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1.
Cytopathology ; 33(1): 23-38, 2022 01.
Article in English | MEDLINE | ID: covidwho-1799272

ABSTRACT

Lung cancer is a leading cause of cancer mortality worldwide but recent years have seen a rapidly rising proportion of cases of advanced non-small cell carcinoma amenable to increasingly targeted therapy, initially based on the differential response to systemic treatment of tumours of squamous or glandular differentiation. In two-thirds of the cases, where patients present with advanced disease, both primary pathological diagnosis and biomarker testing is based on small biopsies and cytopathological specimens. The framework of this article is an overview of the technical aspect of each stage of the specimen pathway with emphasis on maximising potential for success when using small cytology samples. It brings together the current literature addressing pre-analytical and analytical aspects of specimen acquisition, performing rapid onsite evaluation, and undertaking diagnostic and predictive testing using immunocytochemistry and molecular platforms. The advantages and drawbacks of performing analysis on cell block and non-cell block specimen preparations is discussed.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma , Lung Neoplasms , Biomarkers, Tumor/metabolism , Carcinoma/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Lung/pathology , Lung Neoplasms/pathology
2.
Int J Mol Sci ; 23(6)2022 Mar 19.
Article in English | MEDLINE | ID: covidwho-1760653

ABSTRACT

Lung cancer (LC) is the leading cause of cancer-related death worldwide. Although the diagnosis and treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 80% of LC cases, have greatly improved in the past decade, there is still an urgent need to find more sensitive and specific screening methods. Recently, new molecular biomarkers are emerging as potential non-invasive diagnostic agents to screen NSCLC, including multiple microRNAs (miRNAs) that show an unusual expression profile. Moreover, peripheral blood mononuclear cells' (PBMCs) miRNA profile could be linked with NSCLC and used for diagnosis. We developed a molecular beacon (MB)-based miRNA detection strategy for NSCLC. Following PBMCs isolation and screening of the expression profile of a panel of miRNA by RT-qPCR, we designed a MB targeting of up-regulated miR-21-5p. This MB 21-5p was characterized by FRET-melting, CD, NMR and native PAGE, allowing the optimization of an in-situ approach involving miR-21-5p detection in PBMCs via MB. Data show the developed MB approach potential for miR-21-5p detection in PBMCs from clinical samples towards NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic , Humans , Leukocytes, Mononuclear/metabolism , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , MicroRNAs/metabolism
3.
Analyst ; 145(12): 4173-4180, 2020 Jun 21.
Article in English | MEDLINE | ID: covidwho-1721601

ABSTRACT

Studies have shown that microRNAs, which are small noncoding RNAs, hold tremendous promise as next-generation circulating biomarkers for early cancer detection via liquid biopsies. A novel, solid-state nanoplasmonic sensor capable of assaying circulating microRNAs through a combined surface-enhanced Raman scattering (SERS) and plasmon-enhanced fluorescence (PEF) approach has been developed. Here, the unique localized surface plasmon resonance properties of chemically-synthesized gold triangular nanoprisms (Au TNPs) are utilized to create large SERS and PEF enhancements. With careful modification to the surface of Au TNPs, this sensing approach is capable of quantifying circulating microRNAs at femtogram/microliter concentrations. Uniquely, the multimodal analytical methods mitigate both false positive and false negative responses and demonstrate the high stability of our sensors within bodily fluids. As a proof of concept, microRNA-10b and microRNA-96 were directly assayed from the plasma of six bladder cancer patients. Results show potential for a highly specific liquid biopsy method that could be used in point-of-care clinical diagnostics to increase early cancer detection or any other diseases including SARS-CoV-2 in which RNAs can be used as biomarkers.


Subject(s)
Circulating MicroRNA/blood , Fluorescent Dyes/chemistry , Spectrum Analysis, Raman , Urinary Bladder Neoplasms/diagnosis , Betacoronavirus/isolation & purification , Biomarkers, Tumor/blood , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Coronavirus Infections/virology , Gold/chemistry , Humans , Limit of Detection , Microscopy, Confocal , Nanostructures/chemistry , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Point-of-Care Systems , SARS-CoV-2 , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology
4.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1674661

ABSTRACT

Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor.


Subject(s)
Breast Neoplasms/diagnosis , Extracellular Vesicles/metabolism , Urogenital Neoplasms/diagnosis , Animals , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Early Detection of Cancer/methods , Female , Humans , Neoplasms/diagnosis , Neoplasms/metabolism , Nucleic Acids/metabolism , Urogenital Neoplasms/metabolism
5.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1662689

ABSTRACT

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.


