Cancers, Vol. 13, Pages 3733: Targeting Replication Stress Using CHK1 Inhibitor Promotes Innate and NKT Cell Immune Responses and Tumour Regression
. Wells Brian Gabrielli Drugs selectively targeting replication stress have demonstrated significant preclinical activity, but this has not yet translated into an effective clinical treatment. Here we report that targeting increased replication stress with a combination of Checkpoint kinase 1 inhibitor (CHK1i) with a subclinical dose of hydroxyurea targets also promotes pro-inflammatory cytokine/chemokine expression that is independent of cGAS-STING pathway activation and immunogenic cell death in human and murine melanoma cells. In vivo, this drug combination induces tumour regression which is dependent on an adapti...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Martina Proctor Jazmina L. Gonzalez Cruz Sheena M. Daignault-Mill Margaret Veitch Bijun Zeng Anna Ehmann Muhammed Sabdia Cameron Snell Colm Keane Riccardo Dolcetti Nikolas K. Haass James W. Wells Brian Gabrielli Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3734: Radiation-Induced Dyspnea in Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy
In this study, we investigated the prognostic factors for radiation-induced dyspnea after hypo-fractionated radiation therapy (RT) in 106 patients treated with Stereotactic Body RT for Non-Small-Cell Lung Cancer (NSCLC). The median prescription dose was 50 Gy (range: 40–54 Gy), delivered in a median of four fractions (range: 3–12). Dyspnea within six months after SBRT was scored according to CTCAE v.4.0. Biologically Effective Dose (α/β = 3 Gy) volume histograms for lungs and heart were extracted. Dosimetric parameters along with patient-specific and treatment-related factors were analyzed, multivari...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Laura Cella Serena Monti Maria Thor Andreas Rimner Joseph O. Deasy Giuseppe Palma Tags: Brief Report Source Type: research

Cancers, Vol. 13, Pages 3735: Vascular Involvements in Cholangiocarcinoma: Tips and Tricks
Maria Manzia Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract. To date, surgical treatment remains the only hope for definitive cure of CCA patients. Involvement of major vascular structures was traditionally considered a contraindication for resection. Nowadays, selected cases of CCA with vascular involvement can be successfully approached. Intrahepatic CCA often involves the major hepatic veins or the inferior vena cava and might necessitate complete vascular exclusion, in situ hypothermic perfusion, ex situ surgery and reconstruction with autologous, heterologous or synthetic grafts. Hilar ...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Roberta Angelico Bruno Sensi Alessandro Parente Leandro Siragusa Carlo Gazia Giuseppe Tisone Tommaso Maria Manzia Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3737: Targeting RB1 Loss in Cancers
Chiaki Takahashi Retinoblastoma protein 1 (RB1) is encoded by a tumor suppressor gene that was discovered more than 30 years ago. Almost all mitogenic signals promote cell cycle progression by braking on the function of RB1 protein through mono- and subsequent hyper-phosphorylation mediated by cyclin-CDK complexes. The loss of RB1 function drives tumorigenesis in limited types of malignancies including retinoblastoma and small cell lung cancer. In a majority of human cancers, RB1 function is suppressed during tumor progression through various mechanisms. The latter gives rise to the acquisition of various phenotypes t...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Paing Linn Susumu Kohno Jindan Sheng Nilakshi Kulathunga Hai Yu Zhiheng Zhang Dominic Voon Yoshihiro Watanabe Chiaki Takahashi Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3736: Identification of an RNA-Binding-Protein-Based Prognostic Model for Ewing Sarcoma
lix Haglund RNA-binding proteins (RBPs) are important transcriptomic regulators and may be important in tumorigenesis. Here, we sought to investigate the clinical impact of RBPs for patients with Ewing sarcoma (ES). ES transcriptome signatures were characterized from four previously published cohorts and grouped into new training and validation cohorts. A total of three distinct subtypes were identified and compared for differences in patient prognosis and RBP signatures. Next, univariate Cox and Lasso regression models were used to identify hub prognosis-related RBPs and construct a prognostic risk model, and predicti...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Yi Chen Huafang Su Yanhong Su Yifan Zhang Yingbo Lin Felix Haglund Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3738: Gemcitabine Plus Nab-Paclitaxel Induces PD-L1 mRNA Expression in Plasma-Derived Microvesicles in Pancreatic Cancer
This study investigates the effect of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX), and gemcitabine plus nab-paclitaxel (GEMnPAC) regimens on PD-L1 mRNA expression in plasma-derived microvesicles (MVs) in 50 PDAC patients. Plasma was collected before starting chemotherapy and after 3 months of treatment. mRNA was extracted from MVs, and PD-L1 expression was measured by digital droplet PCR. Twenty-eight patients were PD-L1 positive in MVs at baseline, of which 18 were in the GEMnPAC cohort and 10 in the FOLFIRINOX one. The amount of PD-L1 expression in MVs increased from baseline to 3 months of treatment ...
