Current Issues in Molecular Biology

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4 pages, 214 KiB

Open AccessEditorial

Molecules at Play in Cancer

by Dumitru Andrei Iacobas

Curr. Issues Mol. Biol. 2023, 45(3), 2182-2185; https://doi.org/10.3390/cimb45030140 - 7 Mar 2023

Cited by 1 | Viewed by 1371

Abstract

Despite its wide range of incidence, cancer can spontaneously occur in any part of the body and invade regions other than the originally affected tissue [...] Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

Research

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15 pages, 2338 KiB

Open AccessArticle

Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

by Wade R. Gutierrez, Jeffrey D. Rytlewski, Amanda Scherer, Grace A. Roughton, Nina C. Carnevale, Krisha Y. Vyas, Gavin R. McGivney, Qierra R. Brockman, Vickie Knepper-Adrian and Rebecca D. Dodd

Curr. Issues Mol. Biol. 2023, 45(2), 1218-1232; https://doi.org/10.3390/cimb45020080 - 2 Feb 2023

Cited by 3 | Viewed by 2176

Abstract

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research [...] Read more.

Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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13 pages, 2446 KiB

Open AccessArticle

NEAT1–SOD2 Axis Confers Sorafenib and Lenvatinib Resistance by Activating AKT in Liver Cancer Cell Lines

by Hiroyuki Tsuchiya, Ririko Shinonaga, Hiromi Sakaguchi, Yutaka Kitagawa and Kenji Yoshida

Curr. Issues Mol. Biol. 2023, 45(2), 1073-1085; https://doi.org/10.3390/cimb45020071 - 29 Jan 2023

Cited by 8 | Viewed by 2468

Abstract

This study investigated the effects of a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1) on drug resistance in liver cancer cell lines. NEAT1 knockdown activated mitogen-activated protein kinase (MAPK) signaling pathways, including MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK), [...] Read more.

This study investigated the effects of a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1) on drug resistance in liver cancer cell lines. NEAT1 knockdown activated mitogen-activated protein kinase (MAPK) signaling pathways, including MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK), but suppressed AKT. Moreover, NEAT1 knockdown sensitized liver cancer cells to sorafenib and lenvatinib, both clinically used for treating hepatocellular carcinoma, whereas it conferred resistance to an AKT-targeted drug, capivasertib. NEAT1v1 overexpression suppressed MEK/ERK and activated AKT, resulting in resistance to sorafenib and lenvatinib and sensitization to capivasertib. Superoxide dismutase 2 (SOD2) knockdown reverted the effects of NEAT1v1 overexpression on the sensitivity to the molecular-targeted drugs. Although NEAT1 or SOD2 knockdown enhanced endoplasmic reticulum (ER) stress, concomitant with the suppression of AKT, taurodeoxycholate, an ER stress suppressor, did not restore AKT activity. Although further in vivo and clinical studies are needed, these results suggested that NEAT1v1 switches the growth modality of liver cancer cell lines from MEK/ERK-dependent to AKT-dependent mode via SOD2 and regulates sensitivity to the molecular-targeted drugs independent of ER stress. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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12 pages, 1833 KiB

Open AccessArticle

Deuterium Content of the Organic Compounds in Food Has an Impact on Tumor Growth in Mice

by Gábor Somlyai, Lajos I. Nagy, László G. Puskás, András Papp, Beáta Z. Kovács, István Fórizs, György Czuppon and Ildikó Somlyai

Curr. Issues Mol. Biol. 2023, 45(1), 66-77; https://doi.org/10.3390/cimb45010005 - 21 Dec 2022

Cited by 6 | Viewed by 4165

Abstract

Research with deuterium-depleted water (DDW) in the last two decades proved that the deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted yolk (DDyolk) alone and in combination [...] Read more.

Research with deuterium-depleted water (DDW) in the last two decades proved that the deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted yolk (DDyolk) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDyolk, the drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in a 60 ppm D level in dried egg yolk that was used as a deuterium-depleted food additive. In one model, 4T1, a cell line with a high metastatic capacity to the lung was inoculated in the mice’s mammary pad. After three weeks of treatment with DDW and/or DDyolk, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D levels. Tumor growth and survival in mice transplanted with an MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of the D/H ratio in consumed water and in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that the initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDyolk, or the naturally low-D lipids in a ketogenic diet, have a significant effect on tumor growth by preventing the cells from raising the D/H ratio to the threshold. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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17 pages, 2672 KiB

Open AccessArticle

Targeting Mitochondrial ROS Production to Reverse the Epithelial-Mesenchymal Transition in Breast Cancer Cells

by Elena Monti, Alessandro Mancini, Emanuela Marras and Marzia Bruna Gariboldi

Curr. Issues Mol. Biol. 2022, 44(11), 5277-5293; https://doi.org/10.3390/cimb44110359 - 29 Oct 2022

Cited by 7 | Viewed by 2721

Abstract

Experimental evidence implicates reactive oxygen species (ROS) generation in the hypoxic stabilization of hypoxia-inducible factor (HIF)-1α and in the subsequent expression of promoters of tumor invasiveness and metastatic spread. However, the role played by mitochondrial ROS in hypoxia-induced Epithelial-Mesenchymal Transition (EMT) activation is [...] Read more.

