tbuckley/cabot-search huggingface dataset:
Effect of methylnaltrexone inhibition of the mu opioid receptor on Lewis lung carcinoma proliferation, invasion, and angiogenesis.
Authors: B. Mathew, F. E. Lennon, J. Siegler, L. Gerhold, N. Mambetsariev, L. Moreno-Vinasco, J. G. Garcia, R. Salgia, J. Moss, P. A. Singleton
Journal: Journal of Clinical Oncology (2010)

e13597 Background: Expression of the mu opioid receptor (MOR) is increased in patients with non-small cell lung cancer (NSCLC), a disease with poor prognosis and limited therapies. In this study, we investigated MOR as a potential therapeutic target for lung carcinoma. Methods: Lewis lung carcinoma (LLC) cells were treated with MOR siRNA or the peripheral MOR antagonist, methylnaltrexone (MNTX, 250 nM) and in vitro functional (cell proliferation and invasion) and biochemical studies (immunoblotting) were then conducted. For in vivo assays, C57BL/6J mice were injected intravenously with dual color (GFP-RFP labeled) LLC cells, with or without MOR siRNA treatment. In another experiment, MOR knockout as well as wildtype control mice were injected with LLC cells and followed for 12 weeks. In a parallel experiment, LLC tumor bearing C57BL/6J mice received continuous infusion of MNTX (10 mg/kg/day) for 2 weeks. Tumor growth and lung metastasis were evaluated using tumor volume measurements and/or in vivo fluorescent microscopy (Olympus OV-100). In vivo angiogenesis was measured with subcutaneously implanted Matrigel plugs containing 20 ng VEGF with or without 100 nM MNTX. Results: Our data indicate that LLC cells have ∼5 fold increased expression of MOR. Inhibition of MOR with siRNA or MNTX treatment reduced in vitro LLC proliferation (90%) and invasion (50-75%). In vivo lung metastasis was reduced by ∼75% in wildtype C57BL/6J mice with LLC lacking MOR (siRNA) versus control siRNA-treated LLC (3 weeks post-i.v. injection, quantitated with OV-100). In addition, primary LLC tumor volume was substantially reduced (>90%) in MOR knockout mice compared to wildtype mice (flank injection). We observed that continuous infusion of MNTX (10 mg/kg/day) in mice with pre-existing LLC primary tumors attenuates further tumor growth. Finally, Matrigel plugs with MNTX had ∼45% less in vivo angiogenesis versus control (no MNTX) Matrigel plugs. Conclusions: Our data demonstrate that MOR is a potential therapeutic target for inhibition of LLC proliferation, invasion, and angiogenesis. Further study of MNTX as a potential therapeutic agent is warranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Progenics
Efficacy of recent chemotherapy regimen in advanced small bowel carcinoma
Authors: T. Aparicio, L. Costes, V. Moulin, C. Locher, A. Bidault, T. Lecomte, E. Mitry, J. Taieb, B. Landi, D. Malka
Journal: Journal of Clinical Oncology (2007)

