scholarly journals Distribution of Water Phantom BNCT Cyclotron based Using PHITS

2019 ◽  
Vol 4 (1) ◽  
pp. 1-7
Author(s):  
Siti Maimanah ◽  
Siti Maimanah ◽  
Susilo Susilo ◽  
Yohannes Sardjono
Keyword(s):  
Cancer Cells ◽  
Dose Distribution ◽  
Normal Tissue ◽  
Cellular Level ◽  
Healthy Tissue ◽  
Research Purpose ◽  
Powerful Method ◽  
Water Phantom

This research purpose is to estimate the dose distribution of BNCT in water phantom. Some common methods in the treatment of cancer such as brakhiterapi, surgery, chemotherapy, and radiotherapy still have the risk of damaging healthy tissue around cancer cells. BNCT is a selectively-designed technique by targeting high-loaded LET particles to tumors at the cellular level. BNCT proves to be a powerful method of killing cancer without damaging normal tissue. The source of the neutron used from the cyclotron dose in water phantom with the size of 30 cm x 30 cm x 30 cm was calculated using PHITS program. The result from the simulation is that boron water panthom has a dosimetri higher than phantom water without boron.

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization

2020 ◽  
Vol 20 (2) ◽  
pp. 130-145 ◽  
Author(s):  
Keywan Mortezaee ◽  
Masoud Najafi ◽  
Bagher Farhood ◽  
Amirhossein Ahmadi ◽  
Dheyauldeen Shabeeb ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Normal Tissue ◽  
Medical Science ◽  
Treatment Modalities ◽  
Radiation Toxicity ◽  
Normal Tissues ◽  
Normal Tissue Toxicity

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

scholarly journals Grapefruit-Derived Micro and Nanovesicles Show Distinct Metabolome Profiles and Anticancer Activities in the A375 Human Melanoma Cell Line

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2722
Author(s):  
Christopher Stanly ◽  
Mariaevelina Alfieri ◽  
Alfredo Ambrosone ◽  
Antonietta Leone ◽  
Immacolata Fiume ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Fruit Juice ◽  
Substantial Effect ◽  
Cellular Level ◽  
Gas Chromatography Mass Spectrometry ◽  
Anticancer Activities ◽  
Alpha Hydroxy Acids ◽  
Sugar Derivatives ◽  
Cell Adhesion Molecule 1

Fruit juice is one of the most easily accessible resources for the isolation of plant-derived vesicles. Here we found that micro- and nano-sized vesicles (MVs and NVs) from four Citrus species, C. sinensis, C. limon, C. paradisi and C. aurantium, specifically inhibit the proliferation of lung, skin and breast cancer cells, with no substantial effect on the growth of non-cancer cells. Cellular and molecular analyses demonstrate that grapefruit-derived vesicles cause cell cycle arrest at G2/M checkpoint associated with a reduced cyclins B1 and B2 expression levels and the upregulation of cell cycle inhibitor p21. Further data suggest the inhibition of Akt and ERK signalling, reduced intercellular cell adhesion molecule-1 and cathepsins expressions, and the presence of cleaved PARP-1, all associated with the observed changes at the cellular level. Gas chromatography-mass spectrometry-based metabolomics reveals distinct metabolite profiles for the juice and vesicle fractions. NVs exhibit a high relative amount of amino acids and organic acids whereas MVs and fruit juice are characterized by a high percentage of sugars and sugar derivatives. Grapefruit-derived NVs are in particular rich in alpha–hydroxy acids and leucine/isoleucine, myo-inositol and doconexent, while quininic acid was detected in MVs. Our findings reveal the metabolite signatures of grapefruit-derived vesicles and substantiate their potential use in new anticancer strategies.

scholarly journals PD-L1 regulates tumorigenesis and autophagy of ovarian cancer by activating mTORC signaling

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Hongmin Gao ◽  
Juan Zhang ◽  
Xiaohong Ren
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Cancer Cells ◽  
Clinical Significance ◽  
Tumour Cell ◽  
Normal Tissue ◽  
Ovarian Tumour ◽  
Ovarian Cancer Cells ◽  
Adjacent Normal Tissue ◽  
Novel Strategy

Abstract PD-L1 is a well-known immune co-stimulatory molecule that regulates tumour cell escape from immunity by suppressing the immune response. However, the clinical significance of PD-L1 in the progression of ovarian cancer is unclear. Our study demonstrated that PD-L1 is up-regulated in ovarian tumour tissue compared with its expression level in adjacent normal tissue. Furthermore, we confirmed that PD-L1 increases the proliferation of cancer cells by activating the AKT-mTORC signalling pathway, which is also enhanced by the expression of S6K, the substrate of mTORC. In addition, PD-L1 promotes the autophagy of ovarian cancer cells by up-regulating the expression of BECN1, a crucial molecule involved in the regulation of autophagy. In conclusion, PD-L1 may provide a target for the development of a novel strategy for the treatment of ovarian cancer.

