3D microtumors in vitro supported by perfused vascular networks

Scientific Reports, Год журнала: 2016, Номер 6(1)

Опубликована: Авг. 23, 2016

Abstract There is a growing interest in developing microphysiological systems that can be used to model both normal and pathological human organs vitro . This “organs-on-chips” approach aims capture key structural physiological characteristics of the target tissue. Here we describe vascularized microtumors (VMTs). “tumor-on-a-chip” platform incorporates tumor stromal cells grow 3D extracellular matrix depend for survival on nutrient delivery through living, perfused microvessels. Both colorectal breast cancer vigorously respond standard-of-care therapies, showing reduced growth and/or regression. Vascular-targeting agents with different mechanisms action also distinguished, find drugs targeting only VEGFRs (Apatinib Vandetanib) are not effective, whereas VEGFRs, PDGFR Tie2 (Linifanib Cabozantinib) do regress vasculature. Tumors VMT show strong metabolic heterogeneity when imaged using NADH Fluorescent Lifetime Imaging Microscopy and, compared their surrounding stroma, many higher free/bound ratio consistent known preference aerobic glycolysis. The provides unique studying solid tumors

Язык: Английский

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Optical imaging of metabolic dynamics in animals

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Июль 25, 2018

Direct visualization of metabolic dynamics in living animals with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing stimulated Raman scattering (DO-SRS) microscopy image situ activities. Enzymatic incorporation D2O-derived into macromolecules generates carbon-deuterium (C-D) bonds, which track biosynthesis tissues can be imaged by SRS situ. Within the broad vibrational spectra C-D discover lipid-, protein-, DNA-specific shifts develop spectral unmixing methods obtain signals macromolecular selectivity. DO-SRS enables us probe de novo lipogenesis animals, protein without tissue bias, simultaneously visualize lipid metabolism reveal their different dynamics. microscopy, being noninvasive, universally applicable, cost-effective, adapted range systems study development, homeostasis, aging, tumor heterogeneity.

Язык: Английский

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Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment

Journal of Hematology & Oncology, Год журнала: 2017, Номер 10(1)

Опубликована: Март 9, 2017

The 2016 Nobel Prize in Physiology or Medicine was awarded to the researcher that discovered autophagy, which is an evolutionally conserved catabolic process degrades cytoplasmic constituents and organelles lysosome. Autophagy plays a crucial role both normal tissue homeostasis tumor development necessary for cancer cells adapt efficiently unfavorable microenvironment characterized by hypo-nutrient conditions. This protein degradation leads amino acid recycling, provides sufficient substrates cellular survival proliferation. constitutively activated due deregulation of PI3K/Akt/mTOR signaling pathway, enables them exhibit robust proliferation at pre-metastatic niche. That why just activation autophagy with mTOR inhibitor often fails vain. In contrast, disturbance autophagy–lysosome flux endoplasmic reticulum (ER) stress unfolded response (UPR), finally increased apoptotic cell death tissue. Accumulating evidence suggests has close relationship programmed death, while uncontrolled itself induces autophagic cells. Autophagic originally defined as accompanied large-scale vacuolization cytoplasm. However, "double-edged sword" it can either promote suppress microenvironment. Furthermore, several studies drug re-positioning suggest "conventional" agents used treat diseases other than have antitumor therapeutic effects activating/suppressing autophagy. Because ever increasing failure rates high cost associated anticancer development, this strategy attracted attention because safety profiles these medicines are well known. Antimalarial such artemisinin disease-modifying antirheumatic (DMARD) typical examples affect regulation use. review article focuses on recent advances some novel strategies target view treating/preventing malignant neoplasms.

Язык: Английский

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Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Metabolites, Год журнала: 2021, Номер 11(1), С. 28 - 28

Опубликована: Янв. 2, 2021

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of primary site, intravasation into vessels where anchorage-independent is required, colonization distant organs environment distinct from that site. Thus, cancer must reprogram their state every step progression. Metabolic reprogramming now recognized as a hallmark supports growth. Elucidating underlying mechanisms may help identifying targets treatment strategies. This review summarizes our current understanding progression metastasis, cell adaptation to microenvironment, defense against oxidative stress vessels, metastasis.

Язык: Английский

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Linking metabolic reprogramming to therapy resistance in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2017, Номер 1868(1), С. 1 - 6

Опубликована: Янв. 6, 2017

Язык: Английский

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Applications of vibrational tags in biological imaging by Raman microscopy

The Analyst, Год журнала: 2017, Номер 142(21), С. 4018 - 4029

Опубликована: Янв. 1, 2017

In this article, we review the recent successful applications of SRS and vibrational tags for solving biological problems.

Язык: Английский

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Recent advances in heat shock proteins in cancer diagnosis, prognosis, metabolism and treatment

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 142, С. 112074 - 112074

Опубликована: Авг. 20, 2021

Heat shock proteins (HSPs) are a group of proteins, also known as molecular chaperones, which participate in protein folding and maturation response to stresses or high temperature. According their weights, mammalian HSPs classified into HSP27, HSP40, HSP60, HSP70, HSP90, large HSPs. Previous studies have revealed that play important roles oncogenesis malignant progression because they can modulate all six hallmark traits cancer. Because this, been propelled the spotlight biomarkers for cancer diagnosis prognosis, well an exciting anticancer drug target. However, relationship between expression level activity diagnosis, metabolism treatment is not clear has completely established. Herein, this review summarizes discusses recent advances perspectives major regulators therapeutic targets therapy, may provide new directions improve accuracy develop more effective safer therapeutics.

Язык: Английский

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Immune cell metabolism and metabolic reprogramming

Molecular Biology Reports, Год журнала: 2022, Номер 49(10), С. 9783 - 9795

Опубликована: Июнь 13, 2022

Язык: Английский

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TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor

Genes, Год журнала: 2018, Номер 9(4), С. 195 - 195

Опубликована: Апрель 5, 2018

Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) a molecular chaperone involved the regulation of energetic metabolism cancer cells. This protein highly expressed several cancers, such as glioblastoma, colon, breast, prostate lung cancers often associated with drug resistance. However, TRAP1 also downregulated specific tumors, ovarian, bladder renal where its lower expression worst prognoses chemoresistance. only mitochondrial member Heat Shock 90 (HSP90) family that directly interacts respiratory complexes, contributing their stability activity but it still unclear if interactions lead reduced or increased capacity. The role enhance suppress oxidative phosphorylation; effects on development progression are controversial. These observations encourage study mechanisms responsible for dualist oncogene oncosuppressor types. In this review, puzzling functions were recapitulated special focus correlation between We wanted investigate whether metabolism-targeting drugs can efficiently interfere they might be combined chemotherapeutics molecular-targeted agents counteract resistance reduce therapeutic failure.

Язык: Английский

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High-throughput, label-free, single-cell photoacoustic microscopy of intratumoral metabolic heterogeneity

Nature Biomedical Engineering, Год журнала: 2019, Номер 3(5), С. 381 - 391

Опубликована: Апрель 1, 2019

Язык: Английский

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