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Cancers, Volume 15, Issue 12 (June-2 2023) – 200 articles

Cover Story (view full-size image): A high level of programmed death ligand-1 (PD-L1) promotes an immune-depleted (“cold”) tumour microenvironment and is a key factor in immune evasion and aggressive growth of glioblastoma (GBM). It is well recognised that PD-L1 expression is a critical biomarker to predict which patients will respond to PD-1/PD-L1 checkpoint inhibitors; however, it is subjected to spatial and temporal heterogeneity. This underscores the need to monitor PD-L1 distribution over time through real-time immuno-PET imaging. We believe that molecular imaging of this target has great potential to stratify patients accurately and quantitatively for immunotherapy, offering a practical remedy to the drawbacks of conventional techniques such as biopsy and immunohistochemistry staining. View this paper
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12 pages, 428 KiB  
Article
Characteristics and Outcomes of COVID-19 Cancer Patients Admitted to a Portuguese Intensive Care Unit: A Case-Control Study
by Ridhi Ranchor, Nuno Pereira, Ana R. Medeiros, Manuel Magalhães, Aníbal Marinho and António Araújo
Cancers 2023, 15(12), 3264; https://doi.org/10.3390/cancers15123264 - 20 Jun 2023
Viewed by 1407
Abstract
Cancer patients appear to be a vulnerable group in the COVID-19 pandemic. This study aims to compare clinical characteristics and outcomes of cancer and non-cancer patients with COVID-19 admitted to the ICU. All COVID-19 cancer patients (cases) admitted to a Portuguese ICU between [...] Read more.
Cancer patients appear to be a vulnerable group in the COVID-19 pandemic. This study aims to compare clinical characteristics and outcomes of cancer and non-cancer patients with COVID-19 admitted to the ICU. All COVID-19 cancer patients (cases) admitted to a Portuguese ICU between March 2020 and January 2021 were included and matched on age, sex and comorbidities with COVID-19 non-cancer patients (controls); 29 cases and 29 controls were enrolled. Initial symptoms were similar between the two groups. Anemia was significantly superior among cases (76% vs. 45%; p = 0.031). Invasive mechanical ventilation (IMV) need at ICU admission was significantly higher among cases (48% vs. 7%; odds ratio (OR) = 12.600, 95% CI: 2.517–63.063, p = 0.002), but there were no differences for global need for IMV during all-length of ICU stay and mortality rates. In a multivariate model of logistic regression, the risk of IMV need at ICU admission among cases remained statistically significant (adjusted OR = 14.036, 95% CI: 1.337–153.111, p = 0.028). Therefore, compared to critical non-cancer patients, critical cancer patients with COVID-19 had an increased risk for IMV need at the moment of ICU admission, however, not for IMV need during all-length of ICU stay or death. Full article
(This article belongs to the Special Issue Coronavirus Disease (COVID-19) and Its Impact on Patients with Cancer)
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24 pages, 1244 KiB  
Review
Caring for Adolescents and Young Adults (AYA) with Cancer: A Scoping Review into Caregiver Burdens and Needs
by Milou J. P. Reuvers, Asiye Gedik, Kirsty M. Way, Sanne M. Elbersen-van de Stadt, Winette T. A. van der Graaf and Olga Husson
Cancers 2023, 15(12), 3263; https://doi.org/10.3390/cancers15123263 - 20 Jun 2023
Cited by 3 | Viewed by 1976
Abstract
AYAs with cancer (aged 15 to 39 at primary diagnosis) form a specific group within oncology, and there is limited information on the impact on their informal caregivers. This scoping review aimed to gain insight into the burden on caregivers of AYAs with [...] Read more.
AYAs with cancer (aged 15 to 39 at primary diagnosis) form a specific group within oncology, and there is limited information on the impact on their informal caregivers. This scoping review aimed to gain insight into the burden on caregivers of AYAs with cancer and identify the unmet needs they might have. Eligible articles focused on impacts in one of the domains of caregiver burden (physical, psychological, social, on schedule, financial) or unmet needs. In all domains of caregiver burden, impact was reported by caregivers. Caregiving leads to physical problems (such as sleep problems) and psychological symptoms (e.g., depression, anxiety, and negative emotions). Loneliness is reported, and little peer-support. Many different tasks and roles must be undertaken, which is perceived as challenging. In addition, there is a financial impact and there are unmet needs to be met. Several domains of the lives of caregivers of AYA cancer patients are negatively affected by the disease. Some of these are age-specific, and tailored to a particular group of caregivers (parents, partners, or friends). AYA cancer patients represent a wide age range, resulting in the engagement of many different caregivers. Future research will need to take this into account in order to adequately provide support. Full article
(This article belongs to the Special Issue 2nd Edition: Adolescent and Young Adult Oncology)
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10 pages, 1059 KiB  
Communication
Vascular Growth in Lymphomas: Angiogenesis and Alternative Ways
by Domenico Ribatti, Roberto Tamma, Tiziana Annese, Antonio d’Amati, Giuseppe Ingravallo and Giorgina Specchia
Cancers 2023, 15(12), 3262; https://doi.org/10.3390/cancers15123262 - 20 Jun 2023
Cited by 3 | Viewed by 1163
Abstract
The formation of new blood vessels is a critical process for tumor growth and may be achieved through different mechanisms. Angiogenesis represents the first described and most studied mode of vessel formation, but tumors may also use alternative ways to secure blood supply [...] Read more.
The formation of new blood vessels is a critical process for tumor growth and may be achieved through different mechanisms. Angiogenesis represents the first described and most studied mode of vessel formation, but tumors may also use alternative ways to secure blood supply and eventually acquire resistance to anti-angiogenic treatments. These non-angiogenic mechanisms have been described more recently, including intussusceptive microvascular growth (IMG), vascular co-option, and vasculogenic mimicry. Like solid tumors, angiogenic and non-angiogenic pathways in lymphomas play a fundamental role in tumor growth and progression. In view of the relevant prognostic and therapeutic implications, a comprehensive understanding of these mechanisms is of paramount importance for improving the efficacy of treatment in patients with lymphoma. In this review, we summarize the current knowledge on angiogenic and non-angiogenic mechanisms involved in the formation of new blood vessels in Hodgkin’s and non-Hodgkin’s lymphomas. Full article
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25 pages, 1966 KiB  
Review
Pleural Neoplasms—What Could MRI Change?
by Michał Szczyrek, Paulina Bitkowska, Marta Jutrzenka, Aneta Szudy-Szczyrek, Anna Drelich-Zbroja and Janusz Milanowski
Cancers 2023, 15(12), 3261; https://doi.org/10.3390/cancers15123261 - 20 Jun 2023
Viewed by 2160
Abstract
The primary pleural neoplasms constitute around 10% of the pleural tumors. The currently recommended method for their imaging is CT which has been shown to have certain limitations. Strong development of the MRI within the last two decades has provided us with a [...] Read more.
