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BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.
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Biomarcadores Tumorais , Neoplasias Embrionárias de Células Germinativas , Isoformas de Proteínas , Neoplasias Testiculares , Fatores de Transcrição , Humanos , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Masculino , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Biomarcadores Tumorais/metabolismo , Prognóstico , Progressão da Doença , Imuno-Histoquímica , Seminoma/metabolismo , Seminoma/patologia , Adulto , Citoplasma/metabolismo , Núcleo Celular/metabolismo , Análise Serial de TecidosRESUMO
BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P < 0.001, and P < 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. CONCLUSION: Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers.
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Melanoma , Neoplasias Cutâneas , Humanos , Talina/genética , Neoplasias Cutâneas/patologia , Melanoma/patologia , Processos Neoplásicos , Prognóstico , Melanoma Maligno CutâneoRESUMO
BACKGROUND: The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific functions of DCLK1 have shed new light on different functions of DCLK1 short (DCLK1-S) and DCLK1 long (DCLK1-L) isoforms in tumor initiation, growth, and metastasis. Therefore, the current systematic review and meta-analysis aimed to review the available in vitro, in vivo, and clinical evidence on the oncogenic roles and clinical significance of DCLK1 isoforms in colorectal cancer. METHODS: The literature databases of PubMed, Scopus, ISI Web of Science, and Embase were searched to identify eligible articles. The description characteristics of in vitro and pre-clinical studies were extracted from identified reports. In addition, hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded to determine the relationships between DCLK1-L and DCLK1-S expression and prognostic outcomes in patients with CRC. RESULTS: Both in vitro and in vivo evidence have emphasized the potential oncogenic functions of DCLK1 in tumor initiation, self-renewal ability, tumor invasion, epithelial-mesenchymal transition (EMT), and metastasis. However, the anti-DCLK1 antibodies generally utilized in these studies could detect sequence homology epitopes of both isoforms. Recent limited isoform-specific evidence has strongly supported the significant positive expression and rather oncogenic efficacy of DCLK1-S in tumorigenesis, EMT, and invasion compared with DCLK1-L in human CRC cell lines. Our meta-analysis findings of limited clinical studies indicated that only overexpression of DCLK1-S is associated with worse overall survival (OS) (HR = 7.930, 95% CI 2.252-27.924, p = 0.001). Increased expression of both DCLK1-S (HR = 1.610, 95% CI 1.020-2.541, p = 0.041) and DCLK1-L (HR = 5.890, 95% CI 1.219-28.453, p = 0.027) isoforms was closely associated with worse DSS/CSS in CRC patients. Furthermore, the high expression of DCLK1-S was found to be associated with poor DFS/RFS/PFS (HR = 1.913, 95% CI 1.230-2.973, p = 0.004). CONCLUSIONS: The current findings strongly supported that the DCLK1-S isoform may play a crucial role in the invasion, aggressive tumor behavior, and worsened survival outcomes of CRC patients. However, further critical investigations related to the potential preclinical and clinical utilities of DCLK1-S as a specific CRC-CSC marker are warranted.
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BACKGROUND: The crucial oncogenic role of cancer stem cells (CSCs) in tumor maintenance, progression, drug resistance, and relapse has been clarified in different cancers, particularly in colorectal cancer (CRC). The current study was conducted to evaluate the co-expression pattern and clinical significance of epithelial cell adhesion molecules (EpCAM) and activated leukocyte cell adhesion (CD166 or ALCAM) in CRC patients. METHODS: This study was carried out on 458 paraffin-embedded CRC specimens by immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Elevated expression of EpCAM and CD166 was observed in 61.5% (246/427) and 40.5% (164/405) of CRC cases. Our analysis showed a significant positive association of EpCAM expression with tumor size (P = 0.02), tumor stage (P = 0.007), tumor differentiate (P = 0.005), vascular (P = 0.01), neural (P = 0.01), and lymph node (P = 0.001) invasion. There were no significant differences between CD166 expression and clinicopathological parameters. Moreover, the combined analysis demonstrated a reciprocal significant correlation between EpCAM and CD166 expression (P = 0.02). Interestingly, there was a significant positive correlation between EpCAM/CD166 phenotypes expression and tumor stage (P = 0.03), tumor differentiation (P = 0.05), neural, and lymph node invasion (P =0.01). CONCLUSIONS: The significant correlation of EpCAM and CD166 expression and their association with tumor progression and aggressive behavior is the reason for the suggestion of these two CSC markers as promising targets to promote novel effective targeted-therapy strategies for cancer treatment in the present study.
