Cell therapies in ovarian cancer.

Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo, and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy

Higher Equations of Motion in Liouville Field Theory

An infinite set of operator-valued relations in Liouville field theory is established. These relations are enumerated by a pair of positive integers $(m,n)$, the first $(1,1)$ representative being the usual Liouville equation of motion. The relations are proven in the framework of conformal field theory on the basis of exact structure constants in the Liouville operator product expansions. Possible applications in 2D gravity are discussed.Comment: Contribution to the proceedings of the VI International Conference ``CFT and Integrable Models'', Chernogolovka, Russia, September 200

The Statistical Mechanics of the (2+1)-Dimensional Black Hole

The presence of a horizon breaks the gauge invariance of (2+1)-dimensional general relativity, leading to the appearance of new physical states at the horizon. I show that the entropy of the (2+1)-dimensional black hole can be obtained as the logarithm of the number of these microscopic states.Comment: 12 pages, UCD-94-32 and NI-9401

Ovarian Cancer Immunotherapy: Turning up the Heat.

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer

Is hypogammaglobulinemia a constant feature in Good's syndrome?

Thymomas are rare tumors, which can be associated to a variety of paraneoplastic syndromes, including a fatal hypogammaglobulinemia, namely Good's Syndrome (GS). Although the combination of thymoma and hypogammaglobulinemia is regarded as sufficient for diagnosis of Good's syndrome, some thymoma patients with a clear clinical picture of immunodeficiency present normal levels of immunoglobulins. We describe the case of a patient, with a 20-year history of thymoma, who underwent several operations and lines of chemotherapy, and suffered from recurrent infections, including one rare skin infection from Pseudoallescheria boydii. The patient constantly presented normal levels of gammaglobulins

Unusual skin toxicity associated with sustained disease response induced by nivolumab in a patient with non-small cell lung cancer

Introduction: Immunotherapy has shown efficacy in the treatment of different malignancies. Nivolumab, an immune checkpoint inhibitor directed against programmed death-1, has been approved for non-small cell lung cancer (NSCLC) in pretreated patients. Although it is generally well-tolerated, immunotherapy may be complicated by a wide range of immune-mediated adverse events. We describe the case of an uncommon skin toxicity arising as alopecia universalis induced by nivolumab in a patient with NSCLC. Case description: A 58-year-old man received nivolumab for metastatic NSCLC after progression to 3 lines of chemotherapy. The treatment was prescribed in June 2016, and induced a rapid and significant disease response. Nivolumab was well-tolerated until May 2017, when partial alopecia at hair and eyelashes appeared. In the next months, alopecia became complete and extended to the whole body surface. The dermatologic picture was compatible with alopecia areata. A topical steroid therapy was attempted, without benefit. The patient refused systemic treatments and is still undergoing nivolumab without new toxicities and with persistent disease response. Conclusions: This case suggests that alopecia areata may be a rare immune-related adverse event of immune checkpoint agents. Its late onset in our patient is uncommon and unexpected, underlining that the risk of nivolumab-induced toxicity is not limited to the beginning of treatment. Despite its rarity, alopecia areata should be considered in the range of adverse events potentially induced by immune checkpoint inhibitors even in the long term. Potential association between toxicity and efficacy of immunotherapy in NSCLC warrants further investigation

Peripheral relaxant activity of apomorphine and of a D1 selective receptor agonist on human corpus cavernosum strips

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Switchable Solvent Selective Extraction of Hydrophobic Antioxidants from Synechococcus bigranulatus

Hydrophobic molecules, in particular, carotenoids, have been directly extracted from Synechococcus bigranulatus ACUF680 by means of secondary amine switchable solvent N-ethylbutylamine (EBA) without any other pretreatment. EBA was able to extract hydrophobic molecules from both fresh and frozen biomass at the same extent of the conventional procedure (about 20% of dry biomass). In particular, selective extraction of a zeaxanthin-enriched fraction (green fraction, GF) and a β-carotene-enriched fraction (orange fraction, OF) was obtained. The ratio between zeaxanthin and β-carotene was 4.4 ± 1.5 for GF, 0.07 ± 0.06 for OF, and about 1 for conventional extraction. These fractions showed in vitro antioxidant activity (IC50 values of 0.056 ± 0.013 and 0.024 ± 0.008 mg mL-1 for GF and OF, respectively) and biocompatibility on immortalized cells. Moreover, OF and GF were able to protect cells from oxidative stress, both before and after thermal treatment. Results clearly indicate that EBA is a good candidate to specifically extract β-carotene and zeaxanthin from the wet biomass of S. bigranulatus without affecting their biological activity. Skipping energy-intensive operations to break the cells and using either fresh or frozen biomass may be the driving factors to use EBA switchable solvent on an industrial scale

Effects of Topical Application of CHF6467, a Mutated Form of Human Nerve Growth Factor, on Skin Wound Healing in Diabetic Mice

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