Next Issue
Volume 16, November-1
Previous Issue
Volume 16, October-1
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.0
4.5
Journals
Cancers
Volume 16
Issue 20
share announcement

Cancers, Volume 16, Issue 20 (October-2 2024) – 123 articles

Cover Story (view full-size image): Tumors of the central nervous system (CNS) are complex and challenging to treat. This review highlights the importance of the epigenetic marker H3K27me3—the trimethylation of lysine 27 on histone H3—in CNS tumors. H3K27me3 regulates gene expression and chromatin structure. Reduced gene expression levels, often due to mutations like H3F3A and HIST1H3B, are linked to aggressive brain tumors, such as diffuse midline glioma and posterior fossa ependymomas. The loss of H3K27me3 in meningiomas predicts worse outcomes, especially in grade 2 cases. Ultimately, research into H3K27me3 is vital for improving CNS tumor diagnostics, treatment, and personalized medicine. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
11 pages, 2070 KiB  
Article
Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer
by Xiaobo Zhang, Bo Han and Danhua Shen
Cancers 2024, 16(20), 3555; https://doi.org/10.3390/cancers16203555 - 21 Oct 2024
Viewed by 826
Abstract
Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and [...] Read more.
Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People’s Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number—low (CNL), microsatellite instability—high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes. Full article
(This article belongs to the Special Issue Biomarkers for Treatment Prediction, Prognosis and Early Detection of Gynecologic Cancer)
►▼ Show Figures

Figure 1

2 pages, 565 KiB  
Correction
Correction: Becker et al. Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response. Cancers 2023, 15, 5597
by Anne-Sophie Becker, Cornelius Kluge, Carsten Schofeld, Annette Helene Zimpfer, Björn Schneider, Daniel Strüder, Caterina Redwanz, Julika Ribbat-Idel, Christian Idel and Claudia Maletzki
Cancers 2024, 16(20), 3554; https://doi.org/10.3390/cancers16203554 - 21 Oct 2024
Viewed by 471
Abstract
In the original publication [...] Full article
►▼ Show Figures

Figure 3

17 pages, 5439 KiB  
Article
Impact of the Immune Landscape in Follicular Lymphoma: Insights into Histological Transformation in the Rituximab Era
by Marie Hairing Enemark, Maja Lund Jensen, Maja Dam Andersen, Trine Lindhardt Plesner, Stephen Hamilton-Dutoit and Maja Ludvigsen
Cancers 2024, 16(20), 3553; https://doi.org/10.3390/cancers16203553 - 21 Oct 2024
Viewed by 787
Abstract
Background: Follicular lymphoma (FL) presents significant clinical heterogeneity, with some patients experiencing transformation into an aggressive disease, a key contributor to FL-related mortality. Based on gene expression profiles, this study aimed to provide insights into immunological differences associated with transformation. Methods: Gene expression [...] Read more.
Background: Follicular lymphoma (FL) presents significant clinical heterogeneity, with some patients experiencing transformation into an aggressive disease, a key contributor to FL-related mortality. Based on gene expression profiles, this study aimed to provide insights into immunological differences associated with transformation. Methods: Gene expression analysis using the NanoString nCounter Tumor Signaling 360 Panel was performed on diagnostic lymphoma samples from 70 FL patients diagnosed in the rituximab era, either non-transforming FL (nt-FL, n = 34) or subsequently transforming FL (st-FL, n = 36), with paired high-grade transformed FL (tFL, n = 36) samples available. In silico immunophenotyping was performed to infer immune cell infiltration using the CIBERSORTx algorithm. Results: The gene expression analysis revealed 164 significantly differentially expressed genes, distinguishing st-FL from nt-FL and generally presenting an upregulation of B cell-related genes (CD40, IRF4, RELB), immunosuppressive molecules (IL10, SOCS3), and immune checkpoint molecules (CD276, TIM3). Analysis of immune cell proportions indicated significant differences in infiltrates of M1-like macrophages (p = 0.007) and neutrophils (p = 0.012) in nt-FL versus st-FL samples. Transformation-free survival (TFS) was associated with high numbers of both these cellular subsets (p = 0.006 and 0 = 0.002, respectively). This was even more evident when combined with inferior TFS in lymphomas with high infiltrates of both cell types (p < 0.001). After transformation, tFL samples showed a reduction in T follicular helper cells (p = 0.008) and an increase in immunosuppressive M2-like macrophages and neutrophils (p < 0.001 and p = 0.028, respectively). Conclusion: By elucidating the distinct molecular and immune landscapes of FL at the time of diagnosis and transformation, this study underscores the importance of immune microenvironment in FL transformation and patient outcome. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
►▼ Show Figures

Figure 1

13 pages, 1090 KiB  
Article
Introduction of an Educational Video to Enhance the Informed Consent Process in Postoperative Radiation Therapy of Breast Cancer Patients
by Samuel M. Vorbach, Martin Pointner, Jens Lehmann, Julian Mangesius, Tilmann Hart, Claudia Gstir, Theresa Rändler, Thomas Seppi, Ute Ganswindt and Siegfried Kollotzek
Cancers 2024, 16(20), 3552; https://doi.org/10.3390/cancers16203552 - 21 Oct 2024
Viewed by 628
Abstract
Background/Objectives: Informed consent is crucial in medical practice, especially for complex treatments such as postoperative radiotherapy for patients with breast cancer. Conventional consent procedures are often based on verbal declarations with a highly condensed but nevertheless large amount of information, which can exceed [...] Read more.
Background/Objectives: Informed consent is crucial in medical practice, especially for complex treatments such as postoperative radiotherapy for patients with breast cancer. Conventional consent procedures are often based on verbal declarations with a highly condensed but nevertheless large amount of information, which can exceed the recording capacity of patients and lead to misunderstandings. The aim of this study was to develop and test an educational video on breast cancer patients to enhance the informed consent process by improving patients’ understanding and reducing the duration of the subsequent consultation. Methods: The educational video was created after the underlying content was determined by a modified Delphi method in which a panellist of radiation oncologists, nurses, radiation therapists, and former patients participated in successive rounds of topic scoring. After achieving content consent, the video included 19 items to cover key aspects of postoperative radiotherapy in a patient-friendly manner. Fifty breast cancer patients scheduled for postoperative radiotherapy were randomised to watch the video prior to their verbal consultation (n = 25) or to the control group participating in the traditional informed consent process only (n = 25). The duration of the informed consent processes in both arms was recorded. To assess the educational effect of the video, a multiple-choice test was created. In addition, patients’ satisfaction was recorded using a separate questionnaire. Both questionnaires were completed by the patients one to two hours after signing the consent form. Results: The patients in the video group evidenced significantly higher knowledge scores than those who received standard verbal explanations (median number of correct answers 9 vs. 8 out of 10, p = 0.0039). The whole informed consent process was also completed faster in the video group (mean duration 34.7 vs. 46.2 min, p < 0.001). Median satisfaction scores were high in both groups (34 vs. 33 out of 35 points), with no significant differences observed (p > 0.05). Conclusion: The educational video effectively improved patient understanding and streamlined the informed consent process without compromising patients’ satisfaction. This approach also helps to standardise the delivery of complex medical information, and it can also be adapted to improve the informed consent process for other cancer treatments. Full article
(This article belongs to the Special Issue Digital Health Technologies in Oncology)
►▼ Show Figures

