Journal of Carcinogenesis最新文献

Introduction: Gallbladder cancer is an aggressive cancer with short median survival from the time of diagnosis. Improved understanding of the pathological molecular mechanisms of gallbladder carcinogenesis is important to refine the diagnosis, prognosis, and also to develop novel targeted therapies for patients with advanced Gallbladder cancer (GBC) malignancy. Ki-67 is a marker of cell proliferation and its detection by immunohistochemistry is considered to be an effective method for the detection of prognosis in several tumors. In the present study, we have analyzed expression of immunohistochemical marker Ki-67 in gallbladder carcinoma and its correlation with clinicopathological and radiological parameters.

Materials and methods: This prospective observational study was conducted from December 2017 to July 2020. The patients of newly diagnosed gallbladder cancer were enrolled as per the inclusion and exclusion criteria defined in the study protocol. Contrast-enhanced computer tomography of the chest and abdomen and serum tumor markers such as carbohydrate antigen (CA)-19.9, carcinoembryonic antigen, and CA 125 were done. Immunohistochemical expression of Ki-67 was evaluated on biopsy tissue from the gallbladder mass.

Results: Fifty newly diagnosed patients of carcinoma gallbladder were included in the present study. The correlation was studied between clinicodemographic parameters and Ki-67, but no association was found with age, gender, and symptoms. There was a weak positive correlation between Ki-67 and direct bilirubin, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase (P = 0.094; 0.126; 0.542; and 0.328, respectively). There was a weak positive correlation between body mass index (Kg/m²) and Ki-67, but this correlation was not statistically significant (P = 0.304).

Conclusions: Ki-67 is a marker of proliferation and it correlated with histological differentiation, jaundice and liver function tests, presence of stones, and location of metastases but did not correlate with stage and extent of disease.

Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The in silico analysis highlights the potential drugs that may target the genes regulating collagen crosslinking.

Gliomas are more common in males than in females. Emerging evidence from several studies in vitro and in vivo have shown the role of estrogens and androgens in glial tumorigenesis. In recent times, studies have also shed light on the actions of estrogen receptors, alpha and beta, and androgen receptor. Here, we provide a comprehensive overview of the research hitherto on estrogens and androgens along with an emphasis on their receptors in glioma pathophysiology. Studies with conflicting results are discussed and future possibilities are put forward. A collective understanding of the studies on these steroid hormones in glioma may serve to create an amalgamated therapeutic approach; and thereby, augment the efforts in tackling this deadly disease.

Introduction: Metastatic progression in triple-negative breast cancer (TNBC) patients occurs primarily because of nuclear reprogramming that includes chromatin remodeling and epigenetic modifications. The existing and most successful chemotherapies available for metastatic TNBC target nuclear proteins or damage DNA. The objectives here are to investigate an undescribed role for the molecular biology of nuclear angiopoietin-like protein 4 (ANGPTL4) and to characterize the effect of ectopic overexpression of ANGPTL4 in the metastatic biology of TNBC.

Materials and methods: Lentiviral-mediated transduction was used to overexpress ANGPTL4 in the TNBC cell line MD Anderson-metastatic breast cancer 231. The overexpression of ANGPTL4 was confirmed by western blot and ELISA. Subcellular fractionation, western blot, and immunofluorescence microscopy were used to characterize the intracellular localization of ANGPTL4. Mammosphere culture and the anchorage-independent growth assay analyzed the metastatic potential of the cell line. Xenograft assays assessed the effect of ANGPTL4 overexpression on TNBC metastases in vivo.

Results: The ANGPTL4 overexpressing cell line formed larger mammospheres and anchorage-independent colonies in vitro and developed larger primary tumors, more liver metastases, and brain metastatic outgrowth in vivo in comparison to a cell line that expressed endogenous levels of ANGPTL4. ANGPTL4, aurora kinase A (AURKA), a mitotic kinase, and Tat-interacting protein p60 kDa (Tip60), a lysine acetyltransferase, associated with chromatin in the ANGPTL4 overexpressing cells but not in cells that expressed endogenous levels of ANGPTL4.

