11 pages, 254 KiB  
Article
Unique Characteristics of Patients with Von Hippel–Lindau Disease Defined by Various Diagnostic Criteria
by Reut Halperin, Liat Arnon, Yehudit Eden-Friedman and Amit Tirosh
Cancers 2023, 15(6), 1657; https://doi.org/10.3390/cancers15061657 - 8 Mar 2023
Cited by 6 | Viewed by 2204
Abstract
Von Hippel–Lindau (VHL) disease diagnosis is based on two criteria sets: International criteria (IC, two hemangioblastomas, one hemangioblastoma plus one visceral lesion, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion); or Danish criteria (DC, two clinical manifestations, or VHL family history/pathogenic variant plus [...] Read more.
Von Hippel–Lindau (VHL) disease diagnosis is based on two criteria sets: International criteria (IC, two hemangioblastomas, one hemangioblastoma plus one visceral lesion, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion); or Danish criteria (DC, two clinical manifestations, or VHL family history/pathogenic variant plus hemangioblastoma/visceral lesion). We aimed to compare the characteristics of patients with VHL-related pancreatic neuroendocrine tumor (vPNET) meeting either the clinical Danish criteria only (DOC) or IC to those with sporadic PNET (sPNET). The cohort included 33 patients with VHL (20 vPNETs) and 65 with sPNET. In terms of genetic testing and family history of VHL, 90.0% of the patients with vPNET in the IC group had a germline VHL pathogenic variant, and 70.0% had a family history of VHL vs. 20% and 10% in the DOC group, respectively (p < 0.05 for both). Patients with vPNET were younger at diagnosis compared with sPNET (51.6 ± 4.1 vs. 62.8 ± 1.5 years, p < 0.05). Patients in the IC group were younger at diagnosis with VHL, vPNET, pheochromocytoma, or paraganglioma (PPGL) and renal-cell carcinoma (RCC) than those in the DOC group (p < 0.05 for all comparisons). The most prevalent presenting manifestations were hemangioblastoma (42.8%) and PPGL (33.3%) vs. RCC (58.3%) and PNET (41.7%) in the IC vs. DOC groups. In conclusion, patients with vPNET meeting DOC criteria show greater similarity to sPNET. We suggest performing genetic testing, rather than solely using clinical criteria, for establishing the diagnosis of VHL. Full article
(This article belongs to the Special Issue New Perspectives on Multiple Endocrine Neoplasia)
17 pages, 1498 KiB  
Article
Moyamoya Vasculopathy in Neurofibromatosis Type 1 Pediatric Patients: The Role of Rare Variants of RNF213
by Marzia Ognibene, Marcello Scala, Michele Iacomino, Irene Schiavetti, Francesca Madia, Monica Traverso, Sara Guerrisi, Marco Di Duca, Francesco Caroli, Simona Baldassari, Barbara Tappino, Ferruccio Romano, Paolo Uva, Diego Vozzi, Cristina Chelleri, Gianluca Piatelli, Maria Cristina Diana, Federico Zara, Valeria Capra, Marco Pavanello and Patrizia De Marcoadd Show full author list remove Hide full author list
Cancers 2023, 15(6), 1916; https://doi.org/10.3390/cancers15061916 - 22 Mar 2023
Cited by 5 | Viewed by 3021
Abstract
Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by mutations in NF1 gene, coding for neurofibromin 1. NF1 can be associated with Moyamoya disease (MMD), and this association, typical of paediatric patients, is referred to as Moyamoya syndrome (MMS). MMD is a [...] Read more.
Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by mutations in NF1 gene, coding for neurofibromin 1. NF1 can be associated with Moyamoya disease (MMD), and this association, typical of paediatric patients, is referred to as Moyamoya syndrome (MMS). MMD is a cerebral arteriopathy characterized by the occlusion of intracranial arteries and collateral vessel formation, which increase the risk of ischemic and hemorrhagic events. RNF213 gene mutations have been associated with MMD, so we investigated whether rare variants of RNF213 could act as genetic modifiers of MMS phenotype in a pediatric cohort of 20 MMS children, 25 children affected by isolated MMD and 47 affected only by isolated NF1. By next-generation re-sequencing (NGS) of patients’ DNA and gene burden tests, we found that RNF213 seems to play a role only for MMD occurrence, while it does not appear to be involved in the increased risk of Moyamoya for MMS patients. We postulated that the loss of neurofibromin 1 can be enough for the excessive proliferation of vascular smooth muscle cells, causing Moyamoya arteriopathy associated with NF1. Further studies will be crucial to support these findings and to elucidate the possible role of other genes, enhancing our knowledge about pathogenesis and treatment of MMS. Full article
(This article belongs to the Special Issue Frontiers in Neurofibromatosis)
Show Figures