SU-C-BRB-02: Exploring the Correlation Between 3D Spatial Dose Distribution and Toxicity in Normal Tissue

2012 ◽  
Vol 39 (6Part2) ◽  
pp. 3601-3601
Author(s):  
Z Saleh ◽  
A Apte ◽  
G Sharp ◽  
S Rao ◽  
N Lee ◽  
...  
Keyword(s):  
Dose Distribution ◽  
Normal Tissue

scholarly journals Dosimetric and radiobiological comparison of treatment plan between CyberKnife and EDGE in stereotactic body radiotherapy for pancreatic cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhi-tao Dai ◽  
Li Ma ◽  
Ting-ting Cao ◽  
Lian Zhu ◽  
Man Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Spinal Cord ◽  
Stereotactic Body Radiotherapy ◽  
Dose Distribution ◽  
Normal Tissue ◽  
Organs At Risk ◽  
Treatment Plan ◽  
Locally Advanced ◽  
Conformity Index ◽  
Homogeneous Dose

AbstractTo perform a comparison of the different stereotactic body radiotherapy (SBRT) plans between the Varian EDGE and CyberKnife (CK) systems for locally advanced unresectable pancreatic cancer. Fifteen patients with pancreatic cancer were selected in this study. The median planning target volume (PTV) was 28.688 cm3 (5.736–49.246 cm3). The SBRT plans for the EDGE and CK were generated in the Eclipse and Multiplan systems respectively with the same contouring and dose constrains for PTV and organs at risk (OARs). Dose distributions in PTV were evaluated in terms of coverage, conformity index (CI), new conformity index (nCI), homogeneity index (HI), and gradient index (GI). OARs, including spinal cord, bowel, stomach, duodenum and kidneys were statistically evaluated by different dose-volume metrics and equivalent uniform dose (EUD). The volume covered by the different isodose lines (ISDL) ranging from 10 to 100% for normal tissue were also analyzed. All SBRT plans for EDGE and CK met the dose constraints for PTV and OARs. For the PTV, the dosimetric metrics in EDGE plans were lower than that in CK, except that D99 and GI were slightly higher. The EDGE plans with lower CI, nCI and HI were superior to generate more conformal and homogeneous dose distribution for PTV. For the normal tissue, the CK plans were better at OARs sparing. The radiobiological indices EUD of spinal cord, duodenum, stomach, and kidneys were lower for CK plans, except that liver were higher. The volumes of normal tissue covered by medium ISDLs (with range of 20–70%) were lower for CK plans while that covered by high and low ISDLs were lower for EDGE plans. This study indicated that both EDGE and CK generated equivalent plan quality, and both systems can be considered as beneficial techniques for SBRT of pancreatic cancer. EDGE plans offered more conformal and homogeneous dose distribution for PTV, while the CK plans could minimize the exposure of OARs.

scholarly journals BCN057, a Modulator of GSK3b Induces KRAS G12D Mutant Pancreatic Cancer Cell Death

2021 ◽  
Author(s):  
Elizabeth M Singer ◽  
Rishi Mann Chugh ◽  
Payel Bhanja ◽  
Adrian Gomez ◽  
Lucy Gao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Small Molecule ◽  
Normal Tissue ◽  
Synthetic Lethality ◽  
Human Pancreatic Cancer ◽  
Oncogenic Ras ◽  
Cancer Cell Death ◽  
Pancreatic Cancer Cells ◽  
Normal Tissue Toxicity