15112 Background: Small bowel carcinoma (SBC) is a rare tumour. Very few data concerning the chemotherapy efficacy are published. The overall survivals previously reported were 8 to 14 months. The aim of the study was to evaluate the efficacy of recent chemotherapy regimen in advanced SBC. Methods: All the consecutive patients treated recently by first line chemotherapy for advanced SBC were included retrospectively in a multicentric study. Clinical and radiological evaluations were performed every 2 or 3 months according to WHO criteria. Chemotherapy was stopped in case of progression, severe toxicity or patient willing. Results: Fifty seven patients (33 men, 24 women), median age 56 years [32–83] treated from 1994 to 2006 in 10 institutions were included. Primary tumours were: duodenum n=35 (61%), jejunum n=14 (25%) and ileum n=8 (14%). Three patients had Crohn disease and one HNPCC syndrome. The tumour were locally advanced in 6 patients (10%), or with metastasis in 51 (90%), synchronous n=35 or metachronous n=16. The mains metastasis sites were peritoneal carcinomatosis in 29, liver in 19 and nodes in 13 patients. Sixteen patients have had an initial R0 surgery and 8 had received, before inclusion, adjuvant chemotherapy. The regimens used in first line were: FOLFOX n=21 (37%), LV5FU2-cisplatine n=13 (23%), LV5FU2 n=12 (21%), FOLFIRI n=10 (17%). Twenty five (44%) patients have had grade 3 or 4 toxicity. A toxic death occurred after a cure of FOLFOX. Chemotherapy was stopped in relation to toxicity in 7 (12%) patients. A dose reduction was done in 15 (26%) patients for a total of 16% of the cures. Tumor was measurable in 42 (73%) pts. A partial response was observed in 13 patients (31%), stabilisation in 14 (33%) and progression in 15 (36%). Thirty six (63%) pts had a second line chemotherapy. Time to treatment failure was 6 [1–21] months in all patients and 7 [2–19], 7 [2–20], 5 [1–21] and 4 [1–10] months according to treatment by FOLFOX, LV5FU2, FOLFIRI or LV5FU2-cisplatine respectively. Overall survival was 11 months [1–36]. Overall survival according to the primary localization were: duodenum: 9 [1–34], jejunum: 18 [3–32], ileum: 15 [4- 36]. Conclusions: Advanced SBC have a bad prognosis. The chemotherapy regimen used in colon cancer did not reach the same efficacy in SBC. No significant financial relationships to disclose.
6FDG PET scan evaluation of suspicious breast lesions developing after breast conservation therapy for breast cancer
Authors: C. G. Hargon, G. Burton, B. Li, F. Ampil, D. Lillian
Journal: Journal of Clinical Oncology (2004)

612 Background: Breast Conservation Therapy (BCT) for early breast cancer is an effective option in selected patients with primary breast cancer. Mammographic evaluation of breast abnormalities developing after BCT can be difficult. Positron Emission Tomography (PET) is a valuable imaging tool in oncology. We investigated the efficacy of PET imaging in predicting the nature of suspicious breast changes following BCT. Methods: All patients with prior BCT with suspicious mammographic or breast examination findings necessitating biopsy evaluation were offered participation. After signed informed consent, PET imaging was performed using F-18 FDG General Electric PET scanner. Breast biopsy was obtained following the PET scan. Pathologic findings were correlated with the PET findings. Results: 33 patients were enrolled in the study between 6/1997 and 11/2003 with 31 patients completing both PET imaging and breast biopsy. The population characteristics at the time of the original breast cancer diagnosis were as follows: (1) Race and age: African Americans 21 (68%) (mean age = 46.8), Caucasian 10(32%) (mean age = 52.8). (2) Tumor size: 7 tumors ≤ 10mm, 11 between 11–20mm, 11 between 21–30mm, and 2 between 31–50mm. (3) Nodal Status: 21(68%) node negative, 10(32%) node positive. (4) Hormone receptor status: 51% negative, 49% positive.Biopsy/PET Results: 58% of the surgical biopsies were negative while 42% were positive (recurrent disease). 58% of PET scans were negative while 42% were positive. There was 1 false negative PET scans and 1 false positive scan. Overall the sensitivity of PET was 92.31%;while specificity was 94.44%. Positive predictive value of PET was 92.31%. PET scan was highly consistent with biopsy results (Kappa Co-efficient k=0.92). The single patient with a negative biopsy following a positive PET scan was found to have wide spread metastatic disease. The single patient with negative PET, but positive disease by biopsy had DCIS. Conclusions: PET imaging appears to be a reliable radiographic approach for the initial evaluation of suspicious breast lesions developing after BCT. No significant financial relationships to disclose.
Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan
Authors: Filippo Scialò, Ashwin Sriram, Daniel Fernández-Ayala, Nina Gubina, Madis Lõhmus, Glyn Nelson, Angela Logan, Helen M. Cooper, Plácido Navas, Jose Antonio Enríquez, Michael P. Murphy, Alberto Sanz
Journal: Cell Metabolism (2016)

