Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
The Prognostic Value of the Systemic Immune-Inflammation Index (SII) and Red Cell Distribution Width (RDW) in Patients with Cervical Cancer Treated Using Radiotherapy
Cancers 2024, 16(8), 1542; https://doi.org/10.3390/cancers16081542 (registering DOI) - 18 Apr 2024
Abstract
Introduction: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the red cell distribution width (RDW) or systemic immune-inflammation index (SII), with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices
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Introduction: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the red cell distribution width (RDW) or systemic immune-inflammation index (SII), with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and overall survival (OS) in patients treated with radiotherapy for primary localised cervical cancer. Material and Methods: This retrospective analysis included patients treated with definitive chemoradiation therapy (CRT) between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan–Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the Akaike Information Criterion (AIC) serving as a prediction error estimator. Results: The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237, 95.2%) and had FIGO stage III (211, 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32–3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. Conclusions: The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation.
Full article
(This article belongs to the Special Issue Clinical Management and Prognosis of Gynecological Cancer)
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The Prevalence of Orthostatic Hypotension in Cancer Patients
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Mateusz A. Iwański, Aldona Sokołowska, Andrzej Sokołowski, Roman Wojdyła and Katarzyna Styczkiewicz
Cancers 2024, 16(8), 1541; https://doi.org/10.3390/cancers16081541 (registering DOI) - 18 Apr 2024
Abstract
Background: Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This study aimed to assess the prevalence of OH in cancer patients compared to that in the
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Background: Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This study aimed to assess the prevalence of OH in cancer patients compared to that in the noncancer population. Methods: A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer (n = 223) and patients hospitalised for other reasons, but without a cancer diagnosis (n = 188). Medical histories were collected and an orthostatic challenge test was performed. OH was defined as a blood pressure (BP) decrease upon standing of ≥20 mmHg for the systolic or ≥10 mmHg for the diastolic BP after 1 or 3 min; or a systolic BP decrease <90 mmHg. Results: The prevalence of OH in the subjects with cancer was significantly higher than in the subjects without cancer (28.7% vs. 16.5%, respectively, p = 0.003). OH was the most common in the lung cancer patients (57.5%). In a single-variable analysis, the predictors of OH were cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m2. In the multivariable model, the strongest independent predictor of OH was cancer status, which doubled the risk of OH, and BMI ≥ 30 kg/m2 and diabetes. Conclusions: Cancer patients are characterised by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.
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(This article belongs to the Special Issue Correlating Patient-Reported Quality of Life before, during, and after Therapy with Objective Measures and Outcomes)
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Open AccessArticle
BUB1 Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Inhibiting Ferroptosis
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Weiming Wang, Xiang Zhou, Lingming Kong, Zhenyan Pan and Gang Chen
Cancers 2024, 16(8), 1540; https://doi.org/10.3390/cancers16081540 (registering DOI) - 18 Apr 2024
Abstract
The development of chemotherapy resistance severely limits the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC), and the dysregulation of ferroptosis is a crucial factor in the development of chemotherapy resistance. BUB1 Mitotic Checkpoint Serine/Threonine Kinase (BUB1) is highly overexpressed in PC
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The development of chemotherapy resistance severely limits the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer (PC), and the dysregulation of ferroptosis is a crucial factor in the development of chemotherapy resistance. BUB1 Mitotic Checkpoint Serine/Threonine Kinase (BUB1) is highly overexpressed in PC patients and is closely associated with patient prognosis. However, none of the literature reports the connection between BUB1 and ferroptosis. The molecular mechanisms underlying GEM resistance are also not well understood. Therefore, this study first established the high expression levels of BUB1 in PC patients, then explored the role of BUB1 in the process of ferroptosis, and finally investigated the mechanisms by which BUB1 regulates ferroptosis and contributes to GEM resistance in PC cells. In this study, downregulation of BUB1 enhanced the sensitivity of PC cells to Erastin, and inhibited cell proliferation and migration. Mechanistically, BUB1 could inhibit the expression levels of Neurofibromin 2 (NF2) and MOB kinase activator 1 (MOB1), and promote Yes-associated protein (YAP) expression, thereby inhibiting ferroptosis and promoting GEM resistance in PC cells. Furthermore, the combination of BUB1 inhibition with GEM exhibited a synergistic therapeutic effect. These findings reveal the mechanisms underlying the development of GEM chemotherapy resistance based on ferroptosis and suggest that the combined use of BUB1 inhibitors may be an effective approach to enhance GEM efficacy.
