Phase-I randomized trial of doxorubicin hydrochloride liposome injection versus Caelyx<sup>®</sup> in multiple myeloma

Bhowmik, Shravanti; Bhowmick, Subhas; Maiti, Kuntal; Chakra, Amaresh; Shahi, Pradeep; Thennati, Rajamannar

doi:10.1080/10428194.2017.1382692

Cited by 5 publications

(5 citation statements)

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“…In addition, we detect the effect of CXCR4 on the sensitivity of adaCP to chemotherapy drugs. Cisplatin (cis) and adriamycin (also named as doxorubicin [dox]) are common chemotherapy medication used to treat various cancers. Drug treatment reduced the cell viability of adaCP ( P < 0.001) compared with cells with overexpression of CXCR4 (Figure A), indicating that adaCP tumor cells are sensitive to cis and dox.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, we detect the effect of CXCR4 on the sensitivity of adaCP to chemotherapy drugs. Cisplatin (cis) 42 and adriamycin (also named as doxorubicin [dox]) 43 are common chemotherapy medication used to treat various cancers. Drug treatment reduced the cell F I G U R E 6 CXCL12/CXCR4 promotes the proliferation, migration, and invasion of adaCP through PI3K/AKT.…”

Section: Cxcl12/cxcr4 Promotes the Proliferation Migration And Invasion Of Adacp Through Pi3k/aktmentioning

confidence: 99%

“…In addition, we detect the effect of CXCR4 on the sensitivity of adaCP to chemotherapy drugs. Cisplatin (cis) 42 and adriamycin (also named as doxorubicin [dox]) 43 viability of adaCP (P < 0.001) compared with cells with overexpression of CXCR4 (Figure 7A), indicating that adaCP tumor cells are sensitive to cis and dox. Overexpression of CXCR4 increased the cell viability (P < 0.001), and cells transfected with cis or dox and overexpression of CXCR4 could restore the cell viability reduced by cis or dox (Figure 7B), and cancer cells were less sensitive to cis and dox, suggesting that upregulation of CXCR4 resulted in a certain degree of drug resistance in adaCP tumor cells.…”

Section: Cxcr4 Promotes the Proliferation Migration And Invasion Of A...mentioning

confidence: 99%

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CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Yin

Liu

Zhu

et al. 2018

J of Cellular Biochemistry

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Objectives: Adamantinomatous craniopharyngiomas (adaCP) accounts for 5.6% to 15% of intracranial tumors. High expression of chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1 [SDF1]) and its receptor CXC receptor type 4 (CXCR4) are widespread in various malignancy via multiple signal transduction pathways. This study aims to investigate the mechanism of CXCL12/CXCR4 promoting proliferation, migration, and invasion of adaCP. Methods: Quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry were used to evaluate the expression of CXCL12/CXCR4 mRNA and protein in 10 human adaCP tissues. Three successfully primary cell lines were obtained from native mainly solid tumor specimens, and confirmed by the means of inverted contrast microscope directly and following hematoxylin and eosin staining. Immunofluorescence was used to detect protein expression in vivo for the verification of primary cell line. Proliferation, migration, and invasion assays were performed to assess the biological functional role of CXCL12/CXCR4 in adaCP. The signal pathways involved in the action of CXCL12/CXCR4 in adaCP were also evaluated. Results: CXCL12 and CXCR4 were highly expressed in human adaCP samples.Primary adaCP cells were isolated and detected by the means of immunofluorescence for the detection of pan cytokeratin (pan-CK) and vimentin (VIM). Overexpression of CXCL12/CXCR4 significantly promoted the proliferation, migration, and invasion of primary adaCP cells. Moreover, cancer-promoting activity of CXCL12/CXCR4 is partially through its facilitation of PI3K/AKT signal pathway.Conclusions: Our data showed that CXCL12/CXCR4 promotes adaCP proliferation, migration, and invasion through PI3K/AKT signal pathway. These findings suggested that therapeutic strategies regulating CXCL12/CXCR4 expression may provide an effective treatment of adaCP. K E Y W O R D S adamantinomatous craniopharyngiomas, CXCL12/CXCR4, metastasis, PI3K/AKT, progression J Cell Biochem. 2019;120:9724-9736. wileyonlinelibrary.com/journal/jcb 9724 |

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Section: Resultsmentioning

confidence: 99%

Section: Cxcl12/cxcr4 Promotes the Proliferation Migration And Invasion Of Adacp Through Pi3k/aktmentioning

confidence: 99%

Section: Cxcr4 Promotes the Proliferation Migration And Invasion Of A...mentioning

confidence: 99%

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CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Yin

Liu

Zhu

et al. 2018

J of Cellular Biochemistry

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“…According to statistics, the risk of cardiac death in children with malignant tumors after ADM treatment is 8 times higher than that in normal people, with a markedly increased incidence of subclinical cardiac toxicity [ 3 , 4 ]. Doxorubicin hydrochloride liposome injection (DHLI), a new dosage form of ADM wrapped by liposomes, can reduce the drug concentration in cardiomyocytes and thus reduce cardiac toxicity [ 5 ]. ADM has been clinically used in the treatment of osteosarcoma, while paclitaxel is only used as a second-line drug in treating osteosarcoma and is less effective than ADM.…”

Section: Introductionmentioning

confidence: 99%

Effect of Paclitaxel Combined with Doxorubicin Hydrochloride Liposome Injection in the Treatment of Osteosarcoma and MRI Changes before and after Treatment