Increased production of reactive oxygen species (ROS) has long been considered a cause of aging. However, recent studies have implicated ROS as essential secondary messengers. Here we show that the site of ROS production significantly contributes to their apparent dual nature. We report that ROS increase with age as mitochondrial function deteriorates. However, we also demonstrate that increasing ROS production specifically through respiratory complex I reverse electron transport extends Drosophila lifespan. Reverse electron transport rescued pathogenesis induced by severe oxidative stress, highlighting the importance of the site of ROS production in signaling. Furthermore, preventing ubiquinone reduction, through knockdown of PINK1, shortens lifespan and accelerates aging; phenotypes that are rescued by increasing reverse electron transport. These results illustrate that the source of a ROS signal is vital in determining its effects on cellular physiology and establish that manipulation of ubiquinone redox state is a valid strategy to delay aging.
Herpesvirus Infections of Pregnancy
Authors: Sergio Stagno, Richard J. Whitley
Journal: New England Journal of Medicine (1985)

CYTOMEGALOVIRUS and herpes simplex, varicella–zoster, and Epstein–Barr viruses, members of the herpesvirus family, are ubiquitous agents that infect almost all human beings at some point during their lives. Infections with these viruses have been found in all populations tested, although their prevalence varies according to the age of patients at acquisition and to the geographic and socioeconomic settings. A unique characteristic of herpesvirus infections is that viral shedding may persist for weeks or months after the primary infection, as occurs with cytomegalovirus and Epstein–Barr virus. After the primary infection, latency is established and periodic episodes of reactivation can occur. Except . . .
Multicentric phase II trial of cisplatin/etoposide chemotherapy in advanced large-cell neuroendocrine carcinoma of the lung (LCNEC): Study GFPC 03-02 from the Groupe Francais de Pneumo-cancerologie.
Authors: J. H. Le Treut, M. Sault, C. Chouaid, A. Vergnenegre, D. Arpin, L. Geriniere, H. Berard, H. Lena, D. Paillotin, H. Le Caer
Journal: Journal of Clinical Oncology (2010)

e18018 Background: A few prospective studies concerning diagnosis and treatment of large cell neuroendocrine lung cancer have been published. After the new World Health Organization classification of lung tumours in 1999, results of previous or retrospective studies based on the old classification seemed unexplainable. So the GFPC started a prospective study, to establish the efficiency of cisplatinum/etoposide chemotherapy for patients with LCNE lung cancer, diagnosed on the basis of the Travis's criteria. 50 patients were planned. Methods: Patients with stage IV and stage III B (with neoplasic pleural effusion) were selected; treatment was three cycles of cisplatinum 80 mg/m2 d1/etoposide 100 mg/m2 d1d2d3 and two more cycles in case of objective response or stable disease. The primary objective is the efficiency, in term of objective response and survival rate, the secondary objectives, the improvement of the pathologic diagnosis, with validation of the paranuclear granular expression of a large spectrum cytokeratin by immunochemistry. Results: 42 patients were included since May 2004, all had stage IV disease. The diagnosis were controlled by a panel of twenty pathologists and they reviewed thirty-nine slides (three slides lost). Thirty cases were confirmed as LCNEC, six as small-cell carcinoma, one mixed tumour LCNEC/SCLC, one carcinoid tumor and one undifferentiated carcinoma. One patient died after inclusion in the study before the chemotherapy. One patient get out of the study himself after inclusion. 28 patients are assessable for response: after 3 cycles of chemotherapy: no complete response, 10 partial response, 10 stable disease and 8 progression (OR 35.7%). After 5 cycles: no CR, 6 PR, 5 SD and 17 Pr (OR 21.4%). Conclusions: With only forty two patients included since five years, it appears that this cancer is rarely diagnosed. The main diagnosis confusion is between small-cell and large cell-carcinoma. At last, that chemotherapy has a relative efficiency in the treatment of LCNEC. Results will be updated at the Meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, GlaxoSmithKline, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Roche
Dicumarol Therapy in Congestive Heart Failure
Authors: J. H. Wishart, Carleton B. Chapman
Journal: New England Journal of Medicine (1948)

