tbuckley/cabot-search huggingface dataset:
The tumor suppressive function of AMPK in hepatocellular carcinoma
Authors: Heong Fai Michael Liu, Veronica Leong, Irene O.L. Ng, Yick Pang Ching
Journal: Cancer Research (2007)

3686  Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. However, the molecular mechanism underlying the development of HCC is still unclear. AMP-activated protein kinase (AMPK), which is a serine/theronine protein kinase, originally found as a key regulator in glucose and lipid metabolism in response to cellular stress. Recent publications suggest that AMPK activation results in suppressing cell proliferation. Also, AMPK lies upstream and downstream of two tumor suppressors, TSC2 and LKB1, respectively, indicating that AMPK may also involve in carcinogenesis. In this project, we aim to study the molecular mechanism leading to the tumor suppressive function of AMPK in HCC, particularly relating to the p53 pathway. Our preliminary findings have shown that overexpression of AMPKα2 catalytic subunit in HCC cell line HepG2 suppress cell proliferation in focus formation assay. On the other hand, an increase in proliferation rate was observed in HCC cell with AMPKα2 stably knocked down by small hairpin RNA. Also, our data have demonstrated that expression of constitutive active form of AMPKα2 leads to p53 phosphorylation at serine 15 residue and acetylation at lysine 382 residue. In addition, in-vitro kinase assay has shown that AMPK directly phosphorylates p53. Our results suggest that AMPK may mediate its tumor suppression function through regulation of p53.
The Umbilical Cord Blood αβ T-Cell Repertoire: Characteristics of a Polyclonal and Naive but Completely Formed Repertoire
Authors: Laurent Garderet, Nicolas Dulphy, Corinne Douay, Nathalie Chalumeau, Véronique Schaeffer, Marie-Thérèse Zilber, Annick Lim, Jos Even, Nuala Mooney, Catherine Gelin, Eliane Gluckman, Dominique Charron, Antoine Toubert
Journal: Blood (1998)
Clinical research of the malignant hydrothorax or hydroperitoneum treated with intracavitary chemotherapy and local thermotherapy
Authors: H. Song, l. Chen, J. Wang, X. Chu, Q. Zhang, H. Geng
Journal: Journal of Clinical Oncology (2007)

19615 Background: Malignant hydrothorax or hydroperitoneum are common complications of the cancer. Pure chemotherapy couldn’t get good effect. We combined intracavitary chemotherapy with local thermotherapy to cure malignant hydrothorax or hydroperitoneum. In order to observe the recent effects and toxicity of thermochemotherapy and evaluate the change of the immunologic function, and to investigate the mechanism of thermochemotherapy. Methods: Fifty-two patients were treated with weekly intracavitary chemotherapy, and then combined with local thermotherapy twice a week. As the control, another fifty patients received weekly intracavitary chemotherapy. Treated for two weeks and rest for one week, and then observed the recent effects and toxicity. Test the level of the T cell subset, NK cells and VEGF in serum and effusion Results: Overall response rate of the malignant hydrothorax was 86.9% vs 60.0% (P&lt;0.05), Overall response rate of the malignant hydroperitoneum was 79.3% vs 46.7% (P &lt;0.01).The incidence of myelosuppression was 7.7% vs 24% (P&lt;0.05). After thermochemotherapy, the ratio of CD4/CD8 rose significantly (P&lt;0.01), but the ratio of NK cells decreased significantly (P&lt;0.05) in malignant hydrothorax or hydroperitoneum. While in peripheral blood, all the ratio of CD3, CD4, CD8, CD4/CD8 and NK cells rose significantly (P&lt;0.05). Meanwhile the level of VEGF decreased significantly (P&lt;0.05) whether in effusion or blood. Conclusions: Combined intracavitary chemotherapy with local thermotherapy could control the malignant hydrothorax and hydroperitoneum effectively with less-toxicity. The cellular immune function was elevated and the neovascularization of tumor was probablely inhibited. No significant financial relationships to disclose.
Differences in Susceptibility of Human Cells to Mouse Sarcoma Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Vaclav Klement, Melvin H. Freedman, Robert M. McAllister, Walter A. Nelson-Rees, Robert J. Heubner
Journal: JNCI Journal of the National Cancer Institute (1971)

Eighteen different human cell strains and lines were transformed by rat-cell-adapted Kirsten mouse sarcoma virus. The change in morphology was focal and could be quantitatively evaluated. The susceptibility of individual strains to transformation varied more than 300-fold. In general, more susceptible cell strains were found among those derived from individuals with neoplasia and genetic or chromosomal abnormalities than those derived from “normal” individuals and fetuses. Virus released from human cells infected with, and transformed by, mouse sarcoma virus induced foci when assayed on rat cells.
Exercise test with dry air inhalation compared to mannitol test as marker of exercise induced asthma
Authors: Kai-Håkon Carlsen, Leif Bjermer, Barbro Dahlén, Tommy Ekström, Gunilla Hedlin, Trine Stensrud, Leif Jörgensen, Kjell Larsson
Journal: European Respiratory Journal (2011)

Objective: To compare exercise test with dry air inhalation and mannitol test to discriminate between different asthma treatments.

