Journal of Carcinogenesis最新文献

Introduction: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) have been reported in previous studies to assess the prognosis of gall bladder cancer (GBC) individually and in combination. However, the evidence of utility of preoperative CA 19-9, CEA and carbohydrate antigen 125 (CA 125) in determining the resectability and prognosis of GBC is still lacking. In the present study we correlated the serum levels of tumor markers CA 19-9, CEA and CA 125 individually and combined to determine the resectability and prognosis of the GBC.

Materials and methods: Seventy one diagnosed patients of GBC between January 2018 and September 2019 were included in the present study. Serum CA 19-9, CEA and CA 125 were determined by chemiluminescence. Receiver operating characteristic (ROC) curve was used to evaluate the role of tumor markers in determining the resectability of GBC. The Kaplan Meier survival curves were made and log rank analysis was performed to assess the prognostic role of tumor markers in terms of overall median survival.

Results: All the three tumor markers CA19-9, CEA and CA 125 showed high discriminatory power in determining the resectability with respective area under curve of 0.76, 0.68 and 0.78 as determined by ROC. Median survival in patients with high serum CA 19-9, CA 125 was significantly lower than patients with normal serum CA 19-9, CA 125 whereas no significant difference was observed in case of CEA.

Conclusion: The present study suggested that CA 19-9, CEA and CA 125 can predict resectability in GBC and raised levels of CA 19-9 and CA 125 can predict poor prognosis in patients with elevated levels.

Introduction: Targeted therapy using specific inhibitors against tyrosine kinases (TKs) is a paradigm in non-small-cell lung cancer management. However, the success of TK inhibitor (TKI) therapy depends on certain activating or acquired mutations, which render sensitivity or resistance to TKIs in the patients. The acquisition of epidermal growth factor receptor (EGFR) T790M point mutation is the most common mechanism of resistance to TKI in non-small cell lung cancer. A number of molecular strategies are now available for molecular testing of non-small cell lung cancers. However, almost all of them are cost-intensive and laborious and require high-end advanced equipment. Thus, assays that are rapid, simple, and cost-effective, yet sensitive, are most ideal in clinical settings for screening such therapeutically relevant mutations.

Materials and methods: Allele-specific loop-mediated isothermal amplification assay (AS-LAMP), which is a variant of the original LAMP assay, is a promising diagnostic technique for screening single-nucleotide polymorphisms. Using commercially available plasmid constructs as template DNA, AS-LAMP assay for EGFR T790M mutation was optimized with six different sets of reaction mixture containing varying concentrations of buffer and primers. The results of AS-LAMP assay were further validated by ultrasensitive droplet digital polymerase chain reaction.

Results: Only one of the six sets of reaction mixture could accurately distinguish between wild type and mutated DNA, indicating that the primers and buffer are the two most critical components that determine the accuracy of AS-LAMP. The optimized AS-LAMP assay was further used to screen germ line and somatic T790M mutations in non-small cell lung cancer using blood and tissue samples collected from patients.

Conclusion: Development of an accurate and rapid diagnostic assay that can detect resistant mutations without the need for sequencing is highly useful for clinicians in deciding on the eligibility of patients for TKI therapy. Considering its several inherent advantages, AS-LAMP assay could become an effective molecular tool for screening baseline or acquired EGFR T790M mutations in non-small cell lung cancer patients.

Context: Oral cancer metastasis is the leading cause of death globally. The decision-making on the mode of surgical treatment in clinically negative lymph nodes is challenging.

Aim: The aim of this study was to develop a predictive model using clinical and histopathologic parameters that may help in the assessment of the metastatic risk of oral squamous cell carcinoma (OSCC).

Settings and design: Clinical data of histopathologically confirmed primary OSCC from 2014 to 2017 were retrieved from the archives. Histopathological parameters for metastasis that were considered for evaluation in the study were tumor buds, cytoplasmic pseudofragments, tumor grade, depth of invasion, invasive tumor front (ITF) pattern, and lymphovascular invasion (LVI).