Figure 1

23 pages, 1612 KiB  
Article
Mothers with Cancer: An Intersectional Mixed-Methods Study Investigating Role Demands and Perceived Coping Abilities
by Athina Spiropoulos, Julie Deleemans, Sara Beattie and Linda E. Carlson
Cancers 2023, 15(6), 1915; https://doi.org/10.3390/cancers15061915 - 22 Mar 2023
Cited by 5 | Viewed by 3145
Abstract
Mothers with cancer report guilt associated with failing to successfully balance their parental roles and cancer. This study utilized a cross-sectional mixed-methods design and intersectional framework to investigate the multiple roles that mothers with cancer assume and their perceived coping ability. Participants included [...] Read more.
Mothers with cancer report guilt associated with failing to successfully balance their parental roles and cancer. This study utilized a cross-sectional mixed-methods design and intersectional framework to investigate the multiple roles that mothers with cancer assume and their perceived coping ability. Participants included mothers diagnosed with any type or stage of cancer, in treatment or ≤3 years post-treatment, and experiencing cancer-related disability with a dependent child (<18 years, living at home). Participants completed a questionnaire battery, semi-structured interview, and optional focus group. Descriptive statistics, correlations, and thematic inductive analyses are reported. The participants’ (N = 18) mean age was 45 years (SD = 5.50), and 67% were in active treatment. Their role participation (M = 42.74, ±6.21), role satisfaction (M = 43.32, ±5.61), and self-efficacy (M = 43.34, ±5.62) were lower than the general population score of 50. Greater role participation and higher role satisfaction were positively correlated (r = 0.74, p ≤ 0.001). A qualitative analysis revealed that the mothers retained most roles, and that their quality of life depended on their capacity to balance those roles through emotion-focused and problem-focused coping. We developed the intersectional Role Coping as a Mother with Cancer (RCMC) model, which has potential research and clinical utility. Full article
(This article belongs to the Special Issue Parenting and Cancer)
Show Figures

