Cancers

17 pages, 2867 KiB

Open AccessArticle

HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer

by Yiling Li, Kexin Li, Xiaoying Lou, Yue Wu, Samuel Seery, Danfei Xu, Yuqing Pei, Benheng Qian, Yuxin Wu, Shuang Liang, Kui Wu and Wei Cui

Cancers 2023, 15(4), 1367; https://doi.org/10.3390/cancers15051367 - 21 Feb 2023

Cited by 2 | Viewed by 1863

Abstract

MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield [...] Read more.

MicroRNA-92a (miR-92a) may serve as a novel promising biomarker in multiple cancers, including colorectal cancer (CRC); however, the diagnostic accuracy and the underlying molecular mechanism of miR-92a in CRC is poorly understood. We first carried out meta-analysis and found that serum/plasma miR-92a yield better diagnostic efficacy when compared to stool samples and CRC tissues, and this finding was validated by our independent study through stool sample. Multiple bioinformatics assay indicated that miR-92a expression was positively correlated with heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) expression and closely related with the clinical characteristics of CRC. Experimental evidence showed that knockdown of HNRNPA2B1 could significantly decrease miR-92a expression and secretion in RKO cells. HNRNPA2B1 mediated miR-92a via m6A RNA modification. These findings indicate that HNRNPA2B1-m6A RNA modification-derived MicroRNA-92a upregulation and section from the local CRC acts a candidate noninvasive serum biomarker in colorectal cancer. Our study provides a novel insight into miR-92a mechanisms in relation to both expression and secretion for CRC diagnosis. Full article

(This article belongs to the Special Issue Advances in Blood-Based Screening for Cancer)

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20 pages, 466 KiB

Open AccessReview

Use of Telemedicine to Improve Cognitive Functions and Psychological Well-Being in Patients with Breast Cancer: A Systematic Review of the Current Literature

by Andreina Giustiniani, Laura Danesin, Rachele Pezzetta, Fabio Masina, Giulia Oliva, Giorgio Arcara, Francesca Burgio and Pierfranco Conte

Cancers 2023, 15(4), 1353; https://doi.org/10.3390/cancers15041353 - 20 Feb 2023

Cited by 2 | Viewed by 2490

Abstract

The diagnosis and side effects of breast cancer (BC) treatments greatly affect the everyday lives of women suffering from this disease, with relevant psychological and cognitive consequences. Several studies have reported the psychological effects of receiving a diagnosis of BC. Moreover, women undergoing [...] Read more.

The diagnosis and side effects of breast cancer (BC) treatments greatly affect the everyday lives of women suffering from this disease, with relevant psychological and cognitive consequences. Several studies have reported the psychological effects of receiving a diagnosis of BC. Moreover, women undergoing anticancer therapies may exhibit cognitive impairment as a side effect of the treatments. The access to cognitive rehabilitation and psychological treatment for these patients is often limited by resources; women of childbearing age often encounter difficulties in completing rehabilitation programs requiring access to care institutions. Telemedicine, which provides health services using information and communication technologies, is a useful tool to overcome these limitations. In particular, telemedicine may represent an optimal way to guarantee cognitive rehabilitation, psychological support, and recovery to BC patients. Previous studies have reviewed the use of telemedicine to improve psychological well-being in BC patients, and a few have investigated the effect of telerehabilitation on cognitive deficits. This study systematically reviewed the evidence on the cognitive and psychological effects of telemedicine in BC patients. Current evidence suggests that telemedicine may represent a promising tool for the management of some psychological problems experienced by breast cancer patients, but more controlled studies are needed to clarify its effectiveness, especially for cognitive deficits. The results are also discussed in light of the intervening and modulating factors that may mediate both side effect occurrence and the success of the interventions. Full article

(This article belongs to the Collection Breast Cancer—Therapeutic Challenges, Research Strategies and Novel Diagnostics)

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19 pages, 2203 KiB

Open AccessArticle

Canine-Inspired Chemometric Analysis of Volatile Organic Compounds in Urine Headspace to Distinguish Prostate Cancer in Mice and Men

by Mark Woollam, Amanda P. Siegel, Adam Munshi, Shengzhi Liu, Sunil Tholpady, Thomas Gardner, Bai-Yan Li, Hiroki Yokota and Mangilal Agarwal

Cancers 2023, 15(4), 1352; https://doi.org/10.3390/cancers15041352 - 20 Feb 2023

Cited by 6 | Viewed by 1935

Abstract

Canines can identify prostate cancer with high accuracy by smelling volatile organic compounds (VOCs) in urine. Previous studies have identified VOC biomarkers for prostate cancer utilizing solid phase microextraction (SPME) gas chromatography–mass spectrometry (GC-MS) but have not assessed the ability of VOCs to [...] Read more.

Canines can identify prostate cancer with high accuracy by smelling volatile organic compounds (VOCs) in urine. Previous studies have identified VOC biomarkers for prostate cancer utilizing solid phase microextraction (SPME) gas chromatography–mass spectrometry (GC-MS) but have not assessed the ability of VOCs to distinguish aggressive cancers. Additionally, previous investigations have utilized murine models to identify biomarkers but have not determined if the results are translatable to humans. To address these challenges, urine was collected from mice with prostate cancer and men undergoing prostate cancer biopsy and VOCs were analyzed by SPME GC-MS. Prior to analysis, SPME fibers/arrows were compared, and the fibers had enhanced sensitivity toward VOCs with a low molecular weight. The analysis of mouse urine demonstrated that VOCs could distinguish tumor-bearing mice with 100% accuracy. Linear discriminant analysis of six VOCs in human urine distinguished prostate cancer with sensitivity = 75% and specificity = 69%. Another panel of seven VOCs could classify aggressive cancer with sensitivity = 78% and specificity = 85%. These results show that VOCs have moderate accuracy in detecting prostate cancer and a superior ability to stratify aggressive tumors. Furthermore, the overlap in the structure of VOCs identified in humans and mice shows the merit of murine models for identifying biomarker candidates. Full article

(This article belongs to the Collection Cancer Biomarkers in Body Fluids)

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12 pages, 284 KiB

Open AccessArticle

Measuring the Wellbeing of Cancer Patients with Generic and Disease-Specific Instruments

by Gang Chen, Norma B. Bulamu, Ellen McGrane and Jeff Richardson

Cancers 2023, 15(4), 1351; https://doi.org/10.3390/cancers15041351 - 20 Feb 2023

Viewed by 1616

Abstract

Different wellbeing measures have been used among cancer patients. This study aimed to first investigate the sensitivity of health state utility (HSU), capability, and subjective wellbeing (SWB) instruments in cancer. A cancer-specific instrument (QLQ-C30) was included and transferred onto the cancer-specific HSU scores. [...] Read more.