Full article
(This article belongs to the Section Cancer Drug Development)
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Surgical Outcomes after Radiotherapy in Rectal Cancer
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Sofieke J. D. Temmink, Koen C. M. J. Peeters, Per J. Nilsson, Anna Martling and Cornelis J. H. van de Velde
Cancers 2024, 16(8), 1539; https://doi.org/10.3390/cancers16081539 (registering DOI) - 18 Apr 2024
Abstract
Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative
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Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.
Full article
(This article belongs to the Special Issue Advance in Colorectal Cancer: A Themed Issue in Honor of Prof. Bengt Glimelius)
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From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist’s Dual Role in Prostate Cancer
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Abdulrahman Alhajahjeh, Raad Al-Faouri, Hisham F. Bahmad, Taima’ Bader, Ryan W. Dobbs, Ahmed A. Abdulelah, Wassim Abou-Kheir, Elai Davicioni, David I. Lee and Mohammed Shahait
Cancers 2024, 16(8), 1538; https://doi.org/10.3390/cancers16081538 (registering DOI) - 18 Apr 2024
Abstract
Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential
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Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management.
Full article
(This article belongs to the Special Issue New Insights in Molecular Pathology of Cancers: From Biomarkers to Therapeutic Targets)
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Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma
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Joon Hyuk Choi and Swan N. Thung
Cancers 2024, 16(8), 1537; https://doi.org/10.3390/cancers16081537 (registering DOI) - 17 Apr 2024
Abstract
Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified
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Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: the small-duct type and large-duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes—inflammation and proliferation—have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.
Full article
(This article belongs to the Special Issue Current Epidemiologic, Diagnostic, and Therapeutic Aspects of Cholangiocarcinoma (CCA))
Open AccessArticle
The Vanishing Clinical Value of PD-L1 Status as a Predictive Biomarker in the First-Line Treatment of Urothelial Carcinoma of the Bladder
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Alexander Tamalunas, Can Aydogdu, Lena M. Unterrainer, Melanie Schott, Severin Rodler, Stephan Ledderose, Gerald B. Schulz, Christian G. Stief and Jozefina Casuscelli
Cancers 2024, 16(8), 1536; https://doi.org/10.3390/cancers16081536 (registering DOI) - 17 Apr 2024
Abstract
Background: Our study endeavors to elucidate the clinical implications of PD-L1 positivity in individuals afflicted with advanced urothelial carcinoma of the bladder (UCB). Methods: Patients with advanced UCB were prospectively enrolled following a radical cystectomy (RC) performed within January 2017 to December 2022
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Background: Our study endeavors to elucidate the clinical implications of PD-L1 positivity in individuals afflicted with advanced urothelial carcinoma of the bladder (UCB). Methods: Patients with advanced UCB were prospectively enrolled following a radical cystectomy (RC) performed within January 2017 to December 2022 at our tertiary referral center. The clinical outcome, defined as the progression-free survival (PFS) and overall survival (OS) on systemic treatment, was analyzed using an χ2-test, Mann–Whitney U-test, the Kaplan–Meier method, and a log-rank test. Results: A total of 648 patients were included following an RC performed within January 2017 to December 2022. Their PD-L1 status was analyzed with the primary PD-L1-specific antibody (clone SP263, Ventana) and defined both by the CPS and IC-score in 282 patients (43.5%) with a high risk (pT3–pT4 and/or lymph node involvement) or metastatic UCB. While the median PFS was significantly prolonged 5-fold in PD-L1+ patients, we found no difference in OS, regardless of PD-L1 status, or treatment regimen. Conclusions: While PD-L1 positivity indicates prolonged PFS, the presence of PD-L1 does not influence OS rates, suggesting its limited usefulness as a prognostic biomarker in bladder cancer. However, the positive correlation between an PD-L1 status and a sustained response to ICI treatments indicates its potential role as a predictive biomarker. Further research is required to understand how the predictive value of PD-L1 positivity may extend to the use of ICIs in combination with antibody-drug conjugates.
