tbuckley/cabot-search huggingface dataset:
Identification of MYO18A as a novel PAK2 binding partner
Authors: Rae-Mann Hsu, Ming-Hung Tsai, Kuan-Yi Chien, Jau-Song Yu
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3760 

p21-activated kinases (PAKs) are serine/threonine kinases activated by various extracellular stimuli and have recently been found to be key regulators of various signalling networks. PAK2, one of the group I PAKs, has been shown to be involved in the regulation of apoptosis, cell morphology, cell motility, actin reorganization and transformation. To gain insight into the biological functions of PAK2, a proteomic approach was employed to identify the PAK2-interacting proteins. Endogenous PAK2 and its interacting proteins were immunoprecipitated with a polyclonal anti-PAK2 (N17) antibody. Using 1D SDS-PAGE separation and silver staining, a protein band near 200 kDa was observed and identified as MYO18A by MALDI-TOF mass spectrometry. MYO18A has emerged in recent years as a member of the myosin superfamily which is known as eukaryotic actin-dependent molecular motors important for a broad range of functions such as muscle contraction, vision, hearing, cell motility, and host cell invasion of apicomplexan parasites. MYO18A was originally identified in hemopoietic supportive bone marrow stromal lines and is widely expressed in all tissues and cell lines. To test the interaction, a rabbit polyclonal antibody against the C-terminal region of MYO18A was generated. Immunoprecipitation and western blot data confirmed this interaction in several normal and tumor cells. The structure of MYO18A consists of a KE-rich region, an N-terminal PDZ (PSD-95/Dlg/ZO-1) domain, a characteristic myosin homology region of head, neck (with one IQ motif), and coiled-coil tail. Using different MysPDZ deletion mutants, we demonstrated that the amino acid 1768~2054 of MysPDZ was crucial for its interaction with the PAK2-immunocomplexes. Moreover, partial colocalization of MYO18A and PAK2 in the cytoplasm was observed using confocal microscopy suggesting that MYO18A indeed participated in the PAK2-immunocomplexes. In summary, we have shown for the first time that MYO18A is a binding partner of PAK2. More experiments are undergoing to substantiate this observation.
Risks of Young Age for Selected Neurocognitive Deficits in Medulloblastoma Are Associated With White Matter Loss
Authors: Raymond K. Mulhern, Shawna L. Palmer, Wilburn E. Reddick, John O. Glass, Larry E. Kun, June Taylor, James Langston, Amar Gajjar
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To test the hypothesis that inadequate development of normal-appearing white matter (NAWM) is associated with the relationship between young age at the time of craniospinal irradiation (CRT) and deficient neurocognitive performance in survivors of childhood medulloblastoma. PATIENTS AND METHODS: Forty-two patients treated since 1985 participated in this cross-sectional study. All had been treated with CRT with or without chemotherapy and had survived 1 or more years after treatment. Neurocognitive evaluations were conducted with tests of intellect (intelligent quotient; IQ), verbal memory, and sustained attention. Quantitative magnetic resonance imaging, using a hybrid neural network, assessed the volume of NAWM. RESULTS: Neurocognitive test results were below normal expectations for age at the time of testing. A young age at CRT was significantly associated with worse performance on all neurocognitive tests except that of verbal memory. An increased time from completion of CRT was significantly associated with worse performance on all neurocognitive tests except that of sustained attention. After statistically controlling for the effects of time from CRT, we examined the association of NAWM with neurocognitive test results. These analyses revealed that NAWM accounted for a significant amount of the association between age at CRT and IQ, factual knowledge, and verbal and nonverbal thinking, but not sustained attention or verbal memory. CONCLUSION: The present results suggest that, at least for some cognitive functions, deficient development and/or loss of NAWM after CRT may provide a neuroanatomical substrate for the adverse impact of a young age at the time of CRT.
Perifosine (P), active as a single agent for renal cell carcinoma (RCC), now in phase I trials combined with tyrosine kinase inhibitors (TKI)
Authors: J. Stephenson, M. Schreeder, J. Waples, J. Hargis, L. Campos, R. Birch, I. Henderson
Journal: Journal of Clinical Oncology (2007)

