Cancers

15 pages, 1280 KiB

Open AccessArticle

Complex Karyotype Detection in Chronic Lymphocytic Leukemia: A Comparison of Parallel Cytogenetic Cultures Using TPA and IL2+DSP30 from a Single Center

by Joanna Kamaso, Anna Puiggros, Marta Salido, Carme Melero, María Rodríguez-Rivera, Eva Gimeno, Laia Martínez, Leonor Arenillas, Xavier Calvo, David Román, Eugènia Abella, Silvia Ramos-Campoy, Marta Lorenzo, Ana Ferrer, Rosa Collado, Marco Antonio Moro-García and Blanca Espinet

Cancers 2024, 16(12), 2258; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122258 (registering DOI) - 18 Jun 2024

Abstract

Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the [...] Read more.

Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the complexity assessment of two cytogenetic cultures from 255 CLL patients. IL2+DSP30 identified more altered karyotypes than TPA (50 vs. 39%, p = 0.031). Moreover, in 71% of those abnormal by both, IL2+DSP30 identified more abnormalities and/or abnormal metaphases. CK detection was similar for TPA and IL2+DSP30 (10% vs. 11%). However, 11/33 CKs (33%) were discordant, mainly due to the detection of a normal karyotype or no metaphases in the other culture. Patients requiring treatment within 12 months after sampling (active CLL) displayed significantly more CKs than those showing a stable disease (55% vs. 12%, p < 0.001). Disease status did not impact cultures’ concordance (κ index: 0.735 and 0.754 for stable and active). Although CK was associated with shorter time to first treatment (TTFT) using both methods, IL2+DSP30 displayed better accuracy than TPA for predicting TTFT (C-index: 0.605 vs. 0.580, respectively). In summary, the analysis of two parallel cultures is the best option to detect CKs in CLL. Nonetheless, IL2+DSP30 could be prioritized above TPA to optimize cytogenetic assessment in clinical practice. Full article

(This article belongs to the Special Issue Diagnosis of Hematologic Malignancies)

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23 pages, 2134 KiB

Open AccessReview

The Anticancer Application of Delivery Systems for Honokiol and Magnolol

by Katarzyna Dominiak, Aleksandra Gostyńska, Michał Szulc and Maciej Stawny

Cancers 2024, 16(12), 2257; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122257 (registering DOI) - 18 Jun 2024

Abstract

Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular [...] Read more.

Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON’s multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types. Full article

(This article belongs to the Section Cancer Drug Development)

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20 pages, 1166 KiB

Open AccessArticle

Pre- and Post-Operative Quality of Life in Patients with Osteoradionecrosis of the Jaw

by Sven Otto, Shreeja Shreeja, Sara Carina Kakoschke, Mohammed Michael Albittar, Andreas Widenhorn and Tamara Katharina Kakoschke

Cancers 2024, 16(12), 2256; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122256 (registering DOI) - 18 Jun 2024

Abstract

Osteoradionecrosis of the jaw (ORNJ) is a feared complication following radiation therapy performed for oncological treatment of head and neck cancers (HNC). To date, there is no clear evidence regarding the impact of surgical treatment of ORNJ on the quality of life (QoL) [...] Read more.

Osteoradionecrosis of the jaw (ORNJ) is a feared complication following radiation therapy performed for oncological treatment of head and neck cancers (HNC). To date, there is no clear evidence regarding the impact of surgical treatment of ORNJ on the quality of life (QoL) of affected patients. However, understanding the significance of the surgical treatment approach and its effects on QoL is an essential factor in the decision-making process for optimal, individualized therapy. In this prospective clinical study, QoL was assessed in relation to health related QoL (HRQoL) and oral health related QoL (OHQoL) before and after surgical treatment of ORNJ using standardized questionnaires (EORTC QLQ-C30, QLQ-HN35, OHIP-14). The overall QoL scores as well as individual domains of the collected scales regarding functional and symptom-related complaints were statistically analyzed. Subgroups concerning age, gender, different risk factors and type of ORNJ therapy were compared using Kruskal Wallis test. In addition, clinical and demographic patient data were collected and analyzed. QoL improvement correlated with the type of surgical ORNJ and the length of hospitalization. Better QoL scores were achieved post-operatively regarding different symptoms like pain, swallowing and mouth opening. Long-term effects of radiation therapy remained visibly restrictive to QoL and worsen over time. Full article

(This article belongs to the Special Issue Head and Neck Cancer: Epidemiology, Prevention, Treatment, and Quality of Life)

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15 pages, 1150 KiB

Open AccessReview

The Importance of Intestinal Microbiota and Dysbiosis in the Context of the Development of Intestinal Lymphoma in Dogs and Cats

by Wioleta Jadwiga Breczko, Joanna Bubak and Marta Miszczak

Cancers 2024, 16(12), 2255; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122255 (registering DOI) - 18 Jun 2024

Abstract

Recent advancements have significantly enhanced our understanding of the crucial role animal microbiomes play in veterinary medicine. Their importance in the complex intestinal environment spans immune modulation, metabolic homeostasis, and the pathogenesis of chronic diseases. Dysbiosis, a microbial imbalance, can lead to a [...] Read more.

Recent advancements have significantly enhanced our understanding of the crucial role animal microbiomes play in veterinary medicine. Their importance in the complex intestinal environment spans immune modulation, metabolic homeostasis, and the pathogenesis of chronic diseases. Dysbiosis, a microbial imbalance, can lead to a range of diseases affecting both individual organs and the entire organism. Microbial disruption triggers inflammatory responses in the intestinal mucosa and disturbs immune homeostasis, increasing susceptibility to toxins and their metabolites. These dynamics contribute to the development of intestinal lymphoma, necessitating rigorous investigation into the role of microbiota in tumorigenesis. The principles explored in this study extend beyond veterinary medicine to encompass broader human health concerns. There are remarkable parallels between the subtypes of lymphoproliferative disorders in animals and humans, particularly Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Understanding the etiology of a cancer of the lymphatic system formation is critical for developing both preventive strategies and therapeutic interventions, with the potential to significantly improve patient outcomes. The aim of this study is to discuss the optimal composition of the microbiome in dogs and cats and the potential alterations in the microbiota during the development of intestinal lesions, particularly intestinal lymphoma. Molecular and cellular analyses are also incorporated to detect inflammatory changes and carcinogenesis. A review of the literature on the connections between the gut microbiome and the development of lymphomas in dogs and cats is presented, along with potential diagnostic approaches for these cancers. Full article

(This article belongs to the Topic Gut Microbiota and Cancer)

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22 pages, 690 KiB

Open AccessReview

Non-Invasive Markers for the Detection of Gastric Precancerous Conditions

by Marcin Romańczyk, Malgorzata Osmola, Alexander Link, Amaury Drouet, Caroline Hémont, Jerome Martin, Nicolas Chapelle and Tamara Matysiak-Budnik

Cancers 2024, 16(12), 2254; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122254 (registering DOI) - 18 Jun 2024

Abstract

Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, [...] Read more.

Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel^®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

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21 pages, 4482 KiB

Open AccessArticle

Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition

by Seyma Demirsoy, Ha Tran, Joseph Liu, Yunzhan Li, Shengyu Yang, Dawit Aregawi, Michael J. Glantz, Naduparambil K. Jacob, Vonn Walter, Todd D. Schell and Inan Olmez

Cancers 2024, 16(12), 2253; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122253 (registering DOI) - 18 Jun 2024

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given the lack of actionable targets such as ER and HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring high CDK4/6 expression levels, the efficacy of CDK4/6 [...] Read more.

Triple-negative breast cancer (TNBC) is the most aggressive subtype with high metastasis and mortality rates. Given the lack of actionable targets such as ER and HER2, TNBC still remains an unmet therapeutic challenge. Despite harboring high CDK4/6 expression levels, the efficacy of CDK4/6 inhibition in TNBC has been limited due to the emergence of resistance. The resistance to CDK4/6 inhibition is mainly mediated by RB1 inactivation. Since our aim is to overcome resistance to CDK4/6 inhibition, in this study, we primarily used the cell lines that do not express RB1. Following a screening for activated receptor tyrosine kinases (RTKs) upon CDK4/6 inhibition, we identified the TAM (Tyro3, Axl, and MerTK) RTKs as a crucial therapeutic vulnerability in TNBC. We show that targeting the TAM receptors with a novel inhibitor, sitravatinib, significantly sensitizes TNBC to CDK4/6 inhibitors. Upon prolonged HER2 inhibitor treatment, HER2+ breast cancers suppress HER2 expression, physiologically transforming into TNBC-like cells. We further show that the combined treatment is highly effective against drug-resistant HER2+ breast cancer as well. Following quantitative proteomics and RNA-seq data analysis, we extended our study into the immunophenotyping of TNBC. Given the roles of the TAM receptors in promoting the creation of an immunosuppressive tumor microenvironment (TME), we further demonstrate that the combination of CDK4/6 inhibitor abemaciclib and sitravatinib modifies the immune landscape of TNBC to favor immune checkpoint blockade. Overall, our study offers a novel and highly effective combination therapy against TNBC and potentially treatment-resistant HER2+ breast cancer that can be rapidly moved to the clinic. Full article

(This article belongs to the Section Cancer Therapy)

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10 pages, 5187 KiB

Open AccessArticle

Long-Term Survival and Factors Associated with Increased Mortality in Patients with Ocular Adnexal Lymphomas

by Diego Strianese, Maria Paola Laezza, Fabio Tortora, Giancarlo Fusco, Oreste de Divitiis, Antonella D’Aponte, Francesco Briganti and Andrea Elefante

Cancers 2024, 16(12), 2252; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122252 (registering DOI) - 18 Jun 2024

Abstract

Orbital and ocular adnexal lymphoma (OAL) affects the orbit and the surrounding structures and can arise as several subtypes with variable prognoses. We performed an observational study on the relationship between OAL subtype, diagnostic features, and prognosis to offer valuable insights into imaging [...] Read more.

Orbital and ocular adnexal lymphoma (OAL) affects the orbit and the surrounding structures and can arise as several subtypes with variable prognoses. We performed an observational study on the relationship between OAL subtype, diagnostic features, and prognosis to offer valuable insights into imaging techniques, such as Positron Emission Tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with Computed Tomography (¹⁸F-FDG PET-CT), in predicting outcomes. With this aim, we retrospectively reviewed 99 patients with OALs, recording demographics, cancer subtype, location and treatment, ¹⁸FDG avidity, and bone marrow positivity. We divided patients into Group 1 (those presenting with extranodal marginal zone lymphoma—EMZL) and Group 2, including all other subtypes. The primary outcome was long-term cancer-specific survival (CSS) based on key predictors, performed through Kaplan–Meier curves and the log-rank test, with a p < 0.05 significance threshold. The mean patient age was 67 years (57–75.5). The most frequent histopathologic subtypes were EMZL lymphoma in 69 patients (69.7%), small lymphocytic lymphoma (11.1%) and diffuse-large B-cell lymphoma (10.1%). Patients of Group 1 showed a better prognosis (CSS = 80%) compared to those of Group 2 (CSS = 60%) (p = 0.01). In patients with high-grade lymphoma, the occurrence of ¹⁸FDG avidity (p = 0.003) and bone marrow positivity (p = 0.005) were related to a worse prognosis. In our group, EMZL was the most prominent subtype of OALs and exhibited the best prognosis, low 18FDG avidity, and bone marrow negativity. By observing specific patterns in radiological findings, it is possible to increase our understanding of disease progression, treatment response, and the overall prognosis in OAL patients. Full article

(This article belongs to the Section Cancer Survivorship and Quality of Life)

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12 pages, 630 KiB

Open AccessArticle

Real-World Efficacy and Safety of First-Line Nivolumab Plus Chemotherapy in Patients with Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Nationwide Observational Turkish Oncology Group (TOG) Study

by Yasin Kutlu, Shute Ailia Dae, Feride Yilmaz, Dilek Erdem, Mehmet Ali Nahit Sendur, Sinem Akbas, Elif Senocak Tasci, Onur Bas, Faysal Dane, Abdullah Sakin, Ali Osman Kaya, Musa Baris Aykan, Yakup Ergun, Sedat Biter, Umut Disel, Mustafa Korkmaz, Fatih Selcukbiricik, Fatih Kose, Omer Fatih Olmez, Ahmet Bilici, Gokhan Demir and Suayib Yalcin Show full author list Hide full author list

Cancers 2024, 16(12), 2251; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122251 (registering DOI) - 18 Jun 2024

Abstract

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and [...] Read more.

