Unexpected therapeutic effects of cisplatin

Metallomics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1182-1199 ◽  
Author(s):  
Martina Raudenska ◽  
Jan Balvan ◽  
Michaela Fojtu ◽  
Jaromir Gumulec ◽  
Michal Masarik
Keyword(s):  
Dna Binding ◽  
Therapeutic Response ◽  
Therapeutic Effects ◽  
Antineoplastic Action

Mechanisms of cisplatin antineoplastic action are beyond DNA binding. Alternative effects of cisplatin that can support a good therapeutic response are discussed in this review.

scholarly journals A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens—a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems

2012 ◽  
Vol 11 ◽  
pp. CIN.S8185 ◽  
Author(s):  
Xiangfang Li ◽  
Lijun Qian ◽  
Michale L. Bittner ◽  
Edward R. Dougherty
Keyword(s):  
Systems Biology ◽  
Drug Development ◽  
Tumor Growth ◽  
Hybrid Systems ◽  
Anticancer Agents ◽  
Therapeutic Response ◽  
Therapeutic Effects ◽  
Systems Model ◽  
Optimal Drug ◽  
Dosing Regimens

Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing. The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index. A dynamic hybrid systems model is proposed to study drug antitumor effect from the perspective of tumor growth dynamics, specifically the dosing and schedule of the periodic drug intake, and a drug's pharmacokinetics and pharmacodynamics information are linked together in the proposed model using a state-space approach. It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

scholarly journals RAF1 expression is correlated with HAF, a parameter of liver computed tomographic perfusion, and may predict the early therapeutic response to sorafenib in advanced hepatocellular carcinoma patients

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 167-174
Author(s):  
Ninzi Tian ◽  
Dong Wu ◽  
Ming Tang ◽  
Huichuan Sun ◽  
Yuan Ji ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Response ◽  
Therapeutic Effects ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Expression Levels ◽  
Portal Vein Flow ◽  
Tumor Tissues ◽  
Resistant Group

AbstractObjectivesMonitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.MethodsA total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.ResultsAccording to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.ConclusionRAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

Therapeutic Effects of Moxibustion on Experimental Tumor

1999 ◽  
Vol 27 (02) ◽  
pp. 157-166 ◽  
Author(s):  
Dou-Mong Hau ◽  
I-Hsin Lin ◽  
Jaung-Geng Lin ◽  
Yung-Hsich Chang ◽  
Ching-Ha Lin
Keyword(s):  
Therapeutic Response ◽  
Subcutaneous Tissue ◽  
Tumor Therapy ◽  
Radioactive Tracer ◽  
Control Group ◽  
Therapeutic Effects ◽  
Experimental Tumor ◽  
Mean Survival Time ◽  
Reliable Model ◽  
Experimental Group

This work investigated the therapeutic effects of the improved form of moxibustion (MT) on experimental tumor. Sarcoma 180 cells (1 × 107) were transplanted into the subcutaneous tissue in the breast area of female ICR mice. Mice bearing a tumor were divided into one control and four experimental groups. The experimental groups were treated with MT for 1, 2, 3 and 4 times (abbreviated as MT1, MT2, MT3, MT4, respectively). This study showed that the experimental group treated with MT3 displayed the optimal therapeutic response. The longest mean survival time (87.8 days) within 120 days after treatment of MT3 significantly differed from the control group (60.2 days). In addition, uptake of 86Rb-radioactive tracer significantly decreased in tumors treated with MT3. The improved form of moxibustion used in this study is a reliable model of localized hyperthermia in tumor therapy.

scholarly journals AP-2 Family of Transcription Factors: Critical Regulators of Human Development and Cancer

2021 ◽  
Vol 5 (1) ◽  
pp. 1-4
Author(s):  
Yi-Liu Yang ◽  
Lin-Yong Zhao
Keyword(s):  
Transcription Factors ◽  
Survival Rate ◽  
Dna Binding ◽  
Human Development ◽  
Growth And Development ◽  
Therapeutic Response ◽  
Kidney Development ◽  
Dna Binding Proteins ◽  
Diagnosis Classification ◽  
Basic Region