Methods: Hematoxylin and eosin and pan-cytokeratin immunostained sections of metastatic and nonmetastatic OSCC were assessed for histopathological features and correlated with clinical parameters.

Statistical analysis used: SPSS software (Statistical Package for Social Sciences for Windows, Version 22.0 (2013) (IBM Corp., Armonk, NY, USA)) was used for the statistical analysis. Pearson's Chi-square test was done to assess the grades of histopathological and clinical parameters between the study groups. Univariate analysis was performed to develop a clinicopathologic predictive model.

Results: The clinicopathologic model signifies that OSCC with clinical Stage IV, high grades of tumor buds and cytoplasmic pseudofragments, Type V ITF pattern, positive LVI, deeply invasive tumors, and poorly differentiated grades of OSCC have a high risk of developing nodal metastasis. These parameters may be used as early predictors for metastasis of OSCC both in incisional and excisional biopsy specimens.

Conclusions: The proposed predictive model is simple, cost-effective, and user-friendly for the early assessment of nodal metastatic risk in clinically negative lymph nodes.

Background: Cancer invasion is a critical step for tumor growth and its progression. The focus on epithelial changes is shifting to increasing recognition that the microenvironment makes significant contributions to tumor progression. Stromal myofibroblasts play an important role in tumor invasion and metastasis due to its ability to modify the extracellular matrix. Based on this literary evidence, we carried out an immunohistochemical study to observe the expression of myofibroblasts in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC).

Aim: The aim of the study was to evaluate, compare, and correlate the presence of myofibroblasts in normal oral mucosa, oral epithelial dysplasia, and OSCC and to observe different patterns of myofibroblast arrangement using alpha-smooth muscle actin (α-SMA) as a marker, Thus assisting in early diagnosis, treatment, and prognosis of oral carcinomas.

Materials and methods: Thirty-six cases including 12 cases of OSCC, 12 cases of epithelial dysplasia, and 12 cases of normal oral mucosa were stained with hematoxylin and eosin to confirm the diagnosis and immunohistochemically using α-SMA antibody. The slides were evaluated for positivity and intensity of staining.

Statistical analysis: The result was subjected to statistical analysis using Fisher's exact test.

Results: α-SMA expression in the stroma of squamous cell carcinoma was greater than its expression in epithelial dysplasia and normal oral mucosa.

With the introduction of anthracycline-based regimens, 5-year survival rates have significantly improved in patients with early-stage breast cancer. With the addition of trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. Subsequently, lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific tyrosine kinase inhibitor, received Food and Drug Administration (FDA) approval in combination with capecitabine for patients with advanced HER2+ breast cancer. Then, pertuzumab in 2012 and ado-trastuzumab emtansine in 2013 were approved in the US and elsewhere based on evidence showing an improvement in survival outcomes in patients with mostly trastuzumab naïve or trastuzumab-exposed metastatic disease. The FDA also approved 1 year of extended adjuvant neratinib after chemotherapy and a year of trastuzumab for HER2-positive breast cancer on the basis of the ExteNET trial. The clinical benefit demonstrated by those drugs in advanced disease has triggered several adjuvant and neoadjuvant trials testing them in combination with chemotherapy, but also without conventional chemotherapy, using single or dual HER2-targeting drugs. In this article, we review the current data on the therapeutic management of HER2-positive early-stage breast cancer in the adjuvant and neoadjuvant setting. We also review the data the efficacy and safety of anthracycline-based and nonanthracycline-based adjuvant chemotherapy regimens combined with trastuzumab, and optimum chemotherapy regimens in small HER2-positive tumors.

