Angel Concha's research while affiliated with Complejo Hospitalario Universitario a Coruña (CHUAC) and other places
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Publications (80)
The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present stud...
Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non‐CRC) were collected for microbiome analysis. Saliva (28 non‐CRC and 94 CRC), feces (30 non‐CRC and 97 CRC), subgingival fluid (20 CRC) and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approach...
Tumor-derived extracellular vesicles (TD-EVs) have active roles as cancer hallmark enablers. EVs RNA of epithelial and stromal cells carry information that facilitates the communication processes that contribute to oncological progression, so the objective of this work was to validate by RT-PCR the presence of epithelial (KRT19; CEA) and stromal (C...
Stage II colorectal cancer (CRC) recurrence remains a clinical problem. Some of these patients are true stage III CRC with a pN0 pathology stage. This large prospective multicentre cohort study aimed at evaluating the diagnostic ability of lymph node (LN) cytology smears to perform the pN stage and compare it with the conventional haematoxylin and...
The E3 ubiquitin-ligases are important for cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer, however, the implication in colitis-associated can...
Background: The carcinogenesis of colorectal cancer (CRC) is a multifactorial process involving both environmental and host factors, such as human genetics or the gut microbiome, which in CRC patients appears to be enriched in oral microorganisms. The aim of this work was to investigate the presence and activity of Parvimonas micrain CRC patients....
The application to clinical practice of liquid biopsy in patients with lung cancer has led to an advance in the diagnosis and monitoring of the disease. Detection of alterations in EGFR genes related to TKI treatment in EGFR-mutated non-small cell lung cancer patients is a routine method in pathology laboratories. The primary objective of this work...
It is widely accepted that the presence of immune infiltrate in human tumors is considered as an attempt of the host immunosurveillance to detect and eliminate tumor cells in order to prevent tumor progression. However, the interaction of the immune system with the tumor is much more complex and highlights the controversial roles that play innate a...
Different oncogenes that act in different phases of the epithelium–adenoma–carcinoma sequence are involved in the development of colorectal carcinoma. Although this sequence is perfectly known, so far it is only possible to act on specific points of the set of known genetic alterations. Therapies aimed at neutralizing the effects of these alteratio...
There are contradictory data regarding the correlation between HER2 amplification level determined by in situ hybridization and evolution after treatment with anti-HER2 therapies. The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEP17 and number of HER2 signals/nucleus) with pathological response achieved after neoadj...
A correction to this paper has been published: https://doi.org/10.1007/s00428-021-03121-6
Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotox...
The requirement of the E3 ubiquitin-ligase Hakai for the ubiquitination and subsequent degradation of E-cadherin has been associated with enhanced epithelial-to-mesenchymal transition (EMT), tumour progression and carcinoma metastasis. To date, most of the reported EMT-related inhibitors were not developed for anti-EMT purposes, but indirectly affe...
e12641
Background: HER2 targeted therapy in combination with chemotherapy have changed the aggressive natural history of HER2-positive tumors. To select patients to be treated with this type of agents, determination of HER2 status is usually carried out by immunohistochemistry, followed by in situ hybridization in equivocal cases (2+). There are co...
The E3 ubiquitin-ligase Hakai binds to several tyrosine-phosphorylated Src substrates, including the hallmark of the epithelial-to-mesenchymal transition E-cadherin, and signals for degradation of its specific targets. Hakai is highly expressed in several human cancers, including colon cancer, and is considered as a drug target for cancer therapy....
Objective
The aim of this study was to evaluate the efficacy, cardiotoxicity profile and long-term benefits of neoadjuvant therapy in human epidermal growth factor receptor 2-positive operable breast cancer patients.
Patients and methods
A total of 142 patients diagnosed from 2005 to 2016 were included in the study. The treatment consisted of a se...
HLA class I (HLA-I) molecules play a crucial role in the presentation of tumor antigenic peptides to CD8+ T cells. Tumor HLA-I loss provides a route of immune escape from T cell-mediated killing. We analyzed HLA-I expression in 98 cryopreserved breast cancer tissues using a broad panel of anti-HLA-I antibodies. Genomic HLA-I typing was performed us...