Experimental evidence implicates reactive oxygen species (ROS) generation in the hypoxic stabilization of hypoxia-inducible factor (HIF)-1α and in the subsequent expression of promoters of tumor invasiveness and metastatic spread. However, the role played by mitochondrial ROS in hypoxia-induced Epithelial-Mesenchymal Transition (EMT) activation is still unclear. This study was aimed at testing the hypothesis that the inhibition of hypoxia-induced mitochondrial ROS production, mainly at the mitochondrial Complex III UQCRB site, could result in the reversion of EMT, in addition to decreased HIF-1α stabilization. The role of hypoxia-induced ROS increase in HIF-1α stabilization and the ability of antioxidants, some of which directly targeting mitochondrial Complex III, to block ROS production and HIF-1α stabilization and prevent changes in EMT markers were assessed by evaluating ROS, HIF-1α and EMT markers on breast cancer cells, following 48 h treatment with the antioxidants. The specific role of UQCRB in hypoxia-induced EMT was also evaluated by silencing its expression through RNA interference and by assessing the effects of its downregulation on ROS production, HIF-1α levels, and EMT markers. Our results confirm the pivotal role of UQCRB in hypoxic signaling inducing EMT. Thus, UQCRB might be a new therapeutic target for the development of drugs able to reverse EMT by blocking mitochondrial ROS production. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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21 pages, 2467 KiB

Open AccessArticle

Cellular, Molecular and Proteomic Characteristics of Early Hepatocellular Carcinoma

by Athanasios Armakolas, Vasiliki Dimopoulou, Adrianos Nezos, George Stamatakis, Martina Samiotaki, George Panayotou, Maria Tampaki, Martha Stathaki, Spyridon Dourakis and John Koskinas

Curr. Issues Mol. Biol. 2022, 44(10), 4714-4734; https://doi.org/10.3390/cimb44100322 - 10 Oct 2022

Cited by 5 | Viewed by 2542

Abstract

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early detection/diagnosis is vital for the prognosis of HCC, whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on 6-month surveillance of the patient and [...] Read more.

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early detection/diagnosis is vital for the prognosis of HCC, whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on 6-month surveillance of the patient and the use of at least two imaging modalities. The aim of this study was to investigate diagnostic markers for the detection of early HCC based on proteome analysis, microRNAs (miRNAs) and circulating tumor cells (CTCs) in the blood of patients with cirrhosis or early or advanced HCC. We studied 89 patients with HCC, of whom 33 had early HCC and 28 were cirrhotic. CTCs were detected by real-time quantitative reverse transcription PCR and immunofluorescence using the markers epithelial cell adhesion molecule (EPCAM), vimentin, alpha fetoprotein (aFP) and surface major vault protein (sMVP). Expression of the five most common HCC-involved miRNAs (miR-122, miR-200a, miR-200b, miR-221, miR-222) was examined in serum using quantitative real time PCR (qRT-PCR). Finally, patient serum was analyzed via whole proteome analysis (LC/MS). Of 53 patients with advanced HCC, 27 (51%) had detectable CTCs. Among these, 10/27 (37%) presented evidence of mesenchymal or intermediate stage cells (vimentin and/or sMVP positive). Moreover, 5/17 (29%) patients with early HCC and 2/28 (7%) cirrhotic patients had detectable CTCs. Patients with early or advanced HCC exhibited a significant increase in miR-200b when compared to cirrhotic patients. Our proteome analysis indicated that early HCC patients present a significant upregulation of APOA2, APOC3 proteins when compared to cirrhotic patients. When taken in combination, this covers the 100% of the patients with early HCC. miR-200b, APOA2 and APOC3 proteins are sensitive markers and can be potentially useful in combination for the early diagnosis of HCC. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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14 pages, 9164 KiB

Open AccessArticle

MiR-942-3p as a Potential Prognostic Marker of Gastric Cancer Associated with AR and MAPK/ERK Signaling Pathway

by Wenjia Liu, Nanjiao Ying, Xin Rao and Xiaodong Chen

Curr. Issues Mol. Biol. 2022, 44(9), 3835-3848; https://doi.org/10.3390/cimb44090263 - 24 Aug 2022

Cited by 4 | Viewed by 1945

Abstract

Gastric cancer is a common tumor with high morbidity and mortality. MicroRNA (miRNA) can regulate gene expression at the translation level and various tumorigenesis processes, playing an important role in tumor occurrence and prognosis. This study aims to screen miRNA associated with gastric [...] Read more.

