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1.
Role of systemic inflammatory response markers in urological malignancy.
Ohno, Y
International journal of urology : official journal of the Japanese Urological Association. 2019;(1):31-47
Abstract
The systemic inflammatory response is associated with survival in patients with a variety of cancers. This inflammatory response is measured in the peripheral blood, and can be monitored using two categories of indices: concentration of specific serum proteins (albumin, C-reactive protein) and differential blood cell count (neutrophils, lymphocytes and platelets). Furthermore, combinations of these indices, such as the Glasgow Prognostic Score, which consists of the serum C-reactive protein and albumin level; the neutrophil-to-lymphocyte ratio; the platelet-to-lymphocyte ratio; and the prognostic nutritional index, which is based on peripheral blood lymphocyte count and serum albumin level, have also been evaluated and compared in cancer research. To date, there are hundreds of studies that have shown the prognostic value of systemic inflammatory response markers in patients with urological cancer. Most studies have evaluated the prognostic and predictive role of the pretreatment value of the markers, although some have focused on the role of the post-treatment value at specific points during the clinical course. The advantages of systemic inflammatory response markers are that they are easily measurable and inexpensive in the clinical setting. However, it is important to consider how clinicians use these markers in clinical practice. The present review provides a concise overview regarding systemic inflammatory markers in urological cancers, specifically C-reactive protein, Glasgow Prognostic Score/modified Glasgow Prognostic Score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and prognostic nutritional index.
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Changes in metabolic parameters and cardiovascular risk factors after therapeutic control of acromegaly vary with the treatment modality. Data from the Bicêtre cohort, and review of the literature.
Briet, C, Ilie, MD, Kuhn, E, Maione, L, Brailly-Tabard, S, Salenave, S, Cariou, B, Chanson, P
Endocrine. 2019;(2):348-360
Abstract
CONTEXT Untreated acromegaly is associated with increased morbidity and mortality due to malignant, cardiovascular, and cerebrovascular disorders. Effective treatment of acromegaly reduces excess mortality, but its impact on cardiovascular risk factors and metabolic parameters are poorly documented. AIM: We analyzed changes in cardiovascular risk factors and metabolic parameters in patients receiving various treatment modalities. PATIENTS AND METHODS We retrospectively studied 96 patients with acromegaly, both at diagnosis and after IGF-I normalization following surgery alone (n = 51) or medical therapy with first generation somatostatin analogues (SSA, n = 23), or pegvisomant (n = 22). Duration of follow-up was 77 (42-161) months, 75 (42-112) months, and 62 (31-93) months, in patients treated with surgery alone, SSA, and pegvisomant, respectively. In all the cases except four, patients treated medically had underwent previous unsuccessful surgery. RESULTS IGF-I normalization was associated with increased body weight, decreased systolic blood pressure (SBP) in hypertensive patients, decreased fasting plasma glucose (FPG) and HOMA-IR and HOMA-B levels, increased HDL cholesterol (HDLc); whereas, LDL cholesterol (LDLc) was not significantly different. Plasma PCSK9 levels were unchanged in patients with available values. Cardiovascular and metabolic changes varied with the treatment modality: surgery, but not pegvisomant, had a beneficial effect on SBP; FPG decreased after surgery but increased after SSA; the decline in HOMA-IR was only significant after surgery; pegvisomant significantly increased LDLc and total cholesterol; whereas SA increased HDLc and had no effect on LDLc levels. CONCLUSION Treatments used to normalize IGF-I levels in patients with acromegaly could have differential effects on cardiovascular risk factors and metabolic parameters.
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Metabolomic profiling for the identification of novel diagnostic markers and therapeutic targets in prostate cancer: an update.
Lucarelli, G, Loizzo, D, Ferro, M, Rutigliano, M, Vartolomei, MD, Cantiello, F, Buonerba, C, Di Lorenzo, G, Terracciano, D, De Cobelli, O, et al
Expert review of molecular diagnostics. 2019;(5):377-387
Abstract
An altered metabolic regulation is involved in the development and progression of different cancer types. As well as this, many genes associated with tumors are shown to have an important role in control of the metabolism. The incidence of prostate cancer (PCa) is increased in men with metabolic disorders. In particular, obesity is an established risk factor for PCa. An increased body mass index correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. Increased lipogenesis is also one of the most significant events in PCa metabolism reprogramming. Areas covered: In this article, we provide an updated review of the current understanding of the PCa metabolome and evaluate the possibility of unveiling novel therapeutic targets. Expert opinion: Obesity is an established risk factor for PCa, and an increased BMI correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. PCa metabolome is characterized by the accumulation of metabolic intermediates and an increased expression of genes in the tricarboxylic acid cycle, the induction of de novo lipogenesis and cholesterogenesis. PCa cells can induce different alterations in their microenvironment by modulating the crosstalk between cancer and stromal cells.