AMONG the more serious threats to the life of the decompensated cardiac patient are thrombosis and embolism, and some means of combating these phenomena are a very pressing need in cardiovascular therapeutics. Recent work with anticoagulant agents1 , 2 in postoperative patients, in cases of myocardial infarction and in cases of thrombophlebitis suggests that the use of dicumarol offers a safe and effective method of preventing such accidents. To test the effectiveness of this drug, all patients admitted to the Veterans Administration Hospital, Minneapolis, because of cardiac decompensation have been treated with dicumarol since October, 1946. The present report is a preliminary . . .
Somatostatin-receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to<sup>68</sup>Ga-DOTATATE/-TOC uptake
Authors: Katharina Seystahl, Veit Stoecklein, Ulrich Schüller, Elisabeth Rushing, Guillaume Nicolas, Niklaus Schäfer, Harun Ilhan, Athina Pangalu, Michael Weller, Jörg-Christian Tonn, Michael Sommerauer, Nathalie L. Albert
Journal: Neuro-Oncology (2016)

The prognosis of patients with progressive meningioma after failure of surgery and radiotherapy is poor. We retrospectively evaluated the safety and efficacy of somatostatin-receptor (SSTR)-targeted radionuclide therapy (177Lu-DOTATATE [n = 16], 90Y-DOTATOC [n = 3], or both [n = 1]) in patients with progressive, treatment-refractory meningiomas (5 World Health Organization [WHO] grade I, 7 WHO grade II, 8 WHO grade III) and in part multifocal disease (17 of 20 patients). SSTR radionuclide treatment (median of 3 treatment cycles, median administered dose/cycle 7400 MBq) led to a disease stabilization in 10 of 20 patients for a median time of 17 months. Stratification according to WHO grade showed a median progression-free survival (PFS) of 32.2 months for grade I tumors, 7.2 for grade II, and 2.1 for grade III. PFS at 6 months was 100% for grade I, 57% for grade II, and 0% for grade III. Median overall survival was 17.2 months in WHO grade III patients and not reached for WHO I and II at a median follow-up of 20 months. In the analysis of single meningioma lesions, maximal and mean standardized uptake values in pretherapeutic 68Ga-DOTATOC/-TATE PET/CT were significantly higher in those lesions with radiographic stability after 6 months. In line with this, high expression of SSTR via immunohistochemistry was associated with PFS >6 months. SSTR-targeted radionuclide treatment has activity in a subset of patients with meningioma. Expression of SSTR via immunohistochemistry or radionuclide uptake might serve as a predictive biomarker for outcome to facilitate individualized treatment optimization in patients with uni- and multifocal meningiomas.
Suppression of Tumorigenicity Mediated by 5-Azacytidine and Associated With Increased Chromosome Number&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C Walker, A M Matthews, J W Shay
Journal: JNCI Journal of the National Cancer Institute (1987)

5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 μg 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68–94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell's tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell's chromosome complement.
The Incidence of Portal Cirrhosis and Fatty Metamorphosis in Patients Dying with Diabetes Mellitus
Authors: William E. Jaques
Journal: New England Journal of Medicine (1953)

THERE is a discrepancy in the literature regarding the incidence of portal cirrhosis in patients suffering from diabetes mellitus. It was therefore considered advantageous to study the livers from diabetic patients autopsied at the Peter Bent Brigham Hospital.Schleusner1 reviewed 355 autopsy protocols of diabetic patients in Hamburg dying between 1930 and 1936. He found 45 cases (12.7 per cent) with macroscopic evidence of cirrhosis. He noted that only a third were advanced and diagnosed clinically. The diabetes antedated the cirrhosis in 20 available clinical histories. At the other extreme, Joslin et al.2 reported cirrhosis to be an uncommon complication, . . .
Race, APOL1 Risk, and eGFR Decline in the General Population
Authors: Morgan E. Grams, Casey M. Rebholz, Yuan Chen, Andreea M. Rawlings, Michelle M. Estrella, Elizabeth Selvin, Lawrence J. Appel, Adrienne Tin, Josef Coresh
Journal: Journal of the American Society of Nephrology (2016)

