Future Oncology; +28 new citations

payth.elady61 shared this article with you from Inoreader Message: Select search result to email or save 1 Future Oncol 2020 Dec 8. doi: 10.2217/fon-2020-1100. Online ahead of print. PD-L1 testing based on SP142 antibody in metastatic triple-negative breast cancer: summary of an expert round-table discussion Vicente Peg 1, María Ángeles López-García 2, Laura Comerma 3, Gloria Peiró 4, Tomás García-Caballero 5, Ángel Concha López 6, Ana Suárez-Gauthier 7, Irune Ruiz 8, Federico Rojo 9 Affiliations expand PMID: 33289433 DOI: 10.2217/fon-2020-1100 Abstract Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. TNBC is characterized by increased expression of Programmed Death-ligand 1 (PD-L1), a signal used by many tumors to escape the immune response. Expression of PD-L1 is a positive predictor of response to immunotherapy; therefore, it should be investigated in TNBC in order to select patients who may benefit from anti-PD-L1 therapies. While many PD-L1 assays are available, only the VENTANA platform with the anti-PD-L1 (SP142) antibody is licensed as a companion diagnostic device for selecting patients with metastatic/advanced TNBC who are candidates for treatment with atezolizumab. In this article, we provide a summary of an expert round-table discussion about PD-L1 testing, using the SP142 antibody in metastatic TNBC. Keywords: PD-L1; antibody; breast cancer; diagnosis; immunohistochemistry; immunotherapy. supplementary info Grant supportexpand full-text links full-text provider logo Proceed to details Cite Share 2 Review Oncogene 2020 Dec 7. doi: 10.1038/s41388-020-01578-4. Online ahead of print. Nerve fibers in the tumor microenvironment in neurotropic cancer-pancreatic cancer and cholangiocarcinoma Xiuxiang Tan 1 2 3, Shivan Sivakumar 4 5, Jan Bednarsch 2, Georg Wiltberger 2, Jakob Nikolas Kather 6, Jan Niehues 6, Judith de Vos-Geelen 7, Liselot Valkenburg-van Iersel 7, Svetlana Kintsler 8, Anjali Roeth 2 3, Guangshan Hao 9, Sven Lang 2, Mariëlle E Coolsen 1, Marcel den Dulk 1 2, Merel R Aberle 3, Jarne Koolen 1, Nadine T Gaisa 8, Steven W M Olde Damink 1 2 3, Ulf P Neumann 1 2, Lara R Heij 10 11 12 Affiliations expand PMID: 33288884 DOI: 10.1038/s41388-020-01578-4 Abstract Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are both deadly cancers and they share many biological features besides their close anatomical location. One of the main histological features is neurotropism, which results in frequent perineural invasion. The underlying mechanism of cancer cells favoring growth by and through the nerve fibers is not fully understood. In this review, we provide knowledge of these cancers with frequent perineural invasion. We discuss nerve fiber crosstalk with the main different components of the tumor microenvironment (TME), the immune cells, and the fibroblasts. Also, we discuss the crosstalk between the nerve fibers and the cancer. We highlight the shared signaling pathways of the mechanisms behind perineural invasion in PDAC and CCA. Hereby we have focussed on signaling neurotransmitters and neuropeptides which may be a target for future therapies. Furthermore, we have summarized retrospective results of the previous literature about nerve fibers in PDAC and CCA patients. We provide our point of view in the potential for nerve fibers to be used as powerful biomarker for prognosis, as a tool to stratify patients for therapy or as a target in a (combination) therapy. Taking the presence of nerves into account can potentially change the field of personalized care in these neurotropic cancers. supplementary info Publication typesexpand full-text links full-text provider logo Proceed to details Cite Share 3 Blood Adv 2020 Dec 8;4(23):6051-6063. doi: 10.1182/bloodadvances.2020003471. Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations Caroline Diorio 1 2, Kevin O McNerney 1 2, Michele Lambert 1 3, Michele Paessler 1 4, Elizabeth M Anderson 5, Sarah E Henrickson 1 6, Julie Chase 1 7, Emily J Liebling 7, Chakkapong Burudpakdee 1, Jessica H Lee 1, Frances B Balamuth 8, Allison M Blatz 9, Kathleen Chiotos 9 10, Julie C Fitzgerald 1 10, Therese M Giglia 11, Kandace Gollomp 1 3, Audrey R Odom John 9, Cristina Jasen 6, Tomas Leng 1 2, Whitney Petrosa 1, Laura A Vella 9, Char Witmer 3, Kathleen E Sullivan 1 6, Benjamin L Laskin 12, Scott E Hensley 5, Hamid Bassiri 1 9, Edward M Behrens 1 7, David T Teachey 1 2 Affiliations expand PMID: 33290544 DOI: 10.1182/bloodadvances.2020003471 Abstract Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng /mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C. © 2020 by The American Society of Hematology. full-text links full-text provider logo Proceed to details Cite Share 4 Review Cancers (Basel) 2020 Dec 3;12(12):E3616. doi: 10.3390/cancers12123616. Update on the Management of Breast Cancer during Pregnancy Francesca Poggio 1, Marco Tagliamento 2 3, Chiara Pirrone 2 3, Davide Soldato 2 3, Benedetta Conte 2 3, Chiara Molinelli 2 3, Maurizio Cosso 4, Piero Fregatti 5 6, Lucia Del Mastro 1 3, Matteo Lambertini 3 7 Affiliations expand PMID: 33287242 DOI: 10.3390/cancers12123616 Free article Abstract The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy. Keywords: breast cancer; chemotherapy; endocrine therapy; immunotherapy; pregnancy; pregnancy during breast cancer; radiotherapy; surgery; targeted therapy. supplementary info Publication typesexpand full-text links full-text provider logo Proceed to details Cite Share 5 Life (Basel) 2020 Dec 3;10(12):E325. doi: 10.3390/life10120325. Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma? Anna Starzyńska 1, Paulina Adamska 1, Aleksandra Sejda 2, Monika Sakowicz-Burkiewicz 3, Łukasz Jan Adamski 1, Giulia Marvaso 4 5, Piotr Wychowański 6, Barbara Alicja Jereczek-Fossa 4 5 Affiliations expand PMID: 33287350 DOI: 10.3390/life10120325 Free article Abstract Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). PIK3CA gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 t umors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor (r = -0.243) and positive correlation with a 5-year survival (r = 0.235). The number of copies of the PIK3CA gene was associated with the tumor grading (r = 0.208). The present study shows that loss of PTEN protein and the grading (p = 0.040), distant metastases (p = 0.033), smoking (p = 0.016), and alcohol abuse (p = 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival (p = 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results. Keywords: PIK3CA amplification; PTEN loss; oral squamous cell carcinoma; phosphatidylinositol 3-kinase pathway. full-text links full-text provider logo Proceed to details Cite Share 6 Review Clin Lymphoma Myeloma Leuk 2020 Oct 30;S2152-2650(20)30582-6. doi: 10.1016/j.clml.2020.10.015. Online ahead of print. Primary Central Nervous System Lymphoma: Evolving Biologic Insights and Recent Therapeutic Advances Dai Chihara 1, Kieron Dunleavy 2 Affiliations expand PMID: 33288483 DOI: 10.1016/j.clml.2020.10.015 Abstract Primary central nervous system lymphoma (PCNSL) is a rare and clinically aggressive disease entity associated with poor survival. Though high-dose methotrexate-based immunochemotherapy approaches are effective at inducing responses, few patients experience long-term durable remissions. Recently, novel insights into the biology of this unique disease have been elucidated and have paved the way for the investigation of rational approaches such as Bruton tyrosine kinase inhibition and immunomodulation. Although these strategies can induce high response rates in PCNSL, remissions are short lived, with median progression-free survivals in the range of 6 months or less. Moving forward, understanding the mechanisms of treatment resistance with these and other novel agents is key to developing optimal combinatorial strategies. New approaches such as immune checkpoint inhibition and chimeric antigen receptor T-cell therapy are under investigation for PCNSL and thus far demonstrate activity in anecdotal clinical experiences. Future trials should focus on investigating novel rational combinations designed to optimally target the biology of PCNSL and simultaneously investigate mechanisms of resistance leading to treatment failure. Keywords: Activated B-cell (ABC) subtype; BTK; BTK inhibitors; CAR T-cell therapy; Primary central nervous system lymphoma. Copyright © 2020 Elsevier Inc. All rights reserved. supplementary info Publication typesexpand full-text links full-text provider logo Proceed to details Cite Share 7 Medicine (Baltimore) 2020 Dec 4;99(49):e23329. doi: 10.1097/MD.0000000000023329. Correlation analysis and clinical significance of CA125, HE4, DDI, and FDP in type II epithelial ovarian cancer Li Qiao 1, Xinhua Chen 1, Xuxia Xi 1, Xueqin Chen 1, Pengpeng Zhang 1, Hua Dong 1, Xiaohua Wu 2, Xiaojun Chen 2 Affiliations expand PMID: 33285710 PMCID: PMC7717762 DOI: 10.1097/MD.0000000000023329 Free PMC article Abstract Ovarian cancer is one of the common female malignant tumors. The early diagnosis and treatment of ovarian cancer has been a research hotspot. Therefore, we aimed to investigate the correlations between the levels of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), D-dimer (DDI), and fibrinogen degradation product (FDP) in patients with type II epithelial ovarian cancer.From January 2018 to January 2019, a total of 952 patients who underwent initial surgery for epithelial ovarian cancer were enrolled in this study. Peripheral venous blood was taken before operation, and the levels of CA125, HE4, DDI, and FDP were tested. The correlations between the levels of CA125, HE4, DDI, and FDP and other clinical indicators (such as presence or absence of chemotherapy, surgical conditions) were analyzed.The level of DDI or FDP was statistically associated with age, chemotherapy, Figo staging, surgical procedure, HE4 level, and CA125 level, respectively. Moreover, the Figo stag ing was statistically correlated with the levels of HE4 and CA125. Besides, we found the levels of CA125 and HE4 were positively correlated with the levels of DDI and FDP.The levels of CA125 and HE4 are the traditional detection indexes for patients with type II epithelial ovarian cancer, and these 2 indicators reflected the degree of disease and prognosis. The levels of DDI and FDP were closely related to the levels of CA125 and HE4 in type II epithelial ovarian cancer, and they also helped to assess the prognosis of epithelial ovarian cancer. Further larger-scale prospective cohort studies are warranted to determine these associations in the future. Conflict of interest statement There are no potential conflicts of interest to disclose. 