Biological Behavior Of Tumor Research Articles

Loss of NPM2 expression is a potential immunohistochemical marker for malignant peritoneal mesothelioma: a single-center study of 92 cases

BackgroundMalignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. In-depth pathological analysis is essential to assess tumor biological behaviors and explore potential therapeutic targets of MPM. Nucleoplasmin 2 (NPM2) is a molecular chaperone that binds histones and may play a key role in the development and progression of tumors. This study aimed to analyze the correlation between the expression level of NPM2 and the main clinicopathological characteristics and prognosis of MPM.MethodsNinety-two postoperative specimens from MPM patients following cytoreductive surgery were collected. Postoperative specimens were stained with immunohistochemistry. The expression level of NPM2 was quantitatively analyzed by QuPath-0.3.2 software. Univariate and multivariate analyses were conducted to investigate the correlation between NPM2 expression and other conventional clinicopathological characteristics.ResultsAmong the 92 MPM patients, there were 47 males (48.9%) and 45 females (51.1%), with a median age of 56 (range: 24–73). There were 70 (76.0%) cases with loss of NPM2 protein expression, 11 (12.0%) cases with low expression, and 11 (12.0%) cases with high expression. Univariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was negatively correlated with the following three clinicopathological factors: completeness of cytoreduction (CC) score, vascular tumor emboli, and serious adverse events (SAEs) (all P < 0.05). Multivariate analysis showed that NPM2 protein expression level (negative vs. low expression vs. high expression) was independently negatively correlated with the following two clinicopathological factors: CC score [odds ratio (OR) = 0.317, 95% CI: 0.317–0.959, P = 0.042] and vascular tumor emboli (OR = 0.092, 95% CI = 0.011–0.770, P = 0.028). Survival analysis showed that loss of NPM2 protein expression (negative vs. positive) was associated with poor prognosis of MPM.ConclusionsLoss of NPM2 expression is a potential immunohistochemical marker for MPM.

PET-Uptake in Liver Metastases as Method to Predict Tumor Biological Behavior in Patients Transplanted for Colorectal Liver Metastases Developing Lung Recurrence.

Simple SummaryMany colorectal cancer patients with liver-only metastases receiving liver transplantation develop pulmonary metastases after liver transplantation. Pre-transplant PET liver uptake determines overall survival in patients treated by post-transplant resection of pulmonary metastases.The objective of the study was to determine the impact of PET uptake on liver metastases on overall survival (OS) after resection of pulmonary metastases in patients who had received liver transplantation (LT) due to unresectable colorectal liver-only metastases. Resection of pulmonary colorectal metastases is controversial. Some hospitals offer this treatment to selected patients, whereas other hospitals do not perform the procedure in colorectal cancer patients who develop pulmonary metastases. All patients included in the LT studies who developed pulmonary metastases as first site of relapse, and had resection of these as first treatment, were included in this report. Metabolic tumor volume (MTV) in liver was derived from the pre-transplant PET examinations. OS from time of resection was calculated by the Kaplan–Meier method. Patients with low MTV (<70 cm3) had significantly longer OS from time of resection of pulmonary metastases compared to patients with high MTV (>70 cm3). Patients with low MTV in the liver had 10-year OS from time of pulmonary resections of 86%. Liver MTV values from pre-transplant PET examinations may predict long OS in colorectal cancer patients with a resection of pulmonary metastases developing after LT. Thus, in selected colorectal cancer patients developing pulmonary metastases resection of these metastases should be the treatment of choice.

A novel ferroptosis‑related gene signature for overall survival prediction and immune infiltration in patients with breast cancer.