Subject(s)
Breast Neoplasms/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Case-Control Studies , Cohort Studies , Disease Progression , Female , Humans , Immunohistochemistry/methods , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/metabolism , Metalloproteases/genetics , Metalloproteases/metabolism , Middle Aged , Retrospective Studies , Spain , Tissue Inhibitor of Metalloproteinases/metabolism
6.
J Nanobiotechnology ; 19(1): 287, 2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1662419

ABSTRACT

Pancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs' GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).


Subject(s)
Early Detection of Cancer/methods , Pancreatic Neoplasms/diagnosis , RNA, Messenger/isolation & purification , Biomarkers, Tumor/genetics , COVID-19 , Extracellular Vesicles , Glypicans/genetics , Gold , Humans , Metal Nanoparticles , Pancreatic Neoplasms/genetics
7.
Int J Mol Sci ; 23(2)2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1637017

ABSTRACT

Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.


Subject(s)
Antineoplastic Agents/pharmacology , Doxycycline/pharmacology , Minocycline/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Biomarkers, Tumor , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Melanoma, Amelanotic , Membrane Potential, Mitochondrial/drug effects
8.
Gastroenterology ; 161(3): 785-791, 2021 09.
Article in English | MEDLINE | ID: covidwho-1626143

ABSTRACT

Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase in incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving the outcome of patients. On the 4th and 5th of February 2021, three German pancreatic cancer research centers, the Clinical Research Unit 5002 from Göttingen, the Collaborative Research Center 1321 from Munich, and Clinical Research Unit 325 from Marburg organized the 1st Virtual Göttingen-Munich-Marburg Pancreatic Cancer Meeting in order to foster scientific exchange. This report summarizes current research and proceedings presented during that meeting.


Subject(s)
Biomedical Research/trends , Pancreatic Neoplasms , Animals , Biomarkers, Tumor/genetics , COVID-19 , Cell Lineage , Diffusion of Innovation , Genetic Predisposition to Disease , Humans , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Tumor Microenvironment , Videoconferencing
9.
Cancer Med ; 11(2): 530-538, 2022 01.
Article in English | MEDLINE | ID: covidwho-1606588

ABSTRACT

BACKGROUND: An ASCO taskforce comprised of representatives of oncology clinicians, the American Cancer Society National Lung Cancer Roundtable (NLCRT), LUNGevity, the GO2 Foundation for Lung Cancer, and the ROS1ders sought to: characterize U.S. oncologists' biomarker ordering and treatment practices for advanced non-small-cell lung cancer (NSCLC); ascertain barriers to biomarker testing; and understand the impact of delays on treatment decisions. METHODS: We deployed a survey to 2374 ASCO members, targeting U.S. thoracic and general oncologists. RESULTS: We analyzed 170 eligible responses. For non-squamous NSCLC, 97% of respondents reported ordering tests for EGFR, ALK, ROS1, and BRAF. Testing for MET, RET, and NTRK was reported to be higher among academic versus community providers and higher among thoracic oncologists than generalists. Most respondents considered 1 (46%) or 2 weeks (52%) an acceptable turnaround time, yet 37% usually waited three or more weeks to receive results. Respondents who waited ≥3 weeks were more likely to defer treatment until results were reviewed (63%). Community and generalist respondents who waited ≥3 weeks were more likely to initiate non-targeted treatment while awaiting results. Respondents <5 years out of training were more likely to cite their concerns about waiting for results as a reason for not ordering biomarker testing (42%, vs. 19% with ≥6 years of experience). CONCLUSIONS: Respondents reported high biomarker testing rates in patients with NSCLC. Treatment decisions were impacted by test turnaround time and associated with practice setting and physician specialization and experience.


Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/diagnosis , Clinical Decision-Making , Lung Neoplasms/diagnosis , Oncologists , Carcinoma, Non-Small-Cell Lung/therapy , Humans , Lung Neoplasms/therapy , Surveys and Questionnaires , United States
10.
J Surg Oncol ; 125(4): 596-602, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1592572

ABSTRACT

BACKGROUND AND OBJECTIVES: With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. METHODS: Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. RESULTS: We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CONCLUSIONS: CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Clinical Decision Rules , Genomics , Adult , Aged , Aged, 80 and over , Biopsy, Large-Core Needle , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Reproducibility of Results , Risk Assessment
11.
Sci Immunol ; 5(44)2020 02 21.
Article in English | MEDLINE | ID: covidwho-1575907

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.