Figure 1

16 pages, 4264 KiB  
Systematic Review
Stereotactic Radiosurgery for Intracranial Breast Metastases: A Systematic Review and Meta-Analysis
by Neil D. Almeida, Cathleen Kuo, Tyler V. Schrand, Julia Rupp, Venkatesh S. Madhugiri, Victor Goulenko, Rohil Shekher, Chirag Shah and Dheerendra Prasad
Cancers 2024, 16(20), 3551; https://doi.org/10.3390/cancers16203551 - 21 Oct 2024
Viewed by 782
Abstract
Background/Objectives: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. Methods: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes [...] Read more.
Background/Objectives: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. Methods: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes of stereotactic radiosurgery on intracranial metastases from breast cancer were included. Adverse events were defined as leptomeningeal disease, radiation necrosis, seizure, and headache. The pooled estimate was calculated using the DerSimonian and Laird approach. Results: Sixteen studies encompassing 1228 patients met the inclusion criteria. Our analysis revealed a median survival duration of 13.1 ± 3.8 months and a pooled 1-year overall survival rate of 53.1% after SRS treatment. There was a 29% local recurrence rate at 1 year and a 35% overall distant recurrence rate. In addition, our analysis found a relatively low rate of acute adverse events at 15.5%. Conclusions: SRS demonstrates promising efficacy and safety in managing intracranial metastases from breast cancer, with a favorable toxicity profile. Full article
(This article belongs to the Special Issue Breast Cancer Brain Metastasis and Leptomeningeal Disease)
►▼ Show Figures

Figure 1

11 pages, 1876 KiB  
Article
Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection
by Katsuji Sawai, Takanori Goi, Youhei Kimura and Kenji Koneri
Cancers 2024, 16(20), 3550; https://doi.org/10.3390/cancers16203550 - 21 Oct 2024
Viewed by 572
Abstract
Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a [...] Read more.
Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
►▼ Show Figures

Figure 1

16 pages, 2552 KiB  
Article
The Neoangiogenic Transcriptomic Signature Impacts Hepatocellular Carcinoma Prognosis and Can Be Triggered by Transarterial Chemoembolization Treatment
by Rosina Maria Critelli, Federico Casari, Alberto Borghi, Grazia Serino, Cristian Caporali, Paolo Magistri, Annarita Pecchi, Endrit Shahini, Fabiola Milosa, Lorenza Di Marco, Alessandra Pivetti, Simone Lasagni, Filippo Schepis, Nicola De Maria, Francesco Dituri, María Luz Martínez-Chantar, Fabrizio Di Benedetto, Gianluigi Giannelli and Erica Villa
Cancers 2024, 16(20), 3549; https://doi.org/10.3390/cancers16203549 - 21 Oct 2024
Viewed by 677
Abstract
Background/Objectives: We evaluated the relationship between the neoangiogenic transcriptomic signature (nTS) and clinical symptoms, treatment outcomes, and survival in hepatocellular carcinoma (HCC) patients. Methods: This study prospectively followed 328 patients in the derivation and 256 in the validation cohort (with a [...] Read more.
Background/Objectives: We evaluated the relationship between the neoangiogenic transcriptomic signature (nTS) and clinical symptoms, treatment outcomes, and survival in hepatocellular carcinoma (HCC) patients. Methods: This study prospectively followed 328 patients in the derivation and 256 in the validation cohort (with a median follow-up of 31 and 22 months, respectively). The nTS was associated with disease presentation, treatments administered, and overall survival rates. Additionally, this study investigated how multiple treatments influenced changes in nTS status and alterations in microRNA expression. Results: The nTS was identified in 27.4% of patients, linked to aggressive features like multifocality and elevated alpha-fetoprotein (AFP), a pattern consistent with that of the validation cohort. Most patients in both cohorts received treatment for HCC. nTS+ patients had limited access to, and benefited less from, liver transplantation or radiofrequency ablation (RFA) compared to nTS− patients. By the end, 78.9% had died, with nTS− patients showing better median survival and response to treatments than their nTS+ counterparts, who had lower survival across all treatment types. Among those who received transarterial chemoembolization (TACE), 31.2% (21/80 patients after the initial treatment and another four following a second TACE) transitioned from an nTS− to an nTS+ status. This shift was associated with lower survival and alterations in microRNA expressions related to oncogenic pathways. Conclusions: The nTS markedly influences treatment eligibility and survival in patients with HCC. Notably, the nTS can develop after repeated TACE procedures, significantly impacting patient survival and altering oncogenic microRNA expression patterns. These findings highlight the critical role of the nTS in guiding treatment decisions and prognostication in HCC management. Full article
(This article belongs to the Section Cancer Therapy)
►▼ Show Figures

Figure 1

19 pages, 3801 KiB  
Review
Optimizing Niclosamide for Cancer Therapy: Improving Bioavailability via Structural Modification and Nanotechnology
by Russell Wiggins, Jihoo Woo and Shizue Mito
Cancers 2024, 16(20), 3548; https://doi.org/10.3390/cancers16203548 - 21 Oct 2024
Viewed by 939
Abstract
Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical [...] Read more.
Inhibition of multiple cancer-related pathways has made niclosamide a promising candidate for the treatment of various cancers. However, its clinical application has been significantly limited by poor bioavailability. This review will discuss current findings on improving niclosamide bioavailability through modification of its chemical structure and utilization of novel nanotechnologies, like electrospraying and supercritical fluids, to improve drug delivery. For example, niclosamide derivatives, such as o-alkylamino-tethered niclosamide derivates, niclosamide ethanolamine salt, and niclosamide piperazine salt, have demonstrated increased water solubility without compromising anticancer activity in vitro. Additionally, this review briefly discusses recent findings on the first pass metabolism of niclosamide in vivo, the role of cytochrome P450-mediated hydroxylation, UDP-glucuronosyltransferase mediated glucuronidation, and how enzymatic inhibition could enhance niclosamide bioavailability. Ultimately, there is a need for researchers to synthesize, evaluate, and improve upon niclosamide derivatives while experimenting with the employment of nanotechnologies, such as targeted delivery and nanoparticle modification, as a way to improve drug administration. Researchers should strive to improve drug-target accuracy, its therapeutic index, and increase the drug’s efficacy as an anti-neoplastic agent. Full article
►▼ Show Figures

Figure 1

22 pages, 1227 KiB  
Review
Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications—A Literature Review
by Mengjiao Wu, Chenjun Tian, Zhenwei Zou, Min Jin and Hongli Liu
Cancers 2024, 16(20), 3547; https://doi.org/10.3390/cancers16203547 - 21 Oct 2024
Viewed by 1338
Abstract
Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation [...] Read more.
Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy. Full article
(This article belongs to the Section Molecular Cancer Biology)
►▼ Show Figures