Breast cancer is the most prevalent type of cancer among women worldwide. The heterogeneous nature of breast cancer poses a serious challenge for prognostic prediction and individualized therapies. Recently, ferroptosis, an iron-dependent form of programmed cell death, has been reported to serve a significant role in the regulation of the biological behavior of tumors. Several studies have revealed the prognostic significance of the ferroptosis-related gene (FRG) model; however, additional efforts are required to elucidate the details. Moreover, genes that modulate ferroptosis may be promising candidate bioindicators in cancer therapy. The present study systematically assessed the expression profiles of FRGs to reveal the relationship between FRGs and the prognostic features of patients with breast cancer based on data obtained from the Gene Expression Omnibus and Molecular Taxonomy of Breast Cancer International Consortium. Using a non-negative matrix factorization clustering method, patients with breast cancer were classified into two sub-groups (cluster 1 and cluster 2) based on the expression of FRGs. Furthermore, Cox regression, and least absolute shrinkage and selection operator methods were used to construct a risk score formula comprised of nine genes, which stratified patients with breast cancer into two risk groups. Patients belonging to the high-risk group exhibited significantly shorter overall survival (OS) time compared with patients in the low-risk group. The prognostic value of this signature was further verified in the training and validation cohorts. The results for univariate and multivariate Cox regression analyses indicated that risk score acted as an independent predictor for OS. Subsequently, a nomogram was constructed. Receiver operating characteristic analysis further confirmed that the resulting nomogram exhibited powerful discriminatory ability. Functional analysis revealed that the immune environment differed notably between the two groups and indicated an association between ferroptosis and breast cancer proliferation, migration and drug resistance. Taken together, the present study demonstrated that FRGs were significantly associated with breast cancer progression, and thus could be used as novel biomarkers for prognostic prediction and individualized treatment of patients with breast cancer.

Immune checkpoint inhibitors as mediators for immunosuppression by cancer-associated fibroblasts: A comprehensive review

The tumor microenvironment (TME) is a significant contributor to cancer progression containing complex connections between cellular and chemical components and provides a suitable substrate for tumor growth and development. Growing evidence shows targeting tumor cells while ignoring the surrounding TME is not effective enough to overcome the cancer disease. Fibroblasts are essential sentinels of the stroma that due to certain conditions in TME, such as oxidative stress and local hypoxia, become activated, and play the prominent role in the physical support of tumor cells and the enhancement of tumorigenesis. Activated fibroblasts in TME, defined as cancer-associated fibroblasts (CAFs), play a crucial role in regulating the biological behavior of tumors, such as tumor metastasis and drug resistance. CAFs are highly heterogeneous populations that have different origins and, in addition to their role in supporting stromal cells, have multiple immunosuppressive functions via a membrane and secretory patterns. The secretion of different cytokines/chemokines, interactions that mediate the recruitment of regulatory immune cells and the reprogramming of an immunosuppressive function in immature myeloid cells are just a few examples of how CAFs contribute to the immune escape of tumors through various direct and indirect mechanisms on specific immune cell populations. Moreover, CAFs directly abolish the role of cytotoxic lymphocytes. The activation and overexpression of inhibitory immune checkpoints (iICPs) or their ligands in TME compartments are one of the main regulatory mechanisms that inactivate tumor-infiltrating lymphocytes in cancer lesions. CAFs are also essential players in the induction or expression of iICPs and the suppression of immune response in TME. Based on available studies, CAF subsets could modulate immune cell function in TME through iICPs in two ways; direct expression of iICPs by activated CAFs and indirect induction by production soluble and then upregulation of iICPs in TME. With a focus on CAFs’ direct and indirect roles in the induction of iICPs in TME as well as their use in immunotherapy and diagnostics, we present the evolving understanding of the immunosuppressive mechanism of CAFs in TME in this review. Understanding the complete picture of CAFs will help develop new strategies to improve precision cancer therapy.

Proliferative activity of cancer stem cells in the prognosis of hematogenous metastasis of colon adenocarcinoma

The search for prognostic markers to determine the risk of dissemination and metastasis of colon adenocarcinoma is one of the most difficult and actual problems of modern oncomorphology.The aim of this work was to determine the possibility of using indicators of the proliferative activity of cancer stem cells in the prediction of hematogenous metastasis of colon adenocarcinoma. In this work the surgical material from 32 radically operated patients of different ages suffering from a localized colon adenocarcinoma was explored, and relapse-free survival was assessed. A comparative analysis of various components of the tumor differon, including proliferating stem cells and their relationship with the formation of relapse was carried out.An index of stem cell proliferation was proposed to assess the influence of stem cell activity on the biological behavior of tumor. The best rates of relapse-free survival were found in the group of patients with low value of the index of stem cell proliferation compared with patients which index took on high values, which is more typical for elderly and old patients. With a similar comparison of other indicators of tumor differon, including the percentage of ALDH1 and Ki-67-positive cells, as well as cells with the ALDH1+Ki-67+immenophenotype relative to the total tumor differon, no significant relationship with relapse-free survival was found. These results may indicate a high role of ALDH1+ cell proliferation in tumor dissemination, especially in elderly and senile patients, and a lesser influence of both the proliferative activity of Ki-67 and the general population of stem cells on the formation of distant metastases.

