Tumor Metastatic Disease Research Articles

Treatment and Prevention Strategies of Breast Cancer

Abstract. With the increasing trend of late childbearing and low childbearing, the incidence of breast cancer is increasing rapidly worldwide. At present, breast cancer has become one of the more frequent malignant tumor diseases in women and has aroused widespread concern in society. The cause of the disease is not completely clear, with the deepening of research, the relevant detection methods are constantly updated, as far as possible early diagnosis. At present, the main methods of breast cancer prevention are lifestyle adjustment, including reducing alcohol intake, maintaining a healthy weight and chemical prevention, but the methods are limited, so the research on breast cancer prevention is particularly important. At the same time, medical workers should educate the majority of women about disease prevention, so that women can establish a correct concept of prevention and treatment, so as in order to lower the prevalence of breast cancer and improve the women health.

A Multi-Task Transformer With Local-Global Feature Interaction and Multiple Tumoral Region Guidance for Breast Cancer Diagnosis.

Breast cancer, as a malignant tumor disease, has maintained high incidence and mortality rates over the years. Ultrasonography is one of the primary methods for diagnosing early-stage breast cancer. However, correctly interpreting breast ultrasound images requires massive time from physicians with specialized knowledge and extensive experience. Recently, deep learning-based method have made significant advancements in breast tumor segmentation and classification due to their powerful fitting capabilities. However, most existing methods focus on performing one of these tasks separately, and often failing to effectively leverage information from specific tumor-related areas that hold considerable diagnostic value. In this study, we propose a multi-task network with local-global feature interaction and multiple tumoral region guidance for breast ultrasound-based tumor segmentation and classification. Specifically, we construct a dual-stream encoder, paralleling CNN and Transformer, to facilitate hierarchical interaction and fusion of local and global features. This architecture enables each stream to capitalize on the strengths of the other while preserving its unique characteristics. Moreover, we design a multi-tumoral region guidance module to explicitly learn long-range non-local dependencies within intra-tumoral and peri-tumoral regions from spatial domain, thus providing interpretable cues beneficial for classification. Experimental results on two breast ultrasound datasets show that our network outperforms state-of-the-art methods in tumor segmentation and classification tasks. Compared with the second-best competitive method, our network improves the diagnosis accuracy from 73.64% to 80.21% on a large external validation dataset, which demonstrates its superior generalization capability.

Identification and analysis of a cell communication prognostic signature for oral squamous cell carcinoma at bulk and single-cell levels.

Head and neck squamous cancer (HNSC) is a heterogenous malignant tumour disease with poor prognosis and has become the current major public health concern worldwide. Oral squamous cell carcinoma (OSCC) is the majority of HNSC. It is still in lack of comprehensive tumour immune microenvironment analysis and prognostic model development for OSCC's clinic practice. Single-cell sequencing data analysis was conducted to identify immune cell subtypes and illustrate cell-cell interaction status in OSCC via R package 'Seurat', 'Harmony', 'elldex' and 'CellChat'. Base on the bulk sequencing data, WGCNA analysis was employed to identify the CD8+ T cell related gene module. XGBoost was used to construct the gene prognostic model for OSCC. Validation sets and immunotherapy data sets were analysed to further evaluate the model's effectiveness and immunotherapy responsiveness predicting potential. siRNA was used to down regulate FCRL4 expression. Real-time PCR and Western blot were used to validate target gene expression. The effects of FCRL4 on OSCC cells were detected by wound healing, Trans well and clone formation assays. Communication between epithelial cells and tissue stem cells may be the potential key regulators for OSCC progression. By integrating single-cell sequencing data analysis and bulk sequencing data analysis, we constructed a novel immune-related gene prognostic model. The model can effectively predict the prognosis and immunotherapy responsiveness of OSCC patients. In addition, the effects of FCRL4 on OSCC cells were validated. We comprehensively interpreted the immune microenvironment pattern of OSCC based on the single-cell sequencing data and bulk sequencing data analysis. A robust immune feature-based prognostic model was developed for the precise treatment and prognosis evaluation of OSCC.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

ActO, a positive cluster-situated regulator for actinomycins biosynthesis in Streptomyces antibioticus ZS