15622 Background: P is an oral alkylphosphocholine with effects on multiple pathways including Akt, MAPK and JNK. Akt/S6 is often activated in RCC and associated with resistance. In a phase I study of P, 3/6 RCC patients (pts) had stable disease (SD) lasting for 4, 6 and 14 months (m). RCC was further assessed in a broad phase 2 trial, and subsequently, two phase 1 trials combining P with TKIs have been initiated. This is an update of the phase II and first report of the phase I combination trials. Methods: From 3/05 to 5/06 241 pts, including 13 with RCC, were randomized to P, 50 mg daily or 1200 mg weekly. Subsequently the protocol was amended to P, 100 mg daily or 900 mg weekly, and enrollment continues. Pts with measurable disease who received at least 2 courses of P and at least one tumor measurement after initiation of P were considered evaluable for response using RECIST criteria. After demonstrating P activity in RCC, two phase 1 studies of P combined with either sorafenib (SOR) or sunitinib (SUT) were initiated. In each study, the dose of P is escalated from 50 mg qd to 50 mg tid. SOR is escalated from 400 mg qd to 400 mg bid and SUT from 25 to 50 mg qd for 4 weeks out of 6. Results: In the broad phase II study, 6 pts (66%) achieved clinical benefit. (See table ) including 3 pts (33%) with partial responses [duration 4, 6.5 and 9 m] and 3 pts (33%) with SD [9+, 9+ and 10 m]. Three pts progressed. The main toxicities were grade 1 nausea, vomiting, diarrhea, and fatigue. Daily P was significantly better tolerated than weekly and data are presented in detail in another abstract. Enrollment in cohorts 1 and 2 of the P/SOR study is complete. No grade 3 or 4 toxicities and increase in hand foot syndrome has been seen. Accrual to cohort 1 of the P/SUT study is also complete. Enrollment will be complete by May 2007. Conclusions: P is active in RCC. Phase 1 trials of P with TKIs have demonstrated no increased toxicity with less than maximal doses of P and TKI [Table: see text] No significant financial relationships to disclose.
Authors’ reply to Whitlock and Saied and colleagues
Authors: Karim Ladha, Tobias Kurth, Matthias Eikermann
Journal: BMJ (2015)

Whitlock raises the important problem of default ventilator settings.1 2 Sex imbalances in the use of intraoperative protective ventilation have been described previously.3 Default settings on the ventilator probably play a large part in this discrepancy, as does the difference in the calculation of ideal body weight, which is based on sex. The default settings on the ventilators at our institution are almost identical to …
FDG uptake as a predictor of outcome in stage I non-small cell lung cancer
Authors: A. K. Viswanathan, G. Pillot, B. Goodgame, Z. Yang, J. Shriki, F. Gao, F. Dehdashti, B. A. Siegel, R. Govindan
Journal: Journal of Clinical Oncology (2006)

7224 Background: Lung cancer is the leading cause of cancer-related mortality in both men and women in the United States. Over 80% of patients are diagnosed with non-small cell lung cancer (NSCLC) and approximately 30% of patients with NSCLC present with resectable disease. Nearly 40–50% of patients with resected stage I NSCLC develop recurrent disease. Currently there are no clinical, radiological, or molecular markers to predict outcomes following surgery in early stage NSCLC. Positron emission tomography (PET) with 2-[ 18 F] fluoro-2-deoxy-D-glucose (FDG-PET) is used commonly in the staging work up of NSCLC. The standardized uptake value (SUV) is a semiquantitive measure of FDG uptake that correlates with tumor doubling time. We studied the relationship between the maximum preoperative tumor SUV (SUV max ) for FDG and disease-free survival (DFS) in patients with resected stage I NSCLC. Methods: We identified 153 consecutive patients diagnosed with stage I NSCLC between 1999 and 2003 who had undergone FDG-PET before curative surgical resection. Data were collected regarding stage distribution, histology, recurrence and survival. No patient in this cohort received adjuvant chemotherapy or radiotherapy. SUV max above and below the median was correlated with DFS. Results: Of 153 patients with stage I NSCLC, 90 (59%) had T1 and 63 (41%) had T2 tumors. The mean and median follow-up time for the cohort was 2.9 and 3.1 years respectively. The mean and median SUVs were 7.0 and 6.0 respectively. The 5-year DFS categorized by SUV max &lt; 6 vs. SUV max ≥ 6 was 62% vs. 46 (p = 0.0036) for the entire cohort; 64% vs. 54% (p = 0.20) for the T1 subset; and 60% vs. 40% (p = 0.07) for the T2 subset. Conclusions: High SUV max (≥ 6) on preoperative FDG-PET is a predictor of poor outcome in resectable stage I NSCLC. [Table: see text]
Retrospective analysis of patterns of recurrence seen on MRI in patients with recurrent glioblastoma multiforme treated with bevacizumab plus irinotecan
Authors: R. M. Zuniga, R. Torcuator, T. Doyle, J. Anderson, R. Jain, J. Orley, M. Rosenblum, T. Mikkelsen
Journal: Journal of Clinical Oncology (2008)

