tbuckley/cabot-search huggingface dataset:
Prediction of Response to Salvage Radiation Therapy in Patients With Prostate Cancer Recurrence After Radical Prostatectomy
Authors: Angelos K. Leventis, Shahrokh F. Shariat, Michael W. Kattan, E. Brian Butler, Thomas M. Wheeler, Kevin M. Slawin
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To identify factors predictive of local recurrence as defined by a complete response to salvage radiation therapy in patients whose disease recurs after radical prostatectomy. PATIENTS AND METHODS: Ninety-five patients with recurrence after radical prostatectomy who were evaluated by prostatic fossa biopsies, and a subset of 49 of these patients treated with radiation for control of presumed or biopsy-proven local recurrence, were studied. RESULTS: Biopsies were positive in 40 (42%) of the 95 biopsied patients. Multivariate analysis revealed that prebiopsy prostate-specific antigen (PSA) level, postrecurrence PSA doubling time, and positive digital rectal examination (DRE) of the prostatic fossa were all statistically significant predictors of a positive biopsy. For the 49 patients subsequently treated with salvage radiation therapy, the overall actuarial 3- and 5-year PSA relapse-free probabilities were 43% and 24%, respectively. Univariate analysis showed no differences in the PSA relapse-free probabilities associated with any pathologic features of the radical prostatectomy specimen, biopsy confirmation of local recurrence, or DRE of the prostatic fossa. In multivariate analysis, controlling for all other variables, preradiation PSA and postrecurrence PSA doubling time measured before radiation were the only statistically significant predictors of outcome. CONCLUSION: DRE of the prostatic fossa, prebiopsy PSA, and postrecurrence PSA doubling time predict which patients will have biopsy-proven local recurrence. However, response to salvage radiation therapy is associated with postrecurrence PSA doubling time and with preradiation PSA level only. DRE of the prostatic fossa and biopsy confirmation of local recurrence are not associated with salvage radiation outcome.
Phase II Trial of erlotinib (OSI-774) in patients with hepatocellular or biliary cancer
Authors: P. A. Philip, M. Mahoney, J. Thomas, H. Pitot, R. Donehower, G. Kim, J. Picus, T. Fitch, S. Geyer, C. Erlichman
Journal: Journal of Clinical Oncology (2004)

4025 Background: The overexperession of the epidermal growth factor receptor (EGFR) and its ligand is frequently seen in hepatobiliary tumors and may be associated with worse prognosis. Erlotinib (Tarceva) is a receptor tyrosine kinase inhibitor with specificity to the EGFR. Methods: The primary objective of this study was to determine the proportion of patients with either biliary cancer (BILI) or hepatocellular cancer (HCC) who were progression-free at 6 months. A potential benefit was assumed if the proportion of patients who are progression-free at 24 weeks was at least 20%. Thirty-five evaluable patients were targated for each diagnostic category. Patients were not selected on the basis of EGFR expression but tumor samples were submitted for EGFR analysis from all patients. Tarceva was given continuously at a dose of 150 mg per day orally. Dose adjustments were performed for toxicity. Objective response assessment was undertaken every 8 weeks and treatment continued until disease progression and/or undue toxicity. Results: Thirty-nine and 35 patients with BILI and HCC were enrolled, respectively. Median age of patients was 67 and 70 for the BILI and HCC groups, respectively. Median number of cycles (=4 weeks of treatment) was two in both groups. Fewer patients had toxicity-related dose reductions in the BILI group. Greater grade 3/4 skin toxicity and diarrhea was encountered in the HCC group. Of the 36 evaluable patients with BILI, 7 (25%, 95% CI, 10, 38%), were progression-free at 6 months. Seven (35%, 95% CI 18, 52%) of the 20 evaluable patients with HCC were progression free at 6 months. Two and three patients had partial radiological response in the BILI and HCC groups, respectively. Median time to response was 58 days and 214 days for BILI and HCC groups, respectively. Duration of response for the BILI group was 3 and 12+ months. Response duration for patients with HCC was 3, 4+, 7+ months. All responding patients had skin rash. Conclusions: Preliminary results suggest a benefit for EGFR blockade with tarceva in patients with hepatobiliary cancers with acceptable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pharmaceuticals Roche Phamaceuticals
Effect of Acrylonitrile on Primary Syrian Golden Hamster Embryo Cells in Culture: Transformation and DNA Fragmentation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R A Parent, B C Casto
Journal: JNCI Journal of the National Cancer Institute (1979)