26 references full-text links full-text provider logo Proceed to details Cite Share 8 Brain Topogr 2020 Dec 8. doi: 10.1007/s10548-020-00813-1. Online ahead of print. Brain Tissue Conductivity Measurements with MR-Electrical Properties Tomography: An In Vivo Study Stefano Mandija 1 2, Petar I Petrov 3, Jord J T Vink 3, Sebastian F W Neggers 3, Cornelis A T van den Berg 4 5 Affiliations expand PMID: 33289858 DOI: 10.1007/s10548-020-00813-1 Abstract First in vivo brain conductivity reconstructions using Helmholtz MR-Electrical Properties Tomography (MR-EPT) have been published. However, a large variation in the reconstructed conductivity values is reported and these values differ from ex vivo conductivity measurements. Given this lack of agreement, we performed an in vivo study on eight healthy subjects to provide reference in vivo brain conductivity values. MR-EPT reconstructions were performed at 3 T for eight healthy subjects. Mean conductivity and standard deviation values in the white matter, gray matter and cerebrospinal fluid (σWM, σGM, and σCSF) were computed for each subject before and after erosion of regions at tissue boundaries, which are affected by typical MR-EPT reconstruction errors. The obtained values were compared to the reported ex vivo literature values. To benchmark the accuracy of in vivo conductivity reconstructions, the same pipeline was applied to simulated data, which allow knowledge of ground truth conductivity. Provided sufficient boundary erosion, the in vivo σWM and σGM values obtained in this study agree for the first time with literature values measured ex vivo. This could not be verified for the CSF due to its limited spatial extension. Conductivity reconstructions from simulated data verified conductivity reconstructions from in vivo data and demonstrated the importance of discarding voxels at tissue boundaries. The presented σWM and σGM values can therefore be used for comparison in future studies employing different MR-EPT techniques. Keywords: Brain; Conductivity; Electrical properties; MR-EPT. full-text links full-text provider logo Proceed to details Cite Share 9 Review Cancers (Basel) 2020 Dec 3;12(12):E3622. doi: 10.3390/cancers12123622. Epigenetics in Breast Cancer Therapy-New Strategies and Future Nanomedicine Perspectives Verona Buocikova 1, Ivan Rios-Mondragon 2, Eleftherios Pilalis 3 4, Aristotelis Chatziioannou 3 4, Svetlana Miklikova 1, Michal Mego 5, Karlis Pajuste 6, Martins Rucins 6, Naouale El Yamani 7, Eleonora Marta Longhin 7, Arkadij Sobolev 6, Muriel Freixanet 8, Victor Puntes 8 9 10, Aiva Plotniece 6, Maria Dusinska 7, Mihaela Roxana Cimpan 2, Alena Gabelova 1, Bozena Smolkova 1 Affiliations expand PMID: 33287297 DOI: 10.3390/cancers12123622 Free article Abstract Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identifi cation, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics. Keywords: breast cancer; drug resistance; epi-drugs; epigenetics; nanomedicine; targeted delivery. supplementary info Publication types, Grant supportexpand full-text links full-text provider logo Proceed to details Cite Share 10 Cancers (Basel) 2020 Dec 3;12(12):E3612. doi: 10.3390/cancers12123612. Cancer Testis Antigens and Immunotherapy: Expression of PRAME Is Associated with Prognosis in Soft Tissue Sarcoma Markus Albertsmeier 1, Annelore Altendorf-Hofmann 2, Lars H Lindner 3, Rolf D Issels 3, Eric Kampmann 3, Hans-Roland Dürr 4, Gabriele Schubert-Fritschle 5, Martin K Angele 1, Thomas Kirchner 6, Achim A Jungbluth 7, Thomas Knösel 6 Affiliations expand PMID: 33287125 DOI: 10.3390/cancers12123612 Free article Abstract (1) Background: PRAME, NY-ESO-1, and SSX2 are cancer testis antigens (CTAs), which are expressed in testicular germ cells with re-expression in numerous cancer types. Their ability to elicit humoral and cellular immune responses have rendered them promising targets for cancer immunotherapy, but they have never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: On a protein level, we examined PRAME, NY-ESO-1, and SSX2 expression in tumour tissues of 249 high-risk STS using immunohistochemistry. We correlated expression levels with clinicopathological parameters including tumour-infiltrating lymphocyte (TIL) counts, grading, and long-term survival. (3) Results: Expression of PRAME, NY-ESO-1, and SSX2 was observed in 25 (10%), 19 (8%), and 11 (4%) of 249 specimens with distinct patterns for histo-subtypes. Expression of PRAME was associated with shorter patient survival (p = 0.005) and higher grade (G2 vs. G3, p = 0.001), while NY-ESO-1 exp ression was correlated with more favourable survival (p = 0.037) and lower grade (G2 vs. G3, p = 0.029). Both PRAME and NY-ESO-1 expression were more frequent in STS with low TIL counts. In multivariate analysis, high PRAME and low SSX2 expression levels as well as metastatic disease and non-radical resections were independent predictors of shorter overall survival. (4) Conclusions: CTAs PRAME, NY-ESO-1, and SSX2 show distinct expression patterns in different STS subtypes. These results demonstrate their prognostic relevance and may guide future immunotherapeutic approaches in STS. Keywords: NY-ESO-1; PRAME; SSX2; biomarker; cancer/testis antigens; human; immunohistochemistry; soft tissue sarcoma; tumour infiltrating lymphocytes. full-text links full-text provider logo Proceed to details Cite Share 11 Cancer 2020 Dec 8. doi: 10.1002/cncr.33364. Online ahead of print. Phase 2 study of copanlisib in combination with gemcitabine and cisplatin in advanced biliary tract cancers Elaine S Tan 1, Biwei Cao 2, Jongphil Kim 2, Taymeyah E Al-Toubah 1, Rutika Mehta 1, Barbara A Centeno 3, Richard D Kim 1 Affiliations expand PMID: 33289918 DOI: 10.1002/cncr.33364 Abstract Background: Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored. Methods: Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling. Results: Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6.2 months (95% CI, 2.9-10.1 months). Nineteen patients were evaluable for RR: 6 patients achieved a partial response (31.6%), and 11 (57.9%) had stable disease. The most common grade 3/4 adverse events were a decreased neutrophil count (45.83%), anemia (25%), increased lipase (25%), and hypertension (20.8%). Twenty patients had tissue evaluable for the PTEN status. The PFS for low (n = 9) and high PTEN expression (n = 11) was 8.5 and 4.6 months, respectively (P = .19). The median OS for low and high PTEN expression groups was 17.9 and 7.0 months, respectively (P = .19). Conclusions: The addition of copanlisib to gemcitabine and cisplatin does not improve PFS at 6 months. However, future studies using PTEN as a potential biomarker should be considered. Lay summary: The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred. Keywords: PI3K; cholangiocarcinoma; copanlisib; personalized medicine; targeted therapy. © 2020 American Cancer Society. 