Source: Cancers - July 25, 2021 Category: Cancer & Oncology Authors: Marzia Del Re Caterina Vivaldi Eleonora Rofi Francesca Salani Stefania Crucitta Silvia Catanese Lorenzo Fontanelli Valentina Massa Federico Cucchiara Lorenzo Fornaro Annalisa Capuano Stefano Fogli Enrico Vasile Romano Danesi Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3726: Glycosylation: Rising Potential for Prostate Cancer Evaluation
ska Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and ...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Anna Ka łuża Justyna Szczykutowicz Miros ława Ferens-Sieczkowska Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3725: Endogenous and Therapeutic Estrogens: Maestro Conductors of the Microenvironment of ER+ Breast Cancers
doch Estrogen receptor alpha (ERα) marks heterogeneous breast cancers which display a repertoire of somatic genomic mutations and an immune environment that differs from other breast cancer subtypes. These cancers also exhibit distinct biological behaviors; despite an overall better prognosis than HER2+ or triple negative breast cancers, disseminated dormant cells can lead to disease recurrence decades after the initial diagnosis and treatment. Estrogen is the best studied driver of these cancers, and antagonism or reduction of estrogen activity is the cornerstone of therapeutic approaches. In addition to reducin...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Schuler Murdoch Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3728: Geospatial Assessments of DNA Adducts in the Human Stomach: A Model of Field Cancerization
Conclusions: Regarding the DNA adducts investigated, significant differences in quantities and locations in the whole stomach were not noted; thus, these DNA adducts do not explain the preferential occurrence of cancer in particular locations of the human stomach. (Source: Cancers)
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Yuji Iwashita Ippei Ohnishi Yuto Matsushita Shunsuke Ohtsuka Takashi Yamashita Keisuke Inaba Atsuko Fukazawa Hideto Ochiai Keigo Matsumoto Nobuhito Kurono Yoshitaka Matsushima Hiroki Mori Shioto Suzuki Shohachi Suzuki Fumihiko Tanioka Haruhiko Sugimura Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3727: Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors
aniela Ungureanu Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Dafne Jacome Sanz Juuli Raivola Hanna Karvonen Mariliina Arjama Harlan Barker Astrid Murum ägi Daniela Ungureanu Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3724: Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients
Mussolin Valentina Serafin Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin lymphoma in childhood, mainly of T cell origin (T-LBL). Although current treatment protocols allow a complete remission in 85% of cases, the second-line treatment overall survival for patients with progressive or relapsed disease is around 14%, making this the major issue to be confronted. Thus, we performed a Reverse Phase Protein Array study in a cohort of 22 T-LBL patients to find reliable disease risk marker(s) and new therapeutic targets to improve pediatric T-LBL patients’ outcome. Interestingly, we pinp...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Giulia Veltri Chiara Silvestri Ilaria Gallingani Max Sandei Sara Vencato Federica Lovisa Giuliana Cortese Marta Pillon Elisa Carraro Silvia Bresolin Alessandra Biffi Giuseppe Basso Benedetta Accordi Lara Mussolin Valentina Serafin Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3730: The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives
. Ijzermans For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Berend R. Beumer Roeland F. de Wilde Herold J. Metselaar Robert A. de Man Wojciech G. Polak Jan N. M. Ijzermans Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3731: Reproductive Pattern of Parous Women and the Risk of Cancer in Later Life