Figure 1

18 pages, 3742 KiB  
Article
Comparative Study of Cutaneous Squamous Cell Carcinogenesis in Different Hairless Murine Models
by Georgios Gkikas, Dimitrios Katsiris, Andreas Vitsos, Anna Gioran, Dimitra Ieronymaki, Maria Kostaki, Georgios Ladopoulos, Vaya Ioannidou, Elisavet Theodoraki, Niki Chondrogianni, Ioannis Sfiniadakis, Georgios T. Papaioannou and Michail Christou Rallis
Cancers 2024, 16(20), 3546; https://doi.org/10.3390/cancers16203546 - 21 Oct 2024
Viewed by 666
Abstract
Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, [...] Read more.
Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis. Full article
(This article belongs to the Section Methods and Technologies Development)
►▼ Show Figures

Figure 1

23 pages, 2868 KiB  
Review
The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment
by Maria Gonzalez Agurto, Nicolas Olivares, Gisela Canedo-Marroquin, Daniela Espinoza and Sofia C. Tortora
Cancers 2024, 16(20), 3545; https://doi.org/10.3390/cancers16203545 - 21 Oct 2024
Viewed by 1005
Abstract
Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated [...] Read more.
Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes. Full article
(This article belongs to the Special Issue The Oral Microbiome and Its Link to Oral Cancer: Exploring the Role of Infectious Agents)
►▼ Show Figures

Figure 1

18 pages, 2325 KiB  
Article
Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma—A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples
by Ana Catarina Bravo, Bárbara Morão, André Luz, Rúben Dourado, Beatriz Oliveira, Ana Guedes, Catarina Moreira-Barbosa, Catarina Fidalgo, Luís Mascarenhas-Lemos, Maria Pia Costa-Santos, Rui Maio, Jorge Paulino, Pedro Viana Baptista, Alexandra R. Fernandes and Marília Cravo
Cancers 2024, 16(20), 3544; https://doi.org/10.3390/cancers16203544 - 21 Oct 2024
Viewed by 858
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification [...] Read more.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis. Full article
(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)
►▼ Show Figures

Figure 1

10 pages, 1902 KiB  
Article
An Early Increase in IL-10 and TNF-α Levels Following Atezolizumab Plus Bevacizumab Treatment Predicts Survival in Advanced Hepatocellular Carcinoma Patients: A Prospective Cohort Study
by Soon Kyu Lee, Soon Woo Nam, Ji Won Han and Jung Hyun Kwon
Cancers 2024, 16(20), 3543; https://doi.org/10.3390/cancers16203543 - 21 Oct 2024
Viewed by 736
Abstract
Background/Objectives: Reliable biomarkers for predicting outcomes in hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev) are still lacking. Cytokines, which play a crucial role in immune regulation and HCC progression, have potential as predictive markers, but data supporting their use are [...] Read more.
Background/Objectives: Reliable biomarkers for predicting outcomes in hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev) are still lacking. Cytokines, which play a crucial role in immune regulation and HCC progression, have potential as predictive markers, but data supporting their use are limited. This study aimed to evaluate the impact of early changes in cytokine levels on the clinical outcomes of advanced HCC patients. Methods: We prospectively enrolled 32 advanced HCC patients, collecting blood samples before the first and second Ate/Bev treatments. These samples were analyzed for IL-2, IL-6, IL-10, IL-12, IL-17, IFN-γ, and TNF-α levels to assess changes post-treatment. The primary outcome was overall survival, with a secondary focus on progression-free survival (PFS) at 6 months. Results: The mean age of the participants was 64.2 years, with the majority being male (93.8%). Patients showing increased IL-10, IL-17, and TNF-α levels had significantly better survival (p < 0.05) and marginally improved PFS compared to those with decreased cytokine levels. Interestingly, a positive correlation was noted between changes in IL-10 and TNF-α levels (p = 0.009). Furthermore, a multivariable analysis revealed that increased levels of IL-10 and TNF-α were significant predictors of enhanced survival (hazard ratio, 0.07; 95% confidence interval, 0.01–0.46; p = 0.005). Conclusions: An early increases in IL-10 and TNF-α after Ate/Bev treatment may serve as effective biomarkers for clinical outcomes in advanced HCC patients. Full article
(This article belongs to the Special Issue New Trends in Hepatocellular Carcinoma: Artificial Intelligence, Robotics and Innovative Treatments)
►▼ Show Figures

Figure 1

19 pages, 2047 KiB  
Review
Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Regulatory Mechanisms, Functions, and Therapeutic Implications
by Angela Dalia Ricci, Alessandro Rizzo, Annalisa Schirizzi, Rosalba D’Alessandro, Giorgio Frega, Giovanni Brandi, Endrit Shahini, Raffaele Cozzolongo, Claudio Lotesoriere and Gianluigi Giannelli
Cancers 2024, 16(20), 3542; https://doi.org/10.3390/cancers16203542 - 20 Oct 2024
Viewed by 1112
Abstract
Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response [...] Read more.
Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically “cold” tumors to “hot” tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients. Full article
(This article belongs to the Section Cancer Therapy)
►▼ Show Figures

Figure 1

15 pages, 1246 KiB  
Article
Psychosocial Burden of Women Who Are to Undergo Additional Diagnostic Procedures Due to Positive Screening for Cervical Cancer
by Irena Ilic, Goran Babic, Aleksandra Dimitrijevic, Sandra Sipetic Grujicic, Vladimir Jakovljevic and Milena Ilic
Cancers 2024, 16(20), 3541; https://doi.org/10.3390/cancers16203541 - 20 Oct 2024
Viewed by 918
Abstract
Background/Objectives: This study aimed to evaluate psychosocial burden and its associated factors in women who were referred for additional diagnostic procedures following receipt of a positive cervical-cancer-screening smear result. Methods: A cross-sectional study was performed in a consecutive cohort of only [...] Read more.
Background/Objectives: This study aimed to evaluate psychosocial burden and its associated factors in women who were referred for additional diagnostic procedures following receipt of a positive cervical-cancer-screening smear result. Methods: A cross-sectional study was performed in a consecutive cohort of only women who received an abnormal Papanicolaou screening result and therefore presented to a gynecologist for additional diagnostic examinations (colposcopy/biopsy/endocervical curettage) at the Clinic for Gynecology and Obstetrics of the Clinical Center. Multivariate linear regression was used for data analysis, with Bonferroni correction applied for multiple comparisons. Results: Significant independent predictors for the occurrence of psychosocial burden–worry in women with a positive Papanicolaou screening test before diagnostic procedures were the use of oral contraceptives (β = −0.174, p < 0.001), alcohol consumption (β = 0.188, p < 0.001), anxiety (β = −0.189, p = 0.001), high burden of depressive symptoms (β = 0.191, p = 0.001) and insufficient knowledge of the meaning of the term dysplasia/precancerous (β = −0.187, p < 0.001), according to the multivariate linear regression. The significant independent predictor for the occurrence of psychosocial burden–satisfaction with information/support in women with a positive Papanicolaou screening test before diagnostic procedures was psychological distress (β = −0.210, p = 0.001). Conclusions: Providing information in order to improve understanding of the term dysplasia/precancerous, as well as identifying which women are at risk of psychosocial burden, may help protect against this potential harm among women who receive a positive cervical-cancer-screening result and may facilitate their intention to undergo further diagnostic procedures. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
►▼ Show Figures

