Justine Creff, Rémi Courson, Thomas Mangeat, Julie Foncy, Sandrine Souleille, C. Thibault, Arnaud Besson, Laurent Malaquin
Journal: Biomaterials (2019)

The small intestine is a complex tissue with a crypt/villus architecture and high tissue polarity. Maintenance of tissue integrity and function is supported by a constant renewal of the epithelium, with proliferative cells located in the crypts and differentiated cells migrating upward to the top of villi. So far, most in vitro studies have been limited to 2D surfaces or 3D organoid cultures that do not fully recapitulate the tissue 3D architecture, microenvironment and cell compartmentalization found in vivo. Here, we report the development of a 3D model that reproduces more faithfully the architecture of the intestinal epithelium in vitro. We developed a new fabrication process combining a photopolymerizable hydrogel that supports the growth of intestinal cell lines with high-resolution stereolithography 3D printing. This approach offers the possibility to create artificial 3D scaffolds matching the dimensions and architecture of mouse intestinal crypts and villi. We demonstrate that these 3D culture models support the growth and differentiation of Caco-2 cells for 3 weeks. These models may constitute a complementary approach to organoid cultures to study intestinal homeostasis by allowing guided self-organization and controlled differentiation, as well as for in vitro drug screening and testing.
The Tumor Microenvironment Innately Modulates Cancer Progression
Authors: Dominique C. Hinshaw, Lalita A. Shevde
Journal: Cancer Research (2019)

Cancer development and progression occurs in concert with alterations in the surrounding stroma. Cancer cells can functionally sculpt their microenvironment through the secretion of various cytokines, chemokines, and other factors. This results in a reprogramming of the surrounding cells, enabling them to play a determinative role in tumor survival and progression. Immune cells are important constituents of the tumor stroma and critically take part in this process. Growing evidence suggests that the innate immune cells (macrophages, neutrophils, dendritic cells, innate lymphoid cells, myeloid-derived suppressor cells, and natural killer cells) as well as adaptive immune cells (T cells and B cells) contribute to tumor progression when present in the tumor microenvironment (TME). Cross-talk between cancer cells and the proximal immune cells ultimately results in an environment that fosters tumor growth and metastasis. Understanding the nature of this dialog will allow for improved therapeutics that simultaneously target multiple components of the TME, increasing the likelihood of favorable patient outcomes.
Matt Morgan: Hospital doctors should step outside
Authors: Matt Morgan
Journal: BMJ (2019)

Last year I did something I found difficult, unsettling, and risky. Yet, in many ways, it was a simple act that community health workers do every day. It didn’t involve a complex procedure or a new treatment. I even wore a pair of jeans while I did it.

Last year I stepped into the home of a patient I’d cared for while he was critically ill many years before. I left the safe neon confines of “my” hospital and entered “his” softly lit world of home. I was the visitor, the guest in his life rather than he in mine. That experience changed me. It was …
The influence of genetic polymorphisms in drug metabolism enzymes and transporters on the pharmacokinetics of different fluvastatin formulations
Authors: Qian Xiang, Weidang Wu, Nan Zhao, Chuan Li, Junyu Xu, Lingyue Ma, Xiaodan Zhang, Qiufen Xie, Zhuo Zhang, Jiancheng Wang, Weiren Xu, Xia Zhao, Yimin Cui
Journal: Asian Journal of Pharmaceutical Sciences (2019)

