tbuckley/cabot-search huggingface dataset:
Clinical and Pharmacologic Study of the Epirubicin and Paclitaxel Combination in Women With Metastatic Breast Cancer
Authors: Giacomo Grasselli, Lucia Viganò, Giuseppe Capri, Alberta Locatelli, Emiliana Tarenzi, Carlo Spreafico, Alexia Bertuzzi, Antonio Giani, Carlo Materazzo, Sara Cresta, Antonella Perotti, P. Valagussa, Luca Gianni
Journal: Journal of Clinical Oncology (2001)

PURPOSE: A pharmacokinetic interaction may cause increased cardiotoxicity of paclitaxel (PTX) and high cumulative dose of doxorubicin. We tested antitumor activity, tolerability, and pharmacokinetics of the lesser cardiotoxic epirubicin (EPI) and PTX (ET combination). PATIENTS AND METHODS: Twenty-seven women with untreated metastatic breast cancer, median age of 56 years, and prominent visceral involvement (74%) were studied. Three-weekly EPI (90 mg/m 2 ) and PTX (200 mg/m 2 over 3 hours) were given for a maximum nine cycles. EPI was administered 24 hours before PTX (E → T) in cycle 1, and 15 minutes before PTX (ET) thereafter. EPI, epirubicinol (EOL), EPI-glucuronide (EPI-glu), EOL-glucuronide (EOL-glu), PTX, and 6α-OH-PTX were measured in plasma and urine in 14 women. RESULTS: Patients received 205 cycles of ET and a median EPI dose of 720 mg/m 2 . Grade 4 neutropenia (49% of cycles) was the most frequent toxicity. Cardiac contractility was decreased in five patients. Mild congestive heart failure occurred in two (7.4%). Response rate was 76% (28% complete). Median overall survival was 29 months. On the basis of intrapatient comparison in the first 24 hours of E → T and ET cycles, PTX did not affect EPI disposition, but significantly increased plasma exposure to EOL (by 137%), EPI-glu (threefold) and EOL-glu (twofold). Urinary excretion of EPI dose went from 8.2% in E → T to 11.8% in ET cycles. Clearance of PTX was 30% slower in ET than E → T. ET cycles caused lower neutrophil nadir than E → T (644 ± 327 v 195 ± 91, P &lt; .05) CONCLUSION: ET is feasible, devoid of excessive cardiac toxicity, and active. A reciprocal pharmacokinetic interference between the two drugs has pharmacodynamic consequences, and suggests a direct effect of PTX on EPI metabolism requiring ad hoc investigation.
Effect of expansile paclitaxel-loaded nanoparticles on growth of lung cancer in vivo
Authors: J. Walpole, A. Griset, A. Gaffey, M. W. Grinstaff, Y. Colson
Journal: Journal of Clinical Oncology (2008)

7593 Background: Surgical resection remains the most effective treatment for patients with non-small cell lung cancer; however, even in early stage diagnoses the presence of occult microscopic disease at the surgical resection margin significantly impacts long-term patient survival. Thus, the focus of this study is to establish proof of concept that locoregional growth of microscopic tumor burden can be prevented through the application of a novel “expansile” nanoparticle drug delivery system. Methods: Biocompatible polymer nanoparticles that enter tumor cells and swell 300 fold in response to pH were loaded with paclitaxel (Pax-NP) and assessed for efficacy against murine Lewis lung carcinoma (LLC) cells using cell viability assays in vitro and tumor implantation in vivo. Paclitaxel-loaded non-expansile nanoparticles (Pax-neNP) that are not sensitive to pH variation were also produced. For the in vivo studies, 7.5 x 105 LLC tumor cells were co-injected with 0.25 mg unloaded control (expansile) NP, Pax-NP, Pax-neNP or paclitaxel alone in 100μL Cremophor EL/ethanol (each equivalent to a 2.5 μg dose of paclitaxel) subcutaneously in C57Bl/6 mice. Results: In vitro assays demonstrated that co-culture of LLC cells and Pax-NP results in significant inhibition of tumor growth (p<0.01, t-test vs control). In contrast, LLC incubated with unloaded NP did not inhibit tumor growth. Moreover, Pax-NP prevented tumor growth in vivo. Whereas LLC alone (n=11) or LLC with 0.25mg unloaded NP (n=14) or Pax-neNP (n=12) resulted in the development of tumors with volumes of 388±86, 382±82 and 268±63 mm3, respectively (mean ± SE), only one mouse (n=15) developed a small tumor (2±2 mm3) following the injection of LLC and Pax-NP (p<0.05 via ANOVA). Further, injection with an equivalent dose of paclitaxel did not significantly reduce tumor growth (225±95, n=6). Conclusions: These results establish that locoregional growth of microscopic tumor burden can be inhibited by intracellular nanoparticle-mediated drug delivery. These early results suggest that Pax-NP, which undergo cellular uptake with resultant drug release, may afford enhanced local drug delivery aimed at preventing the growth of occult microscopic disease present at the resection margin following parenchyma-sparing surgery for lung cancer. No significant financial relationships to disclose.
Carotid artery intima-media thickness (CIMT) in pediatric and young adult survivors of Hodgkin’s disease (HD)
Authors: K. Kelly, M. A. Weiner, D. Hughes, T. Rundek, K. Cheung, M. Elkind
Journal: Journal of Clinical Oncology (2005)