Figure 1

9 pages, 1344 KiB  
Article
Artificial Intelligence and Colposcopy: Automatic Identification of Vaginal Squamous Cell Carcinoma Precursors
by Miguel Mascarenhas, Inês Alencoão, Maria João Carinhas, Miguel Martins, Tiago Ribeiro, Francisco Mendes, Pedro Cardoso, Maria João Almeida, Joana Mota, Joana Fernandes, João Ferreira, Guilherme Macedo, Teresa Mascarenhas and Rosa Zulmira
Cancers 2024, 16(20), 3540; https://doi.org/10.3390/cancers16203540 - 20 Oct 2024
Viewed by 760
Abstract
Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the [...] Read more.
Background/Objectives: While human papillomavirus (HPV) is well known for its role in cervical cancer, it also affects vaginal cancers. Although colposcopy offers a comprehensive examination of the female genital tract, its diagnostic accuracy remains suboptimal. Integrating artificial intelligence (AI) could enhance the cost-effectiveness of colposcopy, but no AI models specifically differentiate low-grade (LSILs) and high-grade (HSILs) squamous intraepithelial lesions in the vagina. This study aims to develop and validate an AI model for the differentiation of HPV-associated dysplastic lesions in this region. Methods: A convolutional neural network (CNN) model was developed to differentiate HSILs from LSILs in vaginoscopy (during colposcopy) still images. The AI model was developed on a dataset of 57,250 frames (90% training/validation [including a 5-fold cross-validation] and 10% testing) obtained from 71 procedures. The model was evaluated based on its sensitivity, specificity, accuracy and area under the receiver operating curve (AUROC). Results: For HSIL/LSIL differentiation in the vagina, during the training/validation phase, the CNN demonstrated a mean sensitivity, specificity and accuracy of 98.7% (IC95% 96.7–100.0%), 99.1% (IC95% 98.1–100.0%), and 98.9% (IC95% 97.9–99.8%), respectively. The mean AUROC was 0.990 ± 0.004. During testing phase, the sensitivity was 99.6% and 99.7% for both specificity and accuracy. Conclusions: This is the first globally developed AI model capable of HSIL/LSIL differentiation in the vaginal region, demonstrating high and robust performance metrics. Its effective application paves the way for AI-powered colposcopic assessment across the entire female genital tract, offering a significant advancement in women’s healthcare worldwide. Full article
(This article belongs to the Special Issue Novel Approaches to Machine Learning and Artificial Intelligence in Cancer Research and Care)
►▼ Show Figures

Figure 1

15 pages, 5975 KiB  
Review
Emerging Paradigms in Cancer Metastasis: Ghost Mitochondria, Vasculogenic Mimicry, and Polyploid Giant Cancer Cells
by Mateusz Krotofil, Maciej Tota, Jakub Siednienko and Piotr Donizy
Cancers 2024, 16(20), 3539; https://doi.org/10.3390/cancers16203539 - 19 Oct 2024
Viewed by 952
Abstract
The capacity of cancer cells to migrate from a primary tumor, disseminate throughout the body, and eventually establish secondary tumors is a fundamental aspect of metastasis. A detailed understanding of the cellular and molecular mechanisms underpinning this multifaceted process would facilitate the rational [...] Read more.
The capacity of cancer cells to migrate from a primary tumor, disseminate throughout the body, and eventually establish secondary tumors is a fundamental aspect of metastasis. A detailed understanding of the cellular and molecular mechanisms underpinning this multifaceted process would facilitate the rational development of therapies aimed at treating metastatic disease. Although various hypotheses and models have been proposed, no single concept fully explains the mechanism of metastasis or integrates all observations and experimental findings. Recent advancements in metastasis research have refined existing theories and introduced new ones. This review evaluates several novel/emerging theories, focusing on ghost mitochondria (GM), vasculogenic mimicry (VM), and polyploid giant cancer cells (PGCCs). Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cancer Development and Metastasis)
►▼ Show Figures

Figure 1

14 pages, 1232 KiB  
Review
Caseload per Year in Robotic-Assisted Minimally Invasive Esophagectomy: A Narrative Review
by Ibrahim Büdeyri, Nader El-Sourani, Ann-Kathrin Eichelmann, Jennifer Merten, Mazen A. Juratli, Andreas Pascher and Jens P. Hoelzen
Cancers 2024, 16(20), 3538; https://doi.org/10.3390/cancers16203538 - 19 Oct 2024
Viewed by 872
Abstract
Esophageal surgery is deemed one of the most complex visceral operations. There is a well-documented correlation between higher caseload and better outcomes, with hospitals that perform more surgeries experiencing significantly lower mortality rates. The approach to caseload per year varies across different countries [...] Read more.
Esophageal surgery is deemed one of the most complex visceral operations. There is a well-documented correlation between higher caseload and better outcomes, with hospitals that perform more surgeries experiencing significantly lower mortality rates. The approach to caseload per year varies across different countries within Europe. Germany increased the minimum annual required caseload of complex esophageal surgeries from 10 to 26 starting in 2023. Furthermore, the new regulations present challenges for surgical training and staff recruitment, risking the further fragmentation of training programs. Enhanced regional cooperation is proposed as a solution to ensure comprehensive training. This review explores the benefits of robotic-assisted minimally invasive esophagectomy (RAMIE) in improving surgical precision and patient outcomes and aims to evaluate how the caseload per year influences the quality of patient care and the efficacy of surgical training, especially with the integration of advanced robotic techniques. Full article
(This article belongs to the Section Cancer Therapy)
►▼ Show Figures

