Journal of Environmental Pathology Toxicology and Oncology最新文献

Increasing evidence has shown that stromal interaction molecule 1 (STIM1), a key subunit of store-operated Ca2+ entry (SOCE), is closely associated with tumor growth, development, and metastasis. However, there is no report of a comprehensive assessment of STIM1 in pan-cancer. This study aimed to perform a general analysis of STIM1 in human tumors, including its molecular characteristics, functional mechanisms, clinical significance, and immune infiltrates correlation based on pan-cancer data from The Cancer Genome Atlas (TCGA). Gene expression analysis was investigated using TCGA RNA-seq data, the Tumor Immune Estimation Resource (TIMER). Phosphorylation analysis was undertaken using the Clinical Proteomic Tumor Analysis Consortium (CP-TAC) and the PhosphoNET database. Genetic alterations of STIM1 were analyzed using cBioPortal. Prognostic analysis was via the R package "survival" function and the Kaplan-Meier plotter. Functional enrichment analysis was via by the R package "cluster Profiler" function. The association between STIM1 and tumor-infiltrating immune cells and immune markers was by the R package "GSVA" function and TIMER. STIM1 was differentially expressed and associated with distinct clinical stages in multiple tumors. The phosphorylation of STIM1 at S673 is highly expressed in clear cell renal carcinoma and lung adenocarcinoma tumors compared to normal tissues. STIM1 genetic alterations correlate with poor prognosis in several tumors, including ovarian cancer and lung squamous cell carcinomas. High STIM1 expression is associated with good or poor prognosis across diverse tumors. Overall survival (OS) analysis indicated that STIM1 is a favorable prognostic factor for patients with BRCA, KIRC, LIHC, LUAD, OV, SARC, and UCEC, and is a risk prognostic factor for BLCA, KIRP, STAD, and UVM. There is a close correlation between STIM1 expression and immune cell infiltration, immune-regulated genes, chemokines, and immune checkpoints in a variety of tumors. STIM1 functions differently in diverse tumors, playing an oncogenic or antitumor role. Moreover, It may serve as a prognostic biomarker and an immunotherapy target across multiple tumors.

Fluoride toxicity, principally by polluted groundwater, is regarded as a momentous global public health risk, as there is no particular and proven treatment for chronic fluoride toxicity i.e., fluorosis which leads to several serious health complications. Scientific literature reveals several medicinal plants and natural products alleviate experimentally induced fluoride toxicity. The present review attempts to collate those experimental studies on medicinal plants and plant derived natural products with fluoride toxicity ameliorative effects. Literature scrutiny was performed by using online bibliographic databases and the studies for the last 15 years were considered. Minerals and semi-synthetic or synthetic analogs of natural products were excluded. Literature study revealed that 25 medicinal plants and 17 natural products exhibited significant protection from fluoride toxicity in experimental animal models i.e., preclinical studies. Two clinical studies on medicinal plants were also found in literature showing beneficial yet poorly correlated outcome. Relevant research in this field could lead to development of a potentially useful agent in therapeutic management of fluoride toxicity in humans.

Receptor tyrosine kinase pathway is frequently searched for cancer causing mutations in tumors. Emerging targeted therapies are gleam of hope for them. Infiltrating urothelial carcinoma can have many morphological aspects according to their differentiation/variants. To evaluate KRAS, BRAF, and PIK3CA mutations and HER2, EGFR, and p16 expression, we divided urothelial carcinomas into two groups: differentiated/variants (n = 12) and conventional (n = 12). We compared results with clinical, demographic, histopathologic features and survival rates. No statistically significant results could be obtained in the comparison of histopathologic properties/survival rates with mutation analysis and EGFR, HER2, and p16 status. Differentiated/variants urothelial carcinoma showed higher EGFR expression (P < 0.001). Glandular differentiation was the most frequent type, followed by squamous and sarcomatoid differentiation. We observed the most common mutation at KRAS with a propensity for urothelial carcinoma with glandular differentiation. More than one mutation/high protein expression was seen in some tumors. Targeted therapies for KRAS mutation can be effective at urothelial carcinoma with glandular differentiation. Heterologous expression of relevant proteins and genes can be a cause for targeted treatment obstacle. The determination of the molecular characters of tumors is a guide in creating targeted treatment algorithms and in choosing the patient.