Application of acrylonitrile to primary Syrian golden hamster embryo cells (HEC) in culture produced foci of morphologically transformed cells. When similar cells were pretreated with simian adenovirus (SA7) and subsequently treated with acrylonitrile, up to an 8.9-fold increase in frequency of virus-transformed foci was noted over frequency noted for cultures treated only with SA7. When [3H]thymidine-labeled primary Syrian golden HEC were treated with acrylonitrile and cellular DNA was subsequently subjected to alkaline sucrose gradients, a shift in the sedimentation pattern reminiscent of that observed for chemical carcinogens was noted. These observations added support to recent studies indicating that acrylonitrile may be carcinogenic.
Ofatumumab and Lenalidomide for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia: Correlation between Responses and Immune Characteristics
Authors: Candida Vitale, Lorenzo Falchi, Elisa ten Hacken, Hui Gao, Hila Shaim, Katrien Van Roosbroeck, George Calin, Susan O'Brien, Stefan Faderl, Xuemei Wang, William G. Wierda, Katayoun Rezvani, James M. Reuben, Jan A. Burger, Michael J. Keating, Alessandra Ferrajoli
Journal: Clinical Cancer Research (2016)

Abstract Purpose: We evaluated efficacy and tolerability of the combination of ofatumumab and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), and explored whether immune system characteristics could influence the response to treatment. Experimental Design: Thirty-four patients were enrolled in this phase II study. Ofatumumab was administered at a dose of 300 mg on day 1, 1,000 mg on days 8, 15, and 22 during course 1, 1,000 mg on day 1 during courses 3–6, and once every other course during courses 7–24 (28-day courses). Oral lenalidomide (10 mg daily) was started on day 9 and continued for as long as a clinical benefit was observed. Results: The overall response rate was 71%. Eight patients (24%) achieved a complete remission (CR) or CR with incomplete recovery of blood counts, including 9% with minimal residual disease-negative CR. The median progression-free survival was 16 months, and the estimated 5-year survival was 53%. The most common treatment-related toxicity was neutropenia (grade &amp;gt;2 in 18% of the 574 patient courses). The most frequent infectious complications were pneumonia and neutropenic fever (24% and 9% of patients, respectively). We observed that patients who achieved a CR had at baseline higher numbers and a better preserved function of T cells and natural killer cells compared with non-responders. Conclusions: The combination of ofatumumab and lenalidomide is a well-tolerated regimen that induces durable responses in the majority of patients with relapsed/refractory CLL. Our correlative data suggest a role of competent immune system in supporting the efficacy of this treatment. Clin Cancer Res; 22(10); 2359–67. ©2016 AACR.
BRCA mutations: An Appalachian experience
Authors: M. A. Mirza, A. Sehbai, T. Nestor, V. Brown, J. Abraham
Journal: Journal of Clinical Oncology (2006)

