tbuckley/cabot-search huggingface dataset:
Abstract 925: <i>Helicobacter pylori</i> induces phosphorylation of STAT3 at Ser727 to promote mitophagy in gastric cancer cells
Authors: Juan-Yu Piao, Hee Geum Lee, Su-Jung Kim, Do-Hee Kim, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2015)

Abstract Chronic Helicobacter pylori (H. pylori) infection has been considered to be one of the high risk factors of gastric cancer, but the exact mechanism underlying H. pylori-mediated carcinogenesis has not been completely elucidated. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) is implicated in inflammation-associated carcinogenesis. In a canonical STAT3 pathway, phosphorylation of STAT3 at Tyr705 is a major event of STAT3 activation. In the present study, we found that H. pylori induced phosphorylation of STAT3 at not only Tyr705 but also Ser727. Notably, STAT3 Ser727 phosphorylation occurred at late time independently of Tyr705 phosphorylation followed by migration to mitochondrion. It has been reported that mitophagy is a specialized form of autophagy that removes damaged mitochondria to maintain efficient cellular metabolism and reduces cellular stress. In our study, H. pylori infection induced mitophagy with upregulation of LC3 (microtubule-associated chain3), which is an autophagy marker, in mitochondria. H. pylori-induced Ser727 phosphorylation appears to regulate expression of LC3 based on the experiment utilizing the STAT3 mutant vector in which Ser727 is replaced by alanine, suggesting a potential link between mitophagy and STAT3 phosphorylation at Ser727. Furthermore, we found that STAT3 phosphorylated at Ser727 bound to Grim19 which is a component of complex I and heat shock protein 90 in mitochondria. How this binding contributes to mitopagy is under investigation. In conclusion, H. pylori induced STAT3 phosphorylation at Ser727 to promote mitophagy Citation Format: Juan-Yu Piao, Hee Geum Lee, Su-Jung Kim, Do-Hee Kim, Hye-Kyung Na, Young-Joon Surh. Helicobacter pylori induces phosphorylation of STAT3 at Ser727 to promote mitophagy in gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 925. doi:10.1158/1538-7445.AM2015-925
Abstract P176: Associations of Cardiovascular Disease Risk Factors with Aorto-Iliac Bifurcation Location
Authors: Nketi I Forbang, Joachim Ix, Matthew Allison, Christina Wassel, Michael Criqui
Journal: Circulation (2012)

Objectives: We investigated associations of cardiovascular disease (CVD) risk factors and calcified atherosclerosis with the aortic bifurcation location. Background: In older persons, the aorto-iliac bifurcation is found in a more caudal position along the lumbar spine. Little is known about what other factors may play a role in the location of the bifurcation. Methods and Results: We evaluated community living individuals, free of clinical CVD, who had completed abdominal, computed tomography (CT) scans. The aorto-iliac bifurcation distance (AIBD), bifurcation to L5-S1 disc space, was determined from CT scans. The 1,711 participants (51% male) in this study had a mean age of 62 ± 10 years, and a mean AIBD of 26 ± 15mm. Age was a strong correlate of AIBD, such that on average, individuals &gt; 80 years had bifurcations positioned 16mm lower than individuals &lt; 50 years. In multivariable linear regression, standardized for lumbar spine height, older age, smoking, hypertension, and larger aortic diameter (ADD) were each independently associated with a smaller AIBD (more caudal location of the bifurcation). In contrast, diabetes and elevated triglycerides were independently associated with a larger AIBD (more cephalad location). Conclusions: A more caudal position of the aorto-iliac bifurcation is associated with some, but not all, CVD risk factors. Future studies should access the position of the bifurcation as a useful surrogate for vascular aging, or a prognosticator for CVD.
Ultrasensitive PSA nadir on testosterone inactivating pharmaceuticals accurately predicts early prostate cancer progression
Authors: M. C. Scholz, R. Lam, B. Guess, S. Strum, H. Johnson, R. Jenrrich
Journal: Journal of Clinical Oncology (2006)

