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Aptamer-based biosensors and application in tumor theranostics.
Mo, T, Liu, X, Luo, Y, Zhong, L, Zhang, Z, Li, T, Gan, L, Liu, X, Li, L, Wang, H, et al
Cancer science. 2022;(1):7-16
Abstract
An aptamer is a short oligonucleotide chain that can specifically recognize targeting analytes. Due to its high specificity, low cost, and good biocompatibility, aptamers as the targeting elements of biosensors have been applied widely in non-invasive tumor imaging and treatment in situ to replace traditional methods. In this review, we will summarize recent advances in using aptamer-based biosensors in tumor diagnosis. After a brief introduction of the advantage of aptamers compared with enzyme sensors and immune sensors, the different sensing designs and mechanisms based on 3 signal transduction modes will be reviewed to cover different kinds of analytical methods, including: electrochemistry analysis, colorimetry analysis, and fluorescence analysis. Finally, the prospective advantages of aptamer-based biosensors in tumor theranostics and post-treatment monitoring are also evaluated in this review.
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Imaging Prostate Cancer: Clinical Utility of Prostate-Specific Membrane Antigen.
Kuppermann, D, Calais, J, Marks, LS
The Journal of urology. 2022;(4):769-778
Abstract
PURPOSE Our goal was to review the pathway and pertinent materials leading to approval of prostate-specific membrane antigen (PSMA) scanning by the U.S. Food and Drug Administration (FDA). MATERIALS AND METHODS Beginning with the pivotal trials and working backward, we summarize the evolution of PSMA scanning, beginning with the discovery of the molecule, the mechanism of action to identify prostate cancer, the route to the present-day test and some of the major publications leading to each step of the sequence. From the thousands of PSMA articles listed on PubMed®, the present review is focused on the 4 large U.S. trials incorporating university studies of the gallium-68 compound and commercial studies of the fluorine-18 compound. The review further focuses on the role of PSMA scanning for both initial staging of prostate cancer and diagnosis of recurrent prostate cancer. RESULTS PSMA is a transmembrane-bound glycoprotein which is overexpressed by 100-1,000-fold in prostate cancer cells. Preclinical PSMA studies at Cornell and Johns Hopkins in the 1990s were followed by early human studies in Germany in the early 2010s, then pivotal clinical trials at University of California, Los Angeles and University of California, San Francisco, leading to the first FDA approval in December 2020 (68Ga-PSMA-11). In January 2021, a commercially available product (18F-DCFPyL) was approved on the basis of multisite registration trials (CONDOR and OSPREY). Sensitivity and specificity of PSMA scanning exceeds that of any other imaging method currently available for initial staging of prostate cancer and diagnosis of recurrent disease. The accuracy of PSMA scanning is attributed to the great image contrast (high signal-to-noise ratio), a property deriving from the high PSMA tracer uptake by prostate cancer cells. That property can be estimated quantitatively by a metric, the standardized uptake value. A follow-on PSMA compound, the theranostic lutetium-177, is currently pending FDA approval for treatment of metastases. CONCLUSIONS PSMA scanning is a disruptive technology that promises to transform the way prostate cancer is initially staged, recurrence is diagnosed and some advanced cases are treated.
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Inflammation-Related Biomarkers for the Prediction of Prognosis in Colorectal Cancer Patients.
Yamamoto, T, Kawada, K, Obama, K
International journal of molecular sciences. 2021;(15)
Abstract
Colorectal cancer (CRC) is the leading cause of cancer deaths around the world. It is necessary to identify patients with poor prognosis or with high risk for recurrence so that we can selectively perform intensive treatments such as preoperative and/or postoperative chemotherapy and extended surgery. The clinical usefulness of inflammation-related prognostic biomarkers available from routine blood examination has been reported in many types of cancer, e.g., neutrophil-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and so on. Moreover, some scoring systems based on circulating blood cell counts and albumin concentration have been also reported to predict cancer patients' prognosis, such as the Glasgow prognostic score (GPS), systemic inflammation score (SIS), and prognostic nutritional index (PNI). The optimal biomarker and optimal cutoff value of the markers can be different depending on the cancer type. In this review, we summarize the prognostic impact of each inflammation-related marker in CRC.
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Role of GATA3 in tumor diagnosis: A review.