20111 Background: BRCA1 and 2 mutations are rare in general population and women with these mutations confer a significantly increased risk of invasive breast and ovarian cancer (65% to 85%, and 15% to 65% cumulative lifetime risk, respectively). A few of these are variant mutations also known as Variant of unknown significance (VUS). Methods: Observational study of 155 patients who presented to MBRCC, WVU for genetic counseling between November 2001 and March 2005. Patients underwent genetic testing after detailed genetic counseling. Clinical data, such as patient’s age, ethnic origin, follow up period, Myriad risk of mutation, clinical outcome i.e., Mastectomy versus Bilateral Salpingo-oophorectomy versus Surveillance, total numbers of patients screened, tested and reason for not testing, and other data, were available for statistical analysis. Results: In out patient population who underwent genetic counseling, 46% (71 out of 155) underwent genetic testing. A large number of patients (54%; 84 out of 155) who underwent genetic counseling could not undergo the genetic testing. Total number of patients not genetically tested were 84, out of which, 27 were low risk, 35 had insurance denial, 7 were not interested, 14 were awaiting results or insurance approval and 1 was deceased. 27 out of 71 patients (38%) who underwent genetic testing were positive for a mutation. Among these patients (n = 27), 8 had BRCA 1; 3 had BRCA1 VUS; 7 had BRCA 2 and 9 had BRCA2 VUS. The average age for patients who had a genetic mutation was 42 years. The most prevalent genetic mutation in our study population was BRCA2 VUS (33%; 9 out of 27) followed by BRCA 1 mutation (29%; 8 out of 27). 11 out of 27 (40%) who had a mutation underwent mastectomy. 13 out of 27 patients (48%) who had a mutation underwent bilateral salpingo-oophorectomy. 7 out of 27 patients (26%) who had a mutation underwent total abdominal hysterectomy. 4 out of 27 patients (15%) who had a germline mutation were lost to followup. Conclusion: We report the prevalence and the clinical outcomes in patients with BRCA mutations in the state of West Virginia, which is comparable to the national database. High number of patients could not undergo genetic testing because of insurance denial. No significant financial relationships to disclose.
Abstract 18780: Down-regulation of BMPR2 in Pulmonary Hypertension Secondary to Lung Fibrosis
Authors: Ning-Yuan Chen, Tingting Weng, Luis J Garcia Morales, Harry Karmouty Quintana
Journal: Circulation (2014)

Pulmonary Hypertension (PH) is a disorder affecting the vasculature of the lung. A highly prevalent form of PH is that associated with underlying chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). However, little is known about the mechanisms that drive the development of PH secondary to chronic lung diseases. Loss of function mutations in bone morphogenic protein receptor (BMPR) 2 have been strongly linked to familial and non-familial cases of pulmonary arterial hypertension (PAH). In PAH, loss of function BMPR2 mutations lead to pronounced vascular remodeling and increased responsiveness of vascular smooth muscle cells to the pro-fibrotic cytokine, transforming growth factor (TGF)-β. In addition, the loss of BMPR2 function in vascular smooth muscle cells abrogates the anti-proliferative effects of BMP ligands by altering downstream Smad signaling pathways. Our hypothesis is that BMPR2 is down-regulated in PH secondary to lung fibrosis. Usin...
HLA contributes to immune control of hepatitis B in HIV-positive African adults
Authors: Philippa Matthews, Apostolos Beloukas, Amna Malik, Jonathan Carlson, Pieter Jooste, Anthony Ogwu, Roger Shapiro, Lynn Riddell, Fabian Chen, Graz Luzzi, Manjeetha Jaggernath, Gerald Jesuthasan, Katie Jeffery, Thumbi Ndung'u, Philip Goulder, Anna Maria Geretti, Paul Klenerman
Journal: Journal of Infection (2015)
A prospective phase I/II trial of capecitabine with escalating mitomycin C and oxaliplatin in patients with advanced or metastatic esophageal carcinoma
Authors: O. Nehls, B. Klump, F. Kreth, D. Schick, U. Koppenhöfer, U. M. Lauer, M. Gregor, M. Bitzer
Journal: Journal of Clinical Oncology (2008)

15555 Background: In preclinical studies, mitomycin C (MMC) was found to upregulate thymidine phophorylase thereby enhancing cytotoxic activity of capecitabine. Moreover, capecitabine shows promising activity in combination with oxaliplatin in patients with esophageal cancer. Therefore, we conducted a prospective phase I/II trial of the combination of capecitabine, MMC, and oxaliplatin in patients with unresectable advanced esophageal carcinoma. Methods: Capecitabine (2,000 mg/m2, bid, d1–14) and oxaliplatin (100 mg/m2, q3 weeks) were kept constant while MMC was escalated: 6–10 mg/m2, q 6 weeks. Results: 25 pts (3 F, 22 M) received 171 cycles (median 7). Median age was 64 years (41–70). Dose-limiting toxicities were grade 4 thrombocytopenia or grade 4 neutropenia. No patients died from adverse events related drug toxicity. The maximal tolerable dose (MTD) for MMC was 6 mg/m2, q6 weeks. Partial response was seen in 10/25 pts (40%), stable disease in 11/25 pts (44%) and progressive disease in 4/25 pts (16%). Median progression-free survival was 8.9 months (95% CI, 6.2–11.6), and median overall survival was 13.3 months (95% CI, 10.8–15.8). Conclusion: The triple regimen of capecitabine, MMC and oxaliplatin is well tolerated and shows substantial clinical activity in unresectable esophageal carcinoma. The high survival rates suggest the need for prospective randomized studies of this treatment strategy. Updated results will be presented. No significant financial relationships to disclose.
Optimization of sentinel lymph nodes with interstitial magnet resonance lymphography using thermo-resoponsive magnetic nanoparticles in rats
Authors: Kunihiko Hiraiwa, Masakazu Ueda, Yuko Kitagawa, Hiroya Takeuchi, Takashi Ando, Tomoyuki Irino, Takahisa Yoshikawa, Masaki Kitajima
Journal: Cancer Research (2007)

