-
BMC Nephrology Jun 2024Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular... (Randomized Controlled Trial)
Randomized Controlled Trial
Changes in tubular biomarkers with dietary intervention and metformin in patients with autosomal dominant polycystic kidney disease: a post-hoc analysis of two clinical trials.
BACKGROUND
Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury.
METHODS
66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression.
RESULTS
Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m, and baseline BMI was 30.5 ± 5.9 kg/m. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics.
CONCLUSIONS
Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.
Topics: Humans; Metformin; Polycystic Kidney, Autosomal Dominant; Male; Female; Biomarkers; Middle Aged; Kidney Tubules; Caloric Restriction; Adult; Glomerular Filtration Rate; Lipocalin-2; Chemokine CCL2; Fatty Acid-Binding Proteins; Hepatitis A Virus Cellular Receptor 1; Chitinase-3-Like Protein 1; Hypoglycemic Agents
PubMed: 38918734
DOI: 10.1186/s12882-024-03643-6 -
Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
Topics: Humans; Male; Prostatic Neoplasms; ErbB Receptors; Receptor, ErbB-2; Adenocarcinoma; Biomarkers, Tumor; Aged; Middle Aged; Prognosis; Phosphorylation; raf Kinases; Follow-Up Studies; MAP Kinase Signaling System; ras Proteins; Aged, 80 and over; Extracellular Signal-Regulated MAP Kinases; Signal Transduction
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
Asian Pacific Journal of Cancer... Jun 2024Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble...
BACKGROUND
Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases.
METHODS
A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants.
RESULTS
HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages.
CONCLUSIONS
combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Intercellular Signaling Peptides and Proteins; Male; Axl Receptor Tyrosine Kinase; Female; Middle Aged; Receptor Protein-Tyrosine Kinases; Biomarkers, Tumor; Proto-Oncogene Proteins; Hepatitis C, Chronic; Prognosis; Liver Cirrhosis; Follow-Up Studies; Adult; Hepacivirus; Early Detection of Cancer; Aged
PubMed: 38918682
DOI: 10.31557/APJCP.2024.25.6.2185 -
Asian Pacific Journal of Cancer... Jun 2024Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in...
OBJECTIVE
Lung cancer is the most common malignancy and among the leading cause of cancer death worldwide. Therefore, there is an important need for biomarkers that can be used in the early diagnosis of the disease and in the follow-up of treatment. Circular RNAs (circRNAs) have a covalently closed circular structure that lacks 3' and 5' polar ends and is resistant to RNAase enzymes. Due to these properties, they can be stably found in body fluids. Therefore, they can serve as potential biomarkers in the diagnosis, monitoring of therapeutic response and prognosis of cancer. In our study, we aimed to investigate the expression levels of circRNA molecules in the treatment of lung cancer and to determine those that have the potential to be biomarkers.
METHODS
In this in vitro study, expression levels of 163 circRNAs were investigated in A549 cells, a non-small cell lung cancer cell line, before and after treatment with carboplatin and pemetrexed. Total RNA isolation and cDNA synthesis were performed after treatments. Expression levels of circRNA genes were determined by RT-qPCR method with the designed divergent primer sequences.
RESULTS
The study revealed the characterisation of differentially expressed circRNAs by treatment in lung cancer cells. Of them, hsa_circ_0001320 is not expressed in cancer cells, is expressed only after treatment, and increased the level of its expression in response to combination therapy.
CONCLUSION
As a result, while carboplatin, pemetrexed, and combined drug applications changed the expression levels of some circRNAs in lung cancer cells, some circRNAs were expressed only after treatment. In treatment follow-up and management, hsa_circ_0001320 has been identified as potential biomarker candidate.