Khazaeli Najafabadi, M, Mirzaeian, E, Memar Montazerin, S, Tavangar, AR, Tabary, M, Tavangar, SM
Pathology, research and practice. 2021;:153611
Abstract
GATA binding protein 3 (GATA3) belongs to a family of transcription factors comprising six members. These proteins identify G-A-T-A containing sequences in the target gene and bind to DNA target via two zinc-finger domains. The aim of this study was to evaluate the role of GATA3 in the diagnosis of tumors and its value as a prognostic marker. To perform this review, a comprehensive search was conducted through PubMed, Embase, Scopus, Cochrane and Google Scholar databases from 1985 to 2020. Articles were considered thoroughly by independent reviewers and data were extracted in predefined forms. Final synthesis was conducted by using appropriate data from included articles in each topic. Studies have shown that GATA3 has a critical role in the development of epithelial structures in both embryonic and adult tissues. The majority of studies regarding GATA3 expression in tumor evaluation focused on breast and urothelial neoplasms, whether primary or metastatic. Its sensitivity in these neoplasms has been reported to be high and made this marker more valuable than other available immunohistochemistry markers. However, GATA3 expression was not restricted to these tumors. Studies have shown that GATA3 immunostaining could be a useful tool in various tumors in kidney, salivary gland, endocrine system, hematopoietic system, and skin. GATA3 can also be used as a useful prognostic tool. Although GATA3 is a multi-specific immunohistochemical stain, it is a valuable marker in the panel for confirming many epithelial or mesenchymal neoplasms as both a diagnostic and prognostic tool.
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New insights into exosome mediated tumor-immune escape: Clinical perspectives and therapeutic strategies.
Pathania, AS, Prathipati, P, Challagundla, KB
Biochimica et biophysica acta. Reviews on cancer. 2021;(2):188624
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Abstract
Recent advances in extracellular vesicle biology have uncovered a substantial role in maintaining cell homeostasis in health and disease conditions by mediating intercellular communication, thus catching the scientific community's attention worldwide. Extracellular microvesicles, some called exosomes, functionally transfer biomolecules such as proteins and non-coding RNAs from one cell to another, influencing the local environment's biology. Although numerous advancements have been made in treating cancer patients with immune therapy, controlling the disease remains a challenge in the clinic due to tumor-driven interference with the immune response and inability of immune cells to clear cancer cells from the body. The present review article discusses the recent findings and knowledge gaps related to the role of exosomes derived from tumors and the tumor microenvironment cells in tumor escape from immunosurveillance. Further, we highlight examples where exosomal non-coding RNAs influence immune cells' response within the tumor microenvironment and favor tumor growth and progression. Therefore, exosomes can be used as a therapeutic target for the treatment of human cancers.
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Orphan nuclear receptors as regulators of intratumoral androgen biosynthesis in castration-resistant prostate cancer.
Zhou, J, Wang, Y, Wu, D, Wang, S, Chen, Z, Xiang, S, Chan, FL
Oncogene. 2021;(15):2625-2634
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Abstract
Castration-resistant prostate cancer (CRPC) almost invariably occurs after androgen-deprivation therapy (ADT) for the advanced metastatic disease. It is generally believed that among multiple mechanisms and signaling pathways, CRPC is significantly driven by the reactivation of androgen receptor (AR) signaling in ADT-treated patients with castrate levels of androgen, partially at least mediated by the androgen biosynthesis within the tumor, also known as intratumoral or intraprostatic androgen biosynthesis. Steroidogenic enzymes, such as CYP11A1, CYP17A1, HSD3B1, AKR1C3 and SRD5A, are essential to catalyze the conversion of the initial substrate cholesterol into potent androgens that confers the CRPC progression. Accumulating evidences indicate that many steroidogenic enzymes are upregulated in the progression setting; however, little is known about the dysregulation of these enzymes in CRPC. Orphan nuclear receptors (ONRs) are members of the nuclear receptor superfamily, of which endogenous physiological ligands are unknown and which are constitutively active independent of any physiological ligands. Studies have validated that besides AR, ONRs could be the potential therapeutic targets for prostate cancer, particularly the lethal CRPC progression. Early studies reveal that ONRs play crucial roles in the transcriptional regulation of steroidogenic enzyme genes. Notably, we and others show that three distinct ONRs, including liver receptor homolog-1 (LRH-1, NR5A2), steroidogenic factor 1 (SF-1, AD4BP, NR5A1) and estrogen-related receptor α (ERRα, NR3B1), can contribute to the CRPC progression by promotion of the intratumoral androgen synthesis via their direct transcriptional regulation on multiple steroidogenic enzymes. This review presents an overview of the current understanding on the intratumoral androgen biosynthesis in CRPC, with a special focus on the emerging roles of ONRs in this process.
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Research on esophageal cancer: With personal perspectives from studies in China and Kenya.