Resumen
El cáncer de origen desconocido se define como un grupo heterogéneo de tumores que se manifiestan con metástasis y para los que no se ha conseguido identificar su localización original. Sus características biológicas y forma de diseminación difieren del resto de tumores primarios, lo que hace que puedan considerarse como una entidad indepen...
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses...
At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated...
Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expres...
In the last few years, the role of epithelial cell plasticity in cancer biology research has gained increasing attention. This concept refers to the ability of the epithelial cells to dynamically switch between different phenotypic cellular states. This program is particularly relevant during the epithelial-to-mesenchymal transition (EMT) in cancer...
Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning...
Cancer immunosurveillance relies on effector/memory tumor infiltrating CD8+T cells with a Th1 profile. Evidence for an NK cell-based control of human malignancies is still largely missing. The KIT tyrosine kinase inhibitor imatinib mesylate (IM) markedly prolongs the survival of patients with gastrointestinal stromal tumors (GIST) by direct effects...
Background and objectives:
To analyze the prevalence of human papillomavirus (HPV) genotypes and anal dysplasia in a cohort of human immunodeficiency virus (HIV) infected men who have sex with men (MSM) from southern Spain, and the variables associated with the appearance of dysplastic lesions and oncogenic HPV genotypes.
Patients and methods:
A...
Classical MHC molecules present processed peptides from endogenous protein antigens on the cell surface, which allows CD8(+) cytotoxic T lymphocytes (CTLs) to recognize and respond to the abnormal antigen repertoire of hazardous cells, including tumor cells. The light chain, β2-microglobulin (β2m), is an essential constant component of all trimeric...
4089
Background: Overexpression of HER2 is an important biomarker in gastroesophageal junction (GEJ) and gastric cancer (GC) and a predictive factor for trastuzumab (T, Herceptin). The ToGA phase III trial showed the benefit in overall survival of adding trastuzumab to chemotherapy inHER2-positive advanced GEJ/GC patients, following validated scori...
Patients with advanced non-small-cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations can now have specific treatment based on the result of biomarker analysis and patients with rearrangements of the anaplastic lymphoma kinase (ALK) gene will probably soon be able to. This will give them better quality of life and pro...
Patients with advanced non-small cell lung cancer (NSCLC) carrying epidermal growth factor receptor (EGFR) mutations can now have specific treatment based on the result of biomarker analysis. Furthermore, this will probably soon be available for patients with rearrangements of the anaplastic lymphoma kinase (ALK) gene. More than conventional chemot...
We compared the expression of genes related to inflammatory and cytotoxic functions between MSI and MSS (HLA-class I-negative and HLA-class I-positive) colorectal cancers (CRCs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two CRCs were divided into three study groups as a function of HLA class I...
The identification of HER2 alterations in advanced gastric carcinomas is of critical importance in daily clinical practice as such neoplasms require specific treatment with trastuzumab. For these reasons, pathologists and oncologists with expertise in gastric carcinomas and HER2 testing from both organisations (SEAP and SEOM) have endeavoured to di...
The cancer of unknown primary (CUP) concept encompasses a heterogeneous group of cancers that are difficult to diagnose and that show diverse clinical and histopathological features. Currently, CUP is the fifth most frequent cancer diagnosis in women and the eighth in men. The ongoing development of new therapies specific to the various cancer type...
Accurate HER2 testing is of great clinical value for the identification of breast cancer patients who are eligible for trastuzumab therapy. The aim of this study is to review breast carcinomas diagnosed from 2001 to 2007 at a Spanish National Reference Centre for HER2 testing, evaluating the agreement between HER2 immunohistochemical (IHC) tests an...
The identification of HER2 alterations in advanced gastric carcinomas is critically important in daily clinical practice as such neoplasms require specific treatment with Trastuzumab. For this reason, expert pathologists and oncologists have agreed on national guidelines for HER2 testing in gastric carcinomas. The guidelines are based on the experi...
To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with tumor immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression.
Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadi...
A 54-year-old woman presented a peri-areolar nodule located in the skin of the right breast. Clinical examination showed a 6 x 5 cm exophytic, lobed, ulcerated, and bleeding nodule. The patient reported that the tumor had grown gradually over a period of 3 months. The patient had been diagnosed 8 years prior to presentation with infiltrating ductal...
Embryonic stem cell studies have generated great interest, due to their ability to form a wide variety of matured cells. However, there remains a poor understanding of mechanisms regulating the cell state of embryonic stem cells (ESCs) and of the genes they express during early differentiation. Gene expression analysis may be a valuable tool to elu...
Metastatic follicular thyroid carcinoma is very rare. We report a case of a 42 years old patiente with a retro-orbital and intracranial metastases, as first clinical manifestation of thyroid cancer.
The aim of this study was to determine human papillomavirus (HPV) types distribution in cervical preneoplasic lesions in a Southern Spanish population and their relationship between HPV type and grade of histopathological abnormality. Finally, 232 cervical samples from 135 women with previous cytological abnormalities were included in this study. C...
Identifying breast cancers with HER2 overexpression or amplification is critical as these usually imply the use of HER2-targeted
therapies. DNA (amplification) and protein (overexpression) HER2 abnormalities usually occur simultaneously and both in situ hybridisation and immunohistochemistry may be accurate methods for the evaluation of these abnor...
La identificación de los carcinomas de mama con amplificación/sobreexpresión de HER2 es crítica en la práctica clínica diaria ya que estas neoplasias requieren un tratamiento específico que incluye el uso de terapias dirigidas. Tanto las técnicas de hibridación in situ como las técnicas inmunohistoquímicas son métodos apropiados para la identificac...
In the tumor microenvironment, interleukin (IL)-10 production has a pleiotropic ability to positively and negatively influence the function of innate and adaptive immunity against cancer. This study investigated whether IL-10 genetic polymorphisms that influence gene expression levels play a role in the risk and clinical course of clear-cell renal...
UR-1505 is a novel salicylate derivative compound that has been demonstrated to selectively down-regulate T-cell activation. The aim of the present study was to elucidate the mechanisms involved in the intestinal anti-inflammatory effects of UR-1505 in 2 protocols of a dextran sodium sulfate (DSS) model of rat colitis: acute and established colitis...
The purpose of this review is to evaluate case reports of papillary squamous cell carcinoma (PSCC) of the upper aerodigestive tract (UADT) to assess its relationship with human papillomavirus (HPV). The medical literature was searched for case reports of this condition. A total of 115 cases of PSCC were found that described the condition in suffici...
The purpose of this review was to evaluate the case reports with lymphoproliferative disorders exclusively localized in the allograft transplanted kidney. We also report a rare case of diffuse large B-cell lymphoma originated from the lymphocytes of the recipient with exclusive localization in the kidney allograft. We searched the medical literatur...
Modern high-technology industrial practices like pharmaceutical and stem cell line production demand high-quality environmental conditions to avoid particle contamination in the final product. Particles are important because their presence can affect both the output and the productivity and because they can have repercussion on human health. In thi...
UR-1505 is a novel pentafluoropropoxy derivative of salicylic acid, selected from a series of salicylate derivatives, according to their activity as inhibitors of T-lymphocyte activation. This study describes the anti-inflammatory activity of UR-1505 on trinitrobenzenesulphonic acid-induced colitis in rat, an experimental model that resembles to Cr...
Cell therapy and regenerative medicine are potentially two of the most exciting aspects of the novel therapeutic methods currently under development. However, these treatments present a number of important biosafety issues, like the possible transmission of microorganisms to the recipients. The most common potential form of contamination in these c...
Regenerative medicine and cell therapy are emerging clinical disciplines in the field of stem cell biology. The most important sources for cell transplantation are human embryonic and adult stem cells. The future use of these human stem cell lines in humans requires a guarantee of exhaustive control with respect to quality control, safety and trace...
