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Review Anticancer Res
2020 Nov;40(11):5969-5979. doi: 10.21873/anticanres.14617.
Dickkopf-3 in Human Malignant Tumours: A Clinical Viewpoint
Eun-Ju Lee 1, Que Thanh Thanh Nguyen 2, Mooyul Lee 3
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PMID: 33109534 DOI: 10.21873/anticanres.14617
Abstract
Dickkopf-3 (DKK3), also known as REIC, is a secreted glycoprotein. DKK3 is aberrantly expressed in various types of human malignant tumours. Promoter methylation status, intracellular protein expression, and protein expression in tumour vessels are significantly correlated with clinical prognostic factors, including survival. In malignant cells, DKK3 is involved in the induction of apoptosis, inhibition of invasion, and remodelling of tumour vasculature. These activities are carried out via the regulation of the beta-catenin signalling and c-Jun N-terminal kinase-dependent cellular pathway, both of which are critical for carcinogenesis. This review explores the potential value of DKK3 as a clinical biomarker and a therapeutic candidate in human malignancies.
Keywords: Dickkopf-3; clinical biomarker; malignant tumour; review; therapeutics.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Clinical Trial Anticancer Res
2020 Nov;40(11):6473-6484. doi: 10.21873/anticanres.14669.
Alpha-type-1 Polarized Dendritic Cell-based Vaccination in Newly Diagnosed High-grade Glioma: A Phase II Clinical Trial
Koichi Mitsuya 1 2, Yasuto Akiyama 3 2, Akira Iizuka 1, Haruo Miyata 1, Shoichi Deguchi 2, Nakamasa Hayashi 2, Chie Maeda 1, Ryota Kondou 1, Akari Kanematsu 1, Kyoko Watanabe 1, Tadashi Ashizawa 1, Yoshiaki Abe 4, Ichiro Ito 5, Takuma Oishi 6, Takashi Sugino 6, Yoko Nakasu 2, Ken Yamaguchi 7
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PMID: 33109586 DOI: 10.21873/anticanres.14669
Abstract
Background/aim: Glioblastoma multiforme (GBM) is an intractable tumor that has a very poor prognosis despite intensive treatment with temozolomide plus radiotherapy.
Patients and methods: Sixteen newly diagnosed patients with high-grade gliomas were enrolled in a phase II study of the α-type-1 DC vaccine. Briefly, DCs obtained from the culture of enriched monocytes in the presence of a cytokine cocktail, were pulsed with a cocktail of 5 synthetic peptides and cryopreserved until injection into patients.
Results: The amount of IL-12 produced by activated DCs was higher than that previously reported. Among 15 evaluable patients, 10 showed positive CTL responses to any peptides in an ELISPOT assay. After 6 years of observation, five patients were still alive, and two of these patients were relapse-free. Moreover, a significant survival-prolonging effect was verified in DC-treated glioma patients.
Conclusion: Peptide-cocktail-pulsed α-type-1 DC vaccines have a potential therapeutic effect on survival when used in combination with the standard regimen, which is partly based on IL-12-IFN-γ-mediated T-cell activation.
Keywords: Activated dendritic cell; HLA-A24; high-grade glioma; immunotherapy; phase II trial.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Nov;40(11):6247-6256. doi: 10.21873/anticanres.14645.
Involvement of the MicroRNA-1-LITAF Axis in Gastric Cancer Cell Growth and Invasion
Yen-Chih Chen 1, Chao-Chuan Wu 1, Ya-Ting Tu 2, Yi-Ru Chen 2, Ming-Cheng Lee 2, Kuo-Wang Tsai 3
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PMID: 33109562 DOI: 10.21873/anticanres.14645
Abstract
Background/aim: Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF) has been identified as a tumor suppressor in human cancers. Present study, we assessed biological role of LITAF in human gastric cancer.
Materials and methods: The clinical impacts of LITAF expression were assessed in gastric cancer using public databases. The biological role of LITAF was assessed in gastric cancer cells using siLITAF transfection.