The purpose of the present study was to investigate the impact of genetic polymorphism on fluvastatin pharmacokinetics. In addition, we compared the fluvastatin pharmacokinetics differences between extended-release (ER) 80 mg tablet and immediate-release (IR) 40 mg capsule in terms of drug metabolism enzyme and transporter genetic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study (n = 24), effects of ABCG2, SLCO1B1, ABCB1, CYP2C9 and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed. The administration dosage for IR 40 mg and ER 80 mg were twice and once daily, respectively, for total 7 d. Blood samples for pharmacokinetic evaluation were taken on the 1st and 7th d. The lower exposure following ER was observed. For ER tablets, SLCO1B1 T521C genotype correlated with AUC0-24 of repeat doses (P = 0.010). SLCO1B1 T521C genotype had no statistically significant effect on AUC0-24 of IR capsule of fluvastatin after single or repeated doses. In vitro study demonstrated that when the concentration of fluvastatin was low (< 1 µmol/l), the uptake of fluvastatin in the HEK293-OATP1B1 with SLCO1B1 521TT (Km =0.18 µmol/l) was faster than that with SLCO1B1 521CC (Km =0.49 µmol/l), On the other hand, when concentration reached to higher level (> 1 µmol/l), transport velocity of fluvastatin by HEK293-OATP1B1 with SLCO1B1 521TT (Km = 11.4 µmol/l) and with SLCO1B1 521TCC (Km =15.1 µmol/l) tend to be the same. It suggests that the increased effect of SLCO1B1 T521C genotype on ER formulation of fluvastatin was mainly caused by lower blood concentrations. We recommend that formulation should be incorporated into future pharmacogenomics studies.
Dose-dense pemetrexed (P) and gemcitabine (G) as neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC)
Authors: G. Bepler, L. Robinson, E. Sommers, A. Sharma, C. Williams, A. Chiappori, E. Haura, G. Simon, S. Antonia, T. Tanvetyanon
Journal: Journal of Clinical Oncology (2006)

7129 Background: Adjuvant chemotherapy is standard of care for NSCLC stage IB-III after complete resection. Neoadjuvant therapy has potential advantages. P and G are efficacious in NSCLC with low toxicity. In combination, they can be given dose-dense, which may result in better efficacy, lower toxicity, and higher patient acceptability than traditional platinum-based therapy. Methods: Patients with resectable IB-IIIA and selected IIIB, PS 0–1, w/o prior therapy were eligible. CT, PET, brain MRI, and mediastinoscopy were used for staging. P (500 mg/m 2 ) and G (1,500 mg/m 2 ) were given on d1, 15, 29, and 43. Imaging studies were repeated 7–14 days after treatment and response determined by RECIST. Patients had surgery 3–4 weeks after the last treatment. F/U was every 3 months for 2 years with imaging studies. The primary clinical endpoint is radiographic disease response rate. The secondary endpoints are overall and disease-free survival, pathologic response rate, treatment-related toxicity, and surgical respectability and outcome Results: From 4/04 to 12/05, 45 eligible patients were enrolled. The disease stages were IB in 17, IIA in 3, IIB in 10, IIIA in 12, and IIIB in 3 patient. 8 had adeno, 15 squamous, and 22 large cell or unspecified NSCLC on initial diagnosis. 27 had a PS of 0 and 18 PS 1. 3/45 had weight loss. 22 were women. The median age was 67 (range 42–83 years). 2 were never-smokers, 24 had quit, and 19 were active smokers. Disease response rates to PG were 3% CR, 34% PR, 55% SD, and 8% PD. An R0 resection was performed in 75% of patients, 15% had an incomplete resection, and 10% did not have a thoracotomy. There have been no deaths or unexpected morbidities related to surgery or chemotherapy. Conclusions: Dose-dense PG is well tolerated with acceptable side effects. It appears to be equally as efficacious as platinum-containing chemotherapy doublets in terms of radiographic response rates. Survival rates and the median survival time are forthcoming to allow for a better comparison of this regimen with platinum-containing doublets. No significant financial relationships to disclose.
Introduction of a tobacco-screening initiative for those at risk for bladder cancer in a high volume urology clinic.
Authors: Jeffrey C. Bassett, John L. Gore, William J. McCarthy, Christopher Morrison, Lorna Kwan, Carol J. Bennett, Michael S. Cookson, David F. Penson, Christopher Saigal
Journal: Journal of Clinical Oncology (2013)