Tian

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and the MRI changes before and after treatment. Methods. A total of 108 osteosarcoma patients treated in our hospital (January 2020–April 2022) were selected to carry out a single-center retrospective study. Among them, 54 patients receiving the combination chemotherapy (MDT) with high-dose methotrexate, ifosfamide, cisplatin, and ADM were selected as the control group (COG), while 54 patients receiving MDT with high-dose methotrexate, ifosfamide, cisplatin, paclitaxel, and DHLI were chosen as the study group (STG). The COG and STG had the same dose intensity and chemotherapy cycles, and clinical and MRI evaluations were performed after treatment. Results. The evaluation of postoperative clinical efficacy showed that the disease control rate (DCR) of the STG was markedly higher than that of the COG ( P < 0.05 ). The incidence of cardiac toxicity was remarkably lower in the STG than that in the COG ( P < 0.05 ), with no between-group differences in the incidence of fever, abnormal liver function, myelosuppression, stomatitis, and alopecia ( P > 0.05 ). Obvious differences were found in the semiquantitative parameters of MRI in the STG before and after chemotherapy ( P < 0.05 ) and were also found in the SImax, TTP, SEE, PPE, WOR, and R values in the COG before and after chemotherapy ( P < 0.05 ). After chemotherapy, statistical differences were observed in the semiquantitative parameters of MRI between the two groups, with lower parameters such as Slope, SImax, SEE, and R values and higher parameters such as TTP, PPE, and WOR values in the STG than those in the COG ( P < 0.05 ). Conclusion. Paclitaxel combined with DHLI has definite efficacy in osteosarcoma chemotherapy, which is conducive to narrowing the lesion, controlling the disease, and reducing the occurrence of cardiac-related risk events. In addition, the semiquantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) have a high predictive value for the efficacy of chemotherapy, which can reflect the degree of tumor necrosis and contribute to a timely and objective assessment of the efficacy of osteosarcoma chemotherapy.

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“…Based on the clinical advantages of liposomes as carriers of chemotherapeutics over conventional chemotherapy due to reduced therapeutically side effects and increased anti‐cancer activity [ 43 , 44 ], we exploited a liposomal system using Lipofectamine Messenger MAX Transfection Reagent ® by testing its supportive quality for the delivery of IVT‐mRNA (EGFP‐mRNA, Luc‐mRNA) to the HGSOC cells. To quantitatively study the uptake of the control EGFP‐mRNA, EGFP expression was measured using FACS as a surrogate marker for transfection efficiency.…”

Section: Resultsmentioning

confidence: 99%

Rescue of p53 functions by in vitro‐transcribed mRNA impedes the growth of high‐grade serous ovarian cancer

Raab,

Kostova,

Peña‐Llopis

et al. 2023

Cancer Communications

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BackgroundThe cellular tumor protein p53 (TP53) is a tumor suppressor gene that is frequently mutated in human cancers. Among various cancer types, the very aggressive high‐grade serous ovarian carcinoma (HGSOC) exhibits the highest prevalence of TP53 mutations, present in >96% of cases. Despite intensive efforts to reactivate p53, no clinical drug has been approved to rescue p53 function. In this study, our primary objective was to administer in vitro‐transcribed (IVT) wild‐type (WT) p53‐mRNA to HGSOC cell lines, primary cells, and orthotopic mouse models, with the aim of exploring its impact on inhibiting tumor growth and dissemination, both in vitro and in vivo.MethodsTo restore the activity of p53, WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector system. Moreover, IVT WT p53 mRNA was delivered into different HGSOC model systems (primary cells and patient‐derived organoids) using liposomes and studied for proliferation, cell cycle progression, apoptosis, colony formation, and chromosomal instability. Transcriptomic alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR‐8 and primary HGSOC cells, followed by ingenuity pathway analysis. In vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse models.ResultsReactivation of the TP53 tumor suppressor gene was explored in different HGSOC model systems using newly designed IVT mRNA‐based methods. The introduction of WT p53 mRNA triggered dose‐dependent apoptosis, cell cycle arrest, and potent long‐lasting inhibition of HGSOC cell proliferation. Transcriptome analysis of OVCAR‐8 cells upon mRNA‐based p53 reactivation revealed significant alterations in gene expression related to p53 signaling, such as apoptosis, cell cycle regulation, and DNA damage. Restoring p53 function concurrently reduces chromosomal instability within the HGSOC cells, underscoring its crucial contribution in safeguarding genomic integrity by moderating the baseline occurrence of double‐strand breaks arising from replication stress. Furthermore, in various mouse models, treatment with p53 mRNA reduced tumor growth and inhibited tumor cell dissemination in the peritoneal cavity in a dose‐dependent manner.ConclusionsThe IVT mRNA‐based reactivation of p53 holds promise as a potential therapeutic strategy for HGSOC, providing valuable insights into the molecular mechanisms underlying p53 function and its relevance in ovarian cancer treatment.

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Phase-I randomized trial of doxorubicin hydrochloride liposome injection versus Caelyx^® in multiple myeloma

Cited by 5 publications

References 4 publications

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Effect of Paclitaxel Combined with Doxorubicin Hydrochloride Liposome Injection in the Treatment of Osteosarcoma and MRI Changes before and after Treatment

Rescue of p53 functions by in vitro‐transcribed mRNA impedes the growth of high‐grade serous ovarian cancer

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Phase-I randomized trial of doxorubicin hydrochloride liposome injection versus Caelyx® in multiple myeloma

Cited by 5 publications

References 4 publications

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

CXCL12/CXCR4 promotes proliferation, migration, and invasion of adamantinomatous craniopharyngiomas via PI3K/AKT signal pathway

Effect of Paclitaxel Combined with Doxorubicin Hydrochloride Liposome Injection in the Treatment of Osteosarcoma and MRI Changes before and after Treatment

Rescue of p53 functions by in vitro‐transcribed mRNA impedes the growth of high‐grade serous ovarian cancer

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Product

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Phase-I randomized trial of doxorubicin hydrochloride liposome injection versus Caelyx^® in multiple myeloma