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Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.
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BACKGROUND: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). RESEARCH DESIGN AND METHODS: The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. RESULTS: A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. CONCLUSIONS: The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06021379.
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BACKGROUND: The prevalence of tobacco use among various cancer types in Iran remains a significant concern, necessitating a comprehensive analysis to understand the extent and patterns of consumption. This study aimed to systematically review and analyze existing literature to delineate the prevalence of tobacco use across different cancer types in Iran, thereby providing a robust basis for future interventions and policy formulations. METHODS: Adhering to the PRISMA guidelines, we conducted a systematic review and meta-analysis of literature available in PubMed and Scopus databases. The initial search identified 351 records, out of which 44 studies were selected based on their relevance and design. These studies spanned various time frames, starting from the 2001s up until 2022, and encompassed diverse geographical locations and cancer types in Iran. To avoid bias and potential data overlap, we opted to incorporate a single comprehensive study from the Golestan Cohort, encompassing all data, while excluding 10 other studies. Our final analysis incorporated data from 34 studies, which accounted for 15,425 patients and 5,890 reported smokers. Statistical analyses were performed to calculate the overall proportion of tobacco consumption and to conduct subgroup analyses based on different variables such as cancer types, gender, geographical locations, and types of tobacco used. RESULTS: The analysis revealed a substantial prevalence of tobacco use among cancer patients in Iran, with an overall consumption rate of 43%. This rate varied significantly, ranging from 10 to 88% across individual studies. Subgroup analyses further highlighted disparities in tobacco consumption rates across different demographics, geographic areas, and cancer types. Notably, the 'ever' smokers category exhibited the highest prevalence of tobacco use. The study also identified a worrying trend of high cigarette smoking rates, along with variable consumption patterns of other forms of tobacco, including waterpipe, 'Naas', and 'Pipe'. CONCLUSIONS: This systematic review and meta-analysis underscores a significant association between tobacco consumption and various cancer types in Iran, with a prevalence rate among cancer patients being three times higher than the average Iranian population. The findings indicate substantial heterogeneity in tobacco use patterns, emphasizing the need for targeted interventions to address this pressing health issue. The study serves as a critical resource for shaping future policies and strategies aimed at curbing tobacco use and mitigating its adverse effects on cancer prevalence in Iran.
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Fumar Cigarrillos , Neoplasias , Uso de Tabaco , Humanos , Fumar Cigarrillos/epidemiología , Irán/epidemiología , Neoplasias/epidemiología , Prevalencia , Uso de Tabaco/epidemiologíaRESUMEN
BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.
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Neoplasias Colorrectales , Adicción al Opio , Humanos , Adicción al Opio/epidemiología , Adicción al Opio/complicaciones , Factores de Riesgo , Opio/efectos adversos , Irán/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Estudios de Casos y ControlesRESUMEN
Glioblastoma (GBM) is one of the most aggressive tumors in the brain with high mortality worldwide. Despite recent advances in therapeutic strategies, the survival rate remains low in patients with GBM. The pathogenesis of GBM is a very complicated process involving various genetic mutations affecting several oncogenic signaling pathways like Wnt/ß-catenin axis. Overactivation of the Wnt/ß-catenin signaling pathway is associated with decreased survival and poor prognosis in patients with GBM. MicroRNAs (miRNAs) were shown to play important roles in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis by modulating the expression of their target genes. Aberrant expression of miRNAs were reported in various human malignancies including GBM, breast, colorectal, liver, and prostate cancers, but little is known about their cellular mechanisms. Therefore, recognition of the expression profile and regulatory effects of miRNAs on the Wnt/ß-catenin pathway may offer a novel approach for the classification, diagnosis, prognosis, and treatment of patients with GBM. This review summarizes previous data on the modulatory role of miRNAs on the Wnt/ß-catenin pathway implicated in tumorigenesis of GBM.
