Transfer of malignant traits as opposed to migration of cells: A novel concept to explain metastatic disease

Abstract Metastatic disease is believed to develop following dissemination of cells to target organs. Inability of this theory to effectively explain certain phenomena such as patterns of metastatic spread, late metastasis formation, different gene patterns between primary cancer and metastasis have brought forward the need for alternative models. Recent discoveries have strengthened the validity of theories supporting a humoral transfer of malignant traits as opposed to migration of malignant cells to explain metastatic disease in cancer patients. In light of this new evidence, we would like to highlight a model that offers a new perspective to explain cancer metastasis. In the system that we theorize, genetic material released by cancer cells would travel, either free or packed in exosomes, through the blood. Target cells located in organs deriving from the same embryological layer might uptake this genetic material due to expression of specific receptors. Interplay with the immune system would determine the fate of these oncofactors and would regulate their ability to circulate in the blood, integrate in the genome and be transcribed. We also hypothesize that the expression of cell membrane receptors such as integrins, to which cancer exosomes ligate might be mediated by inherited or acquired oncosuppressor mutations

An extension of a theorem by M. I. Freidlin to good solutions to elliptic nondivergence equations

In the context of second order linear uniformly elliptic equations with measurable coefficients, a result of Freidlin [9], which deals with homogenization type properties for elliptic equations with smooth periodic coefficients, is extended to generalized solutions for equations with measurable coefficients

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

A remark on differentiability properties of solutions of some elliptic equations

A class of nondivergence unifrmly elliptic equations with measurable coefficients is studied. The oscillation of the coefficients near a Lebesgue point is assumed to be controlled by increasing functions satisfying Dini's condition.Under this assumption, slightly weaker than that of L. A. Caffarelli [2], a pointwise estimate for "good solutions" is established and related second order differentiability properties are pointed out

A class of elliptic operators in R^3 in non divergence form with measurable coefficients

In an open cylinder of R3 a linear uniformly elliptic operator in non-divergence form, with coefficients time independent but measurable only, is investigated. Existence and uniqueness results in suitable Sobolev spaces for the Dirichlet problem are obtained

Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection

We reported that single oncosuppressor-mutated (SOM) cells turn malignant when exposed to cancer patients’ sera. We tested the possibility to incorporate this discovery into a biological platform able to detect cancer in healthy individuals and to predict metastases after tumor resection. Blood was drawn prior to tumor resection and within a year after surgery. Blood samples from healthy individuals or metastatic patients were used as negative and positive controls, respectively. Patients at risk for cancer were included in the screening cohort. Once treated, cells were injected into nonobese diabetic/severe combined immunodeficiency mice to monitor tumor growth. All samples of sera coming from metastatic patients transformed SOM cells into malignant cells. Four samples from screened patients transformed SOM cells. Further clinical tests done on these patients showed the presence of early cancerous lesions despite normal tumor markers. Based on the xenotransplants size, we were able to predict metastasis in three patients before diagnostic tests confirmed the presence of the metastatic lesions. These data show that this serum-based platform has potentials to be used for cancer screening and for identification of patients at risks to develop metastases regardless of the Tumor Node Metastasis (TNM) stage or tumor markers level