Subject(s)
Breast Neoplasms/pathology , Myeloid-Derived Suppressor Cells/pathology , Single-Cell Analysis , Transcriptome , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Breast Neoplasms/immunology , Cell Differentiation/genetics , Female , Humans , Mice , Mice, Inbred Strains , Mice, Transgenic , Myeloid-Derived Suppressor Cells/immunology , RNA, Neoplasm/genetics , RNA, Neoplasm/immunology , Signaling Lymphocytic Activation Molecule Family/genetics , Signaling Lymphocytic Activation Molecule Family/immunology
12.
Chest ; 160(6): e645-e650, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544869

ABSTRACT

CASE PRESENTATION: A 30-year-old man with a history of childhood asthma, a 15-pack-year smoking history, and methamphetamine abuse was intubated and started on mechanical ventilation because of acute hypoxic respiratory failure after experiencing progressive dyspnea and a nonproductive cough over the previous year. During the previous 3 months, he had multiple clinic visits, with chest radiographs showing diffuse, bilateral, reticulonodular opacities and small bilateral pleural effusions and was treated for community-acquired pneumonia. Testing for COVID pneumonia was negative, and he failed to respond to antimicrobial therapy. Physical examination on admission showed diffuse fine crackles bilaterally on lung auscultation. Admission laboratory test results were unremarkable.


Subject(s)
Adenocarcinoma/diagnosis , Carcinoma/diagnosis , Lung Neoplasms/diagnosis , Lymphangitis/diagnosis , Adenocarcinoma/pathology , Adrenal Gland Neoplasms/secondary , Adult , Biomarkers, Tumor/analysis , Carcinoma/pathology , Diagnosis, Differential , Dyspnea , Fatal Outcome , Humans , Lung Neoplasms/pathology , Lymphangitis/pathology , Lymphatic Metastasis , Male , Neoplasm Invasiveness , Tomography, X-Ray Computed
13.
J Cancer Res Clin Oncol ; 148(3): 599-608, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1527467

ABSTRACT

INTRODUCTION: Cathepsin L (CTSL) is a kind of the SARS-entry-associated CoV-2's proteases, which plays a key role in the virus's entry into the cell and subsequent infection. We investigated the association between the expression level of CTSL and overall survival in Glioblastoma multiforme (GBM) patients, to better understand the possible route and risks of new coronavirus infection for patients with GBM. METHODS: The expression level of CTSL in GBM was analyzed using TCGA and CGGA databases. The relationship between CTSL and immune infiltration levels was analyzed by means of the TIMER database. The impact of CTSL inhibitors on GBM biological activity was tested. RESULTS: The findings revealed that GBM tissues had higher CTSL expression levels than that of normal brain tissues, which was associated with a significantly lower survival rate in GBM patients. Meanwhile, the expression level of CTSL negatively correlated with purity, B cell and CD8+ T cell in GBM. CTSL inhibitor significantly reduced growth and induced mitochondrial apoptosis. CONCLUSION: According to the findings, CTSL acts as an independent prognostic factor and can be considered as promising therapeutic target for GBM.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19/pathology , Cathepsin L/metabolism , Dipeptides/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Apoptosis , COVID-19/drug therapy , COVID-19/enzymology , COVID-19/virology , Case-Control Studies , Cell Proliferation , Female , Glioblastoma/drug therapy , Glioblastoma/enzymology , Humans , Male , Middle Aged , Prognosis , SARS-CoV-2/physiology , Survival Rate , Tumor Cells, Cultured
14.
Int J Biol Sci ; 17(1): 20-31, 2021.
Article in English | MEDLINE | ID: covidwho-1526974

ABSTRACT

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global infection, and is seriously threatening human life, especially cancer patients. Thus, we sought to determine the clinical roles of ACE2 (the cell entry receptor of SARS-CoV-2) in ccRCC (clear cell renal cell carcinoma). TCGA, GEO and TIP datasets, and immunohistochemistry and western blot results were used to determine the prognostic and clinicopathological characteristics of ACE2. ACE2 expression was down-regulated in ccRCC tissues and cell lines. The multivariate Cox regression analysis results indicated that increased ACE2 expression was independent predictor of longer OS (HR: 0.8259, 95%CI: 0.7734-0.8819, P<0.0001) and RFS (HR: 0.8023, 95%CI: 0.7375-0.8729, P<0.0001) in ccRCC patients. Lower ACE2 expression was also associated with advanced tumor stage, higher histological grade and pathological stage, and metastasis. Besides, ACE2 expression was significantly positively and negatively correlated with CD4 Naïve infiltration and CD4 Memory infiltration, respectively. Moreover, higher CD4 Naïve and lower CD4 Memory infiltration levels were associated with better pathological features and longer OS and RFS. Furthermore, high ACE2 expression group in decreased CD4 Naïve, enriched CD4 Naïve and enriched CD4 memory cohort had favorable prognosis. These findings identified that AEC2 was significantly reduced in ccRCC, and decreased ACE2 was related to worse pathological features and poor prognosis. Low ACE2 expression in ccRCC may partially affect the prognosis due to altered immune cells infiltration levels.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Carcinoma, Renal Cell/immunology , Humans , Kidney Neoplasms/immunology , Prognosis , SARS-CoV-2/isolation & purification
15.
Int J Biol Sci ; 17(12): 3224-3238, 2021.
Article in English | MEDLINE | ID: covidwho-1524470