Actinomycins are a class of cyclic lipopeptide antibiotics produced by Streptomyces, which have rich biological activities and demonstrate great potential value. Among them, actinomycin D is currently the effective drug for some malignant tumor diseases. Although the chemical properties, biological activities and biosynthesis of actinomycins have been extensively studied, the regulation of their biosynthesis remains poorly understood. Streptomyces antibioticus ZS isolated from deep-sea corals is a producer of actinomycin D and actinomycin V. Here, we reported the characterization of a cluster-situated regulator ActO in actinomycins biosynthetic gene cluster (act cluster) of S. antibioticus ZS, which belongs to LmbU family. Deletion of actO completely blocked the synthesis of actinomycins. Overexpression of actO increased the yields of actinomycin D and actinomycin V by 4.4 fold and 2.6 fold, respectively. The result of RT-qPCR showed that ActO activates the transcription of all genes in act cluster. However, no specific binding of His6-ActO to the promoters of target genes was observed after electrophoretic mobility shift assay (EMSA). These results proved that ActO serves as a positive regulator involved in the biosynthesis of actinomycins, affecting the transcription of all genes related to the synthesis of intermediates, skeleton modification and extracellular transportation of final products. Moreover, we demonstrated that overexpression of actO is a novel strategy to increase the yields of actinomycins.

The silent epidemic: exploring the link between loneliness and chronic diseases in China’s elderly

BackgroundChronic diseases, such as heart disease, cancer, and diabetes, are the leading causes of death and disability. Loneliness is linked to a greater risk of chronic disease. However, the lack of loneliness may change this relationship.MethodsThe 4th Survey of the Aged Population in Urban and Rural China (SSAPUR) was performed. 222,179 people over 60 years old were recruited. Chronic disease was defined by self-reported tumble incidents using the fourth SSAPUR questionnaire. We found that the residuals were well normally distributed. Subsequently, we analyzed the association between each studied factor and chronic disease by univariate logistic regression analysis. Finally, we stratified the population by age, gender, and urban and rural.Results77,448 individuals experienced loneliness, while 137,593 did not. Loneliness correlated significantly with urban-rural classification, age, and gender (P < 0.001). There was a significant association between chronic diseases and loneliness (P < 0.05). Compared to lonely individuals, those with low level of loneliness had a lower incidence of gastric diseases (OR = 0.752, 95% CI, 0.736–0.769, P < 0.001), osteoarthritis (OR = 0.685, 95% CI, 0.673–0.697, P < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 0.678, 95% CI, 0.659–0.698, P < 0.001), asthma (OR = 0.608, 95% CI, 0.583–0.633, P < 0.001), malignant tumors (OR = 0.892, 95% CI, 0.822–0.968, P = 0.006), and reproductive system diseases (OR = 0.871, 95% CI, 0.826–0.918, P < 0.001).ConclusionIn summary, loneliness is an important risk factor in the occurrence and development of chronic diseases in the elderly in China, and it has adverse effects on hypertension, stomach disease, cataract or glaucoma, osteoarthrosis, chronic lung disease, asthma, malignant tumor, and reproductive system diseases.

Label-Free Identification of AML1-ETO Positive Acute Myeloid Leukemia Using Single-Cell Raman Spectroscopy.

Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.

Automatic detection method of bladder tumor cells based on color and shape features

Bladder urothelial carcinoma is the most common malignant tumor disease in urinary system, and its incidence rate ranks ninth in the world. In recent years, the continuous development of hyperspectral imaging technology has provided a new tool for the auxiliary diagnosis of bladder cancer. In this study, based on microscopic hyperspectral data, an automatic detection algorithm of bladder tumor cells combining color features and shape features is proposed. Support vector machine (SVM) is used to build classification models and compare the classification performance of spectral feature, spectral and shape fusion feature, and the fusion feature proposed in this paper on the same classifier. The results show that the sensitivity, specificity, and accuracy of our classification algorithm based on shape and color fusion features are 0.952, 0.897, and 0.920, respectively, which are better than the classification algorithm only using spectral features. Therefore, this study can effectively extract the cell features of bladder urothelial carcinoma smear, thus achieving automatic, real-time, and noninvasive detection of bladder tumor cells, and then helping doctors improve the efficiency of pathological diagnosis of bladder urothelial cancer, and providing a reliable basis for doctors to choose treatment plans and judge the prognosis of the disease.

Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma.