Different wellbeing measures have been used among cancer patients. This study aimed to first investigate the sensitivity of health state utility (HSU), capability, and subjective wellbeing (SWB) instruments in cancer. A cancer-specific instrument (QLQ-C30) was included and transferred onto the cancer-specific HSU scores. Furthermore, it examined the relative importance of key life domains explaining overall life satisfaction. Data were drawn from the Multi-instrument Comparison survey. Linear regression was used to explore the extent to which the QLQ-C30 sub-scales explain HSU and SWB. Kernel-based Regularized Least Squares (KRLS), a machine learning method, was used to explore the life domain importance of cancer patients. As expected, the QLQ-C30 sub-scales explained the vast majority of the variance in its derived cancer-specific HSU (R² = 0.96), followed by generic HSU instruments (R² of 0.65–0.73) and SWB and capability instruments (R² of 0.33–0.48). The cancer-specific measure was more closely correlated with generic HSU than SWB measures, owing to the construction of these instruments. In addition to health, life achievements, relationships, the standard of living, and future security all play an important role in explaining the overall life satisfaction of cancer patients. Full article

(This article belongs to the Special Issue New Era of Cancer Research: From Large-Scale Cohorts to Big-Data)

3 pages, 194 KiB

Open AccessEditorial

Molecular Links between Cancer and Metabolic Diseases: New Perspectives and Therapeutic Strategies for Cancer Prevention and Treatment by Targeting Nutritional Patterns and Metabolic Alterations

by Mohamed Zaiou and Hamid Morjani

Cancers 2023, 15(4), 1350; https://doi.org/10.3390/cancers15041350 - 20 Feb 2023

Cited by 2 | Viewed by 1380

Abstract

Cancer-related mortality is reported to be elevated in cases with metabolic dysfunction [...] Full article

(This article belongs to the Special Issue Molecular Links between Cancer and Metabolic Diseases: New Perspectives and Therapeutic Strategies for Cancer Prevention and Treatment by Targeting Nutritional Patterns and Metabolic Alterations)

23 pages, 1511 KiB

Open AccessReview

Optimal Use of Novel Immunotherapeutics in B-Cell Precursor ALL

by Federico Lussana, Gianluca Cavallaro, Pantaleo De Simone and Alessandro Rambaldi

Cancers 2023, 15(4), 1349; https://doi.org/10.3390/cancers15041349 - 20 Feb 2023

Cited by 1 | Viewed by 2284

Abstract

Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated [...] Read more.

Novel immune therapies are currently being used for patients with R/R ALL based on their ability to induce not only hematologic but also molecular remission. Despite promising results, specific clinical conditions, such as high tumor burden or extra medullary relapse, are still associated with a remarkably poor clinical outcome. Therefore, how to optimize the choice and the timing of such new treatments within different clinical settings remains a matter of debate. In addition, with the aim of increasing the rate and depth of molecular remission, clinical studies are currently evaluating the combination of these immunotherapies with chemotherapy in the contest of frontline treatment. The preliminary data suggest that this approach may increase the cure rate and perhaps reduce the use of allogeneic stem cell transplantation (alloHSCT) in first remission. In Ph-positive ALL, reproducible results are showing that frontline treatment programs, based on the combination of tyrosine kinase inhibitors and immunotherapy, can achieve unprecedented rates of hematologic and molecular remission as well as a long-term cure, even in the absence of chemotherapy and alloHSCT. The results from these studies have led to the development of potentially curative treatment modalities, even for older ALL patients who cannot be treated with conventional intensive chemotherapy. The present review examined the evidence for an appropriate use of the new immunotherapies in ALL patients and provided some appraisal of the current and future possible uses of these drugs for achieving further therapeutic improvement in the treatment of this disease. Full article

(This article belongs to the Special Issue Therapeutic Progress in Adult Acute Lymphoblastic Leukemia)

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19 pages, 1752 KiB

Open AccessReview

Deepening Our Understanding of the Factors Affecting Landscape of Myeloproliferative Neoplasms: What Do We Know about Them?

by María Luz Morales and Francisca Ferrer-Marín

Cancers 2023, 15(4), 1348; https://doi.org/10.3390/cancers15041348 - 20 Feb 2023

Cited by 2 | Viewed by 1828

Abstract

Myeloproliferative neoplasms (MPNs) arise from the uncontrolled proliferation of hematopoietic stem and progenitor cells in bone marrow. As with all tumors, the development of MPNs is a consequence of alterations in malignant cells and their interaction with other extrinsic factors that support and [...] Read more.