Figure 1

16 pages, 1698 KiB  
Article
Functional Targets for Epstein-Barr Virus BART MicroRNAs in B Cell Lymphomas
by Devin N. Fachko, Bonnie Goff, Yan Chen and Rebecca L. Skalsky
Cancers 2024, 16(20), 3537; https://doi.org/10.3390/cancers16203537 - 19 Oct 2024
Viewed by 966
Abstract
MicroRNAs are key post-transcriptional regulators of gene expression and their dysregulation is often linked to cancer. Epstein-Barr virus encodes 22 BamHI A Rightward Transcript (BART) miRNAs, which are expressed in nearly all EBV-associated cancers and implicated in viral pathogenesis. To investigate biological targets [...] Read more.
MicroRNAs are key post-transcriptional regulators of gene expression and their dysregulation is often linked to cancer. Epstein-Barr virus encodes 22 BamHI A Rightward Transcript (BART) miRNAs, which are expressed in nearly all EBV-associated cancers and implicated in viral pathogenesis. To investigate biological targets for BART miRNAs in B cell lymphomas, we performed a meta-analysis of publicly available Ago-CLIP datasets from EBV-positive Burkitt lymphomas (BLs), primary effusion lymphomas (PELs), AIDS-associated diffuse large B cell lymphomas (DLBCLs), and lymphoblastoid cell lines (LCLs). Our analysis focused on comparing targets of EBV BART miRNAs across the different types of transformed B cells. Using reporter assays, we then experimentally validated over 50 functional interactions between BART miRNAs and cellular protein-coding transcripts involved in activities such as B cell differentiation (PRDM1, IRF4, and MYC), cell cycle regulation (UHMK1, CDKN1A, MDM2, and NPAT), apoptosis (MCL1), signaling and intracellular trafficking (GAB1, SOS1, MAPK1, RAB11A, CAV1, and RANBP9), and tumor suppression (CCDC6). Moreover, ectopic BART miRNA expression in several EBV-negative BL cells induced transcriptional changes that may influence molecular signatures of EBV-associated BLs. Collectively, our findings reveal novel, functional interactions for BART miRNAs in lymphomas and provide insights into their roles in these B cell cancers. Full article
(This article belongs to the Special Issue Epstein–Barr Virus (EBV) Associated Cancers)
►▼ Show Figures

Figure 1

18 pages, 969 KiB  
Review
A TRilogy of ATR’s Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer
by Yoon Ki Joo, Carlos Ramirez and Lilian Kabeche
Cancers 2024, 16(20), 3536; https://doi.org/10.3390/cancers16203536 - 19 Oct 2024
Viewed by 793
Abstract
Ataxia Telangiectasia and Rad3-related protein (ATR) is an apical kinase of the DNA Damage Response (DDR) pathway responsible for detecting and resolving damaged DNA. Because cancer cells depend heavily on the DNA damage checkpoint for their unchecked proliferation and propagation, ATR has gained [...] Read more.
Ataxia Telangiectasia and Rad3-related protein (ATR) is an apical kinase of the DNA Damage Response (DDR) pathway responsible for detecting and resolving damaged DNA. Because cancer cells depend heavily on the DNA damage checkpoint for their unchecked proliferation and propagation, ATR has gained enormous popularity as a cancer therapy target in recent decades. Yet, ATR inhibitors have not been the silver bullets as anticipated, with clinical trials demonstrating toxicity and mixed efficacy. To investigate whether the toxicity and mixed efficacy of ATR inhibitors arise from their off-target effects related to ATR’s multiple roles within and outside the DDR pathway, we have analyzed recently published studies on ATR’s non-canonical roles. Recent studies have elucidated that ATR plays a wide role throughout the cell cycle that is separate from its function in the DDR. This includes maintaining nuclear membrane integrity, detecting mechanical forces, and promoting faithful chromosome segregation during mitosis. In this review, we summarize the canonical, DDR-related roles of ATR and also focus on the non-canonical, multifaceted roles of ATR throughout the cell cycle and their clinical relevance. Through this summary, we also address the need for re-assessing clinical strategies targeting ATR as a cancer therapy based on these newly discovered roles for ATR. Full article
(This article belongs to the Special Issue Genome Instability and Human Cancer)
►▼ Show Figures

Figure 1

24 pages, 689 KiB  
Review
Underwater Techniques in Gastrointestinal Endoscopy: Diving into the Depths
by Sandro Sferrazza, Giulio Calabrese, Roberta Maselli, Rui Morais, Antonio Facciorusso, Georgios Mavrogenis, Roberto Di Mitri, Alessandro Repici and Marcello Maida
Cancers 2024, 16(20), 3535; https://doi.org/10.3390/cancers16203535 - 19 Oct 2024
Viewed by 716
Abstract
The endoscopic resection of gastrointestinal tract lesions embraces different types of techniques, ranging from conventional polypectomy/endoscopic mucosal resection (EMR) to the field of third-space endoscopy, including endoscopic submucosal dissection (ESD), full-thickness resection and peroral endoscopic myotomy (POEM). Parallelly, the advent of underwater techniques [...] Read more.
The endoscopic resection of gastrointestinal tract lesions embraces different types of techniques, ranging from conventional polypectomy/endoscopic mucosal resection (EMR) to the field of third-space endoscopy, including endoscopic submucosal dissection (ESD), full-thickness resection and peroral endoscopic myotomy (POEM). Parallelly, the advent of underwater techniques has served as an add-on for both basic and advanced procedures, since its first report in 2012. We aimed to provide a comprehensive update on the state of the art about the feasibility of underwater basic and advanced techniques for GI endoscopy. Underwater EMR (U-EMR) has proved effective and safe in treating > 10 mm sessile or flat or all-size recurrent colonic lesions. Conversely, although data show good effectiveness and safety for <10 mm lesions, it is preferred when high-grade dysplasia is suspected, favouring cold snare polypectomy for all other cases. Moreover, promising data are emerging regarding the feasibility of U-ESD for difficult-to-resect colonic lesions. U-EMR represents a standard of care for treating < 25 mm superficial non-ampullary duodenal epithelial tumours. Data regarding oesophageal, gastric and ampullary lesions remains limited to small cohorts. Finally, using water immersion for POEM has shown a reduction in procedure time compared to the CO2 insufflation technique for vessel coagulation, albeit in a single-centre experience. Based on these results, U-EMR has become a standard for treating intermediate-size colonic and non-ampullary duodenal lesions, as highlighted also in the European Society of Gastrointestinal Endoscopy guidelines. Promising results have been shown in third-space endoscopy studies, even though further prospective studies are awaited to standardise the technique for both ESD and POEM. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
►▼ Show Figures