The AP-2 family of transcription factors consist of DNA-binding proteins: AP-2α to AP-2ε. Members and homologs of this family are also known in frogs, fish and invertebrates. These proteins have the same central basic region and a helix-span-helix dimerization motif, which is necessary for dimerization and DNA binding. This family have been found to influence facial, limbs and kidney development in embryogenesis while regulating differentiation and apoptosis. These proteins are also involved in regulation of endocrine processes. In addition to their influence on growth and development, this family have also been reported to correlate with tumorigenesis and development of cancer. At present, this family have been related to tumors of ovary, melanoma, lung, nasopharynx, breast, glioma, neuroblastoma, colon, etc. They regulate expression of many cancer-related genes and affect the occurrence, development, invasiveness and therapeutic response of cancers. Different expression levels of AP-2s are also related to different survival rate. These findings may bring new idea to the diagnosis, classification, treatment and prognosis of cancer.

Comparative Toxic and Therapeutic Effects of Adriamycin and Bleomycin in Malignant Lymphoma

1972 ◽  
Vol 58 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Mario De Lena ◽  
Gianni Beretta
Keyword(s):  
Therapeutic Response ◽  
Limiting Factor ◽  
Therapeutic Effects ◽  
Prolonged Administration ◽  
Malignant Lymphomas ◽  
Pulmonary Lesions ◽  
Therapeutic Trials ◽  
Therapeutic Results ◽  
Pretreated Patients ◽  
Therapeutic Properties

The toxic and therapeutic results obtained during phase I and phase II evaluation of adriamycin (ADM) and bleomycin (BLM) in 92 adequately treated cases with malignant lymphomas are reviewed. The number of pretreated patients as well as the different histologic expression of lymphoma are given together with the incidence of toxic manifestations (table 3, text-fig. 1). Stomatitis and alopecia are caused by both drugs and show about the same incidence as first sign of toxicity. Interstitial pulmonary lesions produced by BLM were observed in a fairly large percentage of cases and represent at the dosage used a limiting factor to prolonged administration. The therapeutic response has been evaluated on the Karnofsky's scale. With ADM category I response occurred in 72.2% of cases and with BLM in 50% (table 5, 6). Complete remissions for more than 1 year occurred in 3 patients treated with ADM and 1 with BLM. With both drugs all types of lesions responded, including bone marrow invasion. In responsive patients remissions occurred promptly (average 13.7 days with ADM and 10.3 days with BLM) (table 4). Because of their toxic and therapeutic properties, both drugs appear suitable for therapeutic trials in combination with conventional agents.

scholarly journals Weekends-Off Lenvatinib for Unresectable Hepatocellular Carcinoma Improves Therapeutic Response and Tolerability Toward Adverse Events

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1010 ◽  
Author(s):  
Hideki Iwamoto ◽  
Hiroyuki Suzuki ◽  
Shigeo Shimose ◽  
Takashi Niizeki ◽  
Masahito Nakano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Dose Reduction ◽  
Therapeutic Response ◽  
Incidence Rates ◽  
Therapeutic Effects ◽  
Mouse Hepatoma ◽  
High Incidence Rate ◽  
Grade 3 ◽  
Hepatoma Model