Methods: Exercise test with dry air inhalation (EIA test) (Aiolos bronchial challenge®, Sweden) was compared to inhaled mannitol test in a randomized trial (NCT 00989833) on budesonide/formoterol (B/F) as needed (n=23), budesonide (B; n=21) once daily, terbutaline (T) as needed (n=22) on exercise induced asthma (EIA) in mild asthmatic adults and adolescents. EIA test: 6 minutes treadmill run at 90% of max aerobic capacity; FEV1 measured before, and 0, 5, 10, 15, 30, 45 minutes after exercise. EIA test was positive with max fall in FEV1 ≥ 10% of baseline. Dry powder mannitol was inhaled in cumulative doses from 5 - 635 mg, to find the dose causing 15% FEV1 fall (PD15). EIA test was performed at trial start, after 3 and 6 weeks, mannitol test at trial start and after 6 weeks.

Results: Mean max FEV1 fall after EIA test was 16.34% at baseline and 13.11% after 6 weeks treatment. There was a significant improvement in B/F (ΔFEV1: LS mean (95% CI) -5.4 (-8.93, -1.83) and B (-6.6 (-10.3, -2.96)) groups after 6 weeks, but not in the T group (+1.48 (-2.1, 5.09)). The mannitol test was positive (PD15<635 mg) in only 31/66 subjects at start, and in 22 at 6 weeks. All 66 subjects had a positive EIA test.

Conclusion: All patients had positive EIA test at baseline. The response to the EIA test improved significantly in two of the treatment groups (B/F and B) and discriminated between the treatments. The mannitol test was positive in less than 50% of the subjects, and could not be used as outcome in the present study.

The study was sponsored by AstraZeneca.
Protection by 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) Against Mammary Tumors and Leukemia During Prolonged Feeding of 7,12-Dimethylbenz[a] anthracene to Female Rats2
Authors: K. Charles Silinskas, Allan B. Okey
Journal: JNCI Journal of the National Cancer Institute (1975)

Female Sprague-Dawley rats, 36 days old, were pretreated for 2 weeks either with 100 ppm 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) or 250 ppm S-(1,2-dicarbeth-oxyethyl)OO-dimethyldithiophosphate (Malathion) in the diet. From day 50 they were given, via stomach tube, 21 consecutive daily doses of 0.714 mg 7,12-dimethylbenz[a]anthracene (DMBA). Pesticide diets and observation of the animals for mammary tumors continued until necropsy, 230 days after the start of DMBA administration. DDT-treated rats had a significantly lower mammary tumor incidence, prolonged tumor latency period, and fewer tumors per rat than did the control group. Animals given Malathion (an organophosphate pesticide) had a higher mammary tumor incidence, shortened latency period, more tumors per rat, and more actively growing tumors than did the control group (DMBA only). Leukemia incidence in rats surviving to necropsy (230 days after the start of DMBA administration) was 11/20 for control, 2/29 for DDT, and 8/12 for Malathion-treated rats. Leukemia was primarily myelogenous. DDT may inhibit DMBA-induced mammary tumors and leukemia by stimulating hepatic metabolism and excretion of DMBA so that less carcinogen is available to peripheral tissues. Malathion may potentiate DMBA induction of mammary tumors and leukemia by inhibiting the same enzyme systems induced by DDT.
Clinico-pathological prognostic factors for relapse in early stage non-small cell lung cancer after radical surgical resection
Authors: Tatjana Sarcev, Slobodanka Pena-Karan, Aleksandra Ilic, Branislav Perin, Bojan Zaric, Aleksandar Tepavac, Zivka Eri, Marijela Potic, Aleksandra Andjelkovic, Jelena Stanic
Journal: European Respiratory Journal (2013)

