bluuebunny/crossref_metadata_2025_split huggingface dataset:
Septal coronary artery fistula after left bundle branch area pacing assessed by multi‐imaging modalities and shunt volume quantification
Authors: Kato Hiroyuki , Yanagisawa Satoshi , Ota Ryusuke , Murakami Hisashi , Kada Kenji , Tsuboi Naoya , Inden Yasuya , Murohara Toyoaki 
Published: June 2022

AbstractSeptal coronary artery fistula is a rare but concerning complication of left bundle branch area pacing (LBBAP). We report the case of an 82‐year‐old man who was indicated for cardiac resynchronization therapy and underwent LBBAP. The patient had no chest symptoms during or after implantation. Postoperative echocardiography demonstrated a new abnormal tunnel inside the interventricular septum (IVS) and shunt flow from the IVS toward the right ventricle. Coronary angiography confirmed a septal coronary artery fistula, which might have been formed by failed deep screw attempts. Since the shunt volume assessed by the Qp/Qs was small, the patient was treated conservatively.
Flame Spread Pulsation Characteristics of Transformer Oil Vertical Spill Fire
Authors: Li Liyang , Chen Peng , Sun Ruibang , Zhai Xu , Shi Congling 
Published: June 2022

Abstract
To investigate the effects of fuel discharge rate and initial fuel temperature on flame pulsation characteristics of vertical spill fire, a series of experiments under continuous leakage conditions are conducted on a specially designed experimental setup, for which transformer oil is selected as the fuel. Results show that the vertical spill fire burning area can be divided into three parts. Both the main flame and the flash flame are involved in the flame pulsation behavior, and the essence of the flame pulsation of the vertical spill fire is the periodic alternation of the diffusion flame and the premixed flame. Flame pulsation frequency shows a linear negative correlation with the fuel leakage rate, it decreases from 3.56 Hz (4.98 ml m−1s−1) to 2.439 Hz (15.93 ml m−1s−1), and it has a positive correlation with the initial fuel temperature. As the fuel discharge rate increases, the pulsation amplitude increases while the flame transient spread rate decreases, both of them have no significant correlation with the initial fuel temperature. The ratio of the average flame pulsation amplitude to the maximum pulsation amplitude is between 0.57 and 0.76. The flame transient spread rate shows a negative correlation with the fuel discharge rate, the maximum flame spread velocity reaches 3.17 m/s and 2.85 m/s in the growing phase and shrinking phase respectively. Due to the entrainment effect of the flame plume, the flame transient spread rate in the shrinking phase is higher than that in the growing phase. Analyzed the diffusion process of fuel vapor and the heat transfer mechanism of vertical spill fire, the control of fuel leakage rate and initial temperature on the flame pulsation characteristics is mainly manifested in its influence on the fuel evaporation and diffusion process and the length of preheating area. This work provides data supplement on the flame spread of liquid fuel spill fire.
LINEAR STABILITY OF A FILTRATION FLOW WITH GAS–OIL INTERFACE WITHIN THE BRINKMAN APPROACH
Authors: Tsypkin G. G. , Shargatov V. A. 
Published: June 2022

Abstract—The problem of vertical flow stability in an oil reservoir with a gas cap is considered, when the oil flow obeys the Brinkman equation. Boundary conditions at the moving boundary of the gas-oil interface are derived and a basic solution is obtained. The normal mode method is used to study the stability of the gas–oil interface. The obtained dispersion equation is investigated. Conditions for flow stability are found for all values of the parameters, and it is shown that, in the linear approximation, the growth rate of short-wave perturbations tends to zero with increasing wave number.
Arthrodesis for Primary Osteoarthritis of Trapeziometacarpal Joint Using Multiple Kirschner Wires and Tension Band Wire in Female Patients Older than 40
Authors: HATTORI Yasunori , HAYASHI Kota , CHIA Dawn Sinn Yii , SAKAMOTO Sotestu , DOI Kazuteru 
Published: June 2022