Myeloproliferative neoplasms (MPNs) arise from the uncontrolled proliferation of hematopoietic stem and progenitor cells in bone marrow. As with all tumors, the development of MPNs is a consequence of alterations in malignant cells and their interaction with other extrinsic factors that support and promote tumor progression. Since the discovery of driver mutations, much work has focused on studying and reviewing the genomic features of the disease but has neglected to delve into the important role that many other mechanisms may play. This review discusses the genetic component of MPNs but focuses mainly on some of the most relevant work investigating other non-genetic factors that may be crucial for the disease. The studies summarized here address MPN cell-intrinsic or -extrinsic factors and the interaction between them through transcriptomic, proteomic and microbiota studies, among others. Full article

(This article belongs to the Special Issue Unique Perspectives in Cancer Signaling)

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13 pages, 824 KiB

Open AccessArticle

Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period

by Pierluca Piselli, Diego Serraino, Claudia Cimaglia, Lucrezia Furian, Luigi Biancone, Ghil Busnach, Nicola Bossini, Paola Todeschini, Maurizio Iaria, Franco Citterio, Mariarosaria Campise, Massimiliano Veroux, Giuseppe Tisone, Vincenzo Cantaluppi, Margherita Mangino, Simona Simone, Davide Argiolas, Andrea Ambrosini, Francesco Pisani, Flavia Caputo and Martina Taborelli Show full author list Hide full author list

Cancers 2023, 15(4), 1347; https://doi.org/10.3390/cancers15041347 - 20 Feb 2023

Cited by 2 | Viewed by 1476

Abstract

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. [...] Read more.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997–2004; 2005–2012; and 2013–2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997–2004 to 21.0 in 2013–2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76–1.07 in 2005–2012; IRR = 0.72, 95% CI: 0.60–0.87 in 2013–2021 vs. 1997–2004; P_trend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi’s sarcoma (KS; IRR = 0.37, 95% CI: 0.24–0.57 in 2005–2012; IRR = 0.09, 95% CI: 0.04–0.18 in 2013–2021; P_trend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26–2.85 in 1997–2004; SIR = 1.99, 95% CI: 1.83–2.16 in 2013–2021; P_trend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients. Full article

(This article belongs to the Section Cancer Epidemiology and Prevention)

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20 pages, 920 KiB

Open AccessReview

Prognostic and Predictive Biomarkers in Familial Breast Cancer

by Siddhartha Deb, Anannya Chakrabarti and Stephen B. Fox

Cancers 2023, 15(4), 1346; https://doi.org/10.3390/cancers15041346 - 20 Feb 2023

Cited by 1 | Viewed by 2358

Abstract

Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different [...] Read more.

Large numbers of breast cancers arise within a familial context, either with known inherited germline mutations largely within DNA repair genes, or with a strong family history of breast and/or ovarian cancer, with unknown genetic underlying mechanisms. These cancers appear to be different to sporadic cases, with earlier age of onset, increased multifocality and with association with specific breast cancer histological and phenotypic subtypes. Furthermore, tumours showing homologous recombination deficiency, due to loss of BRCA1, BRCA2, PALB2 and CHEK2 function, have been shown to be especially sensitive to platinum-based chemotherapeutics and PARP inhibition. While there is extensive research and data accrued on risk stratification and genetic predisposition, there are few data pertaining to relevant prognostic and predictive biomarkers within this breast cancer subgroup. The following is a review of such biomarkers in male and female familial breast cancer, although the data for the former are particularly sparse. Full article

(This article belongs to the Special Issue Hereditary Breast Cancer in Men and Women: Genetic Mutations, Cancer Risk and Treatment)

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11 pages, 1128 KiB

Open AccessArticle

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer

by Po-Ting Lin, Wei-Kang Hung, Ying-Hsu Chang, Ming-Li Hsieh, Chung-Yi Liu, Liang-Kang Huang, Yuan-Cheng Chu, Hung-Cheng Kan, Po-Hung Lin, Kai-Jie Yu, Cheng-Keng Chuang, Chun-Te Wu, See-Tong Pang and I-Hung Shao

Cancers 2023, 15(4), 1345; https://doi.org/10.3390/cancers15041345 - 20 Feb 2023

Viewed by 1490

Abstract

Background: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. Methods: This retrospective study included patients with intermediate- [...] Read more.

Background: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. Methods: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). Results: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Conclusions: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage. Full article

(This article belongs to the Special Issue Advances and Perspectives in Diagnosis and Treatment Strategies for Bladder Cancer)

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19 pages, 3604 KiB

Open AccessArticle

Repurposing Atovaquone as a Therapeutic against Acute Myeloid Leukemia (AML): Combination with Conventional Chemotherapy Is Feasible and Well Tolerated

by Alexandra McLean Stevens, Eric S. Schafer, Minhua Li, Maci Terrell, Raushan Rashid, Hana Paek, Melanie B. Bernhardt, Allison Weisnicht, Wesley T. Smith, Noah J. Keogh, Michelle C. Alozie, Hailey H. Oviedo, Alan K. Gonzalez, Tamilini Ilangovan, Alicia Mangubat-Medina, Haopei Wang, Eunji Jo, Cara A. Rabik, Claire Bocchini, Susan Hilsenbeck, Zachary T. Ball, Todd M. Cooper and Michele S. Redell Show full author list Hide full author list

Cancers 2023, 15(4), 1344; https://doi.org/10.3390/cancers15041344 - 20 Feb 2023

Cited by 3 | Viewed by 2097

Abstract

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited [...] Read more.

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) and blood/marrow pharmacokinetics (PK) were collected during Induction 1. Correlative studies assessed AQ-induced apoptosis and effects on OXPHOS. PDX models were treated with AQ. A total of 26 patients enrolled (ages 7.2 months–19.7 years, median 12 years); 24 were evaluable. A total of 14 (58%) and 19 (79%) evaluable patients achieved plasma concentrations above the known anti-leukemia concentration (>10 µM) by day 11 and at the end of Induction, respectively. Seven (29%) patients achieved adequate concentrations for PJP prophylaxis (>40 µM). Mean ease of administration score was 3.8. Correlative studies with AQ in patient samples demonstrated robust apoptosis, OXPHOS suppression, and prolonged survival in PDX models. Combining AQ with chemotherapy for AML appears feasible and safe in pediatric patients during Induction 1 and shows single-agent anti-leukemic effects in PDX models. AQ appears to be an ideal concomitant AML therapeutic but may require intra-patient dose adjustment to achieve concentrations sufficient for PJP prophylaxis. Full article

(This article belongs to the Special Issue Advances in Pediatric Acute Myeloid Leukemia)

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18 pages, 4835 KiB

Open AccessArticle

Development of Deep Learning with RDA U-Net Network for Bladder Cancer Segmentation

by Ming-Chan Lee, Shao-Yu Wang, Cheng-Tang Pan, Ming-Yi Chien, Wei-Ming Li, Jin-Hao Xu, Chi-Hung Luo and Yow-Ling Shiue

Cancers 2023, 15(4), 1343; https://doi.org/10.3390/cancers15041343 - 20 Feb 2023

Cited by 3 | Viewed by 1622

Abstract

In today’s high-order health examination, imaging examination accounts for a large proportion. Computed tomography (CT), which can detect the whole body, uses X-rays to penetrate the human body to obtain images. Its presentation is a high-resolution black-and-white image composed of gray scales. It [...] Read more.