Conclusions: The ANGPTL4 overexpressing cell line showed in vitro and in vivo activities that suggest that nuclear ANGPTL4, AURKA, and Tip60 may cooperatively modulate TNBC metastases within chromatin-remodeling complexes or DNA-associated machinery.

Introduction: Gall bladder cancer (GBC) accounts for 80%-95% of biliary tract malignancies in the world. There is however striking variability in the global incidence of gallbladder cancer, reaching epidemic levels for some regions and ethnicities. The aim of this study was to evaluate the demographic and clinicopathological profile of the gallbladder cancer patients.

Materials and methods: All patients of carcinoma gall bladder presenting to department of surgery in hepatopancreaticobiliary unit from July 2017 to November 2020 were included in this study. A proforma containing all the relevant details including history, examination, blood, radiology, and pathological investigations was filled.

Results: A total of 326 patients of GBC were analyzed. The majority (75%) were found to be females with a mean age of 55 years. Pain abdomen was the most common presenting symptom in 81% of patients. The most common stage of presentation was stage IV and only 6 were in stage I. Two hundred and thirty three (71.4%) patients had metastatic disease at presentation. Liver infiltration at the time of diagnosis was present in 89% of patients. The most common site of metastasis was found in the liver (23.3%). GBC was more common in patients with A blood group. Baseline serum albumin levels were found to be significantly associated with the staging of GBC.

Conclusions: Due to the non specific symptoms patients of GBC present at very advanced stages, high index of suspicion and health education seems to play an important role in early detection and improvement of survival.

Introduction: Gallbladder cancer exhibits striking variability in the global rates, reaching epidemic levels for some regions and ethnicities. The basis of its variability resides in differences in environmental exposure and intrinsic genetic predisposition to carcinogenesis. There is little information present regarding genetic and molecular alterations in gall bladder cancer (GBC). We, therefore, have evaluated the molecular marker expression in GBC and studied their correlation with clinicopathological staging.

Materials and methods: This prospective observational study was conducted on newly diagnosed GBC patients from July 2017 to July 2020. After complete staging workup, the GBC biopsy samples paraffin block was tested for molecular markers estrogen receptor (ER), progesterone receptor (PR), p53, p16, Human epidermal growth factor receptor 2 (HER 2-neu), Survivin, Enhancer of zeste homolog-2 (EZH2), and Cyclooxygenase-2 (COX-2) expression by immunohistochemistry.

Results: Fifty newly diagnosed patients of carcinoma gall bladder were included in the present study. Age was ranged from 29 - 69 years (mean 53.42). p53 was the most common positive marker in 74% of patients, survivin in 58%, COX-2 in 44%, and p16 in 42% whereas Her 2 neu and EZH-2 were positive in 16% of patients each. None of the patients of GBC were ER or PR positive. There was a significant difference between the various groups in terms of the distribution of histological grade and Her 2 neu (χ² = 9.886, P = 0.014) but not with other markers. Furthermore, there was a significant difference in terms of distribution of p16 and p53 with stage (χ² = 7.017, P = 0.037 and χ² = 5.861, P = 0.033) respectively.

Conclusions: The present study shows the expression of molecular markers Her2 neu, p53, p16, survivin, COX-2, and EZH-2 in GBC. Now the time has come, and it is also the need of the day to establish early biomarkers of this highly lethal malignancy. It can be used in future for the detection of disease in the early phase and targeted therapy.

Context: Chemoresistance is a major issue in patients with locally advanced oral squamous cell carcinoma (OSCC). In this study, we evaluated the effectiveness of melatonin in conjunction with neoadjuvant chemotherapy (NC) on hypoxia-inducible factor-1α (HIF-1α) expression and clinical response in locally advanced OSCC patients.

Aims: To study the effects of melatonin on HIF-1α expression and its effect on the clinical response of patients with locally advanced OSCC.

Settings and design: A randomized controlled trial was conducted, wherein patients were recruited from several hospitals in Jakarta, Indonesia. Patients were randomized into two groups using computerized block randomization.

Subjects and methods: Both groups were given NC, with treatment group receiving melatonin. Outcomes measured in this study were HIF-1α expression from tissue samples and clinical response based on the RECIST 1.1 criteria. Twenty-five patients completed the study protocol and were included in the data analysis.