Yang, CS, Chen, XL
International journal of cancer. 2021;(2):264-276
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Abstract
The most common form of esophageal cancer (EC), esophageal squamous cell carcinoma (ESCC), is prevalent in many unindustrialized societies, among people with lower socioeconomic status and those who frequently use tobacco and alcohol. In some areas, ESCC mortality ranked top among all cancer. In this review, we begin with discussions of the extensive research on EC in Linxian in northern China that started 60 years ago and the recent studies in Kenya from our personal perspectives. Based on the results obtained from these studies and information from the literature, we summarize our current understanding about the risk factors for ESCC including lifestyle factors (smoking, alcohol, consumption of food and beverages at high temperature and other unhealthy habits), poor diet and nutritional insufficiencies and genetic susceptibility. Elimination or minimization of these environmental risk factors, as well as early detection and treatment of precancerous lesions, would be effective means for the prevention of ESCC. Current knowledge of molecular alterations in ESCC (gene mutations, hypermethylation and amplification or overexpression), as well as treatment of ESCC and the potential of targeted therapy, are also discussed. Finally, we propose effective approaches for the prevention of ESCC by adapting a healthy lifestyle, including a healthy diet that would also prevent other diseases. Community outreach, public education and international collaboration are important for achieving this public health goal.
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Regulation of autophagy by microRNAs in human breast cancer.
Chong, ZX, Yeap, SK, Ho, WY
Journal of biomedical science. 2021;(1):21
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Abstract
Breast cancer is the most common solid cancer that affects female population globally. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate post-transcriptional modification of multiple downstream genes. Autophagy is a conserved cellular catabolic activity that aims to provide nutrients and degrade un-usable macromolecules in mammalian cells. A number of in vitro, in vivo and clinical studies have reported that some miRNAs could modulate autophagy activity in human breast cancer cells, and these would influence human breast cancer progression and treatment response. Therefore, this review was aimed to discuss the roles of autophagy-regulating miRNAs in influencing breast cancer development and treatment response. The review would first introduce autophagy types and process, followed by the discussion of the roles of different miRNAs in modulating autophagy in human breast cancer, and to explore how would this miRNA-autophagy regulatory process affect the disease progression or treatment response. Lastly, the potential applications and challenges of utilizing autophagy-regulating miRNAs as breast cancer biomarkers and novel therapeutic agents would be discussed.
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Calcitonin Stimulation Tests: Rationale, Technical Issues and Side Effects: A Review.
Băetu, M, Olariu, CA, Moldoveanu, G, Corneci, C, Badiu, C
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2021;(6):355-363
Abstract
Calcitonin (CT) stimulation tests have great value and could help to: differentiate thyroid causes of elevated CT apart from non-thyroid sources, determine whether the patients with slightly elevated basal CT could/could not be candidates for surgery, and indicate the right moment for prophylactic thyroidectomy in children with MEN syndromes when with normal basal CT. This triggered the requests for development of CT stimulation tests, taking into consideration their safety and aimed us to write a systematic review of literature regarding the rationale, technical issues, and side effects of CT stimulating tests used for diagnosis of MTC. After a thorough review of the literature, we classified the reported side effects by severity, as defined by United States Food and Drug Administration. A statistical analysis was performed using IBM SPSS Statistics version 20. Various side effects were noticed during stimulation tests that differ by intensity, duration and severity, depending on types of substances and protocols used. The side effects after pentagastrin test were significantly more severe than those reported after calcium stimulation test (p=0.0396). There are also significant gender-specific differences in side effects induced by stimulation tests. In conclusion, we recommend performing Ca CT stimulation test when needed, considering preventive evaluation of some clinical, instrumental, and biochemical aspects of each patient. Precise instructions should be followed before a stimulation test and furthermore continuous cardiac monitoring is essential during and after the test to minimize the possibility of a serious event.
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New Insight into Triple-Negative Breast Cancer Therapy: The Potential Roles of Endoplasmic Reticulum Stress and Autophagy Mechanisms.
Ashrafizadeh, M, Mohammadinejad, R, Tavakol, S, Ahmadi, Z, Sahebkar, A
Anti-cancer agents in medicinal chemistry. 2021;(6):679-691
Abstract
BACKGROUND Breast cancer is accounted as the fifth leading cause of mortality among the other cancers. Notwithstanding, Triple Negative Breast Cancer (TNBC) is responsible for 15-20% of breast cancer mortality. Despite many investigations, it remains incurable in part due to insufficient understanding of its exact mechanisms. METHODS A literature search was performed in PubMed, SCOPUS and Web of Science databases using the keywords autophagy, Endoplasmic Reticulum (ER) stress, apoptosis, TNBC and the combinations of these keywords. RESULTS It was found that autophagy plays a dual role in cancer, so that it may decrease the viability of tumor cells or act as a cytoprotective mechanism. It then appears that using compounds having modulatory effects on autophagy is of importance in terms of induction of autophagic cell death and diminishing the proliferation and metastasis of tumor cells. Also, ER stress can be modulated in order to stimulate apoptotic and autophagic cell death in tumor cells. CONCLUSION Perturbation in the signaling pathways related to cell survival leads to the initiation and progression of cancer. Regarding the advancement in the cancer pathology, it seems that modulation of autophagy and ER stress are promising.