Figure 1

9 pages, 1218 KiB  
Communication
Concomitant Cervical and Anal Screening for Human Papilloma Virus (HPV): Worth the Effort or a Waste of Time?
by Camille Chilou, Iolanda Espirito Santo, Seraina Faes, Pénélope St-Amour, Martine Jacot-Guillarmod, Basile Pache, Martin Hübner, Dieter Hahnloser and Fabian Grass
Cancers 2024, 16(20), 3534; https://doi.org/10.3390/cancers16203534 - 19 Oct 2024
Viewed by 690
Abstract
Background: This study represents a follow-up analysis of the AnusGynecology (ANGY) study. Methods: This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or [...] Read more.
Background: This study represents a follow-up analysis of the AnusGynecology (ANGY) study. Methods: This prospective, cross-sectional, single-center study recruited women for concomitant cervical and anal screening of HPV genotypes and cytology during a single appointment. All women with findings of either HPV or any type of dysplastic lesions on anal smears were offered follow-up in a specialized high-resolution anoscopy (HRA) outpatient clinic, representing the study cohort for this follow-up study. Results: Overall, 275 patients (mean age 42 ± 12) were included. Among them, 102 (37%) had cervical high-risk (HR) HPV. In total, HPV was (incidentally) revealed in 91 patients (33%) on anal smears, while any degree of anal squamous intraepithelial lesion (SIL) was found in 30 patients (11%), 6 if which were high-grade SIL (H-SIL). Furthermore, 10 out of 19 biopsies were positive (3 H-SIL lesions). Only half (48/91, 53%) of the women agreed to undergo the recommended specialized follow-up evaluation. Of them, 18 (38%) were diagnosed with dysplastic lesions (9 low grade (L-SIL) and 9 H-SIL, respectively) on biopsies, while the remaining visits revealed no abnormalities. Multivariable analysis revealed cervical HR-HPV infection (OR 4, 95% CI 2.2–7.5) and anal intercourse (OR 3.1, 95% CI 1.7–5.9) as independent risk factors for anal HR-HPV infection. Conclusions: Close follow-up of these women is hence strongly recommended. Full article
(This article belongs to the Special Issue Advances in Human-Papillomavirus-Related Squamous Cell Carcinoma: From Pathogenesis to Treatment)
►▼ Show Figures

Figure 1

16 pages, 3569 KiB  
Article
Implications of GPIIB-IIIA Integrin and Liver X Receptor in Platelet-Induced Compression of Ovarian Cancer Multi-Cellular Spheroids
by Zitha Redempta Isingizwe, Virginie Sjoelund and Doris Mangiaracina Benbrook
Cancers 2024, 16(20), 3533; https://doi.org/10.3390/cancers16203533 - 19 Oct 2024
Viewed by 690
Abstract
Background: Platelets have been shown to promote ovarian cancer; however, the mechanism is poorly understood. Previously, we demonstrated that platelets reduce the size and increase the density of multi-cellular ovarian cancer spheroids in cell cultures. The objectives of this study were to determine [...] Read more.
Background: Platelets have been shown to promote ovarian cancer; however, the mechanism is poorly understood. Previously, we demonstrated that platelets reduce the size and increase the density of multi-cellular ovarian cancer spheroids in cell cultures. The objectives of this study were to determine if platelet inhibitors could counteract these effects, and to explore the mechanisms involved. Methods: FDA-approved platelet inhibitors were screened for their abilities to alter platelet effects on ovarian cancer spheroids. Mass spectrometry was used to identify proteins significantly altered in cancer cells upon exposure to platelets. The effects of platelets and/or liver x receptor agonists or antagonists on LXR activity were measured using ES-2 ovarian cancer cells transduced with an LXR-reporter vector. Results: Eptifibatide, a GPIIB-IIIA integrin inhibitor, and dipyridamole, an adenosine reuptake inhibitor, reduced and enhanced platelet effects on ovarian cancer spheroids, respectively. Proteomic studies identified the LXR/RXR and integrin pathways as mediators of platelet effects on ovarian cancer, and downstream effectors of eptifibatide. Conclusions: Integrin pathways and their downstream LXR/RXR effectors are implicated in how platelets alter ovarian cancer spheroid morphology. These results support studying eptifibatide and LXR/RXR agonists as candidate drugs for repurposing as therapeutic strategies to counteract platelet promotion of ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Drug Repurposing to Overcome Cancers)
►▼ Show Figures

Figure 1

12 pages, 2042 KiB  
Article
Analysis of Molecular Imaging Biomarkers Derived from [18F]FDG PET/CT in mCRPC: Whole-Body Total Lesion Glycolysis (TLG) Predicts Overall Survival in Patients Undergoing [225Ac]Ac-PSMA-617-Augmented [177Lu]Lu-PSMA-617 Radioligand Therapy
by Caroline Burgard, Fadi Khreish, Lukas Dahlmanns, Arne Blickle, Moritz B. Bastian, Tilman Speicher, Stephan Maus, Andrea Schaefer-Schuler, Mark Bartholomä, Sven Petto, Samer Ezziddin and Florian Rosar
Cancers 2024, 16(20), 3532; https://doi.org/10.3390/cancers16203532 - 19 Oct 2024
Viewed by 832
Abstract
Background/Objectives: The augmentation of [177Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [225Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [18F]FDG PET/CT-derived molecular [...] Read more.
Background/Objectives: The augmentation of [177Lu]Lu-PSMA-617 radioligand therapy by alpha emitting [225Ac]Ac-PSMA-617, known as the tandem therapy concept, is a promising escalating treatment option in advanced mCRPC. In this study, we evaluated the value of [18F]FDG PET/CT-derived molecular imaging biomarkers for predicting response and outcome to PSMA tandem RLT in n = 33 patients with insufficient response on [177Lu]Lu-PSMA-617 monotherapy. Methods: Six different molecular imaging parameters at baseline, i.e., before initiation of PSMA tandem RLT with respect to SUVmax, SUVpeak, SUV5, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were tested for association with response and overall survival (OS). Results: After the initiation of augmentation, 24.2% of patients with a previously insufficient response experienced partial remission, and 39.4% experienced stable disease. The median OS was 7 months (95% CI: 4–11 months). None of the tested parameters were able to predict the response (all p > 0.529). In contrast, the [18F]FDG PET/CT-derived whole-body molecular imaging parameter TLG was significantly (p = 0.029) associated with OS of patients undergoing [225Ac]Ac-PSMA-617 augmented [177Lu]Lu-PSMA-617 RLT after insufficient response to [177Lu]Lu-PSMA-617 monotherapy. Conclusion: Implementing [18F]FDG PET/CT in the management of PSMA-RLT in clinical practice may contribute to outcome prediction and provide a route to more individualized management in mCRPC. Full article
(This article belongs to the Collection Imaging Biomarker in Oncology)
►▼ Show Figures