4540 Background: Tobacco use is causal or contributory in 50% of bladder cancer diagnoses. Continued use after diagnosis may negatively impact recurrence, progression, and mortality. Despite its relevance, tobacco screening was infrequently occurring in a regional urology clinic. We hypothesized that the clinic was fertile ground for a tobacco-screening initiative given the number of referrals for bladder cancer, hematuria, and other tobacco-related urologic conditions. Methods: An EMR-based tobacco-screening prompt was designed using the same informatics architecture and clinical reporting system used in primary care. The prompt was introduced for all new patient encounters beginning January 2010. We prospectively collected the proportion of patients asked about tobacco use, advised to quit, and assisted with smoking cessation. Results: For the two years ending December 2011, 4,617 patients were seen in urologic consultation; 31% (n = 1,444) were referred for tobacco-related urologic diagnoses, 36% (n = 518) of whom were referred for bladder cancer or hematuria. The tobacco-screening prompt was used 57% (n = 2,626) of the time. Attending physicians utilized the template in 17% of their encounters, resident physicians in 71%, and nurse practitioners in 97% (p &lt; 0.001). 49% (n = 255) of those referred for bladder cancer or hematuria were screened for tobacco use. Active smokers comprised 21% (n = 558) of screened patients. Relative to former and never smokers, active smokers were more likely referred for bladder cancer or hematuria (p = 0.005). 40% (n = 225) of active smokers desired to quit. Those counseled by an attending physician were more likely ready to quit and trended toward a more intensive cessation program (p = 0.004 and p = 0.07, respectively). Conclusions: Our data suggest that urology clinics may be important sites for tobacco-screening initiatives, particularly for those with tobacco-related urologic diagnoses. Screening patients referred for bladder cancer or hematuria is likely high yield due to the increased proportion of active smokers. Given the disparate utilization of the prompt, identification of provider-level facilitators and barriers to tobacco screening is worthy of study.
Alveolar macrophages generate a noncanonical NRF2-driven transcriptional response <i>to Mycobacterium tuberculosis</i> in vivo
Authors: Alissa C. Rothchild, Gregory S. Olson, Johannes Nemeth, Lynn M. Amon, Dat Mai, Elizabeth S. Gold, Alan H. Diercks, Alan Aderem
Journal: Science Immunology (2019)

Induction of an NRF2-dependent cell-protective signature impairs alveolar macrophages from controlling M.tb. infection in vivo.
Effect of denosumab on bone mineral density (BMD) in women with breast cancer (BC) and men with prostate cancer (PC) undergoing hormone ablation therapy
Authors: M. R. Smith, G. Ellis, F. Saad, T. Tammela, H. Bone, B. Egerdie, C. Ke, S. Jun, R. Dansey, C. Goessl
Journal: Journal of Clinical Oncology (2009)

9520 Background: Hormone ablation therapies, including adjuvant aromatase inhibitor (AI) therapy and androgen deprivation therapy (ADT), improve recurrence-free survival in patients (pts) with BC and PC, respectively. However, these treatments increase bone resorption, leading to bone loss and fractures. RANKL is a key mediator of osteoclast-mediated bone resorption. In this 24 month (mo) comparison, we investigated the effects of denosumab, a fully human monoclonal antibody against RANKL, on preserving BMD across both populations. Methods: Two trials were conducted: a 24-mo BC study and a 36-mo PC study. Postmenopausal women with low BMD receiving AI therapy for nonmetastatic BC and men receiving ADT for nonmetastatic PC (with low BMD or history of osteoporotic fracture if &lt; 70 yrs) were randomized to receive placebo or denosumab 60mg subcutaneously every 6 mos. All pts in both studies were prescribed calcium and vitamin D supplements. The primary endpoint was % change from baseline in lumbar spine (LS) BMD at 12 mos for the BC study and at 24 mos for the PC study. Herein, we present changes in BMD at 24 mos at LS, total hip (TH), and 1/3 radius from both studies. Power calculations were based on enrollment of at least 208 patients in the BC study (for primary endpoint only) and 1226 in the PC study (for primary and key secondary endpoints). The actual numbers randomized were 252 and 1468, respectively. Results: Denosumab increased BMD of the LS, TH, and 1/3 radius compared with placebo at 24 mos in both pt populations ( Table ). In both studies, differences between denosumab and placebo at each skeletal site were consistent, and the effects of denosumab were statistically significantly different from placebo as early as 1 month at the LS in both studies. The overall safety profile was similar to placebo in each study. Conclusions: Denosumab consistently increased BMD at all 3 skeletal sites compared with placebo in both women with BC undergoing AI therapy and in men with PC undergoing ADT. [Table: see text] [Table: see text]
Characterization of health care resource utilization and costs in women with metastatic breast cancer in Medicaid.
Authors: Zhixiao Wang, Xuan Li, Claudio Faria
Journal: Journal of Clinical Oncology (2012)