Full article
(This article belongs to the Special Issue Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors)
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Multiparametric Characterization of the DSL-6A/C1 Pancreatic Cancer Model in Rats
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Patrick Schmidt, Johannes Lindemeyer, Pranali Raut, Markus Schütz, Sven Saniternik, Jannika Jönsson, Heike Endepols, Thomas Fischer, Alexander Quaas, Hans Anton Schlößer, Martin Thelen and Holger Grüll
Cancers 2024, 16(8), 1535; https://doi.org/10.3390/cancers16081535 - 17 Apr 2024
Abstract
The DSL-6A/C1 murine pancreatic ductal adenocarcinoma (PDAC) tumor model was established in Lewis rats and characterized through a comprehensive multiparametric analysis to compare it to other preclinical tumor models and explore potential diagnostic and therapeutical targets. DSL-6A/C1 tumors were histologically analyzed to elucidate
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The DSL-6A/C1 murine pancreatic ductal adenocarcinoma (PDAC) tumor model was established in Lewis rats and characterized through a comprehensive multiparametric analysis to compare it to other preclinical tumor models and explore potential diagnostic and therapeutical targets. DSL-6A/C1 tumors were histologically analyzed to elucidate PDAC features. The tumor microenvironment was studied for immune cell prevalence. Multiparametric MRI and PET imaging were utilized to characterize tumors, and 68Ga-FAPI-46-targeting cancer-associated fibroblasts (CAFs), were used to validate the histological findings. The histology confirmed typical PDAC characteristics, such as malformed pancreatic ductal malignant cells and CAFs. Distinct immune landscapes were identified, revealing an increased presence of CD8+ T cells and a decreased CD4+ T cell fraction within the tumor microenvironment. PET imaging with 68Ga-FAPI tracers exhibited strong tracer uptake in tumor tissues. The MRI parameters indicated increasing intralesional necrosis over time and elevated contrast media uptake in vital tumor areas. We have demonstrated that the DSL-6A/C1 tumor model, particularly due to its high tumorigenicity, tumor size, and 68Ga-FAPI-46 sensitivity, is a suitable alternative to established small animal models for many forms of preclinical analyses and therapeutic studies of PDAC.
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(This article belongs to the Section Cancer Pathophysiology)
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A Prospective Study on Deep Inspiration Breath Hold Thoracic Radiation Therapy Guided by Bronchoscopically Implanted Electromagnetic Transponders
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Yuzhong Jeff Meng, Nikhil P. Mankuzhy, Mohit Chawla, Robert P. Lee, Ellen D. Yorke, Zhigang Zhang, Emily Gelb, Seng Boh Lim, John J. Cuaron, Abraham J. Wu, Charles B. Simone II, Daphna Y. Gelblum, Dale Michael Lovelock, Wendy Harris and Andreas Rimner
Cancers 2024, 16(8), 1534; https://doi.org/10.3390/cancers16081534 (registering DOI) - 17 Apr 2024
Abstract
Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung
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Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study. Methods: We enrolled patients with primary lung cancer or lung metastases. Three transponders were implanted near the tumor, followed by simulation with DIBH, free breathing, and 4D-CT as backup. The initial gating window for treatment was ±5 mm; in a second cohort, the window was incrementally reduced to determine the smallest feasible gating window. The primary endpoint was feasibility, defined as completion of RT using transponder-guided DIBH. Patients were followed for assessment of transponder- and RT-related toxicity. Results: We enrolled 48 patients (35 with primary lung cancer and 13 with lung metastases). The median distance of transponders to tumor was 1.6 cm (IQR 0.6–2.8 cm). RT delivery ranged from 3 to 35 fractions. Transponder-guided DIBH was feasible in all but two patients (96% feasible), where it failed because the distance between the transponders and the antenna was >19 cm. Among the remaining 46 patients, 6 were treated prone to keep the transponders within 19 cm of the antenna, and 40 were treated supine. The smallest feasible gating window was identified as ±3 mm. Thirty-nine (85%) patients completed one year of follow-up. Toxicities at least possibly related to transponders or the implantation procedure were grade 2 in six patients (six incidences, cough and hemoptysis), grade 3 in three patients (five incidences, cough, dyspnea, pneumonia, and supraventricular tachycardia), and grade 4 pneumonia in one patient (occurring a few days after implantation but recovered fully and completed RT). Toxicities at least possibly related to RT were grade 2 in 18 patients (41 incidences, most commonly cough, fatigue, and pneumonitis) and grade 3 in four patients (seven incidences, most commonly pneumonia), and no patients had grade 4 or higher toxicity. Conclusions: Bronchoscopically implanted electromagnetic transponder–guided DIBH lung RT is feasible and safe, allowing for precise tumor targeting and reduced normal tissue exposure. Transponder–antenna distance was the most common challenge due to a limited antenna range, which could sometimes be circumvented by prone positioning.
