Molecular and cellular pharmacology最新文献

Sacituzumab govitecan for hormone receptor-positive and triple-negative breast cancers. Sacituzumab govitecan用于激素受体阳性和三阴性乳腺癌。

Molecular and cellular pharmacology Pub Date : 2023-01-01

Siem A Satti, M Saeed Sheikh

{"title":"Sacituzumab govitecan for hormone receptor-positive and triple-negative breast cancers.","authors":"Siem A Satti, M Saeed Sheikh","doi":"","DOIUrl":"","url":null,"abstract":"Sacituzumab govitecan is an antibody-drug conjugate. It is composed of a humanized monoclonal antibody raised against the trophoblast cell-surface antigen 2 (Trop-2), and linked to SN-38, which is an active metabolite of topoisomerase I inhibitor anticancer drug irinotecan. A hydrolyzable linker conjugates the antibody and the drug. Trop-2 is overexpressed in various tumors including the triple-negative breast cancers (TNBCs) that are more aggressive with limited therapeutic options. Sacituzumab govitecan has proven to be an important therapeutic modality to manage the TNBCs. It has shown progression-free survival (PFS) and overall survival (OS) benefits when compared to standard-of-care chemotherapeutics. Accordingly, it is approved for the treatment of TNBCs in the United States and the European Union. Sacituzumab govitecan has also shown PFS and OS benefits for hormone receptor-positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancers. Therefore, sacituzumab govitecan appears to be an option for HR+/HER2- metastatic breast cancers that are heavily pretreated and exhibit endocrine resistance. Although sacituzumab govitecan has shown promise, it also is toxic. Additional studies are therefore needed to further refine the use of sacituzumab govitecan in improving the management of metastatic breast cancer.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"15 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118000/pdf/nihms-1890430.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein Kinase D: A Potential Therapeutic Target in Prostate Cancer. 蛋白激酶D:前列腺癌的潜在治疗靶点。

Molecular and cellular pharmacology Pub Date : 2017-01-01

Adhiraj Roy, Q Jane Wang

引用次数: 0

mTOR Inhibitors at a Glance. mTOR 抑制剂一览。

Molecular and cellular pharmacology Pub Date : 2015-01-01

Yin Zheng, Yu Jiang

引用次数: 0

Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake. 姜黄素包封纳米凝胶作为细胞内摄取的有效抗癌制剂。

Molecular and cellular pharmacology Pub Date : 2015-01-01 DOI: 10.4255/MCPHARMACOL.15.04

Anna E. Reeves, S. Vinogradov, P. Morrissey, M. Chernin, Mansoor M Ahmed

{"title":"Curcumin-encapsulating Nanogels as an Effective Anticancer Formulation for Intracellular Uptake.","authors":"Anna E. Reeves, S. Vinogradov, P. Morrissey, M. Chernin, Mansoor M Ahmed","doi":"10.4255/MCPHARMACOL.15.04","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.15.04","url":null,"abstract":"Nanoscale drug delivery systems represent an attractive strategy to improve both the efficacy and safety of anticancer drugs. In this work, we describe nanoformulation of curcumin, a most potent natural anticancer compound capable of killing cancer cells while sparing the normal tissues. Since curcumin is a natural hydrophobic polyphenol, it has a low aqueous solubility and bioavailability, which are challenging to its therapeutic efficacy. We developed and evaluated a novel colloidal nanogel carrier for encapsulation of curcumin to increase its solubility and cytotoxicity. Amphiphilic Poloxamer-cationic network in the nanogel NG127 was designed to efficiently encapsulate curcumin. Homogenous drug complexes were obtained with 20-25% content of curcumin and the particle size of ca. 150 nm. Using ImageStream multispectral imaging flow cytometry, we demonstrated that the curcumin-nanogel formulation (C-NG) was readily internalized into MDA-231 breast cancer cells. A real-time cell growth electronic sensing assay was used to measure proliferation responses of various breast cancer cells to C-NG treatments. Our results indicated that the C-NG formulation was 70-85% more effective in inhibiting growth, at concentrations lower than IC50 of free curcumin. This was also confirmed morphologically by modified acridine orange/ethidium bromide staining and fluorescent microscopy. Importantly, nanocarrier NG127 alone displayed practically no cytotoxicity. We conclude that nanogel carriers offer an innovative way to encapsulate curcumin and to obtain more effective anticancer therapeutics than curcumin alone with a potential to specific tumor targeting, such as using antibodies against surface receptors specific to breast cancer cells.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"231 1","pages":"25-40"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87035884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