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Glioblastoma , MicroARNs , Masculino , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Glioblastoma/genética , Glioblastoma/patología , Vía de Señalización Wnt/genética , beta Catenina/genética , Línea Celular Tumoral , Carcinogénesis/genética , Transformación Celular Neoplásica , Proliferación Celular/fisiología , Regulación Neoplásica de la Expresión GénicaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on identifying new biomarkers for its early diagnosis and the prediction of patient survival. Genome-wide RNA and microRNA sequencing, bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs), followed by validation in an additional cohort of PDAC patients has been undertaken. To identify DEGs, genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA). We used Kaplan-Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest (RF), Max Voting, Adaboost, Gradient boosting machines (GBM), and Extreme Gradient Boosting (XGB) techniques were used, and Gradient boosting machines (GBM) were selected with 100% accuracy for analysis. Moreover, protein-protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs, and a combination of these obtained from machine learning algorithms and survival analysis. The results of Machine learning identified 23 genes with negative regulation, five genes with positive regulation, seven microRNAs with negative regulation, and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of the disease. In addition, the survival analysis showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9, and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in the disease pathogenesis can be used to detect patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.
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Carcinoma Ductal Pancreático , MicroARNs , Neoplasias Pancreáticas , Humanos , Catepsina W/genética , Catepsina W/metabolismo , Regulación hacia Abajo , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Pronóstico , Biomarcadores , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Neoplasias PancreáticasRESUMEN
Recently, miRNAs have been regarded as potential candidates for mediating therapeutic functions by targeting genes related to drug response. In this study, we suggested that plasma miRNAs may be correlated with response to trastuzumab in HER2-positive breast cancer patients. To determine whether miR-195, miR-23b-3p, miR-1246, and miR-34c-3p are involved in trastuzumab resistance, we screened their expressions in the BT-474 cell line, which was followed by plasma analysis from 20 trastuzumab-resistant HER2-positive breast cancer patients and 20 nonresistance subjects. Then, TargetScan, Pictar, and miRDB were applied to find the possible targets of the selected miRNAs. In addition, the expression status of admitted targets was evaluated. Our results showed that in resistant BT-474 cells, miR-1246, and miR-23b-3p were significantly upregulated, and miR-195-5p and miR-34c-3p were downregulated. In plasma analysis, we found miR-195-5p, miR-34c-3p, and miR-1246 meaningfully diminished in the resistant group, while the expression of miR-23b-3p was not statistically different. The expression levels of confirmed targets by qRT-PCR showed that the expression of RAF1, AKT3, c-MET, CCND1, PHLPP2, MYB, MAP2K1, and PTEN was significantly upregulated, while the expression of CCNG2 was significantly downregulated. The networks of miRNAs with their confirmed targets improved comprehension of miRNA-mediated therapeutic responses to trastuzumab and might be proposed for more characterization of miRNA functions. Moreover, these data indicated that miR-195-5p, miR-34c-3p, and miR-1246 could be possible biomarkers for prognosis and early detection of the trastuzumab-resistant group from the sensitive group of HER2-positive breast cancer patients.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Trastuzumab/farmacología , Trastuzumab/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Detección Precoz del Cáncer , MicroARNs/metabolismo , Biomarcadores , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Fosfoproteínas Fosfatasas/metabolismoRESUMEN
Preclinical models are extensively employed in cancer research because they can be manipulated in terms of their environment, genome, molecular biology, organ systems, and physical activity to mimic human behavior and conditions. The progress made in in vivo cancer research has resulted in significant advancements, enabling the creation of spontaneous, metastatic, and humanized mouse models. Most recently, the remarkable and extensive developments in genetic engineering, particularly the utilization of CRISPR/Cas9, transposable elements, epigenome modifications, and liquid biopsies, have further facilitated the design and development of numerous mouse models for studying cancer. In this review, we have elucidated the production and usage of current mouse models, such as xenografts, chemical-induced models, and genetically engineered mouse models (GEMMs), for studying esophageal cancer. Additionally, we have briefly discussed various gene-editing tools that could potentially be employed in the future to create mouse models specifically for esophageal cancer research.