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(This article belongs to the Special Issue Advances in Modern Radiation Oncology)
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Understanding the Role of Connexins in Hepatocellular Carcinoma: Molecular and Prognostic Implications
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Stavros P. Papadakos, Elena Chatzikalil, Konstantinos Arvanitakis, Georgios Vakadaris, Ioanna E. Stergiou, Maria-Loukia Koutsompina, Alexandra Argyrou, Vasileios Lekakis, Ippokratis Konstantinidis, Georgios Germanidis and Stamatios Theocharis
Cancers 2024, 16(8), 1533; https://doi.org/10.3390/cancers16081533 (registering DOI) - 17 Apr 2024
Abstract
Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent
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Connexins, a family of tetraspan membrane proteins forming intercellular channels localized in gap junctions, play a pivotal role at the different stages of tumor progression presenting both pro- and anti-tumorigenic effects. Considering the potential role of connexins as tumor suppressors through multiple channel-independent mechanisms, their loss of expression may be associated with tumorigenic activity, while it is hypothesized that connexins favor the clonal expansion of tumor cells and promote cell migration, invasion, and proliferation, affecting metastasis and chemoresistance in some cases. Hepatocellular carcinoma (HCC), characterized by unfavorable prognosis and limited responsiveness to current therapeutic strategies, has been linked to gap junction proteins as tumorigenic factors with prognostic value. Notably, several members of connexins have emerged as promising markers for assessing the progression and aggressiveness of HCC, as well as the chemosensitivity and radiosensitivity of hepatocellular tumor cells. Our review sheds light on the multifaceted role of connexins in HCC pathogenesis, offering valuable insights on recent advances in determining their prognostic and therapeutic potential.
Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Advances and Challenges in Research and Treatment)
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Lysine Methyltransferase 9 (KMT9) Is an Actionable Target in Muscle-Invasive Bladder Cancer
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Sainab Totonji, Anna Ramos-Triguero, Dominica Willmann, Manuela Sum, Sylvia Urban, Helena Bauer, Astrid Rieder, Sheng Wang, Holger Greschik, Eric Metzger and Roland Schüle
Cancers 2024, 16(8), 1532; https://doi.org/10.3390/cancers16081532 (registering DOI) - 17 Apr 2024
Abstract
Novel treatment modalities are imperative for the challenging management of muscle-invasive and metastatic BC to improve patient survival rates. The recently identified KMT9, an obligate heterodimer composed of KMT9α and KMT9β, regulates the growth of various types of tumors such as prostate, lung,
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Novel treatment modalities are imperative for the challenging management of muscle-invasive and metastatic BC to improve patient survival rates. The recently identified KMT9, an obligate heterodimer composed of KMT9α and KMT9β, regulates the growth of various types of tumors such as prostate, lung, and colon cancer. While the overexpression of KMT9α was previously observed to be associated with aggressive basal-like MIBC in an analysis of patients’ tissue samples, a potential functional role of KMT9 in this type of cancer has not been investigated to date. In this study, we show that KMT9 regulates proliferation, migration, and invasion of various MIBC cell lines with different genetic mutations. KMT9α depletion results in the differential expression of genes regulating the cell cycle, cell adhesion, and migration. Differentially expressed genes include oncogenes such as EGFR and AKT1 as well as mediators of cell adhesion or migration such as DAG1 and ITGA6. Reduced cell proliferation upon KMT9α depletion is also observed in Pten/Trp53 knockout bladder tumor organoids, which cannot be rescued with an enzymatically inactive KMT9α mutant. In accordance with the idea that the catalytic activity of KMT9 is required for the control of cellular processes in MIBC, a recently developed small-molecule inhibitor of KMT9 (KMI169) also impairs cancer cell proliferation. Since KMT9α depletion also restricts the growth of xenografts in mice, our data suggest that KMT9 is an actionable novel therapeutic target for the treatment of MIBC.