Figure 1

19 pages, 2921 KiB  
Article
Thai Rat-Tailed Radish Prevents Hepatocarcinogenesis in Rats by Blocking Mutagenicity, Inducing Hepatic Phase II Enzyme, and Decreasing Hepatic Pro-Inflammatory Cytokine Gene Expression
by Piman Pocasap, Natthida Weerapreeyakul and Rawiwan Wongpoomchai
Cancers 2023, 15(6), 1906; https://doi.org/10.3390/cancers15061906 - 22 Mar 2023
Cited by 5 | Viewed by 2226
Abstract
Raphanus sativus L. var. caudatus Alef (RS) is an indigenous Thai plant with nutritional and medicinal values such as anticancer activity, but only in vitro. The chemopreventive effects of RS were, therefore, investigated in the initial stage of hepatocarcinogenesis in rats. Diethylnitrosamine (DEN), [...] Read more.
Raphanus sativus L. var. caudatus Alef (RS) is an indigenous Thai plant with nutritional and medicinal values such as anticancer activity, but only in vitro. The chemopreventive effects of RS were, therefore, investigated in the initial stage of hepatocarcinogenesis in rats. Diethylnitrosamine (DEN), a carcinogen, was intraperitoneally injected into rats to induce liver cancer. Along with the DEN injection, either aqueous (RS-H2O) or dichloromethane (RS-DCM) extract was administered orally. Immunohistochemistry was used to detect glutathione S-transferase placental (GST-P) positive foci and apoptotic cells in rat livers as indicators of initial-stage carcinogenesis. The underlying mechanisms of chemoprevention were investigated with (a) antimutagenic activity, (b) hepatic phase II enzyme induction, and (c) hepatic pro-inflammatory cytokine gene expression. The results showed that RS-DCM was more potent than RS-H2O in decreasing GST-P positive foci and apoptotic cells induced by DEN. The mechanisms of RS-DCM (phenolics and sulforaphene contents) against liver carcinogenesis (1) block the activity of carcinogens; (2) elevate phase II detoxifying enzymes; and (3) suppress the pro-inflammatory gene expression. RS-H2O (phenolics contents), in contrast, only decreases pro-inflammatory gene expression. In conclusion, the RS extract consisting of phenolics and isothiocyanates exerted significant chemopreventive activity against DEN-induced liver carcinogenesis. Full article
Show Figures

Graphical abstract

22 pages, 4304 KiB  
Article
Simultaneous Inhibition of Ceramide Hydrolysis and Glycosylation Synergizes to Corrupt Mitochondrial Respiration and Signal Caspase Driven Cell Death in Drug-Resistant Acute Myeloid Leukemia
by Kelsey H. Fisher-Wellman, Miki Kassai, James T. Hagen, P. Darrell Neufer, Mark Kester, Thomas P. Loughran, Jr., Charles E. Chalfant, David J. Feith, Su-Fern Tan, Todd E. Fox, Johnson Ung, Gemma Fabrias, Jose’ Luis Abad, Arati Sharma, Upendarrao Golla, David F. Claxton, Jeremy J. P. Shaw, Debajit Bhowmick and Myles C. Cabot
Cancers 2023, 15(6), 1883; https://doi.org/10.3390/cancers15061883 - 21 Mar 2023
Cited by 5 | Viewed by 3279
Abstract
Acute myelogenous leukemia (AML), the most prevalent acute and aggressive leukemia diagnosed in adults, often recurs as a difficult-to-treat, chemotherapy-resistant disease. Because chemotherapy resistance is a major obstacle to successful treatment, novel therapeutic intervention is needed. Upregulated ceramide clearance via accelerated hydrolysis and [...] Read more.
Acute myelogenous leukemia (AML), the most prevalent acute and aggressive leukemia diagnosed in adults, often recurs as a difficult-to-treat, chemotherapy-resistant disease. Because chemotherapy resistance is a major obstacle to successful treatment, novel therapeutic intervention is needed. Upregulated ceramide clearance via accelerated hydrolysis and glycosylation has been shown to be an element in chemotherapy-resistant AML, a problem considering the crucial role ceramide plays in eliciting apoptosis. Herein we employed agents that block ceramide clearance to determine if such a “reset” would be of therapeutic benefit. SACLAC was utilized to limit ceramide hydrolysis, and D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-threo-PDMP) was used to block the glycosylation route. The SACLAC D-threo-PDMP inhibitor combination was synergistically cytotoxic in drug-resistant, P-glycoprotein-expressing (P-gp) AML but not in wt, P-gp-poor cells. Interestingly, P-gp antagonists that can limit ceramide glycosylation via depression of glucosylceramide transit also synergized with SACLAC, suggesting a paradoxical role for P-gp in the implementation of cell death. Mechanistically, cell death was accompanied by a complete drop in ceramide glycosylation, concomitant, striking increases in all molecular species of ceramide, diminished sphingosine 1-phosphate levels, resounding declines in mitochondrial respiratory kinetics, altered Akt, pGSK-3β, and Mcl-1 expression, and caspase activation. Although ceramide was generated in wt cells upon inhibitor exposure, mitochondrial respiration was not corrupted, suggestive of mitochondrial vulnerability in the drug-resistant phenotype, a potential therapeutic avenue. The inhibitor regimen showed efficacy in an in vivo model and in primary AML cells from patients. These results support the implementation of SL enzyme targeting to limit ceramide clearance as a therapeutic strategy in chemotherapy-resistant AML, inclusive of a novel indication for the use of P-gp antagonists. Full article
Show Figures

