Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

Mark A. D’Andrea,G. Kesava Reddy, 대한방사선종양학회 2019 Radiation Oncology Journal Vol.37 No.4

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain’s distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient’s tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms such as headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient’s CNS metastases improved significantly within weeks of her therapy. The patient’s non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy

Travel Books and Urban Identity. British Travellers in Messina, 1770-1815: A Preliminary Study

( Diletta D`andrea ) 부산외국어대학교 지중해연구소 2014 The Mediterranean Review Vol.7 No.1

Patrick Brydone`s Tour through Sicily and Malta, first published in 1773, was a primary guide-book for all those travellers who reached Sicily from Northern Europe for the first time. Thanks to Brydone`s enthusiastic survey, Sicily and especially Messina became part of the itinerary of the Italian Grand Tour. Regular flows of travellers arrived. During the Napoleonic Wars and mostly during the British Decade (1806-1815) in Sicily, when His Majesty`s military forces occupied the Bourbons` island and protected it from a possible French invasion, Messina became the site of the British military head-quarters; at the same time, its port was either the final destination or the starting point for many travellers, whose striking descriptions helped build a new identity for Messina and put the city among the most favoured destinations of the Grand Tour in the Mediterranean. A strong connection was then created between the Sicilian town and England, a connection that lasted over ‘the long nineteenth century’.

Restoration and conservation of anatomic pieces

Camila Cárdenas Guerrero Guzmán,Karen Alejandra Pérez Díaz,María Paula Ruíz Díaz,Valentina Díaz Sánchez,Andrés Camilo Ariza Aguirre,Laura Catalina Cantor Alfonso,Camila Andrea Suárez Ortiz,Davide Fali 대한해부학회 2019 Anatomy & Cell Biology Vol.52 No.3

In this study, a restoration process was developed with potassium hydroxide (KOH), in order to improve each of the structures for their posterior fixation, through the use of new methods such as the Chilean conservative fixative solution (SFCCh), with exceptional results. Restore anatomical pieces corresponding to corpse and organs, being these last set with the SFCCh. In this work dealt with processes of restoration with potassium hydroxide, sodium chloride, and sodium hypochlorite, the process began with the cleanliness and suture of the structures for subsequent fixing in Chilean conservative fixative solution, making use of a corpse and different anatomical parts. Work based on items found in the database, Elsevier, Science Direct, ProQuest, and MEDLINE. At the end of the process of restoration and conservation of the anatomical pieces, was observed an improvement in muscle pigment with decrease of rigidity in the specimen, additionally a recovery of appearance in the vascular-nervous elements was achieved. The organs were much more malleable and the structures facilitate the identification of specific details, its subsequent immersion in SFCCh allows the longer preservation of the obtained results. The restoration with potassium hydroxide allows the improvement in the appearance of the different anatomical structures and simultaneously to facilitate its study. The SFCCh is an alternative that replaces partially the use of formaldehyde. In addition, it presents toxicity reduction.

Silk fibroin, gelatin, and human placenta extracellular matrix-based composite hydrogels for 3D bioprinting and soft tissue engineering

Karl Heinrich Schneider,Benjamin J. Goldberg,Onur Hasturk,Xuan Mu,Marvin Dötzlhofer,Gabriela Eder,Sophia Theodossiou,Luis Pichelkastner,Peter Riess,Sabrina Rohringer,Herbert Kiss,Andreas H. Teuschl‑Wo 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background There is a great clinical need and it remains a challenge to develop artificial soft tissue constructs that can mimic the biomechanical properties and bioactivity of natural tissue. This is partly due to the lack of suitable biomaterials. Hydrogels made from human placenta offer high bioactivity and represent a potential solution to create animal-free 3D bioprinting systems that are both sustainable and acceptable, as placenta is widely considered medical waste. A combination with silk and gelatin polymers can bridge the biomechanical limitations of human placenta chorion extracellular matrix hydrogels (hpcECM) while maintaining their excellent bioactivity. Method In this study, silk fibroin (SF) and tyramine-substituted gelatin (G-TA) were enzymatically crosslinked with human placental extracellular matrix (hpcECM) to produce silk-gelatin-ECM composite hydrogels (SGE) with tunable mechanical properties, preserved elasticity, and bioactive functions. The SGE composite hydrogels were characterized in terms of gelation kinetics, protein folding, and bioactivity. The cyto- and biocompatibility of the SGE composite was determined by in vitro cell culture and subcutaneous implantation in a rat model, respectively. The most cell-supportive SGE formulation was then used for 3-dimensional (3D) bioprinting that induced chemical crosslinking during extrusion. Conclusion Addition of G-TA improved the mechanical properties of the SGE composite hydrogels and inhibited crystallization and subsequent stiffening of SF for up to one month. SGE hydrogels exhibit improved and tunable biomechanical properties and high bioactivity for encapsulated cells. In addition, its use as a bioink for 3D bioprinting with free reversible embedding of suspended hydrogels (FRESH) has been validated, opening the possibility to fabricate highly complex scaffolds for artificial soft tissue constructs with natural biomechanics in future.