hattacharya We assessed the risk of any and site-specific cancers in a case-control study of parous women living in northeast Scotland in relation to: total number of pregnancies, cumulative time pregnant, age at first delivery and interpregnancy interval. We analysed 6430 women with cancer and 6430 age-matched controls. After adjustment for confounders, women with increasing number of pregnancies had similar odds of cancer diagnosis as women with only one pregnancy. The adjusted odds of cancer diagnosis were no higher in women with cumulative pregnancy time 50-150 weeks compared to those pregnant ≤ 50 weeks. Compar...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Zahra Pasdar Neil W Scott Lisa Iversen Philip C Hannaford Phyo Kyaw Myint Sohinee Bhattacharya Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3729: The Human Fetal and Adult Stem Cell Secretome Can Exert Cardioprotective Paracrine Effects against Cardiotoxicity and Oxidative Stress from Cancer Treatment
ilvia Ravera Roberta Tasso Sveva Bollini Cardiovascular side effects are major shortcomings of cancer treatments causing cardiotoxicity and late-onset cardiomyopathy. While doxorubicin (Dox) has been reported as an effective chemotherapy agent, unspecific impairment in cardiomyocyte mitochondria activity has been documented. We demonstrated that the human fetal amniotic fluid-stem cell (hAFS) secretome, namely the secreted paracrine factors within the hAFS-conditioned medium (hAFS-CM), exerts pro-survival effects on Dox-exposed cardiomyocytes. Here, we provide a detailed comparison of the cardioprotective potential...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Federico Villa Silvia Bruno Ambra Costa Mingchuan Li Michele Russo James Cimino Paola Altieri Clarissa Ruggeri Cansu Gorgun Pierangela De Biasio Dario Paladini Domenico Coviello Rodolfo Quarto Pietro Ameri Alessandra Ghigo Silvia Ravera Roberta Tasso Svev Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3732: Differentiated Thyroid Cancer in Children and Adolescents: Long Term Outcome and Risk Factors for Persistent Disease
Conclusion: P-DTC has an excellent prognosis. Modified ATA-R is a useful prognostic tool in P-DTC to guide management. (Source: Cancers)
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Giulia Sapuppo Dana Hartl Brice Fresneau Julien Hadoux Ingrid Breuskin Eric Baudin Charlotte Rigaud Joanne Guerlain Abir Al Ghuzlan Sophie Leboulleux Martin Schlumberger Livia Lamartina Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3721: Immunotherapy in Glioblastoma: A Clinical Perspective
ger Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, ...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Nicolas Desbaillets Andreas Felix Hottinger Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3722: Combined Simplified Molecular Classification of Gastric Adenocarcinoma, Enhanced by Lymph Node Status: An Integrative Approach
ieri Cathomas Gastric adenocarcinoma (GAC) is a heterogeneous disease and at least two major studies have recently provided a molecular classification for this tumor: The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ARCG). Both classifications quote four molecular subtypes, but these subtypes only partially overlap. In addition, the classifications are based on complex and cost-intensive technologies, which are hardly feasible for everyday practice. Therefore, simplified approaches using immunohistochemistry (IHC), in situ hybridization (ISH) as well as commercially available next generation sequenci...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Till Daun Ronny Nienhold Aino Paasinen-Sohns Angela Frank Melanie Sachs Inti Zlobec Gieri Cathomas Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3723: Site-Specific Variation in Radiomic Features of Head and Neck Squamous Cell Carcinoma and Its Impact on Machine Learning Models
abvash Stefan P. Haider Amit Mahajan Caroline Reinhold Behzad Forghani Brian O’Sullivan Eugene Yu Reza Forghani Current radiomic studies of head and neck squamous cell carcinomas (HNSCC) are typically based on datasets combining tumors from different locations, assuming that the radiomic features are similar based on histopathologic characteristics. However, molecular pathogenesis and treatment in HNSCC substantially vary across different tumor sites. It is not known if a statistical difference exists between radiomic features from different tumor sites and how they affect machine learning model per...