Background: Although lenvatinib has become the standard therapy for hepatocellular carcinoma (HCC), the high incidence rate of adverse events (AEs) is an issue. This study aimed to clarify the AEs of lenvatinib and the therapeutic impact of five days-on/two days-off administration (i.e., weekends-off strategy) for lenvatinib. Methods: We retrospectively assessed the therapeutic effects and AEs of 135 patients treated with lenvatinib, and the improvement of tolerability and therapeutic efficacy of 30 patients treated with the weekends-off strategy. We also evaluated lenvatinib-induced vascular changes in tumors and healthy organs using a mouse hepatoma model. Results: The incidence rates of any grade and grade ≥ 3 AEs were 82.1% and 49.6%. Fatigue was the most important AE since it resulted in dose reduction and discontinuation. Of the 30 patients who received weekends-off lenvatinib, 66.7% tolerated the AEs. Although 80.8% of the patients showed progression after dose reduction, the therapeutic response improved in 61.5% of the patients by weekends-off lenvatinib. Notably, weekends-off administration significantly prolonged the administration period and survival (p < 0.001 and p < 0.05). The mouse hepatoma model showed that weekends-off administration contributed to recovery of vascularity in the organs. Conclusion: Weekends-off administration of lenvatinib was useful to recover the therapeutic response and tolerability toward AEs.

Intravoxel incoherent motion MRI for monitoring the therapeutic response of hepatocellular carcinoma to sorafenib treatment in mouse xenograft tumor models

2016 ◽  
Vol 58 (9) ◽  
pp. 1045-1053 ◽  
Author(s):  
Yedaun Lee ◽  
Seung Soo Lee ◽  
Hyunhee Cheong ◽  
Chang Kyung Lee ◽  
Namkug Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Diffusion Coefficient ◽  
Therapeutic Response ◽  
Post Treatment ◽  
Control Group ◽  
Therapeutic Effects ◽  
Tumor Cell Death ◽  
Mouse Xenograft ◽  
Tumor Periphery

Background With the introduction of targeted therapies, there has been a growing need for non-invasive imaging methods which accurately evaluate therapeutic effects and overcome the limitations of tumor size-based therapeutic response assessments. Purpose To assess diagnostic values of intra-voxel incoherent motion (IVIM) imaging in evaluating therapeutic effects of sorafenib on hepatocellular carcinoma (HCC) using mouse xenograft model. Material and Methods Twenty-four mice bearing Huh-7 were divided into a control group and two treatment groups received sorafenib doses of 5 mg/kg (5 mg-Tx) or 30 mg/kg (30 mg-Tx). IVIM imaging was performed using 10 b-values (0–900 s/mm2). The apparent diffusion coefficient (ADC), diffusion coefficient ( D), and perfusion fraction ( f) were measured for whole tumors and tumor periphery. Changes between baseline and post-treatment parameters ( Δ ADC, Δ D, and Δ f) were calculated, and these parameters were compared with microvessel density (MVD) and area of tumor cell death. Results The post-treatment f and Δ f for tumor periphery were significantly higher in control group, followed by 5 mg-Tx and 30 mg-Tx ( P < 0.001). MVD showed significant positive correlation with post-treatment f ( r = 0.584, P = 0.003) and negative correlation with D ( r = –0.495, P = 0.014) for tumor periphery, while no parameter showed significant correlation with area of tumor cell death. Conclusion The f is significantly correlated with MVD of HCC, and could potentially be used to evaluate the anti-angiogenic effects of sorafenib.

The effects of olanzapine in treatment of panic disorder with and without agoraphobia

2011 ◽  
Vol 26 (S2) ◽  
pp. 165-165
Author(s):  
N. Mokhber ◽  
F. Savadkoohi
Keyword(s):  
Panic Disorder ◽  
Functional Assessment ◽  
Panic Attack ◽  
Low Dose ◽  
Therapeutic Response ◽  
Panic Attacks ◽  
Psychiatric Clinic ◽  
Therapeutic Effects ◽  
Drug Resistant ◽  
Cognition Scale