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.
Prevalence of the Rickettsial Agent of Human Granulocytic Ehrlichiosis in Ticks from a Hyperendemic Focus of Lyme Disease
Authors: Ira Schwartz, Durland Fish, Thomas J. Daniels
Journal: New England Journal of Medicine (1997)

To the Editor: Human granulocytic ehrlichiosis, a newly discovered tick-borne infection originally described in the upper Midwest,1 has recently been reported in 29 patients from Westchester County, New York.2 We used the polymerase chain reaction (PCR) to examine 173 host-seeking ticks (Ixodes scapularis) collected from vegetation in Westchester County for the presence of the agent of human granulocytic ehrlichiosis, as well as the agent of Lyme disease, Borrelia burgdorferi. After extracting DNA from dissected tissues, we used the 23S ribosomal DNA (rDNA) primers of Schwartz et al.3 for B. burgdorferi and the 16S rDNA primers of Pancholi . . .
A Population-Based Study of Survival and Childbearing among Female Subjects with Birth Defects and the Risk of Recurrence in Their Children
Authors: Rolv Skjærven, Allen J. Wilcox, Rolv T. Lie
Journal: New England Journal of Medicine (1999)

Persons with birth defects are at high risk for death during the perinatal period and infancy. Less is known about the later survival or reproduction of such persons. We studied a cohort that comprised 8192 women and adolescent girls with registered birth defects and 451,241 women and adolescent girls with no birth defects, all of whom were born in Norway from 1967 through 1982. The rate of survival was determined through 1992, and the rate of childbearing was determined through October 1997. We also estimated the risk of birth defects in the children of these subjects.
All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo
Authors: Hayley S. Ma, Sarah M. Greenblatt, Courtney M. Shirley, Amy S. Duffield, J. Kyle Bruner, Li Li, Bao Nguyen, Eric Jung, Peter D. Aplan, Gabriel Ghiaur, Richard J. Jones, Donald Small
Journal: Blood (2016)
Quantitative Observations of Circulating Megakaryocytes in the Blood of Patients with Cancer
Authors: Roxane Hume, John T. West, Richard A. Malmgren, Elizabeth A. Chu
Journal: New England Journal of Medicine (1964)

IN the course of a systematic search for tumor cells in the blood of patients with cancer of the female genital tract or of the head and neck areas, cells with the characteristics of megakaryocytes were frequently observed. It is the purpose of this paper to report and analyze these observations as follows: to compare the numbers of megakaryocytes in the antecubital-vein blood of cancer patients with the numbers in the antecubital-vein blood of normal controls; to compare the numbers of megakaryocytes in the antecubital-vein blood of cancer patients with the numbers found in local venous blood draining the site . . .
Sclerotherapy with or without Octreotide for Acute Variceal Bleeding
Authors: Isabelle Besson, Pierre Ingrand, Bruno Person, Dominique Boutroux, Denis Heresbach, Pierre Bernard, Patrick Hochain, Jacques Larricq, Alain Gourlaouen, Didier Ribard, Nassim Mostefa Kara, Jean-Louis Legoux, Bernard Pillegand, Marie-Claude Becker, Jacques Di Costanzo, Jean-Michel Metreau, Christine Silvain, Michel Beauchant
Journal: New England Journal of Medicine (1995)

Sclerotherapy is considered the most effective way to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with a high risk of rebleeding and death. We compared sclerotherapy alone with sclerotherapy and octreotide to control acute variceal bleeding and prevent early rebleeding in patients with cirrhosis.
Posttraumatic stress disorder: a thirty-year delay in a World War II veteran
Authors: C Van Dyke, N J Zilberg, J A McKinnon
Journal: American Journal of Psychiatry (1985)

Some clinicians doubt the validity of a diagnosis of delayed posttraumatic stress disorder for Vietnam veterans. Precombat psychopathology, drug abuse, factitious symptoms, and malingering in pursuit of disability compensation are cited as alternative explanations for the syndrome. The authors discuss the case of a much decorated World War II veteran whose symptoms of posttraumatic stress disorder first occurred more than 30 years after combat. They consider the alternative explanations for his symptoms to be inadequate.