The primary pleural neoplasms constitute around 10% of the pleural tumors. The currently recommended method for their imaging is CT which has been shown to have certain limitations. Strong development of the MRI within the last two decades has provided us with a number of sequences that could potentially be superior to CT when it comes to the pleural malignancies’ detection and characterization. This literature review discusses the possible applications of the MRI as a diagnostic tool in patients with pleural neoplasms. Although selected MRI techniques have been shown to have a number of advantages over CT, further research is required in order to confirm the obtained results, broaden our knowledge on the topic, and pinpoint the sequences most optimal for pleural imaging, as well as the best methods for reading and analysis of the obtained data. Full article
(This article belongs to the Special Issue Novel Insight of MRI for Lung Cancer and Thoracic Neoplasm)
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15 pages, 2153 KiB  
Article
E-Cadherin Expression Varies Depending on the Location within the Primary Tumor and Is Higher in Colorectal Cancer with Lymphoid Follicles
by Adam R. Markowski, Konstancja Ustymowicz, Anna J. Markowska, Wiktoria Romańczyk and Katarzyna Guzińska-Ustymowicz
Cancers 2023, 15(12), 3260; https://doi.org/10.3390/cancers15123260 - 20 Jun 2023
Viewed by 1297
Abstract
Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending [...] Read more.
Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time. Full article
(This article belongs to the Topic Advances in Tumor Microenvironment)
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16 pages, 4451 KiB  
Review
The Histological Background of Recurrence in Laryngeal Squamous Cell Carcinoma: An Insight into the Modifications of Tumor Microenvironment
by Giorgia Arcovito, Annarita Palomba, Oreste Gallo and Alessandro Franchi
Cancers 2023, 15(12), 3259; https://doi.org/10.3390/cancers15123259 - 20 Jun 2023
Cited by 1 | Viewed by 1642
Abstract
Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response [...] Read more.
Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications. Full article
(This article belongs to the Special Issue Head and Neck Cancer Recurrence: Diagnosis, Treatment and Prognosis)
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15 pages, 457 KiB  
Review
PET Radiomics and Response to Immunotherapy in Lung Cancer: A Systematic Review of the Literature
by Laura Evangelista, Francesco Fiz, Riccardo Laudicella, Francesco Bianconi, Angelo Castello, Priscilla Guglielmo, Virginia Liberini, Luigi Manco, Viviana Frantellizzi, Alessia Giordano, Luca Urso, Stefano Panareo, Barbara Palumbo and Luca Filippi
Cancers 2023, 15(12), 3258; https://doi.org/10.3390/cancers15123258 - 20 Jun 2023
Cited by 5 | Viewed by 1727
Abstract
The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy. Materials and Methods: A systematic review was conducted on databases [...] Read more.
The aim of this review is to provide a comprehensive overview of the existing literature concerning the applications of positron emission tomography (PET) radiomics in lung cancer patient candidates or those undergoing immunotherapy. Materials and Methods: A systematic review was conducted on databases and web sources. English-language original articles were considered. The title and abstract were independently reviewed to evaluate study inclusion. Duplicate, out-of-topic, and review papers, or editorials, articles, and letters to editors were excluded. For each study, the radiomics analysis was assessed based on the radiomics quality score (RQS 2.0). The review was registered on the PROSPERO database with the number CRD42023402302. Results: Fifteen papers were included, thirteen were qualified as using conventional radiomics approaches, and two used deep learning radiomics. The content of each study was different; indeed, seven papers investigated the potential ability of radiomics to predict PD-L1 expression and tumor microenvironment before starting immunotherapy. Moreover, two evaluated the prediction of response, and four investigated the utility of radiomics to predict the response to immunotherapy. Finally, two papers investigated the prediction of adverse events due to immunotherapy. Conclusions: Radiomics is promising for the evaluation of TME and for the prediction of response to immunotherapy, but some limitations should be overcome. Full article
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15 pages, 2019 KiB  
Article
Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma
by Risako Kohya, Goki Suda, Masatsugu Ohara, Takashi Sasaki, Tomoka Yoda, Naofumi Sakurai, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa and Naoya Sakamotoadd Show full author list remove Hide full author list
Cancers 2023, 15(12), 3257; https://doi.org/10.3390/cancers15123257 - 20 Jun 2023
Viewed by 1188
Abstract
Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib [...] Read more.
Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC. Full article
(This article belongs to the Section Cancer Biomarkers)
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15 pages, 7183 KiB  
Article
Spatial Distribution of Immune Cells in Primary and Recurrent Glioblastoma: A Small Case Study
by Delphine Loussouarn, Lisa Oliver, Celine Salaud, Edouard Samarut, Raphaël Bourgade, Christophe Béroud, Emilie Morenton, Dominique Heymann and Francois M. Vallette
Cancers 2023, 15(12), 3256; https://doi.org/10.3390/cancers15123256 - 20 Jun 2023
Cited by 3 | Viewed by 1418
Abstract
Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors [...] Read more.
Only a minority of patients with glioblastoma (GBM) respond to immunotherapy, and always only partially. There is a lack of knowledge on immune distribution in GBM and in its tumor microenvironment (TME). To address the question, we used paired primary and recurrent tumors from GBM patients to study the composition and the evolution of the immune landscape upon treatment. We studied the expression of a handful of immune markers (CD3, CD8, CD68, PD-L1 and PD-1) in GBM tissues in 15 paired primary and recurrent GBM. In five selected patients, we used Nanostring Digital Spatial Profiling (DSP) to obtain simultaneous assessments of multiple biomarkers both within the tumor and the microenvironment in paired primary and recurrent GBM. Our results suggest that the evolution of the immune landscape between paired primary and recurrent GBM tumors is highly heterogeneous. However, our study identifies B3-H7 and HLA-DR as potential targets in primary and recurrent GBM. Spatial profiling of immune markers from matched primary and recurrent GBM shows a nonlinear complex evolution during the progression of cancer. Nonetheless, our study demonstrated a global increase in macrophages, and revealed differential localization of some markers, such as B7-H3 and HLA-DR, between GBM and its TME. Full article
(This article belongs to the Special Issue The Role of Immune Cells in the Tumor Microenvironment)
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11 pages, 1260 KiB  
Article
Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases
by Camilo E. Fadul, Guneet Sarai, Joseph A. Bovi, Alissa A. Thomas, Wendy Novicoff, Roger Anderson, Ryan F. Amidon, Samantha Schuetz, Rohit Singh, Amy Chang, Ryan D. Gentzler, Elizabeth M. Gaughan and Jason P. Sheehan
Cancers 2023, 15(12), 3255; https://doi.org/10.3390/cancers15123255 - 20 Jun 2023
Cited by 2 | Viewed by 1690
Abstract
Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival [...] Read more.
Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan–Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases. Full article
(This article belongs to the Section Cancer Metastasis)
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21 pages, 5297 KiB  
Article
RNA Aptamer Targeting of Adam8 in Cancer Growth and Metastasis
by Zhiyong Mi, Marissa C. Kuo and Paul C. Kuo
Cancers 2023, 15(12), 3254; https://doi.org/10.3390/cancers15123254 - 20 Jun 2023
Viewed by 1082
Abstract
Cancer progression depends on an accumulation of metastasis-supporting physiological changes, which are regulated by cell-signaling molecules. In this regard, a disintegrin and metalloproteinase 8 (Adam8) is a transmembrane glycoprotein that is selectively expressed and induced by a variety of inflammatory stimuli. In this [...] Read more.
Cancer progression depends on an accumulation of metastasis-supporting physiological changes, which are regulated by cell-signaling molecules. In this regard, a disintegrin and metalloproteinase 8 (Adam8) is a transmembrane glycoprotein that is selectively expressed and induced by a variety of inflammatory stimuli. In this study, we identified Adam8 as a sox2-dependent protein expressed in MDA-MB-231 breast cancer cells when cocultured with mesenchymal-stem-cell-derived myofibroblast-like cancer-associated fibroblasts (myCAF). We have previously found that myCAF-induced cancer stemness is required for the maintenance of the myCAF phenotype, suggesting that the initiation and maintenance of the myCAF phenotype require distinct cell-signaling crosstalk pathways between cancer cells and myCAF. Adam8 was identified as a candidate secreted protein induced by myCAF-mediated cancer stemness. Adam8 has a known sheddase function against which we developed an RNA aptamer, namely, Adam8-Apt1-26nt. The Adam8-Apt1-26nt-mediated blockade of the extracellular soluble Adam8 metalloproteinase domain abolishes the previously initiated myCAF phenotype, or, termed differently, blocks the maintenance of the myCAF phenotype. Consequently, cancer stemness is significantly decreased. Xenograft models show that Adam8-Apt-1-26nt administration is associated with decreased tumor growth and metastasis, while flow cytometric analyses demonstrate a significantly decreased fraction of myCAF after Adam8-Apt-1-26nt treatment. The role of soluble Adam8 in the maintenance of the myCAF phenotype has not been previously characterized. Our study suggests that the signal pathways for the induction or initiation of the myCAF phenotype may be distinct from those involved with the maintenance of the myCAF phenotype. Full article
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12 pages, 570 KiB  
Article
Peripherally Inserted Central Venous Catheter (PICC) Related Bloodstream Infection in Cancer Patients Treated with Chemotherapy Compared with Noncancer Patients: A Propensity-Score-Matched Analysis
by Romaric Larcher, Koko Barrigah-Benissan, Jerome Ory, Claire Simon, Jean-Paul Beregi, Jean-Philippe Lavigne and Albert Sotto
Cancers 2023, 15(12), 3253; https://doi.org/10.3390/cancers15123253 - 20 Jun 2023
Cited by 1 | Viewed by 1840
Abstract
The use of peripherally inserted central catheters (PICCs) has increased in cancer patients. This study aimed to compare the incidence of PICC-related bloodstream infections (PICCR-BSIs) in cancer patients treated with chemotherapy and in noncancer patients. We performed a secondary analysis from a retrospective, [...] Read more.
The use of peripherally inserted central catheters (PICCs) has increased in cancer patients. This study aimed to compare the incidence of PICC-related bloodstream infections (PICCR-BSIs) in cancer patients treated with chemotherapy and in noncancer patients. We performed a secondary analysis from a retrospective, single-center, observational cohort. The PICCR-BSI incidence rates in cancer and noncancer patients were compared after 1:1 propensity-score matching. Then, the factors associated with PICCR-BSI were assessed in a Cox model. Among the 721 PICCs (627 patients) included in the analysis, 240 were placed in cancer patients for chemotherapy and 481 in noncancer patients. After propensity-score matching, the PICCR-BSI incidence rate was 2.6 per 1000 catheter days in cancer patients and 1.0 per 1000 catheter days in noncancer patients (p < 0.05). However, after adjusting for variables resulting in an imbalance between groups after propensity-score matching, only the number of PICC lumens was independently associated with PICCR-BSI (adjusted hazard ratio 1.81, 95% confidence interval: 1.01–3.22; p = 0.04). In conclusion, the incidence rate of PICCR-BSI is higher in cancer patients treated with chemotherapy than in noncancer patients, but our results also highlight the importance of limiting the number of PICC lumens in such patients. Full article
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12 pages, 2370 KiB  
Article
The Role of Native T1 and T2 Mapping Times in Identifying PD-L1 Expression and the Histological Subtype of NSCLCs
by Chandra Bortolotto, Gaia Messana, Antonio Lo Tito, Giulia Maria Stella, Alessandra Pinto, Chiara Podrecca, Riccardo Bellazzi, Alessia Gerbasi, Francesco Agustoni, Fei Han, Marcel Dominik Nickel, Domenico Zacà, Andrea Riccardo Filippi, Olivia Maria Bottinelli and Lorenzo Preda
Cancers 2023, 15(12), 3252; https://doi.org/10.3390/cancers15123252 - 20 Jun 2023
Viewed by 1374
Abstract
We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 [...] Read more.