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4.
The latest progress on miR-374 and its functional implications in physiological and pathological processes.
Bian, H, Zhou, Y, Zhou, D, Zhang, Y, Shang, D, Qi, J
Journal of cellular and molecular medicine. 2019;(5):3063-3076
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Abstract
Non-coding RNAs (ncRNAs) have been emerging players in cell development, differentiation, proliferation and apoptosis. Based on their differences in length and structure, they are subdivided into several categories including long non-coding RNAs (lncRNAs >200nt), stable non-coding RNAs (60-300nt), microRNAs (miRs or miRNAs, 18-24nt), circular RNAs, piwi-interacting RNAs (26-31nt) and small interfering RNAs (about 21nt). Therein, miRNAs not only directly regulate gene expression through pairing of nucleotide bases between the miRNA sequence and a specific mRNA that leads to the translational repression or degradation of the target mRNA, but also indirectly affect the function of downstream genes through interactions with lncRNAs and circRNAs. The latest studies have highlighted their importance in physiological and pathological processes. MiR-374 family member are located at the X-chromosome inactivation center. In recent years, numerous researches have uncovered that miR-374 family members play an indispensable regulatory role, such as in reproductive disorders, cell growth and differentiation, calcium handling in the kidney, various cancers and epilepsy. In this review, we mainly focus on the role of miR-374 family members in multiple physiological and pathological processes. More specifically, we also summarize their promising potential as novel prognostic biomarkers and therapeutic targets from bench to bedside.
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5.
GLIS rearrangements in thyroid nodules: A key to preoperative diagnosis of hyalinizing trabecular tumor.
Nikiforova, MN, Nikiforov, YE, Ohori, NP
Cancer cytopathology. 2019;(9):560-566
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Abstract
Hyalinizing trabecular tumor (HTT) is a rare thyroid neoplasm with peculiar morphologic features that overlap with those of papillary thyroid carcinoma (PTC). Specifically, the presence of enlarged oval nuclei, nuclear grooves, and intranuclear pseudoinclusions makes precise cytopathologic diagnosis challenging. If the cytopathologic diagnosis is suspicious for malignancy (Bethesda V) or is malignant (Bethesda VI), a total thyroidectomy, which would be considered an overtreatment, may follow. The recent discovery of the strong association between GLIS fusions and HTT sheds light on its pathogenesis and offers a pathway for its presurgical identification. Although the number of cases analyzed is limited, the recent landmark study shows that GLIS fusions are highly specific for HTT and that lobectomy is the likely appropriate surgical treatment, because these neoplasms, which lack invasion, are benign. For overall success, cytopathologic recognition of the subtle features is important to avoid false-positive diagnoses and directing potential HTT cases toward indeterminate cytopathologic diagnoses, which would trigger further molecular testing. Additional studies are needed to determine whether a malignant counterpart of GLIS fusion-positive HTT exists and if more conservative approaches may be taken.
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Real-time detection of breast cancer at the cellular level.
Carver, GE, Locknar, SA, Weaver, DL, Stein, JL, Stein, GS
Journal of cellular physiology. 2019;(5):5413-5419
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Abstract
Novel optoelectronic instrumentation has been developed for the multispectral imaging of autofluorescence emitted by metabolic fluorophores. The images resolve individual cells while spectra are collected for each pixel in the images. These datacubes are generated at a rate of 10 per second-fast enough for surgical guidance. The data is processed in real time to provide a single color-coded image to the surgeon. To date, the system has been applied to fresh, ex vivo, human surgical specimens and has distinguished breast cancer from benign tissue. The approach is applicable to in vivo measurements of surgical margins and needle-based optical biopsies. Ongoing work demonstrates that the system has great potential for translation to a hand-held probe with high sensitivity and specificity.
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Leukemia-derived exosomes: Bringing oncogenic signals to blood cells.
Sharifi, H, Shafiee, A, Molavi, G, Razi, E, Mousavi, N, Sarvizadeh, M, Taghizadeh, M
Journal of cellular biochemistry. 2019;(10):16307-16315
Abstract
Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.