Source: Cancers - July 24, 2021 Category: Cancer & Oncology Authors: Xiaoyang Liu Farhad Maleki Nikesh Muthukrishnan Katie Ovens Shao Hui Huang Almudena P érez-Lara Griselda Romero-Sanchez Sahir Rai Bhatnagar Avishek Chatterjee Marc Philippe Pusztaszeri Alan Spatz Gerald Batist Seyedmehdi Payabvash Stefan P. Haider Amit M Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3697: Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs
harma Metastatic progression and tumor recurrence pertaining to TNBC are certainly the leading cause of breast cancer-related mortality; however, the mechanisms underlying TNBC chemoresistance, metastasis, and tumor relapse remain somewhat ambiguous. TNBCs show 77% of the overall 4-year survival rate compared to other breast cancer subtypes (82.7 to 92.5%). TNBC is the most aggressive subtype of breast cancer, with chemotherapy being the major approved treatment strategy. Activation of ABC transporters and DNA damage response genes alongside an enrichment of cancer stem cells and metabolic reprogramming upon chemothera...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Qitong Wu Sumit Siddharth Dipali Sharma Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3698: Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors
Maeda Most pediatric cancers are highly chemo-sensitive, and cytotoxic chemotherapy has always been the mainstay of treatment. Anthracyclines are highly effective against most types of childhood cancer, such as neuroblastoma, hepatoblastoma, nephroblastoma, rhabdomyosarcoma, Ewing sarcoma, and so forth. However, acute and chronic cardiotoxicity, one of the major disadvantages of anthracycline use, limits their utility and effectiveness. Hydroxypropyl acrylamide polymer-conjugated pirarubicin (P-THP), which targets tumor tissue highly selectively via the enhanced permeability and retention (EPR) effect, and secondarily ...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Atsushi Makimoto Jun Fang Hiroshi Maeda Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3699: Combined Inhibition of AKT and KIT Restores Expression of Programmed Cell Death 4 (PDCD4) in Gastrointestinal Stromal Tumor
aret von Mehren Lori Rink The majority of gastrointestinal stromal tumor (GIST) patients develop resistance to the first-line KIT inhibitor, imatinib mesylate (IM), through acquisition of secondary mutations in KIT or bypass signaling pathway activation. In addition to KIT, AKT is a relevant target for inhibition, since the PI3K/AKT pathway is crucial for IM-resistant GIST survival. We evaluated the activity of a novel pan-AKT inhibitor, MK-4440 (formerly ARQ 751), as monotherapy and in combination with IM in GIST cell lines and preclinical models with varying IM sensitivities. Dual inhibition of KIT and AKT demonstr...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Marya Kozinova Shalina Joshi Shuai Ye Martin G. Belinsky Dinara Sharipova Jeffrey M. Farma Sanjay S. Reddy Samuel Litwin Karthik Devarajan Alex Rosa Campos Yi Yu Brian Schwartz Margaret von Mehren Lori Rink Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3700: Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes
a Ramesh C. Gupta Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Raghuram Kandimalla Farrukh Aqil Sara S. Alhakeem Jeyaprakash Jeyabalan Neha Tyagi Ashish Agrawal Jun Yan Wendy Spencer Subbarao Bondada Ramesh C. Gupta Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3702: Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study
k K. Główka Prognosis of advanced non-small cell lung carcinoma (NSCLC) is poor. Even though it can improve with anti-PD-1/PD-L1 agents, most patients do not respond to treatment. We hypothesized that the serum soluble form of the unit α of the interleukin-2 receptor (sCD25) could be used as a biomarker of successful immunotherapy in NSCLC. We recruited patients dosed with atezolizumab (n = 42) or pembrolizumab (n = 20) and collected samples at baseline and during the treatment. Levels of sCD25 were quantified with the ELISA kits. Patients with a high sCD25 at baseline (sCD25.0 ≥ 5.99 ng/mL) or/and at ...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Anna Siemi ątkowska Maciej Bryl Katarzyna Kosicka-Noworzy ń Jakub Tvrdo ň Iwona Go łda-Gocka Aleksander Barinow-Wojew ódzki Franciszek K. G łówka Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3703: Definitive Chemoradiotherapy versus Radical Hysterectomy Followed by Tailored Adjuvant Therapy in Women with Early-Stage Cervical Cancer Presenting with Pelvic Lymph Node Metastasis on Pretreatment Evaluation: A Propensity Score Matching Analysis