We investigated the association of T1/T2 mapping values with programmed death-ligand 1 protein (PD-L1) expression in lung cancer and their potential in distinguishing between different histological subtypes of non-small cell lung cancers (NSCLCs). Thirty-five patients diagnosed with stage III NSCLC from April 2021 to December 2022 were included. Conventional MRI sequences were acquired with a 1.5 T system. Mean T1 and T2 mapping values were computed for six manually traced ROIs on different areas of the tumor. Data were analyzed through RStudio. Correlation between T1/T2 mapping values and PD-L1 expression was studied with a Wilcoxon–Mann–Whitney test. A Kruskal–Wallis test with a post-hoc Dunn test was used to study the correlation between T1/T2 mapping values and the histological subtypes: squamocellular carcinoma (SCC), adenocarcinoma (ADK), and poorly differentiated NSCLC (PD). There was no statistically significant correlation between T1/T2 mapping values and PD-L1 expression in NSCLC. We found statistically significant differences in T1 mapping values between ADK and SCC for the periphery ROI (p-value 0.004), the core ROI (p-value 0.01), and the whole tumor ROI (p-value 0.02). No differences were found concerning the PD NSCLCs. Full article
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9 pages, 249 KiB  
Opinion
DCVax-L Vaccination in Patients with Glioblastoma: Real Promise or Negative Trial? The Debate Is Open
by Lidia Gatto, Vincenzo Di Nunno, Alicia Tosoni, Stefania Bartolini, Lucia Ranieri and Enrico Franceschi
Cancers 2023, 15(12), 3251; https://doi.org/10.3390/cancers15123251 - 20 Jun 2023
Cited by 5 | Viewed by 2335
Abstract
The lack of significant improvement in the prognosis of patients with GB over the last decades highlights the need for innovative treatments aimed at fighting this malignancy and increasing survival outcomes. The results of the phase III clinical trial of DCVax-L (autologous tumor [...] Read more.
The lack of significant improvement in the prognosis of patients with GB over the last decades highlights the need for innovative treatments aimed at fighting this malignancy and increasing survival outcomes. The results of the phase III clinical trial of DCVax-L (autologous tumor lysate-loaded dendritic cell vaccination), which has been shown to increase both median survival and long-term survival in newly diagnosed and relapsed glioblastoma, have been enthusiastically received by the scientific community. However, this study deserves some reflections regarding methodological issues related to the primary endpoint change, the long accrual period, and the suboptimal validity of the external control population used as the comparison arm. Full article
(This article belongs to the Special Issue Rare Primary Brain Tumors in Adults)
13 pages, 2623 KiB  
Article
Genomic Mapping of Epidermal Growth Factor Receptor and Mesenchymal–Epithelial Transition-Up-Regulated Tumors Identifies Novel Therapeutic Opportunities
by Lucía Paniagua-Herranz, Bernard Doger, Cristina Díaz-Tejeiro, Adrián Sanvicente, Cristina Nieto-Jiménez, Víctor Moreno, Pedro Pérez Segura, Balazs Gyorffy, Emiliano Calvo and Alberto Ocana
Cancers 2023, 15(12), 3250; https://doi.org/10.3390/cancers15123250 - 20 Jun 2023
Viewed by 1404
Abstract
Background: The identification of proteins in the cellular membrane of the tumoral cell is a key to the design of therapeutic agents. Recently, the bi-specific antibody amivantamab, targeting the oncogenic membrane proteins EGFR and MET, received regulatory approval for the treatment of adult [...] Read more.
Background: The identification of proteins in the cellular membrane of the tumoral cell is a key to the design of therapeutic agents. Recently, the bi-specific antibody amivantamab, targeting the oncogenic membrane proteins EGFR and MET, received regulatory approval for the treatment of adult patients with locally advanced or metastatic NSCLC. Methods: The authors interrogated several publicly available genomic datasets to evaluate the expression of both receptors and PD-L1 in most of the solid and hematologic malignancies and focused on prostate adenocarcinoma (PRAD) and pancreatic adenocarcinoma (PAAD). Results: In PAAD, EGFR highly correlated with PD-L1 and MET, and MET showed a moderate correlation with PD-L1, while in PRAD, EGFR, MET and PD-L1 showed a strong correlation. In addition, in tumors treated with immune checkpoint inhibitors, including anti-PD(L)1 and anti-CTLA4, a high expression of EGFR and MET predicted detrimental survival. When exploring the relationship of immune populations with these receptors, the authors observed that in PAAD and PRAD, EGFR moderately correlated with CD8+ T cells. Furthermore, EGFR and MET correlated with neutrophils in PRAD. Conclusions: The authors identified tumor types where EGFR and MET were highly expressed and correlated with a high expression of PD-L1, opening the door for the future combination of bi-specific EGFR/MET antibodies with anti-PD(L)1 inhibitors. Full article
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9 pages, 577 KiB  
Article
A Comparison of Two Different FFPE Tissue Dissection Methods for Routine Diagnostics in Molecular Pathology: Manual Macrodissection versus Automated Microdissection Using the Roche “AVENIO Millisect” System
by Jan Jeroch, Tobias Riedlinger, Christina Schmitt, Silvana Ebner, Ria Winkelmann, Peter J. Wild and Melanie Demes
Cancers 2023, 15(12), 3249; https://doi.org/10.3390/cancers15123249 - 20 Jun 2023
Viewed by 1362
Abstract
Currently, in routine diagnostics, most molecular testing is performed on formalin-fixed, paraffin-embedded tissue after a histomorphological assessment. In order to find the best possible and targeted individual therapy, knowing the mutational status of the tumour is crucial. The “AVENIO Millisect” system Roche introduced [...] Read more.
Currently, in routine diagnostics, most molecular testing is performed on formalin-fixed, paraffin-embedded tissue after a histomorphological assessment. In order to find the best possible and targeted individual therapy, knowing the mutational status of the tumour is crucial. The “AVENIO Millisect” system Roche introduced an automation solution for the dissection of tissue on slides. This technology allows the precise and fully automated dissection of the tumour area without wasting limited and valuable patient material. In this study, the digitally guided microdissection was directly compared to the manual macrodissection regarding the precision and duration of the procedure, their DNA concentrations as well as DNA qualities, and the overall costs in 24 FFPE samples. In 21 of 24 cases (87.5%), the DNA yields of the manually dissected samples were higher in comparison to the automatically dissected samples. Shorter execution times and lower costs were also benefits of the manual scraping process. Nevertheless, the DNA quality achieved with both methods was comparable, which is essential for further molecular testing. Therefore, it could be used as an additional tool for precise tumour enrichment. Full article
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22 pages, 648 KiB  
Review
Targeted Therapies and Developing Precision Medicine in Gastric Cancer
by Rille Pihlak, Caroline Fong and Naureen Starling
Cancers 2023, 15(12), 3248; https://doi.org/10.3390/cancers15123248 - 19 Jun 2023
Cited by 6 | Viewed by 1758
Abstract
Gastric cancer is an aggressive disease with survival remaining poor in the advanced setting. More than a decade after the first targeted treatment was approved, still only HER2, MSI and PDL-1 status have reached everyday practice in terms of guiding treatment options for [...] Read more.