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes. Full article

(This article belongs to the Topic Cancer Immunity and Immunotherapy: Early Detection, Diagnosis, Systemic Treatments, Novel Biomarkers, and Resistance Mechanisms)

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17 pages, 1041 KiB

Open AccessArticle

Initial versus Staged Thyroidectomy for Differentiated Thyroid Cancer: A Retrospective Multi-Dimensional Cohort Analysis of Effectiveness and Safety

by Eman A. Toraih, Mohammad H. Hussein, Jessan A. Jishu, Madeleine B. Landau, Ahmed Abdelmaksoud, Yaser Y. Bashumeel, Mahmoud A. AbdAlnaeem, Rithvik Vutukuri, Christine Robbie, Chelsea Matzko, Joshua Linhuber, Mohamed Shama, Salem I. Noureldine and Emad Kandil

Cancers 2024, 16(12), 2250; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122250 (registering DOI) - 18 Jun 2024

Abstract

The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify [...] Read more.

The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify the optimal timing for completion thyroidectomy using a multi-dimensional analysis of four cohorts: an institutional series (n = 148), the National Surgical Quality Improvement Program (NSQIP) database (n = 39,992), the TriNetX repository (n > 30,000), and a pooled literature review (10 studies, n = 6015). Institutional data revealed higher overall complication rates with total thyroidectomy (18.3%) compared to completion thyroidectomy (6.8%), primarily due to increased temporary hypocalcemia (10% vs. 0%, p = 0.004). The NSQIP analysis demonstrated that total thyroidectomy was associated with a 72% increased risk of transient hypocalcemia (p < 0.001) and a 25% increased risk of permanent hypocalcemia (p < 0.001). TriNetX data confirmed these findings and identified obesity and concurrent neck dissection as risk factors for complications. A meta-analysis showed that total thyroidectomy increased the rates of transient (RR = 1.63) and permanent (RR = 1.23) hypocalcemia (p < 0.001). Institutional and TriNetX data suggested that performing completion thyroidectomy between 1 and 6 months after the initial lobectomy minimized permanent complication rates compared to delays beyond 6 months. In conclusion, for differentiated thyroid cancer, total thyroidectomy is associated with higher risks of transient and permanent hypocalcemia compared to staged completion thyroidectomy. However, performing completion thyroidectomy within 1–6 months of the initial lobectomy may mitigate the risk of permanent complications. These findings can inform personalized surgical decision-making for patients with differentiated thyroid cancer. Full article

(This article belongs to the Special Issue New Insights into Thyroid Cancer Surgery)

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Graphical abstract

26 pages, 2421 KiB

Open AccessReview

Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies

by Hasan Slika, Aanya Shahani, Riddhpreet Wahi, Jackson Miller, Mari Groves and Betty Tyler

Cancers 2024, 16(12), 2249; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122249 - 18 Jun 2024

Abstract

Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, [...] Read more.

Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, and treatment resistance is a rising issue. The development of this resistance results from the interplay of a myriad of anatomical properties, cellular processes, molecular pathways, and genetic and epigenetic alterations. In fact, several efforts have been directed towards this domain and characterizing the major contributors to this resistance. Herein, this review highlights the different mechanisms that drive relapse and are implicated in the occurrence of treatment resistance and discusses them in the context of the latest molecular-based classification of medulloblastoma. These mechanisms include the impermeability of the blood-brain barrier to drugs, the overactivation of specific molecular pathways, the resistant and multipotent nature of cancer stem cells, intratumoral and intertumoral heterogeneity, and metabolic plasticity. Subsequently, we build on that to explore potential strategies and targeted agents that can abrogate these mechanisms, undermine the development of treatment resistance, and augment medulloblastoma’s response to therapeutic modalities. Full article

(This article belongs to the Special Issue Molecular Insights into Drug Resistance in Cancer)

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13 pages, 4553 KiB

Open AccessArticle

A Radiomic Approach for Evaluating Intra-Subgroup Heterogeneity in SHH and Group 4 Pediatric Medulloblastoma: A Preliminary Multi-Institutional Study

by Marwa Ismail, Hyemin Um, Ralph Salloum, Fauzia Hollnagel, Raheel Ahmed, Peter de Blank and Pallavi Tiwari

Cancers 2024, 16(12), 2248; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122248 - 18 Jun 2024

Abstract

Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for [...] Read more.

Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for their intermediate prognosis, studies have reported wide disparities in patient outcomes within these subgroups. This study aims to create a radiomic prognostic signature, medulloblastoma radiomics risk (mRRisk), to identify the risk levels within the SHH and Group 4 subgroups, individually, for reliable risk stratification. Our hypothesis is that this signature can comprehensively capture tumor characteristics that enable the accurate identification of the risk level. In total, 70 MB studies (48 Group 4, and 22 SHH) were retrospectively curated from three institutions. For each subgroup, 232 hand-crafted features that capture the entropy, surface changes, and contour characteristics of the tumor were extracted. Features were concatenated and fed into regression models for risk stratification. Contrasted with Chang stratification that did not yield any significant differences within subgroups, significant differences were observed between two risk groups in Group 4 (p = 0.04, Concordance Index (CI) = 0.82) on the cystic core and non-enhancing tumor, and SHH (p = 0.03, CI = 0.74) on the enhancing tumor. Our results indicate that radiomics may serve as a prognostic tool for refining MB risk stratification, towards improved patient care. Full article

(This article belongs to the Special Issue Advances in Radiomic, Genomic and Radiogenomic Techniques in Pediatric Medulloblastoma)

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4 pages, 174 KiB

Open AccessEditorial

Diabetes and Cancer: The Perfect Storm and a PRICE to Pay

by Marco Gallo

Cancers 2024, 16(12), 2247; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122247 - 18 Jun 2024

Abstract

Diabetes, obesity, cardiovascular diseases, and cancer are noncommunicable diseases representing the main global health challenges of the current century [...] Full article

(This article belongs to the Special Issue Cancer and Diabetes: What Connections Lie between Them?)

