CD133: An emerging prognostic factor and therapeutic target in colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Recently, the role of cancer stem cells (CSCs) has been highlighted as a crucial emerging factor in chemoresistance, cancer relapse, and metastasis. CD133 is a surface marker of CSCs and has been argued to have prognostic and therapeutic values in CRC along with its related pathways such as Wnt, Notch, and hedgehog. Several studies have successfully applied targeted therapies against CD133 in CRC models namely bispecific antibodies (BiAbs) and anti‐Wnt and notch pathways agents. These studies have yielded initial promising results in this regard. However, none of the therapeutics have been used in the clinical setting and their efficacy and adverse effects profile are yet to be elucidated. This review aims to gather the old and most recent data on the prognostic and therapeutic values of CD133 and CD133‐targeted therapies in CRC.     

TGFβ1‐induced leucine limitation uncovered by differential ribosome codon reading

Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine. Further analyses indicated that TGFβ1 treatment of human breast epithelial cells reduces the expression of SLC3A2, a subunit of the leucine transporter, which diminishes leucine uptake and inhibits cell proliferation. Thus, we identified a specific amino acid limitation associated with the TGFβ1 response, a vulnerability that might be associated with aggressiveness in cancer.     

Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions

Dietary flaxseed has been shown to have potent antiatherogenic effects in rabbits. The purpose of the present study was to investigate the antiatherogenic capacity of flaxseed in an animal model that more closely represents the human atherosclerotic condition, the LDL receptor-deficient mouse (LDLrKO), and to identify the cellular mechanisms for these effects. LDLrKO mice were administered a regular diet (RG), a 10% flaxseed-supplemented diet (FX), or an atherogenic diet containing 2% cholesterol alone (CH) or supplemented with 10% flaxseed (CF), 5% flaxseed (CF5), 1% flaxseed (CF1), or 5% coconut oil (CS) for 24 wk. LDLrKO mice fed a cholesterol-supplemented diet exhibited a rise in plasma cholesterol without a change in triglycerides and an increase in atherosclerotic plaque formation. The CS mice exhibited elevated levels of plasma cholesterol, triglycerides, and saturated fatty acids and an increase in plaque development. Supplementation of the cholesterol-enriched diet with 10% (wt/wt) ground flaxseed lowered plasma cholesterol and saturated fatty acids, increased plasma ALA, and inhibited plaque formation in the aorta and aortic sinus compared with mice fed a diet supplemented with only dietary cholesterol. The expression of proliferating cell nuclear antigen (PCNA) and the inflammatory markers IL-6, mac-3, and VCAM-1 was increased in aortic tissue from CH and CS mice. This expression was significantly reduced or normalized when flaxseed was included in the diet. Our results demonstrate that dietary flaxseed can inhibit atherosclerosis in the LDLrKO mouse through a reduction of circulating cholesterol levels and, at a cellular level, via antiproliferative and anti-inflammatory actions.     

Genome re-diploidization occurs spontaneously just prior to anthesis in artificially induced auto-tetraploid maize (Zea mays L.) inbred lines

Plant Cell, Tissue and Organ Culture (PCTOC) - In this study, various concentrations of oryzalin (0, 5, 10, 50, and 100 mg l?1), trifluralin (0, 5, 10, 50, and...     

Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma

Multiple myeloma (MM) is a clonal B‐cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. The immune checkpoint inhibitors against programmed death‐1/programmed death‐1 ligand and cytotoxic T‐lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. The evidence shows that multiple tumor‐intrinsic and tumor‐extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor‐related factor effects on immune checkpoints blockade in MM immunotherapy.     

DIEL VARIATIONS IN OPTICAL PROPERTIES OF IMANTONIA ROTUNDA (HAPTOPHYCEAE) AND THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE) EXPOSED TO DIFFERENT IRRADIANCE LEVELS1

Diel variations of cellular optical properties were examined for cultures of the haptophyte Imantonia rotunda N. Reynolds and the diatom Thalassiosira pseudonana (Hust.) Hasle et Heimdal grown under a 14:10 light:dark (L:D) cycle and transferred from 100 μmol photons · m^?2 · s^?1 to higher irradiances of 250 and 500 μmol photons · m^?2 · s^?1. Cell volume and abundance, phytoplankton absorption coefficients, flow‐cytometric light scattering and chl fluorescence, and pigment composition were measured every 2 h over a 24 h period. Results showed that cell division was more synchronous for I. rotunda than for T. pseudonana. Several variables exhibited diel variability with an amplitude >100%, notably mean cell volume for the haptophyte and photoprotective carotenoids for both species, while optical properties such as flow‐cytometric scattering and chl a–specific phytoplankton absorption generally showed <50% diel variability. Increased irradiance induced changes in pigments (both species) and mean cell volume (for the diatom) and amplified diel variability for most variables. This increase in amplitude is larger for pigments (factor of 2 or more, notably for cellular photoprotective carotenoid content in I. rotunda and for photosynthetic pigments in T. pseudonana) than for optical properties (a factor of 1.5 for chl a–specific absorption, at 440 nm, in I. rotunda and a factor of 2 for the absorption cross‐section and the chl a–specific scattering in T. pseudonana). Consequently, diel changes in optical properties and pigmentation associated with the L:D cycle and amplified by concurrent changes in irradiance likely contribute significantly to the variability in optical properties observed in biooptical field studies.     

New emerging roles of CD133 in cancer stem cell: Signaling pathway and miRNA regulation

Cancer stem cells (CSC) are rare immortal cells within a tumor that are able to initiate tumor progression, development, and resistance. Advances studies show that, like normal stem cells, CSCs can be both self-renewed and given rise to many cell types, therefore form tumors. A number of cell surface markers, such as CD44, CD24, and CD133 are frequently used to identify CSCs. CD133, a transmembrane glycoprotein, either alone or in collaboration with other markers, has been mainly considered to identify CSCs from different solid tumors. However, the exactness of CD133 as a cancer stem cell biomarker has not been approved yet. The clinical importance of CD133 is as a CSC marker in many cancers. Also, it contributes to shorter survival, tumor progression, and tumor recurrence. The expression of CD133 is controlled by many extracellular or intracellular factors, such as tumor microenvironment, epigenetic factors, signaling pathways, and miRNAs. In this study, it was attempted to determine: 1) CD133 function; 2) the role of CD133 in cancer; 3) CD133 regulation; 4) the therapeutic role of CD133 in cancers.