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Rosario Mazzola Giulio Francolini Luca Triggiani Giuseppe Napoli Francesco Cuccia Luca Nicosia Lorenzo Livi Stefano Maria Magrini Matteo Salgarello Filippo Alongi 《Clinical genitourinary cancer》2021,19(3):230-236
BackgroundThe present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)–guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC).Materials and MethodsInclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered.ResultsA total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET–guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT.ConclusionIn the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated. 相似文献
3.
Lorenzo Alibardi 《Developmental dynamics》2022,251(9):1404-1413
An evolutionary hypothesis explaining failure of regeneration among vertebrates is presented. Regeneration derives from postembryonic processes present during the life cycles of fish and amphibians that include larval and metamorphic phases with broad organ reorganizations. Developmental programs imprinted in their genomes are re-utilized with variations also in adults for regeneration. When vertebrates colonized land adopting the amniotic egg, some genes driving larval changes, and metamorphosis were lost and new genes evolved, further limiting regeneration. These included neural inhibitors for maintaining complex nervous systems, behavior and various levels of intelligence, and adaptive immune cells. The latter, that in anamniotes are executioners of metamorphic reorganization, became intolerant to embryonic-oncofetal-antigens impeding organ regeneration, a process that requires de-differentiation of adult cells and/or expansion of stem cells where these early antigens are formed. The evolution of terrestrial lifecycles produced vertebrates with complex bodies but no longer capable to regenerate their organs, mainly repaired by regengrow. Efforts of regenerative medicine to improve healing in humans should determine the diverse developmental pathways evolved between anamniotes and amniotes before attempting genetic manipulations such as the introduction of “anamniote regenerative genes” in amniotes. This operation may determine alteration in amniote developmental programs leading to teratomes, cancer, or death. 相似文献
4.
Nikhat Parveen Mark C. Fernandez Austin M. Haynes Rui-Li Zhang B. Charmie Godornes Arturo Centurion-Lara Lorenzo Giacani 《Vaccine》2019,37(13):1807-1818
Background
Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens.Methods
To test our hypothesis, we engineered non-infectious Borrelia burgdorferi strains to express the tp0897 (tprK) and tp0435 genes of Treponema pallidum subsp. pallidum and immunized two groups of rabbits by injecting recombinant strains intramuscularly with no adjuvant. TprK is a putative integral outer membrane protein of the syphilis agent, while tp0435 encodes the highly immunogenic T. pallidum 17-kDa lipoprotein, a periplasmic antigen that was also shown on the pathogen surface. Following development of a specific host immune response to these antigens as the result of immunization, animals were challenged by intradermal inoculation of T. pallidum. Cutaneous lesion development was monitored and treponemal burden within lesions were assessed by dark-field microscopy and RT-qPCR, in comparison to control rabbits.Results
Partial protection was observed in rabbits immunized with B. burgdorferi expressing TprK while immunity to Tp0435 was not protective. Analysis of the humoral response to TprK antigen suggested reactivity to conformational epitopes.Conclusions
Immunization with native antigens might not be sufficient to obtain complete protection to infection. Nonetheless we showed that non-infectious B. burgdorferi can be an effective carrier to deliver and elicit a specific host response to T. pallidum antigens to assess the efficacy of syphilis vaccine candidates. 相似文献5.
Danilo Bontadi Lorenzo Bergamo Paola Torri Pietro Antonio Patan Antonella Bertoldi Ubaldo Lonardi 《La Medicina del lavoro》2020,111(5):404
«Effectiveness of the measures aimed at containing Sars-cov-2 virus spreading in work settings: a survey in companies based in the Veneto region of Italy».Introduction:During the Sars-Cov-2 pandemic, occupational health physicians worked to respond to different needs of workers, employers, and health authorities. In collaboration with the Prevention Department of the Veneto region of Italy, a survey was promoted in nine manufacturing companies in the province of Padua, to investigate the prevalence of asymptomatic SarsCov-2 virus and the immunological status of 1,267 workers.Scope:The study was aimed at verifying the effectiveness of measures to contain the virus spread among workers in the workplace as required by the agreement between the social partners signed on March 14, 2020.Methods:The survey was carried out at workplaces by trained health physicians and almost all company workers enrolled on a voluntary basis. Each worker was tested for viral RNA using nasopharyngeal swab and for IgM and IgG antibodies by drawing venous or capillary blood, according to the availability of tests at that difficult period.Results:Swab-positive workers were 0.3%, and subjects with positive serological tests were 1.6% of the total workers examined.Discussion:The diagnostic test is based on the search for viral RNA through nasopharyngeal swab. To evaluate the immunological status of workers the CLIA or Elisa quantitative serological test should be preferred. Measures to contain the virus spreading at the workplace seem to be effective, as working settings do not entail any additional risk of SarsCov-2 infection.Key words: COVID-19, epidemiology, prevention at workplace 相似文献
6.
Chiara Tanzi Gaia Fallani Francesco Magnani Giovanni Marozza Silvia Pizzarotti Bruno Zoppi Davide Lazzeroni Lorenzo Brambilla Paolo Coruzzi Luca Moderato 《La Medicina del lavoro》2020,111(2):107
Background:Cardiovascular diseases (CVD), particularly the ischemic heart disease, are a growing public health issue. In addition, the return to work after an acute cardiovascular attack represents a complex challenge.Objectives:To evaluate utility and safety of cardiopulmonary exercise testing (CPET), particularly performed “on site”, to promote a return to work in line with the residual working capacity.Methods:Fifty-nine workers affected by a major cardiovascular event, aged 18-63 years, have been enrolled between 2015 and 2018. All the patients underwent a CPET in outpatient clinic. Eleven workers also underwent the “on site” CPET, recorded during their working activities.Results:Outpatient clinic CPET outcomes (i.e. normal, mild impairment or moderate/severe impairment of cardiopulmonary function) were associated with the subjective perception of workers’ health status after returning to work. The “on site” CPET was found to be safe and reliable to promote a personalized return to work of patients. In 7 out of 11 patients, the values of O2 consumption (VO2) during the working activity were higher than 40% of VO2 max as obtained from laboratory CPET.Conclusions:This study provides evidence for safety and usefulness of “on site” CPET for a personalized statement of fitness for work. This may facilitate the job retention of patients characterized by a high risk of unnecessary job loss. The use of CPET represents a first step of energy expenditure evaluation associated with specific working tasks.Key words: Acute coronary syndrome, cardiopulmonary exercise testing, return to work 相似文献
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Thais Basili Higinio Dopeso Sarah H. Kim Lorenzo Ferrando Fresia Pareja Arnaud Da Cruz Paula Edaise M. da Silva Anthe Stylianou Ana Maroldi Caterina Marchiò Brian P. Rubin Mauro Papotti Britta Weigelt Carlos Gil Moreira Ferreira José Roberto Lapa e Silva Jorge S. Reis-Filho 《International journal of cancer. Journal international du cancer》2020,147(8):2253-2264
Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway. 相似文献
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10.
Rosa Della Monica Mariella Cuomo Roberta Visconti Annabella di Mauro Michela Buonaiuto Davide Costabile Giulia De Riso Teodolinda Di Risi Elia Guadagno Roberto Tafuto Sabrina Lamia Alessandro Ottaiano Paolo Cappabianca Maria Laura Del Basso de Caro Fabiana Tatangelo Juergen Hench Stephan Frank Salvatore Tafuto Lorenzo Chiariotti 《Oncology research》2020,28(9):837-845
Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches.
Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response
rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation
status of the MGMT gene, as its product, O6
-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we
have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two
different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma
management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing
and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT
methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results,
we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation
status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs. 相似文献