Patients with type 2 diabetes mellitus (T2DM) have large fluctuations in blood glucose (BG), abnormal metabolic function and low immunity to varying degrees, which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy. Controlling hyperglycemia may have important therapeutic implications for cancer patients. To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma (LC). The clinical data of 60 T2DM + LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed. All patients underwent chemotherapy and were grouped as a control group (CG; normal BG fluctuation with a mean fluctuation < 3.9 mmol/L) and an observation group (OG; high BG fluctuation with a mean fluctuation ≥ 3.9 mmol/L) based on their BG fluctuations, with 30 cases each. BG-related indices, tumor markers, serum inflammatory cytokines and adverse reactions were comparatively analyzed. Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers. The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG, together with markedly higher mean amplitude of glycemic excursions (MAGE), mean of daily differences, largest amplitude of glycemic excursions and standard deviation of blood glucose (P < 0.05). In addition, the OG exhibited evidently higher levels of carbohydrate antigen 19-9, carbohydrate antigen 125, carcinoembryonic antigen, neuron-specific enolase, cytokeratin 19, tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein than the CG (P < 0.05). Pearson analysis revealed a positive association of MAGE with serum tumor markers. The incidence of adverse reactions was significantly higher in the OG than in the CG (P < 0.05). The greater the BG fluctuation in LC patients after chemotherapy, the more unfavorable the therapeutic effect of chemotherapy; the higher the level of tumor markers and inflammatory cytokines, the more adverse reactions the patient experiences.

Keap1-Nrf2 pathway: a key mechanism in the occurrence and development of cancer.

The Keap1-Nrf2 signaling pathway is a major regulator of the cytoprotective response, participating in endogenous and exogenous stress caused by ROS (reactive oxygen species). Nrf2 is the core of this pathway. We summarized the literature on Keap1-Nrf2 signaling pathway and summarized the following three aspects: structure, function pathway, and cancer and clinical application status. This signaling pathway is similar to a double-edged sword: on the one hand, Nrf2 activity can protect cells from oxidative and electrophilic stress; on the other hand, increasing Nrf2 activity can enhance the survival and proliferation of cancer cells. Notably, oxidative stress is also considered a marker of cancer in humans. Keap1-Nrf2 signaling pathway, as a typical antioxidant stress pathway, is abnormal in a variety of human malignant tumor diseases (such as lung cancer, liver cancer, and thyroid cancer). In recent years, research on the Keap1-Nrf2 signaling pathway has become increasingly in-depth and detailed. Therefore, it is of great significance for cancer prevention and treatment to explore the molecular mechanism of the occurrence and development of this pathway.

Innovative Surgical Approaches That Improve Individual Outcomes in Advanced Breast Cancer.

Breast cancer is the most common cause of cancer death in women and the second cause in the general population. The incidence has increased over time. Women in developing countries often present at an advanced stage where initial surgery is not feasible. Short disease-free intervals, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival. Surgery is an integral part of the therapeutic plan for locally advanced breast cancer. The integration of surgical care into the management of patients with advanced cancer has changed substantially with the use of neoadjuvant chemotherapy. Also, more recently, neoadjuvant endocrine therapy and targeted therapies offer new opportunities to downsize the tumor burden and transform the role of surgery for this population from palliation to largely curative intent. Innovative surgical approach to the primary tumor in metastatic disease may provide survival benefits and local control in some patients. Similar to systemic therapy, surgical therapy for secondary dissemination should be considered in certain cases for improved individual outcomes. Advances in reconstructive techniques have improved the quality of life of these patients.

Adult Renal Cell Carcinoma – Rare - Acquired Cystic Disease Associated Renal Cell Carcinoma: Review and Update

For more than twenty-three years ago acquired cystic kidney disease had become increasingly recognised as a significant risk in patients who have end-stage kidney disease, especially in those patients who are maintained on chronic haemodialysis and peritoneal dialysis. A review of the global literature had suggested that nearly fifty percent (50%) of patients who have been undergoing dialysis for more than 3 years do develop kidney cystic changes. The major complications emanating from this condition include neoplasia and spontaneous kidney haemorrhage. The risk for the development of carcinoma of the kidney had been estimated to be more than 30 times higher in dialysis patients with cystic changes in comparison with in the general population. Acquired cystic kidney disease has become increasingly recognised as a significant risk in patients with end-stage renal disease, especially in those maintained on chronic haemodialysis and peritoneal dialysis. A review of the literature indicates that nearly 50% of patients on dialysis for more than 3 years develop renal cystic changes. The major complications of this condition are neoplasia and spontaneous renal haemorrhage. The risk of developing renal carcinoma has been estimated to be more than 30 times higher in dialysis patients with cystic changes than in the general population. It is important for clinicians all over the world to be aware of the possibility of patients undergoing medium to long-term dialysis developing cystic renal disease ensued by the development of malignant kidney disease. Careful surveillance of dialysis patients utilizing yearly ultrasound scan of renal tract and computed tomography would be recommended for the regular and careful follow-up assessment of patients who are undergoing medium-term to medium-term for chronic kidney disease. Various aspects related to cystic kidney disease associated malignant tumour disease has been discussed in the ensuing article to update information related to the diagnosis, management and outcome of the tumour.