Figure 1

14 pages, 609 KiB  
Review
A Review of How Lasers Are Used in UTUC Surgery: Can the Choice of Laser Affect Outcomes?
by Mark Taratkin, Nirmish Singla, Diana Babaevskaya, Alexander Androsov, Shahrokh F. Shariat, Harun Fajkovic, Jack Baniel and Dmitry Enikeev
Cancers 2023, 15(6), 1874; https://doi.org/10.3390/cancers15061874 - 21 Mar 2023
Cited by 5 | Viewed by 2496
Abstract
Upper tract urothelial carcinoma (UTUC) is a relatively rare disease with an aggressive phenotype compared to urothelial carcinoma in the bladder. In recent years, kidney-sparing surgery (KSS) and, in particular, endoscopic surgery have become the procedure of choice among urologists where the treatment [...] Read more.
Upper tract urothelial carcinoma (UTUC) is a relatively rare disease with an aggressive phenotype compared to urothelial carcinoma in the bladder. In recent years, kidney-sparing surgery (KSS) and, in particular, endoscopic surgery have become the procedure of choice among urologists where the treatment of localized UTUC is concerned. Endoscopy tends to result in satisfactory oncological disease control while lowering morbidity and minimizing complications amongst the appropriately selected cohort of patients. While endoscopic surgery for UTUC might appear to be standardized, it, in fact, differs considerably depending on the source of energy used for resection/ablation. There has been little reliable data up to now on which laser energy source is the most superior. The goal of this review is, therefore, to outline the results of endoscopic UTUC treatment using different lasers and to analyze how these laser-tissue interactions may affect the surgery. We start by pointing out that the data remains insufficient when trying to determine which laser is the most effective in the endoscopic management of UTUC. The ever-growing number of indications for minimally invasive treatment and the increasing number of centers using laser surgery will, hopefully, lead to novel randomized controlled trials that compare the performance characteristics of the lasers as well as the effects of UTUC on patients. Full article
(This article belongs to the Special Issue Urothelial Carcinoma of the Upper Urinary Tract: What Changed?)
Show Figures

Figure 1

20 pages, 2625 KiB  
Article
Detection of Cellular Senescence Reveals the Existence of Senescent Tumor Cells within Invasive Breast Carcinomas and Related Metastases
by Cristina L. Cotarelo, Arno Schad, Marcus Schmidt, Arnd Hönig, Jonathan P. Sleeman and Sonja Thaler
Cancers 2023, 15(6), 1860; https://doi.org/10.3390/cancers15061860 - 20 Mar 2023
Cited by 5 | Viewed by 2746
Abstract
Oncogene-induced senescence is thought to constitute a barrier to carcinogenesis by arresting cells at risk of malignant transformation. However, numerous findings suggest that senescent cells may conversely promote tumor growth and metastatic progression, for example, through the senescence-associated secretory phenotype (SASP) they produce. [...] Read more.
Oncogene-induced senescence is thought to constitute a barrier to carcinogenesis by arresting cells at risk of malignant transformation. However, numerous findings suggest that senescent cells may conversely promote tumor growth and metastatic progression, for example, through the senescence-associated secretory phenotype (SASP) they produce. Here, we investigated the degree to which senescent tumor cells exist within untreated human primary breast carcinomas and whether the presence of senescent cancer cells in primary tumors is recapitulated in their matched lymph node metastases. For the detection of senescence, we used SA-β-galactosidase (SA-β-gal) staining and other senescence markers such as Ki67, p21, p53, and p16. In patients with invasive luminal A and B breast carcinomas, we found broad similarities in the appearance of cancer cells between primary tumors and their corresponding metastases. Analysis of lymph nodes from patients with other breast cancer subtypes also revealed senescent tumor cells within metastatic lesions. Collectively, our findings show that senescent tumor cells exist within primary breast carcinomas and metastatic lesions. These results suggest a potential role for senescent breast tumor cells during metastatic progression and raise the question as to whether the targeting of senescent tumor cells with anti-senescent drugs might represent a novel avenue for improved treatment of breast and other cancers. Full article
Show Figures