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Antígenos CD/genética , Moléculas de Adesão Celular Neuronais/genética , Neoplasias Colorretais , Molécula de Adesão da Célula Epitelial/genética , Proteínas Fetais/genética , Biomarcadores Tumorais , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Células-Tronco Neoplásicas , PrognósticoRESUMO
BACKGROUND: Skin cancer is the most common cancer worldwide and commonly classified into malignant melanoma (MM) and Nonmelanoma skin cancers (NMSCs), which mainly include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The extent to which Long Interspersed Element-1 (LINE-1, L1) ORF1p is expressed in cutaneous malignancies remains to be evaluated. This study aimed to assess LINE-1 ORF1p immunoreactivity in various skin cancer subtypes. METHOD: The expression level of LINE-1 ORF1p was evaluated in 95 skin cancer specimens comprising 36 (37.9%) BCC, 28 (29.5%) SCC, and 31 (32.6%) melanoma using the tissue microarray (TMA) technique. Then the association between expression of LINE-1 encoded protein and clinicopathological parameters was analyzed. RESULTS: We showed that LINE-1 ORF1p expression level was substantially higher in BCC and SCC patients compared with melanoma samples (p < 0.001). BCC cases had a higher LINE-1 histochemical score (H-score) compared with SCC cases (p = 0.004). In SCC samples, a lower level of LINE-1 ORF1p expression was associated with age younger than the mean (p = 0.041). At the same time, no significant correlation was found between LINE-1 ORF1p expression and other clinicopathological parameters (all p > 0.05). CONCLUSIONS: According to our observation, LINE-1 ORF1p immunoreactivity in various skin tumor subtypes extends previous studies of LINE-1 expression in different cancers. LINE-1ORF1p overexpression in NMSCs compared with MM can be considered with caution as a tumor-specific antigen for NMSCs.
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Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Melanoma/patologia , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Proteínas de Ligação a RNA/análise , Pele/patologia , Análise Serial de TecidosRESUMO
In vitro experiments demonstrated that stimulation of Toll-like receptor 9 (TLR-9) by synthetic TLR-9 ligands induces the invasion of TLR-9-expressing prostate cancer cells through matrix metalloproteinase 13 (MMP-13). However, the clinical value of TLR-9 and MMP-13 co-expression in the pathophysiology of the prostate is unknown. In the study, we evaluated the expression levels and clinical significance of the TLR-9 and MMP-13 in a series of prostate tissues. One hundred and eighty prostate tissues including prostate cancer (PCa) (n = 137), high-grade prostatic intraepithelial neoplasia (HPIN) (n = 18) and benign prostatic hyperplasia (BPH) (n = 25) were immunostained for the TLR-9 and MMP-13 markers. Subsequently, the correlation between the TLR-9 and MMP-13 staining scores and clinicopathological parameters was obtained. Higher expressions of TLR-9 and MMP-13 were found in PCa and high-grade prostatic intraepithelial neoplasia compared to benign prostatic hyperplasia tissues. Among PCa samples, a positive relationship was revealed between the MMP-13 expression and Gleason score (P < 0.001). There was a significant correlation between TLR-9 expression and regional lymph node involvement (P = 0.04). The expression patterns of TLR-9 and MMP-13 markers demonstrated a reciprocal significant correlation between the two markers in the same series of prostate samples (P < 0.001). Furthermore, the Gleason score of TLR-9high /MMP-13high and TLR-9low /MMP-13low phenotypes showed a significant difference (P = 0.002). Higher expressions of TLR-9 and MMP-13 can confer aggressive behaviour to PCa. Therefore, these markers may be used as a valuable target for tailored therapy of PCa.