Comparative Study of Immune Cells Infiltration in Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma of the Head and Neck

Background: The role of tumor-associated tissue eosinophils and mast cells in the biological behavior of tumors remains unclear. Objectives: This study was performed to compare the eosinophil and mast cell counts in the cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) of the head and neck and to evaluate their relationship with clinicopathologic factors. Methods: The current descriptive-analytical study was conducted on the histopathologic slides of 46 BCC and 30 cSCC samples prepared by using Sirius red and Toluidine blue staining techniques for eosinophil and mast cell counts, respectively. The data were analyzed, using Pearson’s correlation, t test, and ANOVA test. Results: The BCC and cSCC samples had mean eosinophil counts of 35.43 ± 35 and 331.27 ± 321.68 eosinophil/10 HPF, respectively, and this difference was statistically significant (P = 0.001). The levels of the mast cell infiltration were obtained as 55.33 ± 39.90 and 63.67 ± 40.86 in BCC and cSCC, respectively. However, this variable was not significantly different between the two groups of BCC and cSCC samples (P = 0.380). In addition, the mean eosinophil and mast cell counts were higher in cSCC grade III than in other grades; however, this difference was statistically significant only for the mast cells. Furthermore, the mean eosinophil/mast cell count in cSCC and BCC showed no significant relationship with age and gender. Conclusions: Considering the greater presence of eosinophils in cSCC than in BCC, eosinophils may be concluded to be among the factors responsible for more biologically and clinically invasive behaviors of cSCC, compared to those of BCC.

The expression of SOX10 and its value for predicting tumor biological behaviors in patients suffering gastric adenocarcinoma, cross sectional study

BackgroundSpecial attention has been recently paid to the expression of the SOX10 marker, which is actually responsible for coordinating the signaling process of the Wnt/B-catenin evolutionary pathway and therefore responsible for cell proliferation and differentiation in tumor cells. We aimed to study the expression of this marker in different types of gastric adenocarcinomas and to find its relationship with histopathologic features of the tumor. MethodsThis cross-sectional study was performed on patients with gastric adenocarcinoma (diffuse or intestinal type) whose malignancy could be confirmed by tissue. Subjects were classified according to CAP criteria based on pathology results. Patients underwent immunohistochemical staining to evaluate SOX10 expression. Tumor behavior was determined based on histological studies. ResultsSOX10 positivity was reported in 22.5% of all tissue samples assessed. The assessment of relationship between SOX10 expression and baseline and tumor characteristics showed no significant association of SOX10 expression and patients’ gender, age, tumor location, tumor size, its type and also lymphovascular and perineural invasions. ConclusionThe expression of the SOX10 marker is expected only in 22.5% of patients diagnosed with gastric cancer. In our society, the expression of this marker has nothing to do with the biological and aggressive behaviors of this tumor.

Recurrent Hepatocellular Carcinoma: Patterns, Detection, Staging and Treatment.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with the incidence of recurrence being as high as 88% even among patients who have undergone curative-intent treatment. Despite improvements in overall survival, recurrence remains a challenge necessitating accurate reappraisal of patient and disease status. To that end, accurate staging of recurrent HCC is a necessity to provide better care for these patients. Risk factors for poor survival after HCC recurrence have been identified and include characteristics of the primary disease, such as tumor multifocality, large size (≥5 cm), macroscopic vascular or microscopic lymphovascular invasion, preoperative a-fetoprotein (AFP) levels, R0 resection, and the presence of impaired liver function. Close surveillance with imaging is warranted following curative-intent therapy, with magnetic resonance imaging (MRI) being the preferred approach to identify small, early recurrent HCCs. Treatment decisions at the time of recurrence involve ruling out extrahepatic disease and identifying candidates for potentially curative-intent repeat treatment options. Patients with recurrent disease are, however, very diverse in terms of tumor morphology and biologic behavior, as well as residual hepatic functional reserve. Patients with preserved liver function may benefit from repeat liver resection or ablation. Patients with recurrence within the Milan criteria may even be candidates for salvage liver transplantation, while multimodality treatment with combination of liver-directed therapies appears to enhance oncologic outcomes for individuals with advanced recurrent disease. A “one-size-fits-all” approach in staging recurrent HCC does not exist. Rather, individualized and evidence-based decision-making is necessary in order to optimize outcomes for patients with recurrent HCC.