In today’s high-order health examination, imaging examination accounts for a large proportion. Computed tomography (CT), which can detect the whole body, uses X-rays to penetrate the human body to obtain images. Its presentation is a high-resolution black-and-white image composed of gray scales. It is expected to assist doctors in making judgments through deep learning based on the image recognition technology of artificial intelligence. It used CT images to identify the bladder and lesions and then segmented them in the images. The images can achieve high accuracy without using a developer. In this study, the U-Net neural network, commonly used in the medical field, was used to extend the encoder position in combination with the ResBlock in ResNet and the Dense Block in DenseNet, so that the training could maintain the training parameters while reducing the overall identification operation time. The decoder could be used in combination with Attention Gates to suppress the irrelevant areas of the image while paying attention to significant features. Combined with the above algorithm, we proposed a Residual-Dense Attention (RDA) U-Net model, which was used to identify organs and lesions from CT images of abdominal scans. The accuracy (ACC) of using this model for the bladder and its lesions was 96% and 93%, respectively. The values of Intersection over Union (IoU) were 0.9505 and 0.8024, respectively. Average Hausdorff distance (AVGDIST) was as low as 0.02 and 0.12, respectively, and the overall training time was reduced by up to 44% compared with other convolution neural networks. Full article

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22 pages, 2755 KiB

Open AccessReview

DNA Methylation and Histone Modification in Low-Grade Gliomas: Current Understanding and Potential Clinical Targets

by Ahmad Ozair, Vivek Bhat, Reid S. Alisch, Atulya A. Khosla, Rupesh R. Kotecha, Yazmin Odia, Michael W. McDermott and Manmeet S. Ahluwalia

Cancers 2023, 15(4), 1342; https://doi.org/10.3390/cancers15041342 - 20 Feb 2023

Cited by 13 | Viewed by 3195

Abstract

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors [...] Read more.

Gliomas, the most common type of malignant primary brain tumor, were conventionally classified through WHO Grades I–IV (now 1–4), with low-grade gliomas being entities belonging to Grades 1 or 2. While the focus of the WHO Classification for Central Nervous System (CNS) tumors had historically been on histopathological attributes, the recently released fifth edition of the classification (WHO CNS5) characterizes brain tumors, including gliomas, using an integration of histological and molecular features, including their epigenetic changes such as histone methylation, DNA methylation, and histone acetylation, which are increasingly being used for the classification of low-grade gliomas. This review describes the current understanding of the role of DNA methylation, demethylation, and histone modification in pathogenesis, clinical behavior, and outcomes of brain tumors, in particular of low-grade gliomas. The review also highlights potential diagnostic and/or therapeutic targets in associated cellular biomolecules, structures, and processes. Targeting of MGMT promoter methylation, TET-hTDG-BER pathway, association of G-CIMP with key gene mutations, PARP inhibition, IDH and 2-HG-associated processes, TERT mutation and ARL9-associated pathways, DNA Methyltransferase (DNMT) inhibition, Histone Deacetylase (HDAC) inhibition, BET inhibition, CpG site DNA methylation signatures, along with others, present exciting avenues for translational research. This review also summarizes the current clinical trial landscape associated with the therapeutic utility of epigenetics in low-grade gliomas. Much of the evidence currently remains restricted to preclinical studies, warranting further investigation to demonstrate true clinical utility. Full article

(This article belongs to the Special Issue Updates on Molecular Targeted Therapies for CNS Tumors)

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12 pages, 1182 KiB

Open AccessArticle

Blood–Brain Barrier Disruption (BBBD)-Based Immunochemotherapy for Primary Central Nervous System Lymphoma (PCNSL), Early Results of a Phase II Study

by Hanne K. Kuitunen, Aino L. K. Rönkä, Eila M. Sonkajärvi, Juha-Matti Isokangas, Marja Pyörälä, Kari A. A. Palosaari, Anna S. Jokimäki, Anu E. Partanen, Harri J. Littow, Merja A. Vakkala, Esa J. Jantunen, Mirja E. Huttunen, Katja J. Marin, Annikki M. K. Aromaa-Häyhä, Päivi K. Auvinen, Tuomas Selander, Inka K. Puhakka and Outi M. Kuittinen

Cancers 2023, 15(4), 1341; https://doi.org/10.3390/cancers15041341 - 20 Feb 2023

Cited by 2 | Viewed by 1900

Abstract

Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood–brain barrier disruption treatment combined [...] Read more.

Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood–brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood–brain barrier disruption treatment was initiated 3–4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood–brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood–brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile. Full article

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13 pages, 2172 KiB

Open AccessArticle

Treatment Pathways and Prognosis in Advanced Sarcoma with Peritoneal Sarcomatosis

by Fabian Klingler, Hany Ashmawy, Lena Häberle, Irene Esposito, Lars Schimmöller, Wolfram Trudo Knoefel and Andreas Krieg

Cancers 2023, 15(4), 1340; https://doi.org/10.3390/cancers15041340 - 20 Feb 2023

Cited by 2 | Viewed by 1601

Abstract

Sarcomas represent a heterogeneous group of mesenchymal malignancies that most commonly occur in the extremities, retroperitoneum, and head and neck. Intra-abdominal manifestations are rare and prove particularly difficult to treat when peritoneal sarcomatosis is present. Because of the overall poor prognosis of the [...] Read more.