4744   Background  Recent studies have shown the potential of magnetic resonance imaging (MRI) with interstitial administration of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO), although SPIO and USPIO were not retained in sentinel lymph nodes (SLNs). The ideal SLN imaging agent needs to be small enough to enter the lymphatic vessels, yet large enough to be retained in the SLNs.  Our hypothesis is that newly developed intelligent thermo-responsive magnetic nanoparticles (Therma-Max®) are small enough to enter the lymphatic vessels, flocculate according to body temperature, and become large enough to be retained in the SLNs. And that they are useful for SLN mapping with MRI. In this study, we investigated the capability of MRI using thermo-responsive magnetic nanoparticles for optimization of SLNs.  Materials and methods  In study 1, three types of magnetic nanoparticles were examined; the thermo-responsive magnetic nanoparticles flocculating at 36 °C, those flocculating at 42 °C, and the magnetic nanoparticles which were not coated with thermo-responsive polymers. All these three nanoparticles were around 100 nm in diameter. The injection sites, the SLNs, and the distant lymph nodes were resected after these nanoparticles were injected into the subserosa of cecum in rats.  In study 2, pre- and postcontrast MRI were obtained following subdermal injection of thermo-responsive magnetic nanoparticles flocculating at 42 °C into the chest wall in rats.  Results  In study 1, histological evaluation revealed that the magnetic nanoparticles flocculating at 36 °C were observed only at the injection site, because they flocculated according to body temperature and did not migrate to SLNs. The magnetic nanopaticles flocculating at 42 °C were found both at the injection site and at the SLNs, but not at the distant lymph nodes. They flocculated and became large enough to be retained in the SLNs. The magnetic nanoparticles which were not coated with thermo-responsive polymers were found at all of the injection site, the SLNs and the distant lymph nodes.  In study 2, MRI showed that the signal-to-noise ratio in axillary SLNs was significantly lower than that found on precontrast images at 20 minutes after injection of thermo-responsive magnetic nanoparticles flocculating at 42 °C (P   Conclusion  >The present study showed that thermo-responsive magnetic nanoparticles could target sentinel lymph nodes by adjusting the temperature at which they flocculate. And that they could be used as an contrast agent for SLN mapping with MRI.
Abstract 18933: Regulation of Impaired Angiogenesis in Diabetes by Microrna26a
Authors: Basak Icli, Christoph Nabzdyk, Jorge Lujan Hernandez, Megan Cahi, Dennis Orgill, Mark Feinberg
Journal: Circulation (2014)