Background: The purpose of this study was to evaluate the results of arthrodesis with multiple Kirschner (K)-wires and tension band wire for primary osteoarthritis of trapeziometacarpal (TM) joint in female patients aged 40 years or older. Methods: We retrospectively obtained data regarding all female patients 40 years or older who underwent TM joint arthrodesis for TM joint osteoarthritis with K-wires and tension band wire over a 10-year period from 2009 till 2019. Thumb length, active range of motion (ROM) at the metacarpophalangeal (MCP) joint, active ROM of radial and volar adduction and abduction and key pinch strength was measured. Patient-reported outcomes were assessed using a pain and satisfaction questionnaire and the DASH score. We also recorded postoperative complications. Results: The study included 60 thumbs in 49 patients with an average age 60 years and a mean follow-up of 40 ± 21 months. All but one thumb had radiographic evidence of fusion within 6 months and the union rate was 98%. Key pinch strength increased from 2.3 to 4.9 kg after surgery. Total arc of motion in radial adduction–abduction decreased from 16° to 10°. Total arc of motion in volar adduction–abduction decreased from 25° to 9°. One patient experienced attritional rupture of the flexor pollicis longus tendon attributed to a K-wire penetration into the carpal tunnel. Although 46 thumbs (77%) had no or mild hardware-related symptoms, they underwent hardware removal after solid bone union. In 23 thumbs with follow-up period longer than 48 months, two thumbs developed scaphotrapeziotrapezoid joint arthritis and two thumbs developed metacarpophalangeal joint arthritis. Conclusions: We found that arthrodesis with multiple K-wires and tension band wire is a valuable option in the management of trapeziometacarpal joint osteoarthritis in female patients aged 40 years or older. Level of Evidence: Level IV (Therapeutic)
Combination therapy of inhibitors of epidermal growth factor receptor/vascular endothelial growth factor receptor 2 (AEE788) and the mammalian target of rapamycin (RAD001) offers improved glioblastoma tumor growth inhibition
Authors: Goudar Ranjit K. , Shi Qing , Hjelmeland Mark D. , Keir Stephen T. , McLendon Roger E. , Wikstrand Carol J. , Reese Elizabeth D. , Conrad Charles A. , Traxler Peter , Lane Heidi A. , Reardon David A. , Cavenee Webster K. , Wang Xiao-Fan , Bigner Darell D. , Friedman Henry S. , Rich Jeremy N. 
Published: June 2022

AbstractMalignant gliomas are highly lethal tumors that display striking genetic heterogeneity. Novel therapies that inhibit a single molecular target may slow tumor progression, but tumors are likely not dependent on a signal transduction pathway. Rather, malignant gliomas exhibit sustained mitogenesis and cell growth mediated in part through the effects of receptor tyrosine kinases and the mammalian target of rapamycin (mTOR). AEE788 is a novel orally active tyrosine kinase inhibitor that decreases the kinase activity associated with the epidermal growth factor receptor and, at higher concentrations, the vascular endothelial growth factor receptor 2 (kinase domain region). RAD001 (everolimus) is an orally available mTOR inhibitor structurally related to rapamycin. We hypothesized that combined inhibition of upstream epidermal growth factor receptor and kinase domain region receptors with AEE788 and inhibition of the downstream mTOR pathway with RAD001 would result in increased efficacy against gliomas compared with single-agent therapy. In vitro experiments showed that the combination of AEE788 and RAD001 resulted in increased rates of cell cycle arrest and apoptosis and reduced proliferation more than either agent alone. Combined AEE788 and RAD001 given orally to athymic mice bearing established human malignant glioma tumor xenografts resulted in greater tumor growth inhibition and greater increases in median survival than monotherapy. These studies suggest that simultaneous inhibition of growth factor receptor and mTOR pathways offer increased benefit in glioma therapy.
Gene expression changes induced by green tea polyphenol (−)-epigallocatechin-3-gallate in human bronchial epithelial 21BES cells analyzed by DNA microarray
Authors: Vittal Ragini , Selvanayagam Zachariah E. , Sun Yi , Hong Jungil , Liu Fang , Chin Khew-Voon , Yang Chung S. 
Published: June 2022

Abstract
Many studies suggest green tea is a cancer chemopreventive agent. This effect has been attributed to its major constituent (−)-epigallocatechin-3-gallate (EGCG). EGCG is also observed to have cytotoxic anticancer effects, especially when used in combination with certain chemotherapeutic agents. The biochemical actions of EGCG in chemoprevention and anticancer effects have been studied; however, the mechanisms of action are not clearly understood. We show here by expression genomics the effects of EGCG (25 μmol/L) in the Ha-ras gene transformed human bronchial epithelial 21BES cells. We found induction of temporal changes in gene expression and the coalescence of specific genetic pathways by EGCG. In this experimental system, hydrogen peroxide (H2O2) was produced. By treating cells with EGCG in the presence or absence of catalase, we further distinguished gene expression changes that are mediated by H2O2 from those that are H2O2 independent. Many genes and cellular pathways, including genes of the transforming growth factor-β signaling pathway, were H2O2 dependent because the effects were abolished by catalase. Gene expression changes that were not affected by catalase included those of the bone morphogenetic protein signaling pathway, peptidylprolyl isomerase (cyclophilin)–like 2, alkylated DNA repair enzyme alkB, polyhomeotic-like 2, and homeobox D1. We show further that EGCG and H2O2 differentially transactivated the bone morphogenetic protein and the transforming growth factor-β response element promoter reporters, respectively, thus confirming results from DNA microarray analysis. The elucidation of gene expression changes between H2O2-dependent and H2O2-independent responses helps us better understand the cancer chemopreventive and anticancer actions of EGCG.
Topoisomerase-IIα expression as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel
Authors: Durbecq Virginie , Paesmans Marianne , Cardoso Fatima , Desmedt Christine , Di Leo Angelo , Chan Stephen , Friedrichs Kay , Pinter Tamas , Van Belle Simon , Murray Elizabeth , Bodrogi István , Walpole Euan , Lesperance Bernard , Korec Stefan , Crown John , Simmonds Peter , Perren Thimothy J. , Leroy Jean-Yves , Rouas Ghizlane , Sotiriou Christos , Piccart Martine , Larsimont Denis 
Published: June 2022

