53pimmune related adverse events correlate with clinical outcomes in non small cell lung cancer nsclc patients treated with nivolumab in the italian expanded access programme

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Microbiocenosis of periodontal pockets of patients with generalized aggressive severe periodontitis according to real time PCR

The aim of the study was to investigate the presence of the five most aggressive periopathogens in patients with generalized aggressive severe periodontitis before treatment. A total of 86 systemic healthy people, from 11 to 35 years old, were included in the study. Real time PCR was used for detection of periopathogens. The quantity of Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola in patients with aggressive periodontitis was significantly higher than in patients with chronic periodontitis.Целью исследования было изучить содержание пяти наиболее патогенных микроорганизмов у пациентов с агрессивным генерализованным пародонтитом тяжелой степени до лечения. Всего в исследование было включено 86 соматически сохранных пациентов от 11 до 35 лет. Для детекции пародонтопатогенов использовали метод ПЦР в реальном времени. Частота выявления и количество Porphyromonas gingivalis, Tannerella forsythensis и Treponema denticola у больных агрессивным пародонтитом было статистически значимо выше, чем у пациентов с хроническим пародонтитом

Microbiological evaluation of the effectiveness of complex treatment of aggressive periodontitis with laser curettage of periodontal pockets

The aim of the study was to investigate the effectiveness of complex treatment including curettage using a diode laser in patients with generalized aggressive periodontitis. A total of 112 systemic healthy people, from 11 to 35 years old, were included in the study. The real-time Polymerase Chain Reaction (PCR) method was used for detection of periopathogens. The present study showed that the complex treatment may lead to a significant reduction of periopathogens over the 1 - year monitoring period. After the first stage of treatment identifying the most aggressive microorganisms P.g., T.f. and T.d. in an amount of more than 105 decreased from over 60 % to 32 %, 39 % and 34 % respectively. After 1 month of using diode laser incidence of these bacteria has decreased even more and reached 9 %, 19 % and 11 % respectively. Median content of anaerobic microorganisms decreased from more than 106 before treatment to 103 after 1 month of using a diode laser. The results were maintained over one year of observations with regular maintenance therapy.Целью работы было изучение эффективности комплексного лечения, включающего лазерный юоретаж, у больных с генерализованным агрессивным пародонтитом. В общей сложности 112 соматически здоровых людей в возрасте от 11 до 35 лет были включены в исследование. Метод полимеразной цепной реакции в реальном времени (ПЦР-РВ) использовали для обнаружения пародонтопатогенных бактерий. Настоящее исследование показало, что комплексное лечение приводит к существенному сокращению содержания основных пародонтопатогенов в течение 1 года наблюдения. После первого этапа лечения, идентификация наиболее агрессивных микроорганизмов P.g., T.f. и T.d. в количестве, превышающем 105, снизилась с более чем 60% до 32%, 39% и 34% соответственно. Через 1 месяц после использования диодного лазера частота встречаемости этих бактерий еще больше уменьшилась и составила 9 %, 19 % и 11% соответственно. Медианы содержания анаэробных микроорганизмов снижались с более чем 106 до лечения до 103 через 1 месяц после использования диодного лазера. Достигнутые результаты сохранялись в течение одного года наблюдений при регулярном проведении поддерживающей терапии

Early clear cell “sugar” lung cancer management. A case report and a brief literature review

A clear cell tumor is a histological entity that rarely originates outside of the kidney. We describe a rare case of a clear cell tumor of the lung, also known as “sugar cancer,” that occurred in a 74 year-old male patient, and perform a brief literature review. This report highlights the importance of an adequate disease management team, including surgeons, oncologists, and pathologists, to identify the best therapeutic approach to improve survival rates and the quality of life of patients affected by this rare disease

Intermittent β-adrenergic blockade downregulates the gene expression of β-myosin heavy chain in the mouse heart