Glioma is the most common tumor of the central nervous system (CNS). Drug resistance, and lack of effective treatment methods make the treatment effect of glioma patients unsatisfactory. The recent discovery of cuproptosis has led to new thinking about the therapeutic and prognostic targets of glioma. The transcripts and clinical data of glioma samples were obtained from The cancer genome atlas (TCGA). The cuproptosis-related lncRNA (CRL)-based glioma prognostic models were built through least absolute shrinkage and selection operator (LASSO) regression analysis in the train set and validated in the test set. Kaplan-Meier survival curve, risk curve analysis, and time-dependent receiver operating characteristic (ROC) curve were used to assess the predictive ability and risk differentiation ability of the models. Univariate and multivariate COX regression analyses were conducted on the models and various clinical features, and then nomograms were constructed to verify their predictive efficacy and accuracy. Finally, we explored potential associations of the models with immune function, drug sensitivity, and the tumor mutational burden of glioma. Four CRLs were selected from the training set of 255 LGG samples and the other four CRLs were selected from the training set of 79 GBM samples to construct the models. Follow-up analysis showed that the models have commendable prognostic value and accuracy for glioma. Notably, the models were also associated with the immune function, drug sensitivity, and tumor mutational burden of gliomas. Our study showed that CRLs were prognostic biomarkers of glioma, closely related to glioma immune function. CRLs may affect uniquely the sensitivity of glioma treatment. It will be a potential therapeutic target for glioma. CRLs will offer new perspectives on the prognosis and therapy of gliomas.

Melatonin is a serotonin-derived pineal gland hormone with many biological functions like regulating the sleep-wake cycle, circadian rhythm, menstrual cycle, aging, immunity, and antioxidants. Melatonin synthesis and release are more pronounced during the night, whereas exposure to light decreases it. Evidence is mounting in favor of the therapeutic effects of melatonin in cancer prevention, treatment and delayed onset in various cancer subtypes. Melatonin exerts its anticancer effect through modification of its receptors such as melatonin 1 (MT1), melatonin 2 (MT2), and inhibition of cancer cell proliferation, epigenetic alterations (DNA methylation/demethylation, histone acetylation/deacetylation), metastasis, angiogenesis, altered cellular energetics, and immune evasion. Melatonin performs a significant function in immune modulation and enhances innate and cellular immunity. In addition, melatonin has a remarkable impact on epigenetic modulation of gene expression and alters the transcription of genes. As an adjuvant to cancer therapies, it acts by decreasing the side effects and boosting the therapeutic effects of chemotherapy. Since current treatments produce drug-induced unwanted toxicities and side effects, they require alternate therapies. A recent review article attempts to summarize the mechanistic perspective of melatonin in different cancer subtypes like skin cancer, breast cancer, hepatic cancer, renal cell cancer, non-small cell lung cancer (NSCLC), colon oral, neck, and head cancer. The various studies described in this review will give a firm basis for the future evolution of anticancer drugs.

To illustrate the benefits of surgery in conjunction with neoadjuvant chemotherapy in patients with limited-stage small cell lung cancer (LS-SCLC), and to evaluate risk factors affecting patient's survival. Forty-six LS-SCLC patients who received surgery in our center from September 2012 to December 2018 were retrospectively analyzed. Twenty-five patients with LS-SCLC diagnosed after surgery who received postoperative adjuvant chemotherapy were classified into control group, and 21 patients with LS-SCLC who received preoperative neoadjuvant chemotherapy were classified into observation group. The observation group were divided into subgroup 1 (negative lymph nodes) and subgroup 2 (positive lymph nodes). Progression-free survival (PFS) and overall survival (OS) of patients were analyzed. Univariate and multivariate Cox regression were utilized to analyze independent risk factors affecting patient's survival. PFS and OS of patients in the control group and observation group had similar outcomes (P > 0.05). Subgroup 1 and subgroup 2 had similar PFS and OS (P > 0.05). PT2, pN2, BM, and two or more positive lymph nodes were significantly associated with poor PFS and OS (P < 0.05). Furthermore, the pT, number of lymph node positive stations and BM were independent risk factors affecting patient's survival (P < 0.05). Surgery combined with neoadjuvant chemotherapy can achieve long-term survival benefit for some patients with LS-SCLC. It is necessary to find a better plan that enables to select patients suitable for surgery after neoadjuvant chemotherapy.