14531 Background: Prostate cancer has a variable natural history. Researchers and clinicians sorely need a marker identifying men destined for early progression to bone metastasis (EPBM). Prostate cancer is uniquely sensitive to testosterone inactivating pharmaceuticals (TIP) especially when TIP is initiated prior to the onset of bone metastasis. Moul 1 reported 10 year median response in men with a rising PSA after surgery. With such effective therapy, predicting EPBM requires a marker signaling TIP resistance. Elevated PSA nadir is a likely candidate. Methods: Retrospective chart review of 159 men with prostate cancer started on TIP before 1/1/00 with negative bone scan and PSA &lt; 100. The predictive value of Gleason score, initial PSA, PSA doubling-time (DT), clinical stage, and ultra-sensitive PSA nadir were evaluated for their ability to predict EPBM within 72 months of starting TIP. TIP consisted of an antiandrogen and LHRH agonist. Results: Median follow was 9.25 years. Median values for patient age, initial PSA, PSA nadir, and PSA doubling time were 65.9, 9.6, 0.03 and 10 months respectively. Sixty men were staged as: T1c-T3b, 46 PSA relapse, and 53 stages T3c, D0 or D1. Thirty-five men developed EPBM. PSA nadir was the most accurate predictor of EPBM (see Table). Only 8% of men with PSA nadir ≤0.05 had EPBM compared to 78% with high nadirs. Cox regression analysis indicated that PSA nadir, Gleason score, and PSA doubling time &lt; 12 months independently predicted EPBM. Median and maximum time to PSA nadir were 4 and 8 months respectively. Conclusions: Ultra-sensitive PSA nadir is a more accurate indicator of early progression to bone metastasis (90%) than Gleason score (75%) as well as being more sensitive and specific (72% vs. 37%) and (95% vs. 86%) respectively. This prognostic information provided by PSA nadir is obtainable within the first 8 months of starting TIP in virtually all patients (97%). 1. Moul JW et al. J Urol 2005, 171: 1141–7. [Table: see text] No significant financial relationships to disclose.
Comparison of serum osteopontin levels in patients with exacerbations and stable chronic obstructive pulmonary disease
Authors: Yu Cho, Ho Kim, Yi Jeong, Jong Lee, Young Hwang
Journal: European Respiratory Journal (2012)

Background: Osteopontin is reconized as an important adhesive bone matrix and a key cytokine involved in immune cell recruitment, tissue repair and remodeling. Then serum levels of osteopontin have not been evaluated in patients with chronic obstructive pulmonary disease(COPD). The aim of this study is to evaluate and compare the serum levels of osteopontin in patients with exacerbations and stable COPD  Methods: Serum samples were obtained from 22 healthy control subjects, 18 stable COPD patients, and 15 COPD with exacerbation patients. Serum concentrations of ostepontin were measured by the ELISA metnod.  Results: Serum levels of osteopontin were higher in patients with exacerbation than with stable COPD and in healthy control(62.4±51.9 ng/mL, 36.9±11.1 ng/mL,30.0±11.0 ng/mL, p=0.003). Osteopontin levels were significantly decreased after clinical improvement than during exacerbation (45±52.1 ng/mL, 62.4±51.9 ng/mL, p=0.160). Also osteopontin levels showed a significantly negative correlation with forced expiration volume in one second(FEV1%) in healthy controls and stable COPD (r= -0.389, p=0.013). C-reactive protein was positively correlated with osteopontin levels in patients with COPD exacerbations(r=0.775, p=0.002).  Conclusions: The serum levels of osteopontin were increased in patients with COPD exacerbations and tended to decrease after clinical improvement. These results suggest the possible role of osteopontin as a biomarker of COPD with exacerbation.
Exhaled air dispersion during non-invasive ventilation via helmet masks
Authors: David Hui, Benny Chow, Thomas Lo, Matthew Chan
Journal: European Respiratory Journal (2013)

Rationale: Application of non-invasive ventilation (NIV) via helmet masks is an option for managing infectious patients with severe respiratory failure before haemodynamic instability. However it is unknown whether there is any leakage of exhaled air during NIV application via helmet masks.  Methods: We examined the exhaled air dispersion during application of NIV by a servo ventilator with double circuits and filters via different helmet masks on a high fidelity human patient simulator (HPS) in a negative pressure room with 12 air changes/hr. Exhaled air was marked by intrapulmonary smoke particles, illuminated by laser light sheet, and captured by a high definition video camera for data analysis.  Results: During application of NIV via the SeaLong oxygen head tent with the HPS programmed in mild lung injury, exhaled air was noted to leak through the neckseal interface with a radial distance of 150 to 230mm when IPAP was increased from 12 to 20cmH20 respectively while keeping the EPAP at 10cmH20. During application of NIV via the StarMed CaStar R helmet mask with a tight air cushion around the neck interface, there was negligible air leakage.  Conclusion: Helmet mask with a good neckseal is needed to prevent air leakage during application of NIV.
Abstract 451: Platelet Activation and Thrombosis by Antibodies against VEGF and CD40 Ligand: Extending the mechanism of HIT
Authors: Ali Amirkhosravi, Todd Meyer, Florian Langer, Theresa Robson, Liza Robles, Hina Desai, Monica Davila, Mildred Amaya, John L Francis
Journal: Circulation (2007)