e16521 Background: The costs of treating patients with metastatic breast cancer (mBC) have been examined in several studies, but there is very limited information regarding healthcare resource utilization (HCRU) and costs of mBC among Medicaid beneficiaries. The objective of this study was to characterize HCRU and costs in Medicaid among women with mBC. Methods: Women with mBC who were younger than 65 were identified using Thomson Reuters’ Medicaid claims data from 12-13 states (2005-2009). Overall HCRU and medical costs were estimated in those patients and compared to breast cancer (BC) patients without metastasis identified in the same population. Index date is the date of BC (or mBC) diagnosis and patients were followed to the date of disenrollment or the end of the study period, whichever occurred first. Mean (95% CI) cumulative healthcare costs were estimated using Kaplan-Meier Sample Average method. Results: 4,745 patients were included in the analysis. Among them, 3,767 were BC patients without metastasis and 978 with mBC. During an average of 14 months of follow up time, mBC patients on average incurred 1.56 hospital admissions, 9.01 inpatient days, and 1.97 emergency room (ER) visits, 25.54 physician office visits, 21.43 hospital outpatient visits, and 40.96 prescriptions. The total medical cost averaged at $63,068 (95% CI: $59,504, $66,624) per mBC patient, of which 33.0% were hospitalization costs, followed by hospital outpatient cost (27.4%) and physician office visit cost (14.8%). The average follow up time for BC patients was 18 months, during which BC patients on average incurred 0.69 hospital admissions, 3.79 inpatient days, 1.96 ER visits, 19.96 physician office visits, 12.27 hospital outpatient visits, and 40.89 prescriptions, and the total cost averaged at $29,776 (95% CI: $28,795, $30,762). Major cost drivers by type of service are similar to mBC. Conclusions: Overall HCRU and costs are substantially higher in mBC patients compared to BC patients of earlier stages in the Medicaid population, and the major cost drivers are similar in mBC and BC. Continuous Medicaid coverage is essential for BC/mBC patients in financial disadvantage to have access to quality medical care.
Pilot study on antitumor efficacy of intravenously applied synergistic combinations of salicylic acids in patients with advanced solid tumors.
Authors: Joachim Drevs, Holger Spangenberger, Matthias Jenny, Jonas Mueller-Huebenthal, Izumi Kamijo, Werner Kreutz
Journal: Journal of Clinical Oncology (2012)

e13508 Background: Due to chronic hypoxia cancer cells are growing in a more acidic environment compared to physiological tissue. Using this differentiation a new therapy method has been developed for targeted chemotherapy. Recent preclinical in vitro and in vivo data have shown direct pH-sensitive anti-tumor activity by pore formation and apoptosis when synergistically acting combinations of diflunisal, paraaminosalicylic acid (PAS) and aspirin were applied. Therefore, a pilot study was performed to evaluate its clinical relevance. Methods: A total of 30 patients (n=30) with advanced solid tumors and the lack of standard treatments were treated with a protocol consisting of 3-5 weeks with 2 daily i.v. infusions of diflunisal and aspirin for 4 days per week after they had signed an informed consent form. Response evaluation was assessed by PET/CT differentiating in metabolic and metric (RECIST) response. Results: Out of 30 patients treated 4 patients suffered from colorectal cancer, 11 from breast cancer, 2 from ovarian cancer, 2 from lung cancer, 2 from gastric cancer, 2 from glioblastoma, 1 from CUP, 1 from hemangioendothelioma, 1 from pleuramesothelioma, 1 from non-Hodgkin lymphoma, 1 from pancreatic cancer, 1 from choledochus cancer, 1 from prostate cancer, respectively. Side effects related to the therapy have been fatigue (6,7%), nausea (13,3%), tinnitus (10%), hypertension (6,7%), dyspnea (3,3%) and burning sensation in tumor areas (3,3%). Out of 30 patients treated, until today 14 were evaluable for metric response, 12 for metabolic and 13 for tumor marker response assessment. For tumor marker follow up 2 patientis (6,7 %) had a CR, 6 (20 %) a PR, 4 (13,3 %) a SD of &gt; 3 month and 1 (3,3 %) a PD. For metric follow up 0 patients (0 %) had a CR, 6 (20 %) a PR, 5 (16,7 %) a SD of &gt; 3 month and 3 (10 %) a PD. For metabolic follow up 1 patients (3,3 %) had a CR, 3 (10 %) a PR, 5 (16,7 %) a SD of &gt; 3 month and 3 (10 %) a PD. Conclusions: This pilot study confirms a direct pH-sensitive synergistic anti-tumor activity of intravenous salicylic acids in patients with advanced solid tumors. Therefore, a further evaluation in a controlled clinical phase II study will be performed.