Full article
(This article belongs to the Special Issue Advances in Genetics and Epigenetics of Bladder Cancer)
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The Role of Ion Channels and Chemokines in Cancer Growth and Metastasis: A Proposed Mode of Action using Peptides in Cancer Therapy
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Gerald J. Mizejewski
Cancers 2024, 16(8), 1531; https://doi.org/10.3390/cancers16081531 - 17 Apr 2024
Abstract
Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint.
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Metastasis (Met) largely contributes to the major cause of cancer deaths throughout the world, rather than the growth of the tumor mass itself. The present report brings together several of the pertinent contributors to cancer growth and metastatic processes from an activity standpoint. Such biological activities include the following: (1) cell adherence and detachment; (2) cell-to-cell contact; (3) contact inhibition; (4) the cell interfacing with the extracellular matrix (ECM); (5) tumor cell-to-stroma communication networks; (6) chemotaxis; and (7) cell membrane potential. Moreover, additional biochemical factors that contribute to cancer growth and metastasis have been shown to comprise the following: (a) calcium levels in the extracellular matrix and in intracellular compartments; (b) cation voltage and ATP-regulated potassium channels; (c) selective and non-selective cation channels; and (d) chemokines (cytokines) and their receptors, such as CXCL12 (SDF-1) and its receptor/binding partner, CXCR4. These latter molecular components represent a promising group of an interacting and synchronized set of candidates ideal for peptide therapeutic targeting for cancer growth and metastasis. Such peptides can be obtained from naturally occurring proteins such as alpha-fetoprotein (AFP), an onco-fetal protein and clinical biomarker.
Full article
(This article belongs to the Special Issue Factors Regulating Cancer Cell Growth, Migration, Invasion, and Apoptosis)
Open AccessReview
Colorectal Cancer: Epidemiology, Risk Factors, and Prevention
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Gholamreza Roshandel, Fatemeh Ghasemi-Kebria and Reza Malekzadeh
Cancers 2024, 16(8), 1530; https://doi.org/10.3390/cancers16081530 - 17 Apr 2024
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related
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Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.
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(This article belongs to the Special Issue Colorectal Cancer: Epidemiology and Prevention)
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Drug Cost Avoidance Resulting from Participation in Clinical Trials: A 10-Year Retrospective Analysis of Cancer Patients with Solid Tumors
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Maria-Josep Carreras, Berta Renedo-Miró, Carolina Valdivia, Elena Tomás-Guillén, Anna Farriols, Laura Mañós, Jana Vidal, María Alcalde, Isabel De la Paz, Inés Jiménez-Lozano, Maria-Eugenia Palacio-Lacambra, Nuria Sabaté, Enriqueta Felip, Elena Garralda, Margarita Garau, Maria-Queralt Gorgas, Josep Monterde and Josep Tabernero
Cancers 2024, 16(8), 1529; https://doi.org/10.3390/cancers16081529 - 17 Apr 2024
Abstract
The objective of this single-center retrospective study was to describe the clinical characteristics of adult patients with solid tumors enrolled in cancer clinical trials over a 10-year period (2010–2019) and to assess drug cost avoidance (DCA) associated with sponsors’ contributions. The sponsors’ contribution
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The objective of this single-center retrospective study was to describe the clinical characteristics of adult patients with solid tumors enrolled in cancer clinical trials over a 10-year period (2010–2019) and to assess drug cost avoidance (DCA) associated with sponsors’ contributions. The sponsors’ contribution to pharmaceutical expenditure was calculated according to the actual price (for each year) of pharmaceutical specialties that the Vall d’Hebron University Hospital (HUVH) would have had to bear in the absence of sponsorship. A total of 2930 clinical trials were conducted with 10,488 participants. There were 140 trials in 2010 and 459 in 2019 (228% increase). Clinical trials of high complexity phase I and basket trials accounted for 34.3% of all trials. There has been a large variation in the pattern of clinical research over the study period, whereas, in 2010, targeted