Figure 1

30 pages, 883 KiB  
Systematic Review
Molecular Alterations in Cutaneous Squamous Cell Carcinoma in Immunocompetent and Immunosuppressed Hosts—A Systematic Review
by Denise Ann Tsang, Steve Y. C. Tam and Choon Chiat Oh
Cancers 2023, 15(6), 1832; https://doi.org/10.3390/cancers15061832 - 17 Mar 2023
Cited by 5 | Viewed by 2498
Abstract
The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the [...] Read more.
The characterization of cutaneous squamous cell carcinoma (cSCC) at the molecular level is lacking in the current literature due to the high mutational burden of this disease. Immunosuppressed patients afflicted with cSCC experience considerable morbidity and mortality. In this article, we review the molecular profile of cSCC among the immunosuppressed and immunocompetent populations at the genetic, epigenetic, transcriptomic, and proteometabolomic levels, as well as describing key differences in the tumor immune microenvironment between these two populations. We feature novel biomarkers from the recent literature which may serve as potential targets for therapy. Full article
Show Figures

Figure 1

21 pages, 4170 KiB  
Article
Epigenetic Silencing of LRP2 Is Associated with Dedifferentiation and Poor Survival in Multiple Solid Tumor Types
by Martin Q. Rasmussen, Gitte Tindbæk, Morten Muhlig Nielsen, Camilla Merrild, Torben Steiniche, Jakob Skou Pedersen, Søren K. Moestrup, Søren E. Degn and Mette Madsen
Cancers 2023, 15(6), 1830; https://doi.org/10.3390/cancers15061830 - 17 Mar 2023
Cited by 5 | Viewed by 3503
Abstract
More than 80% of human cancers originate in epithelial tissues. Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known [...] Read more.
More than 80% of human cancers originate in epithelial tissues. Loss of epithelial cell characteristics are hallmarks of tumor development. Receptor-mediated endocytosis is a key function of absorptive epithelial cells with importance for cellular and organismal homeostasis. LRP2 (megalin) is the largest known endocytic membrane receptor and is essential for endocytosis of various ligands in specialized epithelia, including the proximal tubules of the kidney, the thyroid gland, and breast glandular epithelium. However, the role and regulation of LRP2 in cancers that arise from these tissues has not been delineated. Here, we examined the expression of LRP2 across 33 cancer types in The Cancer Genome Atlas. As expected, the highest levels of LRP2 were found in cancer types that arise from LRP2-expressing absorptive epithelial cells. However, in a subset of tumors from these cancer types, we observed epigenetic silencing of LRP2. LRP2 expression showed a strong inverse correlation to methylation of a specific CpG site (cg02361027) in the first intron of the LRP2 gene. Interestingly, low expression of LRP2 was associated with poor patient outcome in clear cell renal cell carcinoma, papillary renal cell carcinoma, mesothelioma, papillary thyroid carcinoma, and invasive breast carcinoma. Furthermore, loss of LRP2 expression was associated with dedifferentiated histological and molecular subtypes of these cancers. These observations now motivate further studies on the functional role of LRP2 in tumors of epithelial origin and the potential use of LRP2 as a cancer biomarker. Full article
(This article belongs to the Special Issue The Role of Genetic and Epigenetic Aberrations in Cancer)
Show Figures