Results: High LITAF expression was correlated well with worse prognosis, including pathological stage (p=0.034) and pathological T stage (p=0.047), as well as with shorter survival. Herein, we present a novel finding that miR-1-3p could inhibit LITAF expression by directly binding to the 3'-untranslated region of LITAF mRNA. Cell functional assays revealed that LITAF knockdown could significantly suppress gastric cancer growth and motility.
Conclusion: High LITAF expression resulting from low miR-1-3p expression is a biomarker for poor prognosis or therapeutic targets in gastric cancer.
Keywords: Gastric cancer; LITAF; miR-1.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Nov;40(11):6437-6441. doi: 10.21873/anticanres.14665.
Effect of Computer-aided Detection System Use on the Duration of MRI-guided Biopsy of the Breast
Masafumi Shimoda 1, Seung Jin Kim 2, Yukiko Tokuda 3, Yoshiaki Sota 1, Tomohiro Miyake 1, Tomonori Tanei 1, Naofumi Kagara 1, Yasuto Naoi 1, Shinzaburo Noguchi 1, Kenzo Shimazu 1
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PMID: 33109582 DOI: 10.21873/anticanres.14665
Abstract
Background/aim: Magnetic resonance imaging (MRI)-guided breast biopsy is a complex and time-consuming procedure. This study aimed to clarify the factors that affect the duration of the procedure.
Patients and methods: Twenty-eight examinations performed at our institute for 27 lesions detected solely on MRI were analyzed. The correlations between the clinicopathological factors and duration of the procedure were estimated.
Results: The needle guidance method was the only factor that significantly affected the duration of the MRI-guided vacuum-assisted breast biopsy (VAB) (p=0.012). The use of a computer-aided detection (CAD) system with grid breast compression plates had significantly shorter durations (62±12 min) than the manual calculation of coordinates with pillar-type compression plates (76±13 min).
Conclusion: This preliminary study showed that the use of a CAD system might shorten the duration of MRI-guided VAB.
Keywords: Magnetic resonance imaging; computer-aided detection; vacuum-assisted biopsy.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Nov;40(11):6539-6543. doi: 10.21873/anticanres.14678.
Usefulness of Omentoplasty to Reduce Perineal Wound Complications in Abdominoperineal Resection After Neoadjuvant Chemoradiotherapy
Machiko Nagata 1, Takeru Matsuda 2 3, Hiroshi Hasegawa 1, Masako Utsumi 1, Kimihiro Yamashita 1, Masashi Yamamoto 1, Shingo Kanaji 1, Taro Oshikiri 1, Tetsu Nakamura 1, Satoshi Suzuki 1, Yoshihiro Kakeji 1
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PMID: 33109595 DOI: 10.21873/anticanres.14678
Abstract
Background: Omentoplasty is sometimes used to prevent perineal wound complications after abdominoperineal resection (APR) following neoadjuvant chemoradiotherapy (NACRT). However, recent studies have raised some controversy about its clinical benefit.
Patients and methods: Outcomes for rectal cancer patients who received APR after NACRT were retrospectively compared between the groups with omentoplasty (n=28) and without omentoplasty (n=14).
Results: The operative time was significantly longer in the omentoplasty group (575 vs. 404 min, p<0.001). Laparoscopic surgery was performed more frequently in the omentoplasty group. Perineal wound problems including dehiscence and infection were significantly reduced in the omentoplasty group (46.4% vs. 78.6%, p<0.001). Univariate and multivariate analyses revealed that omentoplasty was the most important factor in reducing perineal wound complications (odds ratio=0.020, 95% confidence intervaI=0.001-0.393; p=0.001).
Conclusion: Omentoplasty was useful in reducing perineal wound complications after APR following NACRT.
Keywords: NACRT; Omentoplasty; abdominoperineal resection; perineal wound complication.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Nov;40(11):6319-6325. doi: 10.21873/anticanres.14652.