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Neoplasias Esofágicas , Edición Génica , Animales , Ratones , Humanos , Edición Génica/métodos , Ingeniería Genética , Modelos Animales de Enfermedad , Neoplasias Esofágicas/genéticaRESUMEN
Immunosuppressive factors within the tumor microenvironment (TME), such as Transforming growth factor beta (TGF-ß), constitute a crucial hindrance to immunotherapeutic approaches in colorectal cancer (CRC). Furthermore, immune checkpoint factors (e.g., programmed death-ligand 1 [PD-L1]) inhibit T-cell proliferation and activation. To cope with the inhibitory effect of immune checkpoints, the therapeutic value of dual targeting PD-L1 and TGF-ß pathways via M7824 plus 5-FU in CRC has been evaluated. Integrative-systems biology approaches and RNAseq were used to assess the differential level of genes associated with 88 metastatic-CRC patients. The level of PD-L1 and TGF-ß was evaluated in a validation cohort. The anti-proliferative, migratory, and apoptotic effects of PD-L1/TGF-ß inhibitor, M7824, were assessed by MTT, wound-healing assay, and flow cytometry. Anti-tumor activity was assessed in a xenograft model, followed by biochemical studies and histological staining, and gene/protein expression analyses by RT-PCR and ELISA/IHC. The result of differentially expressed genes (DEGs) analysis showed 1268 upregulated and 1074 downregulated genes in CRC patients. Among the highest scoring genes and dysregulated pathways associated with CRC, PD-L1, and TGF-ß were identified and further validated in 92 CRC patients. Targeting of PD-L1-TGF-ß inhibited cell growth and migration, associated with modulation of CyclinD1 and MMP9. Furthermore, M7824 inhibited tumor growth via targeting TGF-ß and PD-L1 pathways, resulting in modulation of inflammatory response and fibrosis via TNF-α/IL6/CD4-8 and COL1A1/1A2, respectively. In conclusion, our data illustrated that co-targeting PD-L1 and TGF-ß pathways increased the effect of Fluorouracil (5-FU) and reduced the tumor growth in PD-L1/TGF-ß expressing tumors, providing a new therapeutic option in the treatment of CRC.
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Antígeno B7-H1 , Neoplasias Colorrectales , Humanos , Antígeno B7-H1/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Microambiente TumoralRESUMEN
Gastrointestinal (GI) cancers, as the most common human malignancies are always considered one of the most important health challenges in the world. Late diagnosis in advanced tumor stages is one of the main reasons for the high mortality rate and treatment failure in these patients. Therefore, investigating the molecular pathways involved in GI tumor progression is required to introduce the efficient markers for the early tumor diagnosis. Epithelial-mesenchymal transition (EMT) is one of the main cellular mechanisms involved in the GI tumor metastasis. Non-coding RNAs (ncRNAs) are one of the main regulatory factors in EMT process. Circular RNAs (circRNAs) are a group of covalently closed loop ncRNAs that have higher stability in body fluids compared with other ncRNAs. Considering the importance of circRNAs in regulation of EMT process, in the present review we discussed the role of circRNAs in EMT process during GI tumor invasion. It has been reported that circRNAs mainly affect the EMT process through the regulation of EMT-specific transcription factors and signaling pathways such as WNT, PI3K/AKT, TGF-ß, and MAPK. This review can be an effective step in introducing a circRNA/EMT based diagnostic panel marker for the early tumor detection among GI cancer patients.
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Neoplasias Gastrointestinales , ARN Circular , Humanos , ARN Circular/genética , Transición Epitelial-Mesenquimal/genética , Fosfatidilinositol 3-Quinasas , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Transducción de Señal/genéticaRESUMEN
Gastric cancer is the high mortality rate cancers globally, and the current survival rate is 30% even with the use of combination therapies. Recently, mounting evidence indicates the potential role of miRNAs in the diagnosis and assessing the prognosis of cancers. In the state-of-art research in cancer, machine-learning (ML) has gained increasing attention to find clinically useful biomarkers. The present study aimed to identify potential diagnostic and prognostic miRNAs in GC with the application of ML. Using the TCGA database and ML algorithms such as Support Vector Machine (SVM), Random Forest, k-NN, etc., a panel of 29 was obtained. Among the ML algorithms, SVM was chosen (AUC:88.5%, Accuracy:93% in GC). To find common molecular mechanisms of the miRNAs, their common gene targets were predicted using online databases such as miRWalk, miRDB, and Targetscan. Functional and enrichment analyzes were performed using Gene Ontology (GO) and Kyoto Database of Genes and Genomes (KEGG), as well as identification of protein-protein interactions (PPI) using the STRING database. Pathway analysis of the target genes revealed the involvement of several cancer-related pathways including miRNA mediated inhibition of translation, regulation of gene expression by genetic imprinting, and the Wnt signaling pathway. Survival and ROC curve analysis showed that the expression levels of hsa-miR-21, hsa-miR-133a, hsa-miR-146b, and hsa-miR-29c were associated with higher mortality and potentially earlier detection of GC patients. A panel of dysregulated miRNAs that may serve as reliable biomarkers for gastric cancer were identified using machine learning, which represents a powerful tool in biomarker identification.
