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A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect

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Acta Pharmaceutica Sinica B 2021年第1期11卷 258-270页

作者： Shuang Zhou Jinbo Li Jiang Yu Liyuan Yang Xiao Kuang Zhenjie Wang Yingli Wang Hongzhuo Liu Guimei Lin Zhonggui He Dan Liu Yongjun Wang Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China cSchool of Pharmaceutical Science Shandong UniversityJinan 250012China

Liposomes have made remarkable achievements as drug delivery vehicles in the *** products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease *** this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by p H gradient ***(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and *** weak acid derivative liposomes were superior to Jevtanaa in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve ***,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippocampus *** advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.

关键词： Non-ionizable drugs Weak acid derivatives Remote loading liposome Cabazitaxel Safety Tolerated doses Cancer lung metastasis

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A stochastic population pharmacodynamic model of QAP14 in the treatment of lung metastases of 4T1 breast cancer

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Journal of Chinese Pharmaceutical Sciences 2021年第10期30卷 794-805页

作者： Mengyi Han Ling Yong Yuchen Guo Xiaoxue Yan Guoshu Chen Daming Kong Tianyan Zhou Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System Department of PharmaceuticsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Chemical Basic Laboratory School of Chemistry and Chemical EngineeringGuangzhou UniversityGuangzhou 510006China

Cancer metastasis is a process with multi-step complexity and apparent randomness. In this study, we aimed to establish a stochastic mathematical model to describe the random process of cancer metastasis and predict the drug effect of QAP14 on metastasis in a mouse model. The data of lung metastases on the 22^(nd) day after cancer cell implantation with or without the treatment of QAP14, a new chemical compound, were collected in 4T1 breast cancer BALB/c mice. Based on the exponential growth of the primary tumor and metastatic loci, a joint distribution model of metastasis size and number was developed. Disease progression of metastasis and preclinical efficacy of QAP14 were modeled. Parameters M and m representing maximum and minimum of metastasis volume were 3.24 and 0.0184 mm^(3), respectively. The metastasis growth rate γ and metastasis promotion time ρ were estimated and fixed to be 0.0216 d^(-1) and 7.8 d, respectively. The efficacy of QAP14 acted on metastasis promotion time and metastasis growth rate constant in an exponential term, and the effect parameter Effectρ and Effectγ were 16.6 and 0.327 g/mg, respectively. In the present study, we comprehensively characterized the random process of lung metastasis and efficacy of QAP14 in 4T1 breast cancer mice, which might provide a useful reference for the establishment of a clinical population model of cancer metastasis.

关键词： Stochastic population model PD model 4T1 lung metastasis Breast cancer

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ROR2 regulates the survival of murine osteosarcoma cells in lung capillaries

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Journal of Cancer metastasis and Treatment 2020年第1期6卷 611-621页

作者： Diem Thi Phuong Tran Takahiro Kuchimaru Mongkol Pongsuchart Kha The Nguyen John Clyde Co Soriano Tetsuya Kadonosono Shinae Kizaka-Kondoh School of Life Science and Technology Tokyo Institute of TechnologyYokohama 226-8501Japan Center for Molecular Medicine Jichi Medical UniversityTochigi 329-0498Japan

Aim:lung metastasis is a leading cause of death in patients with osteosarcoma(OS).No effective therapy exists that improves the five-year overall survival rate of OS patients with ***,finding novel therapeutic targets will help develop new treatment strategies for OS patients with lung ***:Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high(LM8-H)and low(LM8-L)metastatic ability,we have identified Wnt signal-related genes that play an important role in lung metastasis of *** of the genes was investigated by establishing sublines of gene knockout and assessing their metastatic ability using a mouse lung metastasis *** molecular mechanism underlying the function of the genes was further investigated by in vitro ***:We have identified that receptor tyrosine kinase-like orphan receptor 2(ROR2),a receptor of the non-canonical Wnt signaling pathway,was involved in OS cell survival in lung capillaries during ***8-H knocked out of Ror2(H/Ror2-KO)significantly reduced lung metastasis by decreasing the viability in lung capillaries 48 h after intravenous *** vitro study revealed that ROR2 increased anoikis resistance through AKT *** of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in lung ***:The results demonstrate a novel ROR2 function in OS lung metastasis and may inform new treatment strategies for OS patients.

关键词： Osteosarcoma lung metastasis cell survival lung capillary ROR2

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Small molecules regulate homeostasis of cytokines for suppression of pulmonary fibrosis and tumor metastasis

Small molecules regulate homeostasis of cytokines for suppre...

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第二届全国“跨学科蛋白质研究”学术讨论会

作者：梁伟 Protein & Peptide Pharmaceutical Laboratory Institute of BiophysicsChinese Academy of Sciences

Increasing evidence points to involvement of the fibrotic microenvironment in cancer initiation and progression. Here we demonstrate that mice with lung fibrosis challenged with tumors show an increased incidence of lung metastasis and shorter life spans.A fibrotic environment in the lung results in increased abundance of TGF-β1 and CD4+CD25+FoxP3+regulatory T cells and a decreased proportion of activated effector T *** grave immunosuppressive environment favors tumor localization and growth. Naringenin significantly reduces lung metastases in mice with pulmonary fibrosis and increases their survival by improving the immunosuppressive environment through downregulating TGF-β1 and reducing levels of regulatory T *** together,these data indicate that naringenin could be an ideal therapeutic agent in the treatment of both cancer and fibrosis.