26 references supplementary info Grant supportexpand full-text links full-text provider logo Proceed to details Cite Share 12 BMC Public Health 2020 Dec 7;20(1):1885. doi: 10.1186/s12889-020-09980-z. Burnout among Portuguese healthcare workers during the COVID-19 pandemic Ivone Duarte 1 2, Andreia Teixeira 1 2, Luísa Castro 1 2 3, Sílvia Marina 1 2, Carla Ribeiro 4, Cristina Jácome 1 2, Vera Martins 2, Inês Ribeiro-Vaz 1 2 5, Hugo Celso Pinheiro 6, Andreia Rodrigues Silva 7, Miguel Ricou 1 2, Bruno Sousa 8, Cristiana Alves 1, Andreia Oliveira 1, Paula Silva 9, Rui Nunes 1, Carla Serrão 10 Affiliations expand PMID: 33287794 DOI: 10.1186/s12889-020-09980-z Free article Abstract Background: During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. Methods: A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. Results: A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. Conclusions: All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs. Keywords: Burnout; Stress; COVID-19; Depression; Healthcare workers; Life satisfaction; Resilience. supplementary info Grant supportexpand full-text links full-text provider logo Proceed to details Cite Share 13 Med Phys 2020 Dec 8. doi: 10.1002/mp.14644. Online ahead of print. Automated gross tumour volume contour generation for large-scale analysis of early stage lung cancer patients planned with 4D-CT Angela Davey 1, Marcel van Herk 1 2, Corinne Faivre-Finn 1 3, Sean Brown 1 3, Alan McWilliam 1 2 Affiliations expand PMID: 33290579 DOI: 10.1002/mp.14644 Abstract Purpose: Early stage lung cancer patients undergoing stereotactic ablative radiotherapy receive four-dimensional computed tomography (4D-CT) for treatment planning. Often, an internal gross target volume (iGTV), which approximates the motion envelope of a tumour over the breathing cycle, is delineated without defining a gross tumour volume (GTV). However, the GTV volume and shape are important parameters for prognostic and dose modelling, and there is interest in radiomic features extracted from the GTV and surrounding tissue. We demonstrate and validate a method to generate the GTV from an iGTV contour to aid retrospective analysis on routine data. Method: It is possible to reconstruct the geometry of a tumour with knowledge of tumour motion and the motion envelope formed during respiration. To demonstrate this, tumour motion path was estimated with local rigid registration, and the iGTV positioned incrementally at stations along the reverse path. It is shown that tumour volume is the largest set common to the intersection of the iGTV at the different positions, so hence can be derived. This was implemented for 521 lung lesions on 4D-CT. Eleven patients with a GTV delineation performed by a radiation oncologist on a reference phase (50%) were used for validation. The generated GTV was compared to that delineated by expert using distance-to-agreement, volume, and distance between centres of mass. An overall success rate was determined by detecting registration inaccuracy and performing a quality check on the routine iGTV. For successfully generated contours, GTV volume was compared to iGTV volume in a prognostic model for overal l survival. Results: For the validation dataset, distance-to-agreement mean (0.79-1.55mm) and standard deviation (0.68-1.51mm) was comparable to expected observer variation. Difference in volume was less than 5cm3 , and average difference in position was 1.21mm. Deviations in shape and position were mainly caused by delineation interpretation differences between iGTV and GTV as opposed to algorithm performance. For the complete dataset, an acceptable contour was generated for 94% of patients using statistical and visual assessment to detect failures. Generated GTV volumes improved prognostic model performance over iGTV volumes. Conclusion: A method to generate a GTV from an iGTV and 4D-CT dataset was developed. This method facilitates data analysis of early stage lung cancer patients treated in the routine setting i.e. data mining, prognostic modelling, and radiomics. Generation failure detection removes the need for visual assessment of all contours, reducing a time-consuming aspect of big-data analysis. Favourable prognostic performance of generated GTV volumes over iGTV ones demonstrates opportunities to use this methodology for future study. Keywords: 4D-CT; GTV; SABR; iGTV; lung cancer; swept volume; tumour motion. This article is protected by copyright. All rights reserved. full-text links full-text provider logo Proceed to details Cite Share 14 Am J Health Syst Pharm 2020 Dec 8;zxaa373. doi: 10.1093/ajhp/zxaa373. Online ahead of print. Navigating uncharted waters: Developing a standardized approach for evaluating and implementing biosimilar products at a comprehensive cancer center Mara N Villanueva 1, Jennifer E Davis 2, Stacey M Sobocinski 1 Affiliations expand PMID: 33289499 DOI: 10.1093/ajhp/zxaa373 Abstract Purpose: The processes for formulary implementation and electronic health record (EHR) integration of biosimilar products at a comprehensive cancer center are described. Implications for research protocols are