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MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Perfilación de la Expresión Génica , Detección Precoz del Cáncer , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores de Tumor/genética , AlgoritmosRESUMEN
PURPOSE: Fusion transcripts are transcriptome-mediated alterations involved in tumorigenesis and are considered as diagnostic, prognostic, and therapeutic biomarkers. In metastatic colorectal carcinoma (mCRC), fusion transcripts are rarely reported. The main challenge is to identify driver chimeras with a significant role in cancer progression. METHODS: In the present study, 86 RNA sequencing data samples were analyzed to discover driver fusion transcripts. Functional assays included clonogenic cell survival, wound-healing, and transwell cell invasion. Quantitative expression analysis of epithelial-mesenchymal transition (EMT), apoptotic regulators, and metastatic markers were examined for the candidate fusion genes. Kaplan-Meier survival analysis was performed using patient overall survival (OS). RESULTS: A variety of driver fusions were identified. Fourteen fusion genes (51% of mCRC), each at least found in two mCRC samples, were determined as oncogenic fusion transcripts by in silico analysis of their functions. Among them, two recurrent chimeric transcripts confirmed by Sanger sequencing were selected. Positive expression of ADAP1-NOC4L was significantly associated with an increased risk of poor OS in mCRC patients. In vitro transforming potential for the chimera, resulting from the fusion of ADAP1 and NOC4L was assessed. Overexpression of this fusion gene increased cell proliferation and enhanced migration and invasion of CRC cells. In addition, it significantly upregulated EMT and anti-apoptotic markers. CONCLUSIONS: ADAP1-NOC4L transcript chimera, a driver chimera identified in this study, provides new insight into the underlying mechanisms involved in the development and spread of mCRC. It suggests the potential of RNA-based alterations as novel targets for personalized medicine in clinical practice.
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Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinogénesis , Línea Celular Tumoral , Transformación Celular Neoplásica , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Proteínas del Tejido Nervioso/genética , Ribonucleoproteínas Nucleares Pequeñas/metabolismoRESUMEN
Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.
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Carcinoma de Células Pequeñas , Neoplasias Pulmonares , Adicción al Opio , Carcinoma Pulmonar de Células Pequeñas , Humanos , Femenino , Masculino , Adicción al Opio/epidemiología , Estudios de Casos y Controles , Opio/efectos adversos , Irán/epidemiología , Carcinoma Pulmonar de Células Pequeñas/epidemiología , Carcinoma Pulmonar de Células Pequeñas/etiología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiologíaRESUMEN
Gastric cancer (GC) is the fourth most common cause of mortality and the fifth for incidence, globally. Diagnosis, early prognosis, and therapy remains challenging for this condition, and new tumor-associated antigens are required for its detection and immunotherapy. Cancer-testis antigens (CTAs) are a subfamily of tumor-associated antigens (TAAs) that have been identified as potential biomarkers and targets for cancer immunotherapy. The CTAs-restricted expression pattern in tumor cells and their potential immunogenicity identify them as attractive target candidates in CTA-based diagnosis or prognosis or immunotherapy. To date, numerous studies have reported the dysregulation of CTAs in GC. Several clinical trials have been done to assess CTA-based immunotherapeutic potential in the treatment of GC patients. NY-ESO-1, MAGE, and KK-LC-1 have been used in GC clinical trials. We review recent studies that have investigated the potential of the CTAs in GC regarding the expression, function, aggressive phenotype, prognosis, and immunological responses as well as their possible clinical significance as immunotherapeutic targets with a focus on challenges and future interventions.