Gastric cancer is a common tumor with high morbidity and mortality. MicroRNA (miRNA) can regulate gene expression at the translation level and various tumorigenesis processes, playing an important role in tumor occurrence and prognosis. This study aims to screen miRNA associated with gastric cancer prognosis as biomarkers and explore the regulatory genes and related signaling pathways. In this work, R language was used for the standardization and differential analysis of miRNA and mRNA expression profiles. Samples were randomly divided into a testing group and a training group. Subsequently, we built the five miRNAs (has-miR-9-3p, has-miR-135b-3p, has-miR-143-5p, has-miR-942-3p, has-miR-196-3p) prognostic modules, verified and evaluated their prediction ability by the Cox regression analysis. They can be used as an independent factor in the prognosis of gastric cancer. By predicting and analyzing potential biological functions of the miRNA target genes, this study found that the AR gene was not only a hub gene in the PPI network, but also associated with excessive survival of patients. In conclusion, this study demonstrated that hsa-miR-942-3p could be a potential prognostic marker of gastric cancer associated with the AR and MAPK/ERK signaling pathways. The results of this study provide insights into the occurrence and development of gastric cancer. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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18 pages, 4271 KiB

Open AccessArticle

Presence of Human Papillomavirus DNA in Malignant Neoplasia and Non-Malignant Breast Disease

by Erika Maldonado-Rodríguez, Marisa Hernández-Barrales, Adrián Reyes-López, Susana Godina-González, Perla I. Gallegos-Flores, Edgar L. Esparza-Ibarra, Irma E. González-Curiel, Jesús Aguayo-Rojas, Adrián López-Saucedo, Gretel Mendoza-Almanza and Jorge L. Ayala-Luján

Curr. Issues Mol. Biol. 2022, 44(8), 3648-3665; https://doi.org/10.3390/cimb44080250 - 13 Aug 2022

Cited by 9 | Viewed by 3842

Abstract

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease’s development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although [...] Read more.

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease’s development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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22 pages, 2656 KiB

Open AccessArticle

«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer

by Lyudmila V. Bel’skaya and Elena A. Sarf

Curr. Issues Mol. Biol. 2022, 44(7), 3053-3074; https://doi.org/10.3390/cimb44070211 - 5 Jul 2022

Cited by 7 | Viewed by 2209

Abstract

The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 [...] Read more.

The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 patients with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients strictly before the start of treatment and the values of 42 biochemical indicators were determined. It has been established that the saliva of healthy volunteers and patients with various molecular biological subtypes of breast cancer differs in 12 biochemical indicators: concentrations of protein, urea, nitric oxide, malondialdehyde, total amino acid content, and activity of lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, catalase, amylase, superoxide dismutase, and peroxidases. The saliva composition of patients with basal-like breast cancer differs from other subtypes in terms of the maximum number of indicators. Changes in biochemical indicators indicated an increase in the processes of lipid peroxidation and endogenous intoxication and a weakening of antioxidant protection, which correlates with the severity of the disease and the least favorable prognosis for this subtype of breast cancer. An analysis was made of the individual contribution of the expression level of HER2, estrogen, and progesterone receptors to changes in the biochemical composition of saliva. The HER2 (−)/HER2 (+) group, which should be considered as a single group, as well as ER-positive breast cancer, differ statistically significantly from the control group. For ER/PR-positive breast cancer, a more favorable ratio of saliva biochemical indicators was also noted compared to ER/PR-negative breast cancer. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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13 pages, 3742 KiB

Open AccessArticle

Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells

by Zhewen Zhang, Juan Yi, Bei Xie, Jing Chen, Xueyan Zhang, Li Wang, Jingyu Wang, Jinxia Hou and Hulai Wei

Curr. Issues Mol. Biol. 2022, 44(6), 2759-2771; https://doi.org/10.3390/cimb44060189 - 20 Jun 2022

Cited by 4 | Viewed by 2499 | Correction

Abstract

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant [...] Read more.

Parkin is a well-established synergistic mediator of mitophagy in dysfunctional mitochondria. Mitochondria are the main target of arsenic trioxide (ATO) cytotoxicity, and the effect of mitophagy on ATO action remains unclear. In this study, we used stable Parkin-expressing (YFP-Parkin) and Parkin loss-of-function mutant (Parkin C431S) HeLa cell models to ascertain whether Parkin-mediated mitophagy participates in ATO-induced apoptosis/cell death. Our data showed that the overexpression of Parkin significantly sensitized HeLa cells to ATO-initiated proliferation inhibition and apoptosis; however, the mutation of Parkin C431S significantly weakened this Parkin-mediated responsiveness. Our further investigation found that ATO significantly downregulated two fusion proteins (Mfn1/2) and upregulated fission-related protein (Drp1). Autophagy was also activated as evidenced by the formation of autophagic vacuoles and mitophagosomes, increased expression of PINK1, and recruitment of Parkin to impaired mitochondria followed by their degradation, accompanied by the increased transformation of LC3-I to LC3-II, increased expression of Beclin1 and decreased expression of P62 in YFP-Parkin HeLa cells. Enhanced mitochondrial fragmentation and autophagy indicated that mitophagy was activated. Furthermore, during the process of mitophagy, the overproduction of ROS implied that ROS might represent a key factor that initiates mitophagy following Parkin recruitment to mitochondria. In conclusion, our findings indicate that Parkin is critically involved in ATO-triggered mitophagy and functions as a potential antiproliferative target in cancer cells. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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18 pages, 10928 KiB

Open AccessArticle

Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

by Wallax Augusto Silva Ferreira and Edivaldo Herculano Correa de Oliveira

Curr. Issues Mol. Biol. 2022, 44(6), 2472-2489; https://doi.org/10.3390/cimb44060169 - 25 May 2022

Cited by 7 | Viewed by 2871

Abstract

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, [...] Read more.