13013 Background: Glioblastoma multiforme (GBM) is characterized by diffuse parenchymal infiltration and regional angiogenesis. Bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, has shown remarkable response to treatment rates in patients with recurrent GBM. The best way to assess tumor recurrence via MRI studies has yet to be determined. We have observed the development of distant and new foci of increased FLAIR signals that do not correlate with changes seen on gadolinium-enhanced sequences (Gd-MRI). Methods: We retrospectively analyzed Gd-MRI and FLAIR MRI sequences of 24 patients who demonstrated either focal (a new enhancing lesion or FLAIR signal < 2 cm from the original tumor), distant (new focus > 2 cm outside original tumor) or both focal and distal recurrence while treated with bevacizumab and irinotecan. Results: Ten patients (10/24) demonstrated only focal recurrence, one patient (1/24) only distant recurrence (to cerebellum) and nine patients (9/24) both focal and distant recurrences on Gd-MRI. Four patients (4/24) did not show any recurrence on Gd-MRI. These patients only presented with clinical decline and FLAIR changes. Ten patients (10/24) demonstrated only focal recurrence, two patients (2/24) only distant recurrence (both in the cerebellum) and twelve patients (12/24) revealed both focal and distant recurrence on FLAIR (3 to midbrain) sequences. There was concordance of 87% (20/23) in distal only and focal only recurrences on Gd-MRI and FLAIR. Twenty-one percent (5/24) of patients with recurrence seen on FLAIR involved the posterior fossa without concordant findings on Gd-MRI sequences. Conclusions: Although bevacizumab effectively inhibits angiogenesis, there are patients who recur despite stable areas of gad-enhancement. This has been observed by an increase in FLAIR signals without corresponding increased areas of enhancement. Tumor recurrence in patients with inhibited angiogenesis may recur via cooption of pre-existent vasculature. The inclusion of non-enhanced MRI sequences as part of criteria to assess GBM recurrence may be warranted. A larger prospective study is required in order to build upon the understanding of the pattern of recurrence in patients with GBM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech
Management and monitoring of arthralgias in breast cancer patients treated with aromatase inhibitors in an outpatient oncology clinic.
Authors: P. Menas, D. E. Merkel, W. Hui, G. W. Carro, J. Lawton, A. Blankenship, A. Harper
Journal: Journal of Clinical Oncology (2010)