Figure 1

20 pages, 5634 KiB  
Article
Endothelial Progenitor Cells Promote Osteosarcoma Progression and Invasiveness via AKT/PI3K Signaling
by Ofri Doppelt-Flikshtain, Amin Younis, Tal Tamari, Ofir Ginesin, Talia Shentzer-Kutiel, David Nikomarov, Gil Bar-Sela, Benjamin R. Coyac, Yehuda G. Assaraf and Hadar Zigdon-Giladi
Cancers 2023, 15(6), 1818; https://doi.org/10.3390/cancers15061818 - 17 Mar 2023
Cited by 5 | Viewed by 2510
Abstract
Background: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and [...] Read more.
Background: Osteosarcoma (OS) mortality is attributed to lung metastases. Endothelial progenitor cells (EPCs) mediate the angiogenic switch in several cancers. The spatial proximity between EPCs and OS in the bone led to the hypothesis that EPCs-osteosarcoma interactions may possibly promote OS progression and aggressiveness. Methods: A PI3K inhibitor, Bevacizumab (an anti-VEGF-A antibody), and an anti-FGF2 antibody were added to the EPCs’ conditioned medium (EPC-CM), and their impacts on OS cell (U2-OS and 143B) proliferation, migration, invasion, MMP9 expression, and AKT phosphorylation were determined. The autocrine role of VEGF-A was assessed using Bevacizumab treatment and VEGF-A silencing in OS cells. Toward this end, an orthotopic mouse OS model was established. Mouse and human tumors were immunolabeled with antibodies to the abovementioned factors. Results: EPC-CM enhanced osteosarcoma MMP9 expression, invasiveness, and migration via the PI3K/AKT pathway. The addition of Bevacizumab and an anti-FGF2 antibody to the EPC-CM diminished OS cell migration. The autocrine role of VEGF-A was assessed using Bevacizumab and VEGF-A silencing in OS cells, resulting in decreased AKT phosphorylation and, consequently, diminished invasiveness and migration. Consistently, OS xenografts in mice displayed high VEGF-A and FGF2 levels. Remarkably, lung metastasis specimens derived from OS patients exhibited marked immunolabeling of CD31, VEGF-A, and FGF2. Conclusions: EPCs promote OS progression not only by physically incorporating into blood vessels, but also by secreting cytokines, which act via paracrine signaling. EPCs induced in vitro MMP9 overexpression, invasion, and migration. Additional animal studies are warranted to further expand these results. These findings may pave the way toward the development of novel EPCs-targeted therapeutics aimed at blocking OS metastasis. Full article
Show Figures

Figure 1

12 pages, 950 KiB  
Review
Exercise Intervention for Bone Metastasis: Safety, Efficacy and Method of Delivery
by Huong Duong, Meegan Walker and Michelle Maugham-Macan
Cancers 2023, 15(6), 1786; https://doi.org/10.3390/cancers15061786 - 15 Mar 2023
Cited by 5 | Viewed by 2990
Abstract
Background: The benefits of exercise for patients with cancer are well-established, however, for patients with bone metastases, exercise as adjuvant therapy is underutilised due to concerns for safety, efficacy and other barriers such as the method of delivery. This scoping review explores these [...] Read more.
Background: The benefits of exercise for patients with cancer are well-established, however, for patients with bone metastases, exercise as adjuvant therapy is underutilised due to concerns for safety, efficacy and other barriers such as the method of delivery. This scoping review explores these barriers by reviewing the results of clinical trials conducted on participants with bone metastases. Methods: A thorough literature search was undertaken using PubMed, Scopus, NIH Clinical Trials and Google Scholar databases. Articles that involved an exercise intervention and patients with bone metastases were included. Data were pooled, charted, analysed and reported according to PRISMA-ScR standards. Results: A total of 26 trials were reviewed with interventions that included aerobic and resistance training. Only three serious adverse events occurred, not likely related to bone metastases. Nine trials (34.6%) involved unsupervised exercise sessions. Remote exercise delivery had an average of 80.3% compliance, rivalling in-person and mixed supervision. The results of this review reaffirm that exercise helps improve functional capacity, muscle strength, lean mass and cardiovascular function, and is safe in patients with bone metastases irrespective of in-person or remote delivery. Conclusions: Exercise therapy, whether delivered in person or remotely, is safe and efficacious for patients with bone metastases. Full article
Show Figures