Ki-67, p-53, E-Cadherin, and β-Catenin expression of advanced glotto-subglottic and supraglottic larynx carcinomas.

Identifying tumor markers that can be used to determine the biological behavior of tumors and predicting their prognosis may be helpful in choosing treatment strategies. Besides the differences in the embryological and histological anatomy of the larynx in this regard, the possibility of molecular causes that can explain the different clinical behaviors has always been a question for the scientific world. In this study, we aimed to investigate whether there were any immunohistochemically molecular differences among laryngeal carcinoma cases originating from two different anatomical regions of the larynx. The study group consisted of 43 patients. The rate of supraglottic cancers was 41.8%, while the rest had glotto-subglottic tumors. Ki67, β-catenin, E-cadherin, and p53 were examined in pathology preparations obtained by laryngectomy surgeries. The data obtained were analyzed by comparing factors that may affect the prognosis of the disease and between tumors originating from the two different anatomical regions. We did not see any statistically significant difference between groups for stage and grade of tumor, tumor recurrence rate, or lymphovascular or perineural invasion rated in terms of the investigated markers. In addition, there was no statistically significant difference between the two distinct groups in survival analysis. With these results, our study differs from some studies in the literature, and we think that this difference could be because the cases in our study consisted of advanced stage tumors and the groups investigated had similar survival rates.

Analysis of immune status in gastric adenocarcinoma with different infiltrating patterns and origin sites.

Tumor infiltration pattern (INF) and tumor origin site were reported to significantly affect the prognosis of gastric cancer (GC), while the immune status under these contexts is not clear. In this study, we correlated the density and phenotype of tumor-infiltrating lymphocytes (TILs) with INF and the tumor origin site to reflect the biological behavior of tumors from a new perspective and also determined their effects on overall survival (OS) and other related clinicopathological features in archival samples of 147 gastric cancers with 10-year follow-up data. We found that the INFc growth pattern (an invasive growth without a distinct border) of GC lacked immune cell infiltration, particularly the cytotoxic T cells and their activated form. It is also significantly associated with an unfavorable prognosis (P < 0.001) and proximal site (P = 0.001), positive lymph node metastasis (P = 0.002), and later tumor–node–metastasis stage (P < 0.001). Moreover, the density and sub-type of TILs infiltration were significantly different in disparate differentiated areas for the tumor tissue with INFb. Compared with distal gastric cancer, proximal gastric cancers were prone to grow in an INFc pattern (P = 0.001) and infiltrated with fewer TILs, experiencing a shorter survival time (P = 0.013). Multivariate analysis showed that only the INF and the density of TILs were demonstrated to be the independent prognostic factors of OS for the GC. We concluded that GC with an aggressive growth pattern arising from proximal sites always had a weak immune response and resulted in a poor prognosis. The interaction between them and their synergistic or antagonistic effects in the development of tumors need to be further studied. This study opens up a new perspective for research on the biological behavior of the tumor.

The value of BCL2 and CK20 expression in predicting behavioral patterns of bladder cancer, a cross sectional study

BackgroundSeveral biomarkers have been investigated to predict the biological behavior and prognosis of patients with bladder cancer. We evaluated the role of two important markers including BCL2 and CK20 in evaluating the biological behavior of bladder tumors. MethodsThis cross-sectional study was performed on 30 patients suffering from one of the neoplasms of the bladder. To evaluate the expression of BCL2 and CK20 markers, the neoplastic tissue sample was initially extracted and immunohistochemistry staining was employed. ResultsThe positivity of CK20 and BCL2 in the patients’ specimens was found to be 53.3% and 10.0%, respectively. There was no association between CK20 and BCL2 expressions and tumor size, tumor stage, or tumor-related vascular invasion, but BCL2 expression was shown to be higher in the low-grade specimens, while the expression rate of CK20 was found to be significantly higher in high grade samples. ConclusionEvaluation of the expression of CK20 and BCL2 markers can be very valuable in predicting bladder tumor grade.

The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC.