Introduction: Surgery is the first choice in treatment of early stage Non–Small Cell Lung Cancer (ES-NSCLC). Primary aim of this study was the determination of clinico-pathological prognostic factors for relapse in ES-NSCLC after radical surgical resection.  Methods: The study was a retrospective / prospective trial in which we included 118 patients who underwent curative intent resection of stage T1N0 and T2N0. The follow-up period was of 4-6 years. Data included histological type, tumor size, number of removed and histologically examined lymph nodes (LN), time to the occurrence of relapse, relapse site and the number of affected organs.  Results: The most common type was adenocarcinoma (51.7%) in both sexes, significantly higher in female. Both, tumor size greater than 3 cm (p = 0.043) and number of removed and histologically examined LN (p = 0.054) were identified as poor prognostic factors. Relapse was observed in 35 (29.7%) patients in period of 3 to 48 months after surgery. In 50% of patients relapse occurred within the first 20 months after operation. The most common sites of relapse were remaining lobe and contralateral lung, following by bones, brain and liver. None of the analyzed factors were identified as independent prognostic factor by Cox regression.  Conclusions: Tumor size greater than 3 cm and the smaller number of removed and examined LN are identified as prognostic factors for relapse in ES- NSCLC after radical surgery. Clinico-pathological prognostic factors should be accompanied with biomarkers in prediction of tumor relapse in ES-NSCLC after radical surgery.
Proliferative Activity Of Neoplastic B Cells - Impact On The Prognosis Of Follicular Lymphoma
Authors: Dulcineia Pereira, Sergio Pereira Chacim, Margarida dantas Brito, Miguel Abreu, Edgar Mesquita, Margarida Marques, Luisa Viterbo, Isabel Oliveira, Nelson Domingues, Ilidia Moreira, Ana Espirito-Santo, Cecilia Correia, Carlos Palmeira, Emilia Sousa, Ines Godinho, Marta Pires, Rui Henrique, Manuel R. Teixeira, Gabriela Martins, Angelo Martins, Jose Mario Mariz
Journal: Blood (2013)
Ricin A Chain Conjugated With Monoclonal Antibodies Selectively Killing Human Carcinoma Cells In Vitro2
Authors: Silvana Canevari, Rosaria Orlandi, Marina Ripamonti, Elda Tagliabue, Salvatore Aguanno, Silvia Miotti, Sylvie Menard, Maria Ines Colnaghi
Journal: JNCI Journal of the National Cancer Institute (1985)

Ricin A chain was coupled to murine monoclonal antibodies MBr1 and MOv2 respectively raised against human breast and ovarian carcinomas. Inhibition of protein synthesis only occurred in those cultured human tumor cells bearing the appropriate target antigens, demonstrating that both components of the conjugate were unchanged in regards to specificity and toxicity. Conjugates were 125-200 times more efficient in inhibiting [3H]proline incorporation than the uncoupled ricin A chain. They were however unable to kill the entire population of the appropriate cells even after repeated treatment. Although the two monoclonal antibodies had similar binding kinetics, the conjugates differed in their cytotoxicity kinetics. The MBr1-ricin A chain conjugate had slow kinetics, and about 20 hours were needed to obtain a protein synthesis inhibition above 50% on the appropriate line (mammary carcinoma MCF-7). In contrast, the MOv2-ricin A chain conjugate showed very fast kinetics, reaching 50% inhibition after only 30 minutes of treatment on both appropriate cell lines SW626 and HT-29 from ovarian and colon carcinomas, respectively. Growth conditions of cell lines, i.e., adherent cells versus suspended cells, and plating time were found to greatly influence the conjugates' killing efficiencies. These studies confirm the possibility of preparing ricin A chain-antibody conjugates, which retain specific cytotoxicity against tumor cells; but they also underline the need for further in vitro studies of various parameters before one considers a therapeutic use of such conjugates.
NIV and influenza A H1N1 pneumonia
Authors: Antonello Nicolini, Mario Santo, Monica Bonfiglio, Alberto Carrassi
Journal: European Respiratory Journal (2011)

Background: NIV was not recommended for patients with influenza A H1N1 virus pneumonia complicated by ALI or acute ARDS,because, although it could temporarily improve oxygenation, it does not necessarily change the natural disease course.In this regard several authors have reported high rates of NIV failure in pandemic influenza A H1N1 pneumonia.However, other authors have recently reported some cases demonstrating the effectiveness of NIV in ARDS/ALI related to H1N1 pneumonia.

Aim and methods: The objective of this study is to describe the clinical characteristics of patients with diagnosis of Influenza A H1N1 pneumonia with ARDS/ALI with whom NIV has been effective.75 patients affected by Influenza A H1N1 pneumonia were admitted to our Hospitals: among them,29 patients presented ARDS/ALI;5 patients were admitted to ICU, and 24 underwent NIV and admitted to RICU.

