Development of a Gene Risk Signature for Patients of Pancreatic Cancer

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

Nanomedicine-enabled chemotherapy-based synergetic cancer treatments

Chemotherapy remains one of the most prevailing regimens hitherto in the fight against cancer, but its development has been being suffering from various fatal side effects associated with the non-specific toxicity of common chemical drugs. Advances in biomedical application of nanomedicine have been providing alternative but promising approaches for cancer therapy, by leveraging its excellent intrinsic physicochemical properties to address these critical concerns. In particular, nanomedicine-enabled chemotherapy has been established as a safer and promising therapeutic modality, especially the recently proposed nanocatalytic medicine featuring the capabilities to generate toxic substances by initiating diverse catalytic reactions within the tumor without directly relying on highly toxic but non-selective chemotherapeutic agents. Of special note, under exogenous/endogenous stimulations, nanomedicine can serve as a versatile platform that allows additional therapeutic modalities (photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), etc.) to be seamlessly integrated with chemotherapy for efficacious synergistic treatments of tumors. Here, we comprehensively review and summarize the representative studies of multimodal synergistic cancer treatments derived from nanomedicine and nanocatalytic medicine-enabled chemotherapy in recent years, and their underlying mechanisms are also presented in detail. A number of existing challenges and further perspectives for nanomedicine-synergized chemotherapy for malignant solid tumor treatments are also highlighted for understanding this booming research area as comprehensively as possible. Graphical Abstract

Second primary malignancy among malignant solid tumor survivors aged 85 years and older

The cancer burden in the oldest old has increased rapidly. This study aimed to investigate the epidemiology of second primary malignancy (SPM) in malignant solid tumor survivors aged 85 years and older utilizing the Surveillance, Epidemiology, and End Results (SEER) database. A total of 128,466 malignant solid tumor patients had been identified between 2000 and 2011, including 6774 patients who developed a SPM. The overall crude incidence of developing a SPM was 5.3%. Considering death as a competing event, the 3, 5, and 10-year cumulative incidence was 1.9%, 3.2%, and 5.4%, respectively. Relative younger age, male gender, surgery history, local stage and first primary malignancy (FPM) site located in the urinary system were related to higher cumulative incidence. A median time interval of 24.0 months was found between diagnosis of FPM and SPM. The most common SPM site was digestive system, whereas the least common was oral cavity and pharynx. The median overall survival (OS) was 49.0 months, and the median survival after SPM was 13.0 months. Relative older age, male gender and black race were associated with worse OS and survival after SPM, as well as higher hazard ratios of death. In conclusions, this study performed a comprehensive analysis of SPM among malignant solid tumor survivors aged 85 years and older. Additional studies are needed to characterize the specific cancer type of interest.

Аngiogenesis in Uveal Melanoma

Uveal melanoma (UM) is less than 0.5 % in the spectrum of human tumors, and less than 5 % among all types of melanoma, therefore, it is considered to be rare. At the same time, UM is recognized as the most common intraocular malignant neoplasm. Its share among all intraocular tumors is 60 %. Radical local treatments are considered effective, but the frequency of distant metastases is unacceptably high, and the life expectancy of patients with metastatic stage of the disease is short and on average is 4–5 months. Survival rates have remained stable for the past 40 years, reflecting the lack of current effective system strategies. The tumor metastasizes in a haematogenic way, so it is not surprising that angiogenesis is constantly in the focus of scientific developments. The importance of studying angiogenesis in UM is due to the ability to predict based on the quantitative indicators of vessels inside the tumor and to search for potential targets of antiangiogenic therapy in the future. The authors used two methods of studying angiogenesis in UM: morphological with quantitative vascular counting and immunohystochemical method (IHC) with markers of endothelial cells CD34 and CD31, VIII factor, VEGF molecules, bFGF, thrombospondin and others. IHC-staining of vessels in UM allowed to visualize vessels that were not visible due to intense pigmentation of tumors or compression of vessels by tumor cells. Comparison of data obtained by the two methods demonstrated the advantages of IHS analysis over classical morphological methods. It was found that UM, as a malignant solid tumor, differs high averages of vessels per unit area. The highest rates are recorded in epitheloid melanoma, which is associated with a higher rate of growth, and more frequent metastasis, compared to similar rates in revere cell melanoma. The number of vessels per unit area in the viewing area in UM decreases with age, which explained the development of metastases in more distant after enucleation time in elderly patients. Differences in vascular density in tumors of different localization were revealed and described: they were the maximum in pre-equatorial tumors, and minimal — in iris tumors.

