Understanding the effect of mechanical forces on ovarian cancer progression.

OBJECTIVE: Mechanical forces including tension, compression, and shear stress are increasingly implicated in tumor progression and metastasis. Understanding the mechanisms behind epithelial ovarian cancer (EOC) progression and metastasis is critical, and this study aimed to elucidate the effect of oscillatory and constant tension on EOC. METHODS: SKOV-3 and OVCAR-8 EOC cell lines were placed under oscillatory tension for 3 days and compared to cells placed under no tension. Cell proliferation, migration, and invasion were analyzed while RNAseq and Western Blots helped investigate the biological mechanisms underlying the increasingly aggressive state of the experimental cells. Finally, in vivo experiments using SCID mice assisted in confirming the in vitro results. RESULTS: Oscillatory tension (OT) and constant tension (CT) significantly increased SKOV-3 proliferation, while OT caused a significant increase in proliferative genes, migration, and invasion in this cell line. CT did not cause significant increases in these areas. Neither OT nor CT increased proliferation or invasion in OVCAR-8 cells, while both tension types significantly increased cellular migration. Two proteins involved in metastasis, E-cadherin and Snail, were both significantly affected by OT in both cell lines, with E-cadherin levels decreasing and Snail levels increasing. In vivo, tumor growth and weight for both cell types were significantly increased, and ascites development was significantly higher in the experimental OVCAR-8 group than in the control group. CONCLUSIONS: This study found that mechanical forces are influential in EOC progression and metastasis. Further analysis of downstream mechanisms involved in EOC metastasis will be critical for improvements in EOC treatment.

Manipulating the Wnt/ß-catenin signaling pathway to promote anti-tumor immune infiltration into the TME to sensitize ovarian cancer to ICB therapy.

OBJECTIVE: Immune checkpoint blockade (ICB) therapy shows limited efficacy in ovarian cancers due to the "cold" immune phenotype surrounding these tumors. Previous studies have shown that in ovarian cancer Wnt/ß-catenin pathway activation contributes to this immune phenotype. Here, we evaluated the anti-tumor and immune-enhancing properties of the Wnt inhibitor, CGX-1321, used alone or in combination with either DKN-01 or anti-PD-1 therapy, in pre-clinical ovarian cancer models. METHODS: The parental ID8 murine ovarian cancer model harboring a knock-out of p53 (ID8p53-/-) and MISIIR-Tag spontaneous ovarian cancer models were used to test the effects of CGX-1321 alone or in combination therapies on tumor burden and immune cell landscape in the tumor microenvironment (TME). Flow cytometry and NanoString analyses were used to characterize the changes in tumor-intrinsic signaling and immune-related profiles in the TME of ovarian cancer in response to treatments. RESULTS: CGX-1321 significantly reduced tumor burden and constrained tumor progression in the ID8p53-/- and MISIIR-Tag models. Furthermore, CGX-1321 increased infiltrating CD8+ T cells in the TME. Combining CGX-1321 with either DKN-01 or anti-PD-1 therapy also decreased tumor burden and increased CD8+ T cell infiltration in the omentum TME but did not do so to a greater extent that CGX-1321 monotherapy. CONCLUSIONS: CGX-1321 significantly reduced tumor burden and enhanced CD8+ T cell levels in ovarian cancer, nevertheless the addition of DKN-01 or anti-PD-1 therapies did not enhance these effects of CGX-1321. Further investigation is needed to determine if CGX-1321 + DKN-01 combination treatment sensitizes pre-clinical ovarian cancer to ICB therapy.

Supermarket shopping death: the role of forensic investigations in plastic bag suffocation.

Background: Plastic bag suffocation may represent a very complex enigma for the forensic pathologist. The aim of this work is to highlight how the resolution of plastic bag suffocation cases is possible through the use of various forensic investigations, including psychological one (psychological autopsy) and toxicological examinations, in order to be able to define the manner of death. Case report: A 70-year-old man was found by his daughter lying on the bed, with his head inside a plastic bag knotted around his neck. The daughter claimed to have immediately removed the bag, but the father was already dead. An autopsy was performed. The clinical history of the victim was analysed in search of reason that could lead to suicide. The statements of the people on the death scene were examined. Results were compared with the scientific literature: a literature review was performed on the search engine Pubmed, Scopus and Google Scholar using the keywords "plastic bag suffocation" and "death". The autopsy showed no typical signs of asphyxial death. Toxicological examinations revealed benzodiazepines in the urine. Investigations revealed that the victim had been suffering from severe depression. Conclusions: The literature review confirmed that the most used wrapper is the supermarket shopping bag. We emphasize that plastic bag suffocation is a very quick event that does not leave any evident sign: this rapidity does not allow to appreciate the typical elements of asphyxiated death (petechiae, cyanosis). It seems that the fatal mechanism is a cardio-inhibitory, rather than a hypoxic process.

Response to anti-DKK1 therapy in uterine carcinosarcoma: A case report.

Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/ß-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites. Our findings highlight the importance of analyzing tissue from the primary tumor as well as metastatic lesions, especially if there is a discrepancy in their response to treatment.

Kambo: Natural drug or potential toxic agent? A literature review of acute poisoning cases.