Results: NIV failed in 3 of the 24 patients, but in 21 had a good outcome.

None of the patients treated with NIV died.

The duration of NIV was 5.0±1.9 days and the hospital stay 11.2±4.0 days. The average P/F ratio at admission was 184.6±29.2 and SAPSII was17.8±2.6; the average P/F ratio after 1 h of NIV was 239.1±42.3. No patient had multiorgan failure.

Discussion: In our study NIV had a success in 21 of the 24 patients (87.5%) and this the higher rate of success described in the literature: in our opinion the reasons explaining the results could be the choice of the patients to be treated with ALI and mild ARDS (P/F ≥ 150), and the strict following of the predictors of success for NIV as SAPSII ≤ 34 and P/F after 1 hour of NIV ≤175.

Clinicians should be aware of pulmonary complications of influenza A H1N1 and strictly select the patients to undergo niv: perhaps, can we give niv a chance?
Abstract 15020: Second Arterial Graft Selection in Patients With Preserved Renal Function-Second Internal Thoracic Artery versus Radial Artery in OPCAB: Propensity Score-Matching Analysis-
Authors: Chikara Ueki, Genichi Sakaguchi, Tatsuhiko Komiya
Journal: Circulation (2013)

Background: The best selection of second arterial graft in coronary artery bypass grafting (CABG) is still unclear. The aim of this study is to compare the clinical outcomes in patients with preser...
<i>ESR1</i> Mutations in Breast Cancer: Proof-of-Concept Challenges Clinical Action
Authors: Guowei Gu, Suzanne A.W. Fuqua
Journal: Clinical Cancer Research (2015)

Wang and colleagues demonstrate that digital droplet PCR (ddPCR) identified ESR1 mutations in 7% of primary breast cancers. ESR1 mutations were also readily detected in metastatic tissues and circulating tumor DNA in the blood. These results suggest that ddPCR may be amendable for monitoring tumor burden, and to predict relapse. See related article by Wang et al., p. 1130.
CD34-positive cells isolated from cryopreserved peripheral-blood progenitor cells can be expanded ex vivo and used for transplantation with little or no toxicity.
Authors: M J Alcorn, T L Holyoake, L Richmond, C Pearson, E Farrell, B Kyle, D J Dunlop, E Fitzsimons, W P Steward, I B Pragnell, I M Franklin
Journal: Journal of Clinical Oncology (1996)

PURPOSE The objectives of this phase I study were to assess the feasibility of using cryopreserved peripheral-blood progenitor cells (PBPC) for large-scale CD34 selection and subsequent expansion, and the safety of their use for reinfusion following chemoradiotherapy. PATIENTS AND METHODS For 10 patients with nonmyeloid malignancy, an aliquot from a PBPC harvest was recovered from liquid nitrogen, and CD34 selected using the Isolex system (Baxter Healthcare, Newbury, United Kingdom) and expanded for 8 days ex vivo in a medium free of animal proteins but supplemented with autologous serum, stemcell factor (SCF), interleukin-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin. RESULTS The mean increase for cell number was 21-fold, for colony-forming units-granulocyte/macrophage (CFU-GM) 139-fold, and for burst-forming units-erythroid (BFU-E) 114-fold. The expanded cells were reinfused in tandem with unmanipulated material (&gt; or = 25 x 10(4) CFU-GM/kg). The patients did not experience any adverse effects immediately on cell infusion or within 48 hours. The 10 index patients were compared with 10 historical controls for parameters of myelosuppressive morbidity. In this small study, there were no differences in either neutrophil or platelet recovery between the patients who received expanded cells and historical controls. CONCLUSION These data demonstrate that CD34 cells can successfully be selected from cryopreserved material, expanded ex vivo on a large scale, and safely reinfused following myeloablative conditioning regimens.
Abstract 309: Small Heterodimer Partner Blocks Cardiac Hypertrophy By Interfering With GATA6 Signaling
Authors: Yoon Seok Nam, Duk-Hwa Kwon, Gwang Hyeon Eom, Hyun Kook
Journal: Circulation Research (2014)