Development of an Oncolytic Recombinant Vesicular Stomatitis Virus Encoding a Tumor-suppressor MicroRNA
Tomohiko Sakuda 1, Tadahiko Kubo 2, Muhammad Phetrus Johan 3, Taisuke Furuta 2, Takemasa Sakaguchi 4, Nobuo Adachi 2
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PMID: 33109569 DOI: 10.21873/anticanres.14652
Abstract
Background: Attempts have been made to enhance systemic therapy for osteosarcoma. In our previous study, the systemic administration of a vesicular stomatitis virus (VSV) improved the survival rates of mice with osteosarcoma but did not improve the long-term survival of the animals.
Materials and methods: In the present study, we developed a novel oncolytic VSV by incorporating tumor-suppressor microRNA143 (rVSV-miR143) to compare the antitumor effects of various doses (10×10-4, 5×10-4, and 1×10-4 multiplicity of infection) of rVSV-miR143 with those of VSV in vitro.
Results: The cytotoxicity and migration-inhibitory effects of rVSV-miR143 on the osteosarcoma cells were significantly higher than those of VSV alone at a dose of 5×10-4 multiplicity of infection, indicating that rVSV-miRNA143 enhances the antitumor effect at certain doses.
Conclusion: VSV incorporating tumor-suppressor miRNA143 demonstrated a synergistic antitumor effect on osteosarcoma cells in vitro.
Keywords: Vesicular stomatitis virus; osteosarcoma; systemic therapy; tumor-suppressor microRNA.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Nov;40(11):6513-6515. doi: 10.21873/anticanres.14674.
Re-Evaluation of Prognostic Factors for Survival After Radiotherapy of Cerebral Gliomas: A Supplementary Analysis to a Previous Study
Jaspar Witteler 1, Troels W Kjaer 2, Soeren Tvilsted 3, Steven E Schild 4, Dirk Rades 5
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PMID: 33109591 DOI: 10.21873/anticanres.14674
Abstract
Background/aim: Previously, we identified predictors of survival after irradiation of grade II-IV cerebral gliomas. In this supplementary analysis, survival was calculated in a more appropriate way than the original study.
Patients and methods: Ten factors were re-evaluated for survival in patients of the original study including pre-radiotherapy seizures. In the original study, survival was calculated from the end of the last radiotherapy course (primary or re-irradiation). After re-review, this approach was considered inappropriate. Survival should have always been calculated from the first radiotherapy course, as done in this supplementary analysis.
Results: On multivariate analysis, WHO-grade II (p=0.006) and upfront resection (p=0.001) were associated with better survival. Unifocal glioma was significant on univariate analysis (p=0.001), where a trend could be identified for age ≤59 years (p=0.057) and seizures (p=0.060).
Conclusion: The findings of this supplementary analysis regarding the identification of prognostic factors for survival agree with the results of the original study.
Keywords: Cerebral glioma; prognostic factors; radiotherapy; re-evaluation; survival.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Review Anticancer Res
2020 Dec;40(12):6599-6607. doi: 10.21873/anticanres.14684.
Animal Models for the Calculation of Circulating Tumor Cells for Experimental Demonstration
Nikolaos Garmpis 1, Christos Damaskos 2 3, Anastasios Angelou 4, Anna Garmpi 5, Vasiliki E Georgakopoulou 6 7, Serena Valsami 8, Dimitrios Schizas 9, Errika Voutyritsa 10, Athanasios Syllaios 9, Evangelos Diamantis 11, Paraskevi Farmaki 12, Georgios Kyriakos 13, Alexandros Patsouras 14, Markos Psifis 15, Efstathios A Antoniou 1, Konstantinos Kontzoglou 1 10, Nikolaos Trakas 16, Dimitrios Dimitroulis 1
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PMID: 33288554 DOI: 10.21873/anticanres.14684
Abstract
Metastasis is a process which is characterized by the existence of tumor cells in the bloodstream. This is a necessary situation in order for the malignant cells to be transported to other organs. Thus, the importance of circulating tumor cells (CTCs) in the study of carcinogenesis is widely accepted. These tumor cells are nowadays a topic of intensive research all over the world. CTCs are expressed from tumor cells and the clinical analysis of this expression may help the recognition of a tumor in an earlier stage and also there is an effort to monitor the tumor burden according to these cells. Although a plethora of clinical studies has been conducted, it is still unclear whether the use in clinical aspect will prove to be beneficial in the near future. Few animal models with neoplasia have been studied concerning the circulating tumor cells and it is likely that CTCs may have a predictive, diagnostic or therapeutic value. Herein, the authors review all studies in which human CTCs were transplanted into animals. Therefore, more clinical studies using standardized methods for measuring CTCs are required to elucidate these issues.