Gastric cancer is an aggressive disease with survival remaining poor in the advanced setting. More than a decade after the first targeted treatment was approved, still only HER2, MSI and PDL-1 status have reached everyday practice in terms of guiding treatment options for these patients. However, various new targets and novel treatments have recently been investigated and have shown promise in improving survival outcomes. In this review, we will summarise previous and currently ongoing studies on predictive biomarkers, possible new targeted treatments, potential reasons for conflicting trial results and hope for the future of precision medicine in gastric cancer. Full article
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12 pages, 1033 KiB  
Review
RUNX Family as a Promising Biomarker and a Therapeutic Target in Bone Cancers: A Review on Its Molecular Mechanism(s) behind Tumorigenesis
by Selvaraj Vimalraj and Saravanan Sekaran
Cancers 2023, 15(12), 3247; https://doi.org/10.3390/cancers15123247 - 19 Jun 2023
Cited by 3 | Viewed by 1505
Abstract
The transcription factor runt-related protein (RUNX) family is the major transcription factor responsible for the formation of osteoblasts from bone marrow mesenchymal stem cells, which are involved in bone formation. Accumulating evidence implicates the RUNX family for its role in tumor biology and [...] Read more.
The transcription factor runt-related protein (RUNX) family is the major transcription factor responsible for the formation of osteoblasts from bone marrow mesenchymal stem cells, which are involved in bone formation. Accumulating evidence implicates the RUNX family for its role in tumor biology and cancer progression. The RUNX family has been linked to osteosarcoma via its regulation of many tumorigenicity-related factors. In the regulatory network of cancers, with numerous upstream signaling pathways and its potential target molecules downstream, RUNX is a vital molecule. Hence, a pressing need exists to understand the precise process underpinning the occurrence and prognosis of several malignant tumors. Until recently, RUNX has been regarded as one of the therapeutic targets for bone cancer. Therefore, in this review, we have provided insights into various molecular mechanisms behind the tumorigenic role of RUNX in various important cancers. RUNX is anticipated to grow into a novel therapeutic target with the in-depth study of RUNX family-related regulatory processes, aid in the creation of new medications, and enhance clinical efficacy. Full article
(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)
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23 pages, 4433 KiB  
Article
A Clinical Risk Model for Personalized Screening and Prevention of Breast Cancer
by Mikael Eriksson, Kamila Czene, Celine Vachon, Emily F. Conant and Per Hall
Cancers 2023, 15(12), 3246; https://doi.org/10.3390/cancers15123246 - 19 Jun 2023
Cited by 3 | Viewed by 1649
Abstract
Background: Image-derived artificial intelligence (AI) risk models have shown promise in identifying high-risk women in the short term. The long-term performance of image-derived risk models expanded with clinical factors has not been investigated. Methods: We performed a case–cohort study of 8110 women aged [...] Read more.
Background: Image-derived artificial intelligence (AI) risk models have shown promise in identifying high-risk women in the short term. The long-term performance of image-derived risk models expanded with clinical factors has not been investigated. Methods: We performed a case–cohort study of 8110 women aged 40–74 randomly selected from a Swedish mammography screening cohort initiated in 2010 together with 1661 incident BCs diagnosed before January 2022. The imaging-only AI risk model extracted mammographic features and age at screening. Additional lifestyle/familial risk factors were incorporated into the lifestyle/familial-expanded AI model. Absolute risks were calculated using the two models and the clinical Tyrer–Cuzick v8 model. Age-adjusted model performances were compared across the 10-year follow-up. Results: The AUCs of the lifestyle/familial-expanded AI risk model ranged from 0.75 (95%CI: 0.70–0.80) to 0.68 (95%CI: 0.66–0.69) 1–10 years after study entry. Corresponding AUCs were 0.72 (95%CI: 0.66–0.78) to 0.65 (95%CI: 0.63–0.66) for the imaging-only model and 0.62 (95%CI: 0.55–0.68) to 0.60 (95%CI: 0.58–0.61) for Tyrer–Cuzick v8. The increased performances were observed in multiple risk subgroups and cancer subtypes. Among the 5% of women at highest risk, the PPV was 5.8% using the lifestyle/familial-expanded model compared with 5.3% using the imaging-only model, p < 0.01, and 4.6% for Tyrer–Cuzick, p < 0.01. Conclusions: The lifestyle/familial-expanded AI risk model showed higher performance for both long-term and short-term risk assessment compared with imaging-only and Tyrer–Cuzick models. Full article
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17 pages, 1070 KiB  
Review
Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches
by Sara Salucci, Beatrice Aramini, Anna Bartoletti-Stella, Ilaria Versari, Giovanni Martinelli, William Blalock, Franco Stella and Irene Faenza
Cancers 2023, 15(12), 3245; https://doi.org/10.3390/cancers15123245 - 19 Jun 2023
Viewed by 1863
Abstract
Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due [...] Read more.
Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC. Full article
(This article belongs to the Special Issue Prognostic Biomarkers of Lung Cancer)
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10 pages, 277 KiB  
Article
Enhanced Recovery after Surgery and Endometrial Cancers: Results from an Initial Experience Focused on Elderly Patients
by Céline Miguet, Camille Jauffret, Christophe Zemmour, Jean-Marie Boher, Laura Sabiani, Gilles Houvenaeghel, Guillaume Blache, Clément Brun and Eric Lambaudie
Cancers 2023, 15(12), 3244; https://doi.org/10.3390/cancers15123244 - 19 Jun 2023
Viewed by 893
Abstract
Endometrial cancer is the fifth most common cancer among French women and occurs most frequently in the over-70-year-old population. Recent years have seen a significant shift towards minimally invasive surgery and Enhanced Recovery After Surgery (ERAS) protocols in endometrial cancer management. However, the [...] Read more.