10 pages, 767 KiB

Open AccessArticle

Toxicity-Induced Discontinuation of Immune Checkpoint Inhibitors in Metastatic Urothelial Cancer: 6-Year Experience from a Specialized Uro-Oncology Center

by Severin Rodler, Can Aydogdu, Isabel Brinkmann, Elena Berg, Rega Kopliku, Melanie Götz, Troya Ivanova, Alexander Tamalunas, Gerald B. Schulz, Volker Heinemann, Christian G. Stief and Jozefina Casuscelli

Cancers 2024, 16(12), 2246; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122246 - 18 Jun 2024

Abstract

Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but [...] Read more.

Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2–55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients. Full article

(This article belongs to the Special Issue Immune Checkpoint Inhibitors for Urologic Cancers)

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16 pages, 2942 KiB

Open AccessArticle

Development of Traceable Mouse Models of Advanced and Metastatic Bladder Cancer

by Emma Desponds, Konstantina Kioseoglou, Hana Zdimerova, Marco Ongaro, Grégory Verdeil and Marine M. Leblond

Cancers 2024, 16(12), 2245; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122245 - 17 Jun 2024

Abstract

Bladder cancer (BC) is the fourth most common cancer in men, with a poor patient prognosis for advanced disease. The poor survival of patients with muscle-invasive bladder cancer (MIBC) and metastatic status emphasizes the urgent need to develop new therapies. Lacking in the [...] Read more.

Bladder cancer (BC) is the fourth most common cancer in men, with a poor patient prognosis for advanced disease. The poor survival of patients with muscle-invasive bladder cancer (MIBC) and metastatic status emphasizes the urgent need to develop new therapies. Lacking in the field of BC is the availability of relevant advanced BC mouse models, especially metastatic ones, that accurately recapitulate the complexities of human pathology to test and study new therapeutic strategies. Addressing this need, we developed a traceable mouse model of BC that expresses tumor-associated antigens within the context of advanced muscle-invasive BC. This novel system was achieved through the deletion of the tp53 and pten genes, alongside the incorporation of the fusion construct of Firefly luciferase (Luc) and the SIYRYYGL (SIY) T-cell antigen. We validate that the presence of the transgene did not impact on the development of the tumors while allowing us to measure tumor progression by bioluminescence. We show that the transgene did not influence the composition of the immune tumor microenvironment. More importantly, we report that this model was unresponsive to anti-PD-1 treatment, as in the majority of patients with BC. We also develop a new model based on the orthotopic injection of BC clonal cell lines derived from our first model. We demonstrate that this new model invades the muscle layer and has a metastasis development rate of 83%. The advantage of this model is that we can visualize tumor growth and metastasis development in vivo. These mouse models’ characteristics, displaying many similarities with the human pathology, provide a valuable tool for tracking tumor progression, metastasis spread in vivo, and treatment resistance, as well as exploring fundamental and translational aspects of BC biology. This work contributes to the improvement in the landscape of mouse models of advanced BC for testing new therapeutic strategies. Full article

(This article belongs to the Special Issue New Insights into Urologic Oncology)

8 pages, 351 KiB

Open AccessSystematic Review

The Impact of Urine-Sample HPV Testing on the Effectiveness of Screening for Cervical Cancer: An Umbrella Review

by Wojciech Miazga, Tomasz Tatara, Katarzyna Wnuk, Mariusz Gujski, Jarosław Pinkas and Urszula Religioni

Cancers 2024, 16(12), 2244; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122244 - 17 Jun 2024

Abstract

Background: The aim of the study was to evaluate the impact of urine-sample HPV (human papillomavirus) testing on the effectiveness of screening for cervical cancer. Methods: The analysis was based on the results of a systematic review. Secondary studies were searched in the [...] Read more.

Background: The aim of the study was to evaluate the impact of urine-sample HPV (human papillomavirus) testing on the effectiveness of screening for cervical cancer. Methods: The analysis was based on the results of a systematic review. Secondary studies were searched in the following medical databases: Medline, Embase, and the Cochrane Library. The results of the statistical tests presented in the article originate from research conducted by the authors of the included articles. Results: From a total of 1869 citations, 5 studies were included in this review. Sensitivity and specificity for the detection of any HPV from first-void urine samples were 87% [95% CI: (0.74; 0.94)] and 89% [95% CI: (0.81; 0.93)], respectively. Moreover, participants in the analyzed studies had indicated that they felt comfortable with urine testing. Conclusions: The development of methods to detect HPV infection in first-void urine samples and the application of this sampling method in widely available screening tests could significantly increase patients’ willingness to participate in testing. Full article

(This article belongs to the Section Infectious Agents and Cancer)

28 pages, 438 KiB

Open AccessReview

Novel Targets and Advanced Therapies in Diffuse Large B Cell Lymphomas

by Francesco D’Alò, Silvia Bellesi, Elena Maiolo, Eleonora Alma, Flaminia Bellisario, Rosalia Malafronte, Marcello Viscovo, Fabrizia Campana and Stefan Hohaus

Cancers 2024, 16(12), 2243; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122243 - 17 Jun 2024

Viewed by 172

Abstract

Since the introduction of rituximab in the late 1990s, significant progress has been made in advancing targeted therapies for B cell lymphomas, improving patients’ chance of being cured and clinicians’ therapeutic armamentarium. A better understanding of disease biology and pathogenic pathways, coupled with [...] Read more.

Since the introduction of rituximab in the late 1990s, significant progress has been made in advancing targeted therapies for B cell lymphomas, improving patients’ chance of being cured and clinicians’ therapeutic armamentarium. A better understanding of disease biology and pathogenic pathways, coupled with refinements in immunophenotypic and molecular diagnostics, have been instrumental in these achievements. While traditional chemotherapy remains fundamental in most cases, concerns surrounding chemorefractoriness and cumulative toxicities, particularly the depletion of the hemopoietic reserve, underscore the imperative for personalized treatment approaches. Integrating targeted agents, notably monoclonal antibodies, alongside chemotherapy has yielded heightened response rates and prolonged survival. A notable paradigm shift is underway with innovative-targeted therapies replacing cytotoxic drugs, challenging conventional salvage strategies like stem cell transplantation. This review examines the landscape of emerging targets for lymphoma cells and explores innovative therapies for diffuse large B cell lymphoma (DLBCL). From Chimeric Antigen Receptor-T cells to more potent monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, checkpoint inhibitors, and small molecules targeting intracellular pathways, each modality offers promising avenues for therapeutic advancement. This review aims to furnish insights into their potential implications for the future of DLBCL treatment strategies. Full article

(This article belongs to the Special Issue New Precision Medicine Approaches in Haematological Malignancies: Novel Targets and Advanced Therapies (Volume II))

18 pages, 5306 KiB

Open AccessArticle

Does 5-ALA Fluorescence Microscopy Improve Complete Resectability in Cerebral/Cerebellar Metastatic Surgery? A Retrospective Data Analysis from a Cranial Center

by Hraq Mourad Sarkis, Samer Zawy Alsofy, Ralf Stroop, Marc Lewitz, Stephanie Schipmann, Markus Unnewehr, Werner Paulus, Makoto Nakamura and Christian Ewelt

Cancers 2024, 16(12), 2242; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122242 - 17 Jun 2024

Viewed by 127

Abstract

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and [...] Read more.