Sarcomas represent a heterogeneous group of mesenchymal malignancies that most commonly occur in the extremities, retroperitoneum, and head and neck. Intra-abdominal manifestations are rare and prove particularly difficult to treat when peritoneal sarcomatosis is present. Because of the overall poor prognosis of the disease, a tailored approach to surgical management is essential to achieve satisfactory outcomes with limited morbidity. We present the perioperative and long-term outcomes of 19 cases of sarcoma with peritoneal sarcomatosis treated surgically at our hospital. Treatment pathways were reviewed and clinical follow-up was performed. Patient characteristics, medical history, tumor subtype, surgical approach, hospital stay, complications, follow-up, and overall survival (OS) were assessed. Our patients were 9 women and 10 men with a median age of 45.9 years (18–88) and a median survival of 30 months (0–200). In most cases, peritoneal sarcomatosis was either discovered during surgery or the procedure was performed with palliative intent from the beginning. The surgical approach in these cases is very heterogeneous and should consider a variety of factors to tailor an approach for each patient. Sharing our experiences will help to increase knowledge about this rare disease and provide insight into the management of future cases. Full article

(This article belongs to the Special Issue Advances in Soft Tissue and Bone Sarcoma)

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12 pages, 1337 KiB

Open AccessArticle

The Impact of Prior Mammograms on the Diagnostic Performance of Radiologists in Early Breast Cancer Detection: A Focus on Breast Density, Lesion Features and Vendors Using Wholly Digital Screening Cases

by Phuong Dung (Yun) Trieu, Natacha Borecky, Tong Li, Patrick C. Brennan, Melissa L. Barron and Sarah J. Lewis

Cancers 2023, 15(4), 1339; https://doi.org/10.3390/cancers15041339 - 20 Feb 2023

Cited by 1 | Viewed by 1614

Abstract

Background: This study aims to investigate the diagnostic efficacy of radiologists when reading screening mammograms in the absence of previous images, and with the presence of prior images from the same and different vendors. Methods: 612 radiologists’ readings across 9 test sets, consisting [...] Read more.

Background: This study aims to investigate the diagnostic efficacy of radiologists when reading screening mammograms in the absence of previous images, and with the presence of prior images from the same and different vendors. Methods: 612 radiologists’ readings across 9 test sets, consisting of 540 screening mammograms (361-normal and 179-cancer) with 245 cases having prior images obtained from same vendor as current images, 129 from a different vendor and 166 cases having no prior images, were retrospectively analysed. True positive (sensitivity), true negative (specificity) and area under ROC curve (AUC) values of radiologists were calculated for three groups of cases (without prior images (NP), with prior images from same vendor (SP), and with prior images from different vendor (DP)). Logistic regression was used to estimate the odds ratio (OR) of true positive, true negative and true cancer localization among case groups with different levels of breast density and lesion characteristics. Results: Radiologists obtained 12.8% and 10.3% higher sensitivity in NP and DP than SP (0.803-and-0.785 vs. 0.712; p < 0.0001). Specificity in NP and DP cases were 4.8% and 2.0% lower than SP cases (0.749 and 0.771 vs. 0.787). The AUC values for NP and DP were significantly higher than SP cases across different levels of breast density (0.814-and-0.820 vs. 0.782; p < 0.0001). The odds ratio (OR) of true positive for NP relative to SP was 1.6 (p < 0.0001) and DP relative to SP was 1.5 (p < 0.0001). Radiologists were more like to detect architectural distortion in DP than SP cases (OR = 3.2; p < 0.0001), whilst the OR for abnormal calcifications was 2.85 (p < 0.0001). Conclusions: Cases without previous mammograms or with prior mammograms obtained from different vendors were more likely to benefit radiologists in cancer detection, whilst prior mammograms undertaken from the same vendor were more useful for radiologists in evaluating normal cases. Full article

(This article belongs to the Special Issue Breast Cancer: Risk Factors, Prevention and Early Detection)

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10 pages, 499 KiB

Open AccessArticle

Safety of Cryopreserved Stem Cell Infusion through a Peripherally Inserted Central Venous Catheter

by Sławomir Milczarek, Piotr Kulig, Alina Zuchmańska, Bartłomiej Baumert, Bogumiła Osękowska, Anna Bielikowicz, Ewa Wilk-Milczarek and Bogusław Machaliński

Cancers 2023, 15(4), 1338; https://doi.org/10.3390/cancers15041338 - 20 Feb 2023

Cited by 3 | Viewed by 2133

Abstract

The management of patients undergoing stem cell transplantation requires a multipurpose central venous catheter (CVC) to facilitate drug administration, parenteral nutrition, transfusion of blood products, and collection of blood samples. Peripherally inserted central venous catheters (PICCs) appear to meet these requirements but are [...] Read more.

The management of patients undergoing stem cell transplantation requires a multipurpose central venous catheter (CVC) to facilitate drug administration, parenteral nutrition, transfusion of blood products, and collection of blood samples. Peripherally inserted central venous catheters (PICCs) appear to meet these requirements but are rarely used for stem cell infusion. We aimed to retrospectively assess the safety and feasibility of stem cell infusion through PICC and to evaluate its impact on transplantation kinetics. We retrospectively analyzed the outcomes of peripheral blood stem cell (PBSC) transplantation in patients receiving cryopreserved autologous or allogeneic PBSC by PICCs and compared the results with patients receiving transplants through a conventionally inserted central venous catheter (CICC). Despite statistically significant differences in CD34⁺ dose, infusion rate, and total length of administration, the clinical outcomes of transplantation, exemplified by platelet and neutrophil engraftment, along with the length of hospitalization, were not affected by the prolonged infusion time and lower infusion velocity in the PICC group. Our study showed that the clinical outcomes of PBSC transplantation did not differ between the PICC and CICC groups, suggesting that both types of catheters can be implemented in a PBSC transplantation setting. Full article

(This article belongs to the Section Cancer Therapy)

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24 pages, 3408 KiB

Open AccessArticle

Molecular Insight into Drug Resistance Mechanism Conferred by Aberrant PIK3CD Splice Variant in African American Prostate Cancer

by Siyoung Ha and Bi-Dar Wang

Cancers 2023, 15(4), 1337; https://doi.org/10.3390/cancers15041337 - 20 Feb 2023

Cited by 2 | Viewed by 1642

Abstract

Targeting PI3Kδ has emerged as a promising therapy for hematologic and non-hematologic malignancies. Previously, we identified an oncogenic splice variant, PIK3CD-S, conferring Idelalisib resistance in African American (AA) prostate cancer (PCa). In the current study, we employed a comprehensive analysis combining molecular [...] Read more.