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of GOT2 in KIRC remain unclear. This study comprehensively analyzed the transcriptional levels, epigenetic regulation, correlation with immune infiltration, and prognosis of GOT2 in KIRC using rigorous bioinformatics analysis. We discovered that the expression levels of both mRNA and protein of GOT2 were remarkably decreased in KIRC tissues in comparison with normal tissues and were also significantly related to the clinical features and prognosis of KIRC. Remarkably, low GOT2 expression was positively associated with poorer overall survival (OS) and disease-free survival (DFS). Further analysis revealed that GOT2 downregulation is driven by DNA methylation in the promoter-related CpG islands. Finally, we also shed light on the influence of GOT2 expression in immune cell infiltration, suggesting that GOT2 may be a potential prognostic marker and therapeutic target for KIRC patients. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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12 pages, 549 KiB

Open AccessArticle

The Search for Cancer Biomarkers: Assessing the Distribution of INDEL Markers in Different Genetic Ancestries

by Roberta B. Andrade, Giovanna C. Cavalcante, Marcos A. T. Amador, Fabiano Cordeiro Moreira, André S. Khayat, Paulo P. Assumpção, Ândrea Ribeiro-dos-Santos, Ney P. C. Santos and Sidney Santos

Curr. Issues Mol. Biol. 2022, 44(5), 2275-2286; https://doi.org/10.3390/cimb44050154 - 19 May 2022

Cited by 3 | Viewed by 2174

Abstract

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of [...] Read more.

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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9 pages, 793 KiB

Open AccessArticle

sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma

by Katja Seipel, Naomi Porret, Gertrud Wiedemann, Barbara Jeker, Vera Ulrike Bacher and Thomas Pabst

Curr. Issues Mol. Biol. 2022, 44(4), 1463-1471; https://doi.org/10.3390/cimb44040098 - 24 Mar 2022

Cited by 17 | Viewed by 4175

Abstract

BACKGROUND: Novel chimeric antigen receptor T-cells (CAR-T) target the B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. Assays monitoring CAR-T cell expansion and treatment response are being implemented in clinical routine. METHODS: Plasma levels of soluble BCMA (sBCMA) and anti-BCMA CAR-T cell [...] Read more.

BACKGROUND: Novel chimeric antigen receptor T-cells (CAR-T) target the B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. Assays monitoring CAR-T cell expansion and treatment response are being implemented in clinical routine. METHODS: Plasma levels of soluble BCMA (sBCMA) and anti-BCMA CAR-T cell copy numbers were monitored in the blood, following CAR-T cell infusion in patients with relapsed multiple myeloma. sBCMA peptide concentration was determined in the plasma, applying a human BCMA/TNFRS17 ELISA. ddPCR was performed using probes targeting the intracellular signaling domains 4-1BB und CD3zeta of the anti-BCMA CAR-T construct. RESULTS: We report responses in the first five patients who received anti-BCMA CAR- T cell therapy at our center. Four patients achieved a complete remission (CR) in the bone marrow one month after CAR-T infusion, with three patients achieving stringent CR, determined by flow cytometry techniques. Anti-BCMA CAR-T cells were detectable in the peripheral blood for up to 300 days, with copy numbers peaking 7 to 14 days post-infusion. sBCMA plasma levels started declining one to ten days post infusion, reaching minimal levels 30 to 60 days post infusion, before rebounding to normal levels. CONCLUSIONS: Our data confirm a favorable response to treatment in four of the first five patients receiving anti-BCMA CAR-T at our hospital. Anti-BCMA CAR-T cell expansion seems to peak in the peripheral blood in a similar pattern compared to the CAR-T cell products already approved for lymphoma treatment. sBCMA plasma level may be a valid biomarker in assessing response to BCMA-targeting therapies in myeloma patients. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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12 pages, 1926 KiB

Open AccessArticle

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer

by Se-Il Go, Gyung Hyuck Ko, Won Sup Lee, Jeong-Hee Lee, Sang-Ho Jeong, Young-Joon Lee, Soon Chan Hong and Woo Song Ha

Curr. Issues Mol. Biol. 2022, 44(3), 1395-1406; https://doi.org/10.3390/cimb44030093 - 20 Mar 2022

Cited by 3 | Viewed by 2467

Abstract

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor [...] Read more.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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12 pages, 2074 KiB

Open AccessArticle

Zinc Finger E-Box Binding Homeobox 2 as a Prognostic Biomarker in Various Cancers and Its Correlation with Infiltrating Immune Cells in Ovarian Cancer

by Hye-Ran Kim, Choong Won Seo, Sang Jun Han, Jae-Ho Lee and Jongwan Kim

Curr. Issues Mol. Biol. 2022, 44(3), 1203-1214; https://doi.org/10.3390/cimb44030079 - 1 Mar 2022

Cited by 3 | Viewed by 3356

Abstract

This study investigated the expression of zinc finger E-box binding homeobox 2 (ZEB2), its prognostic significance in various cancers, and the correlation between ZEB2 and infiltrating immune cells and ZEB2-related proteins in ovarian cancer (OV). The Gene Expression Profiling Interactive Analysis tool was [...] Read more.