Rationale: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA binding domain. By interacting with other transcription factors, SHP regulates diverse biological events including glucose metabolism in liver. The role of SHP in adult heart diseases has not yet been demonstrated. Objective: We aimed to investigate the role of SHP in adult heart in association with cardiac hypertrophy. Methods and Results: The roles of SHP in cardiac hypertrophy were tested in primary cultured cardiomyocytes and in animal models. SHP null mice showed a hypertrophic phenotype. Hypertrophic stresses repressed the expression of SHP, whereas forced expression of SHP blocked the development of cardiomyocyte hypertrophy. SHP reduced the protein amount of Gata6. By direct physical interaction with Gata6, SHP interfered with the binding of Gata6 to GATA binding elements in the promoter regions of natriuretic peptide precursor type A. Metformin, an anti-diabetic agent, induced SHP and suppressed cardiac hypertrophy. The metformin-induced anti-hypertrophic effect was attenuated either by SHP siRNA in cardiomyocytes or in SHP null mice. Conclusions: These results establish SHP as a novel anti-hypertrophic regulator that acts by interfering with GATA6 signaling. SHP may participate in the metformin-induced anti-hypertrophic response.
Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.
Authors: E Salloum, D S Brandt, V J Caride, E Cornelius, D Zelterman, W Schubert, T Mannino, D L Cooper
Journal: Journal of Clinical Oncology (1997)

PURPOSE To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P &lt; .01). CONCLUSION A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.
Genetic variants in antioxidant genes, Gleason grade, and prostate cancer recurrence after radical prostatectomy.
Authors: Erin L Richman, Vivian K. Weinberg, Eduardo V Sosa, Xiaoling Song, Peter Carroll, John S Witte, June M. Chan
Journal: Journal of Clinical Oncology (2012)

33 Background: Laboratory and genomic data suggest that the antioxidant defense system is important in prostate carcinogenesis, and that this relation may vary by plasma antioxidant status. Methods: Among 567 radical prostatectomy (RP) patients with non-metastatic prostate cancer (CaP), we examined genetic variants in SOD1(5 SNPs), SOD2(6), SOD3(6), TXRND1(5), TXRND2(21), GPX1(3), GPX3(8), GPX4(5), CAT(9), XRCC1(2), SELENBP1(5), SEP15(4), SEPP1(4), SEC14L2(8), and TTPA(4) and risk of high pathologic Gleason sum (8+ or 7 with primary 4+) using logistic regression, and CaP recurrence (PSA rise, second treatment, metastasis) using Cox proportional hazards regression. We also examined whether the genetic variants interacted with plasma selenium, alpha-tocopherol, or gamma-tocopherol in relation to risk of high grade CaP. Results: 21% (n = 117) of men had high grade CaP, and 47 recurrences occurred (median follow-up of all participants = 3 y). Men with 1+ of the less common allele (CT or TT) in rs4880 (SOD2) had a 49% reduced rate of recurrence (hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.28, 0.92), independent of grade, stage, and PSA. In contrast, men with 1+ of the less common allele in 3 of the TXRND1, 4 of the TXRND2, and 1 of the SEP15 SNPs had 2-fold increased rate of recurrence (HRs: 1.93-2.95; p-values: 0.002-0.04), and men with 2 of the less common allele in 2 of the GPX3 SNPs had 3-fold increased rate of recurrence (p-values from additive models: &lt;0.01). For high grade CaP, men with 1+ of the less common allele in 1 of the SOD3 SNPs or 2 of the less common alleles in 2 of the TXRND2 SNPs had 2-fold increased risk (p-values = 0.007-0.02), while men with 1+ of the less common allele in 1 of the GPX1 SNPs had 37% reduced risk (p-value = 0.04). Among men with certain genotypes in 3 TXRND2, 1 GPX3, or 2 CAT SNPs, high plasma selenium reduced risk of high grade CaP by 50-76%. Among men with certain genotypes in 1 SOD1 or 1 SOD2 SNP, high plasma alpha-tocopherol reduced risk of high grade CaP by 65-68%. Conclusions: Genetic variants in antioxidant genes may be associated with CaP recurrence after RP, and may interact with plasma selenium and alpha-tocopherol in relation to risk of high grade CaP.
Abstract 14573: Is a Policy of Measuring Hs-TnT in All Comers to Emergency Department With Suspected Myocardial Infarction Useful?
Authors: Luigi M Biasucci, Maria Giulia Marini, Maria Teresa Cardillo, Chiara Sonnino, Gina Biasillo, Massimo Gustapane, Annalisa Caroli, Alessia Romito, Chiara Cordischi, Francesco Franceschi, Filippo Crea
Journal: Circulation (2013)

Background: The best use of high sensitivity troponin T (hs-TnT) in Emergency Department (ED) is still a matter of debate. Our aim was to evaluate the efficacy of a policy based on the measure of h...