Figure 1

14 pages, 505 KiB  
Article
Intraoperative Allogeneic Blood Transfusion Has No Impact on Postoperative Short-Term Outcomes After Pancreatoduodenectomy for Periampullary Malignancies: A Propensity Score Matching Analysis and Mediation Analysis
by Kristjan Ukegjini, René Warschkow, Henrik Petrowsky, Philip C. Müller, José Oberholzer, Ignazio Tarantino, Jan Philipp Jonas, Bruno M. Schmied and Thomas Steffen
Cancers 2024, 16(20), 3531; https://doi.org/10.3390/cancers16203531 - 18 Oct 2024
Viewed by 713
Abstract
Background/Objectives: The aim of this study was to investigate the association between intraoperative blood transfusion (BT) and the short-term outcomes of pancreatoduodenectomy (PD) for patients with periampullary malignancies. Methods: In a retrospective two-center cohort analysis, we utilized a logistic and mixed-effects [...] Read more.
Background/Objectives: The aim of this study was to investigate the association between intraoperative blood transfusion (BT) and the short-term outcomes of pancreatoduodenectomy (PD) for patients with periampullary malignancies. Methods: In a retrospective two-center cohort analysis, we utilized a logistic and mixed-effects ordinal regression, nonparametric partial correlation, and mediation analysis, complemented by propensity score matching (PSM) and weighting. Results: A total of 491 patients were included. Of these, 18 (3.7%) received an intraoperative BT. An intraoperative BT was associated with blood loss (odds ratio (OR) per 100 mL = 1.42; 95% CI 1.27 to 1.62; p < 0.001) and relatively high ASA classes (OR = 3.75; 95% CI 1.05 to 17.74; p = 0.041). Intraoperative blood loss (r = 0.27; p < 0.001) but not intraoperative BT (r = 0.015; p = 0.698) was associated with postoperative complications. Intraoperative BT was associated with postoperative complications according to the unadjusted regression (OR = 1.95; 95% CI 1.38–2.42, p < 0.001) but not the multivariable ordinal regression. In the mediation analysis for relative risk (RR), intraoperative BT was beneficial (RR = 0.51; 95% CI: 0.01–0.78), and blood loss (RR = 2.49; 95% CI: 1.75–177.34) contributed to the occurrence of major postoperative complications. After PSM, analyses revealed that an intraoperative BT did not have a significant impact on the rates of postoperative major complications (OR = 1.048; p = 0.919), clinically relevant postoperative pancreatic fistula (OR = 0.573; p = 0.439) or postoperative 90-day mortality (OR = 0.714; p = 0.439). Conclusions: When adjusting for intraoperative blood loss, intraoperative BT is not associated with postoperative complications. Full article
(This article belongs to the Special Issue Clinical Surgery for Hepato-Pancreato-Biliary (HPB) Cancer)
►▼ Show Figures

Figure 1

18 pages, 477 KiB  
Review
Risk-Stratified Radiotherapy in Pediatric Cancer
by Rituraj Upadhyay and Arnold C. Paulino
Cancers 2024, 16(20), 3530; https://doi.org/10.3390/cancers16203530 - 18 Oct 2024
Viewed by 932
Abstract
While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible [...] Read more.
While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible for late toxicity. In the past decade, radiotherapy has been omitted in patients achieving excellent response to chemotherapy, such as in Hodgkin lymphoma and some Wilms tumors with lung metastases. Likewise, response to chemotherapy has been used to determine whether lower doses of radiation can be delivered in intracranial germinoma and pediatric nasopharyngeal carcinoma. Molecular subtyping in medulloblastoma is currently being employed, and in WNT-pathway M0 tumors, the reduction in radiotherapy dose to the craniospinal axis and tumor bed is currently being investigated. Finally, dose escalation was recently evaluated in patients with rhabdomyosarcoma > 5 cm who do not achieve a complete response to initial 9 weeks of chemotherapy as well as for unresectable Ewing sarcoma patients to improve local control. Full article
(This article belongs to the Special Issue Personalized Radiotherapy in Cancer Care)
►▼ Show Figures

Figure 1

14 pages, 840 KiB  
Article
Relationship of Immune-Related Adverse Events with Tumor Response and Prognosis in Esophageal Squamous Cell Carcinoma Following Nivolumab Monotherapy
by Yoichi Hamai, Yuta Ibuki, Tomoaki Kurokawa, Ryosuke Hirohata, Manato Ohsawa, Nao Kitasaki, Manabu Emi and Morihito Okada
Cancers 2024, 16(20), 3529; https://doi.org/10.3390/cancers16203529 - 18 Oct 2024
Viewed by 794
Abstract
Background: Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are [...] Read more.
Background: Patients across various cancers who develop immune-related adverse events (irAEs) post-immune checkpoint inhibitor (ICI) treatment tend to experience better tumor response and survival than those who do not. However, studies regarding this association in patients with esophageal squamous cell carcinoma (ESCC) are limited. Methods: We assessed the relationship of irAEs with tumor response and survival in 82 consecutive patients with unresectable advanced or recurrent ESCC treated with second- or later-line nivolumab, an anti-PD-1 antibody, monotherapy. Results: We observed irAEs in 24 (29.3%) patients, with the overall response and disease control rates in the irAE-positive group being significantly better than those in the irAE-negative group (both p < 0.0001). During the entire period and within 8 weeks of nivolumab initiation, progression-free and overall survivals (PFS and OS, respectively) were significantly better in patients with grade1/2 irAEs than in those without. Univariate and multivariate analyses indicated grade1/2 irAEs during the entire period and within 8 weeks as independent covariates for PFS (entire period: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.16–0.49, p < 0.001; within 8 weeks: HR 0.46, 95% CI 0.23–0.93, p = 0.03) and OS (entire period: HR 0.24, 95% CI 0.13–0.44, p < 0.001; within 8 weeks: HR 0.41, 95% CI 0.18–0.92, p = 0.03). Conclusions: Grade1/2 irAEs during the entire treatment period and within 8 weeks of nivolumab initiation were significantly associated with improved tumor response and survival in patients with advanced ESCC treated with nivolumab monotherapy. Therefore, mild irAEs may be predictive markers for the response and prognosis of ESCC following ICI treatment. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitor-Based Immunotherapy in Cancer: Predictive Biomarkers and Mechanisms of Resistance)
►▼ Show Figures

Figure 1

20 pages, 5059 KiB  
Article
Dysbiosis of the Upper Gastrointestinal Tract in Head-and-Neck Cancer Survivors: A Pilot Study Using the Capsule Sponge Device
by Natalia Zeber-Lubecka, Maria Kulecka, Michalina Dabrowska, Anna Kluska, Magdalena Piątkowska, Maryla Helena Turkot, Nastazja Dagny Pilonis, Aisha Yusuf, Karol Nowicki-Osuch, Michal Mikula and Jerzy Ostrowski
Cancers 2024, 16(20), 3528; https://doi.org/10.3390/cancers16203528 - 18 Oct 2024
Viewed by 675
Abstract
Background: A non-endoscopic capsule-sponge device allows sampling the entire length of the esophagus. Here, we compared microbiomes of the oral cavity, esophagus, and gastric corpus collected by oral swab, capsule-sponge device, and endoscopic biopsy, respectively, in patients representing three distinct risk profiles for [...] Read more.
Background: A non-endoscopic capsule-sponge device allows sampling the entire length of the esophagus. Here, we compared microbiomes of the oral cavity, esophagus, and gastric corpus collected by oral swab, capsule-sponge device, and endoscopic biopsy, respectively, in patients representing three distinct risk profiles for esophageal squamous cell carcinoma (ESCC). Methods: The study enrolled 11 patients with esophageal squamous intraepithelial neoplasia, 21 patients after curative treatment for head and neck squamous cell cancer (HNSCC) (HNSCC survivors), and 40 patients with functional dyspeptic (FD) symptoms. Microbial genomic DNA was analyzed using 16S rRNA gene amplicon sequencing. Results: The Shannon index of the capsule-sponge sample microbiota was significantly higher in FD group than in patients after treatment for HNSCC, and the Chao index of gastric samples differed between HNSCC survivors and FD patients. Analysis of the β-diversity of FD patients, HNSCC, and esophageal squamous intraepithelial neoplasia showed that different genera formed at each location. The abundance of 205, 116, and 9 genera differed between FD patients and HNSCC survivors in the gastric, capsule-sponge, and oral samples, respectively; 33 genera differed between the FD group and patients with esophageal squamous intraepithelial neoplasia in capsule-sponge samples. Conclusions: The bacterial communities of the upper digestive tract were clustered according to the anatomic site. Despite substantial differences in gastric and esophageal microbiota samples between FD patients and HNSCC survivors, the microbial members and diversity showed small differences between FD patients and those with esophageal squamous intraepithelial neoplasia. It remains unclear whether gastric and esophageal dysbiosis is associated with or is a consequence of treatment for HNSCC. Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
►▼ Show Figures