This study investigated the expression of zinc finger E-box binding homeobox 2 (ZEB2), its prognostic significance in various cancers, and the correlation between ZEB2 and infiltrating immune cells and ZEB2-related proteins in ovarian cancer (OV). The Gene Expression Profiling Interactive Analysis tool was used to analyze RNA sequencing data and cancer survival rates, based on normal and tumor tissue data available in The Cancer Genome Atlas (TCGA) database. The Kaplan–Meier plotter and PrognoScan databases were used to analyze the prognostic value of ZEB2 in OV (n = 1144). The Tumor Immune Estimation Resource was used to investigate the correlation between ZEB2 and infiltrating immune cells in various cancers, including OV. High ZEB2 expression was associated with a poorer prognosis in OV. In OV, ZEB2 is positively correlated with CD8+T cells, neutrophils, macrophages, and dendritic cell invasion; and ZEB2 is negatively correlated with tumor-infiltrating B cells. The STRING database was used to investigate the correlations with ZEB2-related proteins. The results reveal that ZEB2 was positively correlated with SMAD1 and SMAD2 in OV. Our findings may serve as a potential prognostic biomarker, and provide novel insights into the tumor immunology in OV. Thus, ZEB2 may be a potential diagnostic and therapeutic target in OV. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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14 pages, 1342 KiB

Open AccessArticle

Single Circulating-Tumor-Cell-Targeted Sequencing to Identify Somatic Variants in Liquid Biopsies in Non-Small-Cell Lung Cancer Patients

by Mouadh Barbirou, Amanda Miller, Yariswamy Manjunath, Arturo B. Ramirez, Nolan G. Ericson, Kevin F. Staveley-O’Carroll, Jonathan B. Mitchem, Wesley C. Warren, Aadel A. Chaudhuri, Yi Huang, Guangfu Li, Peter J. Tonellato and Jussuf T. Kaifi

Curr. Issues Mol. Biol. 2022, 44(2), 750-763; https://doi.org/10.3390/cimb44020052 - 2 Feb 2022

Cited by 9 | Viewed by 5246

Abstract

Non-small-cell lung cancer (NSCLC) accounts for most cancer-related deaths worldwide. Liquid biopsy by a blood draw to detect circulating tumor cells (CTCs) is a tool for molecular profiling of cancer using single-cell and next-generation sequencing (NGS) technologies. The aim of the study was [...] Read more.

Non-small-cell lung cancer (NSCLC) accounts for most cancer-related deaths worldwide. Liquid biopsy by a blood draw to detect circulating tumor cells (CTCs) is a tool for molecular profiling of cancer using single-cell and next-generation sequencing (NGS) technologies. The aim of the study was to identify somatic variants in single CTCs isolated from NSCLC patients by targeted NGS. Thirty-one subjects (20 NSCLC patients, 11 smokers without cancer) were enrolled for blood draws (7.5 mL). CTCs were identified by immunofluorescence, individually retrieved, and DNA-extracted. Targeted NGS was performed to detect somatic variants (single-nucleotide variants (SNVs) and insertions/deletions (Indels)) across 65 oncogenes and tumor suppressor genes. Cancer-associated variants were classified using OncoKB database. NSCLC patients had significantly higher CTC counts than control smokers (p = 0.0132; Mann–Whitney test). Analyzing 23 CTCs and 13 white blood cells across seven patients revealed a total of 644 somatic variants that occurred in all CTCs within the same subject, ranging from 1 to 137 per patient. The highest number of variants detected in ≥1 CTC within a patient was 441. A total of 18/65 (27.7%) genes were highly mutated. Mutations with oncogenic impact were identified in functional domains of seven oncogenes/tumor suppressor genes (NF1, PTCH1, TP53, SMARCB1, SMAD4, KRAS, and ERBB2). Single CTC-targeted NGS detects heterogeneous and shared mutational signatures within and between NSCLC patients. CTC single-cell genomics have potential for integration in NSCLC precision oncology. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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23 pages, 3970 KiB

Open AccessArticle

Personalized 3-Gene Panel for Prostate Cancer Target Therapy

by Sanda Iacobas and Dumitru Andrei Iacobas

Curr. Issues Mol. Biol. 2022, 44(1), 360-382; https://doi.org/10.3390/cimb44010027 - 15 Jan 2022

Cited by 6 | Viewed by 3632

Abstract

Many years and billions spent for research did not yet produce an effective answer to prostate cancer (PCa). Not only each human, but even each cancer nodule in the same tumor, has unique transcriptome topology. The differences go beyond the expression level to [...] Read more.