e11062 Background: Aromatase inhibitors (AIs) are often used as first-line adjuvant treatment of breast cancer in postmenopausal women with hormone receptor positive tumors. Recommended length of AI treatment is five years. Arthralgias are common and are often cited as the primary reason for lack of compliance and discontinuation of therapy. The incidence of AI-induced arthralgias in literature ranges from 25%-40%. The initial purpose of this retrospective study was to describe the incidence and management of AI-induced arthralgias in KCCC patients. Further evaluation led to the development and the implementation of a treatment algorithm and electronic chart documentation. Methods: The institutional review board approved study included women with hormone receptor positive breast cancer who received adjuvant therapy with an AI. Data was collected concerning whether patients had experienced arthralgias, onset of arthralgias in relation to previous chemotherapy, and which arthralgia management strategies had been tried. Confidentiality was maintained according to HIPPA. A multidisciplinary oncology team met to develop a standardized treatment algorithm and electronic chart documentation tools. Results: Incidence of arthralgias at KCCC was 48% and of those, 88% were managed without a change in AI therapy. Patients who reported AI-induced arthralgias were younger than patients who did not report arthralgias (61 vs. 65 yrs, p = 0.002). There was no statistical difference in incidence of arthralgias in patients with a history of chemotherapy versus those who did not receive chemotherapy (p = 0.352). Of patients presenting with AI-induced arthralgias, 41% did not have documented physician-managed treatment. Of KCCC patients, 32% were documented as having arthralgias within the first 6 months of therapy initiation. The modality used to manage arthralgias (OTC, Rx meds, herbals or non-pharm) did not affect whether patients were able to continue on initial AI therapy. Conclusions: A standardized treatment algorithm and electronic chart documentation tools were developed and implemented in order to facilitate the management of AI-induced arthralgia patients by their oncologists. No significant financial relationships to disclose.
LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice
Authors: Yasunori Suematsu, Shin‐ichiro Miura, Masaki Goto, Yoshino Matsuo, Tadaaki Arimura, Takashi Kuwano, Satoshi Imaizumi, Atsushi Iwata, Eiji Yahiro, Keijiro Saku
Journal: European Journal of Heart Failure (2016)
Clinical characteristics of non-Hodgkin's lymphoma (NHL) in Vietnam era (V) and non-Vietnam era veterans (Non V).
Authors: S. Srinivas, K. Kim, T. Kalwar, M. Barry, V. T. Chang, M. Bryan, M. L. Gonzalez, J. Cogswell, M. Cholankeril, B. Kasimis
Journal: Journal of Clinical Oncology (2010)

8077 Background: There has been increased interest in V veterans with lymphoid malignancies. We compared the survival and severity of non-Hodgkin's lymphoma in veterans from V and non-V at a VA medical center. Methods: In an IRB- approved protocol, we reviewed the records of veterans diagnosed with NHL from January 1997 to December 2009 at the VANJHCS. Records were reviewed for demographic, clinical, pathological data, Vietnam status, number of chemotherapy treatments, radiation therapy, and total number of treatments and survival. We tabulated the Performance Status (PS), International Prognosis Index (IPI), Follicular Lymphoma International Prognostic Index (FLIPI), Charlson Comorbidity Index (CMI), the Kaplan-Feinstein Comorbidity Index (KFI), the Cumulative Illness Rating Scale (CIRS) and Vietnam status. We then performed Cox regression analyses to determine predictors of survival. Results: There were 114 veterans who met the eligibility criteria and their data was analyzed. There were 61 V and 52 non-V and 1 who did not have a documented status. The groups did not differ in the following characteristics PS, stage, laboratory parameters, IPI, FLIPI. Differences in their clinical features are summarized (Table). Survival predictors for both the V and non-V veterans were the PS, hemoglobin, LDH, albumin, grade. However, in V veterans, beta 2 microglobulin (p< 0.001), IPI (p< 0.04), FLIPI (p< 0.034) and IPIFLIPI (p< 0.005) were additional predictors of survival. Median survival for V veterans was 1,068 days (95% CI 802-?) and Non-V was 1,546 days (95% CI 464-1995) (p<0.0001). Conclusions: The V veterans were significantly younger compared to the Non-V veterans. While their stage and grade of the disease was not different, their survival was significantly shorter. V veterans with NHL may represent a distinct group of lymphoma patients with poor prognosis. Parameters V Non-V p value Age (years) Median 56 (27-67) 73 (37-89) p < 0.001 Race (AA) 17 (33%) 6 (14%) p < 0.029 Charlson comorbidity index 5 (1-12) 7 (2-12) p < 0.009 CIRS15 3 (0-5) 3.5 (1-5) p < 0.029 Number of systemic therapy 1 (0-5) 1 (0-3) p < 0.007 Survival (days) 1,068(95% CI 802-?) 1,546(95% CI 464-1,995) p < 0.0001 No significant financial relationships to disclose.
Clinical care in resource poor countries is often provided by people outside the medical establishment
Authors: F. Cutts, A. Mills
Journal: BMJ (1996)