8516 Background: Long-term survivors of HD are at increased risk of death from coronary artery disease and stroke. Ultrasound measures of CIMT are a valid measure of atherosclerosis and are associated with an increased risk of future vascular disease. Methods: We compared CIMT in 20 HD survivors (14 male, 6 female, mean age 23 yrs) and 8 sibling controls (1 male, 7 female, mean age 25 yrs). 9/20 patients (pts) had “B” symptoms. All pts were in a continuous CR for a mean of 104 months, range 62–241 months. 19/20 pts received chemotherapy (CT), all 19 received doxorubicin. 11 pts received radiotherapy (RT) to bilateral neck, the field in 10/11 included the mediastinum. 8/11 had low dose RT (21–25 Gy), 3/11 had standard dose (36 Gy). CIMT was assessed using a standardized scanning and reading protocol. The CIMT was calculated as the mean of the maximum measurement at 12 sites: near and far walls of the common carotid, bifurcation, and internal carotid arteries bilaterally. Mean CIMT was analyzed by t-test and a linear mixed model was used to assess the effects of HD on CIMT after adjusting for other covariates including age, gender, race, cholesterol, smoking, blood pressure (BP) and C-reactive protein (CRP). Results: Mean CIMT was higher in HD pts than controls, 0.78 mm and 0.71 mm respectively, p=0.003. Analysis of matched sibling pairs confirmed this difference, p=0.002. The difference in CIMT was independent of age, gender, race, cholesterol, smoking, BP, and CRP. Among the HD patients, higher CIMT values were positively associated with increasing age, cholesterol, LDL-C, and diastolic BP. “B” symptoms and RT were not significantly associated with CIMT, although values were higher in the 3/11 pts who received 36 Gy. Conclusion: History of HD is associated with increased CIMT even in pts treated with CT alone. HD survivors had a CIMT of 0.78 mm, a value found in healthy individuals at age 65 suggesting the “vascular age” of the HD pts to be 25 years older than their chronological age. CIMT may be a useful risk screening tool of early cardiovascular disease in pediatric and young adult survivors of HD. No significant financial relationships to disclose.
Treatment of meningeal leukemia.
Authors: J V Simone
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.5.357 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6726292 Treatment of meningeal leukemia. J V SimonexJ V SimoneSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.5.357 PDF "Treatment of meningeal leukemia.." Journal of Clinical Oncology, 2(5), pp. 357–358© 1984 by American Society of Clinical Oncology
Clinical relevance of neutral endopeptidase overexpression in melanoma
Authors: M. Yancovitz, E. Velazquez, P. Christos, A. Pavlick, R. Berman, R. Shapiro, N. Bhardwaj, D. Nanus, D. Polsky, I. Osman
Journal: Journal of Clinical Oncology (2006)