Many years and billions spent for research did not yet produce an effective answer to prostate cancer (PCa). Not only each human, but even each cancer nodule in the same tumor, has unique transcriptome topology. The differences go beyond the expression level to the expression control and networking of individual genes. The unrepeatable heterogeneous transcriptomic organization among men makes the quest for universal biomarkers and “fit-for-all” treatments unrealistic. We present a bioinformatics procedure to identify each patient’s unique triplet of PCa Gene Master Regulators (GMRs) and predict consequences of their experimental manipulation. The procedure is based on the Genomic Fabric Paradigm (GFP), which characterizes each individual gene by the independent expression level, expression variability and expression coordination with each other gene. GFP can identify the GMRs whose controlled alteration would selectively kill the cancer cells with little consequence on the normal tissue. The method was applied to microarray data on surgically removed prostates from two men with metastatic PCas (each with three distinct cancer nodules), and DU145 and LNCaP PCa cell lines. The applications verified that each PCa case is unique and predicted the consequences of the GMRs’ manipulation. The predictions are theoretical and need further experimental validation. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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10 pages, 1928 KiB

Open AccessArticle

Soluble CD147 (BSG) as a Prognostic Marker in Multiple Myeloma

by Piotr Łacina, Aleksandra Butrym, Diana Frontkiewicz, Grzegorz Mazur and Katarzyna Bogunia-Kubik

Curr. Issues Mol. Biol. 2022, 44(1), 350-359; https://doi.org/10.3390/cimb44010026 - 14 Jan 2022

Cited by 8 | Viewed by 3236

Abstract

CD147 (basigin, BSG) is a membrane-bound glycoprotein involved in energy metabolism that plays a role in cancer cell survival. Its soluble form is a promising marker of some diseases, but it is otherwise poorly studied. CD147 is overexpressed in multiple myeloma (MM) and [...] Read more.

CD147 (basigin, BSG) is a membrane-bound glycoprotein involved in energy metabolism that plays a role in cancer cell survival. Its soluble form is a promising marker of some diseases, but it is otherwise poorly studied. CD147 is overexpressed in multiple myeloma (MM) and is known to affect MM progression, while its genetic variants are associated with MM survival. In the present study, we aimed to assess serum soluble CD147 (sCD147) expression as a potential marker in MM. We found that sCD147 level was higher in MM patients compared to healthy individuals. It was also higher in patients with more advanced disease (ISS III) compared to both patients with less advanced MM and healthy individuals, while its level was observed to drop after positive response to treatment. Patients with high sCD147 were characterized by worse progression-free survival. sCD147 level did not directly correlate with bone marrow CD147 mRNA expression. In conclusion, this study suggests that serum sCD147 may be a prognostic marker in MM. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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13 pages, 2318 KiB

Open AccessArticle

Circulating Exosomal miR-1290 for Diagnosis of Epithelial Ovarian Cancer

by Hyeji Jeon, Su Min Seo, Tae Wan Kim, Jaesung Ryu, Hyejeong Kong, Si Hyeong Jang, Yong Soo Jang, Kwang Seock Kim, Jae Hoon Kim, Seongho Ryu and Seob Jeon

Curr. Issues Mol. Biol. 2022, 44(1), 288-300; https://doi.org/10.3390/cimb44010021 - 9 Jan 2022

Cited by 21 | Viewed by 3464

Abstract

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 [...] Read more.

The aim of the study was to develop a new diagnostic biomarker for identifying serum exosomal miRNAs specific to epithelial ovarian cancer (EOC) and to find out target gene of the miRNA for exploring the molecular mechanisms in EOC. A total of 84 cases of ovarian masses and sera were enrolled, comprising EOC (n = 71), benign ovarian neoplasms (n = 13). We detected expression of candidate miRNAs in the serum and tissue of both benign ovarian neoplasm group and EOC group using real-time polymerase chain reaction. Immunohistochemistry were constructed using formalin fixed paraffin embedded (FFPE) tissue to detect expression level of suppressor of cytokine signaling 4 (SOCS4). In the EOC group, miRNA-1290 was significantly overexpressed in serum exosomes and tissues as compared to benign ovarian neoplasm group (fold change ≥ 2, p < 0.05). We observed area under the receiver operating characteristic curve (AUC) for miR-1290, using a cut-off of 0.73, the exosomal miR-1290 from serum had AUC, sensitivity, and specificity values of 0.794, 69.2 and 87.3, respectively. In immunohistochemical study, expression of SOCS4 in EOC was lower than that in benign ovarian neoplasm. Serum exosomal miR-1290 could be considered as a biomarker for differential diagnosis of EOC from benign ovarian neoplasm and SOCS4 might be potential target gene of miR-1290 in EOC. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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9 pages, 1178 KiB

Open AccessCommunication

Possibility of SARS-CoV-2 Infection in the Metastatic Microenvironment of Cancer

by Takuma Hayashi, Kenji Sano and Ikuo Konishi

Curr. Issues Mol. Biol. 2022, 44(1), 233-241; https://doi.org/10.3390/cimb44010017 - 5 Jan 2022

Cited by 3 | Viewed by 2034

Abstract

According to a report from the World Health Organization (WHO), the mortality and disease severity induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher in cancer patients than those of individuals with no known condition. Common and cancer-specific risk [...] Read more.