Targeting PI3Kδ has emerged as a promising therapy for hematologic and non-hematologic malignancies. Previously, we identified an oncogenic splice variant, PIK3CD-S, conferring Idelalisib resistance in African American (AA) prostate cancer (PCa). In the current study, we employed a comprehensive analysis combining molecular biology, biochemistry, histology, in silico simulation, and in vitro functional assays to investigate the PIK3CD-S expression profiles in PCa samples and to elucidate the drug resistance mechanism mediated by PI3Kδ-S (encoded by PIK3CD-S). The immunohistochemistry, RT-PCR, and Western blot assays first confirmed that PI3Kδ-S is highly expressed in AA PCa. Compared with PCa expressing the full-length PI3Kδ-L, PCa expressing PI3Kδ-S exhibits enhanced drug resistance properties, including a higher cell viability, more antiapoptotic and invasive capacities, and constitutively activated PI3K/AKT signaling, in the presence of PI3Kδ/PI3K inhibitors (Idelalisib, Seletalisib, Wortmannin, and Dactolisib). Molecular docking, ATP-competitive assays, and PI3 kinase assays have further indicated a drastically reduced affinity of PI3Kδ inhibitors with PI3Kδ-S vs. PI3Kδ-L, attributed to the lack of core binding residues in the PI3Kδ-S catalytic domain. Additionally, SRSF2 has been identified as a critical splicing factor mediating exon 20 skipping in PIK3CD pre-mRNA. The inhibition of the SRSF2 activity by SRPIN340 successfully sensitizes AA PCa cells to PI3Kδ inhibitors, suggesting a novel therapeutic option for Idelalisib-resistant tumors. Full article

(This article belongs to the Special Issue The Role of Alternative Splicing in Cancer)

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13 pages, 271 KiB

Open AccessFeature PaperArticle

A Contemporary Report of Low-Dose-Rate Brachytherapy for Prostate Cancer Using MRI for Risk Stratification: Disease Outcomes and Patient-Reported Quality of Life

by Mira Patel, William Tyler Turchan, Christopher G. Morris, Dana Augustine, Tianming Wu, Aytek Oto, Gregory P. Zagaja and Stanley L. Liauw

Cancers 2023, 15(4), 1336; https://doi.org/10.3390/cancers15041336 - 20 Feb 2023

Cited by 3 | Viewed by 1908

Abstract

Purpose: We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). Methods: 149 men with prostate [...] Read more.

Purpose: We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). Methods: 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144–145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. Results: Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2–24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. Conclusion: Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease. Full article

(This article belongs to the Special Issue New Insights into Prostate Cancer Radiotherapy)

3 pages, 188 KiB

Open AccessEditorial

Translational and Comparative Research on Innovative Anti-Cancer Therapies

by Felisbina Queiroga and Bruno Cogliati

Cancers 2023, 15(4), 1335; https://doi.org/10.3390/cancers15041335 - 20 Feb 2023

Cited by 2 | Viewed by 1148

Abstract

Oncology research has received considerable attention in recent years due to the increasing prevalence of cancer in human and animal populations worldwide [...] Full article

(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)

15 pages, 317 KiB

Open AccessReview

Occupational Cancers among Employed Women: A Narrative Review

by Federica Teglia, Giulia Collatuzzo and Paolo Boffetta

Cancers 2023, 15(4), 1334; https://doi.org/10.3390/cancers15041334 - 20 Feb 2023

Cited by 2 | Viewed by 1865

Abstract

The facts that occupational cancer in women is under-investigated, with few in-depth analyses are well known. In recent decades the workforce has changed, with an increasing number of women employed. Therefore, the inclusion of women in occupational cancer studies has become more urgent [...] Read more.

The facts that occupational cancer in women is under-investigated, with few in-depth analyses are well known. In recent decades the workforce has changed, with an increasing number of women employed. Therefore, the inclusion of women in occupational cancer studies has become more urgent and feasible than in the past decades. The difficulties to evaluate occupational causes of female gynecologic tumors in most past cohorts and the potential variation in outcome responses between men and women must be taken into consideration. This narrative review discusses women’s occupational cancer as a current area of research, focusing on three groups of workers characterized by peculiar exposure to occupational carcinogens and where women are often employed: beauticians and hairdressers; farmers; and healthcare workers. We discuss the most relevant cancers in each working category, with a particular focus on female breast cancer. In the three industries reviewed in detail, there are some risk factors which may affect primarily women, inducing breast cancer and cervical cancer, as well as risk factors that are carcinogenic in both genders, but whose effects are less well known in women. Full article

(This article belongs to the Special Issue Occupational Cancers)

24 pages, 1135 KiB

Open AccessReview

A Comprehensive View of the Cancer-Immunity Cycle (CIC) in HPV-Mediated Cervical Cancer and Prospects for Emerging Therapeutic Opportunities

by Jonathan Peña Avila, Bruno Melo Carvalho and Eliane Campos Coimbra

Cancers 2023, 15(4), 1333; https://doi.org/10.3390/cancers15041333 - 20 Feb 2023

Cited by 2 | Viewed by 4153

Abstract

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC [...] Read more.