Topics: Humans; RNA, Circular; Lung Neoplasms; Biomarkers, Tumor; Prognosis; Carcinoma, Non-Small-Cell Lung; Carboplatin; Pemetrexed; Gene Expression Regulation, Neoplastic; Tumor Cells, Cultured
PubMed: 38918678
DOI: 10.31557/APJCP.2024.25.6.2147 -
Asian Pacific Journal of Cancer... Jun 2024The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in...
OBJECTIVE
The aim of this study was to evaluate the expression profiles of PIWI-like protein- 2 (PIWIL2), and HepPar1 and their immunohistochemical (IHC) characteristics in Hepatocellular Carcinoma (HCC), and determine their correlation with clinicopathological parameters of this type of cancer to determine their diagnostic value in combination.
METHODS
Seventy-five patients with HCC were assessed for the expression of PIWIL2 in serum and tissue using real-time polymerase chain reaction (RT-PCR) and IHC was performed for PIWIL2 and HepPar1 was performed on all patients.
RESULTS
A statistically significantly higher level of PIWIL2 was found in HCC compared to controls (p≤0.001). Both HepPar1 and PIWIL2 were detected in 84% of HCC cases, the diagnostic and prognostic factors for PIWIL2 were found to be significant in liver tumour tissue samples and non-tumorous sections p<0.001, and the same was observed for serum samples and results of healthy serum controls (p<0.001) when compared to AFP.
CONCLUSION
Our results affirm the hypothesis that reactivation of PIWI expression in various caner types is crucial for cancer development, and that a possible panel maybe used for these markers HCC diagnosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Argonaute Proteins; Biomarkers, Tumor; Male; Female; Middle Aged; Prognosis; Case-Control Studies; Follow-Up Studies; Adult; alpha-Fetoproteins; Aged
PubMed: 38918675
DOI: 10.31557/APJCP.2024.25.6.2123 -
Asian Pacific Journal of Cancer... Jun 2024The lack of indicators to measure tumor's invasive biological behavior is an important issue. The aim of this study was to examine the effect of miRNAs 129 and 145 on...
OBJECTIVE
The lack of indicators to measure tumor's invasive biological behavior is an important issue. The aim of this study was to examine the effect of miRNAs 129 and 145 on tumor progression as well as patient survival.
METHOD
Seventy five breast cancer (BC) patients and 75 controls were included in this research. Two miRNA expressions were estimated using real-time PCR. Biomarkers for BC detection was tested using ROC curves and AUC.
RESULT
miR-129 and miR-145 expressions were significant. miR-129 and miR-145 classifiers (AUC = 0.943 and 0.748, respectively) help diagnose BC. Unlike miR-145, miR-129 did not affect the Kaplan-Meier survival curve analysis for progression-free survival at the end of the trial. The development of transitional cell carcinoma disease was found to have a strong correlation with miR-145 in both univariate and multivariate Cox regression analyses. Additionally, infiltrating + invasive urothelial carcinoma was also found to be correlated with miR-145. Conversely, elevated miR-129 expression in BC patients did not lead to an increase in cancer-specific recurrence or mortality, as observed in both univariate and multivariate Cox regression studies.
CONCLUSION
The miRNA signature can help detect survival-associated miRNAs and develop BC miRNA therapeutics.
Topics: Humans; MicroRNAs; Urinary Bladder Neoplasms; Female; Biomarkers, Tumor; Neoplasm Recurrence, Local; Case-Control Studies; Middle Aged; Prognosis; Survival Rate; Aged; Follow-Up Studies; Carcinoma, Transitional Cell; Male; ROC Curve
PubMed: 38918674
DOI: 10.31557/APJCP.2024.25.6.2113 -
Asian Pacific Journal of Cancer... Jun 2024Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic...
OBJECTIVE
Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Oral carcinogenesis is a complex, multistep process in which genetic events within signal transduction pathways governing normal cellular physiology are quantitatively or qualitatively altered. There are various molecular targets like Cyclin D and PI3k- alpha Ras Binding Domain receptor protein involved in the pathogenesis of Oral Squamous Cell Carcinoma. The aim of the study is to demonstrate the computer aided drug design to identify a potent natural molecule for targeting cyclin D4 and PI3K RAS binding protein.