also discussed. Summary: The existing literature focuses on practical considerations for formulary addition of biosimilar products, but there is a lack of guidance on how to implement the change, particularly within the EHR. Before building the ordering tools for biosimilars, the clinical and informatics teams should determine the role of biosimilars at the institution, identify drug-specific product characteristics that affect medication build, and characterize implications of future formulary changes or drug shortages. Leveraging an orderable record provides the ability to include logic that maps to multiple products and also allows for future implementation of changes within the medication record rather than requiring "swaps" at the treatment protocol level. The institutional review board should coordinate changes in affected research protocols and consent forms and work with principal investigators to amend protocols when necessary. Pharmacy leaders should develop processes to oversee inventory during the transition period and minimize the risk of errors. Conclusion: The development of a standardized approach for evaluating and implementing biosimilar products improves efficiency and collaboration among the various team members responsible for the products' integration into existing workflows, including implications for clinical research. Implementing biosimilars for agents used to treat cancer will pose new challenges and require additional considerations. Partial implementation of biosimilars continues to pose multiple challenges in the provision of patient care. Keywords: biological products; biosimilar pharmaceuticals; electronic health records; formulary; pharmacists. Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2020. full-text links full-text provider logo Proceed to details Cite Share 15 Int Immunopharmacol 2020 Dec 3;90:107186. doi: 10.1016/j.intimp.2020.107186. Online ahead of print. JAK2 expression is correlated with the molecular and clinical features of breast cancer as a favorable prognostic factor Qiang Liu 1, Bolun Ai 1, Xiangyi Kong 1, Xiangyu Wang 1, Yihang Qi 1, Zhongzhao Wang 2, Yi Fang 3, Jing Wang 4 Affiliations expand PMID: 33290964 DOI: 10.1016/j.intimp.2020.107186 Abstract Janus kinases are a family of non-receptor tyrosine kinases involved in autoimmune diseases and malignancies. In breast cancer, the immune related role of JAK2 remains unclear. We aimed to investigate its role at transcriptome level and its relationship with the clinical outcome of breast cancer. This study enrolled a total of 2994 breast cancer samples with transcriptome data, including 1090 samples from The Cancer Genome Atlas (TCGA) and 1904 from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). JAK2 expression was significantly upregulated in both PR positive group (P < 0.01) and HER2 negative group (P < 0.01), and was correlated with American Joint Committee on Cancer (AJCC) stage and tumor malignancies of breast cancer. Functional enrichment analysis revealed that genes correlated with JAK2 were mainly involved in essential functions associated with immune response. Intriguingly, we investigated the association between JAK2 and immune modulators in pa n-cancer, JAK2 expression was positively correlated with most of these immune modulators. In clinical aspect, higher expression of JAK2 was an independent indicator of favorable prognosis in breast cancer patients. The expression of JAK2 is tightly related to the pathology and molecular pathology of breast cancer, and synergistic with other checkpoint members thereby playing a specific role in regulating tumor immune microenvironment. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of JAK2 and its special immune functions together with its prognostic values in breast cancer. These findings might shed novel sights for future research in cancer immunotherapy by targeting immune checkpoint molecules. Keywords: Breast cancer; Cancer immunotherapy; Immune infiltrates; JAK2; Prognostic factor. Copyright © 2020 Elsevier B.V. All rights reserved. full-text links full-text provider logo Proceed to details Cite Share 16 Curr Med Chem 2020 Dec 7. doi: 10.2174/0929867328666201207202012. Online ahead of print. Targeting the JAK/STAT Signaling Pathway for Breast Cancer Fei Shao 1, Xiaonan Pang 1, Gyeong Hun Baeg 2 Affiliations expand PMID: 33290193 DOI: 10.2174/0929867328666201207202012 Abstract Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, includ-ing radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibi-tors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment. Keywords: Breast cancer; Inhibitors; JAK/STAT pathway; STAT3 dimerization; Targeted therapy; Therapeutics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. Proceed to details Cite Share 17 Trends Microbiol 2020 Nov 6;S0966-842X(20)30270-5. doi: 10.1016/j.tim.2020.10.008. Online ahead of print. Joining European Scientific Forces to Face Pandemics M Helena Vasconcelos 1, Stefano Alcaro 2, Virginia Arechavala-Gomeza 3, Jan Baumbach 4, Fernanda Borges 5, Tiziana A L Brevini 6, Javier De Las Rivas 7, Yvan Devaux 8, Pavel Hozak 9, Minna M Keinänen-Toivola 10, Giovanna Lattanzi 11, Thomas Mohr 12, Modra Murovska 13, Bhupesh K Prusty 14, Roy A Quinlan 15, Dolores Pérez-Sala 16, Carmen Scheibenbogen 17, Harald H H W Schmidt 18, Isabel Silveira 19, Paolo Tieri 20, Alexander Tolios 21, Chiara Riganti 22 Affiliations expand PMID: 33288385 PMCID: PMC7716745 DOI: 10.1016/j.tim.2020.10.008 Free PMC article Abstract Despite the international guidelines on the containment of the coronavirus disease 2019 (COVID-19) pandemic, the European scientific community was not sufficiently prepared to coordinate scientific efforts. To improve preparedness for future pandemics, we have initiated a network of nine European-funded Cooperation in Science and Technology (COST) Actions that can help facilitate inter-, multi-, and trans-disciplinary communication and collaboration. Keywords: COST Actions; COVID-19; interdisciplinary network; pandemic. Copyright © 2020 Elsevier Ltd. All rights reserved. 