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with more than 500,000 new cases each year and a mortality rate of around 55%. Over 80% of these deaths occur in developing countries. The most important risk factor for CC is persistent infection by a sexually transmitted virus, the human papillomavirus (HPV). Conventional treatments to eradicate this type of cancer are accompanied by high rates of resistance and a large number of side effects. Hence, it is crucial to devise novel effective therapeutic strategies. In recent years, an increasing number of studies have aimed to develop immunotherapeutic methods for treating cancer. However, these strategies have not proven to be effective enough to combat CC. This means there is a need to investigate immune molecular targets. An adaptive immune response against cancer has been described in seven key stages or steps defined as the cancer-immunity cycle (CIC). The CIC begins with the release of antigens by tumor cells and ends with their destruction by cytotoxic T-cells. In this paper, we discuss several molecular alterations found in each stage of the CIC of CC. In addition, we analyze the evidence discovered, the molecular mechanisms and their relationship with variables such as histological subtype and HPV infection, as well as their potential impact for adopting novel immunotherapeutic approaches. Full article

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

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17 pages, 1737 KiB

Open AccessReview

Implications of Transglutaminase-Mediated Protein Serotonylation in the Epigenetic Landscape, Small Cell Lung Cancer, and Beyond

by Jason Lin and Shang-Chuen Wu

Cancers 2023, 15(4), 1332; https://doi.org/10.3390/cancers15041332 - 20 Feb 2023

Cited by 1 | Viewed by 2204

Abstract

In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own [...] Read more.

In the case of small-cell lung carcinoma, the highly metastatic nature of the disease and the propensity for several chromatin modifiers to harbor mutations suggest that epigenetic manipulation may also be a promising route for oncotherapy, but histone deacetylase inhibitors on their own do not appear to be particularly effective, suggesting that there may be other regulatory parameters that dictate the effectiveness of vorinostat’s reversal of histone deacetylation. Recent discoveries that serotonylation of histone H3 alters the permissibility of gene expression have led to renewed attention to this rare modification, as facilitated by transglutaminase 2, and at the same time introduce new questions about whether this modification belongs to a part of the concerted cohort of regulator events for modulating the epigenetic landscape. This review explores the mechanistic details behind protein serotonylation and its possible connections to the epigenome via histone modifications and glycan interactions and attempts to elucidate the role of transglutaminase 2, such that optimizations to existing histone deacetylase inhibitor designs or combination therapies may be devised for lung and other types of cancer. Full article

(This article belongs to the Special Issue Evolving Role of the Thoracic Oncologic Surgeon in the Era of Molecular and Immune-Targeted Therapies for Lung Cancer)

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19 pages, 851 KiB

Open AccessReview

Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma

by Xiaoyang Lan, Gabrielle Robin, Jessica Kasnik, Grace Wong and Omar Abdel-Rahman

Cancers 2023, 15(4), 1331; https://doi.org/10.3390/cancers15041331 - 20 Feb 2023

Cited by 8 | Viewed by 2353

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients. Full article

(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment of Pancreatic Cancer)

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14 pages, 3708 KiB

Open AccessArticle

Mebendazole Treatment Disrupts the Transcriptional Activity of Hypoxia-Inducible Factors 1 and 2 in Breast Cancer Cells

by Natalie S. Joe, Yuanfeng Wang, Harsh H. Oza, Inês Godet, Nubaira Milki, Gregory J. Riggins and Daniele M. Gilkes

Cancers 2023, 15(4), 1330; https://doi.org/10.3390/cancers15041330 - 20 Feb 2023

Cited by 2 | Viewed by 3275

Abstract

Breast cancer is the most diagnosed cancer in women in the world. Mebendazole (MBZ) has been demonstrated to have preclinical efficacy across multiple cancers, including glioblastoma multiforme, medulloblastoma, colon, breast, pancreatic, and thyroid cancers. MBZ was also well tolerated in a recent phase [...] Read more.

Breast cancer is the most diagnosed cancer in women in the world. Mebendazole (MBZ) has been demonstrated to have preclinical efficacy across multiple cancers, including glioblastoma multiforme, medulloblastoma, colon, breast, pancreatic, and thyroid cancers. MBZ was also well tolerated in a recent phase I clinical trial of adults diagnosed with glioma. The mechanisms of action reported so far for MBZ include tubulin disruption, inhibiting angiogenesis, promoting apoptosis, and maintaining stemness. To elucidate additional mechanisms of action for mebendazole (MBZ), we performed RNA sequencing of three different breast cancer cell lines treated with either MBZ or vehicle control. We compared the top genes downregulated upon MBZ treatment with expression profiles of cells treated with over 15,000 perturbagens using the clue.io online analysis tool. In addition to tubulin inhibitors, the gene expression profile that correlated most with MBZ treatment matched the profile of cells treated with known hypoxia-inducible factor (HIF-1α and -2α) inhibitors. The HIF pathway is the main driver of the cellular response to hypoxia, which occurs in solid tumors. Preclinical data support using HIF inhibitors in combination with standard of care to treat solid tumors. Therefore, we tested the hypothesis that MBZ could inhibit the hypoxia response. Using RNA sequencing and HIF-reporter assays, we demonstrate that MBZ inhibits the transcriptional activity of HIFs in breast cancer cell lines and in mouse models of breast cancer by preventing the induction of HIF-1α, HIF-2α, and HIF-1β protein under hypoxia. Taken together, our results suggest that MBZ treatment has additional therapeutic efficacy in the setting of hypoxia and warrants further consideration as a cancer therapy. Full article

(This article belongs to the Section Tumor Microenvironment)

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3 pages, 196 KiB

Open AccessEditorial

Special Issue: Diagnostic and Predictive Tissue Markers in G.I. Cancers

by Stefano Chillotti and Francesco Vasuri

Cancers 2023, 15(4), 1329; https://doi.org/10.3390/cancers15041329 - 20 Feb 2023

Viewed by 1056

Abstract

The compelling advancements in systemic targeted therapies for cancer drastically changed the role of histopathological analyses in recent decades [...] Full article

(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)