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Neoplasias Gástricas , Masculino , Humanos , Neoplasias Gástricas/metabolismo , Testículo/metabolismo , Antígenos de Neoplasias/genética , Inmunoterapia , Proteínas de la Membrana/genética , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND: Colorectal-cancer (CRC) is amongst the most lethal-cancers, mainly due to its metastatic spread and drug chemoresistance. Hence there is a need for new approaches to either increase the efficacy of current therapy or introduce new therapies that have greater efficacy. There is increasing evidence that dysregulation of WNT-signaling-pathway plays an essential role in the development and prognosis of CRC. Here we have investigated the therapeutic potential of targeting the WNT/b-catenin pathway using a novel Wnt/b-catenin inhibitor, PNU-74654, in combination with 5-FU in CRC. METHODS: The anti-proliferative-effect of PNU-74654 was evaluated in two-/three-dimensional cell models. The activity of agents on cell growth, migration, invasion, cell cycle and apoptosis was evaluated by MTT, wound healing assay, invasion, FACS, and annexin V staining, respectively. The oxidant/antioxidant levels were also assessed by determining the level of MDA, SOD, as well as using the DCFH-DA assay. We used a xenograft model of CRC to investigate PNU-74654 activity alone and in combination with 5-FU follow by histological staining and biochemical and gene expression analyses by RT-PCR and western blot. RESULTS: PNU-74654 inhibited cell-growth and synergistically affected the anti-tumor properties of 5-FU via modulation of Cyclin D1 and survivin. This agent inhibited the migration/invasion of colorectal cancer cells via perturbation of E-cadherin. Furthermore, PNU-74654 inhibited the tumor growth, which was more pronounced using the PNU-74654 plus 5-FU combination via induction of reactive oxygen species, down-regulation of SOD and modulation of MCP-1, P53, TNF-α. CONCLUSIONS: Our finding demonstrated that PNU-74654 can target Wnt-pathway, interfere with cell-proliferation, induced-cell death, reduced-migration and interact with 5-FU, supporting further investigations on this therapeutic-approach for colorectal cancer.
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Cateninas , Neoplasias Colorrectales , Animales , Apoptosis , Benzamidas , Cateninas/metabolismo , Cateninas/farmacología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Superóxido Dismutasa/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismoRESUMEN
BACKGROUND: Bladder cancer (BC) is the 10th most common type of cancer worldwide and the fourth most common type of cancer in Iran. Opium use is considered as one of the risk factors for BC. We aim to assess the association between various parameters of opium use, which in Iran is mainly ingested or smoked in various forms, and the risk of BC. METHOD: In this multi-centre case-referent study in Iran, 717 BC cases and 3477 referents were recruited to the study from May 2017 until July 2020. Detailed histories of opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure adjusted odds ratio (OR) and 95% confidence intervals (CI). The ORs were adjusted for age, gender, place of residence and pack-years of cigarette smoking. RESULTS: Regular opium consumption was associated with an increased risk of BC (OR 3.5, 95% CI: 2.8, 4.3) compared with subjects who never used opium. Compared with continuous users, the risk decreased to one-third for those who stopped opium more than 10 years ago. The adjusted OR for those who used both crude opium (teriak) and opium juice was 7.4 (95% CI: 4.1, 13.3). There was a joint effect of opium and tobacco (OR for users of both opium and tobacco 7.7, 95% CI: 6.0, 9.7). CONCLUSIONS: Regular opium use is associated with an approximately 4-fold risk for BC. The OR decreases along with the increasing time since stopping opium use.