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[An integral view of cancer (II). Fields of investigation and emerging biomarkers].
Noguera, R, Burgos-Panadero, R, Gamero-Sandemetrio, E, de la Cruz-Merino, L, Álvaro Naranjo, T
Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia. 2019;(4):222-233
Abstract
Pathology and clinical oncology work hand in hand so that techniques and treatments, biomarkers and antibodies share the common goal of identifying integral new treatment regimens that are more effective and less aggressive. Evidence shows how tissue mechanics affect carcinogenesis and that tumor heterogeneity depends on metabolic stromal alteration and the Warburg effect of malignant cells, regulated directly by PD-1, becoming a target for immunotherapy. Proliferation and apoptosis depend on mitochondrial dysfunction in tumor cells, determining the grade of chemo/radio-resistance. The status of intestinal microbiota regulates immune response, tumor microenvironment structure and oncologic treatment response, whilst the Vitamin D receptor allows reprogramming of tumor stroma. Current collaboration between basic and clinical research paves the way for future investigation into areas such as tumor microenvironment and molecular mechanotherapy, metabolism and immunotherapy, mitochondria and oncogenesis, microbiota and chemotherapy, psychoneuroendocrine axis and homeostatic imbalance, epigenetics and reprogramming possibilities of the tumor phenotype. We review new prognostic and predictive biomarkers emerging from these fields of knowledge, opening up new therapeutic possibilities.
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Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics.
Quintero Escobar, M, Maschietto, M, Krepischi, ACV, Avramovic, N, Tasic, L
Biomolecules. 2019;(12)
Abstract
Most childhood cancers occur as isolated cases and show very different biological behavior when compared with cancers in adults. There are some solid tumors that occur almost exclusively in children among which stand out the embryonal solid tumors. These cancers main types are neuroblastoma, nephroblastoma (Wilms tumors), retinoblastoma and hepatoblastomas and tumors of the central nervous system (CNS). Embryonal solid tumors represent a heterogeneous group of cancers supposedly derived from undifferentiated cells, with histological features that resemble tissues of origin during embryogenesis. This key observation suggests that tumorigenesis might begin during early fetal or child life due to the errors in growth or pathways differentiation. There are not many literature data on genomic, transcriptomic, epigenetic, proteomic, or metabolomic differences in these types of cancers when compared to the omics- used in adult cancer research. Still, metabolomics by nuclear magnetic resonance (NMR) in childhood embryonal solid tumors research can contribute greatly to understand better metabolic pathways alterations and biology of the embryonal solid tumors and potential to be used in clinical applications. Different types of samples, such as tissues, cells, biofluids, mostly blood plasma and serum, can be analyzed by NMR to detect and identify cancer metabolic signatures and validated biomarkers using enlarged group of samples. The literature search for biomarkers points to around 20-30 compounds that could be associated with pediatric cancer as well as metastasis.
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Expression Analysis of RbBP6 in human cancers: a Prospective biomarker.
Mbita, Z, Hull, R, Mbele, M, Makhafola, T, Dlamini, Z
Anti-cancer drugs. 2019;(8):767-773
Abstract
Retinoblastoma binding protein 6 (RBBP6) is a cancer-related protein that has been implicated in the regulation of cell cycle and apoptosis. RBBP6 isoform 1 has been demonstrated to interact with two tumour suppressors, p53 and pRB. Isoform 1 been shown to regulate p53 through its ubiquitin ligase activity, thus implicating in cell cycle regulation and apoptosis. Isoforms 1 and 2 are multidomain proteins containing a domain with no name (DWNN) domain, a Zinc Finger, a RING Finger, an Rb-binding domain and a p53-binding domain. The RBBP6 isoform 3 comprises the DWNN domain only. Isoform 4 lacks the Rb-binding domain but its role is less understood. RBBP6 isoform 3 has been reported as a cell cycle regulator with anticancer potential. There have been several studies that have clearly demonstrated that RBBP6 may be an important biomarker for cancer diagnosis and a potential drug target for cancer treatment. This work focused on differential expression of RBBP6 transcripts in different cancers, providing detailed analysis of their potential as diagnostic biomarkers for different cancers. These cancers include breast, liver, cervical and colon carcinomas. The expression of RBBP6 transcripts may further provide better understanding of the role of the RBBP6 in carcinogenesis and cell homeostasis.