Abstract
Purpose: The predictive value of topoisomerase-IIα (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel. Experimental design: Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m2 q3wks) with docetaxel (100 mg/m2 q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1). Results: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03–1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94–1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content &gt;10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87–6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04–0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content &gt;10% (OR, 8.31; 95% confidence interval, 1.86–37.03; P = 0.05). Conclusions: (a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.
Genistein potentiates inhibition of tumor growth by radiation in a prostate cancer orthotopic model
Authors: Hillman Gilda G. , Wang Yu , Kucuk Omer , Che Mingxin , Doerge Daniel R. , Yudelev Mark , Joiner Michael C. , Marples Brian , Forman Jeffrey D. , Sarkar Fazlul H. 
Published: June 2022

Abstract
Objective: We have shown previously that pretreatment with genistein potentiated cell killing induced by radiation in human PC-3 prostate carcinoma cell line in vitro. We tested this approach in vivo using an orthotopic prostate carcinoma model of PC-3 cells in nude mice. Methods: Established prostate tumors were pretreated with p.o. genistein at a dose of 5 mg/d for 2 days followed by tumor irradiation with 5 Gy photons. One day after radiation, genistein was resumed and given every other day for 4 weeks. Results: Genistein combined with radiation caused a significantly greater inhibition of primary tumor growth (87%) compared with genistein (30%) or radiation (73%) alone. The number of metastatic lymph nodes was also significantly decreased following genistein and radiation. Paradoxically, genistein alone increased the size of lymph nodes associated with heavy tumor infiltration. Genistein-treated prostate tumors were large with necrosis, apoptotic cells, and giant cells and have a lower proliferation index than in control tumors. Following radiation, areas of tumor destruction replaced by fibrotic tissue and inflammatory cells as well as giant cells were observed, which are typical of radiation effect. After radiation and genistein treatment, an increase in giant cells, apoptosis, inflammatory cells, and fibrosis was observed with decreased tumor cell proliferation consistent with increased tumor cell destruction. Long-term therapy with genistein after prostate tumor irradiation significantly increased survival. Conclusions: Genistein combined with prostate tumor irradiation led to a greater control of the growth of the primary tumor and metastasis to lymph nodes than genistein or radiation alone, resulting in greater survival.
Targeting tumor microvessels using doxorubicin encapsulated in a novel thermosensitive liposome
Authors: Chen Qing , Tong Sheng , Dewhirst Mark W. , Yuan Fan 
Published: June 2022

Abstract
Liposomal drugs accumulate only in perivascular regions in tumors after i.v. injection. Thus, they cannot kill tumor cells in deeper tissue layers. To circumvent this problem, we investigated effects of doxorubicin (DOX) encapsulated in a lysolecithin-containing thermosensitive liposome (LTSL) on tumor microcirculation because damaging microvessels would stop nutrient supply to deeper tumor cells. We used LTSL-DOX in combination with hyperthermia to treat a human squamous carcinoma xenograft (FaDu) implanted in dorsal skinfold chambers in nude mice. Before the treatment, the RBC velocity in tumors was 0.428 ± 0.037 mm/s and the microvascular density was 3.93 ± 0.44 mm/mm2. At 24 hours after the treatment, they were reduced to 0.003 ± 0.003 mm/s and 0.86 ± 0.27 mm/mm2, respectively. The same treatment, however, caused only 32% decrease in the RBC velocity and no apparent change in microvascular networks in normal s.c. tissues over the same period. LTSL and LTSL-DOX alone had no effect on tumor microcirculation, and LTSL plus hyperthermia caused only a transient decrease in the RBC velocity in tumors. At 24 hours after treatments, tumor microcirculation in all these control experiments was insignificantly different from that before the treatments. We also examined apoptosis of cells in tumors at different time points after LTSL-DOX plus hyperthermia treatment and observed few apoptotic cells in tumor microvessels. In conclusion, the rapid release of DOX during hyperthermia could make the drug to shutdown tumor blood flow while have only minor effects on normal microcirculation in s.c. tissues.
Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
Authors: Fry David W. , Harvey Patricia J. , Keller Paul R. , Elliott William L. , Meade MaryAnne , Trachet Erin , Albassam Mudher , Zheng XianXian , Leopold Wilbur R. , Pryer Nancy K. , Toogood Peter L. 
Published: June 2022