15 references1 figure full-text links full-text provider logo Proceed to details Cite Share 18 Future Oncol 2020 Dec 8. doi: 10.2217/fon-2020-1071. Online ahead of print. Proximal versus total gastrectomy for proximal gastric cancer: a Surveillance, Epidemiology, and End Results Program database analysis Jianchang Wei 1, Ping Yang 1, Qing Huang 1, Zhuanpeng Chen 1, Tong Zhang 1, Feng He 1, He Hu 1, Junbin Zhong 1, Wanglin Li 1, Fang Wei 1, Qiang Wang 1, Jie Cao 1 Affiliations expand PMID: 33289395 DOI: 10.2217/fon-2020-1071 Abstract Aims: To addresses whether surgical procedure (proximal gastrectomy [PG] vs total gastrectomy [TG]) influences survival outcomes. Methods: Patients were selected from Surveillance, Epidemiology and End Results Program (SEER) database. Survival curve was used to evaluate the differences in overall survival (OS) and cancer-specific survival (CSS). Results: No significant difference was detected in OS and CSS time between PG and TG groups. Also, no significant differences were observed in OS and CSS times between the two groups with respect to clinical stage, tumor stage, node stage, age, gender and tumor differentiation. Tumor differentiation, tumor size, tumor stage, node stage and age were independent prognostic factors in patients with proximal gastric cancer. Conclusions: TG was not necessary for proximal gastric cancer patients, and PG may be considered as an ideal surgery approach. Keywords: proximal gastrectomy; proximal gastric cancer; total gastrectomy. supplementary info Grant supportexpand full-text links full-text provider logo Proceed to details Cite Share 19 Future Oncol 2020 Dec 8. doi: 10.2217/fon-2020-0907. Online ahead of print. Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma Cyrille Touzeau 1 2 3, Chloé Antier 1, Philippe Moreau 1 2 3 Affiliations expand PMID: 33289427 DOI: 10.2217/fon-2020-0907 Abstract The therapeutic landscape of relapsed multiple myeloma (MM) is constantly evolving. To date, a large proportion of patients present with lenalidomide refractory disease at time of first or second relapse. In this context, few efficient options are currently available. Carfilzomib and daratumumab are approved in the relapse setting. Recently, Phase Ib and Phase III trials evaluated the triplet drug combination daratumumab-carfilzomib-dexamethasone in the relapse setting and demonstrated strong clinical efficacy, especially in lenalidomide refractory patients. Based on these results, this combination has been approved by the US FDA for relapsed MM patients. The present review discusses the safety and efficacy of daratumumab-carfilzomib-dexamethasone in MM. Keywords: carfilzomib; daratumumab; lenalidomide; monoclonal antibody; myeloma; proteasome inhibitor. full-text links full-text provider logo Proceed to details Cite Share 20 Jpn J Clin Oncol 2020 Dec 9;hyaa220. doi: 10.1093/jjco/hyaa220. Online ahead of print. Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck Susumu Okano 1, Akihiro Homma 2, Naomi Kiyota 3, Makoto Tahara 1, Nobuhiro Hanai 4, Takahiro Asakage 5, Kazuto Matsuura 6, Takenori Ogawa 7, Yuki Saito 8, Daisuke Sano 9, Takeshi Kodaira 10, Atsushi Motegi 11, Koichi Yasuda 12, Shunji Takahashi 13, Kaoru Tanaka 14, Takuma Onoe 15, Tomoya Yokota 16, Yoshinori Imamura 3, Yosuke Ariizumi 5, Tetsuo Akimoto 11, Ryuichi Hayashi 6 Affiliations expand PMID: 33290543 DOI: 10.1093/jjco/hyaa220 Abstract In order to maximize the benefit of induction chemotherapy, practice based on a comprehensive interpretation of a large number of clinical trials, as in this review, is essential. The standard treatment for locally advanced squamous cell carcinoma of the head and neck is surgery or chemoradiation. However, induction chemotherapy followed by (chemo) radiotherapy may be used in some circumstances. Although many clinical trials of induction chemotherapy have been conducted, a rationale other than to preserve the larynx is still controversial. Selection of this modality should therefore be made with care. The current standard regimen for induction chemotherapy is docetaxel, cisplatin and 5-FU, but concerns remain about toxicity, cost and the duration of treatment. Regarding treatment after induction chemotherapy, it is also unclear whether radiation alone or chemoradiation is the better option. Furthermore, there is no answer as to what drugs should be used in combination with radiation therapy after induction chemotherapy. Several new induction chemotherapy treatment developments are currently underway, and future developments are expected. This review article summarizes the current position of induction chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment. Keywords: chemotherapy; head and neck; induction; organ preservation; squamous cell carcinoma. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. full-text links full-text provider logo Proceed to details Cite Share Future Oncology; +28 new citations Via pubmed: future oncology 28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Future Oncology These pubmed results were generated on 2020/12/09 PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CNS Invasion in Meningioma-How the Intraoperative Assessment Can Improve the Prognostic Evaluation of Tumor Recurrence.