8028 Background: Neutral Endopeptidase (NEP/CD10) is a cell surface peptidase expressed in a variety of normal and neoplastic tissue. Both loss of and overexpression of NEP have been reported in different types of tumors. Defining the role of NEP in the clinical progression of melanoma is particularly relevant given the availability of NEP inhibitors. Our aim was to determine if NEP expression correlated with clinicopathological parameters and survival. We also investigated the upregulation of NEP transcription as a possible mechanism of NEP overexpression. Methods: Eighty-four patients who were prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group database at the New York University School of Medicine were studied. Ninety-three specimens from the 84 patients were examined for NEP protein expression using an immunohistochemical assay, including 33 primary melanoma (thickness &lt;1mm, N=15; 1–4mm, N=15; &gt;4mm, N=3) and 60 metastatic melanoma specimens. NEP overexpression was defined as either moderate or diffuse. NEP transcript expression was assessed using Affymetrix U133Plus2.0 GeneChips in 37 metastatic melanoma cases. NEP transcript upregulation was defined as &gt;2 fold increase compared to NEP transcript expression in normal lymph node tissue. Results: A statistically significant difference was observed between NEP overexpression in primary [1/33 (3%)] versus metastatic disease [18/60 (30%)] (Fisher’s exact test, p=0.002). In addition, there was a statistically observed association between NEP transcript upregulation and NEP protein overexpression (p=0.002). Among patients with metastatic disease, median survival time was shorter for patients who overexpressed NEP compared to those who had normal NEP expression (10.2 yrs. versus 12.7 yrs., respectively); however this difference was not statistically significant (p=0.74 by log-rank test). Conclusions: Our data support a role for increased NEP expression in the progression of melanoma to metastatic disease. Functional studies are needed to better understand the role of NEP upregulation in melanoma pathogenesis and progression and to determine if there is a role for NEP inhibitors in the treatment of melanoma. No significant financial relationships to disclose.
Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Hong Sun, David W Dodick, Stephen Silberstein, Peter J Goadsby, Uwe Reuter, Messoud Ashina, Joel Saper, Roger Cady, Yun Chon, Julie Dietrich, Robert Lenz
Journal: The Lancet Neurology (2016)
Junk reporting
Authors: Des Spence
Journal: BMJ (2007)

Lady Heroin's remorseless hunt continues. A young man dies from endocarditis in the baking heat of the ward, his family sobbing, silhouetted in the orange sunset of a psychedelic hospital curtain shroud. Other wounded beasts sweat, tremble, and vomit in withdrawal but, denied opiate substitution, pull out their lines and run off without their deep vein thromboses being treated. Countless victims of heroin roll into casualty—cyanotic, cold, and close to death or dead. We save the ones we can with naloxone, but they simply retreat to the wilderness of the housing estates. I stood by as the safari passed on.

And on the savannah of general practice, male and female patients have turned to selling their bodies on the streets. Others maintain their dignity by shoplifting, stealing cars, or breaking into houses. Hepatitis B and C are rampant. Their children are caged and taken into social work captivity in ever increasing numbers. But this vast dark continent of problems is also somehow tragically attractive: it is full of documentary producers and charities. 

In another unforgiving terrain the National Treatment Agency is under attack. Its representatives have been dragged into a dimly lit studio and given a hiding by the red top gang—hoodie reporters high on the fumes of a good story. Even “liberal,” politically correct BBC Radio 4 types have revelled in the attacks, perhaps seeing them as retribution for some car radio stolen long ago. The blunt instrument used to bludgeon the agency is the claim that, despite a budget increase of 50% over two years, only 3% of “junkies” who are treated become free of drugs. The crude inference—the usual tabloid subplot—is that treatment is a pointless waste of public money if users don't become drug free.