We report a case of extranodal NK/T-cell lymphoma, nasal type, with exclusive cerebral localization in a patient with AIDS. The patient presented with neurological alterations, fever and convulsions, so the initial presumptive diagnosis was an opportunistic brain infection. MRI showed a left parietal necrotic lesion and a stereotactic brain biopsy...
hESCs (human embryonic stem cells) are pluripotent cells derived from the ICM (inner cell mass) of blastocysts that can be used to derive several kinds of cells of the human body for the treatment of some previously untreated diseases. In considering the future use of hESCs in regenerative medicine and cell-therapy programmes, several research cent...
The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L...
Inflammatory bowel disease is associated with intestinal oxidative stress. In the present study we test the preventative effect of Lactobacillus fermentum, a probiotic that produces per se glutathione, in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis.
Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissol...
The development of human embryonic stem cell (hESC) lines for research and therapy is hampered by the need to improve the basic methodologies for cell culture expansion. In most current methods hESC lines are cultured on a mouse or human feeder cell layer which appears to be the most reliable way to maintain cells stably in the undifferentiated sta...
With the introduction of regenerative medicine and cell therapy programmes by means of human embryonic stem cells (hESC), several research centres have begun projects of derivation of hESC lines. In some stem cell banks, such as the Andalusian Stem Cell Bank, the law also permits the creation of these cell lines. Therefore, the recovery of cryopres...
There is increased interest in the study of manipulation of the flora with pro- and prebiotics regarding inflammatory bowel disease. The aim of this work was to evaluate the effect of oligosaccharides from goat milk in a rat model of dextran sodium sulfate- (DSS-) induced colitis.
Twenty rats were fed the same diet but with different sources of fib...
The processing of stem cell lines for application in human therapy requires a physical environment in which air quality (i.e., the number of airborne particles) is controlled to minimize risk of contamination. The processing facility should be constructed and operated to minimise the introduction, generation and retention of particles and microorga...
Some stem cell lines may contain an endogenous virus or can be contaminated with exogenous viruses (even of animal origin) and may secrete viral particles or express viral antigens on their surface. Moreover, certain biotechnological products (e.g. bovine fetal serum, murine feeder cells) may contain prion particles. Viral and prion contamination o...
Recent data suggest that chemokines and chemokine receptors mediate leukocyte recruitment of all components of the antitumor response. This study aimed to phenotypically characterize the immune lymphocyte infiltrate in human renal cell carcinomas RCCs and at the invasive margin (tumor-host interface) and to define the association of these findings...
The transplant of cells of human origin is an increasingly complex sector of medicine which entails great opportunities for the treatment of a range of diseases. Stem cell banks should assure the quality, traceability and safety of cultures for transplantation and must implement an effective programme to prevent contamination of the final product....
To investigate the intestinal anti-inflammatory effect and mechanism of a probiotic Lactobacillus salivarius ssp. salivarius CECT5713 in the TNBS model of rat colitis.
Female Wistar rats (180-200 g) were used in this study. A group of rats were administered orally the probiotic L. salivarius ssp. salivarius (5x10(8) CFU suspended in 0.5 mL of skimm...
Previous studies proposed a protective role of the dietary intake of (n-3) PUFA in human inflammatory bowel disease (IBD), but almost no studies have been performed using olive oil. The aims of the present study were to test the beneficial effects of an olive oil-based diet with or without fish oil, rich in (n-3) PUFA, in the dextran sodium sulfate...
Lactulose is a drug used as a laxative that has been shown to promote the growth of lactobacilli and bifidobacteria, acting as a prebiotic and with a potential beneficial effect in inflammatory bowel disease. The present study describes the preventive antiinflammatory activity of lactulose in the trinitrobenzenesulphonic acid (TNBS) model of rat co...
Quercitrin, 3-rhamnosylquercetin, is a bioflavonoid with antioxidant properties, which exerts anti-inflammatory activity in experimental colitis. In the present study, different in vivo experiments were performed in order to evaluate the mechanisms of action involved in this effect, with special attention to its effects on proinflammatory mediators...