payth.elady61 shared this article with you from Inoreader CNS Invasion in Meningioma-How the Intraoperative Assessment Can Improve the Prognostic Evaluation of Tumor Recurrence. Via pubmed: clinical neuropathol... CNS Invasion in Meningioma-How the Intraoperative Assessment Can Improve the Prognostic Evaluation of Tumor Recurrence. Cancers (Basel). 2020 Dec 03;12(12): Authors: Behling F, Fodi C, Gepfner-Tuma I, Machetanz K, Renovanz M, Skardelly M, Bornemann A, Honegger J, Tabatabai G, Tatagiba M, Schittenhelm J Abstract The detection of the infiltrative growth of meningiomas into CNS tissue has been integrated into the WHO classification as a stand-alone marker for atypical meningioma. However, its prognostic impact has been questioned. Infiltrative growth can also be detected intraoperatively. The prognostic impact of the intraoperative detection of the central nervous system tissue invasion of meningiomas was analyzed and compared to the histopathological assessment. The clinical data of 1517 cases with follow-up data regarding radiographic recurrence was collected. Histopathology and operative reports were reviewed and invasive growth was seen during resection in 23.7% (n = 345) while histopathology detected it in 4.8% (n = 73). The histopathological and intraoperative assessments were compatible in 63%. The prognostic impact of histopathological and intraoperative assessment was significant in the univariate but not in the multivariate analysis. Both methods of assessment combined reache d statistical significance in the multivariate analysis (p = 0.0409). A score including all independent prognostic factors divided the cohort into three prognostic subgroups with a risk of recurrence of 33.8, 64.7 and 88.5%, respectively. The intraoperative detection of the infiltrative growth of primary meningiomas into the central nervous system tissue can complement the histopathological assessment of CNS invasion. The combined assessment is an independent prognostic factor regarding tumor recurrence and allows a risk-adapted tumor stratification. PMID: 33287241 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features.

payth.elady61 shared this article with you from Inoreader MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features. Via pubmed: clinical neuropathol... MAPT subhaplotypes in corticobasal degeneration: assessing associations with disease risk, severity of tau pathology, and clinical features. Acta Neuropathol Commun. 2020 Dec 07;8(1):218 Authors: Valentino RR, Koga S, Walton RL, Soto-Beasley AI, Kouri N, DeTure MA, Murray ME, Johnson PW, Petersen RC, Boeve BF, Uitti RJ, Wszolek ZK, Dickson DW, Ross OA, Heckman MG Abstract The microtubule-associated protein tau (MAPT) H1 haplotype is the strongest genetic risk factor for corticobasal degeneration (CBD). However, the specific H1 subhaplotype association is not well defined, and it is not clear whether any MAPT haplotypes influence severity of tau pathology or clinical presentation in CBD. Therefore, in the current study we examined 230 neuropathologically confirmed CBD cases and 1312 controls in order to assess associations of MAPT haplotypes with risk of CBD, severity of tau pathology (measured as semi-quantitative scores for coiled bodies, neurofibrillary tangles, astrocytic plaques, and neuropil threads), age of CBD onset, and disease duration. After correcting for multiple testing (P < 0.0026 considered as significant), we confirmed the strong association between the MAPT H2 haplotype and decreased risk of CBD (Odds ratio = 0.26, P = 2 × 10-12), and also observed a novel association between the H1d subhaplotype and an inc reased CBD risk (Odds ratio = 1.76, P = 0.002). Additionally, although not statistically significant after correcting for multiple testing, the H1c haplotype was associated with a higher risk of CBD (Odds ratio = 1.49, P = 0.009). No MAPT haplotypes were significantly associated with any tau pathology measures, age of CBD onset, or disease duration. Though replication will be important and there is potential that population stratification could have influenced our findings, these results suggest that several MAPT H1 subhaplotypes are primarily responsible for the strong association between MAPT H1 and risk of CBD, but that H1 subhaplotypes are unlikely to play a major role in driving tau pathology or clinical features. Our findings also indicate that similarities in MAPT haplotype risk-factor profile exist between CBD and the related tauopathy progressive supranuclear palsy, with H2, H1d, and H1c displaying associations with both diseases. PMID: 33287913 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly.

payth.elady61 shared this article with you from Inoreader Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly. Via pubmed: clinical neuropathol... Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly. Clin Neuropathol. 2020 Dec 08;: Authors: Sarnat HB, Yu W, Flores-Sarnat L Abstract BACKGROUND: Keratan sulfate (KS) is an abundant proteoglycan in the developing human CNS where it functions as an extracellular axonal guidance molecule, repelling glutamatergic while facilitating -GABAergic axons. It ensheaths axonal fascicles. In fetal brain maturation, KS acts as a barrier to axonal penetration. Its possible role in the pathogenesis of fetal holoprosencephaly (HPE) was studied. MATERIALS AND METHODS: Forebrains of 6 human fetuses with HPE identified by prenatal ultrasound were examined at autopsy with KS immunoreactivity and other markers of cellular maturation and synaptogenesis, with age-matched controls. RESULTS: KS was strongly expressed in astrocytes in the thalamus from 13 weeks gestational age (GA) and in globus pallidus but not corpus striatum. Cortical plate reactivity was limited to the molecular zone, where KS was excessive, ensheathing individual transverse molecular zone axons. Axonal envelopment preceding myelination also was seen in the internal capsule and thalamocortical projections, but perifascicular KS was diminished. KS was not expressed in hippocampus in either HPE or controls. Glutamate receptor-2 (GluR2) was evident in hippocampal granular and pyramidal neurons at mid-gestation. KS distribution did not, however, correlate with synaptophysin. CONCLUSION: Excessive ensheathment of axons by KS provides additional protection of GABAergic inhibitory axons and synapses that may help suppress epileptogenesis. Though involved in selection of excitatory and inhibitory synaptogenesis, KS does not follow a developmental sequence corresponding to synaptophysin or GluR2 reactivities in either HPE or in normal fetal brain. PMID: 33287953 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Oligodendroglioma Workshop.