istration is focusing on this in its "health in the next millennium" work programme, as is the Medical Research Council in its Gambia project, and the Liverpool School of Tropical Medicine now incorporates non-communicable diseases into its diploma courses.We suggest that the specialty of tropical medicine should shift towards a broader specialty of "health in developing countries," with the multidisciplinary inputs that the authors recommend, rather than be subsumed into infectious diseases.
Toward incident reporting (IR) systems: A safety culture survey within the oncology network of a northern Italian region
Authors: M. Aita, L. Zanier, E. Rijavec, V. Merlo, J. Menis, V. Della Mea, L. Deroma, R. Donato, F. Puglisi, G. Fasola
Journal: Journal of Clinical Oncology (2009)

e17527 Background: Physicians are reluctant partners in error reporting. Insufficient evidence exists on what may affect IR in a specific cultural and organizational context. The primary endpoint of our study was to offer a critical perspective on the dominant attitudes toward IR systems among health operators of Friuli-Venezia Giulia cancer network. The survey was part of a Health Department patient safety project. Methods: A preliminary PubMed and ASCO database search was performed (keywords: incident/error reporting, attitudes, barriers, blame/safety culture, cancer, oncology, chemotherapy). Two web-based questionnaires were administered to health personnel of Oncology Units (OU) with developing and existing IR systems, respectively. Data were collected in a MySQL database and managed by PhpMyAdmin. SAS 9.1 was used for the analysis of frequency distributions. Results: Target population: 14 OU; 2 University Hospitals, 1 Scientific Institute for Research, Hospitalization, and Health Care (SIRHHC) (2 OU), 10 Hospital Centers; 262 operators (83 physicians, 172 nurses, 2 pharmacists, 5 technicians). Overall response rate: 44.6%; physician/nurse 59/36%; University Hospital (n = 99)/SIRHHC (n = 55)/Hospital Center (n = 101) 73%/9%/38%. Knowledge of risk management issues: 86% (90% of untrained operators from IR-free centers). Eighty-six percent of all operators showed a favourable attitude toward voluntary IR systems. Main reasons: patient safety improvement (65%); organizational growth (38%); professional duty (20.5%). A 78.5% preference for computerized forms was recorded. On a five-point scale, IR features rating 5 in &gt;50% of the answers were: simplicity (85%); getting a feed-back (76%); exhaustivity (66%); adoption of organization more than individual recommendations (59%). Specific training, feedback guarantee and plainness of reporting forms were suggested by 90, 64, and 51% of all operators as essential measures for system acceptance and user satisfaction. Conclusions: Logistic and organizational factors (i.e., time constraints, work overload, resource allocation to incident reporting more than investigation and learning back) should be taken in account by county health directors aiming for successful reporting systems. No significant financial relationships to disclose.
Estimation of travel time and costs required for patients with cancer to receive outpatient treatment using electronic medical record data.
Authors: Takahiro Isshiki, Yuko Kimura, Naoko Takei, Noboru Hagino, Tsunehiko Komatsu
Journal: Journal of Clinical Oncology (2013)

270 Background: Cancer creates a tremendous financial burden. Cancer-related costs are categorized into direct, indirect and psychosocial costs. Although there have been many reports on medical care costs, which are direct, those on other costs are extremely scarce. We estimated travel time and costs required for cancer patients to receive outpatient treatment. Methods: We studied 524 cancer patients given anti-cancer treatment between February 2009 and December 2012 at the Outpatient Chemotherapy Center of Teikyo University Chiba Medical Center. Address data were extracted from Data Warehouse electronic medical records, and travel distance and time required for outpatient treatment were calculated via MapInfo and ACT Distance Calculator Package. Transportation costs were estimated on the basis of ¥274 (= $3.00) per kilometer. Results: Average round-trip travel distances, times, and costs by cancer type are shown below. Average round-trip travel distance, time, and cost for all patients were 26.7 km, 72.5 minutes, and ¥7,303 ($79.99), respectively. Conclusions: Cancer patients incurred a travel cost of approximately ¥4,000 to ¥9,000 ($40.00 to $100.00) for each outpatient treatment. With population aging, seniors living alone and senior households are increasing, and outpatient visits are becoming a common burden. [Table: see text]