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In this paper, we consider estimation problems involving constrained nonlinear systems with the unknown time-delays and unknown system parameters. These unknown quantities are to be estimated such that a least-squares error function between the system output and a set of noisy measurements is minimized subject to the characteristic time constraints specifying the restrictions. We first present the classical estimation formulation, where the expectation of the error function is regarded as the cost function. Then, in order to obtain robust estimates against the noises in measurements, we propose a robust estimation formulation, in which the cost function is the variance of the error function and an additional constraint indicates an allowable sacrifice from the optimal expectation value of the classical estimation problem. For these two estimation problems, we derive the gradients of the corresponding cost and constraint functions with respect to time-delays and system parameters by solving some auxiliary time-delay systems backward in time. On this basis, we develop gradient-based optimization algorithms to determine the optimal time-delays and system parameters. Finally, we consider two example problems, including a parameter estimation problem in microbial batch fermentation process, to illustrate the effectiveness and applicability of our proposed algorithms. [ABSTRACT FROM AUTHOR]

In this paper, we consider a class of optimal switching control problems with multiple time-delays and a cost on changing control and subject to terminal state constraints. A computational method involving three stages is developed to solve this class of optimal control problems. First, by param- eterizing the control function with piecewise-constant functions, the optimal switching control problem is approximated by a sequence of finite-dimensional optimization problems, where the original switching times, the control heights and the control switching times are decision variables. Second, by introduc- ing new variables, the total variation of the control variables is transformed into an equivalently smooth function. Third, we convert the constrained op- timization problem into one only with box constraints by an exact penalty function method. The gradients of the cost functional are then derived, which can be combined with any gradient-based optimization method to determine the optimal solution. Finally, a numerical example is given to illustrate the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Aim: To investigate the expression of cyclophilin A (CypA) in human hepatocellular carcinoma (HCC) and explore the effects of CypA on the cell cycle in HCC., Materials and Methods: CypA expression was assessed by immunohistochemistry in 48 cases of HCC tissues and paired adjacent tissues. CypA plasmid was transfected into HCC cells and the cell cycle was analyzed., Results: Positivity for CypA was higher in HCC tissues than in adjacent tissues (79.1% vs. 12.5%, p<0.05). Positivity for CypA was significantly higher in stage III and IV HCC than in stage I and II (p<0.05). Elevated CypA induced an increase of the percentage of S-phase cells (from 34.79% to 42.14%) and a decrease of G 0 -G 1 phase cells (from 58.10% to 50.64%)., Conclusion: CypA is overexpressed in HCC and is associated with TNM stage. CypA also appears to promote the transition of the cell cycle from G 1 to S phase., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Bevacizumab combined with standard chemotherapeutics has become a choice of treatment for several kinds of cancers. Hypertension, third-degree albuminuria, thrombosis and cardiotoxicity are the reported side-effects of bevacizumab. Among them, cardiotoxicity is a most severe, but rare outcome. We report a case of a 62-year-old female with colorectal carcinoma who was given bevacizumab-containing chemotherapy for more than 20 months and achieved a stable disease during the entire course of treatment. Thereafter, she developed cardiotoxicity including grade 3 hypertension, tricuspid regurgitation, pulmonary hypertension, left ventricular diastolic dysfunction and pericardial effusion, and was discontinued from the regimen with bevacizumab., Conclusion: Although clinically-effective, the severe cardiotoxicity of bevacizumab developed after over 20 courses of treatment prompted us to look for optimal chemotherapy prescription in order to achieve a better clinical outcome., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion., Patients and Methods: Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis., Results: The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group., Conclusion: The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Biomarkers are essential in early diagnosis and understanding of the molecular mechanism of human cancer. The expression of cyclophilin J, a novel member of the cyclophilin family, was investigated in primary gastric adenocarcinoma., Materials and Methods: Western blot analysis was carried out on 36 paired tumor and normal tissue samples; immunohistochemical analysis was carried out on 120 gastric carcinoma tissues and normal adjacent tissue., Results: Cyclophilin J protein was overexpressed in 72.2% of gastric carcinoma tissues compared to adjacent normal tissues. Immunohistochemical analysis revealed that cyclophilin J was overexpressed in 49.2% (59/120) and 23.3% (28/120) of gastric carcinoma tissues and adjacent tissues, respectively (p<0.05). Expression of cyclophilin J was associated with the degree of differentiation, but not with lymph node metastasis, gender or depth of tumor infiltration. The overall survival of patients showed no association with the overexpression of cyclophilin J protein., Conclusion: Cyclophilin J expression was up-regulated in gastric carcinoma compared to normal gastric tissues. However, in order to confirm its association with the survival of patients with gastric cancer, more cases need to be studied., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Case Report: This case study reports on a patient who relapsed with thymoma (mixed type) nine years after tumor resection. After four courses of rescue chemotherapy (docetaxel and cisplatinum), the patient was further diagnosed with pure red cell aplasia. It was noticed that cyclosporin A (CsA), which was administered to treat aplasia, could reverse chemoresistance. Its mechanism is not completely clear, but the hypothesis of CsA inhibiting P-glycoprotein mediated drug efflux is the most acceptable., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To record the efficacy and toxicity of combining bevacizumab with cisplatin in treating malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion., Patients and Methods: Forty-three patients were admitted to the Oncology Department of Yantai Yuhuangding Hospital with confirmed malignant effusion since January, 2011. Twenty of them received intrapleural and intraperitoneal perfusion of 200 mg bevacizumab plus 60 mg cisplatin every three weeks, and 23 patients received 60 mg cisplatin alone after draining effusion as much as possible. Reduction of effusion was determined by type-B ultrasonography., Results: The complete remission rate and effective rate of bevacizumab group was superior to that of the cisplatin group. The quality of life recovery rate of bevacizumab group was superior to that of the cisplatin group. The anhelation and abdominal distention of bevacizumab group was significantly improved. There was no significant difference in level III/IV toxicities and adverse effects between two groups., Conclusion: Bevacizumab significantly improved the objective response rate and quality of life of patients with malignant pleural effusion and ascites, while not causing notable adverse events., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To characterize the biochemical features of the newest member of cyclophilin family of peptidyl-prolyl cis/trans-isomerases (PPIases), cyclophilin J (CYPJ)., Materials and Methods: PPIase assays were performed on purified hCYPJ and its mutated variants. The substrate specificity, half-maximal inhibitory concentration (IC50) of cyclosporin A (CsA) inhibition and circular dichroism (CD) spectrum of CYPJ were measured. Mercury pathway profiling luciferase assays were also performed., Results: The catalytic number/Michaelis constant (kcat/KM) value of CYPJ was 9.5×10(4) s(-1)M(-1). CYPJ additionally catalyzed norleucine-proline, isoleucine-proline and glutamine-proline peptides compared to CYPA and Escherichia coli PPIases. CYPJ was inhibited by CsA in a dose-dependent manner with IC50 of 12.1±0.9 μM. The CD spectrum of CYPJ was similar to CYPA. CYPJ significantly up-regulated the transcription of E-box, E2F, retinoblastoma (Rb), p53, activator protein 1 (AP1), NF-κB and phospho-cAMP response element (CRE) cis-response element in 293T cells., Conclusion: CYPJ structurally resembles CYPA. It is sensitive to inhibition by CsA and plays a role in regulating cell growth, proliferation, and apoptosis., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)