Treating pathological metastatic fractures of the humerus by compound osteosynthesis: a retrospective cohort study

BackgroundThe number of malignant tumors is increasing as are bone metastases, such as those in the humerus. Arm function is important for an independent everyday life. In this study, compound osteosynthesis of metastatic fractures of the humerus is examined for its suitability in light of the competing risk of death. Materials and MethodsThis retrospective monocentric study includes a cohort of tumor patients who underwent primary compound osteosynthesis for pathological humeral fractures. The main endpoint was the continued existence of compound osteosynthesis using competing risk analysis (CRA) to contrast failure and death. Failure was defined as mechanical failure of the osteosynthesis construct like re-fracture or plate-and-screw dislocation or loosening, which provides an indication for re-intervention. Other complications are also described. ResultsWe included 36 consecutive patients (64% male, mean age 71.6 yrs.) from September 2007 to October 2020. In 58% of the cases, the left humerus was fractured. Lung carcinoma was the most common cause of bone metastases (27.8%). Compound osteosynthesis was performed with a median delay of five days after diagnosis of the pathologic fracture. Postoperative complications occurred in seven of the 36 patients (19.4%): radial nerve palsy (n = 3), postoperative hematoma (n = 2), re-fracture (n = 2) and screw loosening (n = 1). Few mechanical failures (8.3%) occurred within the first year; only one patient needed revision of the osteosynthesis (2.8%). Median patient survival after compound osteosynthesis was 26.6 weeks. CRA showed that for up to two years, the risk of death is clearly dominant over the risk of osteosynthesis failure from surgery. ConclusionOur study shows that compound osteosynthesis of the humerus is a suitable option for patients with pathologic humerus fractures. Compound osteosynthesis of the humerus usually survives the duration of malignant tumor disease.

PROSPECTS OF THE USE OF MELATONIN IN RADIATION THERAPY

Summary. Radiation therapy (RT) plays a key role in the treatment of malignant tumor diseases in the majority of cancer patients. Unfortunately, despite the improvement of RT methods and tools (in particular, its conformal strategy) and modern methods of dosimetry, RT has a harmful effect not only on the tumor, but also on normal tissues surrounding the tumor. In some cases, this leads to the development of radiation reactions and complications, the treatment of which is a long, sometimes ineffective process. One of the strategies to prevent or reduce these complications is the use of natural radioprotectors, among which the pineal hormone melatonin deserves attention. It is a powerful antioxidant with immunoregulatory properties that can reduce toxicity caused by ionizing radiation (IR) in various organs. These effects are mediated by the modulatory effects of melatonin at different levels of tissue response to IR. The most important are the effects on the DNA repair system, antioxidant enzymes, immune cells, cytokine secretion, transcription factors and protein kinases. The data highlighted in this review indicate that melatonin has great potential to prevent the side effects of RT and its inclusion as an adjuvant in RT would enable the use of higher radiation doses in treatment. In addition, due to the antitumor and radiosensitizing properties of melatonin, its use can increase tumor damage. Therefore, melatonin is a promising radioprotective agent of normal tissues surrounding the tumor with the effect of increasing the therapeutic efficiency/toxicity ratio of chemoradiation treatment of patients.