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Biomarcadores Tumorais/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Neoplasias da Próstata/metabolismo , Receptor Toll-Like 9/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diferenciação Celular , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/metabolismo , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasias da Próstata/patologiaRESUMO
Doublecortin-like kinase 1 (DCLK1) has been characterized as a novel potential cancer stem cell (CSC) marker in several types of cancer. It is considered as one of the most specific markers for distinguishing colorectal CSCs from normal stem cells. Yet, there are limited reports on the role of DCLK1 as a putative CSC marker in bladder cancer. Using immunohistochemistry, DCLK1 expression was examined in a well-defined tissue microarray series of 472 bladder cancer tissues. The association between DCLK1 protein expression and clinicopathological features, as well as survival outcomes, was assessed. Our findings showed strong, moderate, and weak DCLK1 expression in 123 (26.1%), 230 (48.7%), and 119 (25.2%) of the bladder cancer specimens, respectively. Higher expression of DCLK1 was significantly associated with increase in histological grade (Pâ¯≤â¯.001), pT stage (Pâ¯=â¯.014), lamina propria (Pâ¯=â¯.006), and lamina propria/muscularis (L/M) involvement (Pâ¯=â¯.014). On multivariate analysis, pT stage (Pâ¯<â¯.001), histological grade (Pâ¯=â¯.021), and lamina propria involvement (Pâ¯=â¯.001) were independent prognostic factors in DCLK1 expression. Moreover, the expression of DCLK1 was found to be an independent marker of poor prognosis for disease- specific survival (DSS) (Pâ¯=â¯.048) in bladder carcinomas. Our observations showed that DCLK1 expression was associated with more aggressive tumor behavior, more advanced disease, and poorer DSS in patients with bladder carcinomas. However, any potential clinical applications of DCLK1 as a novel target molecule in bladder cancer patients would require further investigations.
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Biomarcadores Tumorais/biossíntese , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Bexiga Urinária/metabolismo , Idoso , Quinases Semelhantes a Duplacortina , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/patologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
Methylphenidate (MPH) abuse damages brain cells. The neuroprotective effects of topiramate (TPM) have been reported previously, but its exact mechanism of action still remains unclear. This study investigated the in vivo role of various doses of TPM in the protection of rat amygdala cells against methylphenidate-induced oxidative stress and inflammation. Seventy adult male rats were divided into seven groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg), respectively, for 21 days. Groups 3, 4, 5, 6, and 7 were concurrently treated with MPH (10 mg/kg) and TPM (10, 30, 50, 70, and 100 mg/kg), respectively, for 21 days. elevated plus maze (EPM) was used to assess motor activity disturbances. In addition, oxidative, antioxidantand inflammatory factors and CREB, Ak1, CAMK4, MAPK3, PKA, BDNF, and c FOS gene levels were measured by RT-PCR, and also, CREB and BDNF protein levels were measured by WB in isolated amygdalae. MPH significantly disturbed motor activity and TPM (70 and 100 mg/kg) neutralized its effects. MPH significantly increased lipid peroxidation, mitochondrial GSSG levels and IL-1ß and TNF-α level and CAMK4 gene expression in isolated amygdala cells. In contrast, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and CREB, BDNF Ak1, MAPK3, PKA, BDNF, and c FOS expression significantly decreased. The various doses of TPM attenuated these effects of MPH. It seems that TPM can be used as a neuroprotective agent and is a good candidate against MPH-induced neurodegeneration.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação a CREB/metabolismo , Encefalite/prevenção & controle , Frutose/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Estimulantes do Sistema Nervoso Central/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Encefalite/induzido quimicamente , Frutose/farmacologia , Frutose/uso terapêutico , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Metilfenidato/toxicidade , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Ratos , Superóxido Dismutase/metabolismo , TopiramatoRESUMO
Methotrexate (MTX), a folic acid antagonist, is commonly prescribed as a cytotoxic drug to treat several conditions such as leukemia and inflammation-related diseases, including rheumatoid arthritis and psoriasis. However, its use in clinical practice has been limited due to its fatal side effects, especially hepatotoxicity. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has recently been reported to exhibit anti-inflammatory and anti-oxidative properties. This study was aimed to evaluate the effect of Empagliflozin on liver injury induced by MTX in rats. The rats were divided into five groups as control, MTX (20 mg/kg; i.p.), Empagliflozin (30 mg/kg/day; i.p.), MTX and Empagliflozin (10 and 30 mg/kg/day; i.p.). Histopathologic alterations were examined for assessment of the liver injury. Furthermore, the levels of tissue malondialdehyde (MDA) and activity of anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated. Our results revealed that treatment with Empagliflozin significantly improved histopathologic alterations, and elevated levels of AST and ALT induced by MTX administration. Additionally, altered activities of SOD, GPx, and catalase were significantly improved followed by Empagliflozin treatment. However, the higher dose of Empagliflozin was observed to have several benefits compared to the lower dose. Our data suggest that Empagliflozin might possess a protective role against MTX-induced hepatotoxicity by inhibiting oxidative stress in liver tissue.