Wound healing is a physiological reparative response to injury that involves hemostasis, cellular migration, proliferation, angiogenesis, extracellular matrix deposition, wound contraction and re-epithelialization. However, patients with type 2 diabetes mellitus (T2D) are frequently afflicted with impaired wound healing that progresses into chronic wounds or diabetic ulcers, and may lead to complications including limb amputation. In recent years, microRNAs (miRNAs) has been implicated in a wide-range of disease states. We have investigated the potential role of microRNA-26a (miR-26a) in a diabetic model of wound healing. Expression of miR-26a is rapidly induced in response to diabetic stimuli (e.g. high glucose, PKC activation) in endothelial cells (ECs). Punch skin biopsy wounding of db/db mice revealed increased expression of miR-26a (~2-fold) four days post wounding compared to that of WT mice. Local administration of a miR-26a inhibitor, LNA-anti-miR-26a, induced angiogenesis (up to 80%), increased granulation tissue thickness (by 2.5 fold) and accelerated wound closure (by 50% after nine days) compared to scrambled anti-miR controls using a db/db mouse model of diabetes. These effects were independent of altered M1/M2 macrophage ratios. Mechanistically, inhibition of miR-26a increased its target gene, SMAD1, both at the mRNA and protein levels in ECs. In addition, increased SMAD1 levels correlated with increased ID1, a downstream modulator or SMAD1, and decreased expression of the cell cycle inhibitor p27 nine days post-wounding of diabetic mice. Interestingly, inhibition of miR-26a increased migration and growth of both human microvascular ECs (HMVECs), human umbilical endothelial cells (HUVECs), and fibroblasts under normal glucose conditions. However, in the presence of high glucose, anti-miR-26a functional effects were abolished in fibroblasts, but not in HUVECs or HMVECs, suggesting cell-specific miR-26a regulated effects under diabetic conditions. These findings establish miR-26a as an important regulator on the progression of skin wounds of diabetic mice by specifically regulating the angiogenic response after injury, and demonstrate that neutralization of miR-26a may serve as a novel approach for therapy.
Using the MD Anderson Symptom Inventory (MDASI) to assess symptom burden and interference: Interim results of an open-label study of darbepoetin Alfa 200 mcg every 2 weeks (Q2W) for the treatment of chemotherapy-induced anemia (CIA)
Authors: C. Cleeland, J. Crawford, D. Lubeck, D. Tomita
Journal: Journal of Clinical Oncology (2004)

8065 Background: Cancer patients (pts) receiving chemotherapy experience symptoms related to both their disease and its treatment, including CIA. The MDASI is a list of 19 questions that focus on both core symptoms and symptom interference with life activities (Cleeland et al, 2000). Methods: This fully enrolled, ongoing, 26 week, multicenter, open-label, community-based study (N = 2423) was designed to prospectively assess the relationship between hemoglobin (Hb) and changes in symptom burden in pts with CIA receiving darbepoetin alfa (DA). Eligibility criteria included concurrent multicycle chemotherapy for nonmyeloid malignancies and Hb ≤11 g/dL. DA was administered at 200 mcg Q2W. Hb was measured Q2W and the MDASI administered weekly. This interim analysis includes data through week 17 for 1053 pts who completed 16 weeks of study treatment. Results: The mean (SD) baseline (BL) Hb was 10.1 (0.8) g/dL. The Kaplan-Meier percentage (95% CL) of pts with a hematopoietic response was 72% (70, 74) after 16 weeks. Exploratory analyses of the MDASI items have been performed and indicate the impact of treatment on the severity of symptoms. For example, the percent of pts with MDASI scores indicating moderate to severe symptom burden (score ≥ 4 where 10 = maximum burden) at baseline and after 16 weeks are presented (Table). Conclusion: DA treatment is associated with significant improvement in a breadth of symptoms for pts with moderate to severe burden as measured by the MDASI. This study provides additional support that DA 200 mcg Q2W is both well tolerated and efficacious in improving symptoms in pts with CIA. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen; Merck Amgen Amgen Amgen
The emergence of "boutique medicine"
Authors: Uwe E Reinhardt
Journal: BMJ (2003)

From BMJ USA 2002;August:468 

The January 26, 2002 issue of the BMJ featured a news report by a Florida doctor, Fred Charatan, raising concerns about the emergence in the US of “boutique medicine,” ie, practices that offer premium service for patients willing to pay large fees (http://www.bmj.com/cgi/content/full/324/7331/187/a). This generated a letter to the editor of the BMJ by Uwe Reinhardt, a professor of economics at Princeton University, which in turn set off an exchange of Rapid Responses (see http://www.bmj.com/cgi/content/full/324/7331/187/a). Among the entries in that exchange was the following (abridged)—EDITOR

Physicians pursue a variety of objectives, among which income quite legitimately ranks high. In the economist's book, there is nothing wrong with the pursuit of income. Furthermore, economists believe that persons who have accumulated the human capital that physicians have ought to earn commensurately high incomes.

The problem is that an informal etiquette …