Treatment of lung cancer with conventional therapies, which include radiation, surgery, and chemotherapy results in multiple undesirable adverse or side effects. The major clinical challenge in developing new drug therapies for lung cancer is resistance, which involves mutations and disturbance in various signaling pathways. Molecular abnormalities related to epidermal growth factor receptor (EGFR), v-Raf murine sarcoma viral oncogene homolog B1 (B-RAF) Kirsten rat sarcoma virus (KRAS) mutations, translocation of the anaplastic lymphoma kinase (ALK) gene, mesenchymal-epithelial transition factor (MET) amplification have been studied to overcome the resistance and to develop new therapies for non-small cell lung cancer (NSCLC). But, inevitable development of resistance presents limits the clinical benefits of various new drugs. Here, we review current progress in the development of molecularly targeted therapies, concerning six clinical biomarkers: EGFR, ALK, MET, ROS-1, KRAS, and B-RAF for NSCLC treatment.

Dental implants are medical devices that are surgically inserted into the patient's jawbone by an orthodontist to act as roots of missing teeth. After the implantation, the maxilla or mandible integrates with the surface of the dental implant. This process, called "osseointegration," is an important period to ensure the long-term use of dental implants and prevent implant failures. Metal implants are the most used implant materials. However, they have disadvantages such as corrosion, metal ion release from metal implant surfaces and associated toxicity. To avoid these adverse effects and improve osseointegration, alternative dental implant materials such as ceramics, polymers, composites, and novel surface modification technologies have been developed. The safety of these materials are also of concern for toxicologists. This review will give general information about dental implant materials, osseointegration and successful implantation process. Moreover, we will focus on the new surface coatings materials for of dental implants and their toxicity and safety concerns will be discussed.

Dysregulation of pseudogene expression is closely related to the progression of various cancers, including glioma. Proliferation-associated 2G4 pseudogene 4 (PA2G4P4) could affect cell viability and apoptosis of glioma cells. However, the specific regulatory mechanism of PA2G4P4 is not clear. In this paper, we found that PA2G4P4 overexpres-sion promoted glioma cell proliferation, migration and cell cycle progression, whereas PA2G4P4 knockdown inhibited cancer progression. Knockdown of PA2G4P4 also suppressed the tumorigenesis of glioma cells in vivo. Furthermore, knockdown of PA2G4 after overexpression of PA2G4P4 decreased the cell viability and migration ability to normal level. The protein level of a tumor suppressor gene phosphatase and tensing homolog (PTEN) was greatly decreased in U87 cells after PA2G4P4 overexpression, while increased after PA2G4 knockdown; on the contrary, the protein levels of P-AKT and P-S6 were obviously induced in U87 cells after PA2G4P4 overexpression, and decreased after PA2G4 knockdown. The cell ability, colony formation ability and cell migration ability were all recovered to normal level by adding an AKT inhibitor MK2206 to the glioma cells, which were induced by PA2G4P4 overexpression. Our results revealed that PA2G4P4 could regulate glioma cell proliferation and migration through PTEN/AKT/mTOR signaling pathway by targeting PA2G4 gene. PA2G4P4 may become a target for glioma treatment.

Heavy metal toxicity imposes a potential worldwide threat to environment and humans. Mercury toxicity is regarded as a serious global community health risk, as there is no particular and proven treatment for chronic mercury toxicity. Probiotics include the live apathogenic microorganisms, which are administered orally to revamp the gut microbial equilibrium thus bestowing benefit to the host. Scientific literature demonstrates different probiotic microorganisms can obviate mercurey toxicity. The present article puts together the experiments on probiotics with mercury toxicity alleviation effects in pursuit of the mechanistic hypotheses. Literature scrutiny was performed by using online bibliographic databases. Literature survey revealed that, eight types of probiotic microorganisms demonstrated significant protection from mercury toxicity in experimental pre-clinical studies. Clinical investigation with noteworthy outcome was not reported yet. Results of these studies indicate that probiotic microorganisms may hold the promise in amelioration and therapeutics of mercury toxicity. Probiotic supplementation may serve as a dietary therapeutic approach against mercurials along with extant therapies.