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Doença Hepática Induzida por Substâncias e Drogas , Metotrexato , Ratos , Animais , Metotrexato/efeitos adversos , Catalase/metabolismo , Ratos Wistar , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Fígado , Superóxido Dismutase/metabolismoRESUMO
PURPOSE: Breast cancer is one of the most common cancers in the world. It is a multifaceted malignancy with different histopathological and biological features. Molecular biomarkers play an essential role in accurate diagnosis, classification, prognosis, prediction of treatment response, and cancer surveillance. This study investigated the clinico-pathological and prognostic significance of HER3 and ROR1 in breast cancer samples. METHODS: Tissue microarrays (TMA) were constructed using tissue blocks of 444 Iranian breast cancer patients diagnosed with breast cancer. Overall survival (OS) and disease-free survival (DFS) were assessed after 5 years follow-up. TMA slides were stained with monoclonal antibodies against ROR1, HER3, ER, PR, Ki67, P53, HER2 and CK5/6 using IHC and correlation between the investigated tumor markers and the clinico-pathological parameters of patients were analyzed. RESULTS: Our results showed a significant correlation between ROR1 and ER, PR, HER3, and CK5/6 expression. Additionally, there was a significant correlation between HER3 and ER, PR, HER2, and Ki67 expression. Ki67 was also correlated with HER2 and P53 expression. HER3 expression was significantly correlated with tumor stage, lymph node metastasis, perineural invasion, and multifocal tumors. Furthermore, ROR1 expression was significantly associated with tumor metastasis, lympho-vascular invasion, and perineural invasion. While HER2-HER3 coexpression was significantly associated with poor OS, HER3-ROR1 coexpression was associated with lymph node invasion, lymph node metastasis, and distant metastasis. CONCLUSION: ROR1 and HER3 displayed significant association with different clinic-pathological features and in addition to the other tumor biomarkers could be considered as diagnostic and prognostic biomarkers in breast cancer patients.
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Neoplasias da Mama , Humanos , Feminino , Biomarcadores Tumorais , Prognóstico , Irã (Geográfico) , Receptor ErbB-2/metabolismo , Antígeno Ki-67/metabolismo , Metástase Linfática , Proteína Supressora de Tumor p53 , Receptores de Progesterona/metabolismoRESUMO
Based on the cancer stem cell (CSC) concept model, a small population of cells with unique self-renewal properties and malignant potential exists in tumors. Immunohistochemistry was performed to detect the expression of CSC markers, CD133 and CD44, in a series of pediatric tumors. The association between expression of these markers and tumor characteristics was then analyzed. In Wilms tumors (WT), a significant positive correlation was found between expression of CD133 and the National Wilms Tumor Stage (NWTS) (p = 0.047). In neuroblastomas (NB), expression of CD133 was positively correlated with the International Neuroblastoma Staging System (INSS) (p-value = 0.012), indicating that the rate of CD133 positivity increased with the stage of these tumors. CD133, as a putative stem cell marker, is associated with more advanced stages of Wilms and NB tumors; therefore, this molecule can be a potential clinical prognostic marker in children suffering from NB or Wilms tumor.
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Antígenos CD/metabolismo , Glicoproteínas/metabolismo , Doença de Hodgkin/metabolismo , Receptores de Hialuronatos/metabolismo , Neoplasias Renais/metabolismo , Neuroblastoma/metabolismo , Peptídeos/metabolismo , Tumor de Wilms/metabolismo , Antígeno AC133 , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/cirurgia , Humanos , Lactente , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Estadiamento de Neoplasias , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Prognóstico , Estudos Retrospectivos , Células-Tronco/metabolismo , Células-Tronco/patologia , Análise Serial de Tecidos , Tumor de Wilms/patologia , Tumor de Wilms/cirurgiaRESUMO
Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients. Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Thereafter, immunohistochemical (IHC) staining was used to study the expression patterns of the talin-1 protein using 46 paraffin-embedded OSC tissue specimens, 25 benign tumors, and 20 normal tissues, which were assembled in tissue microarrays (TMAs). We also assessed the potential association between the expression of the talin-1 protein, various clinicopathological parameters, and survival outcomes. Results: Our IHC examination for talin-1 was significantly overexpressed in OSC tissues compared to benign tumors and normal tissues. The Kaplan-Meier survival analysis has also indicated statistically significant differences in terms of disease-specific survival (DSS) and progression-free survival (PFS) between the patients with high and low expression levels of talin-1, respectively. Conclusion: The talin-1 protein was overexpressed in OSC tissues, and a high expression level of talin-1 was found to be significantly associated with tumor aggressiveness and poorer DSS or PFS. Therefore, talin-1 may serve as a molecular marker of cancer progression and a novel prognostic biomarker in these patients.