Comprehensive Analysis and Risk Identification of Pulmonary Cryptococcosis in Non-HIV Patients

Pulmonary cryptococcosis in the non-human immunodeficiency virus-infected population is uncommon. We aimed to explore the relevance between clinical presentations, radiological findings, and comorbidities and identify the outcome predictors. A total of 321 patients at Taichung Veterans General Hospital between 2005 and 2019 were included; of them, 204 (63.6%) had at least one comorbidity, while 67 (20.9%) had two or more. The most common comorbidities were diabetes mellitus (27.4%), malignant solid tumor (19.6%), autoimmune disease (15.6%), and chronic kidney disease (8.4%). Patients experiencing comorbidity, particularly those with multiple comorbidities, had a higher multilobar and extrapulmonary involvement, which could explain these patients being more symptomatic. In the overall population, extrapulmonary involvement independently predicted disease recurrence and death. Amongst patients with isolated pulmonary cryptococcosis, age, cryptococcal antigen (CrAg) titer in blood, and comorbidities not only predicted the extent of disease, but also its outcome. Of note, patients simultaneously with age ≥ 65 years, CrAg test ≥ 1:128, and multiple comorbidities had the lowest disease control of antifungal treatment (76.9%) and the highest rate of disease recurrence or death from any cause (40.0%). In conclusion, approximately two-thirds of patients had at least one underlying comorbidity. In addition to extrapulmonary involvement, old age, high CrAg titer in blood, and multiple comorbidities could act as risk factors for predicting the extent of disease and outcome.

Enzymatic Spermine Metabolites Induce Apoptosis Associated with Increase of p53, Caspase-3 and miR-34a in Both Neuroblastoma Cells, SJNKP and the N-Myc-Amplified Form IMR5

Neuroblastoma (NB) is a common malignant solid tumor in children and accounts for 15% of childhood cancer mortality. Amplification of the N-Myc oncogene is a well-established poor prognostic marker in NB patients and strongly correlates with higher tumor aggression and resistance to treatment. New therapies for patients with N-Myc-amplified NB need to be developed. After treating NB cells with BSAO/SPM, the detection of apoptosis was determined after annexin V-FITC labeling and DNA staining with propidium iodide. The mitochondrial membrane potential activity was checked, labeling cells with the probe JC-1 dye. We analyzed, by real-time RT-PCR, the transcript of genes involved in the apoptotic process, to determine possible down- or upregulation of mRNAs after the treatment on SJNKP and the N-Myc-amplified IMR5 cell lines with BSAO/SPM. The experiments were carried out considering the proapoptotic genes Tp53 and caspase-3. After treatment with BSAO/SPM, both cell lines displayed increased mRNA levels for all these proapoptotic genes. Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis.

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.

Combination immunotherapy using G-CSF and oncolytic virotherapy reduces tumor growth in osteosarcoma

BackgroundOsteosarcoma is the most common malignant solid tumor that affects bones, however, survival rates of patients with relapsed osteosarcoma have not improved in the last 30 years. Oncolytic virotherapy, which uses viruses designed to selectively replicate in cancer cells, has emerged as a promising treatment for solid tumors. Our group uses mesenchymal stem cells (MSCs) to transport oncolytic adenoviruses (OAds) to the tumor site, a therapeutic strategy called Celyvir. This treatment has been already applied in human patients, canine patients and different mouse models. In parallel, previous results have probed that administration of granulocyte-colony stimulating factor (G-CSF) increased immune infiltration in tumors. We then hypothesized that the mobilization of immune cells by G-CSF may increase the antitumor efficacy of Celyvir treatment by increasing the immune infiltration into the tumors.MethodsIn this study, we use a murine version of Celyvir consisting in murine MSCs carrying the murine OAd dlE102—here called OAd-MSCs—in an immunocompetent model of osteosarcoma. We tested the antitumoral efficacy of the combination of OAd-MSCs plus G-CSF.ResultsOur results show that treatment with OAd-MSCs or the union of OAd-MSCs with G-CSF (Combination) significantly reduced tumor growth of osteosarcoma in vivo. Moreover, treated tumors presented higher tumor infiltration of immune cells—especially tumor-infiltrating lymphocytes—and reduced T cell exhaustion, which seems to be enhanced in tumors treated with the Combination. The comparison of our results to those obtained from a cohort of pediatric osteosarcoma patients showed that the virotherapy induces immunological changes similar to those observed in patients with good prognosis.ConclusionsThe results open the possibility of using cellular virotherapy for the treatment of bone cancers. Indeed, its combination with G-CSF may be considered for the improvement of the therapy.

Anti-glomerular basement membrane nephritis with bronchial carcinoma: a case report

Renal insufficiency is common among patients with various types of malignant tumors. However, the occurrence of anti-glomerular basement membrane (GBM) nephritis in a patient with a malignant tumor is relatively rare. Here, we describe a patient with bronchial carcinoma who exhibited acute kidney injury, hematuria, and non-nephrotic-range proteinuria. The patient had positive serum anti-GBM antibody findings and biopsy-proven anti-GBM nephritis. This is a rare instance of anti-GBM nephritis in a patient with a malignant solid tumor. Neoplasia was presumed to contribute to the development of anti-GBM nephritis through secretion of tumor-related antigens or unusual exposure to GBM.