Figure 1

20 pages, 5785 KiB  
Article
Data-Driven Assisted Decision Making for Surgical Procedure of Hepatocellular Carcinoma Resection and Prognostic Prediction: Development and Validation of Machine Learning Models
by Liyang Wang, Danjun Song, Wentao Wang, Chengquan Li, Yiming Zhou, Jiaping Zheng, Shengxiang Rao, Xiaoying Wang, Guoliang Shao, Jiabin Cai, Shizhong Yang and Jiahong Dong
Cancers 2023, 15(6), 1784; https://doi.org/10.3390/cancers15061784 - 15 Mar 2023
Cited by 5 | Viewed by 2434
Abstract
Background: Currently, surgical decisions for hepatocellular carcinoma (HCC) resection are difficult and not sufficiently personalized. We aimed to develop and validate data driven prediction models to assist surgeons in selecting the optimal surgical procedure for patients. Methods: Retrospective data from 361 [...] Read more.
Background: Currently, surgical decisions for hepatocellular carcinoma (HCC) resection are difficult and not sufficiently personalized. We aimed to develop and validate data driven prediction models to assist surgeons in selecting the optimal surgical procedure for patients. Methods: Retrospective data from 361 HCC patients who underwent radical resection in two institutions were included. End-to-end deep learning models were built to automatically segment lesions from the arterial phase (AP) of preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Clinical baseline characteristics and radiomic features were rigorously screened. The effectiveness of radiomic features and radiomic-clinical features was also compared. Three ensemble learning models were proposed to perform the surgical procedure decision and the overall survival (OS) and recurrence-free survival (RFS) predictions after taking different solutions, respectively. Results: SegFormer performed best in terms of automatic segmentation, achieving a Mean Intersection over Union (mIoU) of 0.8860. The five-fold cross-validation results showed that inputting radiomic-clinical features outperformed using only radiomic features. The proposed models all outperformed the other mainstream ensemble models. On the external test set, the area under the receiver operating characteristic curve (AUC) of the proposed decision model was 0.7731, and the performance of the prognostic prediction models was also relatively excellent. The application web server based on automatic lesion segmentation was deployed and is available online. Conclusions: In this study, we developed and externally validated the surgical decision-making procedures and prognostic prediction models for HCC for the first time, and the results demonstrated relatively accurate predictions and strong generalizations, which are expected to help clinicians optimize surgical procedures. Full article
(This article belongs to the Collection Artificial Intelligence and Machine Learning in Cancer Research)
Show Figures

Figure 1

23 pages, 1845 KiB  
Article
Association of Clinical Aspects and Genetic Variants with the Severity of Cisplatin-Induced Ototoxicity in Head and Neck Squamous Cell Carcinoma: A Prospective Cohort Study
by Ligia Traldi Macedo, Ericka Francislaine Dias Costa, Bruna Fernandes Carvalho, Gustavo Jacob Lourenço, Luciane Calonga, Arthur Menino Castilho, Carlos Takahiro Chone and Carmen Silvia Passos Lima
Cancers 2023, 15(6), 1759; https://doi.org/10.3390/cancers15061759 - 14 Mar 2023
Cited by 5 | Viewed by 2608
Abstract
Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. Methods: HNSCC patients [...] Read more.
Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. Methods: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases (GSTT1, GSTM1, GSTP1), nucleotide excision repair (XPC, XPD, XPF, ERCC1), mismatch repair (MLH1, MSH2, MSH3, EXO1), and apoptosis (P53, CASP8, CASP9, CASP3, FAS, FASL)-related proteins were analyzed regarding ototoxicity. Results: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m2. Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of GSTM1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A, EXO1 c.1762G>A, MSH3 c.3133A>G, FASL c.-844A>T, and P53 c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity. Conclusions: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models. Full article
Show Figures