Simple SummaryThis review takes the extracellular matrix (ECM) as the starting point, and describes its influence and related mechanisms on the biological behavior of pancreatic ductal carcinoma (PDAC). It focuses on how the ECM regulates cancer stem cells and thus affects the metastasis and drug resistance of PDAC. Finally, current and ongoing treatment strategies for ECM are presented. ECM-related factors and mechanisms are both the focus and difficulty of current therapeutic strategy research, but further exploration is crucial for effectively eradicating the disease and improving patient survival.Pancreatic ductal adenocarcinoma (PDAC) is rich in dense fibrotic stroma that are composed of extracellular matrix (ECM) proteins. A disruption of the balance between ECM synthesis and secretion and the altered expression of matrix remodeling enzymes lead to abnormal ECM dynamics in PDAC. This pathological ECM promotes cancer growth, survival, invasion, and alters the behavior of fibroblasts and immune cells leading to metastasis formation and chemotherapy resistance, which contribute to the high lethality of PDAC. Additionally, recent evidence highlights that ECM, as a major structural component of the tumor microenvironment, is a highly dynamic structure in which ECM proteins establish a physical and biochemical niche for cancer stem cells (CSCs). CSCs are characterized by self-renewal, tumor initiation, and resistance to chemotherapeutics. In this review, we will discuss the effects of the ECM on tumor biological behavior and its molecular impact on the fundamental signaling pathways in PDAC. We will also provide an overview of how the different ECM components are able to modulate CSCs properties and finally discuss the current and ongoing therapeutic strategies targeting the ECM. Given the many challenges facing current targeted therapies for PDAC, a better understanding of molecular events involving the interplay of ECM and CSC will be key in identifying more effective therapeutic strategies to eliminate CSCs and ultimately to improve survival in patients that are suffering from this deadly disease.

TRIM65 Promotes Malignant Cell Behaviors in Triple-Negative Breast Cancer by Impairing the Stability of LATS1 Protein.

TNBC is a malignant tumor that easily relapses and metastasizes, with a poor prognosis in women. Ubiquitination plays a key role in promoting the tumor process. In various tumors, TRIM65 can affect malignant biological tumor behavior by ubiquitination of related proteins. We aimed to investigate TRIM65 expression in TNBC and whether it promotes malignant biological behavior in TNBC cells using Cell Counting Kit-8, colony formation, and transwell assays. Mechanically, we confirmed that TRIM65 promoted TNBC invasion and metastasis by ubiquitination of LATS1 protein through Co-IP, CHX, and endogenous ubiquitination experiments. The expression of TRIM65 was abnormally high and accelerated the proliferation, invasion, and migration of MDA-MB-231 and MDA-MB-453 cells. In vivo animal experiments also revealed that TRIM65 accelerated TNBC cell proliferation. Mechanistically, TRIM65 degraded LATS1 protein expression through ubiquitination in the Co-IP, CHX, and endogenous ubiquitination experiments. Rescue assays confirmed that TRIM65 degraded LATS1 protein expression, accelerating the proliferation, invasion, and migration ability of TNBC cells. Our results show that TRIM65 is upregulated in TNBC, and TRIM65 degrades LATS1 protein expression through ubiquitination and promotes malignant biological behavior in TNBC cells. TRIM65 may play an important role as a new oncogene in TNBC.

Predictors of Long-Time Survivors in Nonmetastatic Colorectal Signet Ring Cell Carcinoma: A Large Population-Based Study.

Background Colorectal signet ring cell carcinoma (SRCC) is a rare and distinct subtype of colorectal cancer (CRC), with extremely poor prognosis and aggressive tumor biological behavior. In this study, we aimed to analyze the clinicopathological characteristics and to identify the independent predictors of long-time survivors (LTSs) of nonmetastatic colorectal SRCC. Methods Patients diagnosed with nonmetastatic colorectal SRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared and analyzed the clinicopathological characteristics between LTSs (patients survived over 5 years) and non-LTSs (patients survived of or less than 5 years). Afterwards, multivariate logistic regression analysis was used to identify independent predictors of LTSs, which were further used to construct a nomogram model to predict the probability of being LTSs. Results We enrolled 2050 patients with nonmetastatic colorectal SRCC, consisting of 1441 non-LTSs and 609 LTSs. Multivariate logistic regression analysis revealed that race, marital status, tumor infiltration, lymph node involvement, and primary tumor treatment were independent predictors of LTSs. In addition, these five parameters were incorporated into a nomogram model to predict the probability of being LTSs. In terms of the model performance, the calibration curve revealed good agreement between observed and predicted probability of LTSs, and receiving operator characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion Collectively, we analyzed and profiled the clinicopathological characteristics of LTSs in patients with nonmetastatic colorectal SRCC. Race, marital status, T stage, N stage, and primary tumor treatment were independent predictors of LTSs.