According to a report from the World Health Organization (WHO), the mortality and disease severity induced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are significantly higher in cancer patients than those of individuals with no known condition. Common and cancer-specific risk factors might be involved in the mortality and severity rates observed in the coronavirus disease 2019 (COVID-19). Similarly, various factors might contribute to the aggravation of COVID-19 in patients with cancer. However, the factors involved in the aggravation of COVID-19 in cancer patients have not been fully investigated so far. The formation of metastases in other organs is common in cancer patients. Therefore, the present study investigated the association between lung metastatic lesion formation and SARS-CoV-2 infectivity. In the pulmonary micrometastatic niche of patients with ovarian cancer, alveolar epithelial stem-like cells were found adjacent to ovarian cancer. Moreover, angiotensin-converting enzyme 2, a host-side receptor for SARS-CoV-2, was expressed in these alveolar epithelial stem-like cells. Furthermore, the spike glycoprotein receptor-binding domain (RBD) of SARS-CoV-2 was bound to alveolar epithelial stem-like cells. Altogether, these data suggested that patients with cancer and pulmonary micrometastases are more susceptible to SARS-CoV-2. The prevention of de novo niche formation in metastatic diseases might constitute a new strategy for the clinical treatment of COVID-19 for patients with cancer. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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11 pages, 1804 KiB

Open AccessArticle

PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

by Wen-Jung Chen, Wen-Wei Sung, Chia-Ying Yu, Yu-Ze Luan, Ya-Chuan Chang, Sung-Lang Chen and Tsung-Hsien Lee

Curr. Issues Mol. Biol. 2022, 44(1), 222-232; https://doi.org/10.3390/cimb44010016 - 4 Jan 2022

Cited by 2 | Viewed by 2518

Abstract

Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to [...] Read more.

Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to inhibit this pathway has identified a small molecule, PNU-74654, as an inhibitor of the β-catenin/TCF4 interaction. We evaluated the therapeutic role of PNU-74654 in two TC cell lines, NCCIT and NTERA2, by measuring cell viability, cell cycle transition and cell death. Potential pathways were evaluated by protein arrays and Western blots. PNU-74654 decreased cell viability and induced apoptosis of TC cells, with significant increases in the sub G1, Hoechst-stained, Annexin V-PI-positive rates. PNU-74654 treatment of both TC cell lines inhibited the TNFR1/IKB alpha/p65 pathway and the execution phase of apoptosis. Our findings demonstrate that PNU-74654 can induce apoptosis in TC cells through mechanisms involving the execution phase of apoptosis and inhibition of TNFR1/IKB alpha/p65 signaling. Therefore, small molecules such as PNU-74654 may identify potential new treatment strategies for TC. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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17 pages, 4450 KiB

Open AccessArticle

Lessons from a Single Amino Acid Substitution: Anticancer and Antibacterial Properties of Two Phospholipase A₂-Derived Peptides

by José R. Almeida, Bruno Mendes, Marcelo Lancellotti, Gilberto C. Franchi, Jr., Óscar Passos, Maria J. Ramos, Pedro A. Fernandes, Cláudia Alves, Nuno Vale, Paula Gomes and Saulo L. da Silva

Curr. Issues Mol. Biol. 2022, 44(1), 46-62; https://doi.org/10.3390/cimb44010004 - 22 Dec 2021

Cited by 16 | Viewed by 4899

Abstract

The membrane-active nature of phospholipase A₂-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA₂ toxins (p-AppK and p-Acl), differing by a leucine/phenylalanine substitution, were synthesized and their bioactivity [...] Read more.

The membrane-active nature of phospholipase A₂-derived peptides makes them potential candidates for antineoplastic and antibacterial therapies. Two short 13-mer C-terminal fragments taken from snake venom Lys49-PLA₂ toxins (p-AppK and p-Acl), differing by a leucine/phenylalanine substitution, were synthesized and their bioactivity was evaluated. Their capacity to interfere with the survival of Gram-positive and Gram-negative bacteria as well as with solid and liquid tumors was assessed in vitro. Toxicity to red blood cells was investigated via in silico and in vitro techniques. The mode of action was mainly studied by molecular dynamics simulations and membrane permeabilization assays. Briefly, both peptides have dual activity, i.e., they act against both bacteria, including multidrug-resistant strains and tumor cells. All tested bacteria were susceptible to both peptides, Pseudomonas aeruginosa being the most affected. RAMOS, K562, NB4, and CEM cells were the main leukemic targets of the peptides. In general, p-Acl showed more significant activity, suggesting that phenylalanine confers advantages to the antibacterial and antitumor mechanism, particularly for osteosarcoma lines (HOS and MG63). Peptide-based treatment increased the uptake of a DNA-intercalating dye by bacteria, suggesting membrane damage. Indeed, p-AppK and p-Acl did not disrupt erythrocyte membranes, in agreement with in silico predictions. The latter revealed that the peptides deform the membrane and increase its permeability by facilitating solvent penetration. This phenomenon is expected to catalyze the permeation of solutes that otherwise could not cross the hydrophobic membrane core. In conclusion, the present study highlights the role of a single amino acid substitution present in natural sequences towards the development of dual-action agents. In other words, dissecting and fine-tuning biomembrane remodeling proteins, such as snake venom phospholipase A₂ isoforms, is again demonstrated as a valuable source of therapeutic peptides. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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Review

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10 pages, 2382 KiB

Open AccessReview

Exceptional Repositioning of Dog Dewormer: Fenbendazole Fever

by Tania Sultana, Umair Jan, Hyunsu Lee, Hyejin Lee and Jeong Ik Lee

Curr. Issues Mol. Biol. 2022, 44(10), 4977-4986; https://doi.org/10.3390/cimb44100338 - 17 Oct 2022

Cited by 4 | Viewed by 16144

Abstract

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult [...] Read more.