The sex steroid control of the endometrial cycle is mediated by transcription factors, four of which are the estrogen and progesterone receptors, c-jun and c-fos, all expressed by the endometrium. The aim of this study was to analyze the distribution of the transcription factors in the different endometrial compartments during natural cycles.
We st...
Previous studies have revealed the beneficial effects exerted by dietary fiber in human inflammatory bowel disease, which were associated with an increased production of SCFA in distal colon. The aim of the present study was to elucidate the probable mechanisms involved in the beneficial effects of a fiber-supplemented diet (5% Plantago ovata seeds...
HLA expression is frequently altered in tumours compared to the tissue from which they originate. Given the central role of MHC products in the restriction of T-cell recognition, regulation of tumour HLA expression might be a strategy for the evasion of immune surveillance by the malignant cells. Federico Garrido, Peter Stern and colleagues present...
Two grade 2 ovarian immature, predominantly endodermal teratomas are reported. The teratomas were in stage I and occurred in two girls, 9 and 10 years of age, who were treated with triple chemotherapy. These neoplasms differed from the usual immature ovarian teratoma as they contained no neuroectodermal components and had high α-fetoprotein and low...
A series of 10 normal cervix epithelia, 38 condylomas, 17 CIN (cervical intraepithelial neoplasm) I/II (low-grade CIN), 10 CIN III (high-grade CIN), 27 squamous cell carcinomas and 7 adenocarcinomas of the cervix were studied in paraffin-embedded sections for the expression of MHC class I antigens, using antibodies against HLA antigens and the immu...
A case of cesarean scar endometriosis with massive decidualization is presented. The 25-year-old patient had an extensive, ulcerated lesion that mimicked malignancy microscopically due to myxoid change with alveolar patterns reminiscent of some soft tissue sarcomas, signet ring-like cells similar to mucin-producing carcinoma, and pseudoinfiltration...
Fifty basal cell carcinomas (BCC) and 8 samples of healthy skin were studied for HLA class I and class II antigen expression and for the presence of mutations in codon 12 of the K-ras and H-ras genes. All samples of healthy skin and of epithelium near the tumor showed high levels of class I molecules, whereas 38% of the tumors showed complete absen...
The expression of class I and II histocompatibility antigens was studied in 43 specimens of skeletal and in 36 specimens of cardiac muscle. Expression was also analyzed in the tumoral counterpart of striated muscle tissue, in 21 rhabdomyosarcomas (13 embryonic, 2 alveolar and 6 pleomorphic). Normal striated muscle showed very weak HLA class I antig...
There is evidence indicating that changes in the expression of HLA-ABC antigens can modulate the biological behavior and metastatic potential of certain neoplasms. We studied 15 samples of normal breast epithelium, 94 breast carcinomas and 24 benign and pre-malignant lesions of the mammary gland. All cases of normal breast epithelium and non-malign...
Molecular characterization of HLA-class-I expression was investigated in human tumor cell lines at the protein and mRNA levels using locus-specific monoclonal antibodies (MAbs) and probes. Some cell lines exhibited a differential expression of HLA-A and HLA-B products and also showed differences in the inducibility of HLA-class-I genes by gamma-IFN...
Citations
... While any microbiome-related field of study is of interest, our specific focus lies within the biomedical sphere, particularly in cancer research. This paper, in particular, centres on the examination of formalin-fixed paraffin-embedded (FFPE) microbiome samples from colorectal cancer (CRC) patients (Conde-Pérez et al., 2023). Sequencing of these samples was conducted using the 16S Amplicon Metagenomic Sequencing technique, a next-generation, highthroughput methodology that emphasizes amplifying specific, short, targeted regions known as amplicons. ...
... Consequently, the clusters were grouped based on the expression of distinct cell type markers, leading to the classi cation of cells into four clusters (epithelial cells, endothelial cells, immune cells, and broblasts). A similar analytical pipeline was applied to immune cells, where the identi cation of immune cell types was achieved by matching each cluster-speci c gene set with known signature genes of cell populations reported in previous literature [17][18][19][20][21][22][23][24] . ...
