Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field, and can lead to development of novel therapeutic options. Recent findings A series of biological processes induced by TTFields to exert anti-cancer effects have been identified, and applications of TTFields in oncology have been increasingly reported. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategies, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

Background: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS. Aims: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy / fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy. Methods and Results: Patients >18-years-old with rHGG (WHO grade III and IV) receiving ICI+SBRT or ICI monotherapy between 1/1/16-1/1/19 were included. Adverse events, 6-month PFS and overall survival (OS) were assessed. Log-rank tests were used to evaluate PFS and OS. Histogram analyses of apparent diffusion coefficient maps and dynamic contrast-enhanced magnetic resonance perfusion metrics were performed. Twenty-one patients with rHGG (ICI+SBRT: 16; ICI: 5) were included. The ICI+SBRT and ICI groups received a mean 7.25 and 6.2 ICI cycles, respectively. There were five grade 1, one grade 2 and no grade 3-5 AEs in the ICI+SBRT group, and four grade 1 and no grade 2-5 AEs in the ICI group. Median PFS was 2.85 and 1 month for the ICI+SBRT and ICI groups; median OS was 7 and 6 months among ICI+SBRT and ICI groups, respectively. There were significant differences in pre- and post-treatment tumor volume in the cohort (12.35 vs. 20.51; p=0.03), but not between treatment groups. Conclusions: In this heavily pretreated cohort, ICI with re-irradiation utilizing SBRT was well tolerated. Prospective studies are warranted to evaluate potential therapeutic benefits to re-irradiation with ICI+SBRT in rHGG.

Background: Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which can arise upon viral integration into the host genome and concurrent loss of viral regulatory gene E2. Gene-based delivery approaches show that E2 reintroduction reduces proliferative capacity and promotes apoptosis in vitro. This work explored if our calcium-dependent protein-based delivery system, TAT-CaM could deliver functional E2 protein directly into cervical cancer cells to limit proliferative capacity and induce cell death. Methods: TAT-CaM and the HPV16 E2 protein containing a CaM-binding sequence (CBS-E2) were expressed and purified from E. coli. Calcium-dependent binding kinetics were verified by Biolayer Interferometry. Equimolar TaT-CaM:CBS-E2 constructs were delivered into the HPV16+ SiHa cell line and uptake verified by confocal microscopy. Proliferative capacity was measured by MTS assay and cell death was measured by release of lactate dehydrogenase. As a control for specificity to HPV+ cells, human microvascular cells (HMECs) were used. Results: TAT-CaM bound CBS-E2 with high affinity in the presence of calcium and rapidly disassociated in its absence. After introduction by TAT-CaM, E2 was detected in cellular interiors by orthogonal projects taken at the depth of the nucleus. In dividing cells, E2 relocalized to regions associated with the mitotic spindle. Cells receiving a single daily dose of CBS-E2 for 4 days showed a significant reduction in metabolic activity at low doses and cell death at high doses compared to controls. This phenotype was retained for 7 days with no further treatments. When subcultured at day 12, treated cells regained their proliferative capacity. Conclusions: Using the TAT-CaM platform, bioactive E2 protein was delivered into living cervical cancer cells, inducing senescence and cell death in a time- and dose-dependent manner. These results suggest that this nucleic acid and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics.

Background Multiple myeloma (MM) patients have variable responses to mRNA vaccination to COVID-19. Little is known regarding their vaccine-induced antibody levels over time. Methods We monitored spike IgG antibody levels over 24 weeks among a subset of 18 MM patients who showed a full response after two mRNA vaccinations. MM patients had a more rapid decline in antibody levels as compared to 8 healthy controls, with power law half-lives of 72 days (versus 107 days) and exponential half-lives of 37 days (versus 51 days). Results The patients with longer SARS-CoV-2 antibody half-lives were more likely to have undetectable monoclonal protein than those with shorter half-lives, suggesting better disease control may correlate with longer duration of vaccine-induced antibodies. Regardless, by 16 weeks post-second dose of mRNA vaccination, the majority of patients had antibody levels below 250 binding arbitrary units per milliliter, which would be unlikely to contribute significantly to preventing COVID-19. Conclusions Thus, even MM patients who respond adequately to vaccination are likely to require more frequent booster doses than the general population.