Introduction: The vascular endothelial growth factor (VEGF) monoclonal antibody, bevaci-zumab (Avastin), has been associated with arterial thromboembolic events in some cancer patients. Another therapeutic antibody, hu5c8, which targets CD40L, also produced unexpected thrombosis in lupus clinical trials. Because platelets play a crucial role in arterial thrombosis, we hypothesized that antibodies against VEGF and CD40L may activate platelets via a mechanism similar to that responsible for thrombosis in Heparin-Induced Thrombocytopenia (HIT). Methods: Immune complexes (ICs) were prepared by combining these monoclonal IgG antibodies with their antigens: M90 (or hu5c8) with CD40L (“M90+CD40L”), or bevacizumab with VEGF and heparin (“BVH”). VEGF binds heparin (as does platelet factor 4, the HIT antigen). We measured platelet activation by serotonin release assay, platelet aggregometry, and flow cytometry. We also evaluated IC-induced thrombosis in hFc mice, transgenic for the human IgG receptor, CD32. Results: Similar to HIT antibodies, these ICs potently induced platelet activation dependent on CD32, IC concentration (&gt;10nM) and optimal stoichiometry. Intravenous injection of M90+CD40L or BVH into hFc, but not wild-type mice rapidly produced signs of thrombotic shock, thrombocytopenia and pulmonary thrombosis. However, wild-type control mice (lacking platelet CD32) were unaffected by IC injection. Similarly as with HIT antibodies, bevacizumab IC activity was reduced in the absence or excess of heparin both in vitro and in vivo, whilst M90+CD40L-induced platelet activation was abolished in vitro by blockade of the platelet CD40L receptor, CD40, demonstrating a requirement for Fab-dependent anchoring. Furthermore, VEGF 121 (which lacks the heparin-binding domain of VEGF 165 ) and bevacizumab with or without heparin failed to activate platelets or cause thrombosis in hFc mice. Conclusions: Together, these findings demonstrate that Fab-dependent anchoring of anti-CD40L and anti-VEGF ICs is required for potent platelet activation and thrombosis, as is the case in HIT, suggesting common mechanistic elements. Clinical implications may apply in patients with cardiovascular comorbidity receiving immunotherapy.
The prognostic significance of autologous bone marrow transplant in advanced neuroblastoma.
Authors: J J Shuster, A B Cantor, N McWilliams, J G Pole, R P Castleberry, R Marcus, T Pick, E I Smith, F A Hayes
Journal: Journal of Clinical Oncology (1991)

This report provides strong evidence for conducting a controlled randomized clinical trial of autologous bone marrow transplantation versus conventional chemotherapy in childhood neuroblastoma, which is disseminated beyond the intracavity nodes, and which is diagnosed in children older than 12 months of age. On the basis of two Pediatric Oncology Group (POG) studies, one a surgery plus conventional chemotherapy study (POG 8441) and the other an elective autologous transplant pilot protocol (POG 8340), there was no significant prognostic benefit of switching in remission from the surgery plus chemotherapy protocol to the transplant protocol (P = .91) or of switching in remission from the surgery plus chemotherapy protocol to any transplant (P = .75). The analysis is based on 116 patients achieving a complete or partial remission, 32 of whom received transplants on the pilot protocol, and 17 of whom received transplants outside the pilot protocol. While potential selection bias precludes cause-effect conclusions, these data strongly suggest that a large randomized trial of autologous bone marrow transplantation should be conducted before accepting this form of therapy as standard.
Prevalence and correlates of fatigue and depression in breast cancer survivors: Breast cancer quality care study
Authors: S. H. Kim, B. W. Park, S. H. Ahn, D. Y. Noh, S. J. Nam, E. S. Lee, Y. H. Yun
Journal: Journal of Clinical Oncology (2006)