Joo-Young Kim To compare the oncologic outcomes between chemoradiotherapy (CRT) and radical hysterectomy followed by tailored adjuvant therapy in patients with early cervical cancer presenting with pelvic lymph node metastasis. We retrospectively analyzed the medical records of women with early cervical cancer presenting with positive pelvic nodes identified on pretreatment imaging assessment. Propensity score matching was employed to control for the heterogeneity between two groups according to confounding factors. Overall survival, disease-free survival, and pattern of failure were compared between the two groups. A ...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Jongmoo Park Yeon-Joo Kim Mi-Kyung Song Joo-Hyun Nam Sang-Yoon Park Young-Seok Kim Joo-Young Kim Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3704: Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients: A Systematic Review and Network Meta-Analysis
Hironori Sagara To date, there have been no head-to-head randomized controlled trials (RCTs) comparing the safety and efficacy of lorlatinib and alectinib in anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) ALK-inhibitor‒naïve advanced non-small cell lung cancer (NSCLC). We performed a network meta-analysis comparing six treatment arms (lorlatinib, brigatinib, alectinib, ceritinib, crizotinib, and platinum-based chemotherapy) in overall participants and in Asian and non-Asian subgroups. Primary endpoints were progression-free survival (PFS), overall survival (OS), and grade 3 or higher adverse eve...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Koichi Ando Ryo Manabe Yasunari Kishino Sojiro Kusumoto Toshimitsu Yamaoka Akihiko Tanaka Tohru Ohmori Hironori Sagara Tags: Systematic Review Source Type: research

Cancers, Vol. 13, Pages 3705: Systematic Roadmap for Cancer Drug Screening Using Zebrafish Embryo Xenograft Cancer Models: Melanoma Cell Line as a Case Study
This study aims to help the wider cancer research community to consider the adoption of this versatile model for cancer drug screening projects. (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Patricia Letrado Holly Mole Mar ía Montoya Irene Palacios Jorge Barriuso Adam Hurlstone Roberto D íez-Martínez Julen Oyarzabal Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3706: Hsp70 in Liquid Biopsies —A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer
Cancers, Vol. 13, Pages 3706: Hsp70 in Liquid Biopsies—A Tumor-Specific Biomarker for Detection and Response Monitoring in Cancer Cancers doi: 10.3390/cancers13153706 Authors: Caroline Werner Stefan Stangl Lukas Salvermoser Melissa Schwab Maxim Shevtsov Alexia Xanthopoulos Fei Wang Ali Bashiri Dezfouli Dennis Thölke Christian Ostheimer Daniel Medenwald Martin Windberg Matthias Bache Martin Schlapschy Arne Skerra Gabriele Multhoff In contrast to normal cells, tumor cells of multiple entities overexpress the Heat shock protein 70 (Hsp70) not only in the cytosol, but also prese...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Caroline Werner Stefan Stangl Lukas Salvermoser Melissa Schwab Maxim Shevtsov Alexia Xanthopoulos Fei Wang Ali Bashiri Dezfouli Dennis Th ölke Christian Ostheimer Daniel Medenwald Martin Windberg Matthias Bache Martin Schlapschy Arne Skerra Gabriele Mult Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3701: Cancer Organoids in Basic Science and Translational Medicine
zolio Organoids are revolutionizing approaches to cancer therapy and even diagnosis [...] (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Lorenzo Memeo Vincenzo Canzonieri Flavio Rizzolio Tags: Editorial Source Type: research

Cancers, Vol. 13, Pages 3708: Selective Inhibition of Aurora Kinase A by AK-01/LY3295668 Attenuates MCC Tumor Growth by Inducing MCC Cell Cycle Arrest and Apoptosis
In this study, we examined the efficacy of the recently developed and highly selective AURKA inhibitor, AK-01 (LY3295668), in six patient-derived MCC cell lines and two MCC cell-line-derived xenograft mouse models. We found that AK-01 potently suppresses MCC survival through apoptosis and cell cycle arrest, particularly in MCPyV-negative MCC cells without RB expression. Despite the challenge posed by its short in vivo durability upon discontinuation, the swift and substantial tumor suppression with low toxicity makes AK-01 a strong potential candidate for MCC management, particularly in combination with existing regimens. (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Bhaba K. Das Aarthi Kannan Quy Nguyen Jyoti Gogoi Haibo Zhao Ling Gao Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3707: ‘Palliative-D’—Vitamin D Supplementation to Palliative Cancer Patients: A Double Blind, Randomized Placebo-Controlled Multicenter Trial
In conclusion, correction of vitamin D deficiency may have positive effects on opioid use and fatigue in palliative cancer patients, but only in those with a survival time more than 12 weeks. (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Maria Helde Frankling Caritha Klasson Carina Sandberg Marie Nordstr öm Anna Warnqvist Jenny Bergqvist Peter Bergman Linda Bj örkhem-Bergman Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3709: Machine Learning Models to Predict Survival Outcomes According to the Surgical Approach of Primary Radical Hysterectomy in Patients with Early Cervical Cancer