Endometrial cancer is the fifth most common cancer among French women and occurs most frequently in the over-70-year-old population. Recent years have seen a significant shift towards minimally invasive surgery and Enhanced Recovery After Surgery (ERAS) protocols in endometrial cancer management. However, the impact of ERAS on endometrial cancer has not been well-established. We conducted a prospective observational study in a comprehensive cancer center, comparing the outcomes between endometrial cancer patients who received care in an ERAS pathway (261) and those who did not (166) between 2006 and 2020. We performed univariate and multivariate analysis. Our primary objective was to evaluate the impact of ERAS on length of hospital stay (LOS), with the secondary objectives being the determination of the rates of early discharge, post-operative morbidity, and rehospitalization. We found that patients in the ERAS group had a significantly shorter length of stay, with an average of 3.18 days compared to 4.87 days for the non-ERAS group (estimated decrease −1.69, p < 0.0001). This effect was particularly pronounced among patients over 70 years old (estimated decrease −2.06, p < 0.0001). The patients in the ERAS group also had a higher chance of early discharge (47.5% vs. 14.5% in the non-ERAS group, p < 0.0001), for which there was not a significant increase in post-operative complications. Our study suggests that ERAS protocols are beneficial for the management of endometrial cancer, particularly for older patients, and could lead to the development of ambulatory pathways. Full article
15 pages, 2635 KiB  
Article
Relationship between Accurate Diagnosis of Sarcopenia and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab Combination Therapy
by Kyoko Oura, Asahiro Morishita, Takushi Manabe, Kei Takuma, Mai Nakahara, Tomoko Tadokoro, Koji Fujita, Shima Mimura, Joji Tani, Masafumi Ono, Chikara Ogawa, Akio Moriya, Tomonori Senoo, Akemi Tsutsui, Takuya Nagano, Koichi Takaguchi, Takashi Himoto and Tsutomu Masaki
Cancers 2023, 15(12), 3243; https://doi.org/10.3390/cancers15123243 - 19 Jun 2023
Cited by 3 | Viewed by 1263
Abstract
Although there have been advances in the prevention and diagnosis of hepatocellular carcinoma (HCC) in recent years, many HCC patients are still diagnosed with advanced stage. Systemic therapy is indicated for unresectable HCC (uHCC) with major vascular invasion and/or extrahepatic metastases, and the [...] Read more.
Although there have been advances in the prevention and diagnosis of hepatocellular carcinoma (HCC) in recent years, many HCC patients are still diagnosed with advanced stage. Systemic therapy is indicated for unresectable HCC (uHCC) with major vascular invasion and/or extrahepatic metastases, and the atezolizumab plus bevacizumab (atezo/bev) combination is currently recommended as first-line treatment for uHCC. Recently, sarcopenia-related factors, including decreased skeletal muscle index (SMI), have been reportedly associated with prognosis in uHCC patients treated with sorafenib or lenvatinib. There are few reports on muscle strength assessments, including grip strength (GS), despite their importance in accurate sarcopenia diagnosis, and furthermore, there is no evidence regarding atezo/bev therapy. In this study, we investigated whether sarcopenia affects the clinical outcome of atezo/bev therapy. This study included 64 uHCC patients on atezo/bev therapy and assessed their GS and SMI, and SMI was measured using bioelectrical impedance analysis (BIA). We diagnosed sarcopenia based on GS and BIA-SMI and compared the clinical outcomes in the sarcopenia and non-sarcopenia groups. Of these patients, 28 had sarcopenia, and 36 had non-sarcopenia. Adverse events (AEs) frequently occurred, and the albumin-bilirubin score significantly decreased after atezo/bev therapy in the sarcopenia group than in the non-sarcopenia group. The median progression-free survival was 4.7 (0.4–26.4) and 10.6 (1.1–24.5) months in the sarcopenia and non-sarcopenia groups, respectively. The median overall survival (OS) was 12.6 (1.4–27.7) months in the sarcopenia group and was not reached in the non-sarcopenia group, indicating a significant difference in the Kaplan-Meier survival curves for both groups (p < 0.01). In multivariate analysis, sarcopenia was significantly associated with OS. In conclusion, sarcopenia was significantly associated with poor clinical outcomes based on the occurrence of AEs and decreased liver function in uHCC patients on atezo/bev therapy. GS and SMI are important parameters for accurately diagnosing sarcopenia. Full article
(This article belongs to the Section Cancer Therapy)
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24 pages, 2251 KiB  
Article
Serum Metabolite Biomarkers for Pancreatic Tumors: Neuroendocrine and Pancreatic Ductal Adenocarcinomas—A Preliminary Study
by Karolina Skubisz, Krzysztof Dąbkowski, Emilia Samborowska, Teresa Starzyńska, Anna Deskur, Filip Ambrozkiewicz, Jakub Karczmarski, Mariusz Radkiewicz, Katarzyna Kusnierz, Beata Kos-Kudła, Tadeusz Sulikowski, Patrycja Cybula and Agnieszka Paziewska
Cancers 2023, 15(12), 3242; https://doi.org/10.3390/cancers15123242 - 19 Jun 2023
Cited by 2 | Viewed by 1638
Abstract
Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal [...] Read more.
Background: Pancreatic cancer is the most common pancreatic solid malignancy with an aggressive clinical course and low survival rate. There are a limited number of reliable prognostic biomarkers and a need to understand the pathogenesis of pancreatic tumors; neuroendocrine (PNET) and pancreatic ductal adenocarcinomas (PDAC) encouraged us to analyze the serum metabolome of pancreatic tumors and disturbances in the metabolism of PDAC and PNET. Methods: Using the AbsoluteIDQ® p180 kit (Biocrates Life Sciences AG, Innsbruck, Austria) with liquid chromatography–mass spectrometry (LC-MS), we identified changes in metabolite profiles and disrupted metabolic pathways serum of NET and PDAC patients. Results: The concentration of six metabolites showed statistically significant differences between the control group and PDAC patients (p.adj < 0.05). Glutamine (Gln), acetylcarnitine (C2), and citrulline (Cit) presented a lower concentration in the serum of PDAC patients, while phosphatidylcholine aa C32:0 (PC aa C32:0), sphingomyelin C26:1 (SM C26:1), and glutamic acid (Glu) achieved higher concentrations compared to serum samples from healthy individuals. Five of the tested metabolites: C2 (FC = 8.67), and serotonin (FC = 2.68) reached higher concentration values in the PNET serum samples compared to PDAC, while phosphatidylcholine aa C34:1 (PC aa C34:1) (FC = −1.46 (0.68)) had a higher concentration in the PDAC samples. The area under the curves (AUC) of the receiver operating characteristic (ROC) curves presented diagnostic power to discriminate pancreatic tumor patients, which were highest for acylcarnitines: C2 with AUC = 0.93, serotonin with AUC = 0.85, and PC aa C34:1 with AUC = 0.86. Conclusions: The observations presented provide better insight into the metabolism of pancreatic tumors, and improve the diagnosis and classification of tumors. Serum-circulating metabolites can be easily monitored without invasive procedures and show the present clinical patients’ condition, helping with pharmacological treatment or dietary strategies. Full article
(This article belongs to the Special Issue Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment)
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19 pages, 3025 KiB  
Review
LIN28B and Let-7 in Diffuse Midline Glioma: A Review
by Truman Knowles, Tina Huang, Jin Qi, Shejuan An, Noah Burket, Scott Cooper, Javad Nazarian and Amanda M. Saratsis
Cancers 2023, 15(12), 3241; https://doi.org/10.3390/cancers15123241 - 19 Jun 2023
Cited by 5 | Viewed by 1905
Abstract
Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. DMGs are driven by histone-tail-mutation-mediated epigenetic dysregulation and partner mutations in genes controlling proliferation and migration. One result of this epigenetic and genetic landscape is the overexpression of LIN28B RNA binding [...] Read more.
Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. DMGs are driven by histone-tail-mutation-mediated epigenetic dysregulation and partner mutations in genes controlling proliferation and migration. One result of this epigenetic and genetic landscape is the overexpression of LIN28B RNA binding protein. In other systems, LIN28B has been shown to prevent let-7 microRNA biogenesis; however, let-7, when available, faithfully suppresses tumorigenic pathways and induces cellular maturation by preventing the translation of numerous oncogenes. Here, we review the current literature on LIN28A/B and the let-7 family and describe their role in gliomagenesis. Future research is then recommended, with a focus on the mechanisms of LIN28B overexpression and localization in DMG. Full article
(This article belongs to the Section Molecular Cancer Biology)
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20 pages, 2371 KiB  
Review
Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors
by Rebecca Leah Benhaghnazar and Lali Medina-Kauwe
Cancers 2023, 15(12), 3240; https://doi.org/10.3390/cancers15123240 - 19 Jun 2023
Viewed by 1669
Abstract
Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic [...] Read more.
Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic drivers. Delivery of biological therapeutics into tumor cells requires a robust system of cell penetration to access therapeutic targets within the cell interior. A highly effective means of accomplishing this may be borrowed from cell-penetrating pathogens such as viruses. In particular, the cell entry function of the adenovirus penton base capsid protein has been effective at penetrating tumor cells for the intracellular deposition of macromolecular therapies and membrane-impermeable drugs. Here, we provide an overview describing the evolution of tumor-targeted penton-base-derived nano-capsids as a framework for discussing the requirements for overcoming key barriers to macromolecular delivery. The development and pre-clinical testing of these proteins for therapeutic delivery has begun to also uncover the elusive mechanism underlying the membrane-penetrating function of the penton base. An understanding of this mechanism may unlock the potential for macromolecular therapeutics to be effectively delivered into cancer cells and to provide a treatment option for tumors resisting current clinical therapies. Full article
(This article belongs to the Section Cancer Therapy)
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10 pages, 785 KiB  
Article
Full-Dose Intraoperative Electron Radiotherapy for Early Breast Cancer: Evidence from a Single Center’s Experience
by Antonio Stefanelli, Eleonora Farina, Edoardo Mastella, Sara Fabbri, Alessandro Turra, Simona Bonazza, Alessandro De Troia, Margherita K. Radica and Paolo Carcoforo
Cancers 2023, 15(12), 3239; https://doi.org/10.3390/cancers15123239 - 19 Jun 2023
Cited by 1 | Viewed by 1061
Abstract
To evaluate the clinical response rate and cosmetic outcome after full-dose intraoperative electron radiotherapy (IOERT) in early breast cancer (BC) treated with conserving surgery. Inclusion criteria were: >60 years old, clinical tumor size ≤2 cm, luminal A carcinoma, patological negative lymph nodes, excluded [...] Read more.
To evaluate the clinical response rate and cosmetic outcome after full-dose intraoperative electron radiotherapy (IOERT) in early breast cancer (BC) treated with conserving surgery. Inclusion criteria were: >60 years old, clinical tumor size ≤2 cm, luminal A carcinoma, patological negative lymph nodes, excluded lobular carcinoma histology. IOERT was delivered with a dose of 21 Gy at 90% isodose. Clinical, cosmetic and/or instrumental follow-up were performed 45 days after IOERT, 6 months after the first check, and every 12 months thereafter. Acute and late toxicities were assessed with the CTCAE v.4.03 and EORTC-RTOG scales, respectively. Cosmetic outcome was evaluated using the Harvard/NSABO/RTOG Breast Cosmesis Grading Scale. Overall, 162 consecutive patients were included in this analysis (median follow-up: 54 months, range: 1–98 months). The overall response rate was 97.5% (CI 95%: 0.93–0.99%). Locoragional relapse occurred in 2.5% of patients. No patient showed distant metastases. No patient showed radiation-related acute complications, with 3.7% showing late G2–3 toxicity. Only 3.7% of patients showed poor cosmetic results. Our data confirmed that IOERT is a feasible and valid therapeutic option in low-risk BC patients treated with lumpectomy. A low local recurrence rate combined with good cosmetic results validates the settings of our operative method in routinely clinical practice. Full article
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20 pages, 24290 KiB  
Article
Identification, and Experimental and Bioinformatics Validation of an Immune-Related Prognosis Gene Signature for Low-Grade Glioma Based on mRNAsi
by Yuan Wang, Shengda Ye, Du Wu, Ziyue Xu, Wei Wei, Faliang Duan and Ming Luo
Cancers 2023, 15(12), 3238; https://doi.org/10.3390/cancers15123238 - 19 Jun 2023
Viewed by 1249
Abstract
Background: Low-grade gliomas (LGGs), which are the second most common intracranial tumor, are diagnosed in seven out of one million people, tending to develop in younger people. Tumor stem cells and immune cells are important in the development of tumorigenesis. However, research on [...] Read more.