therapy accounted for 79.4% of expenditure and cytotoxic drugs for 20.6%; in 2019, immunotherapy accounted for 68.4%, targeted therapy for 24.4%, and cytotoxic drugs for only 7.1%. A total of four hundred twenty-one different antineoplastic agents were used, the variability of which increased from forty-seven agents in 2010, with only seven of them accounting for 92.8% of the overall pharmaceutical expenditure) to three hundred seventeen different antineoplastic agents in 2019, with thirty-three of them accounting for 90.6% of the overall expenditure. The overall expenditure on antineoplastic drugs in clinical care patients not included in clinical trials was EUR 120,396,096. The total cost of antineoplastic drugs supplied by sponsors in a clinical trial setting was EUR 107,306,084, with a potential DCA of EUR 92,662,609. Overall, clinical trials provide not only the best context for the progress of clinical research and healthcare but also create opportunities for reducing cancer care costs.
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(This article belongs to the Special Issue Advances in Cancer Data and Statistics)
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Perioperative and Oncological Outcomes of Percutaneous Radiofrequency Ablation versus Partial Nephrectomy for cT1a Renal Cancers: A Retrospective Study on Groups with Similar Clinical Characteristics
by
Milosz Jasinski, Przemyslaw Wisniewski, Marta Bielinska, Jerzy Siekiera, Krzysztof Kamecki and Maciej Salagierski
Cancers 2024, 16(8), 1528; https://doi.org/10.3390/cancers16081528 - 17 Apr 2024
Abstract
Over the recent years, progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is
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Over the recent years, progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the results of US-guided percutaneous radiofrequency ablation (RFA) and partial nephrectomy (PN) in the treatment of cT1a renal cancers. Between August 2016 and February 2022, 271 patients with renal tumours underwent percutaneous RFA as initial treatment in our institution. In the same period, 396 patients with renal tumours underwent surgical tumour excision. For the purpose of this study, only patients with confirmed renal cancer with matched age and tumour characteristics (size, location) were selected for both groups. Thus, a group of 44 PN patients and 41 RFA patients were formed with the same qualification criteria for both groups. Parameters such as procedure length, blood loss, hospital stay, analgesics used, and pre- and post-procedural serum creatinine were compared between these groups. Patients followed up with contrast-enhanced CT. There was no significant difference in age, tumour size, tumour location, and creatinine levels between these groups. All procedures were generally well tolerated. During a median follow-up of 28 months, two cases of recurrence/residual disease were found in each group. The overall survival was 100% in both groups, and all patients were disease-free at the end of observation. Percutaneous RFA was associated with a significantly shorter procedure length and hospital stay, lower blood loss, and lower analgesics used than PN. In the selected group of renal cancer patients, US-guided percutaneous RFA was associated with a shorter hospital stay, less analgesics used, and a shorter procedure length than PN, without differences in the oncological results or kidney function.
Full article
(This article belongs to the Special Issue Optimizing Surgical Procedures and Outcomes in Renal Cancer)
Open AccessArticle
Perioperative Evaluation of the Physical Quality of Life of Patients with Non-Small Cell Lung Cancer: A Prospective Study
by
Ryuta Fukai, Tomoki Nishida, Hideyasu Sugimoto, Makoto Hibino, Shigeto Horiuchi, Tetsuri Kondo, Shinichi Teshima, Masahiro Hirata, Keiko Asou, Etsuko Shimizu, Yuichi Saito and Yukinori Sakao
Cancers 2024, 16(8), 1527; https://doi.org/10.3390/cancers16081527 - 17 Apr 2024
Abstract
Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality
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Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), −9.37 (−13.43–−5.32) and −10.22 (−13.74–−7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1–2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), −4.90 (−8.78–1.0), p = 0.014), lower performance status (8.90 (5.10–12.70), p < 0.0001), living alone (5.76 (1.39–10.13), p = 0.01), and higher comorbid burden (−6.94 (−11.78–−2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery.