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Airflow limitation in patients with obstructive sleep apnea (OSA) leads to arousal, increased sympathetic nervous system activity, and elevated blood pressure, which causes a decrease in pulse transit time (PTT). The present study aims to evaluate the effect of CPAP therapy on PTT in patients with moderate to severe OSA. This was a cross-sectional study. Split-night polysomnography (PSG) study was performed for each participant with apnea-hypopnea index (AHI) ≥ 15 before and during CPAP therapy. The PTT was calculated as the time interval between the R wave of the electrocardiogram and the following arrival point in fingertip photoplethysmography. PTT drop was defined as a fall in the PTT curve of ≥15 ms lasting at least for 3 s and at most for 30 s. PTT drop index was defined as the number of drops in PTT that occur per hour of sleep. A total of 30 patients were included. PTT significantly increased, and PTT drop index significantly decreased during CPAP therapy (P < 0.001). PTT was significantly correlated to sleep efficiency (rs = -0.376, P = 0.049) and oxygen desaturation index (ODI) (rs = -0.428, P = 0.018). PTT drop index was strongly correlated to AHI (rs = 0.802, P < 0.001), respiratory disturbance index (RDI) (rs = 0.807, P < 0.001), ODI (rs = 0.693, P < 0.001), arousal index (rs = 0.807, P < 0.001), and periodic leg movement (PLM) index (rs = 0.400, P = 0.035). Overall, the findings from this study indicated that the PTT drop index is a non-invasive and useful marker for evaluating the severity of OSA and the effectiveness of treatment in patients with moderate to severe OSA.
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Apneia Obstrutiva do Sono , Pressão Positiva Contínua nas Vias Aéreas , Estudos Transversais , Humanos , Oxigênio , Polissonografia , Análise de Onda de Pulso , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/terapiaRESUMO
INTRODUCTION: Melanoma-associated antigen A2 (MAGE-A2) is a member of the cancer-testis antigen family differentially overexpressed in a variety of malignancies and is associated with tumor development. However, clinical significance and prognostic value of MAGE-A2 in different histological subtypes of testicular germ cell tumors (TGCTs) have not been explored. MATERIALS AND METHODS: Here, we aimed to investigate the clinical significance and prognostic impact of MAGE-A2 expression in TGCTs compared to benign tumors as well as adjacent normal tissues and then between seminomas and non-seminomas groups using immunohistochemistry on tissue microarrays. RESULTS: The results indicated a statistically significant difference between overexpression of MAGE-A2 and histological subtypes of TGCTs. A statistically significant association was found between a high level of nuclear expression of MAGE-A2 protein and advanced pT stage (P = 0.022), vascular invasion (P = 0.037), as well as involvement of rete testis (P = 0.022) in embryonal carcinomas. Increased nuclear expression of MAGE-A2 was observed to be associated with more aggressive behaviors and tumor progression rather than cytoplasmic expression in these cases. Further, high level nuclear expression of MAGE-A2 had shorter disease-specific survival (DSS) or progression-free survival (PFS) compared to patients with moderate and low expression of MAGE-A2, however, without a statistically significant association. CONCLUSION: Our results confirm that increased nuclear expression of MAGE-A2 has a clinical significance in embryonal carcinomas and is associated with progression of disease. Moreover, MAGE-A2 may act as a potential predictive biomarker for the prognosis in embryonal carcinomas if follow-up period becomes longer. Further investigations for the biological function of MAGE-A2 are required in future studies.