Keywords: Circulating tumor cells; animal models; animal study; cancer detection; neoplasia; review.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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9
Anticancer Res
2020 Nov;40(11):6505-6511. doi: 10.21873/anticanres.14673.
Using the Bolus in Post-mastectomy Radiation Therapy (PMRT): A National Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Breast Cancer Group
Marianna Nuzzo 1, Lucia Anna Ursini 1, Fabiola Patani 1, Consuelo Rosa 2 3, Marianna Trignani 1, Monica DI Tommaso 1, Icro Meattini 4 5, Fabiana Gregucci 6, Antonella Ciabattoni 7, Domenico Genovesi 1 3, Luciana Caravatta 1
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PMID: 33109590 DOI: 10.21873/anticanres.14673
Abstract
Background/aim: This study aimed to investigate the bolus practice among Italian radiation oncologists.
Patients and methods: In 2018, a survey on bolus application was sent to all members of the Italian Association of Radiotherapy and Clinical Oncology.
Results: The survey was joined by 102 radiation oncologists. Not all respondents answered to every question. A 69.5% of 82 respondents used bolus in case of skin infiltration and 52 of 68 respondents (76.5%) applied it every day. Skin was included as part of chest wall Clinical Target Volume both in the absence or the presence of breast reconstruction. Five mm bolus was the most used. 3D Conformal radiotherapy was the most used technique, in 73.5% of cases. Acute RTOG G2-G3 skin toxicity was recorded by 93.9% physicians.
Conclusion: There was heterogeneity in the use of bolus, though an agreement was found in some topics. The achievement of a National Consensus may represent an interesting future goal.
Keywords: Breast cancer; bolus; clinical practice; mastectomy; radiotherapy.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Review Anticancer Res
2020 Dec;40(12):6609-6612. doi: 10.21873/anticanres.14685.
Younger Age as a Risk Factor for Gynecologic Cancer-related Lymphedema: A Systematic Review
Gunel Guliyeva 1, Maria T Huayllani 1, Francisco R Avila 1, Daniel Boczar 1, Xiaona Lu 2, Antonio Jorge Forte 3
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PMID: 33288555 DOI: 10.21873/anticanres.14685
Abstract
Background/aim: Treatment of gynecologic cancers may lead to the development of lower limb lymphedema. As the course of lymphedema is chronic and progressive, early diagnosis plays a significant role in decreasing morbidity. Therefore, risk assessment is of utmost importance. In this study, we aimed to investigate the impact of age on lymphedema development after treatment for gynecologic cancers.
Materials and methods: The search of 3 databases (PubMed, Scopus, and Cochrane) revealed 7 relevant articles, which reported either odds ratios or hazard ratios as an outcome measure.
Results: A positive relationship between younger age and lower limb lymphedema was shown by 3 articles, while 2 noted increased incidence with older age. The remaining articles reported no significant relationship.
Conclusion: Younger age is a risk factor for gynecologic cancer-related lymphedema. However, as individual studies have not included all types of gynecologic cancers, results may not be generalizable.
