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Huan-Rong Lan

Bio: Huan-Rong Lan is an academic researcher from Zhejiang University. The author has contributed to research in topics: Cancer & Tumor microenvironment. The author has an hindex of 5, co-authored 14 publications receiving 119 citations.

Papers
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Journal Article
TL;DR: The structural and functional abnormalities of the tumor microvasculature are summarized to highlight the importance of this phenomenon for chemotherapeutics distribution and the limitations of anti-angiogenic strategy in cancer treatment are summarized.
Abstract: Enhancing chemotherapy delivery to tumors, improving tumor growth control, reducing metastasis, and increasing survival are all critical objectives of improved cancer therapy. One of the obstacles to the success of anticancer therapies is related to the inefficient distribution of drugs to tumor cells. To be effective, chemotherapeutics must reach a concentration in cancer cells that is sufficient to inhibit its targets. In the past years, the vascular normalization theory has gained widespread acceptance for explaining additional antitumor effects of inhibitors of vascular endothelial growth factor (VEGF) signaling, when combined with chemotherapeutics. Vascular normalization is a strategy to enhance the antitumor effects of chemotherapeutics, but this is time and dose dependent and therefore difficult to implement clinically. Thus, alternative strategies that overcome these issues are needed. Accumulating scientific data demonstrate an alternative approach called "vascular promotion therapy" can increase chemotherapeutics delivery and intracellular uptake of the drug and reduces hypoxia by increasing tumor blood vessel density, blood flow, leakiness, and dilation, which leads to reduced cancer growth and metastasis. In this article, we first summarize the structural and functional abnormalities of the tumor microvasculature to highlight the importance of this phenomenon for chemotherapeutics distribution. Next, we summarize the limitations of anti-angiogenic strategy in cancer treatment, discuss some key prototypical underlying mechanisms of vascular normalization and initial clinical evidence of vascular promotion therapy, and speculate on the clinical potential of anticoagulation as a novel paradigm to improve cancer treatment.

42 citations

Journal ArticleDOI
TL;DR: The advances in this area through the review of novel NP drug formulations developed over the last year are described, focusing specifically on lung, colon, cervical, and breast cancers, and the future of NPs as potential treatment options are discussed.
Abstract: Chemotherapy drugs are cytotoxic to tumor cells, but their lack of specificity leads to a range of side effects. The off-target effects of such drugs can be improved through the use of nanoparticles (NPs). Administered NPs show enhanced accumulation in tumor tissue near the blood vessels, enhancing both anticancer drug permeability and tumor retention. Several nanocarriers are now approved for clinical use in a range of cancer therapies, and many novel formulations are in the later stages of clinical trials. Here, we describe the advances in this area through the review of novel NP drug formulations developed over the last year. We focus specifically on lung, colon, cervical, and breast cancers and discuss the future of NPs as potential treatment options in these areas.

38 citations

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TL;DR: Zhang et al. as discussed by the authors found that the density of macrophages infiltrated into colorectal cancer tissues from OX-resistant patients was significantly higher compared with the OX sensitive patients.
Abstract: As a third-generation platinum drug, oxaliplatin (OX) is widely used as the first-line chemotherapeutic agent in the treatment of colorectal cancer (CRC). CRC cells acquire resistance to chemotherapy and develop resistance, which is a major challenge for the treatment of advanced CRC. Recent studies have suggested that the therapeutic resistance of tumors is affected by the tumor microenvironment (TME). As a critical role among TME, tumor-associated macrophages (TAMs) play an important role. However, their regulatory mechanism underlying the drug resistance in CRC remains largely unknown. In the present study, we found that the density of macrophages infiltrated into the CRC tissues from OX-resistant patients was significantly higher compared with the OX-sensitive patients. Interestingly, both the total N6-methyladenosine (m6A) RNA content and the expression of its critical methyltransferase METTL3 were increased in the CRC tissues from OX-resistant patients compared with the OX-sensitive patients. Furthermore, we demonstrated that the M2-polarized TAMs enabled the OX resistance via the elevation of METTL3-mediated m6A modification in cells. Through whole-genome CRISPR screening and further validation, we found that TRAF5 contributes to the METTL3-triggered OX resistance in CRC cells. This study unveiled that M2-TAMs were important mediators for the acquisition of OX resistance. Furthermore, we provided evidence that targeting of M2-TAMs and METTL3-mediated m6A modification might be a promising adjuvant therapeutic strategy for CRC patients, especially for OX-resistant CRC patients.

36 citations

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TL;DR: The present review describes the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.
Abstract: Cancer is a complex multifactorial disease for which many promising therapeutic strategies such as immunotherapy are emerging. Malignant cells frequently express aberrant cell surface carbohydrates, which differentiate them from normal “healthy” cells. This characteristic presents a window for the development of synthetic carbohydrate antigen-based cancer vaccines which can be recognized by the immune system and can bring about T cell-dependent immune responses. Antibodies generated against the carbohydrate antigens partake in the inactivation of carbohydrate-decorated cancer cells, by slowing down tumor cell growth and inducing cancer cell apoptosis. Novel synthetic strategies for carbohydrate antigens have led to several synthetic cancer vaccine candidates. In the present review, we describe the latest progress in carbohydrate-based cancer vaccines and their clinical evaluation in various cancers.

34 citations

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TL;DR: The authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers and suggest that the quantification of C TCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.
Abstract: The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real-time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a "liquid biopsy") and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.

20 citations


Cited by
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Journal ArticleDOI
TL;DR: Current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment are focused on.
Abstract: The use of nanomedicine for cancer treatment takes advantage of its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect. The development of cancer nanomedicine has promised highly effective treatment options unprecedented by standard therapeutics. However, the therapeutic efficacy of passively targeted nanomedicine is not always satisfactory because it is largely influenced by the heterogeneity of the intensity of the EPR effect exhibited within a tumor, at different stages of a tumor, and among individual tumors. In addition, limited data on EPR effectiveness in human hinders further clinical translation of nanomedicine. This unsatisfactory therapeutic outcome in mice and humans necessitates novel approaches to improve the EPR effect. This review focuses on current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment. This review will provide valuable insight to researchers who seek to overcome the limitations of relying on the EPR effect alone in cancer nanomedicine and go "beyond the EPR effect".

204 citations

Journal ArticleDOI
Shu Yang1, Huile Gao1
TL;DR: Current strategies developed to modulate TME, including modulating tumor vasculature permeability, tumorassociated macrophage phenotypes, tumor associated fibroblasts, tumor stroma components, tumor hypoxia, and multiple interventions simultaneously are reviewed.

174 citations

Journal ArticleDOI
TL;DR: This review highlights some of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer and provides examples of modified protein formats and modifications allowing tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity.

130 citations

Journal ArticleDOI
TL;DR: Clinical data was analyzed to identify key parameters affecting the extent of the enhanced permeability and retention effect and propose 2 strategies for identification of suitable patient subpopulations, with respect to the EPR effect, in order to maximize therapeutic outcome.

102 citations

Journal ArticleDOI
TL;DR: Despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction.

80 citations