683 Background: Fatigue and depression may persist for months or even years after completion of breast cancer treatment. We investigated the prevalence and correlates of fatigue and depression in disease-free breast cancer survivors. Methods: 1,933 breast cancer survivors recruited from five large hospitals in Korea completed standardized questionnaires as part of a survey study, including the patient demographics, Brief Fatigue Inventory, Beck Depression Inventory, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and QLQ-BR23. Women were eligible to participate if they had a past diagnosis of breast cancer (stage 0, I, II, or III) and were currently free of the disease more than one year. Eligible patients were contacted by telephone, and those who agreed to participate were sent the questionnaire with consent forms and a postage-paid return envelope. Multivariate logistic regression models were used to identify factors associated with fatigue and depression. Results: Sixty six percent of the breast cancer survivors reported moderate to severe fatigue, which was defined as a “fatigue worst” rating of 4 or greater, 24.9% reported clinical moderate to severe depression, which was defined as a rating of 19 or greater. Fatigue and depression were highly correlated (Pearson r=.593). Fatigue was associated with significantly employment status (OR=1.58), low income (OR=1.29), having gastrointestinal disease (OR=1.94), dyspnea (OR=2.15), appetite loss (OR=3.02), insomnia (OR=2.72), breast symptoms (OR=1.82), and hair loss (OR=1.75). Depression was strongly related to low income (OR=2.50), fatigue (OR=4.52), insomnia (OR=1.98), appetite loss (OR=2.24), constipation (OR=2.12), and financial difficulties (OR=1.89), systemic therapy side effect (OR=3.12). Fatigue and depression were negatively associated to QOL. Conclusion: There were subgroups of survivors who report more severe and persistent fatigue and depression. This information may be helpful in elucidating the mechanisms underlying fatigue and depression in this population, as well as directing intervention efforts. No significant financial relationships to disclose.
Correlation between everolimus discontinuation or dose reduction induced by stomatitis or cutaneous toxicity and clinical outcome in patients with metastatic renal cell carcinoma.
Authors: Salvatore Luca Burgio, Matteo Santoni, Matelda Medri, Emanuela Scarpi, Luciano Burattini, Lorena Rossi, Agnese Savini, Rossana Berardi, Ignazio Stanganelli, Vincenza Conteduca, Stefano Cascinu, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2015)

448 Background: Patients (pts) presenting with persistent moderate to severe stomatitis or cutaneous toxicity during everolimus may need of treatment discontinuation or a dose reduction. We assessed the correlation between stomatitis or cutaneous toxicity associated with either everolimus discontinuation or dose reduction and clinical outcome pts with metastatic renal cell cancer (mRCC). Methods: We retrospectively reviewed the clinical data of pts with mRCC treated with everolimus in two Italian Centers. Clinical evidence of stomatitis or cutaneous toxicity toxicity inducing a treatment discontinuation or a dose reduction were considered stomatitis-cutaneous toxicity events (SCTE). SCTE were evaluated and corresponding clinical data were reviewed for response and clinical outcome. Response was evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria. Results: Seventy-nine mRCC pts treated with everolimus (57 male, 22 female; median age 69 years, range 44–88) were evaluated. Fifty-two pts (66%) received everolimus as second-line therapy, while 27 (34%) as third-line. SCTE were observed in 20/79 pts (25%) at a median of 30.5 days on everolimus treatment (range 10–270 days). Tumor response was evaluable in 77 of 79 patients (19 of 20 SCTE pts and 58 of 59 non-SCTE). Partial response or stable disease was achieved in 15 of 19 pts with SCTE (79%) compared to 28 of 58 (48%) with no SCTE (p=0.03). After a median follow up of 19 months (range, 1 to 39), the median progression-free survival (PFS) was 5.5 months (95% CI 3.4-7.7) and the median overall survival (OS) was 17.2 months (95% CI 13.2-24.4). A significant difference was found in the median PFS equal to 7.5 months (95% CI 3.4-24.4) in SCTE pts vs. 3.7 months (95% CI 2.7-7.5) in non-SCTE, p = 0.047, and in the median OS equal to 30.6 months (95% CI 14.8-not reached) in SCTE pts vs. 14.0 months (95% CI 9.9-17.7) in non-SCTE, p=0.004. Conclusions: These data suggest that SCTE may be a predictive marker of favorable outcome in mRCC pts treated with everolimus.
Abstract 12680: Silencing miR-145 Prevents Potentiating Effects of Human Electronegative Low-Density Lipoprotein on Platelet Activation
Authors: Ming-YI Shen, Fang-Yu Chen, An-Sheng Lee, Joen-Rong Sheu, Tatsuya Sawamura, Richard A Dixon, Chung Y Hsu, Chu-Huang Chen
Journal: Circulation (2013)

Background: During ST-elevation myocardial infarction (STEMI) and ischemic stroke, platelet activation triggers thrombosis. Low-density lipoprotein in human plasma can be chromatographically resolv...
Fertility-sparing treatment by high dose oral medroxyprogesterone acetate for endometrial cancer and atypical hyperplasia in young women: A multicentric phase II study
Authors: K. Ushijima, H. Yoshikawa, T. Hirakawa, T. Yasugi, T. Saito, M. Yasuda, K. Kuzuya, T. Fujii, M. Hatae, T. Kamura
Journal: Journal of Clinical Oncology (2005)