Expression of the β-myosin heavy chain (β-MHC), a major component of the cardiac contractile apparatus, is tightly regulated as even modest increases can be detrimental to heart under stress. In healthy hearts, continuous inhibition of β-adrenergic tone upregulates β-MHC expression. However, it is unknown whether the duration of the β-adrenergic inhibition and β-MHC expression are related. Here, we evaluated the effects of intermittent β-blockade on cardiac β-MHC expression. To this end, the β-blocker propranolol, at the dose of 15mg/kg, was administered once a day in mice for 14 days. This dosing schedule caused daily drug-free periods of at least 6 h as evidenced by propranolol plasma concentrations and cardiac β-adrenergic responsiveness. Under these conditions, β-MHC expression decreased by about 75% compared to controls. This effect was abolished in mice lacking β1- but not β2-adrenergic receptors (β-AR) indicating that β-MHC expression is regulated in a β1-AR-dependent manner. In β1-AR knockout mice, the baseline β-MHC expression was fourfold higher than in wild-type mice. Also, we evaluated the impact of intermittent β-blockade on β-MHC expression in mice with systolic dysfunction, in which an increased β-MHC expression occurs. At 3 weeks after myocardial infarction, mice showed systolic dysfunction and upregulation of β-MHC expression. Intermittent β-blockade decreased β-MHC expression while attenuating cardiac dysfunction. In vitro studies showed that propranolol does not affect β-MHC expression on its own but antagonizes catecholamine effects on β-MHC expression. In conclusion, a direct relationship occurs between the duration of the β-adrenergic inhibition and β-MHC expression through the β1-AR

β-blockers reverse agonist-induced β2-AR downregulation regardless of their signaling profile

Altered β-adrenergic receptor (β-AR) density has been reported in cells, animals, and humans receiving β-blocker treatment. In some cases, β-AR density is upregulated, but in others, it is unaffected or even reduced. Collectively, these results would imply that changes in β-AR density and β-blockade are not related. However, it has still not been clarified whether the effects of β-blockers on receptor density are related to their ability to activate different β-AR signaling pathways. To this aim, five clinically relevant β-blockers endowed with inverse, partial or biased agonism at the β2-AR were evaluated for their effects on β2-AR density in both human embryonic kidney 293 (HEK293) cells expressing exogenous FLAG-tagged human β2-ARs and human lymphocytes expressing endogenous β2-ARs. Cell surface β2-AR density was measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Treatment with propranolol, carvedilol, pindolol, sotalol, or timolol did not induce any significant change in surface β2-AR density in both HEK293 cells and human lymphocytes. On the contrary, treatment with the β-AR agonist isoproterenol reduced the number of cell surface β2-ARs in the tested cell types without affecting β2-AR-mRNA levels. Isoproterenol-induced effects on receptor density were completely antagonized by β-blocker treatment. In conclusion, the agonistic activity of β-blockers does not exert an important effect on short-term regulation of β2-AR density

Heat shock factor 1 represses estrogen-dependent transcription through association with MTA1

Heat shock factor 1 (HSF1), the transcriptional activator of the heat shock genes, is increasingly implicated in cancer. We have shown that HSF1 binds to the corepressor metastasis-associated protein 1 (MTA1) in vitro and in human breast carcinoma samples. HSF1-MTA1 complex formation was strongly induced by the transforming ligand heregulin and complexes incorporated a number of additional proteins including histone deacetylases (HDAC1 and 2) and Mi2α, all components of the NuRD corepressor complex. These complexes were induced to assemble on the chromatin of MCF7 breast carcinoma cells and associated with the promoters of estrogen-responsive genes. Such HSF1 complexes participate in repression of estrogen-dependent transcription in breast carcinoma cells treated with heregulin and this effect was inhibited by MTA1 knockdown. Repression of estrogen-dependent transcription may contribute to the role of HSF1 in cancer.Fil: Khaleque, M. A.. Harvard Medical School; Estados Unidos. North South University; BangladeshFil: Bharti, A.. Boston University; Estados UnidosFil: Gong, J.. Boston University; Estados UnidosFil: Gray, P. J.. Harvard Medical School; Estados UnidosFil: Sachdev, V.. Boston University; Estados UnidosFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Stati, Arturo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Calderwood, S. K.. Boston University; Estados Unidos. Harvard Medical School; Estados Unido