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician’s knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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10 pages, 959 KiB

Open AccessReview

Nematode-Applied Technology for Human Tumor Microenvironment Research and Development

by Eric di Luccio, Satoru Kaifuchi, Nobuaki Kondo, Ryota Chijimatsu, Andrea Vecchione, Takaaki Hirotsu and Hideshi Ishii

Curr. Issues Mol. Biol. 2022, 44(2), 988-997; https://doi.org/10.3390/cimb44020065 - 21 Feb 2022

Cited by 2 | Viewed by 3764

Abstract

Nematodes, such as Caenorhabditis elegans, have been instrumental to the study of cancer. Recently, their significance as powerful cancer biodiagnostic tools has emerged, but also for mechanism analysis and drug discovery. It is expected that nematode-applied technology will facilitate research and development [...] Read more.

Nematodes, such as Caenorhabditis elegans, have been instrumental to the study of cancer. Recently, their significance as powerful cancer biodiagnostic tools has emerged, but also for mechanism analysis and drug discovery. It is expected that nematode-applied technology will facilitate research and development on the human tumor microenvironment. In the history of cancer research, which has been spurred by numerous discoveries since the last century, nematodes have been important model organisms for the discovery of cancer microenvironment. First, microRNAs (miRNAs), which are noncoding small RNAs that exert various functions to control cell differentiation, were first discovered in C. elegans and have been actively incorporated into cancer research, especially in the study of cancer genome defects. Second, the excellent sense of smell of nematodes has been applied to the diagnosis of diseases, especially refractory tumors, such as human pancreatic cancer, by sensing complex volatile compounds derived from heterogeneous cancer microenvironment, which are difficult to analyze using ordinary analytical methods. Third, a nematode model system can help evaluate invadosomes, the phenomenon of cell invasion by direct observation, which has provided a new direction for cancer research by contributing to the elucidation of complex cell–cell communications. In this cutting-edge review, we highlight milestones in cancer research history and, from a unique viewpoint, focus on recent information on the contributions of nematodes in cancer research towards precision medicine in humans. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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2 pages, 1512 KiB

Open AccessCorrection

Correction: Zhang et al. Parkin, as a Regulator, Participates in Arsenic Trioxide-Triggered Mitophagy in HeLa Cells. Curr. Issues Mol. Biol. 2022, 44, 2759–2771

by Zhewen Zhang, Juan Yi, Bei Xie, Jing Chen, Xueyan Zhang, Li Wang, Jingyu Wang, Jinxia Hou and Hulai Wei

Curr. Issues Mol. Biol. 2023, 45(10), 7843-7844; https://doi.org/10.3390/cimb45100495 - 26 Sep 2023

Viewed by 919

Abstract

In the published publication [...] Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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11 pages, 1851 KiB

Open AccessCase Report

Familial Hyperaldosteronism Type 3 with a Rapidly Growing Adrenal Tumor: An In Situ Aldosterone Imaging Study

by Nae Takizawa, Susumu Tanaka, Koshiro Nishimoto, Yuki Sugiura, Makoto Suematsu, Chisato Ohe, Haruyuki Ohsugi, Yosuke Mizuno, Kuniaki Mukai, Tsugio Seki, Kenji Oki, Celso E. Gomez-Sanchez and Tadashi Matsuda

Curr. Issues Mol. Biol. 2022, 44(1), 128-138; https://doi.org/10.3390/cimb44010010 - 28 Dec 2021

Cited by 8 | Viewed by 2663

Abstract

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause [...] Read more.

Primary aldosteronism is most often caused by aldosterone-producing adenoma (APA) and bi-lateral adrenal hyperplasia. Most APAs are caused by somatic mutations of various ion channels and pumps, the most common being the inward-rectifying potassium channel KCNJ5. Germ line mutations of KCNJ5 cause familial hyperaldosteronism type 3 (FH3), which is associated with severe hyperaldosteronism and hypertension. We present an unusual case of FH3 in a young woman, first diagnosed with primary aldosteronism at the age of 6 years, with bilateral adrenal hyperplasia, who underwent unilateral adrenalectomy (left adrenal) to alleviate hyperaldosteronism. However, her hyperaldosteronism persisted. At the age of 26 years, tomography of the remaining adrenal revealed two different adrenal tumors, one of which grew substantially in 4 months; therefore, the adrenal gland was removed. A comprehensive histological, immunohistochemical, and molecular evaluation of various sections of the adrenal gland and in situ visualization of aldosterone, using matrix-assisted laser desorption/ionization imaging mass spectrometry, was performed. Aldosterone synthase (CYP11B2) immunoreactivity was observed in the tumors and adrenal gland. The larger tumor also harbored a somatic β-catenin activating mutation. Aldosterone visualized in situ was only found in the subcapsular regions of the adrenal and not in the tumors. Collectively, this case of FH3 presented unusual tumor development and histological/molecular findings. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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