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Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Embrionário/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/patologia , Neoplasias Testiculares/patologia , Adolescente , Adulto , Idoso , Carcinoma Embrionário/metabolismo , Carcinoma Embrionário/cirurgia , Estudos de Casos e Controles , Criança , Pré-Escolar , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/cirurgia , Prognóstico , Estudos Retrospectivos , Seminoma/metabolismo , Seminoma/cirurgia , Taxa de Sobrevida , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/cirurgia , Adulto JovemRESUMO
BACKGROUND: Isoform-specific function of doublecortin-like kinase 1 (DCLK1) has highlighted the key role of the DCLK1-S (short isoform) in the maintenance, progression, and invasion of the tumor. OBJECTIVE: This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. METHODS: The expression pattern and clinical significance of DCLK1-S were assessed in a well-defined tissue microarray (TMA) series of 348 CRC and 51 adjacent normal tissues during a follow-up period of 108 months. RESULTS: Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P< 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at the advanced stage of cancer and with poorer differentiation (P< 0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P= 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p= 0.04) by multivariate analysis. CONCLUSIONS: Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered an independent prognostic factor influencing DSS.
Assuntos
Neoplasias Colorretais , Quinases Semelhantes a Duplacortina , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Isoformas de Proteínas/genética , Proteínas Serina-Treonina Quinases/genéticaRESUMO
BACKGROUND: Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC). METHODS: The association between SALL4 and ALDH1A1 was observed based on literature review and bioinformatics tools. Therefore, this study aimed to investigate the association between the co-expression of SALL4/ALDH1A1 proteins and clinicopathological parameters and their prognostic value in SOC patients using immunohistochemical staining on tissue microarrays (TMAs). Furthermore, benign tumors and normal tissue samples were compared with the expression of the tumor tissue samples. RESULTS: Increased co-expression of SALL4/ALDH1A1 was found to be significantly associated with the advanced FIGO stage (P = 0.047), and distant metastasis (P = 0.028). The results of Kaplan-Meier survival analysis indicated significant differences between disease- specific survival (DSS; P = 0.034) or progression-free survival (PFS; P = 0.018) and the patients with high and low co-expression of SALL4/ALDH1A1, respectively. Furthermore, high level co-expression of SALL4/ALDH1A1 was a significant predictor of worse DSS and PFS in the univariate analysis. The data also indicated that the co-expression of SALL4/ALDH1A1 was an independent prognostic factor affecting PFS. Moreover, the co-expression of SALL4/ALDH1A1 added prognostic values of DSS in patients with SOC who had grade III versus grade I in multivariate analysis. CONCLUSIONS: Our data demonstrated that high co-expression of SALL4/ALDH1A1 was found to be significantly associated with tumor aggressiveness and worse DSS or PFS in SOC patients. Therefore, co-expression of SALL4/ALDH1A1 may serve as a potential prognostic biomarker of cancer progression in these cases.
Assuntos
Família Aldeído Desidrogenase 1/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Ovarianas/metabolismo , Retinal Desidrogenase/metabolismo , Fatores de Transcrição/metabolismo , Adolescente , Adulto , Idoso , Família Aldeído Desidrogenase 1/genética , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Células-Tronco Neoplásicas , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/metabolismo , Ovário/patologia , Prognóstico , Mapas de Interação de Proteínas , Retinal Desidrogenase/genética , Fatores de Transcrição/genética , Adulto JovemRESUMO
Data on the prevalence of bacterial co-infections and secondary infection among adults with COVID-19 admitted to the intensive care unit (ICU) are rare. We aimed to determine the frequency of secondary bacterial infection, antibiotic use, and clinical characteristics in patients admitted to the ICU with severe SARS-CoV-2 pneumonia. This was a retrospective cohort study of adults with severe COVID-19 admitted to two ICUs from March 6 to September 7, 2020 in an academic medical center in Isfahan, Iran. To detect COVID-19, reverse transcription real-time polymerase chain reaction was performed and also typical pattern of CT scan was used for the diagnosis of COVID-19. Data collection included the age, gender, main symptoms, history of underlying disease, demographics, hospital stay, outcomes, and antibiotic regimen of the patient. Antimicrobial susceptibility testing was carried out according to the CLSI guidelines. During the study period, 553 patients were referred to the both ICUs for COVID-19 with severe pneumonia. Secondary bacterial infection was detected in 65 (11.9%) patients. The median age was 69.4 (range 21-95) years; 42 (63.6%) were men. Notably, 100% (n = 65) of the patients with superinfection were prescribed empirical antibiotics before first positive culture, predominantly meropenem (86.2%) with a median duration of 12 (range 2-32) days and levofloxacin (73.8%) with a median duration of nine (range 2-24) days. Most prevalent causative agents for secondary bacterial infection were Klebsiella pneumoniae (n = 44) and Acinetobacter baumannii (n = 33). Most patients with secondary bacterial infection showed extensive drug-resistance. The mortality among patients who acquired superinfections was 83% against an overall mortality of 38.1% in total admitted COVID-19 patients. We found a high prevalence of carbapenem-resistant Gram-negative bacilli in COVID-19 patients admitted to our ICUs, with a high proportion of K. pneumoniae followed by A. baumannii. These findings emphasize the importance of implementation of strict infection control measures and highlight the role of antimicrobial stewardship during a pandemic.