Sang Song Yong Beom Kim We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients’ clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Se Ik Kim Sungyoung Lee Chel Hun Choi Maria Lee Dong Hoon Suh Hee Seung Kim Kidong Kim Hyun Hoon Chung Jae Hong No Jae-Weon Kim Noh Hyun Park Yong-Sang Song Yong Beom Kim Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3710: Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population
taci L. Sudenga The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Sylvie Muhimpundu Rebecca Baqiyyah N. Conway Shaneda Warren Andersen Loren Lipworth Mark D. Steinwandel William J. Blot Xiao-Ou Shu Staci L. Sudenga Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3711: The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives —State of the Art
Cancers, Vol. 13, Pages 3711: The Role of Surgery in Lung Cancer Treatment: Present Indications and Future Perspectives—State of the Art Cancers doi: 10.3390/cancers13153711 Authors: François Montagne Florian Guisier Nicolas Venissac Jean-Marc Baste Non-small cell lung cancers (NSCLC) are different today, due to the increased use of screening programs and of innovative systemic therapies, leading to the diagnosis of earlier and pre-invasive tumors, and of more advanced and controlled metastatic tumors. Surgery for NSCLC remains the cornerstone treatment when it can be performed. The role of surge...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Fran çois Montagne Florian Guisier Nicolas Venissac Jean-Marc Baste Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3714: Differences in Extracellular Vesicle Protein Cargo Are Dependent on Head and Neck Squamous Cell Carcinoma Cell of Origin and Human Papillomavirus Status
her Walline To identify potential extracellular vesicle (EV) biomarkers in head and neck squamous cell carcinoma (HNSCC), we evaluated EV protein cargo and whole cell lysates (WCL) from HPV-positive and -negative HNSCC cell lines, as well as normal oral keratinocytes and HPV16-transformed cells. EVs were isolated from serum-depleted, conditioned cell culture media by polyethylene glycol (PEG) precipitation/ultracentrifugation. EV and WCL preparations were analyzed by LC-MS/MS. Candidate proteins detected at significantly higher levels in EV compared with WCL, or compared with EV from normal oral keratinocytes, were ide...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Christine Goudsmit Felipe da Veiga Leprevost Venkatesha Basrur Lila Peters Alexey Nesvizhskii Heather Walline Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3715: Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives
Kambiz Rahbar Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a g...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Konstantin Egon Seitzer Robert Seifert Katharina Kessel Wolfgang Roll Katrin Schlack Martin Boegemann Kambiz Rahbar Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3716: Primary Aldosteronism: Metabolic Reprogramming and the Pathogenesis of Aldosterone-Producing Adenomas
In conclusion, APAs exhibit metabolic reprogramming towards fatty acid β-oxidation and glycolysis. Increased lipid metabolism via PPARα may serve as a key mechanism to modulate lipid peroxidation, a hallmark of regulated cell death by ferroptosis. These findings highlight survival advantages for APA tumor cells with metabolic reprogramming properties. (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Siyuan Gong Martina Tetti Martin Reincke Tracy Ann Williams Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3713: Novel Insights of T2-Weighted Imaging: Significance for Discriminating Lung Cancer from Benign Pulmonary Nodules and Masses
Hidetaka Uramoto Diffusion-weighted imaging is useful for discriminating lung cancer from benign pulmonary nodules and masses (BPNMs), however the diagnostic capability is not perfect. The aim of this research was to clarify whether T2-weighted imaging (T2WI) is efficient in discriminating lung cancer from BPNMs, especially from pulmonary abscesses. A T2 contrast ratio (T2 CR) for a pulmonary nodule is defined as the ratio of T2 signal intensity of a pulmonary nodule divided by the T2 signal intensity of the rhomboid muscle. There were 52 lung cancers and 40 inflammatory BPNMs (mycobacteria disease 12, pneumonia 13, p...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Katsuo Usuda Shun Iwai Aika Yamagata Yoshihito Iijima Nozomu Motono Munetaka Matoba Mariko Doai Keiya Hirata Hidetaka Uramoto Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3717: The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma
ra Nuyts Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed the role of DDR in the radioresistance process of HNSCC by generating radioresistant clones from both HPV-positive SCC154 and HPV-negative SCC61 cells. We show that fractionated RT decreased RT response of HPV-positive and HPV-negative radioresistant clones in vitro and in vivo. Moreover, HPV-positive and HPV-negative radioresistant clones were...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Marieke Bamps R üveyda Dok Sandra Nuyts Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3718: Factor VIIa Regulates the Level of Cell-Surface Tissue Factor through Separate but Cooperative Mechanisms
le Ettelaie Procoagulant activity of tissue factor (TF) in response to injury or inflammation is accompanied with cellular signals which determine the fate of cells. However, to prevent excessive signalling, TF is rapidly dissipated through release into microvesicles, and/or endocytosis. To elucidate the mechanism by which TF signalling may become moderated on the surface of cells, the associations of TF, fVII/fVIIa, PAR2 and caveolin-1 on MDA-MB-231, BxPC-3 and 786-O cells were examined and compared to that in cells lacking either fVII/fVIIa or TF. Furthermore, the localisation of labelled-recombinant TF with choleste...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Yahya Madkhali Araci M. R. Rondon Sophie Featherby Anthony Maraveyas John Greenman Camille Ettelaie Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3719: Missense Variants of Uncertain Significance: A Powerful Genetic Tool for Function Discovery with Clinical Implications
ai Aura Carreira The breast cancer susceptibility gene BRCA2 encodes a multifunctional protein required for the accurate repair of DNA double-strand breaks and replicative DNA lesions. In addition, BRCA2 exhibits emerging important roles in mitosis. As a result, mutations in BRCA2 may affect chromosomal integrity in multiple ways. However, many of the BRCA2 mutations found in breast cancer patients and their families are single amino acid substitutions, sometimes unique, and their relevance in cancer risk remains difficult to assess. In this review, we focus on three recent reports that investigated variants of uncer...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Gaetana Sessa Åsa Ehlén Catharina von Nicolai Aura Carreira Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3720: Effectiveness of a Novel Covered Stent without External Thread Fixation for Anastomotic Leakage after Total or Proximal Gastrectomy for Gastric Cancer
In conclusion, the Niti-S Beta stent is an effective treatment for anastomotic leakage from total or proximal gastrectomy for gastric cancer. Stent maintenance is possible without hospitalization. (Source: Cancers)
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Young-Il Kim Chan Gyoo Kim Jong Yeul Lee Il Ju Choi Bang Wool Eom Hong Man Yoon Keun Won Ryu Young-Woo Kim Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3696: Overview of Oral Potentially Malignant Disorders: From Risk Factors to Specific Therapies
cía Paolo Bossi Paolo Nuciforo Sara Simonetti Oral squamous cell carcinoma (OSCC) is a very aggressive cancer, representing one of the most common malignancies worldwide. Oral potentially malignant disorders (OPMDs) regroup a variegate set of different histological lesions, characterized by the potential capacity to transform in OSCC. Most of the risk factors associated with OSCC are present also in OPMDs’ development; however, the molecular mechanisms and steps of malignant transformation are still unknown. Treatment of OSCC, including surgery, systemic therapy and radiotherapy (alone or in combinat...
Source: Cancers - July 23, 2021 Category: Cancer & Oncology Authors: Luigi Lorini Coro Besc ós Atín Selvam Thavaraj Urs M üller-Richter Margarita Alberola Ferranti Jorge Pamias Romero Manel S áez Barba Alba de Pablo Garc ía-Cuenca Irene Bra ña García Paolo Bossi Paolo Nuciforo Sara Simonetti Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3670: NUPR1: A Critical Regulator of the Antioxidant System
an Iovanna Nuclear protein 1 (NUPR1) is a small intrinsically disordered protein (IDP) activated in response to various types of cellular stress, including endoplasmic reticulum (ER) stress and oxidative stress. Reactive oxygen species (ROS) are mainly produced during mitochondrial oxidative metabolism, and directly impact redox homeostasis and oxidative stress. Ferroptosis is a ROS-dependent programmed cell death driven by an iron-mediated redox reaction. Substantial evidence supports a maintenance role of the stress-inducible protein NUPR1 on cancer cell metabolism that confers chemotherapeutic resistance by upregula...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Can Huang Patricia Santofimia-Casta ño Juan Iovanna Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3671: Anastasis: Return Journey from Cell Death