Full article
(This article belongs to the Special Issue The Role of Surgery in Thoracic Cancers (Volume II))
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Open AccessArticle
A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer
by
Nicola Mosca, Mariaceleste Pezzullo, Ilenia De Leo, Anna Truda, Giovanna Marchese, Aniello Russo and Nicoletta Potenza
Cancers 2024, 16(8), 1526; https://doi.org/10.3390/cancers16081526 - 17 Apr 2024
Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Non-coding RNAs are emerging as critical players for the onset and progression of cancer. Analyses of three different datasets revealed that the lncRNA JPX was overexpressed in adenocarcinoma tissues in comparison to normal
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Lung cancer is the leading cause of cancer-related death worldwide. Non-coding RNAs are emerging as critical players for the onset and progression of cancer. Analyses of three different datasets revealed that the lncRNA JPX was overexpressed in adenocarcinoma tissues in comparison to normal lungs, as expected for an oncogene. Intriguingly, the predicted binding miR-378a-3p showed a significant inverse correlation with JPX expression. The lncRNA/miRNA physical interaction was validated by reporter vectors. Then, the oncogenic activity of JPX, the tumor-suppressive role of miR-378a-3p, and the contribution of their functional interaction to cancer hallmarks were demonstrated using assays for cell proliferation, migration, invasion, and 3D-spheroid formation. Finally, molecular circuits were investigated by boosting the expression of both JPX and miR-378a-3p, singularly and in combination, demonstrating that JPX counteracted miR-378a-3p silencing activity toward its oncogenic targets GLUT1, NRP1, YY1, and Wnt5a. Overall, the data unveil a novel ceRNET (competing endogenous RNA network), wherein JPX acts as a ceRNA by binding to miR-378a-3p, thus reducing the miRNA silencing activity toward its downstream targets, and eliciting oncogenic pathways driving lung cancer. The knowledge of the network may pave the way to develop new diagnostic panels, and innovative RNA-targeted and RNA-based therapeutic strategies.
Full article
(This article belongs to the Special Issue RNA in Non-Small-Cell Lung Cancer)
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Open AccessArticle
Dichloroacetate and Quercetin Prevent Cell Proliferation, Induce Cell Death and Slow Tumor Growth in a Mouse Model of HPV-Positive Head and Neck Cancer
by
Yongxian Zhuang, Joseph D. Coppock, Allison B. Haugrud, John H. Lee, Shanta M. Messerli and W. Keith Miskimins
Cancers 2024, 16(8), 1525; https://doi.org/10.3390/cancers16081525 - 17 Apr 2024
Abstract
Elevated glucose uptake and production of lactate are common features of cancer cells. Among many tumor-promoting effects, lactate inhibits immune responses and is positively correlated with radioresistance. Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase that decreases lactate production. Quercetin is a
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Elevated glucose uptake and production of lactate are common features of cancer cells. Among many tumor-promoting effects, lactate inhibits immune responses and is positively correlated with radioresistance. Dichloroacetate (DCA) is an inhibitor of pyruvate dehydrogenase kinase that decreases lactate production. Quercetin is a flavonoid compound found in fruits and vegetables that inhibits glucose uptake and lactate export. We investigated the potential role and mechanisms of DCA, quercetin, and their combination, in the treatment of HPV-positive head and neck squamous cell carcinoma, an antigenic cancer subtype in need of efficacious adjuvant therapies. C57Bl/6-derived mouse oropharyngeal epithelial cells, a previously developed mouse model that was retrovirally transduced with HPV type-16 E6/E7 and activated Ras, were used to assess these compounds. Both DCA and quercetin inhibited colony formation and reduced cell viability, which were associated with mTOR inhibition and increased apoptosis through enhanced ROS production. DCA and quercetin reduced tumor growth and enhanced survival in immune-competent mice, correlating with decreased proliferation as well as decreased acidification of the tumor microenvironment and reduction of Foxp (+) Treg lymphocytes. Collectively, these data support the possible clinical application of DCA and quercetin as adjuvant therapies for head and neck cancer patients.