关键词： Pulmonary fibrosis lung metastasis Naringenin TGF-β1 Antifibrosis Antimetastasis Treg.

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Mechanisms and anatomical risk factors of pneumothorax after Bevacizumab use:A case report

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World Journal of Clinical Oncology 2020年第7期11卷 504-509页

作者： Yuri Ozaki Akiyo Yoshimura Masataka Sawaki Masaya Hattori Naomi Gondo Haruru Kotani Yayoi Adachi Ayumi Kataoka Kayoko Sugino Nanae Horisawa Yuka Endo Kazuki Nozawa Shoko Sakamoto Hiroji Iwata Department of Breast Oncology Aichi Cancer Center HospitalNagoya 464-8681Japan

BACKGROUND Bevacizumab is an antiangiogenic agent,and that synergizes with chemotherapeutic *** used in combination therapies,Bevacizumab is associated with adverse events such as hemorrhage,gastrointestinal perforation,delayed wound healing,and ***,the molecular mechanisms underlying these adverse events are not fully *** SUMMARY A 45-year-old female with multiple lung metastases that were derived from primary breast cancer,was placed on Bevacizumab+paclitaxel therapy,since this combination has a potent antitumor *** reported dyspnea before cycle 3,day 1 and we therefore ran a chest X-ray,which detected a right *** coronal plane computed tomography revealed that one solid mass rapidly necrosed and was replaced by a cavity that passed through the bronchus in the right lower *** cavity eventually ruptured the pleura and made the bronchopleural fistula that led to this *** cavity drainage using an intercostal catheter was *** the 7th day of drainage,the patient was discharged from our hospital on *** of pneumothorax was not reported,and continuation of chemotherapy was made possible by changing the *** Patients with lung metastases surrounding the bronchi and on the pleura should be monitored for pneumothorax by Bevacizumab-containing chemotherapies.

关键词： Breast cancer lung metastasis Bevacizumab Adverse event Pneumothorax Case report

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Recurrent giant cell tumors of bone:treatment and outcome of 73 cases

Recurrent giant cell tumors of bone:treatment and outcome of...

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第20届中国康协肢残康复学术年会

作者：孔清泉屠重棋周勇段宏高博裴福兴 Department of Orthopaedic Surgery West China HospitalSichuan University

[Objective]It is reported that the re-recurrence rate of recurrent giant cell tumors of bone(GCTB)is relatively high,however,the related documents and the data are very *** now,the principle of treatment option is not very clear for recurrent giant cell tumors of bone from repeated intralesional curettage towide resection.[Methods]Three hundred and twenty patients with histologically certified GCTB in bone of the extremities have been treated from 1988 to 2008 at the Orthopedics Department of the West China Hospital in Sichuan University(China).Seventy-three patients with at least one local recurrence were included in this study.25 of these patients received their first surgical treatment at our hospital,48 were referred from other hospitals due to local *** mean age of the patients at diagnosis was 33.4 years(range,15-72 years);The male to female ratio was 1.09:*** mean follow-up was 72.3 months(range,18

关键词： Giant cell tumor bone tumor recurrence bone cement lung metastasis

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Anti-tumor effects of VnA in in vitro cultured Colon26-L5 cells and in vivo Colon26-L5 cells planted mice

Anti-tumor effects of VnA in in vitro cultured Colon26-L5 ce...

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两岸三地药理学与临床药理学术会议

作者： UENO Yuko SAKURAI Hiroaki SAIKI Ikuo Division of Pathogenic Biochemistry Institute of Natural MedicineToyama University

Objective To investigate the antitumor effects of VnA,the total alkaloids isolated from Veratrum Nigrum *** Nakai("Wusuli Lilu"in Chinese),and the underlying mechanisms with em- phasis on its anti-metastatic *** The effects of VnA on in vitro proliferation,invasion,migra- tion and adhesion in Colon26-L5 cells were *** effect of VnA on experimental lung metastasis of Colon26-L5 cells in mice was also be studied by means of measuring the numbers of tumor colonies in lungs after single *** of Colon26-L5 cells to mice followed by q.d.i.p VnA for consecutive 14 *** effect of VnA on the production of matrix metalloproteinases(MMPs)from Colon26-L5 cell in vitro was determined by means of gelatin *** In in vitro experiments,VnA was found to significantly reduce the number of tumor colonies at dosage of 20.0-40.0μg·*** in vitro experi- ments,VnA inhibited the adhesion(at 1.6-12.5μg·mL)and migration(at 3.1-50.0μg·mL)of Colon26-L5 cell to extracellular matrix components and suppressed invasion into reconstituted basement membrane matrigel(at 3.1-50.0μg·mL),meanwile cell proliferation(at 25.0-50.0μg·mL)was at- *** also showed a concentration-dependent inhibition of MMP2 and MMP9 production(at 3.1- 50.0μg·mL).Conclusions VnA has anti-metastatic protential by decreasing invasiveness of cancer cells as one of its anti-tumor pharmacological effects.

关键词： VnA antitumor lung metastasis MMPs

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