... Their results were validated by Diaz-Mercedes et al., observing a mean TTL in pN0 of 433.6 copies/µL, pN1 of 35,782.6 copies/µL, and pN2 of 144,651.8 copies/µL [14,27,63]. In our study, the tumour burden in the LNs of pT1 CRC with pN0 determined with H&E was lower, with a median of 990 copies/µL (mean 1540.6 copies/µL), while pN1 cases had a median of 5000 copies/µL (mean 9241 copies/µL). ...
... The human CBLL1 gene encodes the Hakai protein. It has been reported that the Hakai protein is highly expressed in colon and gastric cancer tissues compared to normal epithelial tissues [20,27]. Furthermore, Hakai expression progressively increases in adenoma (non-malignant tissue) and in different TNM stages (I-IV) of colon cancer patients compared to adjacent colon healthy tissues, highlighting the potential of Hakai as a biomarker for CRC progression [22]. ...
... FAP is abundant in the stroma which is related to tumor staging and aggressiveness in BCa patients. According to Gil et al. [64], FAP + CAFs have been associated with immune-cold TMEs characterized by inadequate infiltration of CD8 + T-cells and a significant loss of human leukocyte antigen expression on tumor cells. The deposition of a highly crosslinked ECM, which serves as a physical barrier to exclude lymphocytes in peritumour regions, is another factor that FAP + CAFs contribute to poor CD8 + T cell infiltration [65]. ...
... The response of patients with HER2-positive BC to HER2-targeted therapy is significant; however, the response is not universal, and a proportion of patients with HER2-positive BC do not respond [5][6][7]. In addition, conflicting data exist in the literature regarding the relationship between anti-HER2 therapeutic response and HER2 protein expression or HER2 ISH parameters, including HER2 and centromeric 17 (CEP17) copy numbers and HER2 /CEP17 copy number ratios, in both adjuvant and neoadjuvant settings [7][8][9][10][11][12][13][14][15][16]. Neoadjuvant HER2-directed therapy provides an opportunity to determine the in vivo response to therapy, as patients who achieve a pathological complete response (pCR) can anticipate a higher probability of avoiding both disease recurrence and death from BC [17][18][19]. ...
... Briefly, FTO inhibitors (FTOi) include rhein [86], MO-I-500 [87], MA/MA2 [88], fluorescein [89], R-2HG [90], FB23/FB23-2 [91], entacapone [92], CS1/CS2 [93], Dac51 [94], FTO-4 [95], FTO-43 [96], 18097 [97], and C6 [98], while ALKBH5 inhibitors (ALKBH5i) include IOX1 [99], MV1035 [100], ALK04 [101], Ena15 [102], 20m [103], and DDO-2728 [104]. Finally, the development of drugs aiming to target other m 6 A effector proteins and epitranscriptomic marks is still ongoing, with focus on the inhibition of HAKAI [105] and METTL1 [106], respectively. ...
Reference: Clinical Perspectives in Epitranscriptomics
... The proportion of HER2-positive cases in 11 local laboratories was 12.0%, which is similar to the positivity rate (13%) of another Chinese study [13]. However, it is lower than those of the ToGA study (IHC 3+ or IHC 2+/FISH+: 16.0%) and the Spanish results [20] of the HER-EAGLE study (14.1%). These apparent discrepancies between Chinese studies and other two studies may be due to differences in patient characteristics, in particular the Lauren classification and the location of the tumor. ...
... However, cancer cells differ from normal cells in many aspects, including altered expression levels and functional states of mitochondrial Hsp90 and TRAP1 (102,103). Many cancer cells express higher levels of mitochondrial Hsp90 and TRAP1, upregulate the associated signaling pathways and depend on them for survival, (e.g. ...
... Doxorubicin (DOX), a precursor of anthracyclines, is the most extensively used, beneficial, and successful antineoplastic agent. It is derived from a gram-positive bacteria called Streptomyces peucetius [7][8][9] to treat a variety of malignancies, including breast cancer and lymphoma. However, its therapeutic application is restricted due to its cardiotoxic effects [10]. ...