ovsky For over 20 years, it has been a dogma that once the integrity of mitochondria is disrupted and proapoptotic proteins that are normally located in the intermembrane space of mitochondria appeared in the cytoplasm, the process of cell death becomes inevitable. However, it has been recently shown that upon removal of the death signal, even at the stage of disturbance in the mitochondria, cells can recover and continue to grow. This phenomenon was named anastasis. Here, we will critically discuss the present knowledge concerning the mechanisms of cell death reversal, or development of anastasis, methods for its dete...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Victoria Zaitceva Gelina S. Kopeina Boris Zhivotovsky Tags: Review Source Type: research

Cancers, Vol. 13, Pages 3672: Oncolytic Virus Immunotherapy
lcher Oncolytic viruses (OVs) were originally developed as direct cytotoxic agents but have been increasingly recognised as a form of immunotherapy [...] (Source: Cancers)
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Antonio Marchini Carolina S. Ilkow Alan Melcher Tags: Editorial Source Type: research

Cancers, Vol. 13, Pages 3673: Abdominal Desmoid: Course, Severe Outcomes, and Unique Genetic Background in a Large Local Series
Conclusions: Abdominal desmoids are mostly FAP-related and are associated with severe outcomes. We also report a group of non-FAP abdominal desmoids, which includes patients with additional cancer-related gene alterations. This interesting group should be further explored. (Source: Cancers)
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Gilad Ophir Shamai Sivan Strul Hana Rosner Guy Gluck Nathan Fliss Isakov Naomi Klausner Joseph Wolf Ido Merimsky Ofer Goldberg Yael Levi Zohar Zer Alona Kariv Revital Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3674: Collapse of Intra-Tumor Cooperation Induced by Engineered Defector Cells
i Anti-cancer therapies promote clonal selection of resistant cells that evade treatment. Effective therapy must be stable against the evolution of resistance. A potential strategy based on concepts from evolutionary game theory is to impair intra-tumor cooperation using genetically modified cells in which genes coding for essential growth factors have been knocked out. Such engineered cells would spread by clonal selection, driving the collapse of intra-tumor cooperation and a consequent reduction in tumor growth. Here, I test this idea in vitro in four cancer types (neuroendocrine pancreatic cancer, mesothelioma, lun...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Marco Archetti Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3675: Optimization of New Catalytic Topoisomerase II Inhibitors as an Anti-Cancer Therapy
v Xuesen Dong Clinically used topoisomerase II (TOP2) inhibitors are poison inhibitors that induce DNA damage to cause cancer cell death. However, they can also destroy benign cells and thereby show serious side effects, including cardiotoxicity and drug-induced secondary malignancy. New TOP2 inhibitors with a different mechanism of action (MOA), such as catalytic TOP2 inhibitors, are needed to more effectively control tumor growth. We have applied computer-aided drug design to develop a new group of small molecule inhibitors that are derivatives of our previously identified lead compound T60. Particularly, the compo...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Victor M. Matias-Barrios Mariia Radaeva Chia-Hao Ho Joseph Lee Hans Adomat Nada Lallous Artem Cherkasov Xuesen Dong Tags: Article Source Type: research

Cancers, Vol. 13, Pages 3677: Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis
Langevin Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary surv...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Anish Sharma Alice L. Tang Vinita Takiar Trisha M. Wise-Draper Scott M. Langevin Tags: Systematic Review Source Type: research

Cancers, Vol. 13, Pages 3678: Follicular Helper T Cells Remodel the Immune Microenvironment of Pancreatic Cancer via Secreting CXCL13 and IL-21 (Stage-1)
g Heli Gao Xianjun Yu Liang Liu Immunosuppression is an important factor for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Follicular helper T cells (Tfh cells) play an anti-tumor role in various malignant solid tumors and predict better patient prognosis. In the present study, we aimed to determine the immunosuppressive mechanism associated with Tfh cells and explore a new strategy to improve the tumor microenvironment of PDAC. Flow cytometry was used to detect the infiltration and proportion of Tfh cells in tumor tissues and peripheral blood from patients with PDAC. The spatial correlations of ...
Source: Cancers - July 22, 2021 Category: Cancer & Oncology Authors: Xuan Lin Longyun Ye Xu Wang Zhenyu Liao Jia Dong Ying Yang Rulin Zhang Hao Li Pengcheng Li Lei Ding Tianjiao Li Wuhu Zhang Shuaishuai Xu Xuan Han Huaxiang Xu Wenquan Wang Heli Gao Xianjun Yu Liang Liu Tags: Article Source Type: research