MATERIALS AND METHODS
Target selection (Cyclin D1 and PI3K-alpha Ras Binding Domain receptor) was done and structures were derived from protein data bank. Ligands (Apigenin, Chrysoeriol and Luteolin) selection was done and structure derived. Final docking was performed by Autodock.
RESULTS
From the docking results it can be seen that luteolin has the highest binding energy (-5.45) with the Cyclin D receptor molecule followed by Chrysoeriol (-4.99) and Apigenin (-4.96). The binding energies of the ligands against PI3K-alpha Ras Binding Domain receptors were Apigenin (-4.51), Chrysoeriol (-4.6) and Luteolin (-4.56).
CONCLUSION
The study concludes that all the three selected ligands possess high binding energy with both the target proteins involved in carcinogenesis with highest binding energy possessed by Luteolin against the Cyclin D receptor and by Chrysoeriol against PI3K-RAS binding protein. Thus their activity can be utilized to derive potential Anti-cancer therapeutic drugs.
Topics: Humans; Molecular Docking Simulation; Mouth Neoplasms; Phytochemicals; Ligands; Biomarkers, Tumor; Cyclin D1; Apigenin; Carcinoma, Squamous Cell; Luteolin; Computer Simulation
PubMed: 38918669
DOI: 10.31557/APJCP.2024.25.6.2069 -
Asian Pacific Journal of Cancer... Jun 2024This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid...
OBJECTIVE
This study was designed to determine the role of BRAF V600E and TERT mutations in the incidence of neck lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC).
METHODS
This was a cross-sectional study, involving PTC patients at Dr. Cipto Mangunkusumo Hospital, Jakarta. Data were obtained retrospectively based on medical records, except for BRAF V600E and TERT promoter mutations. Tumor tissue specimens of PTC's patients were transferred to the Integrated Laboratory of Faculty of Medicine, Universitas Indonesia. BRAF gene multiplication was performed with KOD One PCR Master Mix (Toyobo KMM-201), while TERT gene multiplication was performed with PCR Master Mix. Data analysis was performed with SPSS version 20. The data were analyzed using univariate and bivariate analysis with the Chi-Square test.
RESULT
42 PTC patients were included in the study; 19 (45%) had BRAF mutation, 20 (48%) had TERT mutation, and 20 (48%) had LN metastases. BRAF V600E mutation was associated with LN metastasis [p<0.001, OR = 25.33 (95% CI 4.92 - 130.34)], while TERT mutation was not. Patients with BRAF+ and TERT- mutations were 18.00 times (95% CI 2.01 - 161.05) more likely to develop LN metastasis than patients with BRAF- and TERT-. Furthermore, the presence of TERT mutation along with BRAF mutation increased the risk to 60.00 (95% CI 4.72 - 763.04) higher than patients with BRAF- and TERT-.
CONCLUSION
BRAF mutation was associated with LN metastasis in PTC patients, but not TERT mutations. However, the presence of TERT mutation in PTC's patients with BRAF mutation increased the risk of LN metastasis.
Topics: Humans; Telomerase; Proto-Oncogene Proteins B-raf; Female; Lymphatic Metastasis; Male; Promoter Regions, Genetic; Thyroid Neoplasms; Cross-Sectional Studies; Mutation; Adult; Middle Aged; Retrospective Studies; Thyroid Cancer, Papillary; Prognosis; Follow-Up Studies; Carcinoma, Papillary; Indonesia; Biomarkers, Tumor
PubMed: 38918666
DOI: 10.31557/APJCP.2024.25.6.2043 -
Asian Pacific Journal of Cancer... Jun 2024Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in...