ABSTRACT

Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-positive breast cancer. BC-N102 treatment exhibits dose-dependent cytotoxic effects against ER+ breast cancer cell lines. BC-N102 exhibited time course- and dose-dependent cell cycle arrest via downregulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-Akt, CDK2, and CDK4 while increasing p38 mitogen-activated protein kinase (MAPK), and mineralocorticoid receptor (MR) signaling in breast cancer cell line. In addition, we found that BC-N102 suppressed breast cancer tumorigenesis in vivo and prolonged the survival of animals. Our results suggest that the proper application of BC-N102 may be a beneficial chemotherapeutic strategy for ER+ breast cancer patients.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/metabolism , G1 Phase/drug effects , Receptors, Estrogen/metabolism , Resting Phase, Cell Cycle/drug effects , Animals , Biomarkers, Tumor/genetics , Blotting, Western , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Division , Cell Line, Tumor , Cyclin-Dependent Kinase 2/genetics , Cyclin-Dependent Kinase 4/genetics , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic/physiology , Humans , Maximum Tolerated Dose , Mice , Mice, Nude , Xenograft Model Antitumor Assays
16.
Environ Sci Pollut Res Int ; 29(15): 22012-22030, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1514070

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues as a global pandemic. Patients with lung cancer infected with COVID-19 may develop severe disease or die. Treating such patients severely burdens overwhelmed healthcare systems. Here, we identified potential pathological mechanisms shared between patients with COVID-19 and lung adenocarcinoma (LUAD). Co-expressed, differentially expressed genes (DEGs) in patients with COVID-19 and LUAD were identified and used to construct a protein-protein interaction (PPI) network and to perform enrichment analysis. We used the NetworkAnalyst platform to establish a co-regulatory of the co-expressed DEGs, and we used Spearman's correlation to evaluate the significance of associations of hub genes with immune infiltration and immune checkpoints. Analysis of three datasets identified 112 shared DEGs, which were used to construct a protein-PPI network. Subsequent enrichment analysis revealed co-expressed genes related to biological process (BP), molecular function (MF), and cellular component (CC) as well as to pathways, specific organs, cells, and diseases. Ten co-expressed hub genes were employed to construct a gene-miRNA, transcription factor (TF)-gene, and TF-miRNA network. Hub genes were significantly associated with immune infiltration and immune checkpoints. Finally, methylation level of hub genes in LUAD was obtained via UALCAN database. The present multi-dimensional study reveals commonality in specific gene expression by patients with COVID-19 and LUAD. These findings provide insights into developing strategies for optimising the management and treatment of patients with LUAD with COVID-19.


Subject(s)
Adenocarcinoma of Lung , COVID-19 , Lung Neoplasms , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , COVID-19/genetics , Computational Biology/methods , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology
17.
Int J Mol Sci ; 22(21)2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1512375

ABSTRACT

Adult rhabdomyosarcoma (RMS) represents an uncommon entity with an incidence of less than 3% of all soft tissue sarcomas (STS). Consequently, the natural history and the clinical management of this disease are infrequently reported. In order to fill this gap, we investigated the molecular biology of an adult RMS case series. The expression of epithelial mesenchymal transition-related gene and chemoresistance-related gene panels were evaluated. Moreover, taking advantage of our STS translational model combining patient-derived primary culture and 3D-scaffold, the pharmacological profile of an adult head and neck sclerosing RMS was assessed. Furthermore, NGS, microsatellite instability, and in silico analyses were carried out. RT-PCR identified the upregulation of CDH1, SLUG, MMP9, RAB22a, S100P, and LAPTM4b, representing promising biomarkers for this disease. Pharmacological profiling showed the highest sensitivity with anthracycline-based regimen in both 2D and 3D culture systems. NGS analysis detected RAB3IP-HMGA2 in frame gene rearrangement and FGFR4 mutation; microsatellite instability analysis did not detect any alteration. In silico analysis confirmed the mutation of FGFR4 as a promising marker for poor prognosis and a potential therapeutic target. We report for the first time the molecular and pharmacological characterization of rare entities of adult head and neck and posterior trunk RMS. These preliminary data could shed light on this poorly understood disease.