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Adicción al Opio , Neoplasias de la Vejiga Urinaria , Estudios de Casos y Controles , Humanos , Irán/epidemiología , Opio/efectos adversos , Adicción al Opio/epidemiología , Factores de Riesgo , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/etiologíaRESUMEN
Coronavirus disease 2019 (COVID-19) is a serious viral disease caused by SARS-CoV-2, associated with high morbidity and mortality, and represents a significant public health crisis worldwide. Despite recent efforts for developing novel antiviral agents, no specific drugs are approved for the management and treatment of COVID-19. The immune responses to viral infection followed by cytokine storm and acute respiratory distress syndrome are serious issues that may cause death in patients with severe COVID-19. Therefore, developing a novel therapeutic strategy for the management of COVID-19 is urgently needed to control the virus spread and to improve the patient survival rate and clinical outcomes. In this mini-review, we summarize the symptoms, pathogenesis, and therapeutic approaches currently being used to manage the spread of SARS-CoV-2.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Síndrome de Dificultad Respiratoria , Antivirales/uso terapéutico , COVID-19/diagnóstico , Humanos , SARS-CoV-2RESUMEN
BACKGROUND: Pre-operative chemoradiotherapy (NACRT) of patients with proximal gastric and esophagogastric junction (EGJ) adenocarcinoma may result in increased local control and improved patients' survival rate. This study aimed to investigate the effect of NACRT on resectability of tumor in patients with proximal gastric and EGJ adenocarcinoma. METHODS: In this single-arm clinical trial, patients with locally advanced proximal gastric and EGJ adenocarcinoma were included. Two courses of paclitaxel/carboplatin chemotherapy alone followed by NACRT with a similar treatment regimen and a total radiation dose of 45-50.4/1.8-2 Grays were prescribed. After surgery, patients were evaluated for resection rate, pathologic response rate, and post-surgical complications. RESULTS: A total of 61 patients with a mean age of 65.9 years participated. Grades 1 and 2 were the most prevalent side effects, with grade 3 being the worst grade and exhibiting as leukopenia (4.9%) and thrombocytopenia (1.6%). 25 (41%) patients underwent surgery after NACRT. Post-surgery complication was reported in 20% of cases (including 8% mortality and 12% morbidity). R0 and R2 resection was observed in 88% and 12% of cases, respectively. Complete pathologic-response was achieved in 24% of patients. CONCLUSION: Paclitaxel/carboplatin based neoadjuvant chemotherapy was associated with potential resectability and appropriate pathologic response in patients with locally advanced proximal gastric and EGJ adenocarcinoma. However, by reducing patient tolerance to complete courses of weekly chemotherapy, induction chemotherapy lowered the effectiveness of concurrent chemotherapy and radiotherapy (as a sensitizing agent). Hence, induction chemotherapy proved to be more unbeneficial causing delayed treatment and reducing concurrent chemoradiotherapy tolerance.
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BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic imposes serious problems to health systems around the world and its rapid expansion makes it difficult to serve patients with certain health conditions such as cancer patients which might be at high risk for mortality if they are infected by the severe acute respiratory syndrome coronavirus 2. AIM: To compare the outcomes of cancer patients admitted due to COVID-19 and compare them with data of COVID-19 infected patients without a history of cancer. METHODS: In this case-controlled study, 93 healthy people and 92 patients with malignancy admitted for COVID-19 were enrolled. The clinical features and laboratory indicators were assessed at the presentation and both groups were followed-up for treatment options and outcomes prospectively and compared at the level of P ≤ .05. RESULTS: COVID-19 related mortality rate in malignant patients was significantly higher than patients without malignancy (41.3% vs 17.2%, P = .0001). The risk of death increased significantly in patients with malignancy (OR = 8.4, P = .007) and mechanical ventilation (OR = 3.3, P = .034) independent of other variables. Fever (64.5% vs 43.5%, P = .004), chill (35.5% vs 14.1%, P = .001), malaise (49.5% and 30.4%, P = .008), dry cough (51.6% vs 26.1%, P = .0001), and vomiting (17.2% vs 5.4%, P = .012) were reported significantly lower in cancer patients. CONCLUSION: The results suggest that cancer patients who were infected by COVID-19 may present with atypical symptoms are at higher risk of mortality independent of the demographic data, comorbidities, and treatments.
Asunto(s)
COVID-19/mortalidad , Neoplasias/epidemiología , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/terapia , Estudios de Casos y Controles , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Irán , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/inmunología , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/patogenicidad , Índice de Severidad de la EnfermedadRESUMEN
Prostate cancer (P.C.) is one of the most frequent diagnosed cancers among men and the first leading cause of death with an annual incidence of 1.4 million worldwide. Prostate-specific antigen is being used for screening/diagnosis of prostate disease, although it is associated with several limitations. Thus, identification of novel biomarkers is warranted for diagnosis of patients at earlier stages. MicroRNAs (miRNAs) are recently being emerged as potential biomarkers. It has been shown that these small molecules can be circulated in body fluids and prognosticate the risk of developing P.C. Several miRNAs, including MiR-20a, MiR-21, miR-375, miR-378, and miR-141, have been proposed to be expressed in prostate cancer. This review summarizes the current knowledge about possible molecular mechanisms and potential application of tissue specific and circulating microRNAs as diagnosis, prognosis, and therapeutic targets in prostate cancer.