Statistical analysis used: Shapiro-Wilk test was used to test the data normality. For data with normal distribution, we conducted an independent t-test to compare between the two groups. Data with abnormal distribution were analyzed using Mann-Whitney U-test. The mean difference between the two groups was analyzed using Shapiro-Wilk normality test.

Results: Our study showed a significant decrease in HIF-1α expression in the melatonin group compared to the placebo group (P < 0.05, relative risk 3.08). However, the degree of reduction of HIF-1α expression in the melatonin group did not differ significantly (P = 0.301).

Conclusions: Our study showed that melatonin administered at 20 mg/day could reduce the expression of HIF-1α and residual tumor percentage, but did not affect the clinical response in OSCC patients.

Preclinical studies and clinical trials have emphasized the decisive role of lipid metabolism in tumor proliferation and metastasis. This systematic review aimed to explore the existing literature to evaluate the role and significance of the genes and pathways most commonly involved in the regulation of lipid metabolism in cancer. The literature search was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analyses. Approximately 2396 research articles were initially selected, of which 215 were identified as potentially relevant for abstract review. Upon further scrutiny, 62 of the 215 studies were reviews, seminars, or presentations, and 44 were original study articles and were thus included in the systematic review. The predominant gene involved in lipid metabolism in cancer was stearoyl-coenzyme A desaturase 1 (SCD1), followed by fatty acid synthase (FASN). The pathway most commonly involved in lipid metabolism in cancer was the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, followed by the mitogen activated protein kinase (MAPK) pathway. SCD1 and FASN play significant roles in the initiation and progression of cancer and represent attractive targets for potentially effective anti-cancer treatment strategies. The regulation of cancer metabolism by the Akt kinases will be an interesting topic of future study.

Context and aim: The inaccuracies in clinical examination have been well documented, while advanced imaging modalities, including computed tomography and magnetic resonance imaging (MRI), have been shown to have superior diagnostic accuracy in detecting occult and nodal metastasis. The aim of the present study was to identify as well as evaluate the inaccuracies in clinical examination and of clinical diagnostic criteria in known cases of oral squamous cell carcinomas (OSCCs) with the help of MRI.

Materials and methods: A total of 24 patients attending as outpatients were included in the study, while clinically diagnosed and histopathologically proven cases of OSCC were examined clinically and then subjected to advanced imaging with the help of MRI.

Statistical analysis used: Statistical analysis was done using Statistical Package for the Social Sciences (SPSS) version 17.0 (SPSS Inc., Chicago, IL, USA), while paired t-test was performed for evaluating the size of tumor and lymph node recorded on clinical and imaging findings. A P < 0.05 was considered statistically significant.

Results: Detection of tumor size and lymph node metastasis was found to be higher in case of MRI than when accomplished by clinical staging alone, while paired t-test values for difference in results were found to be statistically significant (P < 0.05).

Conclusions: The present study showed that clinical diagnostic criteria alone were not sufficient and reliable for detecting metastatic lymphadenopathy, highlighting the significance of advanced imaging modalities such as MRI for an efficient preoperative diagnostic workup, as well a tool for planning treatment in patients with OSCCs.

Upregulation or aberrant expression of genes such as special AT-rich sequence-binding protein 2 (SATB2) is necessary for normal cell differentiation and tissue development and is often associated with carcinogenesis and metastatic progression. SATB2 is a critical transcription factor for biological development of various specialized cell lineages, such as osteoblasts and neurons. The dysregulation of SATB2 expression has recently been associated with various types of cancer, while the mechanisms and pathways by which it mediates tumorigenesis are not well elucidated. Runt-related transcription factor 2 (RUNX2) is a master regulator for osteogenesis, and it shares common pathways with SATB2 to regulate bone development. Interestingly, these two transcription factors co-occur in several epithelial and mesenchymal cancers and are linked by multiple cancer-related proteins and microRNAs. This review examines the interactions between RUNX2 and SATB2 in a network necessary for normal bone development and the circumstances in which the expression of RUNX2 and SATB2 in the wrong place and time leads to carcinogenesis.