Citopatologia das neoplasias cutâneas e subcutâneas na espécie felina: estudo retrospectivo

It is estimated that a quarter of all feline neoplasms affect the integumentary system. Cytological examination is of admirable importance for detection of neoplasms in companion animals, being considered a simple and non-invasive method. To date, there are limited information regarding the prevalence of feline skin cancer as well as the use of cytopathology as a diagnostic tool. In this sense, the study aimed to characterize cutaneous and subcutaneous tumors in 192 cats from the archives of a private clinic in São Paulo-SP, Brazil, specialized in the care of felines. Data regarding the animal (breed definition, sex, and age group) and tumor characteristics (biological behavior, cytomorphological category of neoplasm, and cytological suggestion for neoplasm) were obtained in a five-year period. A 95% confidence interval (CI) was estimated to verify the statistical difference between the animal and tumor characteristics. The chi-square test was carried out to verify the association between the tumor biological behavior and animal variables, as well as other tumor characteristics. Most cats were mixed breed and aged 11 to 15 years. Malignant tumors were predominant. A statistical association was observed between cytomorphological category of neoplasm and biological behavior (p&lt;0.001). Mesenchymal (24.5%) and epithelial tumors (25%) presented the highest frequency among those benign and malignant, respectively. The cytological suggestion for neoplasm was also statistically associated with biological behavior (p&lt;0.001). The highest percentage of occurrence of benign and malignant tumors consisted of lipomas (22.9%) and sarcomas (19.3%), respectively.

Long-term survival after sequential local treatments for oligometastatic esophageal squamous cell carcinoma: A case report.

Patients with metastatic esophageal cancer generally have a poor prognosis. In patients with oligometastatic disease (OMD), local treatment of metastases may improve overall survival (OS). This case report describes a 57-year-old female with a cT4bN2M1 mid-esophageal squamous cell carcinoma with ingrowth in the aorta and pathologic para-aortic lymph node metastases in the left thorax (i.e. synchronous OMD). The patient first underwent a robot-assisted thoracoscopic para-aortic lymph node dissection (R1, aorta). After response to definitive chemoradiotherapy (ycT4aN1), a salvage robot-assisted minimally-invasive esophagectomy was performed (ypT0N1, R0). During follow-up, metastasectomy and repeated cryoablations for pulmonary metastases were performed (repeat OMD). The patient is currently alive in very good condition without evidence of disease 4.5 years after the first diagnosis of OMD and free of systemic therapy. Clinical decision-making, local treatment options, and favorable biological tumor behavior in OMD are discussed. In this case of oligometastatic esophageal squamous cancer with favorable biological behavior, sequential local treatment of OMD (i.e. metastasectomy and cryoablations) combined with primary tumor resection was associated with long-term OS. • Oligometastatic disease (OMD) is associated with favorable tumor biology. • Local treatment for OMD may improve overall survival (OS). • Treatment for OMD is highly complex and requires a multidisciplinary team.

Annexin A5 suppression promotes the progression of cervical cancer.

Cervical cancer is a common malignant gynecological disease that threatens the health of women all over the world. The abnormal expression of Annexin A5 (ANXA5) is closely related to the biological behavior of various malignant tumors, however, the relationship between ANXA5 and cervical cancer is still unclear. Therefore, the effects of low expression of ANXA5 on the proliferation, apoptosis, migration and invasion of cervical cancer cells (HeLa) and its related mechanism were explored. The cells were divided into three groups: ANXA5-si group, negative control group and blank group. RNA interference was used to suppress ANXA5 expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, flow cytometry and propidium iodide (PI) staining, wound healing assay and transwell assay were employed to detect cell proliferation, apoptosis, migration and invasion respectively. Meanwhile, gene expression was detected by qPCR and Western blotting. ANXA5 suppression lead to the increase of proliferation, migration, invasion and the decrease of apoptosis of cervical cancer HeLa cells. Furthermore, the expression of both pPI3K and pAkt increased. ANXA5 might inhibit Hela cells proliferation and metastasis by regulating PI3K/Akt signal pathway.

Identification of potential matrix metalloproteinase-2 inhibitors from natural products through advanced machine learning-based cheminformatics approaches.

