In vivo pharmacokinetic and tissue distribution investigation of sustained-release cisplatin implants in the normal esophageal submucosa of 12 beagle dogs

Yin, Jia-Xue; Wei, Zhi; Juan, Xu; Sun, Zhaoxia

doi:10.1007/s00280-015-2823-7

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…The mean half-life of free platinum in plasma ranged from 6 to 25 min 21 , 23 , 24 . On the other hand, platinum of various tissues were detected at the same concentration for 10 days after cisplatin injection 22 , 25 . In erythrocytes, a platinum concentration peak occurring within the 3 h following the end of infusion.…”

Section: Discussionmentioning

confidence: 95%

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Uno

Yoshikawa

Tazaki

et al. 2022

Sci Rep

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Most patients with ovarian cancer experience recurrence and develop resistance to platinum-based agents. The diagnosis of platinum resistance based on the platinum-free interval is not always accurate and timely in clinical settings. Herein, we used laser ablation inductively coupled plasma mass spectrometry to visualize the platinum distribution in the ovarian cancer tissues at the time of interval debulking surgery after neoadjuvant chemotherapy in 27patients with advanced high-grade serous ovarian cancer. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum throughout the tumor and adjacent stroma. The type A patients treated post-surgery with platinum-based adjuvant chemotherapy showed significantly shorter periods of recurrence after the last platinum-based chemotherapy session (p = 0.020) and were diagnosed with “platinum-resistant recurrence”. Moreover, type A was significantly correlated with worse prognosis (p = 0.031). Post-surgery treatment with non-platinum-based chemotherapy could be effective for the patients classified as type A. Our findings indicate that the platinum resistance can be predicted prior to recurrence, based on the platinum distribution; this could contribute to the selection of more appropriate adjuvant chemotherapy, which may lead to improves prognoses.

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Section: Discussionmentioning

confidence: 95%

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Uno

Yoshikawa

Tazaki

et al. 2022

Sci Rep

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“…Cell viability assay of organoids was performed as described previously . Taking into consideration the therapeutic dose in clinic and pharmacokinetics in dogs, we determined the appropriate concentration to be used for each drug in the cell viability assay. Briefly, 5 × 10 3 cells of each BC organoid were seeded into 10 μL Matrigel in a 96‐well culture plate and incubated for 24 h. Next, cells were treated with anticancer drugs at variable concentrations for 3 d. Cell viability was examined using an alamar blue kit (Thermo Fisher Scientific Inc.).…”

Section: Methodsmentioning

confidence: 99%

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

et al. 2019

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In human and dogs, bladder cancer (BC) is the most common neoplasm affecting the urinary tract. Dog BC resembles human muscle‐invasive BC in histopathological characteristics and gene expression profiles, and could be an important research model for this disease. Cancer patient‐derived organoid culture can recapitulate organ structures and maintains the gene expression profiles of original tumor tissues. In a previous study, we generated dog prostate cancer organoids using urine samples, however dog BC organoids had never been produced. Therefore we aimed to generate dog BC organoids using urine samples and check their histopathological characteristics, drug sensitivity, and gene expression profiles. Organoids from individual BC dogs were successfully generated, expressed urothelial cell markers (CK7, CK20, and UPK3A) and exhibited tumorigenesis in vivo. In a cell viability assay, the response to combined treatment with a range of anticancer drugs (cisplatin, vinblastine, gemcitabine or piroxicam) was markedly different in each BC organoid. In RNA‐sequencing analysis, expression levels of basal cell markers (CK5 and DSG3) and several novel genes (MMP28, CTSE, CNN3, TFPI2, COL17A1, and AGPAT4) were upregulated in BC organoids compared with normal bladder tissues or two‐dimensional (2D) BC cell lines. These established dog BC organoids might be a useful tool, not only to determine suitable chemotherapy for BC diseased dogs but also to identify novel biomarkers in human muscle‐invasive BC. In the present study, for the 1st time, dog BC organoids were generated and several specifically upregulated organoid genes were identified. Our data suggest that dog BC organoids might become a new tool to provide fresh insights into both dog BC therapy and diagnostic biomarkers.

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“…DDP has poor pharmacokinetic properties; it binds off target to plasma proteins, spontaneously degrades in the bloodstream, and is rapidly cleared from the blood by glomerular excretion (Yu et al, 2015). It is also toxic, with urinary concentrations of DDP positively correlated with the degree of nephrotoxicity (Yin et al, 2015). Synthesis of diplatin was motivated by increasing the water solubility of DDP to overcome issues related to toxicity; this was done by modification of the leaving ligands of DDP (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Diplatin, a Novel and Low-Toxicity Anti-Lung Cancer Platinum Complex, Activation of Cell Death in Tumors via a ROS/JNK/p53-Dependent Pathway, and a Low Rate of Acquired Treatment Resistance

et al. 2019

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Background: Platinum-based drugs prevail as the main treatment of lung cancer; this is caused by their relative effectiveness despite known side effects, such as neurotoxicity. The risk reward of the treatment and side effects is confronted when dosage is considered and when resistance to treatment develops. Development of new compounds that improve effectiveness and safety profiles addresses this ongoing need in clinical practice. Objectives: The novel water-soluble platinum complex, diplatin, was synthesized, and its antitumor potency and toxicology profile were evaluated in murine xenograft tumor models and in lung cancer cell lines. Methods: The effects of diplatin, cisplatin (DDP), and carboplatin (CBP) on the viability of nine lung tumor cell lines and one normal human lung epithelial cell line were evaluated using the MTT assay. Therapeutic index was calculated as LD50/ED50 to identify and compare the ideal therapeutic windows of the above compounds. Diplatin’s antitumor effects were assessed in lung xenograft tumors of nude mice; molecular mechanisms of therapeutic effects were identified. Results: Diplatin had desirable IC50 compared to CBP in a variety of cultured tumor cells, notably lung tumor cells. In the mouse xenograft lung tumor, diplatin led to a substantially improved therapeutic index when compared to the effects of DDP and CBP. Importantly, diplatin inhibited the growth of DDP-resistant lung tumor cells. Diplatin’s mode of action was characterized to be through cell cycle arrest in the G2/M phase and induction of lung tumor apoptosis via ROS/JNK/p53-mediated pathways. Conclusion: Diplatin was observed to have antitumor effects in mice with both greater potency and safety compared with DDP and CBP. These observations indicate that diplatin is promising as a potential treatment in future clinical applications.

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In vivo pharmacokinetic and tissue distribution investigation of sustained-release cisplatin implants in the normal esophageal submucosa of 12 beagle dogs

Abstract: CDDP-NP implants can be used to achieve a smooth pharmacokinetic curve and higher drug concentration, as well as a longer mean residence time at the implantation site, with reduced side effects compared with intravenous CDDP.

Cited by 10 publications

References 33 publications

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy

Establishment of a novel experimental model for muscle‐invasive bladder cancer using a dog bladder cancer organoid culture

Diplatin, a Novel and Low-Toxicity Anti-Lung Cancer Platinum Complex, Activation of Cell Death in Tumors via a ROS/JNK/p53-Dependent Pathway, and a Low Rate of Acquired Treatment Resistance

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