BackgroundIn this study, we have evaluated the effects of Olanzapine in treatment of panic disorder with and without agoraphobia.Method and materialsPatients whit resistant panic disorder (resistant to tow SSRI agents) who came to psychiatric clinic of Ibn-e-Sina and Ghaem Hospitals-Mashhad during 2004–2005 were enrolled in this study. Low dose Olanzapine (2.5 milligram per day) was administered initially. ALL cases were evaluated by different psychiatric tests such as agoraphobic cognitions questionnaire panic attack and anticipatory anxiety scale, Hamilton depression test and general functional assessment.ResultsIn this study, 30 patients were divided into two groups of panic disorder with agoraphobia (13 cases) and panic disorder without agrophobia (17 cases). Comparing these two groups, all indexes were improved significantly by time but The frequency of panic attacks in the last week minor panic attack duration of panic attacks agoraphobic cognition scale and Hamilton depression indexes were Improved significantly especially in those cases with panic disorder and agoraphobia Although the therapeutic response according to anxiety score, total panic attacks Hamilton depression test and general functional assessment was not showed any Difference.ConclusionOlanzapine augmentation has acceptable effects in the treatment of drug resistant panic disorder with agoraphobia and therapeutic effects were more significant among patients with panic disorder without agoraphobia.

scholarly journals Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma.

1995 ◽  
Vol 182 (6) ◽  
pp. 1951-1958 ◽  
Author(s):  
I M Adcock ◽  
S J Lane ◽  
C R Brown ◽  
T H Lee ◽  
P J Barnes
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Nuclear Translocation ◽  
Steroid Resistance ◽  
Therapeutic Effects ◽  
Activator Protein 1 ◽  
Binding Studies ◽  
Nf Kappa B ◽  
Steroid Resistant ◽  
Activator Protein

Glucocorticosteroids are a very effective treatment for asthma and other chronic inflammatory diseases. However, a small proportion of patients is resistant to the therapeutic effects of glucocorticoids. Pharmacokinetic and ligand binding studies suggest that the molecular abnormality in steroid resistance lies distal to nuclear translocation. We have previously reported that there is a decreased ability of glucocorticoid receptors (GR) to bind to the DNA-binding site in peripheral blood mononuclear cells (PBMC) after dexamethasone treatment. This reduced DNA binding was due to a decrease in the number of receptors available rather than an alteration in affinity for DNA. To study this reduced DNA binding, we examined the ability of the nuclear translocated transcription factors activator protein 1 (AP-1), nuclear factor kappa B (NF-kappa B) and cyclic AMP response element-binding protein (CREB) to bind to their DNA-binding sites and to interact with GR in PBMC from patients with steroid-sensitive and steroid-resistant asthma. There was a significant reduction in the interaction between GR and AP-1 in these steroid-resistant patients, although interaction with other transcription factors activated in inflammation (NF-kappa B and CREB) was unaffected. An increase in the basal levels of AP-1 DNA binding was also detected in the nuclei from steroid-resistant asthmatic patients. There were no differences in the amount of messenger RNA detected for the components of AP-1, c-Fos and c-Jun, nor in the sequences of these messenger RNAs. These results suggest either that the ability of the GR to bind to glucocorticoid response elements and AP-1 is altered in steroid-resistant patients or that increased levels of AP-1 prevent GR DNA binding, and that this may be the molecular basis of resistance to the antiinflammatory effect of steroids in these cells.

scholarly journals Does the VerifyNow P2Y12 assay overestimate “therapeutic response” to clopidogrel?

2014 ◽  
Vol 111 (06) ◽  
pp. 1150-1159 ◽  
Author(s):  
Vikram Khanna ◽  
Alex Hobson ◽  
Rand Mikael ◽  
Nalyaka Sambu ◽  
Nicola Englyst ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Prostaglandin E1 ◽  
Therapeutic Response ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Therapeutic Effects ◽  
P2y12 Inhibitors ◽  
High Platelet Reactivity

SummaryIn contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone. A higher proportion of individuals had a result indicating high platelet reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naïve volunteers (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naïve patients (93.5% vs 78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = < 0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater proportion had a “therapeutic response” with VN-P2Y12 compared to s-TEG, regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units ≥ 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti-aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN-P2Y12 overestimates the functional effects of clopidogrel in some individuals, possibly because it utilises PGE1 in addition to ADP. This could have implications for the ability of VN-P2Y12 to stratify patients as “responders” or “non-responders” to clopidogrel.

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