Graphical abstract

18 pages, 1898 KiB  
Article
Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications
by Thuy Thi Nguyen, Diaddin Hamdan, Eurydice Angeli, Jean-Paul Feugeas, Quang Van Le, Frédéric Pamoukdjian and Guilhem Bousquet
Cancers 2023, 15(6), 1728; https://doi.org/10.3390/cancers15061728 - 12 Mar 2023
Cited by 5 | Viewed by 3015
Abstract
Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, [...] Read more.
Breast cancer brain metastases are a challenging daily practice, and the biological link between gene mutations and metastatic spread to the brain remains to be determined. Here, we performed a meta-analysis on genomic data obtained from primary tumors, extracerebral metastases and brain metastases, to identify gene alterations associated with metastatic processes in the brain. Articles with relevant findings were selected using Medline via PubMed, from January 1999 up to February 2022. A critical review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement (PRISMA). Fifty-seven publications were selected for this meta-analysis, including 37,218 patients in all, 11,906 primary tumor samples, 5541 extracerebral metastasis samples, and 1485 brain metastasis samples. We report the overall and sub-group prevalence of gene mutations, including comparisons between primary tumors, extracerebral metastases and brain metastases. In particular, we identified six genes with a higher mutation prevalence in brain metastases than in extracerebral metastases, with a potential role in metastatic processes in the brain: ESR1, ERBB2, EGFR, PTEN, BRCA2 and NOTCH1. We discuss here the therapeutic implications. Our results underline the added value of obtaining biopsies from brain metastases to fully explore their biology, in order to develop personalized treatments. Full article
(This article belongs to the Section Molecular Cancer Biology)
Show Figures

Figure 1

11 pages, 1750 KiB  
Review
Minimally Invasive ALPPS Procedure: A Review of Feasibility and Short-Term Outcomes
by Luigi Cioffi, Giulio Belli, Francesco Izzo, Corrado Fantini, Alberto D’Agostino, Gianluca Russo, Renato Patrone, Vincenza Granata and Andrea Belli
Cancers 2023, 15(6), 1700; https://doi.org/10.3390/cancers15061700 - 10 Mar 2023
Cited by 5 | Viewed by 2540
Abstract
Background: Associated liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a recent strategy to improve resectability of extensive hepatic malignancies. Recent surgical advances, such as the application of technical variants and use of a mini-invasive approach (MI-ALPPS), have been proposed [...] Read more.
Background: Associated liver partition with portal vein ligation for staged hepatectomy (ALPPS) represents a recent strategy to improve resectability of extensive hepatic malignancies. Recent surgical advances, such as the application of technical variants and use of a mini-invasive approach (MI-ALPPS), have been proposed to improve clinical outcomes in terms of morbidity and mortality. Methods: A total of 119 MI-ALPPS cases from 6 series were identified and discussed to evaluate the feasibility of the procedure and short-term clinical outcomes. Results: Hepatocellular carcinoma were widely the most common indication for MI-ALPPS. The median estimated blood loss was 260 mL during Stage 1 and 1625 mL in Stage 2. The median length of the procedures was 230 min in Stage 1 and 184 in Stage 2. The median increase ratio of future liver remnant volume was 87.8%. The median major morbidity was 8.14% in Stage 1 and 23.39 in Stage 2. The mortality rate was 0.6%. Conclusions: MI-ALPPS appears to be a feasible and safe procedure, with potentially better short-term outcomes in terms of blood loss, morbidity, and mortality rate if compared with those of open series. Full article
(This article belongs to the Special Issue Advances in Minimally Invasive Liver Resection for Cancer Therapies)
Show Figures

Figure 1