Keywords: Age; Gynecologic cancer-related lymphedema; iatrogenic lymphedema; lymphedema; plastic surgery; review; secondary lymphedema.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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11
Case Reports Anticancer Res
2020 Nov;40(11):6375-6379. doi: 10.21873/anticanres.14658.
Sequencing of Sclerosing Microcystic Adenocarcinoma Identifies Mutational Burden and Somatic Variants Associated With Tumorigenesis
Roy Jiang 1, Jonathan Marquez 2, Jacob I Tower 3, Daniel Jacobs 3, Wenqian Chen 4, Saral Mehra 5, Manju Lata Prasad 4, Benjamin L Judson 3
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PMID: 33109575 DOI: 10.21873/anticanres.14658
Abstract
Background/aim: Sclerosing microcystic adenocarcinoma (SMA) is a rare oral cavity neoplasia, histologically resembling microcystic adnexal carcinoma (MAC) of the skin. Only nine SMA cases have been reported in the literature, frequently in the context of immunosuppression; SMA has not been recognized in the most recent WHO tumor classification. We sought to identify potential molecular mechanisms of tumorigenesis in a case of SMA relative to those known for MAC.
Case report: A 41-year-old female with psoriatic arthritis undergoing immunosuppression therapy presented with a tongue mass. Biopsy revealed a diagnosis of SMA. Partial glossectomy and neck dissection showed no residual tumor or nodal disease.
Results: whole exome sequencing revealed moderate mutational burden and putative loss of function mutations in CDK11B but no overlap with known MAC mutations.
Conclusion: We characterized the genomic profile of SMA for the first time, identifying both mutational burden and unique somatic variants associated with tumorigenesis.
Keywords: Next-generation sequencing; immunosuppression; oral cancer; sclerosing microcystic adenocarcinoma.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Case Reports Anticancer Res
2020 Nov;40(11):6159-6170. doi: 10.21873/anticanres.14636.
Novel Two MRT Cell Lines Established from Multiple Sites of a Synchronous MRT Patient
Yasumichi Kuwahara 1, Tomoko Iehara 2, Eisuke Ichise 2, Yoshiki Katsumi 2, Kazutaka Ouchi 2, Kunihiko Tsuchiya 2, Mitsuru Miyachi 2, Eiichi Konishi 3, Hiroyasu Sasajima 4, Satoaki Nakamura 5, Shigehisa Fumino 6, Tatsuro Tajiri 6, Pascal D Johann 7, Michael C FrÜhwald 8, Tatsushi Yoshida 1, Tsukasa Okuda 9, Hajime Hosoi 10
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PMID: 33109553 DOI: 10.21873/anticanres.14636
Abstract
Background/aim: Malignant rhabdoid tumor (MRT) is a rare, aggressive neoplasm found in young children, caused by inactivation of a single gene, SNF5 (INI1, SMARCB1). MRT cases with multifocal tumors at diagnosis are categorized as synchronous MRT, often with a germline mutation of SNF5. The aim of this study was to establish new models useful in clarifying the biological basis of synchronous MRT.
Materials and methods: We established two novel MRT cell lines, designated as KP-MRT-KS and KP-MRT-KSa, derived from different lesions and at a different time from a synchronous multifocal 7-month-old female MRT patient.
Results: Both cells showed typical morphology of MRT, with a compound genomic mutation in exons 2 and 5 of the SNF5 gene. The exon 2 mutation was found in the germline.
Conclusion: These cell lines could serve as powerful tools for unveiling the molecular mechanism of refractory synchronous MRT.
Keywords: DNA methylation analysis; Synchronous rhabdoid tumor; cell line; germline mutation.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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13
Anticancer Res
2020 Dec;40(12):6835-6844. doi: 10.21873/anticanres.14705.
ADGRF4 Regulates Non-small Cell Lung Cancer Cell Invasiveness
Ji-Hye Yoon 1, Sung-Gook Cho 2
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PMID: 33288575 DOI: 10.21873/anticanres.14705
Abstract
Background/aim: Adhesion G protein-coupled receptors (aGPCRs) have a crucial role in cancer. However, the role of ADGRF4, one of aGPCRs, in cancer has yet to be revealed. Therefore, we investigated its role in lung cancer, a leading cause of cancer-related deaths worldwide.