(1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. Full article

(This article belongs to the Section Cancer Metastasis)

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23 pages, 1200 KiB

Open AccessSystematic Review

Exercise Intervention on Insomnia in Patients with a Cancer: A Systematic Review of the Literature

by Chloé Drozd, Elsa Curtit, Valérie Gillet, Quentin Jacquinot, Nathalie Meneveau and Fabienne Mougin

Cancers 2024, 16(12), 2241; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122241 - 17 Jun 2024

Viewed by 130

Abstract

Cancer is associated with increased muscle weakness, reduced physical functioning, increased fatigue, but also sleep disturbances, including insomnia, that affect quality of life (QoL). Physical activity demonstrated benefits on functional capacity, resilience and cancer-related fatigue, but there is a paucity of available data [...] Read more.

Cancer is associated with increased muscle weakness, reduced physical functioning, increased fatigue, but also sleep disturbances, including insomnia, that affect quality of life (QoL). Physical activity demonstrated benefits on functional capacity, resilience and cancer-related fatigue, but there is a paucity of available data regarding its effects on insomnia in patients with cancer. This systematic review aims to examine the efficacy of exercise levels with insomnia in cancer patients. A systematic search was performed for articles published in PubMed and Cochrane Library databases from December 2013 to February 2023. Included studies explored insomnia during or after cancer treatment, with various exercise interventions. The search identified nine studies included in this review. Due to substantial heterogeneity in the interventions across studies, meta-analysis was not performed. Three studies reported positive results for insomnia reduction by self-reported outcomes under a supervised aerobic exercise program alone or combined with strength training. The present systematic review establishes the role of exercise interventions for reducing cancer-related insomnia. Further studies are indeed warranted to improve the level of evidence for exercise interventions for implementation in the care of cancer-related insomnia. Full article

(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)

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23 pages, 793 KiB

Open AccessReview

Pancreatic Ductal Adenocarcinoma (PDAC): A Review of Recent Advancements Enabled by Artificial Intelligence

by Ashwin Mukund, Muhammad Ali Afridi, Aleksandra Karolak, Margaret A. Park, Jennifer B. Permuth and Ghulam Rasool

Cancers 2024, 16(12), 2240; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122240 - 17 Jun 2024

Viewed by 160

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) and machine learning (ML) are emerging as pivotal tools in revolutionizing PDAC care across various dimensions. Consequently, many studies [...] Read more.

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most formidable challenges in oncology, characterized by its late detection and poor prognosis. Artificial intelligence (AI) and machine learning (ML) are emerging as pivotal tools in revolutionizing PDAC care across various dimensions. Consequently, many studies have focused on using AI to improve the standard of PDAC care. This review article attempts to consolidate the literature from the past five years to identify high-impact, novel, and meaningful studies focusing on their transformative potential in PDAC management. Our analysis spans a broad spectrum of applications, including but not limited to patient risk stratification, early detection, and prediction of treatment outcomes, thereby highlighting AI’s potential role in enhancing the quality and precision of PDAC care. By categorizing the literature into discrete sections reflective of a patient’s journey from screening and diagnosis through treatment and survivorship, this review offers a comprehensive examination of AI-driven methodologies in addressing the multifaceted challenges of PDAC. Each study is summarized by explaining the dataset, ML model, evaluation metrics, and impact the study has on improving PDAC-related outcomes. We also discuss prevailing obstacles and limitations inherent in the application of AI within the PDAC context, offering insightful perspectives on potential future directions and innovations. Full article

(This article belongs to the Section Methods and Technologies Development)

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19 pages, 6526 KiB

Open AccessArticle

Mixtures of Three Mortaparibs with Enhanced Anticancer, Anti-Migration, and Antistress Activities: Molecular Characterization in p53-Null Cancer Cells

by Renu Wadhwa, Shi Yang, Hazna Noor Meidinna, Anissa Nofita Sari, Priyanshu Bhargava and Sunil C. Kaul

Cancers 2024, 16(12), 2239; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122239 - 17 Jun 2024

Viewed by 150

Abstract

Mortalin, a member of the Hsp70 family of proteins, is commonly enriched in many types of cancers. It promotes carcinogenesis and metastasis in multiple ways of which the inactivation of the tumor suppressor activity of p53 has been firmly established. The downregulation of [...] Read more.

Mortalin, a member of the Hsp70 family of proteins, is commonly enriched in many types of cancers. It promotes carcinogenesis and metastasis in multiple ways of which the inactivation of the tumor suppressor activity of p53 has been firmly established. The downregulation of mortalin and/or disruption of mortalin–p53 interactions by small molecules has earlier been shown to activate p53 function yielding growth arrest/apoptosis in cancer cells. Mortaparibs (Mortaparib, Mortaparib^Plus, and Mortaparib^Mild) are chemical inhibitors of mortalin isolated by cell-based two-way screening involving (i) a shift in the mortalin staining pattern from perinuclear (characteristics of cancer cells) to pancytoplasmic (characteristics of normal cells) and (ii) the nuclear enrichment of p53. They have similar structures and also cause the inhibition of PARP1 and hence were named Mortaparibs. In the present study, we report the anticancer and anti-metastasis activity of Mortaparib^Mild (4-[(4-amino-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanylmethyl]-N-(4-methoxyphenyl)-1,3-thiazol-2-amine) in p53-null cells. By extensive molecular analyses of cell proliferation, growth arrest, and apoptosis pathways, we demonstrate that although it causes relatively weaker cytotoxicity compared to Mortaparib and Mortaparib^Plus, its lower concentrations were equally potent to inhibit cell migration. We developed combinations (called Mortaparib^Mix-AP, Mortaparib^Mix-AM, and Mortaparib^Mix-AS) consisting of different ratios of three Mortaparibs for specifically enhancing their anti-proliferation, anti-migration, and antistress activities, respectively. Based on the molecular analyses of control and treated cells, we suggest that the three Mortaparibs and their mixtures may be considered for further laboratory and clinical studies validating their use for the treatment of cancer as well as prevention of its relapse and metastasis. Full article