Vitamin C enhances the sensitivity of osteosarcoma to arsenic trioxide via inhibiting aerobic glycolysis

Osteosarcoma (OS) is a common malignant tumor disease in the department of orthopedics, which is prone to the age of adolescents and children under 20 years old. Arsenic trioxide (ATO), an ancient poison, has been reported to play a critical role in a variety of tumor treatments, including OS. However, due to certain poisonous side effects such as cardiotoxicity and hepatotoxicity, clinical application of ATO has been greatly limited. Here we report that low doses of ATO (1 μM) observably reduced the half-effective inhibitory concentration (IC50) of vitamin C on OS cells. Compared with the treatment alone, the synthetic application of vitamin C (VitC, 800 μM) and ATO (1 μM) significantly further inhibited the proliferation, migration, and invasion of OS cells and promoted cell apoptosis in vitro. Meanwhile, we observed that the combined application of VitC and ATO directly suppresses the aerobic glycolysis of OS cells with the decreased production of pyruvate, lactate, and ATP via inhibiting the expression of the critical glycolytic genes (PGK1, PGM1, and LDHA). Moreover, the combination of VitC (200 mg/kg) and ATO (1 mg/kg) with tail vein injection significantly delayed OS growth and migration of nude mice by inhibiting aerobic glycolysis of OS. Thus, our results demonstrate that VitC effectively increases the sensitivity of OS to low concentrations of ATO via inhibiting aerobic glycolysis to alleviate the toxic side effects of high doses of arsenic trioxide, suggesting that synthetic application of VitC and ATO is a promising approach for the clinical treatment of human OS.

RNA-binding protein NOVA1 promotes acute T-lymphocyte leukemia progression by stabilizing USP44 mRNA.

Acute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with NOVA1, and RNA immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. The knockdown of NOVA1 had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function might be achieved by binding to and stabilizing USP44 mRNA.

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

Causes of death among patients with testicular cancer during the survivorship

ObjectiveThe aim was to evaluate the causes of death for patients with testicular cancer (TC), and calculate mortality risks for each cause. MethodsPatients diagnosed between 2000 and 2017 were identified. Main causes of death including TC, second malignant tumor (SMT) and non-tumor diseases, and the standardized mortality rate (SMR) of each cause were analyzed. Results27,143 patients with localized TC were included, and 1171 of them died including 215 TC deaths, 236 SMT deaths, and 720 non-tumor deaths. Main SMT deaths were cancer from lung and bronchus, colon and rectum, etc. Main non-cancer causes were diseases of heart, accidents and adverse effects and suicide and self-inflicted injury. Compared with the general population, the mortality risks from diseases of heart and accidents and adverse effects were significantly reduced. For 11,719 patients with regional and distant metastasis TC, 1733 died including 964 TC deaths, 345 SMT deaths and 424 non-tumor deaths. The main SMT and non-tumor deaths were lung and bronchus, diseases of heart and suicide and self-inflicted injury. ConclusionThe leading causes of death besides TC were lung and bronchus cancer, colon and rectum cancer, diseases of heart, accidents and adverse effects, suicide and self-inflicted injury for TC patients. The localized TC patients were associated with similar risks of SMT deaths and lower risks of main non-tumor causes of death. ImpactWe evaluated all causes of death of TC patients and SMR for each cause of death. Our results could provide valuable information about the priority of healthcare during testicular cancer survival.

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach.

Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

Glucose oxidase virus-based nanoreactors for smart breast cancer therapy.

Breast cancer is the most common malignant tumor disease and the leading cause of female mortality. The evolution of nanomaterials science opens the opportunity to improve traditional cancer therapies, enhancing therapy efficiency and reducing side effects. Herein, protein cages conceived as enzymatic nanoreactors were designed and produced by using virus-like nanoparticles (VLPs) from Brome mosaic virus (BMV) and containing the catalytic activity of glucose oxidase (GOx) enzyme. The GOx enzyme was encapsulated into the BMV capsid (VLP-GOx), and the resulting enzymatic nanoreactors were coated with human serum albumin (VLP-GOx@HSA) for breast tumor cell targeting. The effect of the synthesized GOx nanoreactors on breast tumor cell lines was studied in vitro. Both nanoreactor preparations VLP-GOx and VLP-GOx@HSA showed to be highly cytotoxic for breast tumor cell cultures. Cytotoxicity for human embryonic kidney cells was also found. The monitoring of nanoreactor treatment on triple-negative breast cancer cells showed an evident production of oxygen by the catalase antioxidant enzyme induced by the high production of hydrogen peroxide from GOx activity. The nanoreactors containing GOx activity are entirely suitable for cytotoxicity generation in tumor cells. The HSA functionalization of the VLP-GOx nanoreactors, a strategy designed for selective cancer targeting, showed no improvement in the cytotoxic effect. The GOx containing enzymatic nanoreactors seems to be an interesting alternative to improve the current cancer therapy. In vivo studies are ongoing to reinforce the effectiveness of this treatment strategy.