RNA-binding Protein, GADD45-alpha, p27^Kip1, p53 and Genotoxic Stress Response in Relation to Chemoresistance in Cancer. rna结合蛋白、gadd45 - α、p27Kip1、p53和基因毒性应激反应与癌症化疗耐药的关系

Molecular and cellular pharmacology Pub Date : 2015-01-01

M Saeed Sheikh

{"title":"RNA-binding Protein, GADD45-alpha, p27Kip1, p53 and Genotoxic Stress Response in Relation to Chemoresistance in Cancer.","authors":"M Saeed Sheikh","doi":"","DOIUrl":"","url":null,"abstract":"Genotoxic chemotherapeutics particularly cisplatin remain effective for clinical management of various malignancies including lung cancer. However, the development of chemoresistance leads to treatment failure. The mechanisms by which tumor cells acquire resistance to chemotherapy are multifaceted in nature and some remain to be fully elucidated. Recently, a potential role of RNA-binding protein hnRNPA0 in chemoresistance of p53-defective lung cancer cells was reported. Genotoxic (DNA damaging) chemotherapy was reported to activate hnRNPA0 which in turn post-transcriptionally regulated p27Kip1 and Gadd45-alpha by stabilizing their mRNAs. Regulation of p27Kip1 and Gadd45-alpha led to enforcement of G1/S and G2/M checkpoints thereby providing time for DNA repair and thus, resistance to chemotherapy. The identification of a signaling network involving the kinase MK2, hnRNPA0, p27Kip1 and Gadd45-alpha that may predict response to chemotherapy is an interesting finding. Further studies are now needed to gain additional insights as to whether this network is restricted only to a subset of tumors or more broadly relevant across multiple tumor types.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"7 3","pages":"41-45"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4824310/pdf/nihms-761602.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34391705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation. tenfigen -DMAT纳米胶囊向前列腺癌异种移植肿瘤递送CK2抑制剂DMAT，抑制细胞增殖。

Molecular and cellular pharmacology Pub Date : 2014-01-01

Janeen H Trembley, Gretchen M Unger, Omar Cespedes Gomez, J Abedin, Vicci L Korman, Rachel I Vogel, Gloria Niehans, Betsy T Kren, Khalil Ahmed

{"title":"Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation.","authors":"Janeen H Trembley, Gretchen M Unger, Omar Cespedes Gomez, J Abedin, Vicci L Korman, Rachel I Vogel, Gloria Niehans, Betsy T Kren, Khalil Ahmed","doi":"","DOIUrl":"","url":null,"abstract":"CK2 is a master regulator protein kinase which demonstrates heightened expression in diverse cancer types and is considered a promising target for therapy. Given its ubiquitous expression and potent influence on cell survival, cancer cell-directed targeting of the CK2 signal is an important factor for development of an anti-CK2 therapeutic. We previously reported on the malignant cell specificity and effect on CK2 signaling of a tenfibgen (TBG) based nanocapsule for delivery of the CK2 small molecule inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) in cultured prostate cancer cells. Here we tested the ability of TBG-DMAT to affect the growth of prostate xenograft tumors in mice. Our results show that treatment of PC3-LN4 xenograft tumors with TBG-DMAT caused loss of proliferative Ki-67 signal as well as Nuclear Factor-kappa B (NF-κB) expression in the tumors. Further, the TBG-DMAT nanocapsule was detected in tumors and not in liver or testis. In conclusion, TBG-based nanocapsule delivery of anti-CK2 small molecule drugs holds significant promise for treatment of prostate cancer.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"6 2","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397568/pdf/nihms663666.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33233349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation. tenfigen -DMAT纳米胶囊向前列腺癌异种移植肿瘤递送CK2抑制剂DMAT，抑制细胞增殖。

Molecular and cellular pharmacology Pub Date : 2014-01-01 DOI: 10.4255/MCPHARMACOL.14.02