But opiate substitution is pragmatic harm reduction, not a “cure.” It enables drug users to sleep, to butter a piece of toast for their kids, and collect them from school. It frees them from stealing or prostitution, from injecting into their groins in a cold stairwell, from the torture of self loathing. Treatment lets users function as “normal” people again. They may not be free from methadone for many years, but that's not the point. Until we invest in the infrastructure to mend society's broken sense of community, the National Treatment Agency needs us to support it rather than standing by passively watching an ill informed media kicking.
Immune Response to Avian Leukosis Virus Determined by the Cell-Mediated Focus-Reduction (CEMFOR) Assay2
Authors: Raymond W. Loan, R. Stephen Whiteaker
Journal: JNCI Journal of the National Cancer Institute (1986)

A cell-mediated focus-reduction (CEMFOR) assay was used to determine the sequential development of cell-mediated immunity to avian oncornaviruses and the nature of the cells participating in this immune reaction. Peripheral blood leukocytes of Leghorn chickens that had regressed Rous sarcoma virus-induced tumors or were immune to avian leukosis virus had CEMFOR activity. The response was biphasic early in the infection. Peripheral blood leukocytes from nonimmune chickens or viremic, immunologically tolerant chickens did not have CEMFOR activity. Sera from leukosis virus-immune chickens blocked CEMFOR activity. The early CEMFOR response was mediated by T-cells. The late response was mediated by an adherent cell population possibly augmented by the presence of T-cells.
Factors Associated With Point-of-Care Treatment Decisions for Hidradenitis Suppurativa
Authors: Amit Garg, Justin Besen, Aaron Legler, Christina S. Lam
Journal: JAMA Dermatology (2016)

Studies evaluating factors associated with disease severity in hidradenitis suppurativa (HS) are limited, and the existing data are controversial. It is also unclear whether severity assessed by HS scoring methods correlate with partnered decision-making on treatment strategies, and thus the clinical relevance of these severity assessments is unknown.To assess factors associated with disease severity as measured by point-of-care decisions on receipt or escalation of treatment for HS.The retrospective cohort comprised 437 patients with HS ages 18 to 64 years at enrollment with at least 5 monitoring periods of 3 months' duration. The study was performed at an academic medical center.Receipt of treatment and treatment escalation.The average monitoring time of patients with HS was 4.2 person-years. The frequency of patients with HS with no treatment decreased over the monitoring period, while the frequency for receipt of treatment increased. Care by a dermatologist (odds ratio [OR], 6.7; 95% CI, 5.2-8.6) provided the strongest predictor of having received treatment for HS, and it was also associated with increased odds of escalating treatment (OR, 3.0; 95% CI, 2.4-3.7). Tobacco smoking was associated with treatment escalation (OR, 1.4; 95% CI, 1.1-1.7) over time, whereas obesity was not associated with treatment or escalation. The likelihood of receiving (OR, 1.4; 95% CI, 1.2-1.8) or escalating treatment (OR, 1.2; 95% CI, 1.0-1.4) was increased between ages 18 and 39 years. Male sex was not associated with treatment escalation.Clinician type, tobacco smoking, and age may be important clinical factors that patients and clinicians may consider in developing partnered short- and long-term treatment strategies. Obesity and sex do not seem to influence treatment decisions for HS.
만성 B형 간염 환자에서 자발성 급성 악화의 원인 및 임상 경과
Authors: 채명종 ( Myung Jong Chae ), 김병호 ( Byung Ho Kim ), 정경환 ( Kyung Hwan Jeong ), 김남훈 ( Nam Hoon Kim ), 동석호 ( Seok Ho Dong ), 김효종 ( Hyo Jong Kim ), 장영운 ( Young Woon Chang ), 이정일 ( Joung Il Lee ), 장린 ( Rin Chang )
Journal: Clinical and Molecular Hepatology (2004)