Background: Low-grade gliomas (LGGs), which are the second most common intracranial tumor, are diagnosed in seven out of one million people, tending to develop in younger people. Tumor stem cells and immune cells are important in the development of tumorigenesis. However, research on prognostic factors linked to the immune microenvironment and stem cells in LGG patients is limited. We critically need accurate related tools for assessing the risk of LGG patients. Methods: In this study, we aimed to identify immune-related genes (IRGs) in LGG based on the mRNAsi score. We employed differentially expressed gene (DEG) methods and weighted correlation network analysis (WGCNA). The risk signature was then further established using a lasso Cox regression analysis and a multivariate Cox analysis. Next, we used immunohistochemical sections (HPA) and a survival analysis to identify the hub genes. A nomogram was built to assess the prognosis of patients based on their clinical information and risk scores and was validated using a DCA curve, among other methods. Results: Four hub genes were obtained: C3AR1 (HR = 0.98, p < 0.001), MSR1 (HR = 1.02, p < 0.001), SLC11A1 (HR = 1.01, p < 0.01), and IL-10 (HR = 1.01, p < 0.001). For LGG patients, we created an immune-related prognostic signature (IPS) based on mRNAsi for estimating risk scores; different risk groups showed significantly different survival rates (p = 3.3 × 10−16). Then, via an evaluation of the IRG-related signature, we created a nomogram for predicting LGG survival probability. Conclusion: The outcome suggests that, when predicting the prognosis of LGG patients, our nomogram was more effective than the IPS. In this study, four immune-related predictive biomarkers for LGG were identified and proven to be IRGs. Therefore, the development of efficient immunotherapy techniques can be facilitated by the creation of the IPS. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and the Management of Intracranial Tumors)
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26 pages, 5208 KiB  
Article
Identification of Novel Diagnostic and Prognostic Gene Signature Biomarkers for Breast Cancer Using Artificial Intelligence and Machine Learning Assisted Transcriptomics Analysis
by Zeenat Mirza, Md Shahid Ansari, Md Shahid Iqbal, Nesar Ahmad, Nofe Alganmi, Haneen Banjar, Mohammed H. Al-Qahtani and Sajjad Karim
Cancers 2023, 15(12), 3237; https://doi.org/10.3390/cancers15123237 - 18 Jun 2023
Cited by 4 | Viewed by 3468
Abstract
Background: Breast cancer (BC) is one of the most common female cancers. Clinical and histopathological information is collectively used for diagnosis, but is often not precise. We applied machine learning (ML) methods to identify the valuable gene signature model based on differentially expressed [...] Read more.
Background: Breast cancer (BC) is one of the most common female cancers. Clinical and histopathological information is collectively used for diagnosis, but is often not precise. We applied machine learning (ML) methods to identify the valuable gene signature model based on differentially expressed genes (DEGs) for BC diagnosis and prognosis. Methods: A cohort of 701 samples from 11 GEO BC microarray datasets was used for the identification of significant DEGs. Seven ML methods, including RFECV-LR, RFECV-SVM, LR-L1, SVC-L1, RF, and Extra-Trees were applied for gene reduction and the construction of a diagnostic model for cancer classification. Kaplan–Meier survival analysis was performed for prognostic signature construction. The potential biomarkers were confirmed via qRT-PCR and validated by another set of ML methods including GBDT, XGBoost, AdaBoost, KNN, and MLP. Results: We identified 355 DEGs and predicted BC-associated pathways, including kinetochore metaphase signaling, PTEN, senescence, and phagosome-formation pathways. A hub of 28 DEGs and a novel diagnostic nine-gene signature (COL10A, S100P, ADAMTS5, WISP1, COMP, CXCL10, LYVE1, COL11A1, and INHBA) were identified using stringent filter conditions. Similarly, a novel prognostic model consisting of eight-gene signatures (CCNE2, NUSAP1, TPX2, S100P, ITM2A, LIFR, TNXA, and ZBTB16) was also identified using disease-free survival and overall survival analysis. Gene signatures were validated by another set of ML methods. Finally, qRT-PCR results confirmed the expression of the identified gene signatures in BC. Conclusion: The ML approach helped construct novel diagnostic and prognostic models based on the expression profiling of BC. The identified nine-gene signature and eight-gene signatures showed excellent potential in BC diagnosis and prognosis, respectively. Full article
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14 pages, 6790 KiB  
Article
Drug-Eluting Embolic Loaded with Tyrosine Kinase Inhibitor Targeted Therapies for Transarterial Chemoembolization in a VX2 Model
by Nadine Abi-Jaoudeh, Ben Sadeghi, Hanna Javan, Jim Na, Graham Beaton, Fabio Tucci, Satheesh Ravula and David K. Imagawa
Cancers 2023, 15(12), 3236; https://doi.org/10.3390/cancers15123236 - 18 Jun 2023
Cited by 1 | Viewed by 1425
Abstract
Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, [...] Read more.
Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation. Full article
(This article belongs to the Special Issue Translational Research of Liver Cancer)
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17 pages, 1878 KiB  
Review
Role of Therapeutic Endoscopic Ultrasound in Management of Pancreatic Cancer: An Endoscopic Oncologist Perspective
by Dushyant Singh Dahiya, Saurabh Chandan, Hassam Ali, Bhanu Siva Mohan Pinnam, Manesh Kumar Gangwani, Hashem Al Bunni, Andrew Canakis, Harishankar Gopakumar, Ishaan Vohra, Jay Bapaye, Mohammad Al-Haddad and Neil R. Sharma
Cancers 2023, 15(12), 3235; https://doi.org/10.3390/cancers15123235 - 18 Jun 2023
Viewed by 2377
Abstract
Pancreatic cancer is a highly lethal disease with an aggressive clinical course. Patients with pancreatic cancer are usually asymptomatic until significant progression of their disease. Additionally, there are no effective screening guidelines for pancreatic cancer in the general population. This leads to a [...] Read more.
Pancreatic cancer is a highly lethal disease with an aggressive clinical course. Patients with pancreatic cancer are usually asymptomatic until significant progression of their disease. Additionally, there are no effective screening guidelines for pancreatic cancer in the general population. This leads to a delay in diagnosis and treatment, resulting in poor clinical outcomes and low survival rates. Endoscopic Ultrasound (EUS) is an indispensable tool for the diagnosis and staging of pancreatic cancer. In the modern era, with exponential advancements in technology and device innovation, EUS is also being increasingly used in a variety of therapeutic interventions. In the context of pancreatic cancer where therapies are limited due to the advanced stage of the disease at diagnosis, EUS-guided interventions offer new and innovative options. Moreover, due to their minimally invasive nature and ability to provide real-time images for tumor localization and therapy, they are associated with fewer complication rates compared to conventional open and laparoscopic approaches. In this article, we detail the most current and important therapeutic applications of EUS for pancreatic cancer, namely EUS-guided Fine Needle Injections, EUS-guided Radiotherapy, and EUS-guided Ablations. Furthermore, we also discuss the feasibility and safety profile of each intervention in patients with pancreatic cancer to provide gastrointestinal medical oncologists, radiation and surgical oncologists, and therapeutic endoscopists with valuable information to facilitate patient discussions and aid in the complex decision-making process. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment of Pancreatic Cancer)
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