Kambo is the name of a natural substance derived from the glandular secretions of the amphibian Phyllomedusa bicolor, a species native to regions in South America. The communities living in these areas administer the substance generally transdermally during rituals for religious-purifying purposes, producing small skin burns. The scientific literature has reported some cases of intoxication following the use of Kambo but this aspect is still poorly understood. In fact, no shared therapy protocols exist for these events nor any real legislation on Kambo. The purpose of this work was to examine all cases of acute intoxication resulting from the administration of Kambo and published over the last 10 years, illustrating clinical signs, laboratory findings, instrumental tests, and therapy. The several cases identified in our review confirm that acute Kambo intoxication can occur, with serious and life-threatening effects. We developed a protocol aimed at the early diagnosis of cases of suspected acute intoxication by creating a treatment algorithm. The study aims to investigate the pathophysiology of these events in humans, proposing a protocol for the diagnosis and treatment of these cases that can be used by healthcare professionals.

The Marigliano-Cacciafesta polypathology scale (MCPS): a tool for predicting the risk of developing disability.

The purpose of the work was to verify whether our MCPS can be a tool for predicting the risk of developing disabilities. We considered 45 elderly subjects divided into three groups of 15 subjects each. Group 1 consisted of cases with a "moderate-severe" degree of polypathology, with no associated condition of disability evaluated by means of the activities of daily living (ADL). Group 2 contained cases with a "moderate" degree of polypathology (with no associated condition of ADL disability). The Group 3 was the control group with a "mild" degree of polypathology (with no disability associated with ADL). All subjects were re-evaluated after 6 and 12 months. Both Groups 1 and 2 of cases over time developed greater disabilities, compared to the control Group 3; in particular, the subjects with "moderate-severe" polypathology were more disabled after 12 months.

The Marigliano-Cacciafesta polypathological scale: a tool for assessing fragility.

The aim of our studies was to establish a standard method of assessment that allows an early identification of frailty in the elderly, i.e., to predict who are at risk of developing disabilities, in order to be able to intervene with preventive global and individualized measures. A new multidimensional scale called Marigliano-Cacciafesta polypathological scale (MCPS) was used on 180 elderly people, together with the Barthel index (BI), the global evaluation functional index (GEFI), the geriatric depression scale (GDS), the mini mental state examination (MMSE), the mini nutritional assessment (MNA), and the Tinetti test. A strongly significant statistical correlation was found between the MCPS and the nutritional state, mood level, motor functionality, level of disability and global functionality. As the fragile patients are at a risk to develop disabilities, we think that our scale can be a significant contribution to the multidimensional geriatric assessment (MGA), aimed at identifying and quantifying the parameter of fragility of each patient, an information which should be known, if we intend to introduce preventive measures.

[Neoplastic inflammation: role of capillary electrophoresis]. / Infiammazioni neoplastiche: ruolo dell'elettroforesi capillare.

Two electrophoretical methods have been compared, in order to evaluate the most precise and sensitive one as to recognize initial inflammatory conditions also of tumoral nature. Consequently, among 5,000 patients observed during one year, only 500 cases have been considered with pathologic electrophoretic diagram and, among those, 245 cases of which alteration of the electrophoretic diagram concerned the alfa 1 band and the alfa 2 band; among the latter only 127 cases were diagnosed various tumors. It is deduced from the obtained results that there is better sensitiveness with the capillary method, which is evidenced in the more substantial increase of the alfa 1. Such method allows, precociously, to put in evidence a possible presence of inflammation, induced by any kind of tumor, even in absence of positiveness of the specific tumoral markers, in 38% of examined cases.

Pólipos endometriales en pacientes posmenopáusicas tratadas con tamoxifeno / Endometrial polyps in posmenopause patients:trated with tamoxifen

En la presente comunicación informamos sobre 13 pacientes tratadas con tamoxifeno como terapía adyuvante por carcinoma de mama y que presentaron en su evolución pólipos endometriales, Cauatro de las pacientes reportadas presentaron sangrado endometrial y tres de ellas aumento del tamaño uterino. Los conocimientos acerca de la acción del tamoxifeno sobre el endometrio son escasos; sin embargo, la actividad agonista parcial de esta droga, que ha sido observada en pacsientes posmenopáusicas, es posible que contribuya en la hiperplasia quística observada en los pólipos debido a un efecto agonista estrogénico. La valoración de la posible asociación entre el tamoxifeno y patología endometrial requiere de futuros estudios con seguimiento a largo plazo

Pólipos endometriales en pacientes posmenopáusicas tratadas con tamoxifeno / Endometrial polyps in posmenopause patients:trated with tamoxifen

En la presente comunicación informamos sobre 13 pacientes tratadas con tamoxifeno como terapía adyuvante por carcinoma de mama y que presentaron en su evolución pólipos endometriales, Cauatro de las pacientes reportadas presentaron sangrado endometrial y tres de ellas aumento del tamaño uterino. Los conocimientos acerca de la acción del tamoxifeno sobre el endometrio son escasos; sin embargo, la actividad agonista parcial de esta droga, que ha sido observada en pacsientes posmenopáusicas, es posible que contribuya en la hiperplasia quística observada en los pólipos debido a un efecto agonista estrogénico. La valoración de la posible asociación entre el tamoxifeno y patología endometrial requiere de futuros estudios con seguimiento a largo plazo