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   2017| November-December  | Volume 3 | Issue 6  
    Online since December 29, 2017

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“Eating” Cancer cells by blocking CD47 signaling: Cancer therapy by targeting the innate immune checkpoint
Yi-Rong Xiang, Li Liu
November-December 2017, 3(6):200-208
Differing from the adaptive immune checkpoint mediated by programmed cell death-1 (PD-1) PD-1-ligand or CTLA-4, the CD47 and signal regulatory protein α (SIRPα) axis is emerging as a novel innate immune checkpoint of the immune cells of myeloid lineage. A balance should be established between the dual signals, the “Don't eat me signal” of CD47-SIRPα and the “Eat me signal” of calreticulin/low-density lipoprotein receptor-related protein. The enhanced expression of CD47 molecule has been found in many cancer tissues, including malignant blood tumors (acute myeloid leukemia) and solid tumors. A therapeutic value could be achieved by counteracting the expression of CD47 in cancer cells. In the recent years, great progress has been made to develop anticancer therapies by targeting CD47 (e.g., anti-CD47 antibody), in various types of cancer. However, there are a few challenges, like “antigen sink” in the clinical translation of CD47-mediated anticancer therapies, the attention to which is crucial.
  4,618 730 4
Markerless four-dimensional-cone beam computed tomography projection-phase sorting using prior knowledge and patient motion modeling: A feasibility study
Lei Zhang, Yawei Zhang, You Zhang, Wendy B Harris, Fang-Fang Yin, Jing Cai, Lei Ren
November-December 2017, 3(6):185-193
Aim: During cancer radiotherapy treatment, on-board four-dimensional-cone beam computed tomography (4D-CBCT) provides important patient 4D volumetric information for tumor target verification. Reconstruction of 4D-CBCT images requires sorting of acquired projections into different respiratory phases. Traditional phase sorting methods are either based on external surrogates, which might miscorrelate with internal structures; or on 2D internal structures, which require specific organ presence or slow gantry rotations. The aim of this study is to investigate the feasibility of a 3D motion modeling-based method for markerless 4D-CBCT projection-phase sorting. Methods: Patient 4D-CT images acquired during simulation are used as prior images. Principal component analysis (PCA) is used to extract three major respiratory deformation patterns. On-board patient image volume is considered as a deformation of the prior CT at the end-expiration phase. Coefficients of the principal deformation patterns are solved for each on-board projection by matching it with the digitally reconstructed radiograph (DRR) of the deformed prior CT. The primary PCA coefficients are used for the projection-phase sorting. Results: PCA coefficients solved in nine digital phantoms (XCATs) showed the same pattern as the breathing motions in both the anteroposterior and superoinferior directions. The mean phase sorting differences were below 2% and percentages of phase difference < 10% were 100% for all the nine XCAT phantoms. Five lung cancer patient results showed mean phase difference ranging from 1.62% to 2.23%. The percentage of projections within 10% phase difference ranged from 98.4% to 100% and those within 5% phase difference ranged from 88.9% to 99.8%. Conclusion: The study demonstrated the feasibility of using PCA coefficients for 4D-CBCT projection-phase sorting. High sorting accuracy in both digital phantoms and patient cases was achieved. This method provides an accurate and robust tool for automatic 4D-CBCT projection sorting using 3D motion modeling without the need of external surrogate or internal markers.
  1,282 1,363 -
Biomarkers in molecular epidemiology study of oral squamous cell carcinoma in the era of precision medicine
Qing-Hao Zhu, Qing-Chao Shang, Zhi-Hao Hu, Yuan Liu, Bo Li, Bo Wang, An-Hui Wang
November-December 2017, 3(6):214-218
Oral cancer, which occurs in the mouth, lips, and tongue, is a multifactorial disease whose etiology involves environment, genetic, and epigenetic factors. Tobacco use and alcohol consumption are regarded as the primary risk factors for oral squamous cell carcinoma (OSCC), and betel use, other chemicals, radiation, environmental, and genetics are reported as relevant risk factors for oral carcinogenesis. The human papillomavirus infection is an independent risk factor. Traditional epidemiology studies have revealed that environmental carcinogens are risk factors for OSCC. Molecular epidemiology studies have revealed that the susceptibility to OSCC is influenced by both environmental and genetic risk factors. However, the details and mechanisms of risk factors involved in OSCC are unclear. Advanced methods and techniques used in human genome studies provide great opportunities for researchers to explore and identify (a) the details of such risk factors and (b) genetic susceptibility involved in OSCC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era into the era of genome-wide association study. In the era of precision medicine, molecular epidemiology studies should focus on biomarkers for cancer genomics and their potential utility in clinical practice. Here, we briefly reviewed several molecular epidemiology studies of OSCC, focusing on biomarkers as valuable utility in risk assessment, clinical screening, diagnosis, and prognosis prediction of OSCC in the era of precision medicine.
  2,016 318 1
Glycosylation is involved in malignant properties of cancer cells
Kazunori Hamamura, Koichi Furukawa
November-December 2017, 3(6):209-213
Cancer cells express unique carbohydrate structures in glycoproteins and glycolipids, and their structures have been considered to be cancer-associated antigens. However, the involvement of their antigens in the malignant properties has not been well understood. The functional studies of glycosyltransferase genes revealed important regulatory roles of glycosylation in the malignant properties of cancer cells. In particular, we have characterized the molecular signaling pathways that are activated or inactivated by gangliosides in various cancer cells. Our results indicated that disialyl gangliosides GD3 and GD2 enhance malignant properties of human melanoma, osteosarcoma, and small cell lung cancer cells. However, monosialyl ganglioside GM1 attenuates these properties in melanoma and lung cancer cells. In addition to glycolipids, glycoproteins are also reported to be involved in regulating malignant properties and maintenance of cancer stem cells.
  1,919 339 1
The producing capabilities of Interferon-γ and Interleukin-10 of spleen cells in primary and metastasized oral squamous cell carcinoma cells-implanted mice
Yasuka Azuma, Masako Mizuno-Kamiya, Eiji Takayama, Harumi Kawaki, Toshihiro Inagaki, Eiichi Chihara, Yasunori Muramatsu, Nobuo Kondoh
November-December 2017, 3(6):194-199
Aim: The aim of this study is to compare the immunomodulatory effects exerted by primary versus metastasized oral squamous cell carcinoma (OSCC) cells. Methods: Mouse OSCC cell line Sq-1979, 233 cells established from implanted Sq-1979 cells, and L cells established from the metastasized lymph node tissues of Sq-1979-implanted mice were subcutaneously inoculated into the later abdominal area of syngeneic C3H mice. The producing capabilities of interferon (IFN)-γ, a Th1 cytokine, and interleukin (IL)-10, a Th2 cytokine, by anti-CD3 antibody-stimulated spleen cells were investigated in tumor bearing-mice. Results: The quantity of IFN-γ produced by stimulated spleen cells was significantly suppressed in the mice implanted with Sq-1979, 233, and L cells. Conversely, the production of IL-10 was significantly elevated in Sq-1979 and 233 cell-implanted mice while markedly suppressed in L cell-implanted mice. Conclusion: Our results suggest that the metastasized L cells have acquired differential immunomodulatory functions compared to the original Sq-1979 and primary 233 cells.
  1,523 173 2
Erratum: Role of exosome microRNA in breast cancer

November-December 2017, 3(6):219-219
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