Full article
(This article belongs to the Special Issue Chemoprevention Advances in Cancer)
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Automatic Brain Tissue and Lesion Segmentation and Multi-Parametric Mapping of Contrast-Enhancing Gliomas without the Injection of Contrast Agents: A Preliminary Study
by
Jing Liu, Angela Jakary, Javier E. Villanueva-Meyer, Nicholas A. Butowski, David Saloner, Jennifer L. Clarke, Jennie W. Taylor, Nancy Ann Oberheim Bush, Susan M. Chang, Duan Xu and Janine M. Lupo
Cancers 2024, 16(8), 1524; https://doi.org/10.3390/cancers16081524 - 17 Apr 2024
Abstract
This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6
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This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6 min scan. Modified k-means clustering was performed for automatic brain tissue and lesion segmentation using distinct signal evolutions that contained mixed T1/T2/magnetization transfer properties. Multi-compartment modeling was used to derive quantitative multi-parametric maps for tissue characterization. Fourteen patients with contrast-enhancing gliomas were scanned with this sequence prior to the injection of a contrast agent, and their segmented lesions were compared to conventionally defined manual segmentations of T2-hyperintense and contrast-enhancing lesions. Simultaneous T1, T2, and macromolecular proton fraction maps were generated and compared to conventional 2D T1 and T2 mapping and myelination water fraction mapping acquired with MAGiC. The lesion volumes defined with the new method were comparable to the manual segmentations (r = 0.70, p < 0.01; t-test p > 0.05). The T1, T2, and macromolecular proton fraction mapping values of the whole brain were comparable to the reference values and could distinguish different brain tissues and lesion types (p < 0.05), including infiltrating tumor regions within the T2-lesion. Highly efficient, whole-brain, multi-contrast imaging facilitated automatic lesion segmentation and quantitative multi-parametric mapping without contrast, highlighting its potential value in the clinic when gadolinium is contraindicated.
Full article
(This article belongs to the Special Issue Magnetic Resonance Imaging of Brain Tumor)
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Head and Neck Paragangliomas: Overview of Institutional Experience
by
Swar N. Vimawala, Alex Z. Graboyes, Bonita Bennett, Maria Bonanni, Aleena Abbasi, Tanaya Oliphant, Michelle Alonso-Basanta, Christopher Rassekh, Debbie Cohen, Jason A. Brant and Yonghong Huan
Cancers 2024, 16(8), 1523; https://doi.org/10.3390/cancers16081523 - 16 Apr 2024
Abstract
Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with
[...] Read more.
Head and neck paragangliomas (HNPGLs) are rare and have high rates of genetic mutations. We conducted a retrospective review of 187 patients with 296 PGLs diagnosed between 1974 and 2023. The mean age of diagnosis was 48.8 years (range 10 to 82) with 69.0% female and 26.5% patients with multiple PGLs. Among 119 patients undergoing genetic testing, 70 (58.8%) patients had mutations, with SDHB (30) and SDHD (26) being the most common. The rates of metastasis and recurrence were higher among patients with SHDB mutations or SDHD mutations associated with multiple PGLs. Metabolic evaluation showed elevated plasma dopamine levels were the most common derangements in HNPGL. MRI and CT were the most common anatomic imaging modalities and DOTATATE was the most common functional scan used in this cohort. Most patients (81.5%) received surgery as the primary definitive treatment, while 22.5% patients received radiation treatment, mostly as an adjuvant therapy or for surgically challenging or inoperable cases. Systemic treatment was rarely used in our cohort. Our single-center experience highlights the need for referral for genetic testing and metabolic evaluation and for a team-based approach to improve the clinical outcomes of patients with HNPGLs.
Full article
(This article belongs to the Special Issue Update on the Management of Head & Neck Paragangliomas: Papers from the First International Congress, Piacenza, Italy September 20–22, 2023)
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