(This article belongs to the Section Molecular Cancer Biology)

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17 pages, 298 KiB

Open AccessReview

Arterial Thrombosis in Patients with Cancer

by Yan Xu, Marc Carrier and Miriam Kimpton

Cancers 2024, 16(12), 2238; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122238 - 17 Jun 2024

Viewed by 162

Abstract

Patients with cancer are at increased risk of arterial thromboembolic disease due to the presence of risk factors common to both the development of cancer and arterial thrombosis, the cancer itself, and the treatments provided to treat cancer. We review here the epidemiology [...] Read more.

Patients with cancer are at increased risk of arterial thromboembolic disease due to the presence of risk factors common to both the development of cancer and arterial thrombosis, the cancer itself, and the treatments provided to treat cancer. We review here the epidemiology and pathophysiology of arterial thromboembolic disease in cancer, along with its prevention and treatment strategies. We also propose a generalized approach for the management of arterial thromboembolic disease in this patient population. Full article

(This article belongs to the Special Issue Treatment of Cancer-Associated Thrombosis 2.0)

12 pages, 606 KiB

Open AccessArticle

The European Thyroid Imaging and Reporting Data System as a Remedy for the Overdiagnosis and Overtreatment of Thyroid Cancer: Results from the EUROCRINE Surgical Registry

by Andrzej Rafał Hellmann, Piotr Wiśniewski, Maciej Śledziński, Marco Raffaelli, Jarosław Kobiela and Marcin Barczyński

Cancers 2024, 16(12), 2237; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122237 - 17 Jun 2024

Viewed by 140

Abstract

Background: The European Thyroid Imaging and Reporting Data System (EU-TIRADS) aims to reduce the overdiagnosis of thyroid cancer (TC) by guiding the selection of nodules for fine-needle aspiration biopsy (FNAB). This study sought to validate EU-TIRADS nodule selection criteria using data from EUROCRINE, [...] Read more.

Background: The European Thyroid Imaging and Reporting Data System (EU-TIRADS) aims to reduce the overdiagnosis of thyroid cancer (TC) by guiding the selection of nodules for fine-needle aspiration biopsy (FNAB). This study sought to validate EU-TIRADS nodule selection criteria using data from EUROCRINE, an extensive international endocrine surgery registry. Method: We reviewed indications for FNAB among patients with TC compared to those with benign disease who underwent surgery between March 2020 and March 2022, considering preoperative EU-TIRADS scores and dominant nodule size (FNAB is recommended in Category 5 (˃10 mm or ˂10 mm with suspicious lymph nodes), 4 (˃15 mm), and 3 (˃20 mm)). Patients were categorized into three risk groups: minimal risk (patients with papillary microcarcinoma), high risk (patients with pT3b stage or higher, pN1b, or pM1), and low–moderate risk (all other patients). We conducted a Receiver Operating Characteristic (ROC) analysis to assess the diagnostic accuracy of the EU-TIRADS. Results: We analyzed 32,008 operations. Approximately 68% of the surgical records included EU-TIRADS classifications. The EU-TIRADS exhibited diagnostic accuracy across high-volume sites, with a median ROC Area Under the ROC Curve (AUC) of 0.752, indicating its effectiveness in identifying malignancy. Among the cases, 7907 patients had TC. Notably, 55% of patients with TC underwent FNAB despite not initially meeting the EU-TIRADS criteria. These patients were distributed across the minimal- (58%), low–moderate- (36%), and high-risk (5.8%) categories. Of the patients with TC recommended for FNAB, 78% were deemed low–moderate risk, 21% high risk, and only 0.7% minimal risk. Conclusion: The EU-TIRADS offers effective preoperative malignancy risk stratification. Promoting the proper use of the EU-TIRADS in clinical practice is essential to mitigate the overdiagnosis and overtreatment of low-risk TC. Full article

(This article belongs to the Special Issue Advances in Diagnosis, Treatment and Management of Endocrine Neoplasms)

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18 pages, 1628 KiB

Open AccessReview

Gut Microbiota—Adversary or Ally? Its Role and Significance in Colorectal Cancer Pathogenesis, Progression, and Treatment

by Katarzyna Chawrylak, Magdalena Leśniewska, Katarzyna Mielniczek, Katarzyna Sędłak, Zuzanna Pelc, Timothy M. Pawlik, Wojciech P. Polkowski and Karol Rawicz-Pruszyński

Cancers 2024, 16(12), 2236; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122236 - 15 Jun 2024

Viewed by 450

Abstract

In 2022, colorectal cancer (CRC) was the third most prevalent malignancy worldwide. The therapeutic approach for CRC typically involves a multimodal regimen. The human gut microbiota comprises over 35,000 bacterial species. The composition of the gut microbiota is influenced by dietary intake, which [...] Read more.

In 2022, colorectal cancer (CRC) was the third most prevalent malignancy worldwide. The therapeutic approach for CRC typically involves a multimodal regimen. The human gut microbiota comprises over 35,000 bacterial species. The composition of the gut microbiota is influenced by dietary intake, which plays a crucial role in food absorption, nutrient extraction, and the development of low-grade inflammation. Dysbiosis in the gut microbiota is a key driver of inflammation and is strongly associated with CRC development. While the gut microbiome influences CRC initiation and progression, emerging evidence suggests a role for the gut microbiome in modulating the efficacy and toxicity of cancer treatments. Therapeutic strategies targeting the gut microbiome, such as probiotics, hold promise as effective interventions in the modern therapeutical approach to CRC. For example, Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) implementation has resulted in improvements in clinical outcomes, including reduced incidence of anastomotic leakage (AL), surgical site infections (SSIs), reoperation, as well as shorter recovery times and hospital stays compared with the control group. Therefore, this review aims to describe the current state of knowledge regarding the involvement of the gut microbiota in CRC pathogenesis and its potential therapeutic implications to treat CRC. Full article

(This article belongs to the Special Issue Innovations in Diagnosis and Treatment of Colon and Rectal Cancer: Preoperative Optimisation, Multidisciplinary Management, and Surgical Technology Advancement)

23 pages, 2017 KiB

Open AccessReview

Extracellular Vesicle- and Mitochondria-Based Targeting of Non-Small Cell Lung Cancer Response to Radiation: Challenges and Perspectives

by Sergey Leonov, Anna Dorfman, Elizaveta Pershikova, Olumide Inyang, Lina Alhaddad, Yuzhe Wang, Margarita Pustovalova and Yulia Merkher

Cancers 2024, 16(12), 2235; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122235 - 15 Jun 2024

Viewed by 348

Abstract

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), [...] Read more.