Simultaneous Detection of Disseminated and Circulating Tumor Cells in Primary Breast Cancer Patients

Andreas D. Hartkopf,Markus Wallwiener,Markus Hahn,Tanja N. Fehm,Sara Y. Brucker,Florin-Andrei Taran 대한암학회 2016 Cancer Research and Treatment Vol.48 No.1

Purpose Disseminated tumor cells (DTCs) from bone marrow (BM) are a surrogate of minimal residual disease (MRD) in primary breast cancer (PBC) patients and associated with an adverse prognosis. However, BM sampling is an invasive procedure. Although there is growing evidence that circulating tumor cells (CTCs) from the blood are also suitable for monitoring MRD, data on the simultaneous detection of DTCs and CTCs are limited. Materials and Methods We determined the presence of DTCs using immunocytochemistry and the pan-cytokeratin antibody A45-B/B3. CTCs were determined simultaneously using a reverse transcription- polymerase chain reaction–based assay (AdnaTest Breast Cancer) and CellSearch (at least one CTC per 7.5 mL blood). We compared the detection of DTCs and CTCs and evaluated their impact on disease-free and overall survival. Results Of 585 patients, 131 (22%) were positive for DTCs; 19 of 202 (9%) and 18 of 383 (5%) patients were positive for CTCs, as shown by AdnaTest and CellSearch, respectively. No significant association was observed between DTCs and CTCs (p=0.248 and p=0.146 as shown by AdnaTest and CellSearch, respectively). The presence of DTCs (p=0.046) and the presence of CTCs as shown by CellSearch (p=0.007) were predictive of disease-free survival. Conclusion Our data confirm the prognostic relevance of DTCs and CTCs in patients with PBC. As we found no significant relationship between DTCs and CTCs, prospective trials should include their simultaneous detection. Within those trials, the question of whether or not DTCs and CTCs are independent subpopulations of malignant cell clones should be determined by molecular characterization.

A microlocal approach to the enhanced Fourier–Sato transform in dimension one

D'Agnolo, Andrea,Kashiwara, Masaki Elsevier 2018 Advances in Mathematics Vol.339 No.-

<P><B>Abstract</B></P> <P>Let M be a holonomic algebraic D -module on the affine line. Its exponential factors are Puiseux germs describing the growth of holomorphic solutions to M at irregular points. The stationary phase formula states that the exponential factors of the Fourier transform of M are obtained by Legendre transform from the exponential factors of M . We give a microlocal proof of this fact, by translating it in terms of enhanced ind-sheaves through the Riemann–Hilbert correspondence.</P>

Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma

D'Andrea, Mark A.,Reddy, G.K. The Korean Society for Radiation Oncology 2019 Radiation Oncology Journal Vol.37 No.4

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain's distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient's tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms of headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient's CNS metastases improved significantly within weeks of her therapy. The patient's non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.

Fertility-sparing treatment in early endometrial cancer: current state and future strategies

( Andreas Obermair ),( Franzcog ),( Eva Baxter ),( Donal J. Brennan ),( Jessica N. Mcalpine ),( Jennifer J. Mueller ),( Frédéric Amant ),( Mignon D. J. M. Van Gent ),( Robert L. Coleman ),( Shannon N. 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.4

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14-25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.

Subphenotypes of Acute Respiratory Distress Syndrome: Advancing towards Precision Medicine

Andrea R. Levine, M.D., M.S.,Carolyn S. Calfee, M.D., M.A.S. 대한결핵및호흡기학회 2024 Tuberculosis and Respiratory Diseases Vol.87 No.1

Acute respiratory distress syndrome (ARDS) is a common cause of severe hypoxemiadefined by the acute onset of bilateral non-cardiogenic pulmonary edema. The diagnosisis made by defined consensus criteria. Supportive care, including prevention offurther injury to the lungs, is the only treatment that conclusively improves outcomes. The inability to find more advanced therapies is due, in part, to the highly sensitive butrelatively non-specific current syndromic consensus criteria, combining a heterogenouspopulation of patients under the umbrella of ARDS. With few effective therapies,the morality rate remains 30% to 40%. Many subphenotypes of ARDS have been proposedto cluster patients with shared combinations of observable or measurable traits. Subphenotyping patients is a strategy to overcome heterogeneity to advance clinicalresearch and eventually identify treatable traits. Subphenotypes of ARDS have beenproposed based on radiographic patterns, protein biomarkers, transcriptomics, and/ormachine-based clustering of clinical and biological variables. Some of these strategieshave been reproducible across patient cohorts, but at present all have practical limitationsto their implementation. Furthermore, there is no agreement on which strategy isthe most appropriate. This review will discuss the current strategies for subphenotypingpatients with ARDS, including the strengths and limitations, and the future directionsof ARDS subphenotyping.

COVID-19 Impact on the Italian Community-based System of Mental Health Care: Reflections and Lessons Learned for the Future

Andrea Amerio(Andrea Amerio ),Eleonora Vai(Eleonora Vai ),Edoardo Bruno(Edoardo Bruno ),Alessandra Costanza(Alessandra Costanza ),Andrea Escelsior(Andrea Escelsior ),Anna Odone(Anna Odone ),Domenico D 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Despite the unprecedented wave of research and publications sparked by the recent pandemic, only few studies have investigated the impact of COVID-19 on the Italian community-based system of mental health care. We aimed to summarize the available evidence from the literature also considering what we have learned from our daily clinical practice. As hospital care was restricted by COVID-19, although reducing their opening hours and activities, Community Mental Health Centers promoted continuity of care for at-risk populations, supporting them to cope with loneliness and hopelessness during quarantine and self-isolation. Ensuring continuity of care also remotely, via teleconsultation, lowered the risk of psychopathological decompensation and consequent need of hospitalization for mental health patients, with satisfaction expressed both by patients and mental health workers. Considering what we have learned from the pandemic, the organization and the activity of the Italian community-based system of mental health care would need to be implemented through 1) the promotion of a “territorial epidemiology” that makes mental health needs visible in terms of health care workers involved, 2) the increase of mental health resources in line with the other European high-income countries, 3) the formalization of structured initiatives of primary care and mental health cooperation, 4) the creation of youth mental health services following a multidimensional and multidisciplinary approach and encouraging family participation, 5) the promotion of day centers, to build competence and self-identity within a more participatory life, and programs geared to employment as valid models of recovery-oriented rehabilitation.