목적: 저자 등은 만성 B형 간염 경과 중 급성 악화가 심하게 발생한 환자에서 그 원인을 조사하고, 자발적 악화시 HBeAg 혈청전환 및 임상 경과에 대하여 알아보고자 하였다. 대상과 방법: 1992년 1월부터 2001년 12월까지 만성 B형 간염의 급성 악화로 입원하였던 환자를 대상으로 하였다. 중증 급성 악화의 정의는 AST/ALT가 정상 상한치의 10배 이상 증가한 경우로 하였다. 후향적으로 의무기록을 조사하여 성별, 연령, 원인, 간기능검사, 혈청학적 검사 및 생존 등에 대하여 성별 및 연령이 유사한 대조 환자군과 비교 분석하였다. 결과: 중증 급성 악화 환자는 남자 29명, 여자 15명 등 44명으로 평균 38.6±0.1세였다. 급성 악화 원인으로는 자발적 악화가 34예(77%), 약물 복용 7예(16%), 음주 2예(5%), HCV 중복감염 1예(2%)였다. 혈액검사에서 총 빌리루빈은 8.3±8.3 ㎎/dL, 알부민 3.6±0.7 g/dL, ALT 924±597 IU/L, 프로트롬빈 시간 1.58±1.29 (INR), α PF 108±163 ng/mL이었다. 자발적 급성 악화 34예 중 HBeAg 양성인 경우는 27예(79%)였으며, 추적 기간(579±459일) 동안 51.9%에서 HBeAg 혈청전환이 일어났으나, 3개월째 혈청전환율은 15%에 불과하였으며, 12개월 및 24개월째는 각각 18.5%, 48.1%였다. 한편 ALT가 199 IU/L 이하인 대조 환자의 경우는 같은 기간의 혈청전환율이 각각 4.3%, 10.9%로 낮았으며, 기저 ALT치에 따른 누적 혈청전환율도 200 IU/L을 중심으로 유의한 차이가 있었다(P<0.05). 간경변으로의 진행은 대조 환자군에 비하여 높은 경향을 보였으며(17.6% vs. 5.5%, P<0.08), 사망한 경우는 급성 악화군에서만 1예(2%) 있었다. 결론: 만성 B형 간염 환자 중 중증의 급성 악화는 자발적 악화가 가장 흔하였으며, 약 반수에서 2년내 HBeAg 혈청전환되었고 18% 정도에서 간경변으로 진행되었다. 그러나 3개월 이내의 조기 혈청전환은 15%로 낮았으며, 전반적인 혈청전환율도 외국의 보고에 비하여 다소 낮았다.
Respiratory Paralysis in Poliomyelitis
Authors: M AGERHOLM
Journal: BMJ (1953)

RESPIRATORY PARALYSIS IN POLIOMYELITIS.Ill the published accounts of poliomyelitis epidemics, comparatively little attention has been focussed on the part played by the mechanical respirator in the treatment of respiratory paralysis.Our experience of it in Shieldhall Fever Hospital may therefore be of interest.Of 36 cases of poliomyelitis received in Shieldhall Hospital between 11th August and 10th October, 1947, of which 24 showed paralysis, four patients required treatment in the respirator.The type in use here was the Both modification of the Drinker apparatus, with which the staff was already familiar.CASE SUMMARIES.CASE 1. J. M., male, 6 years, admitted 27tli August, on 7tli day of illness.Gravely ill, semiconscious, face grey, respirations shallow and varying between 30 and 80 per minute.Pulse 146, temp.10<!.2?.Left facial paralysis : unable to swallow.Nuchal rigidity and Kernig+ve.Cerebrospinal fluid at increased pressure.Cells 30, Pandy+ve.Put into respirator and given penicillin 50,000 units four-hourly.30tli August: very much better, temperature and pulse-rate normal, lip move- ments indicating attempts at speech.Still cannot swallow.31st August: further improvement.Able to utter sounds.Later in day could ask for a drink.1st September : removed from respirator.Breathing normally and able to swallow
구연 : 만성 B형간염바이러스 감염자에게 중복 감염된 급성 A형간염의 임상상
Authors: 전병준, 김인희, 이석, 고강석, 이상연, 이윤재, 남상우, 김상욱, 이승옥, 이수택, 김대곤, 김성훈
Journal: Clinical and Molecular Hepatology (2009)
Sequential therapy with methotrexate and 5-fluorouracil in the treatment of advanced colorectal carcinoma.
Authors: B A Leone, A Romero, M G Rabinovich, J E Perez, M Macchiavelli, E Strauss
Journal: Journal of Clinical Oncology (1986)