3 pages, 185 KiB

Open AccessEditorial

Cancer Research in Adenocarcinoma, Adenoma, Adenomatous Polyposis Coli, and Colitis-Associated Neoplasia: A Special Issue

by Kentaro Moriichi and Mikihiro Fujiya

Cancers 2023, 15(4), 1328; https://doi.org/10.3390/cancers15041328 - 20 Feb 2023

Viewed by 1119

Abstract

Recent technological advancements have enabled us to analyze a variety of aspects of colorectal cancer (CRC), including both clinical and basic science [...] Full article

(This article belongs to the Special Issue Cancers Research in Adenocarcinoma, Adenoma, Adenomatous Polyposis Coli, Colitis-Associated Neoplasm)

19 pages, 3234 KiB

Open AccessArticle

Nano-Electrochemical Characterization of a 3D Bioprinted Cervical Tumor Model

by Maila Becconi, Simona De Zio, Francesco Falciani, Marzia Santamaria, Marco Malferrari and Stefania Rapino

Cancers 2023, 15(4), 1327; https://doi.org/10.3390/cancers15041327 - 19 Feb 2023

Cited by 3 | Viewed by 2450

Abstract

Current cancer research is limited by the availability of reliable in vivo and in vitro models that are able to reproduce the fundamental hallmarks of cancer. Animal experimentation is of paramount importance in the progress of research, but it is becoming more evident [...] Read more.

Current cancer research is limited by the availability of reliable in vivo and in vitro models that are able to reproduce the fundamental hallmarks of cancer. Animal experimentation is of paramount importance in the progress of research, but it is becoming more evident that it has several limitations due to the numerous differences between animal tissues and real, in vivo human tissues. 3D bioprinting techniques have become an attractive tool for many basic and applied research fields. Concerning cancer, this technology has enabled the development of three-dimensional in vitro tumor models that recreate the characteristics of real tissues and look extremely promising for studying cancer cell biology. As 3D bioprinting is a relatively recently developed technique, there is still a lack of characterization of the chemical cellular microenvironment of 3D bioprinted constructs. In this work, we fabricated a cervical tumor model obtained by 3D bioprinting of HeLa cells in an alginate-based matrix. Characterization of the spheroid population obtained as a function of culturing time was performed by phase-contrast and confocal fluorescence microscopies. Scanning electrochemical microscopy and platinum nanoelectrodes were employed to characterize oxygen concentrations—a fundamental characteristic of the cellular microenvironment—with a high spatial resolution within the 3D bioprinted cervical tumor model; we also demonstrated that the diffusion of a molecular model of drugs in the 3D bioprinted construct, in which the spheroids were embedded, could be measured quantitatively over time using scanning electrochemical microscopy. Full article

(This article belongs to the Special Issue Cancer Nanotherapy and Nanodiagnostic)

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13 pages, 1866 KiB

Open AccessArticle

Prognostic Factors in Pseudomyxoma Peritonei with Emphasis on the Predictive Role of Peritoneal Cancer Index and Tumor Markers

by Sebastian Blaj, David Dora, Zoltan Lohinai, Zoltan Herold, Attila Marcell Szasz, Jonas Herzberg, Roland Kodacsi, Saher Baransi, Hans Jürgen Schlitt, Matthias Hornung, Jens M. Werner, Przemyslaw Slowik, Miklos Acs and Pompiliu Piso

Cancers 2023, 15(4), 1326; https://doi.org/10.3390/cancers15041326 - 19 Feb 2023

Cited by 2 | Viewed by 2385

Abstract

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and [...] Read more.

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease. Methods: Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center. Results: We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status (p = 0.0353 and p = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies. Conclusion: Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients. Full article

(This article belongs to the Section Cancer Metastasis)

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15 pages, 3950 KiB

Open AccessArticle

The Value of Multiparametric Magnetic Resonance Imaging in the Preoperative Differential Diagnosis of Parotid Gland Tumors

by Sebastian Stoia, Manuela Lenghel, Cristian Dinu, Tiberiu Tamaș, Simion Bran, Mihaela Băciuț, Emil Boțan, Daniel Leucuța, Gabriel Armencea, Florin Onișor and Grigore Băciuț

Cancers 2023, 15(4), 1325; https://doi.org/10.3390/cancers15041325 - 19 Feb 2023

Cited by 3 | Viewed by 1779

Abstract

Background: The aim of the present study was to determine the value of multiparametric MRI in the preoperative differential diagnosis of parotid tumors, which is essential for therapeutic strategy selection. Methods: A three-year prospective study was conducted with 65 patients. Each patient was [...] Read more.

Background: The aim of the present study was to determine the value of multiparametric MRI in the preoperative differential diagnosis of parotid tumors, which is essential for therapeutic strategy selection. Methods: A three-year prospective study was conducted with 65 patients. Each patient was investigated preoperatively with multiparametric MRI and surgical excision of the tumor was performed. The preoperative imaging diagnosis was compared with the histopathological report. Several MRI parameters were analyzed, including T1 and T2 weighted image (WI), apparent diffusion coefficient (ADC), time to peak (TTP), and the time intensity curve (TIC). Results: In the differential diagnosis of benign from malignant tumors, T2WI and ADC showed statistically significant differences. Multiparametric MRI had a sensitivity, specificity, and accuracy of 81.8%, 88.6% and 92.3%, respectively. All of the studied parameters (T1, T2, TIC, TTP, ADC) were significantly different in the comparison between pleomorphic adenomas and Warthin tumors. With reference to the scope of this study, the conjunction of multiparametric and conventional MRI demonstrated a sensitivity, specificity, and accuracy of 94.1%, 100%, and 97.8%, respectively. Conclusions: Morphological analysis using conventional MRI combined with diffusion-weighted imaging (DW) and dynamic contrast–enhanced (DCE) multiparametric MRI improved the preoperative differential diagnosis of parotid gland tumors. Full article

(This article belongs to the Special Issue Salivary Glands Tumors, Head and Neck Tumors and Thymoma: Current Understanding and Future Personalized Therapeutic Approach)

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