BACKGROUND
Colorectal cancer (CRC) is a major public health problem and one of leading cancer related death all over the world. One of the prognostic parameters that play a role in different types of cancer is HER2. However, the role of HER2 in CRC and its relation with clinicopathological features and survival is conflicting. We hypothesize that HER2 has different patterns of expression in CRC which may affect the prognosis of patients.
MATERIAL & METHODS
We studied sixty specimens of colorectal carcinoma for HER2 immunohistochemistry and gene amplification and correlate it with clinicopathological features and patients` survival.
RESULTS
Our data showed that negative HER2 expression was statistically associated with female gender (P = 0.010) and low & intermediate tumor budding (P = 0.030). There was a statistically significant relation between HER2 IHC and HER2 FISH amplification (P=0.000). Although neither HER2 immunoexpression and FISH amplification showed significant relation with overall survival nor disease free survival, HER2 amplified CRCs tended to have a worse survival compared with negative CRCs (40 months versus 50 months). The presence of male gender, lymphovascular invasion, nodal metastasis and distant metastasis (P = 0.013, 0.006, 0.006 and 0.000 respectively) were significantly statistically associated with poor overall survival. The presence of tumor grade III and high tumor budding (P = 0.035 and 0.007 respectively) were significantly statistically associated with shorter disease free survival.
CONCLUSIONS
Our results showed that HER2 IHC 3+ staining is highly predictive of HER2 gene amplification in colorectal carcinomas. There is a tendency towards poorer prognosis in amplified HER2 CRC cases.
Topics: Humans; Male; Colorectal Neoplasms; Female; Receptor, ErbB-2; Middle Aged; Egypt; Prognosis; Survival Rate; Biomarkers, Tumor; Gene Amplification; Aged; Adult; Follow-Up Studies; In Situ Hybridization, Fluorescence; Lymphatic Metastasis; Neoplasm Staging; Immunohistochemistry
PubMed: 38918664
DOI: 10.31557/APJCP.2024.25.6.2023 -
Asian Pacific Journal of Cancer... Jun 2024Gastric cancer is a prevalent cancer type worldwide, and significant research efforts are focused on finding effective treatments. Recent studies have highlighted the...
OBJECTIVE
Gastric cancer is a prevalent cancer type worldwide, and significant research efforts are focused on finding effective treatments. Recent studies have highlighted the importance of plasma membrane carriers, particularly solute carriers, in cancer progression. The SLC16A family, notably the SLC16A13 gene, plays a critical role in cancer development and tumor growth. This study aims to explore the impact of reducing SLC16A13 expression in gastric cancer cells on their survival, proliferation, and metastatic potential.
METHODS
Gastric cancer cells (KATO2) were cultured in RPMI medium supplemented with 10% fetal bovine serum. The cells were then transfected with SLC16A13 si-RNA to lower gene expression. The effects of this si-RNA on cell death and apoptosis were assessed using MTT and flow cytometry assays. Cell migration capabilities were evaluated using the scratch test. Western blot and Real-Time PCR were employed to measure SLC16A13 expression levels and protein detection. Additionally, RT-PCR was used to analyze changes in genes related to apoptosis and cell migration.
RESULTS
The reduction of SLC16A13 expression following si-RNA transfection significantly increased apoptosis and cell death in the KATO2 cell line after 72 hours (P < 0.0001). Furthermore, the study revealed that decreased SLC16A13 expression did not impact cancer cell migration. Cell viability, assessed by MTT assay, showed a significant decrease at 48 and 72 hours post-transfection (P < 0.0001).
CONCLUSION
The findings indicate that targeting SLC16A13 can effectively increase cell death and apoptosis in gastric cancer cells, making it a viable therapeutic target.
Topics: Humans; Apoptosis; Stomach Neoplasms; Cell Movement; Cell Proliferation; Biomarkers, Tumor; Monocarboxylic Acid Transporters; Tumor Cells, Cultured; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; RNA, Small Interfering
PubMed: 38918656
DOI: 10.31557/APJCP.2024.25.6.1953