Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor

Darban, Shahrzad Amiri; Nikoofal-Sahlabadi, Sara; Amiri, Nafise; Kiamanesh, Nafiseh; Mehrabian, Amin; Zendehbad, Bamdad; Gholizadeh, Zahra; Jaafari, Mahmoud Reza

doi:10.1016/j.colsurfb.2018.01.035

Cited by 20 publications

(9 citation statements)

References 55 publications

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“…The results of animal experiments revealed the suppression of tumor growth, consistent with the increased doxorubicin concentration in tumor tissue [71]. A similar outcome was published by another group using leptin-derived peptide (LP16, 91-110 of leptin) to reduce tumor growth in a C26 colon carcinoma tumor-bearing mouse model [72].…”

Section: Leptin and Colorectal Cancersupporting

confidence: 77%

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Lin

Hsiao

2021

IJMS

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Leptin is an obesity-associated adipokine that is known to regulate energy metabolism and reproduction and to control appetite via the leptin receptor. Recent work has identified specific cell types other than adipocytes that harbor leptin and leptin receptor expression, particularly in cancers and tumor microenvironments, and characterized the role of this signaling axis in cancer progression. Furthermore, the prognostic significance of leptin in various types of cancer and the ability to noninvasively detect leptin levels in serum samples have attracted attention for potential clinical applications. Emerging findings have demonstrated the direct and indirect biological effects of leptin in regulating cancer proliferation, metastasis, angiogenesis and chemoresistance, warranting the exploration of the underlying molecular mechanisms to develop a novel therapeutic strategy. In this review article, we summarize and integrate transcriptome and clinical data from cancer patients together with the recent findings related to the leptin signaling axis in the aforementioned malignant phenotypes. In addition, a comprehensive analysis of leptin and leptin receptor distribution in a pancancer panel and in individual cell types of specific organs at the single-cell level is presented, identifying those sites that are prone to leptin-mediated tumorigenesis. Our results shed light on the role of leptin in cancer and provide guidance and potential directions for further research for scientists in this field.

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Section: Leptin and Colorectal Cancersupporting

confidence: 77%

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Lin

Hsiao

2021

IJMS

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“…Consequently, the GSH-Caelyx ® post-inserted formulations were prepared by insertion of 25, 50, 100, 200, and 400 ligands on the liposomal surface. The number of peptide molecules per liposomes was calculated based on the following parameters: Caelyx ® phospholipids concentration, liposomal average size and per liposomes' lipid molecules for their average size, liposomal numbers per each milliliter, total peptide content, peptide molecules per each milliliter of peptide-micelles, and peptides' number aimed to put on each liposome surface [54,56,60,61] Release studies were conducted by the dialysis method in three different media with a pH of 7.4 (PBS), 6.5 (dextrose histidine), and 5.5 (dextrose succinate) [63,64]. The dialysis bags with formulations content separately were put in mentioned buffers and incubated at 37℃ overnight.…”

Section: Post-inserted Formulation Preparationmentioning

confidence: 99%

“…In this method, the ligand-coupled PEG-lipid derivatives are applied to the liposomes from a micelle phase [48][49][50][51][52][53]. Previously, we demonstrated the high e ciency and reproducibility of the post-insertion method in the preparation of actively targeted liposomal Dox [54,55]. In a temperature-and time-dependent manner, the micellar DSPE-PEG(2000) Maleimide-GSH complex has been incorporated into the PEGylated liposomal doxorubicin structure.…”

Section: Introductionmentioning

confidence: 99%

Preparation, Characterization, and Biodistribution of Glutathione PEGylated Nanoliposomal Doxorubicin for Brain Drug Delivery with A Post-insertion Approach

Mehrabian¹,

Vakili‐Ghartavol²,

Mashreghi³

et al. 2021

Preprint

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Brain cancer treatments have been largely unsuccessful due to the blood-brain barrier. Several publications support the presence of glutathione (GSH) receptors on the surface of the BBB and consequently the products such as the 2B3-101, which is almost 5% pre-inserted GSH PEGylated liposomal doxorubicin, is under process in clinical studies. Here we conducted the PEGylated nanoliposomal doxorubicin particles that are covalently attached to the glutathione using the post-insertion technique. The post-insertion methodology is noticeably simpler, faster, and more cost-effective compared to the pre-insertion method which makes it desirable for large-scale pharmaceutical manufacturing. The 25, 50, 100, 200, and 400 ligands of the DSPE PEG(2000) Maleimide-GSH complexes were incorporated into the available Caelyx. According to the animal studies such as biodistribution, fluorescent microscopy, and pharmacokinetic studies, the 200L and 400L treatment arms were the most promising formulations compared to the Caelyx. They proved that post-inserted nanocarriers with 40 times lower levels of GSH micelles compared to the 2B3-101 have significantly increased the penetrance through the blood-brain barrier. Other tissue analysis showed that the doxorubicin will likely accumulate in the liver, spleen, heart, and lung in comparison with the Caelyx due to the expressed GSH receptors on tissues as an endogenous antioxidant. In conclusion, as was expected, the post-insertion technique was found a successful approach with more pharmaceutical aspects for large-scale production. Moreover, it is highly recommended further investigations to determine the efficacy of 5% post-inserted GSH targeted nanoliposomes versus the 2B3-101 as a similar formulation with a different preparation method.

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“…Although antibodies against leptin receptors have been developed, these have yet to be tested as a CRC treatment [31]. A leptinderived peptide (L16) used to decorate the PEGylated liposomal doxorubicin (Doxil ® ) has increased Doxil's therapeutic efficacy in a murine CRC model, thus showing promise as a future treatment to increase target efficacy to tumour cells [32].…”

Section: Leptinmentioning

confidence: 99%

The prognostic and therapeutic role of hormones in colorectal cancer: a review

et al. 2018

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Colorectal cancer (CRC) is one of the commonest cancers in Western society with a poor prognosis in patients with advanced disease. Targeted therapy is of increasing interest and already, targeted hormone treatment for breast and prostate cancer has improved survival. The aim of this literature review is to summarise the role of hormones in CRC prognosis and treatment. A literature review of all human and animal in vivo and in vitro studies in the last 20 years, which assessed the role of hormones in CRC treatment or prognosis, was carried out. The hormones described in this review have been subdivided according to their secretion origin. Most of the studies are based on in vitro or animal models. The main findings point to adipokines, insulin and the insulin growth factor axis as key players in the link between obesity, type 2 diabetes mellitus and a subset of CRC. Gut-derived hormones, especially uroguanylin and guanylin are being increasingly investigated as therapeutic targets, with promising results. Using hormones as prognostic and therapeutic markers in CRC is still in the preliminary stages for only a fraction of the hormones affecting the GIT. In light of the increasing interest in tailoring treatment strategies, hormones are an important area of focus in the future of CRC management.

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Targeting the leptin receptor: To evaluate therapeutic efficacy and anti-tumor effects of Doxil, in vitro and in vivo in mice bearing C26 colon carcinoma tumor

Cited by 20 publications

References 55 publications

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Leptin and Cancer: Updated Functional Roles in Carcinogenesis, Therapeutic Niches, and Developments

Preparation, Characterization, and Biodistribution of Glutathione PEGylated Nanoliposomal Doxorubicin for Brain Drug Delivery with A Post-insertion Approach

The prognostic and therapeutic role of hormones in colorectal cancer: a review

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