Materials and methods: ADGRF4 gene expression pattern in lung cancer were analyzed by in silico analyses. RNA sequencing was conducted to investigate gene expression pattern altered by ADGRF4 knockdown. Lung cancer cell lines were subjected to cell migration and invasion assays.
Results: In silico analysis data indicated a major role of ADGRF4 in lung cancer. RNA sequencing data showed that ADGRF4 gene silencing in lung cancer cells altered global expression pattern. ADGRF4 gene silencing reduced lung cancer cell invasiveness. Furthermore, PPP2C gene expression was most significantly down-regulated by ADGRF4 gene silencing. PPP2C overexpression rescued cell invasiveness inhibited by ADGRF4 gene silencing, and PPP2C gene silencing blocked lung cancer cell invasiveness.
Conclusion: ADGRF4 regulates lung cancer cell invasiveness via PPP2C.
Keywords: ADGRF4; GPR115; PPP4C; cell invasiveness; lung cancer.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Dec;40(12):6891-6897. doi: 10.21873/anticanres.14712.
Mitochondrial Glutamine Metabolism Determines Senescence Induction After Chemotherapy
Byungjoo Kim 1 2 3, Jihye Gwak 1 2 3, Eun Kyung Lee 1 3, Seung Min Jeong 4 5 6
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PMID: 33288582 DOI: 10.21873/anticanres.14712
Abstract
Background/aim: Cellular senescence is an important tumor-suppressive mechanism that arrests the cell cycle of damaged cells after diverse stresses. This study aimed to elucidate the role of mitochondrial glutamine (Gln) metabolism in senescence cell-fate decision after DNA damage.
Materials and methods: β-galactosidase staining was used to determine senescence induction. The mechanistic target of rapamycin (mTOR) activity and p21 expression were examined by western blot. Cell proliferation and clonogenic growth were evaluated.
Results: Inhibition of mitochondrial Gln metabolism suppressed DNA damage-induced senescence, whereas increased Gln anaplerosis resulted in a profound induction of senescence. Mechanistically, Gln anaplerosis mediated senescence induction by activating mTOR signaling upon DNA damage. Importantly, enhancing Gln anaplerosis could reduce the emergence of proliferative subpopulations of cancer cells after exposure to non-lethal doses of chemotherapeutic agents.
Conclusion: Mitochondrial Gln metabolism is an important regulator of DNA damage-induced senescence, which may be used for developing effective therapeutic approaches.
Keywords: DNA damage; Senescence; glutamine metabolism; mTOR.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Dec;40(12):6677-6684. doi: 10.21873/anticanres.14691.
The Biological Role of the Long Non-coding RNA LINK-A in Ovarian Carcinoma
Natalie Filippov-Levy 1, Ben Davidson 2 3, Reuven Reich 4 5 6
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PMID: 33288561 DOI: 10.21873/anticanres.14691
Abstract
Aim: To analyze the biological role of the long non-coding RNA LINK-A.
Materials and methods: An 850-bp segment from the second exon of LINK-A was removed using the CRISPR/Cas9 system in OVCA433 ovarian serous carcinoma cells. Spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity and expression of cell-signaling proteins were assessed in vitro.
Results: OVCA433 cells with LINK-A deletion were more invasive (p=0.0008) but had reduced migration and MMP9 secretion compared to controls (p=0.003 and p=0.005, respectively). LINK-A deletion did not affect proliferation but induced phosphorylation of extracellular signal-regulated kinase (10-fold; p=0.005). LINK-A knock out additionally reduced spheroid formation.
Conclusion: Added to our previous data from analysis of clinical specimens, LINK-A is likely to be a tumor suppressor.