Matrix metalloproteinase-2 (MMP-2) is capable of degrading Collage TypeIV in the vascular basement membrane and extracellular matrix. Studies have shown that MMP-2 is tightly associated with the biological behavior of malignant tumors. Therefore, the identification of inhibitors targeting MMP-2 could be effective in treating the disease by maintaining extracellular matrix homeostasis. In the pharmaceutical and biomedical fields, many computational tools are widely used, which improve the efficiency of the whole process to some extent. Apart from the conventional cheminformatics approaches (e.g., pharmacophore model and molecular docking), virtual screening strategies based on machine learning also have promising applications. In this study, we collected 2871 compound activity data against MMP-2 from the ChEMBL database and divided the training and test sets in a 3:1 ratio. Four machine learning algorithms were then selected to construct the classification models, and the best-performing model, i.e., the stacking-based fusion model with the highest AUC value in both training and test datasets, was used for the virtual screening of ZINC database. Next, we screened 17 potential MMP-2 inhibitors from the results predicted by the machine learning model via ADME/T analysis. The interactions between these compounds and the target protein were explored through molecular docking calculations, and the results showed that ZINC712249, ZINC4270723, and ZINC15858504 had lower binding free energies than the co-crystal ligand. To further examine the binding stability of the complexes, we performed molecular dynamics simulations and finally identified these three hits as the most promising natural products for MMP-2 inhibitors.

Gastrointestinal Stromal Tümörlerin Klinikopatolojik Özellikleri ve Ki-67 proliferasyon İndeksinin Prognostik Önemi: Yeni Bir Prognostik Belirteç Olabilir

Objective: The biological behavior of gastrointestinal stromal tumors (GISTs) varies widely and it is diffucult to predict their malignant potential with the current risk classification criterias. Therefore, we aimed to analyse the prognostic importance of Ki-67 LI for estimating survival outcomes in patients with GISTs.&#x0D; Methods: For the last 11 years, between 2006 and 2017, who had been treated after surgery were included. A single pathologist re-defined the histologic examples of all cases retrospectively.&#x0D; Results: Totally, 104 patients were included in the study. The median follow-up time was 73 months (range; 6 to 148 months). Seven of the 104 patients (7%) had local recurrence, 26 of the 104 patients (25%) had distant metastases and 11 of the 104 patients (11%) died during the follow-up period. The mean OS was 133 (range; 124 to 141) and the mean DFS was 117 (range; 107 to 127) months for patients. The disease progression or recurrence during follow up and increasing age were the significant prognostic factors for OS. Mitotic count, growth pattern, tumor location and Ki-67 LI were the significant prognostic factors for DFS. According to multivariate analyses, the Ki-67 LI was the only prognostic factor for estimating disease progression or recurrence (p=0.04). &#x0D; Conclusion: The most important prognostic factors that affect OS were the age and disease progression or recurrence of disease. Ki-67 LI was the only prognostic factor for estimating disease progression or recurrence. As the follow-up period increases, we think that Ki-67 LI also will affect overall survival.

The progression-free survival ratio as outcome measure in recurrent ovarian carcinoma patients: Current and future perspectives

ObjectiveClinical efficacy of cytostatic anticancer agents can be determined with the progression-free survival (PFS) ratio. This outcome measure compares PFS achieved by a new treatment (PFS2) to the PFS of the most recent treatment on which the patient has experienced progression (PFS1). Clinical benefit has been defined as a PFS-ratio (PFS2/PFS1) > 1.3. However, in order to demonstrate significant benefit, trial designs require an assumption on the proportion of patients who reach this ratio during palliative options. For ovarian carcinoma, data is lacking to support this assumption. Therefore in this study, we assess the PFS-ratio in recurrent ovarian carcinoma patients treated with current palliative options. MethodsWe included 67 patients with recurrent high-grade serous (HGSC, 73.1%) or low-grade (LGOC, 26.9%) ovarian carcinoma. We determined the median PFS-ratio and investigated the association with clinicopathological characteristics. ResultsOverall, we observed a median PFS-ratio of 0.69. The proportion of patients with a PFS-ratio > 1.3 was 22.4%. For HGSC patients, the median PFS-ratio was significantly lower than for LGOC patients (respectively, 0.58 and 1.26, p = 0.007). Multivariate logistic regression analysis revealed that the LGOC subtype and CA125 tumor marker concentration were independent factors related to a PFS-ratio > 1.3. ConclusionsAlthough the PFS-ratio represents a meaningful outcome measure in studies investigating cytostatic anticancer agents, we conclude that it is influenced by tumor histology and biological behavior. In future research, these factors should be taken into account when determining thresholds for clinical benefit in trial designs.