Recently, an attractive new therapeutic concept called 'acoustic-explosion' was suggested for some functionalized fullerenes, polyhydroxy fullerenes (PHF; C60(OH)xOyNaz) and carboxy fullerenes (CF; C60(C(COOH)2)3). Concomitant with the exposure to low-intensity (2 W cm-2) continuous-wave laser irradiation in the presence or absence of oxygen, sustained glowing of functionalized fullerenes was observed. When this process was performed in cancer cells, a faint pop was heard following irradiation, indicating the photoacoustic properties of functionalized fullerenes. To investigate their potential for cancer imaging, researchers then used a mechanical scanning photoacoustic system with a single transducer to collect the acoustic signal, and embedded it in a phantom together with functionalized fullerenes. After laser irradiation in a water tank, high contrast photoacoustic images of functionalized fullerenes were obtained. Similarly, the photoacoustic imaging experiment yielded promising results in tumor-bearing nude mice. Excellent contrast between tumor and non-tumor regions was shown after intratumoral injection of PHF, and the laser energy used was only one-third of the maximum permissible exposure level of 29.5 mJ cm−2 for a 785 nm pulsed laser as established by the American National Standards Institute [, ]. This new finding suggests potential applications of functionalized fullerenes for obtaining photoacoustic images (Figure ).
Zhang have performed comprehensive work on the modulation of autophagy in cancer cells by fullerene C60 nanocrystals. They found that HeLa cells treated with nano-C60 exhibited autophagic features, such as LC3 puncta formation, and many more autophagic vacuoles including autophagosomes and autolysosomes. Nano-C60 at non-cytotoxic concentrations sensitized chemotherapeutic killing of cancer cells in a photo-enhanced and ROS-dependent pathway, which was further verified via GFP-LC3 dot formation that was effectively reduced by free radical scavengers in the dark treatments . A much greater potential in the induction of autophagy by another C60 derivative, C60(Nd), was also reported . All above results prompt that fullerenes might be available to be an efficient chemo-sensitizer in cancer therapy.
The Cancer Stem Cell Hypothesis
The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors lacking such mutations, although the mechanism of pathway activation is poorly understood. Here we study the role and mechanism of Hh pathway activation in multiple myeloma (MM), a malignancy with a well defined stem cell compartment. In this model, rare malignant progenitors capable of clonal expansion resemble B cells, whereas the much larger tumor cell population manifests a differentiated plasma cell phenotype that pathologically defines the disease. We show that the subset of MM cells that manifests Hh pathway activity is markedly concentrated within the tumor stem cell compartment. The Hh ligand promotes expansion of MM stem cells without differentiation, whereas the Hh pathway blockade, while having little or no effect on malignant plasma cell growth, markedly inhibits clonal expansion accompanied by terminal differentiation of purified MM stem cells. These data reveal that Hh pathway activation is heterogeneous across the spectrum of MM tumor stem cells and their more differentiated progeny. The potential existence of similar relationships in other adult cancers may have important biologic and clinical implications for the study of aberrant Hh signaling.
Stem-like Cells' Exist In Benign Tumors.
Bao S, Wu Q, Sathornsumetee S, Hao Y, LiZ, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD and Rich JN: Stemcell-like glioma cells promote tumor angiogenesis throughvascularendothelial growth factor. Cancer Res. 66:7843–7848. 2006. : :
EUDML | Modeling the Cancer Stem Cell Hypothesis
The main therapeutic goal of cancer treatment is to trigger tumor-selective cell death. One of the cellular pathways receiving much attention in recent years is autophagy, a highly-regulated intracellular process for the degradation of long-lived proteins and damaged organelles. Autophagy can be either a cell death pathway or a cell survival pathway depending on many factors such as the degree of cell damage and intactness of apoptotic pathways . Undoubtedly, promoting autophagy-mediated cell apoptosis is of most concern for tumor therapy.
Modeling the Cancer Stem Cell Hypothesis C ..
Mimeault M and Batra SK: Hypoxia-inducingfactors as master regulators of stemness properties and alteredmetabolism of cancer- and metastasis-initiating cells. J Cell MolMed. 17:30–54. 2013. : :
The cancer stem cell hypothesis applied to oral carcinoma
Clarke MF, Dick JE, Dirks PB, Eaves CJ,Jamieson CH, Jones DL, et al: Cancer stem cells - perspectives oncurrent status and future directions: AACR Workshop on cancer stemcells. Cancer Res. 66:9339–9344. 2006. :
CollinsA tumour stem cell hypothesis for the origins ..
Pellegatta S, Poliani PL, Corno D, MenghiF, Ghielmetti F, Suarez-merino B, Caldera V, Nava S, Ravanini M,Facchetti F, et al: Neurospheres enriched in cancer stem-like cellsare highly effective in eliciting a dendritic cell-mediated immuneresponse against malignant gliomas. Cancer Res. 66:10247–10252.2006. : :