Objective: Immunochemotherapy has become a new treatment for advanced esophageal squamous cell carcinoma (ESCC). We aimed to study the clinical efficacy and toxicity of immunochemotherapy based on PD-1/PD-L1 compared with chemotherapy alone in the treatment of advanced ESCC, focusing on analyzing the influence of PD-L1 expression level. Methods: Randomized controlled trials comparing PD-1/PD-L1 based immunochemotherapy wirh chemotherapy alone for advanced ESCC were included. We extracted efficacy data [objective response rate (ORR), disease control rate (DCR), overall survival (OS) rate, progression-free survival (PFS) rate] and safety data (treatment-related adverse events, treatment-related mortality) and performed meta-analyses. Results: 5 articles were included. Compared with chemotherapy alone, the ORR and DCR of immunochemotherapy increased by 2.05 times and 1.54 times, respectively. Overall, patients receiving immunochemotherapy had a significant long-term survival advantage [OS: hazard ratio (HR)=0.68, 95% hazard ratio (CI) 0.61-0.75; PFS: HR=0.62, 95%CI 0.55, 0.70, respectively]. Even with PD-L1 tumor proportion score <1%, immunochemotherapy also showed a significant survival advantage [OS: HR=0.65, 95%CI 0.46-0.93; PFS: HR=0.56, 95%CI 0.46-0.69, respectively]. However, for PD-L1 combined positive score (CPS)<1, the survival advantage of immunochemotherapy was not significant [OS: HR=0.89, 95%CI 0.42-1.90; PFS: HR=0.71, 95%CI 0.47-1.08, respectively]. The toxicity of immunochemotherapy was higher than that of chemotherapy alone, but there was no statistical difference in treatment-related mortality (odds ratio=1.11, 95%CI 0.67-1.83). Conclusions: In this study, PD-1/PD-L1 based immunochemotherapy significantly could improve survival outcomes in patients with advanced ESCC. For patients with CPS<1, the survival advantage of immunochemotherapy was not significant. The toxicity of immunochemotherapy was acceptable.

Background. Endomertrial adenocarcinoma (EC) with early stage, high grade is rare seen metastasis. Here, we describe a unique case of axillary lymph node and breast metastasis from high grade endomertrial adenocarcinoma after a 4-year period. Cases. We presented a case of a 60-year-old woman with EC and received surgery in 2013. However, a metastatic tumor appeared at the axillary lymph node and the breast 4 years after surgery. Then she received an operation and 6 cycles adjuvant chemotherapy. 31 months following, she is alive without disease. Conclusions. A correct diagnosis should be made by combining the patient’s past clinical history, morphologic and immunohistochemical test results. Knowledge of this rare metastatic site will help the physician make the correct diagnosis.

Background: The role and mechanism of centromeric protein N (CENPN), which has been associated with the development of various cancer types, are yet unclear in Gastric adenocarcinoma (STAD). Methods: Data from The Cancer Genome Atlas and Genotype Tissue Expression were used to examine the expression of CENPN in STAD and neighboring tissues. Xiantao Academic was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on CENPN. By reviewing TCGA database, the relationship between CENPN expression and immune cell infiltration was assessed. The expression of CENPN in STAD and surrounding tissues was confirmed by immunohistochemical staining, and the correlation between CENPN expression and clinicopathological characteristics was examined. CENPN was depleted in AGS cells with siRNAs, and its impact on proliferation was measured by CCK-8 and EdU assays. Following siRNA transfection, flow cytometry was performed to identify cell cycle and apoptotic alterations in AGS cells. Results: CENPN was highly expressed in STAD tissues. The degree of invasion, TNM stage, and lymph node metastases were all substantially linked with CENPN expression. GO|KEGG Enrichment analysis revealed that CENPN was essential for the cell cycle, DNA replication, chromosomal segregation, and nuclear division, among other important signaling pathways. Further investigation revealed a positive correlation between CENPN expression and Th2 cells and NK CD56dim cells and a negative correlation between CENPN expression and mast cells , pDC cells,NK cells and B cells. When CENPN expression in AGS cells was knocked down, cell proliferation dramatically reduced, and the percentage of cells in the S and G2-M phases decreased significantly. In addition, compared to the control group, the proportion of apoptotic AGS cells significantly increased after downregulating the expression level of CENPN. Conclusion: According to our data, CENPN acts as an oncogene in STAD and may be a viable therapeutic target.

Introduction: Monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells that produces a monoclonal protein. To describe the epidemiological and immunochemical characteristics of monoclonal gammopathies diagnosed during a nineteen-year period in a Moroccan teaching hospital was the main objective of this study. Methods: This study was performed from January 2000 to August 2019. It was a retrospective study that included of 545 Moroccan patients with monoclonal gammopathy. Results: The patients who participated in the study, 374 (68.6%) were male and 171(31.4%) were female, with a mean ±SD age of 62.24±13.14 years. The most frequent reasons for admission were bone pain (41,60%), renal failure (19.08%), alteration of the general condition (12.21%) and anemia (10.69). Plasma cell proliferative disorders in our study were as follow, multiple myeloma (MM) (45.65%), Monoclonal gammopathies of undetermined significance (MGUS) (39.05%), Waldenstrom’s macroglobulinemia(5.58%), Lymphoma (2.27%+1.2%), Chronic Lymphocytic Leukemia (2.48%), Plasma cell leukemia (1.86%), Plasmacytoma (0.62%), POEMS syndrome (0.41%), and Amyloidosis (0.84%). The most frequent isotypes in MM were the IgGκ (62) 36.5%, IgGλ(52)30.6%, IgAκ(27)15.9% and the IgAλ (19)11.2%. It is also worthy of note, that Free light chain MM represents 20% of all cases of MM. Conclusions: This is the largest Moroccan cohort, it included 545 patients. The results of this study point to the need for an early diagnosis of monoclonal gammopathies in the Moroccan population