Abstract
PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50, 0.011 μmol/L) and Cdk6 (IC50, 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. It is a potent antiproliferative agent against retinoblastoma (Rb)-positive tumor cells in vitro, inducing an exclusive G1 arrest, with a concomitant reduction of phospho-Ser780/Ser795 on the Rb protein. Oral administration of PD 0332991 to mice bearing the Colo-205 human colon carcinoma produces marked tumor regression. Therapeutic doses of PD 0332991 cause elimination of phospho-Rb and the proliferative marker Ki-67 in tumor tissue and down-regulation of genes under the transcriptional control of E2F. The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors.
Biological impediments to monoclonal antibody–based cancer immunotherapy
Authors: Christiansen Jason , Rajasekaran Ayyappan K. 
Published: June 2022

Abstract
The ability of antibodies to exploit antigenic differences between normal and malignant tissues and to exact a variety of antitumor responses offers significant advantages to conventional forms of therapy. Several monoclonal antibodies (mAb) have already proved to be relatively well tolerated and effective for the treatment of many different malignant diseases. However, mAbs must overcome substantial obstacles to reach antigens presented on target cells to be of therapeutic value. Intravenously administered antibodies must avoid host immune response and contend with low or heterogeneous expression of antigen on tumor cells. Antibodies must also overcome significant physical barriers en route to a solid tumor mass, including the vascular endothelium, stromal barriers, high interstitial pressure, and epithelial barriers. Here we review the application and evolution of mAbs as effective forms of treatment, with particular attention to the barriers and impediments to successful treatment and discuss strategies to overcome these barriers and improve the efficacy of mAb-based therapy.
Different proteome pattern of epidermal growth factor receptor–positive colorectal cancer cell lines that are responsive and nonresponsive to C225 antibody treatment
Authors: Skvortsov Sergej , Sarg Bettina , Loeffler-Ragg Judith , Skvortsova Ira , Lindner Herbert , Werner Ott Helmut , Lukas Peter , Illmensee Karl , Zwierzina Heinz 
Published: June 2022

AbstractThe monoclonal antibody C225 directed against the epidermal growth factor receptor (EGFR) blocks downstream mitogenic signaling and is effective in patients with advanced colorectal cancer. Clinical data, however, suggest the presence of primary and secondary resistance mechanisms that are hardly understood. To define proteins involved in EGFR-triggered growth regulation and potential resistance mechanisms, we characterized the proteome profile of two colorectal cancer cell lines with a high expression of functional EGFR but a different response to treatment with C225. In Caco-2 and HRT-18, a complete saturation of EGFR was achieved after incubation with C225; whereas Caco-2 showed inhibition of proliferation, growth of HRT-18 was not suppressed. Using two-dimensional electrophoresis and subsequent mass spectrometry, we identified 14 proteins differentially expressed in both cell lines. All proteins are involved in metabolic pathways and malignant growth. Expression of enzymes such as ubiquitin carboxyl-terminal hydrolase isozyme 1, glutathione S-transferase P, and chloride intracellular channel protein 1 does not seem to interfere with the antiproliferative effect of anti-EGFR antibody. On the other hand, expression of proteins such as fatty acid binding protein and heat shock protein 27 might constitute strong antiapoptotic effects contributing to the nonresponse of HRT-18 to C225 treatment. Proteome-based investigations can help us better understand the complex protein interactions involved in EGFR signaling and its blockage by therapeutic monoclonal antibodies.
Highly efficient delivery of p16 antitumor peptide into aggressive leukemia/lymphoma cells using a novel transporter system
Authors: Kondo Eisaku , Seto Masao , Yoshikawa Kazuhiro , Yoshino Tadashi 
Published: June 2022

AbstractMolecular targeting of hematopoietic malignancies has been generally hindered by technological obstacles to gene delivery in the neoplastic cells. The development of peptide delivery systems based on protein transduction domains has recently gained attention as a means of potentially overcoming these impediments. Here, we present a novel peptide transporter system that increases the efficiency of peptide delivery more than 10 times compared with the previous methods. The transporter, Wr-T, has an enlarged hydrophobic pocket consisting of triple tryptophan-rich domains fused with nine d-enantiomer polyarginines (r9) via Gly-Pro-Gly spacer, which serves to augment delivery of a cargo peptide. Wr-T–mediated transport of p16INK4a functional peptide dramatically inhibits growth of highly aggressive leukemia/lymphomas by up to 80% through restoration of p16 function. The Wr-T system thus represents a highly effective approach to cargo peptide delivery with the potential for substantially developing p16 peptide–based therapy for hematopoietic malignancies.