5022 Background: Standard treatment for endometrioid adenocarcinoma, stage Ia (EC) and atypical endometrial hyperplasia (AH) is hysterectomy even in young women. High-dose of Medroxyprogesterone Acetate (MPA) is one of the options for patients who desire preserving childbearing potential. Nevertheless, the optimal dose or duration and curative rate of MPA therapy for in EC and AH in young women are still uncertain. Methods: Multicentric prospective study was carried out by 16 institutions in Japan. Twenty-five EC patients with no myometrial or cervical invasion and 17 AH patients under 40 years of age were enrolled. All patients were given MPA 600mg with low dose aspirin orally daily, and the treatment were continued for 26weeks as far as the lesions responded to it. Endometrial tissue was collected and histologically assessed at 8, 16, 26 weeks of the treatment. The diagnoses were confirmed by central pathological review board. Estrogen-progesterone therapy or assisted reproductive technologies were provided for the responders after MPA therapy. Complete response (CR) rate was the primary endpoint and toxicity, rate of pregnancy and progression free interval (PFI) were the secondary endpoints. Results: CR was found in 44% in EC and 82% in AH. Overall CR rate was 60%. Any grade 3 toxicities except body weight increase in two patients or therapeutic death were not observed. So far 9 pregnancies and 4 normal deliveries have been recorded after MPA therapy. Twelve recurrences were found in 30 CR patients (40%) between 7 to 22 months, they rechallenged MPA or underwent hysterectomy. No patients died of disease. PFI of EC and AH were 20.1months and 28.5 months respectively. Conclusions: The efficacy of fertility-sparing treatment by MPA for EC and AH was proved by this first prospective trial. Even in the CR patients, close follow-up is required because of their high recurrence rate. No significant financial relationships to disclose.
Pilot study using carboplatin (C), docetaxel (T) and capecitabine (X) before and during radiotherapy (RT) with concurrent boost as an organ-preservation strategy for locally advanced head and neck squamous cell carcinoma (HNSCC)
Authors: R. A. Schmerling, F. C. Maluf, W. N. William, F. Arruda, J. L. F. Silva, S. Correa, C. E. V. Abreu, F. P. Costa, A. C. Buzaid
Journal: Journal of Clinical Oncology (2005)

5607 Background: The role of neoadjuvant chemotherapy followed by chemotherapy administered concurrently with accelerated RT has not been established. We designed a study to evaluate the feasibility and activity of a novel neoadjuvant triple-drug regimen before and during definitive RT with concomitant boost in locally advanced HNSCC. Methods: Efficacy and toxicity data were available for 8 patients (pts) (7 males, 1 female). Median age: 56 yrs (range 39–68). Stage III: 2 pts and IV: 6 pts. Tumor sites included: oral cavity (2), oropharynx (2), hypopharynx (1), larynx (2), and unknown primary (1). Pts received 2 cycles of capecitabine (1 g/m2/d PO for 28 days), docetaxel (70 mg/m2 IV d1) and carboplatin (AUC 5 IV d1) every 28 days. Response to neoadjuvant chemotherapy was evaluated by imaging and endoscopic studies. For those with at least stable disease, 2 additional cycles with G-CSF support were given concurrently with RT at the total dose of 72Gy over 6 weeks in 42 fx (54 Gy in 30 fx with concurrent BID 18-Gy boost over the last 12 d for the primary tumor site). Neck dissection was performed in N2/N3 pts. Results: Drug dose-intensity was 96% for C; 96% for D, and 91% for X. All pts achieved an objective response to neoadjuvant chemotherapy (CR: 7 pts, PR: 1 pt). To date, all pts remain alive with no evidence of disease at a median follow-up of 10.5 months (range 6.8–19.7). The most common grade 3/4 treatment related-toxicity was mucositis (all pts) and febrile neutropenia (7 episodes). Despite local acute toxicity, all pts discontinued percutaneous gastrostomy after a median of 47 days (-13 to 158) after completion of the RT. None of our pts needed tracheostomy. Conclusions: Our pilot study suggests that the combination of neoadjuvant chemotherapy using C,T and X followed by the same schedule combined to RT with concomitant boost resulted in encouraging antitumor activity in this poor prognosis pt population. Acute toxicity, although severe, was manageable and transient. Pt accrual will continue to further explore the role of multi-agent chemotherapy before and during optimal RT in locally advanced HNSCC. No significant financial relationships to disclose.