During the cell life cycle, extracellular vesicles (EVs) transport different cargos, including organelles, proteins, RNAs, DNAs, metabolites, etc., that influence cell proliferation and apoptosis in recipient cells. EVs from metastatic cancer cells remodel the extracellular matrix and cells of the tumor microenvironment (TME), promoting tumor invasion and metastatic niche preparation. Although the process is not fully understood, evidence suggests that EVs facilitate genetic material transfer between cells. In the context of NSCLC, EVs can mediate intercellular mitochondrial (Mt) transfer, delivering mitochondria organelle (MtO), mitochondrial DNA (mtDNA), and/or mtRNA/proteinaceous cargo signatures (MtS) through different mechanisms. On the other hand, certain populations of cancer cells can hijack the MtO from TME cells mainly by using tunneling nanotubes (TNTs). This transfer aids in restoring mitochondrial function, benefiting benign cells with impaired metabolism and enabling restoration of their metabolic activity. However, the impact of transferring mitochondria versus transplanting intact mitochondrial organelles in cancer remains uncertain and the subject of debate. Some studies suggest that EV-mediated mitochondria delivery to cancer cells can impact how cancer responds to radiation. It might make the cancer more resistant or more sensitive to radiation. In our review, we aimed to point out the current controversy surrounding experimental data and to highlight new paradigm-shifting modalities in radiation therapy that could potentially overcome cancer resistance mechanisms in NSCLC. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: The Functions of Extracellular Vesicles in Cancer)

24 pages, 10892 KiB

Open AccessArticle

Pancreatectomy with En Bloc Superior Mesenteric Vein and All Its Tributaries Resection without PV/SMV Reconstruction for “Low” Locally Advanced Pancreatic Head Cancer

by Viacheslav Egorov, Pavel Kim, Soslan Dzigasov, Eugeny Kondratiev, Alexander Sorokin, Alexey Kolygin, Mikhail Vyborniy, Grigoriy Bolshakov, Pavel Popov, Anna Demchenkova and Tatiana Dakhtler

Cancers 2024, 16(12), 2234; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122234 - 15 Jun 2024

Viewed by 190

Abstract

The “vein definition” for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies [...] Read more.

The “vein definition” for locally advanced pancreatic ductal adenocarcinoma (LA PDAC) assumes portal-to-superior mesenteric vein (PV/SMV) unreconstructability due to tumor involvement or occlusion. Radical pancreatectomies with SMV resection without PV/SMV reconstruction are scarcely discussed in the literature. Retrospective analysis of 19 radical pancreatectomies for “low” LA PDAC with SMV and all its tributaries resection without PV/SMV reconstruction has shown zero mortality; overall morbidity—56%; Dindo–Clavien—3–10.5%; R0—rate—82%; mean operative procedure time—355 ± 154 min; mean blood loss—330 ± 170 mL; delayed gastric emptying—25%; and clinically relevant postoperative pancreatic fistula—8%. In three cases, surgery was associated with superior mesenteric (n2) and common hepatic artery (n1) resection. Surgery was completed without vein reconstruction (n13) and with inferior mesenteric-to-splenic anastomosis (n6). There were no cases of liver, gastric, or intestinal ischemia. A specific complication of the SMV resection without reconstruction was 2–3 days-long intestinal edema (48%). Median overall survival was 25 months, and median progression-free survival was 18 months. All the relapses, except two, were distant. The possibility of successful SMV resection without PV/SMV reconstruction can be predicted before surgery by CT-based reconstructions. The mandatory anatomical conditions for the procedure were as follows: (1) preserved SMV-SV confluence; (2) occluded SMV for any reason (tumor or thrombus); (3) well-developed inferior mesenteric vein collaterals with dilated intestinal veins; (4) no right-sided vein collaterals; and (5) no varices in the upper abdomen. Conclusion: “Low” LA PDACs involving SMV with all its tributaries can be radically and safely resected in highly and specifically selected cases without PV/SMV reconstruction with an acceptable survival rate. Full article

(This article belongs to the Special Issue Advances in Abdominal Surgical Oncology and Intraperitoneal Therapies)

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15 pages, 7809 KiB

Open AccessArticle

Molecular and Histopathological Characterization of Metastatic Cutaneous Squamous Cell Carcinomas: A Case–Control Study

by Alessia Paganelli, Marco Zaffonato, Benedetta Donati, Federica Torricelli, Veronica Manicardi, Michela Lai, Marco Spadafora, Simonetta Piana, Alessia Ciarrocchi and Caterina Longo

Cancers 2024, 16(12), 2233; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122233 - 15 Jun 2024

Viewed by 169

Abstract

Background: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The [...] Read more.

Background: A subset of patients affected by cutaneous squamous cell carcinoma (cSCC) can exhibit locally invasive or metastatic tumors. Different staging classification systems are currently in use for cSCC. However, precise patient risk stratification has yet to be reached in clinical practice. The study aims to identify specific histological and molecular parameters characterizing metastatic cSCC. Methods: Patients affected by metastatic and non-metastatic cSCC (controls) were included in the present study and matched for clinical and histological characteristics. Skin samples from primary tumors were revised for several histological parameters and also underwent gene expression profiling with a commercially available panel testing 770 different genes. Results: In total, 48 subjects were enrolled in the study (24 cases, 24 controls); 67 genes were found to be differentially expressed between metastatic and non-metastatic cSCC. Most such genes were involved in immune regulation, skin integrity, angiogenesis, cell migration and proliferation. Conclusion: The combination of histological and molecular profiles of cSCCs allows the identification of features specific to metastatic cSCC, with potential implications for more precise patient risk stratification. Full article

(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)

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12 pages, 1279 KiB

Open AccessArticle

Real-World Treatment Patterns, Clinical Outcomes, Healthcare Resource Utilization, and Costs in Advanced Hepatocellular Carcinoma in Ontario, Canada

by Soo Jin Seung, Hasnain Saherawala, YongJin Kim, Jimmy Tieu, Sharon Wang, Cal Shephard and Dominick Bossé

Cancers 2024, 16(12), 2232; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122232 - 15 Jun 2024

Viewed by 223

Abstract

The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study [...] Read more.