J. Trembley, G. Unger, O. Gomez, J. Abedin, V. Korman, R. Vogel, G. Niehans, B. Kren, K. Ahmed

{"title":"Tenfibgen-DMAT Nanocapsule Delivers CK2 Inhibitor DMAT to Prostate Cancer Xenograft Tumors Causing Inhibition of Cell Proliferation.","authors":"J. Trembley, G. Unger, O. Gomez, J. Abedin, V. Korman, R. Vogel, G. Niehans, B. Kren, K. Ahmed","doi":"10.4255/MCPHARMACOL.14.02","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.14.02","url":null,"abstract":"CK2 is a master regulator protein kinase which demonstrates heightened expression in diverse cancer types and is considered a promising target for therapy. Given its ubiquitous expression and potent influence on cell survival, cancer cell-directed targeting of the CK2 signal is an important factor for development of an anti-CK2 therapeutic. We previously reported on the malignant cell specificity and effect on CK2 signaling of a tenfibgen (TBG) based nanocapsule for delivery of the CK2 small molecule inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) in cultured prostate cancer cells. Here we tested the ability of TBG-DMAT to affect the growth of prostate xenograft tumors in mice. Our results show that treatment of PC3-LN4 xenograft tumors with TBG-DMAT caused loss of proliferative Ki-67 signal as well as Nuclear Factor-kappa B (NF-κB) expression in the tumors. Further, the TBG-DMAT nanocapsule was detected in tumors and not in liver or testis. In conclusion, TBG-based nanocapsule delivery of anti-CK2 small molecule drugs holds significant promise for treatment of prostate cancer.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"45 1","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89551371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Lipid Signaling in Tumorigenesis. 脂质信号在肿瘤发生中的作用。

Molecular and cellular pharmacology Pub Date : 2014-01-01

Renyan Liu, Ying Huang

引用次数: 0

Melanoma: Molecular Pathogenesis and Therapeutic Management. 黑色素瘤:分子发病机制和治疗管理。

Molecular and cellular pharmacology Pub Date : 2014-01-01

Yuxin Liu, M Saeed Sheikh

引用次数: 0

The immunosuppressant FTY720 (Fingolimod) induces nuclear exit of the proto-oncogene SET/I2PP2A 免疫抑制剂FTY720 (Fingolimod)诱导原癌基因SET/I2PP2A的核退出

Molecular and cellular pharmacology Pub Date : 2013-12-01 DOI: 10.4255/MCPHARMACOL.13.10

B. Lam, E. Anthony, P. Hordijk

{"title":"The immunosuppressant FTY720 (Fingolimod) induces nuclear exit of the proto-oncogene SET/I2PP2A","authors":"B. Lam, E. Anthony, P. Hordijk","doi":"10.4255/MCPHARMACOL.13.10","DOIUrl":"https://doi.org/10.4255/MCPHARMACOL.13.10","url":null,"abstract":"The proto-oncogene SET/I2PP2A, an inhibitor of the phosphatase PP2A and a potential therapeutic target for cancer, interacts with the RhoGTPase Rac1 and regulates cell motility. SET is primarily nuclear but can readily translocate to the cytoplasm. Here, we investigated this translocation in more detail. Using an image analysis method to analyse nucleo-cytoplasmic shuttling of YFP-SET, we find that the protein shows repetitive shuttling in a seemingly random fashion. We found that Rac1 activity increases the frequency of these nuclear exit events of SET. In search for cellular activators of this event, we found FTY720 (fingolimod), an immunomodulator and activator of PP2A, to rapidly induce nucleo-cytoplasmic translocation of SET. Subsequently, SET accumulates in cytoplasmic aggregates of unknown nature. Moreover, we observed that the nuclear pool of Rac1 translocates simultaneously with SET, both during spontaneous as well as FTY720-induced translocation. Finally, FTY720-induced nuclear exit is dependent on the nuclear exporter CRM1, on PP2A activity as well as on microtubule dynamics. These results show that the immunomodulator and PP2A activator FTY720, induces rapid nucleo-cytoplasmic shuttling of SET, suggesting that SET translocation is part of a negative feedback loop. This data may be relevant to the potential use of FTY720 in the treatment of leukemias and inflammatory disorders.","PeriodicalId":18748,"journal":{"name":"Molecular and cellular pharmacology","volume":"104 1","pages":"95-107"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80478578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0