Assuntos
Infecções Bacterianas , COVID-19 , Coinfecção , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , Coinfecção/epidemiologia , Hospitais , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Adulto JovemRESUMO
Cancer stem cells (CSCs) are thought to be a major player in tumor initiation, progression, and metastasis. Targeting CSCs for elimination presents a promising therapeutic strategy; however, this approach will require a stronger understanding of CSC biology and identification of CSC-specific markers. The present study was conducted to examine the correlation between DCLK1 and miR-137 and miR-15a levels in colorectal cancer. A total of 222 samples, including 181 colorectal cancer specimens, 24 adenomatosis, and 17 non-adenomatosis colonic polyps, were stained for DCLK1 expression using immunohistochemistry. Also, expression of miR-137 and miR-15a was assessed in colorectal cancer with high and low DCLK1 expression levels. Most colorectal cancer specimens (76%) showed strong expression of DCLK1, whereas only 21% of adenomatous and none of non-adenomatous colonic polyps showed strong DCLK1 expression. A significant difference in DCLK1 expression was found between colorectal cancer, adenomatous, and non-adenomatous colonic polyps (P < 0.001). Higher expression of DCLK1 was more frequently detected in colorectal cases with larger tumor size (P = 0.03), poor differentiation (P = 0.03), and lymph node involvement (P = 0.04). Comparison of miR-137 and miR-15a in colorectal cancer cases revealed a significant inverse correlation with DCLK1 expression (P = 0.03 and P = 0.04, respectively). DCLK1 may act as a candidate marker for colorectal cancer stem cells. The critical role of DCLK1 in colorectal cancer suggests that it may represent an early diagnostic marker and therapeutic target; however, further investigation is warranted.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , MicroRNAs/genética , Células-Tronco Neoplásicas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Progressão da Doença , Quinases Semelhantes a Duplacortina , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Coronavirus disease 2019 (COVID-19) was first discovered in December 2019 in China and has rapidly spread worldwide. Clinical characteristics, laboratory findings, and their association with the outcome of patients with COVID-19 can be decisive in management and early diagnosis. Data were obtained retrospectively from medical records of 397 hospitalized COVID-19 patients between February and May 2020 in Imam Reza Hospital, northeast Iran. Clinical and laboratory features were evaluated among survivors and nonsurvivors. The correlation between variables and duration of hospitalization and admission to the intensive care unit (ICU) was determined. Male sex, age, hospitalization duration, and admission to ICU were significantly related to mortality rate. Headache was a more common feature in patients who survived (p=0.017). It was also related to a shorter stay in the hospital (p=0.032) as opposed to patients who experienced chest pain (p=0.033). Decreased levels of consciousness and dyspnea were statistically more frequent in nonsurvivors (p=0.003 and p=0.011, respectively). Baseline white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were significantly higher in nonsurvivors (p < 0.001). Patients with higher WBC and CRP levels were more likely to be admitted to ICU (p=0.009 and p=0.001, respectively). Evaluating clinical and laboratory features can help clinicians find ways for risk stratifying patients and even make predictive tools. Chest pain, decreased level of consciousness, dyspnea, and increased CRP and WBC levels seem to be the most potent predictors of severe prognosis.
RESUMO
Echinococcus granulosus causes human cystic echinococcosis as an important public health problem in many regions of the world. There are some problems in primary diagnosis such as cross-reaction with sera from patients with other parasitic disease in serological tests. The use of an appropriate source of antigenic material is a very important and crucial point in the improvement of the serodiagnostic features such as enzyme-linked immunosorbent assay (ELISA) method. We expressed and purified recombinant AgB of Echinococcus granulosus and used as antigen in ELISA method. Serum samples were given from 36 cystic hydatid disease patients that have been confirmed by surgical operation as well as 36 healthy individuals sera were tested by ELISA method using recombinant AgB and compared with commercial kit (Euroimmun) for specificity and sensitivities value. The sensitivity of 91.66% and specificity of 97.22% were determined by homemade kit.