Subject(s)
Rhabdomyosarcoma/genetics , Adult , Aged , Biomarkers, Tumor/genetics , Epithelial-Mesenchymal Transition/genetics , Female , Genomics/methods , Humans , Male , Microsatellite Instability , Mutation/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics , Up-Regulation
18.
Eur Rev Med Pharmacol Sci ; 25(20): 6411-6424, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1503073

ABSTRACT

OBJECTIVE: The heterogeneity of clinical manifestations and mortality rates in Coronavirus disease 2019 (COVID-19) patients may be related to the existence of molecular subtypes in COVID-19. To improve current management, it is essential to find the hub genes and pathways associated with different COVID-19 subtypes. MATERIALS AND METHODS: The whole-genome sequencing information (GSE156063, GSE163151) of nasopharyngeal swabs from normal subjects and COVID-19 patients were downloaded from the Gene Expression Omnibus (GEO) database. The molecular subtypes of patients with COVID-19 were classified using the "consistent clustering" method, and the specific genes associated with each subtype were found. Differentially expressed genes (DEGs) were screened between normal subjects and COVID-19 patients; the Weighted gene co-expression network analysis (WGCNA) method was used to find the key module genes of COVID-19 patients. Subtype-specific, differentially expressed and module-related genes were collected and intersected. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out and protein-protein interaction (PPI) networks were generated. The pathways enriched in COVID-19 subtypes were analyzed by gene set variation analysis (GSVA). RESULTS: Patients with COVID-19 were divided into three subtypes, and there was no significant difference in gender and age distribution between subtypes. 82 differential gene pathways were screened between Subtypes I and II, 131 differential gene pathways were screened between Subtypes I and III, and 107 differential gene pathways were screened between Subtypes II and III. Finally, 44 differentially expressed key genes were screened, including 11 hub genes (RSAD2, IFIT1, MX1, OAS1, OAS2, BST2, IFI27, IFI35, IFI6, IFITM3, STAT2). CONCLUSIONS: There are significant differences in gene activation and pathway enrichment among different molecular subtypes of COVID-19, which may account for the heterogeneity in clinical presentation and the prognosis of patients.


Subject(s)
Biomarkers, Tumor/genetics , COVID-19/genetics , Oligonucleotide Array Sequence Analysis , COVID-19/diagnosis , Genetic Variation/genetics , Humans
19.
Front Endocrinol (Lausanne) ; 12: 727320, 2021.
Article in English | MEDLINE | ID: covidwho-1497068

ABSTRACT

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic. The majority of medullary thyroid cancers present as a thyroid nodule. At the time of diagnosis, cervical lymph nodes and distant metastases are frequently detected. Case Report: Here, we present a case of a 46-year-old man with coronavirus disease (COVID) pneumonia, who had persistently high serum procalcitonin levels despite normal C-reactive protein levels. The attending infectologist happened to be a colleague who spent some time, as part of her internal medicine rotation, in the Endocrine Ward and recalled that medullary thyroid cancer might be the cause. This led to the timely workup and treatment of the medullary cancer.


Subject(s)
COVID-19/complications , Carcinoma, Neuroendocrine/blood , Carcinoma, Neuroendocrine/diagnosis , Endocrinology/methods , Procalcitonin/blood , Thyroid Neoplasms/blood , Thyroid Neoplasms/diagnosis , Biomarkers, Tumor/blood , C-Reactive Protein/biosynthesis , Carcinoma, Neuroendocrine/complications , Humans , Incidental Findings , Lymph Nodes/pathology , Male , Middle Aged , SARS-CoV-2 , Thyroid Neoplasms/complications , Thyroid Nodule
20.
Int J Biol Macromol ; 193(Pt A): 838-846, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1487745

ABSTRACT

Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-ß-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.


Subject(s)
Biomarkers, Tumor/metabolism , COVID-19 , Early Detection of Cancer , Eye Diseases , Neurodegenerative Diseases , SARS-CoV-2/metabolism , Tears/metabolism , COVID-19/diagnosis , COVID-19/metabolism , Eye Diseases/diagnosis , Eye Diseases/metabolism , Humans , Neurodegenerative Diseases/diagnosis , Neurodegenerative Diseases/metabolism
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