payth.elady61 shared this article with you from Inoreader Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Oligodendroglioma Workshop. Via pubmed: clinical neuropathol... Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Oligodendroglioma Workshop. Neurooncol Adv. 2020 Jan-Dec;2(1):vdz048 Authors: Penas-Prado M, Wu J, Cahill DP, Brat DJ, Costello JF, Kluetz PG, Cairncross JG, van den Bent M, Verhaak RGW, Aboud O, Burger P, Chang SM, Cordova C, Huang RY, Rowe LS, Taphoorn MJB, Gilbert MR, Armstrong TS, NCI-CONNECT Oligodendroglioma Workshop Abstract Background: Oligodendroglioma is a rare primary central nervous system (CNS) tumor with highly variable outcome and for which therapy is usually not curative. At present, little is known regarding the pathways involved with progression of oligodendrogliomas or optimal biomarkers for stratifying risk. Developing new therapies for this rare cancer is especially challenging. To overcome these challenges, the neuro-oncology community must be particularly innovative, seeking multi-institutional and international collaborations, and establishing partnerships with patients and advocacy groups thereby ensuring that each patient enrolled in a study is as informative as possible. Methods: The mission of the National Cancer Institute's NCI-CONNECT program is to address the challenges and unmet needs in rare CNS cancer research and treatment by connecting patients, health care providers, researchers, and advocacy organizations to work in partnership. On November 19, 2018, the program convened a workshop on oligodendroglioma, one of the 12 rare CNS cancers included in its initial portfolio. The purpose of this workshop was to discuss scientific progress and regulatory challenges in oligodendroglioma research and develop a call to action to advance research and treatment for this cancer. Results: The recommendations of the workshop include a multifaceted and interrelated approach covering: biology and preclinical models, data sharing and advanced molecular diagnosis and imaging; clinical trial design; and patient outreach and engagement. Conclusions: The NCI-CONNECT program is well positioned to address challenges in oligodendroglioma care and research in collaboration with other stakeholders and is developing a list of action items for future initiatives. PMID: 33289010 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Municipal return to work management in cancer survivors: a controlled intervention study.

payth.elady61 shared this article with you from Inoreader Municipal return to work management in cancer survivors: a controlled intervention study. Via pubmed: "acta oncol"[jour] Municipal return to work management in cancer survivors: a controlled intervention study. Acta Oncol. 2020 Dec 07;:1-8 Authors: Stapelfeldt CM, Momsen AH, Jensen AB, Andersen NT, Nielsen CV Abstract INTRODUCTION: Resuming work during or after cancer treatment has become an important target in cancer rehabilitation. PURPOSE: The aim was in a controlled trial to study the return to work (RTW) effect of an early, individually tailored vocational rehabilitation intervention targeted to improve readiness for RTW in cancer survivors. MATERIAL AND METHODS: Participants diagnosed with breast, cervix, ovary, testicular, colon-rectal, and head-and-neck cancers as well as being employed were allocated to a vocational rehabilitation intervention provided by municipal social workers (n = 83) or to usual municipal RTW management (n = 264). The intervention contained three elements: motivational communication inspired by Acceptance and Commitment Therapy by which RTW barriers were addressed, municipal cancer rehabilitation and finally employer and workplace contact. RTW effect was assessed as relative cumulative incidence proportions (RCIP) in the control and intervention group within 52 weeks of follow-up, estimated from the week where treatment ended at the hospital. RCIP was interpreted and reported as relative risk (RR) with 95% confidence intervals (CI) adjusted for gender, age cancer diagnosis, education, comorbidity, and sick leave weeks. RESULTS: Across cancer diagnoses 69 (83.1%) and 215 (81.4%) returned to work in the intervention and control group, respectively. No statistical effect was seen (RR 1.08 (95% CI 0.98-1.19)). Repeating the analyses solely for participants with breast cancer (n = 290) showed a significant effect of the intervention (RR 1.12 (95% CI 1.01-1.23)). CONCLUSION: More than 80% returned to work in both groups. However, no statistical difference in RTW effect was seen across cancer diagnoses within one year from being exposed to an early, individually tailored vocational rehabilitation intervention compared with usual municipal RTW management. TRIAL REGISTRATION NUMBER: ISRCTN50753764. PMID: 33287597 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

'Anticancer Res'[jour]; +65 new citations

payth.elady61 shared this article with you from Inoreader Message: 1 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 Affiliations expand 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. supplementary info Publication types, MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 2 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 Affiliations expand 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. supplementary info Publication types, MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 3 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 Affiliations expand 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. Cited by 1 article supplementary info MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 4 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 Affiliations expand 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. supplementary info MeSH termsexpand full-text links full-text provider logo Proceed to details Cite Share 5 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 Affiliations expand 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. supplementary info MeSH termsexpand full-text links full-text provider logo Proceed to details Cite Share 6 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 Affiliations expand 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. supplementary info MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 7 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 Affiliations expand 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. supplementary info MeSH termsexpand full-text links full-text provider logo Proceed to details Cite Share 8 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 Affiliations expand 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. supplementary info Publication typesexpand full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. supplementary info MeSH termsexpand full-text links full-text provider logo Proceed to details Cite Share 10 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 Affiliations expand 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. supplementary info Publication typesexpand full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. supplementary info Publication types, MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 12 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 Affiliations expand 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. supplementary info Publication types, MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 14 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 15 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 16 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 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 Affiliations expand 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. full-text links full-text provider logo Proceed to details Cite Share 20 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 Affiliations expand 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. supplementary info Publication types, MeSH terms, Substancesexpand full-text links full-text provider logo Proceed to details Cite Share "Anticancer Res"[jour]; +65 new citations Via pubmed: "anticancer res"[jou... 65 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: "Anticancer Res"[jour] These pubmed results were generated on 2020/12/09 PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. 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