The development of tumour vascular networks

Fouladzadeh, Anahita; Dorraki, Mohsen; Min, Kay K Myo; Cockshell, Michaelia P.; Thompson, Emma J.; Verjans, Johan; Allison, Andrew; Bonder, Claudine S.; Abbott, Derek

doi:10.1038/s42003-021-02632-x

Cited by 21 publications

(18 citation statements)

References 45 publications

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“…The resulted biodistribution of Pt 2+ species in tumors could be explained by the heterogeneity of tumor vasculature, which is generally associated with the tumor surface but also forms an irregular network within the tumor volume. 74,75 The heterogeneous distribution of platinum in the tumor tissue was also observed by Carlier et al via LA−ICP−MS mappings of cisplatin in ovarian cancer tissue. 76 To date, only a few published studies have discussed a comparison of the ability of Pt(IV) prodrugs to penetrate tumors.…”

Section: And Figures S56−s61)supporting

confidence: 58%

“…After the injection of prodrug DNP , Pt 2+ species were detected at a depth of 600 μm; however, the total amount of detected cisplatin after the injection of prodrug 7 was higher. The resulted biodistribution of Pt 2+ species in tumors could be explained by the heterogeneity of tumor vasculature, which is generally associated with the tumor surface but also forms an irregular network within the tumor volume. , The heterogeneous distribution of platinum in the tumor tissue was also observed by Carlier et al via LA–ICP–MS mappings of cisplatin in ovarian cancer tissue …”

Section: Resultsmentioning

confidence: 68%

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Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

et al. 2022

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We report herein the design, synthesis, and biological investigation of a series of novel Pt(IV) prodrugs with non-steroidal anti-inflammatory drugs naproxen, diclofenac, and flurbiprofen, as well as these with stearic acid in the axial position. Six Pt(IV) prodrugs 5–10 were designed, which showed superior antiproliferative activity compared to cisplatin as well as an ability to overcome tumor cell line resistance to cisplatin. By tuning the drug lipophilicity via variation of the axial ligands, the most potent Pt(IV) prodrug 7 was obtained, with an enhanced cellular accumulation of up to 153-fold that of cisplatin and nanomolar cytotoxicity both in 2D and 3D cell cultures. Pt2+ species were detected at different depths of MCF-7 spheroids after incubation with Pt(IV) prodrugs using a Pt-coated carbon nanoelectrode. Cisplatin accumulation in vivo in the murine mammary EMT6 tumor tissue of BALB/c mice after Pt(IV) prodrug injection was proved electrochemically as well. The drug tolerance study on BALB/c mice showed good tolerance of 7 in doses up to 8 mg/kg.

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Section: And Figures S56−s61)supporting

confidence: 58%

Section: Resultsmentioning

confidence: 68%

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

et al. 2022

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“…Cancer cells can differentiate and enhance EC-like characteristics by expressing VE-cadherin and ephrin A2. This process is associated with increased tumour invasiveness and relapses [ 6 ].…”

Section: Resultsmentioning

confidence: 99%

Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows

Cazzaniga

Capici²,

Cordani

et al. 2022

JCM

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Metronomic chemotherapy (mCHT), defined as continuous administration of low-dose chemotherapeutic agents with no or short regular treatment-free intervals, was first introduced to the clinic in international guidelines in 2017, and, since then, has become one of the available strategies for the treatment of advanced breast cancer (ABC). Despite recent successes, many unsolved practical and theoretical issues remain to be addressed. The present review aims to identify the “lights and shadows” of mCHT in preclinical and clinical settings. In the preclinical setting, several findings indicate that one of the most noticeable effects of mCHT is on the tumor microenvironment, which, over the last twenty years, has been demonstrated to be pivotal in supporting tumor cell survival and proliferation. On the other hand, the direct effects on tumor cells have been less well-defined. In addition, critical items to be addressed are the lack of definition of an optimal biological dose (OBD), the method of administration of metronomic schedules, and the recognition and validation of predictive biomarkers. In the clinical context—where mCHT has mainly been used in a metastatic setting—low toxicity is the most well-recognised light of mCHT, whereas the type of study design, the absence of randomised trials and uncertainty in terms of doses and drugs remain among the shadows. In conclusion, growing evidence indicates that mCHT is a suitable treatment option for selected metastatic breast cancer (MBC) patients. Moreover, given its multimodal mechanisms of action, its addition to immunological and targeted therapies might represent a promising new approach to the treatment of MBC. More preclinical data are needed in this regard, which can only be obtained through support for translational research as the key link between basic science and patient care.

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“…Several complex systems have been investigated recently from a networks viewpoint that link the different elements comprising them 31 . The development of tumour vascular networks has recently been explored via graph theory 32 . Network analysis can qualitatively and quantitatively reveal vital information on the unique characteristics of biological phenomena.…”

Section: Introductionmentioning

confidence: 99%

Hip osteoarthritis: A novel network analysis of subchondral trabecular bone structures

Dorraki

Muratovic

Fouladzadeh

et al. 2022

Preprint

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Hip osteoarthritis (HOA) is a degenerative joint disease that leads to the progressive destruction of subchondral bone and cartilage at the hip joint. Development of effective treatments for HOA remains an open problem, primarily due to the lack of knowledge of its pathogenesis and a typically late-stage diagnosis. We describe a novel network analysis methodology for micro-computed tomography (micro-CT) images of human trabecular bone. We explored differences between the trabecular bone microstructure of femoral heads with and without HOA. Large-scale automated extraction of the network formed by trabecular bone revealed significant network properties not previously reported for bone. Profound differences were discovered, particularly in the proximal third of the femoral head, where HOA networks demonstrated elevated numbers of edges, vertices and graph components. When further differentiating healthy joint and HOA networks, the latter showed fewer small-world network properties, due to decreased clustering coefficient and increased characteristic path length. Furthermore, we found that HOA networks had reduced length of edges, indicating the formation of compressed trabecular structures. In order to assess our network approach, we developed a deep learning model for classifying HOA and control cases, and we fed it with two separate inputs: (i) micro-CT images of the trabecular bone, and (ii) the network extracted from them. The model with plain micro-CT images achieves 74.63% overall accuracy while the trained model with extracted networks attains 96.47% accuracy. We anticipate our findings to be a starting point for a novel description of bone microstructure in HOA, by considering the phenomenon from a graph theory viewpoint.

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The development of tumour vascular networks

Cited by 21 publications

References 45 publications

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

Metronomic Chemotherapy for Metastatic Breast Cancer Treatment: Clinical and Preclinical Data between Lights and Shadows

Hip osteoarthritis: A novel network analysis of subchondral trabecular bone structures

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