Figure 1

13 pages, 851 KiB  
Article
AI Survival Prediction Modeling: The Importance of Considering Treatments and Changes in Health Status over Time
by Nabil Adam and Robert Wieder
Cancers 2024, 16(20), 3527; https://doi.org/10.3390/cancers16203527 - 18 Oct 2024
Viewed by 768
Abstract
Background and objectives: Deep learning (DL)-based models for predicting the survival of patients with local stages of breast cancer only use time-fixed covariates, i.e., patient and cancer data at the time of diagnosis. These predictions are inherently error-prone because they do not consider [...] Read more.
Background and objectives: Deep learning (DL)-based models for predicting the survival of patients with local stages of breast cancer only use time-fixed covariates, i.e., patient and cancer data at the time of diagnosis. These predictions are inherently error-prone because they do not consider time-varying events that occur after initial diagnosis. Our objective is to improve the predictive modeling of survival of patients with localized breast cancer to consider both time-fixed and time-varying events; thus, we take into account the progression of a patient’s health status over time. Methods: We extended four DL-based predictive survival models (DeepSurv, DeepHit, Nnet-survival, and Cox-Time) that deal with right-censored time-to-event data to consider not only a patient’s time-fixed covariates (patient and cancer data at diagnosis) but also a patient’s time-varying covariates (e.g., treatments, comorbidities, progressive age, frailty index, adverse events from treatment). We utilized, as our study data, the SEER-Medicare linked dataset from 1991 to 2016 to study a population of women diagnosed with stage I–III breast cancer (BC) enrolled in Medicare at 65 years or older as qualified by age. We delineated time-fixed variables recorded at the time of diagnosis, including age, race, marital status, breast cancer stage, tumor grade, laterality, estrogen receptor (ER), progesterone receptor (PR), and human epidermal receptor 2 (HER2) status, and comorbidity index. We analyzed six distinct prognostic categories, cancer stages I–III BC, and each stage’s ER/PR+ or ER/PR− status. At each visit, we delineated the time-varying covariates of administered treatments, induced adverse events, comorbidity index, and age. We predicted the survival of three hypothetical patients to demonstrate the model’s utility. Main Outcomes and Measures: The primary outcomes of the modeling were the measures of the model’s prediction error, as measured by the concordance index, the most commonly applied evaluation metric in survival analysis, and the integrated Brier score, a metric of the model’s discrimination and calibration. Results: The proposed extended patients’ covariates that include both time-fixed and time-varying covariates significantly improved the deep learning models’ prediction error and the discrimination and calibration of a model’s estimates. The prediction of the four DL models using time-fixed covariates in six different prognostic categories all resulted in approximately a 30% error in all six categories. When applying the proposed extension to include time-varying covariates, the accuracy of all four predictive models improved significantly, with the error decreasing to approximately 10%. The models’ predictive accuracy was independent of the differing published survival predictions from time-fixed covariates in the six prognostic categories. We demonstrate the utility of the model in three hypothetical patients with unique patient, cancer, and treatment variables. The model predicted survival based on the patient’s individual time-fixed and time-varying features, which varied considerably from Social Security age-based, and stage and race-based breast cancer survival predictions. Conclusions: The predictive modeling of the survival of patients with early-stage breast cancer using DL models has a prediction error of around 30% when considering only time-fixed covariates at the time of diagnosis and decreases to values under 10% when time-varying covariates are added as input to the models, regardless of the prognostic category of the patient groups. These models can be used to predict individual patients’ survival probabilities based on their unique repertoire of time-fixed and time-varying features. They will provide guidance for patients and their caregivers to assist in decision making. Full article
(This article belongs to the Collection Artificial Intelligence in Oncology)
►▼ Show Figures

Figure 1

12 pages, 1126 KiB  
Article
Enhancing Prostate Cancer Staging: Association of 68Ga-PSMA PET/CT Imaging with Histopathological Grading in Treatment-Naive Patients
by Oleksii Pisotskyi, Piotr Petrasz, Piotr Zorga, Marcin Gałęski, Pawel Szponar, Katarzyna Brzeźniakiewicz-Janus, Tomasz Drewa, Krzysztof Kaczmarek, Michał Cezary Czarnogórski and Jan Adamowicz
Cancers 2024, 16(20), 3526; https://doi.org/10.3390/cancers16203526 - 18 Oct 2024
Viewed by 717
Abstract
Objective: This study aimed to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) [...] Read more.
Objective: This study aimed to evaluate the correlation between 68Ga-PSMA uptake in PSMA PET/CT in primary prostate cancer (PC) and its histopathological grading (Gleason score and ISUP grade). Additionally, we compared preoperative biopsy histopathological findings with definitive pathology results in radical prostatectomy (RP) specimens. Methods: We retrospectively analyzed 86 patients who underwent 68Ga-PSMA PET/CT for primary PC staging, of which 40 patients later underwent radical prostatectomy. PET/CT results, including SUVmax values, were correlated with GS and PSA concentrations. Histopathology reports were analyzed and compared between biopsy and final pathology results following RP. Results: A significant positive correlation was observed between SUVmax and ISUP grades (Pearson’s ρ = 0.34, p < 0.001), with higher SUVmax values associated with more advanced grades. A cut-off SUVmax value of 5.64 was determined to predict upstaging in patients, yielding a sensitivity of 76% and a specificity of 60% (AUC = 0.82, 95% CI: 0.70–0.94). Additionally, 57.5% of patients experienced a grade shift following RP, with a 35% upgrade and 22.5% downgrade in ISUP grades. Conclusion: 68Ga-PSMA PET/CT demonstrated high sensitivity in detecting high-risk prostate cancer, particularly in patients with GS > 7 or PSA levels ≥ 10 ng/mL. The findings suggest that this imaging modality may be less effective for the staging of patients with lower GS or PSA values, that is, low-risk PCa. Further prospective studies are necessary to validate these results. Full article
(This article belongs to the Special Issue Advances in the Management of Pelvic Tumors)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-123
Previous Issue
Next Issue
Back to TopTop