The idea of using the immune system to fight cancer is over 100 years old. A new molecular approach led to a better understanding of the immune system. Checkpoint regulation, understanding the roles of Tregs, Th1, and Th2, development of Chimeric antigen receptor (CAR)-T cells, as well as regulation of dendritic cells and macrophages, are just a few examples of our understating that has also led to the discovery of immune checkpoint inhibitors (ICIs) and modulators. This led the Nobel Prize committee in 2018, to award Dr. James P. Allison the Nobel Prize in medicine for the discovery of Cytotoxic T-lymphocyte-associated antigen-4, and Dr. Tasuku Honjo for the discovery of programmed cell death-1 (PD-1)/PD-1-ligand (PDL-1). Several ICIs are already approved by the regulatory authorities, and many more are currently used in studies of several solid tumors and hematologic malignancies. Positive studies have led to the US Food and Drug Administration (FDA) and European Medicines Agency approval of a number of these compounds, but none to date are approved in breast cancer (BC). Moreover, PD-1/PDL-1, MSI high (and dMMR), and tumor mutational burden are the currently "best" predictive markers for benefit from immunotherapy. BCs have some of these markers positive only in subsets but less frequently expressed than most other solid tumors, for example, malignant melanoma or non-small cell lung cancer. To improve the potential efficacy of ICI in BC, the addition of chemotherapy was one of the strategies. Many early and large clinical trials in all phases are underway in BC. We will discuss the role of immune system in BC editing, and the potential impact of immunotherapy in BC outcomes.

Introduction: Nasopharyngeal cancer is not a common disease in most parts of the world. In India also, nasopharyngeal carcinoma (NPC) is not a common cancer, except for the Northeastern region of the country. Expression of matrix metalloproteinase 9 (MMP9) in the tumor cells is related to tumor invasion and metastasis. The aim of the present study is to analyze the expression of MMP9 in NPC and evaluate its prognostic implications.

Materials and methods: A total of 32 histologically confirmed tissue samples of NPC were examined by immunohistochemical staining to assess the expression of MMP9. Clinicopathological parameters and levels of MMP9 expression in the tumor tissue were analyzed using Chi-square test. Survival analysis was done using the Kaplan-Meier method and was compared using log-rank test. P <0.05 was considered statistically significant.

Results: Of the 32 tissue samples of NPC, 23 (71.9%) were male and 9 (28.1%) were female. 7 (21.9%) patients presented in T1 Stage, 8 (25.0%) in T2, 12 (37.5%) in T3, and 5 (15.6%) in T4 Stages, respectively. 29 (90.6%) patients presented with lymph node metastasis. MMP9 expression level was significantly correlated with patient's age (P = 0.033), tumor histology (P = 0.017), tumor stage (P = 0.021), and lymph node metastasis (P = 0.011). The 5-year overall survival is higher for low-level expression as compared to high-level expression of MMP9 (P = 0.046).

Conclusion: MMP9 is an important prognostic factor for NPC. High expression of MMP9 is associated with cervical lymph nodes metastasis and poor survival outcome.

Several genes and pathways associated with oral squamous cell carcinoma (OSCC) are significant in terms of early detection and prognosis. The objective of this literature review is to evaluate the current research on molecular pathways and genes involved in oral cancer. Articles on the genes involved in oral cancer pathways were evaluated to identify potential biomarkers that can predict survival. In total, 36 articles were retrieved from internet databases, including EBSCO Host, Google Scholar, PubMed, and Science Direct, using the keywords "biomarker of oral cancer," "pathways of oral cancer," "genes involved in oral cancer," and "oral cancer pathways." A total of 36 studies related to OSCC were chosen. Most of the studies used cell lines, while others used archival tissues, few studies followed up the cases. Three major interlinked pathways found were the nuclear factor kappa B (NF-kB), PI3K-AKT, and Wnt pathways. The commonly mutated genes were cyclin D1 (CCND1), Rb, p53, FLJ10540, and TC21. The NF-kB, PI3K-AKT, and Wnt pathways are most frequently involved in the molecular pathogenesis of oral cancer. However, the CCND1, Rb, p53, FLJ10540, and TC21 genes were found to be more accurate in determining patients' overall survival. Polymerase chain reaction, immunohistochemistry, and immunoblotting were the commonly used detection methods.