Effective treatment for Pancreatic Cancer remains a major challenge due to its resistance to radiation/chemotherapy and poor drug permeability. Moreover, treatment induced normal tissue toxicity, mainly to the duodenum and gastrointestinal epithelium, is common and is a dose limiting event, while toxicity to the pancreas is relatively rare. Gastrointestinal toxicity, however, often results in interruption, reduction or premature withdrawal of anti–cancer therapy which is a very significant factor impacting the overall survival of patients being treated. Therefore, development of a therapeutic strategy to selectively sensitize tumor tissue without inducing normal tissue toxicity is important. In this manuscript, we show that the novel small molecule BCN057 can modulate chemo–sensitivity of oncogenic RAS pancreatic cancer cells while conversely protecting normal intestinal epithelium from off target toxicity. In particular, BCN 057 protects Lgr5 positive intestinal stem cells, thereby preserving barrier function. Further, it is demonstrated that BCN057 inhibits GSK3β and thereby induces a pro apoptotic phosphorylation pattern on c–Jun in KRAS G12D mutant pancreatic cancer cells (Panc1) leading to the restoration of PTEN expression and consequent apoptosis. This appears to be a new mechanistic observation for the oncogenic RAS phenotype. Lastly, concurrent with its GSK3β inhibition, BCN057 is a small molecule inhibitor of PD–1 expression on human T–lymphocytes co cultured with human pancreatic cancer cells. In summary, BCN057 can promote synthetic lethality specifically to malignant cells and therefore should be considered to improve the therapeutic ratio in pancreatic and epithelial cancer treatment in conjunction with chemotherapy and radiation.

scholarly journals DEAD-box helicase 27 enhances stem cell-like properties with poor prognosis in breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shan Li ◽  
Jinfei Ma ◽  
Ang Zheng ◽  
Xinyue Song ◽  
Si Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Western Blot ◽  
Cancer Cells ◽  
Normal Tissue ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Prognosis ◽  
Cancer Prognosis ◽  
Dead Box

Abstract Background Although the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer. Methods The expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan–Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer. Results DDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS, p = 0.0087) and disease-free survival (DFS, p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells. Conclusion DDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.

scholarly journals Pigment Epithelium-Derived Factor and its Phosphomimetic Mutant Induce JNK-Dependent Apoptosis and P38-Mediated Migration Arrest

2018 ◽  
Vol 49 (2) ◽  
pp. 512-529 ◽  
Author(s):  
Alexander Konson ◽  
Sunila Pradeep ◽  
Cosimo Walter D’Acunto ◽  
Rony Seger
Keyword(s):  
Cancer Cells ◽  
Present Report ◽  
Pigment Epithelium ◽  
Cellular Level ◽  
Molecular Signaling ◽  
Antiangiogenic Effect ◽  
Signaling Mechanism ◽  
Pigment Epithelium Derived Factor ◽  
And Migration

Background/Aims: Pigment epithelium-derived factor (PEDF) is a potent endogenous inhibitor of angiogenesis, and a promising anticancer agent. We have previously shown that PEDF can be phosphorylated, and that distinct phosphorylations differentially regulate its physiological functions. We also demonstrated that triple phosphomimetic mutant (EEE-PEDF), has significantly increased antiangiogenic activity, and is much more efficient than WT-PEDF in inhibiting neovascularization and tumor growth. The enhanced antiangiogenic effect was associated with a direct ability to facilitate apoptosis of tumor-residing endothelial cells (EC), and subsequently, disruption of intratumoral vascularization. In the present report, we elucidated the molecular mechanism by which EEE-PEDF exerts more profound effects at the cellular level. Methods: Here we used Western blotting, as well as in vitro binding, proliferation, apoptosis and migration assays to follow the signaling components responsible for the PEDF and EEE-PEDF effects. Results: We found that EEE-PEDF suppresses EC proliferation due to caspase-3-dependent apoptosis, and also inhibits migration of the EC much better than WT-PEDF. Although WT-PEDF and EEE-PEDF did not affect proliferation and did not induce apoptosis of cancer cells, these agents efficiently inhibited cancer cell motility, with EEE-PEDF showing stronger effect. The stronger activity of EEE-PEDF was correlated to a better binding to laminin receptors. Furthermore, the proapoptotic and antimigratory activities of WT-PEDF and EEE-PEDF were found respectively regulated by differential activation of two distinct MAPK pathways, namely JNK and p38. We show that JNK and p38 phosphorylation is much higher in cells treated with EEE-PEDF. JNK leads to apoptosis of ECs, while p38 leads to antimigratory effect in both EC and cancer cells. Conclusion: These results reveal the molecular signaling mechanism by which the phosphorylated PEDF exerts its stronger antiangiogenic, antitumor activities.

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