Twenty-nine patients with advanced colorectal carcinoma were entered in this study to evaluate the efficacy and toxicity of a sequential chemotherapeutic schedule with methotrexate (MTX), 200 mg/m2 intravenously (IV) (push injection) and 5-fluorouracil (5-FU), 1,200 mg/m2 in continuous IV infusion, using a 20-hour time interval. All patients received calcium leucovorin (LV), 25 mg, intramuscularly (IM) every six hours for eight doses beginning 24 hours after methotrexate administration. Courses were administered every 15 days. Of the 24 patients evaluable for response, 11 (46%) had major objective regressions (one complete remission [CR] and ten partial remissions [PR]). The survival rate of patients who responded to treatment was 60% at 16 months, whereas patients with no change and those in whom the disease progressed had a median survival of 9 months and 3 months, respectively. The median duration of response has not yet been reached in patients who presented objective tumor regression, and was 7.5 months in those with no change. Significant differences were found between objective regression and no change (P less than .0005) and between no change and tumor progression (P less than .05). All patients were evaluable for toxicity. There were three toxic-related deaths (10%) because of severe myelosuppresion, sepsis, and hemorrhage. These promising results, despite important toxicity, reveal the synergism between the two chemotherapeutic agents and also indicate that the response rate achieved could be a consequence of the 20-hour interval and high dose of 5-FU. Further studies are necessary to determine the optimal time interval and the adequate 5-FU dose.
Long-term follow-up assessment of a HER-2/neu peptide (E75) vaccine for the prevention of recurrence in high-risk prostate cancer patients
Authors: J. D. Gates, L. C. Benavides, M. G. Carmichael, J. P. Holmes, M. T. Hueman, E. A. Mittendorf, D. G. McLeod, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2008)

3067 Background: E75 is an immunogenic peptide from the HER2/neu protein that is expressed in prostate cancer. High-risk prostate cancer (HRPC) patients demonstrating various levels of HER2/neu expression were vaccinated with E75 peptide + GM-CSF to prevent post-prostatectomy prostate-specific antigen (PSA) and clinical recurrences. Methods: 40 HRPC patients were prospectively identified using the validated Center for Prostate Disease Research (CPDR)/CaPSURE high-risk equation and enrolled. HLA-A2+ patients (n=21) were vaccinated (V), and HLA-A2- patients (n=19) were followed as clinical controls (C). HER2/neu over-expressors (OE) were defined as IHC 3+ and low-expressors (LE) as IHC 0–2+. All patients were assessed for clinico-pathologic factors, PSA recurrence (≥0.2ng/ml), clinical recurrence and survival. Results: Comparing the V and C groups, there were no statistical differences in clinico-pathologic factors; however, the V group had larger tumors (≥T3b-T3c: 35% vs. 18%), higher postop Gleason scores (8–9: 33% vs. 26%), more positive margins (71% vs. 53%), and higher HER2/neu expression (OE: 35% vs. 19%). At a median follow-up of 58.2 (18.8–62.7) months, the PSA recurrence rate was not different between V (28%) and C (26%) groups. Median time to recurrence from enrollment was 8.5 (2–50) vs. 4 (1–23) months (p=0.3), respectively. However, 3 V patients had PSA recurrences during the vaccine series. If these patients were excluded, the median time to recurrence for the V group extends to 36 (13–50) months. Studywide, only one clinical recurrence and death occurred in a V patient that was early in the vaccine series. Subset analysis comparing V recurrent patients to C recurrences noted no statistical differences; however, V patients who recurred had larger tumors (≥T3b-T3c: 67% vs. 40%), higher postop Gleason scores (8–9: 67% vs. 40%), more positive margins (83% vs. 40%), higher CPDR scores (very high risk: 83% vs. 60%), and higher HER2/neu expression (OE: 50% vs. 0%). Conclusions: The HER2/neu (E75) vaccine may prevent or delay recurrences in HRPC patients if completed prior to PSA recurrence. A larger randomized Phase II trial will be required to confirm these findings. No significant financial relationships to disclose.
Evaluation Of The Novel, Orally Bioavailable Selective Inhibitor Of Nuclear Export (SINE) Verdinexor (KPT-335) In Spontaneous Canine Cancer: Results Of Phase I and Phase II Clinical Trials
Authors: Cheryl London, Luis feo Bernabe, Sandra Barnard, William Kisseberth, Antonella Borgatti, Michael Henson, Heather Wilson, Kiersten Jensen, Daisuke Ito, Jaime Modiano, Misty Bear, Michael Pennell, Jean-Richard Saint-Martin, Dilara McCauley, Sharon Shacham, Michael Kauffman
Journal: Blood (2013)