Keywords: CRISPR/Cas9; LINK-A; high-grade serous carcinoma; in vitro.; long non-coding RNA; tumorigenesis.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Res
2020 Dec;40(12):7003-7007. doi: 10.21873/anticanres.14725.
Efficacy of Gemcitabine-based Chemotherapy in Clear Cell Sarcoma of Soft Tissue
Elena Cojocaru 1, Khin Thway 1 2, Cyril Fisher 2 3, Christina Messiou 2 4, Shane Zaidi 1 2, Aisha B Miah 1 2, Charlotte Benson 1, Spyridon Gennatas 1, Paul Huang 2, Robin L Jones 5 6
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PMID: 33288595 DOI: 10.21873/anticanres.14725
Abstract
Background/aim: Clear cell sarcoma (CCS) is an aggressive sarcoma subtype, resistant to conventional anthracycline-based chemotherapy and radiation. The diagnosis is often challenging due to similarities with malignant melanoma.
Patients and methods: We aimed to analyse the activity of gemcitabine-based chemotherapy in a cohort of patients with CCS treated at the Royal Marsden Hospital.
Results: Five patients with metastatic CCS received gemcitabine as first- or second-line systemic therapy. The median time-to-progression was 10 weeks. The median number of cycles of gemcitabine-based therapy was 3 (range=2-7 cycles). Median overall survival in our cohort was 66 months from the initial diagnosis but in the metastatic setting, the overall survival was reduced to 28 months.
Conclusion: Gemcitabine-based therapy has modest activity in CCS. There remains a significant unmet medical need for novel, effective therapies for this disease.
Keywords: Clear cell sarcoma; EWSR1 translocation; chemotherapy; gemcitabine.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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17
Anticancer Res
2020 Dec;40(12):7017-7023. doi: 10.21873/anticanres.14727.
Prognostic Significance of Plasma Fibrinogen/Serum Albumin Ratio in the Postoperative Outcome of Pancreatic Ductal Adenocarcinoma
Koichi Tomita 1, Shigeto Ochiai 1, Takahiro Gunji 1, Kosuke Hikita 1, Toshimichi Kobayashi 1, Toru Sano 1, Naokazu Chiba 1, Shigeyuki Kawachi 2
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PMID: 33288597 DOI: 10.21873/anticanres.14727
Abstract
Background/aim: Surgery is an important pancreatic ductal adenocarcinoma (PDAC) treatment; existing markers are inadequate prognostic indexes. We herein evaluated the utility of the FA score (fibrinogen/albumin ratio) for predicting PDAC postoperative outcomes.
Patients and methods: We analysed the data of 67 PDAC patients who underwent surgical resection. The relationship between postoperative outcomes and the FA score was investigated. Performance of the FA score was compared to that of other variables and prognostic indexes.
Results: No patient with FA ≥130 survived >3 years, whereas all patients who survived longer had FA <130. The FA score was superior to all other indexes for predicting postoperative outcomes. Patients with FA ≥130 vs. <130 had significantly shorter overall and recurrence-free survival.
Conclusion: The FA score is useful for predicting PDAC postoperative outcomes. Preoperatively, it may detect patients likely to have poor postoperative prognoses who may benefit from adjuvant or neoadjuvant therapy, thus improving outcomes.
Keywords: FA score; albumin; fibrinogen; pancreatic ductal adenocarcinoma; prognostic index; surgical resection.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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18
Anticancer Res
2020 Dec;40(12):6699-6712. doi: 10.21873/anticanres.14693.
Antitumor Activity of Eribulin After Fulvestrant Plus CDK4/6 Inhibitor in Breast Cancer Patient-derived Xenograft Models
Yuki Niwa 1, Makoto Asano 1, Takayuki Nakagawa 1, Damien France 2, Taro Semba 1, Yasuhiro Funahashi 3
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PMID: 33288563 DOI: 10.21873/anticanres.14693
Abstract
Background/aim: There is no established standard chemotherapy after administration of the combination endocrine plus CDK4/6 inhibitor therapy for luminal-type breast cancer. We used patient-derived xenograft (PDX) models to determine the antitumor activity of eribulin and capecitabine after endocrine therapy plus CDK4/6 inhibitor.