The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options. Full article

(This article belongs to the Special Issue Advanced Strategies in the Care of Hepatocellular Carcinoma Patients)

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8 pages, 237 KiB

Open AccessArticle

Unilateral Post-Chemotherapy Robot-Assisted Retroperitoneal Lymph Node Dissection for Stage II Non-Seminomatous Germ Cell Tumors: Sexual and Reproductive Outcomes

by Antonio Tufano, Simone Cilio, Gianluca Spena, Alessandro Izzo, Luigi Castaldo, Giovanni Grimaldi, Raffaele Muscariello, Dario Franzese, Giuseppe Quarto, Riccardo Autorino, Francesco Passaro and Sisto Perdonà

Cancers 2024, 16(12), 2231; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122231 - 15 Jun 2024

Viewed by 239

Abstract

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage [...] Read more.

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction. Full article

(This article belongs to the Section Clinical Research of Cancer)

17 pages, 4555 KiB

Open AccessArticle

P18: Novel Anticancer Peptide from Induced Tumor-Suppressing Cells Targeting Breast Cancer and Bone Metastasis

by Changpeng Cui, Qingji Huo, Xue Xiong, Sungsoo Na, Masaru Mitsuda, Kazumasa Minami, Baiyan Li and Hiroki Yokota

Cancers 2024, 16(12), 2230; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122230 - 15 Jun 2024

Viewed by 282

Abstract

Background: The skeletal system is a common site for metastasis from breast cancer. In our prior work, we developed induced tumor-suppressing cells (iTSCs) capable of secreting a set of tumor-suppressing proteins. In this study, we examined the possibility of identifying anticancer peptides (ACPs) [...] Read more.

Background: The skeletal system is a common site for metastasis from breast cancer. In our prior work, we developed induced tumor-suppressing cells (iTSCs) capable of secreting a set of tumor-suppressing proteins. In this study, we examined the possibility of identifying anticancer peptides (ACPs) from trypsin-digested protein fragments derived from iTSC proteomes. Methods: The efficacy of ACPs was examined using an MTT-based cell viability assay, a Scratch-based motility assay, an EdU-based proliferation assay, and a transwell invasion assay. To evaluate the mechanism of inhibitory action, a fluorescence resonance energy transfer (FRET)-based GTPase activity assay and a molecular docking analysis were conducted. The efficacy of ACPs was also tested using an ex vivo cancer tissue assay and a bone microenvironment assay. Results: Among the 12 ACP candidates, P18 (TDYMVGSYGPR) demonstrated the most effective anticancer activity. P18 was derived from Arhgdia, a Rho GDP dissociation inhibitor alpha, and exhibited inhibitory effects on the viability, migration, and invasion of breast cancer cells. It also hindered the GTPase activity of RhoA and Cdc42 and downregulated the expression of oncoproteins such as Snail and Src. The inhibitory impact of P18 was additive when it was combined with chemotherapeutic drugs such as Cisplatin and Taxol in both breast cancer cells and patient-derived tissues. P18 had no inhibitory effect on mesenchymal stem cells but suppressed the maturation of RANKL-stimulated osteoclasts and mitigated the bone loss associated with breast cancer. Furthermore, the P18 analog modified by N-terminal acetylation and C-terminal amidation (Ac-P18-NH2) exhibited stronger tumor-suppressor effects. Conclusions: This study introduced a unique methodology for selecting an effective ACP from the iTSC secretome. P18 holds promise for the treatment of breast cancer and the prevention of bone destruction by regulating GTPase signaling. Full article

(This article belongs to the Section Cancer Therapy)

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17 pages, 15592 KiB

Open AccessArticle

Enhancing Early Lung Cancer Diagnosis: Predicting Lung Nodule Progression in Follow-Up Low-Dose CT Scan with Deep Generative Model

by Yifan Wang, Chuan Zhou, Lei Ying, Heang-Ping Chan, Elizabeth Lee, Aamer Chughtai, Lubomir M. Hadjiiski and Ella A. Kazerooni

Cancers 2024, 16(12), 2229; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16122229 - 15 Jun 2024

Viewed by 300

Abstract

Early diagnosis of lung cancer can significantly improve patient outcomes. We developed a Growth Predictive model based on the Wasserstein Generative Adversarial Network framework (GP-WGAN) to predict the nodule growth patterns in the follow-up LDCT scans. The GP-WGAN was trained with a training [...] Read more.

Early diagnosis of lung cancer can significantly improve patient outcomes. We developed a Growth Predictive model based on the Wasserstein Generative Adversarial Network framework (GP-WGAN) to predict the nodule growth patterns in the follow-up LDCT scans. The GP-WGAN was trained with a training set (N = 776) containing 1121 pairs of nodule images with about 1-year intervals and deployed to an independent test set of 450 nodules on baseline LDCT scans to predict nodule images (GP-nodules) in their 1-year follow-up scans. The 450 GP-nodules were finally classified as malignant or benign by a lung cancer risk prediction (LCRP) model, achieving a test AUC of 0.827 ± 0.028, which was comparable to the AUC of 0.862 ± 0.028 achieved by the same LCRP model classifying real follow-up nodule images (p = 0.071). The net reclassification index yielded consistent outcomes (NRI = 0.04; p = 0.62). Other baseline methods, including Lung-RADS and the Brock model, achieved significantly lower performance (p < 0.05). The results demonstrated that the GP-nodules predicted by our GP-WGAN model achieved comparable performance with the nodules in the real follow-up scans for lung cancer diagnosis, indicating the potential to detect lung cancer earlier when coupled with accelerated clinical management versus the current approach of waiting until the next screening exam. Full article

(This article belongs to the Section Cancer Causes, Screening and Diagnosis)

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