Materials and methods: We examined the antitumor activity of fulvestrant, palbociclib, eribulin, and capecitabine in 4 luminal-type breast cancer PDX models (OD-BRE-0188, -0438, -0450, -0745). In OD-BRE-0438, we determined the antitumor activity of chemotherapy after fulvestrant-palbociclib treatment. We also performed immunohistochemical analysis to explore the effects of treatment on E-cadherin in tumor tissues.
Results: Fulvestrant, fulvestrant-palbociclib and chemotherapy had antitumor activity in the 4 PDX models. In OD-BRE-0438 (the most resistant to fulvestrant-palbociclib), eribulin had superior antitumor activity to capecitabine after fulvestrant plus palbociclib. Only eribulin tended to increase E-cadherin expression.
Conclusion: Eribulin had superior antitumor activity to capecitabine after fulvestrant-palbociclib in the OD-BRE-0438 model.
Keywords: CDK4/6 inhibitor; eribulin mesylate; luminal-type breast cancer; patient-derived xenograft model; preclinical trial; reversal of epithelial-mesenchymal transition.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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19
Anticancer Res
2020 Dec;40(12):6997-7001. doi: 10.21873/anticanres.14724. Epub 2020 Dec 7.
Treatment With Mifepristone Allows a Patient With End-stage Pancreatic Cancer in Hospice on a Morphine Drip to Restore a Decent Quality of Life
Jerome H Check 1 2, Diane Check 3, Maya D Srivastava 4, Trina Poretta 5, James K Aikins 6
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PMID: 33288594 DOI: 10.21873/anticanres.14724
Abstract
Background: There is evidence that a unique immunomodulatory protein, known as the progesterone induced blocking factor (PIBF), is utilized by a large variety of cancers to escape immune surveillance. Mifepristone, a progesterone receptor antagonist/modulator, anecdotally, has been found to increase both length and quality of life in many different types of advanced cancers.
Case report: Though there was one previous case of pancreatic cancer that showed a significant reduction in pain for the one month she took mifepristone before changing to an experimental drug, the case presented here provided much greater evidence that this drug can markedly improve both length and quality of life, in at least some patients, with very advanced pancreatic cancer.
Conclusion: It is hoped that this case report will influence others to prescribe mifepristone off-label and hopefully substantiate this finding of marked palliative benefit in the majority of a larger series of patients.
Keywords: Pancreatic cancer; immunosurveillance; natural killer cells; palliation; progesterone induced blocking factor; progesterone receptor antagonists.
Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Review Anticancer Res
2020 Nov;40(11):5981-5988. doi: 10.21873/anticanres.14618.
The Role of Zyxin in Carcinogenesis
Aleksandra Partynska 1, Agnieszka Gomulkiewicz 2, Piotr Dziegiel 2 3, Marzenna Podhorska-Okolow 4
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PMID: 33109535 DOI: 10.21873/anticanres.14618
Abstract
Zyxin (ZYX) is a LIM domain protein whose presence has been detected in the cytoplasm and nucleus. ZYX can translocate between these two compartments and therefore, can take part in the regulation of various cellular processes. VASP and α-actinin are examples of proteins that interact with ZYX. As ZYX is present in focal adhesions (FAs), an immense part of research is focused on the role of this protein in the organisation and function of the cytoskeleton. Other studies aim to explain the impact of zyxin on other intracellular processes. Zyxin has been shown to take part in apoptosis, as well as in wound healing. Additionally, zyxin contribution to cancer development is gaining growing interest. This paper aims to systematise the knowledge on zyxin and its role in carcinogenesis.
Keywords: LIM domain proteins; Zyxin; cancer; review.
Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,