Tumor-Associated Macrophages: Therapeutic Targets for Skin Cancer

Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well as their benefits in cancer immunotherapy

Por Práticas Compartilhadas de Aprender e Ensinar Com as Crianças. Diálogos com Bakhtin e o Círculo

Propomos, neste texto, refletir sobre o ensinar e o aprender no contexto escolar como atos que se constroem com as crianças e não para as crianças. Para isso, optamos por pensar no tema a partir das relações com turmas que estavam em processo de alfabetização, em primeiros anos do Ensino Fundamental. Faremos essa discussão a partir da perspectiva Bakhtiniana, através das materialidades produzidas pelas turmas em aula e mediadas por professoras de escolas públicas do interior do estado de São Paulo. Percebemos que quando o contexto extraverbal foi compartilhado, pois o que as crianças levaram para a escola foi considerado nas propostas desenvolvidas pelas turmas, as crianças pareceram se envolver mais e o ensinar e o aprender passaram a ser compartilhados por elas e as professoras, deixando de ser atos mecânicos para se constituírem como atos singulares. Defendemos, assim, a necessidade de uma escuta responsiva da vida e das culturas produzidas pelas educandas e pelos educandos, de modo a possibilitar a construção de funções e sentidos compartilhados e jeitos de pensar e fazer a leitura e a escrita em contextos reais.

Undifferentiated round cell sarcoma with BCOR internal tandem duplications (ITD) or YWHAE fusions:a clinicopathologic and molecular study

Until recently, undifferentiated round cell sarcomas (URCS) in infants have been considered a wastebasket diagnosis, composed of various pathologic entities and lacking consistent genetic alterations. The recent identification of recurrent BCOR internal tandem duplications (ITD) and less common alternative YWHAE\u2013NUTM2B/E fusions in half of infantile URCS and the majority of so-called primitive myxoid mesenchymal tumors of infancy (PMMTI) suggests a common pathogenesis with clear cell sarcoma of the kidney which also harbors the same genetic alterations. These tumors also share a similar morphology and immunoprofile, including positivity for BCOR, cyclin D1, and SATB2. In this study, we investigate the largest cohort to date of genetically confirmed URCS and PMMTI with BCOR ITD or YWHAE fusions to better define their morphologic spectrum and clinical behavior. Twenty-eight cases harbored BCOR ITD and five YWHAE fusions, occurring in 29 infants and 4 children, 19 males and 14 females. Microscopically, 20 were classified as URCS and 13 as PMMTI. Follow-up was available in 25 patients, with 14 (56%) succumbing to their diseases at a mean duration of 18-months follow-up (range: 2\u201362). Six patients remained with no evidence of disease at a mean follow-up of 63 months (range: 4\u2013192), four patients were still alive with disease (mean follow-up: 46 months, range: 4\u2013120), and one died of other causes. Local recurrence and distant metastasis were each observed in 11/25 (44%) of the patients. The overall survival was 42% at 3 years and 34% at 5 years (median survival: 26 months). There was no statistically significant survival difference between cases diagnosed as URCS and PMMTI and between those with BCOR ITD and YWHAE fusions

Association of Baseline Serum Levels of CXCL5 With the Efficacy of Nivolumab in Advanced Melanoma

Anti-programmed cell death protein 1 (PD1) antibodies are in wide use for the treatment of various cancers. PD1 antibody-based immunotherapy, co-administration of nivolumab and ipilimumab, is one of the optimal immunotherapies, especially in advanced melanoma with high tumor mutation burden. Since this combined therapy leads to a high frequency of serious immune-related adverse events (irAEs) in patients with advanced melanoma, biomarkers are needed to evaluate nivolumab efficacy to avoid serious irAEs caused by ipilimumab. This study analyzed baseline serum levels of CXCL5, CXCL10, and CCL22 in 46 cases of advanced cutaneous melanoma treated with nivolumab. Baseline serum levels of CXCL5 were significantly higher in responders than in non-responders. In contrast, there were no significant differences in baseline serum levels of CXCL10 and CCL22 between responders and non-responders. These results suggest that baseline serum levels of CXCL5 may be useful as a biomarker for identifying patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma

Antibodies against programmed cell death protein 1, such as nivolumab and pembrolizumab, are widely used for treating various cancers, including advanced melanoma. Nivolumab significantly prolongs survival in patients with metastatic melanoma, and sequential administration with lipilimumab may improve outcomes when switched at the appropriate time. Biomarkers are therefore needed to evaluate nivolumab efficacy soon after first administration. This study analyzed serum levels of soluble cluster of differentiation 163 (sCD163) in 59 cases of advanced cutaneous melanoma and 16 cases of advanced mucosal melanoma treated using nivolumab. Serum levels of sCD163 were significantly increased after 6 weeks in responders compared to non-responders after initial administration of nivolumab for cutaneous melanoma. In contrast, no significant difference between responders and non-responders was seen among patients with non-cutaneous melanoma. These results suggest that sCD163 may be useful as a biomarker for selecting patients with advanced cutaneous melanoma most likely to benefit from anti-melanoma immunotherapy

障害支援フィールドにおけるCOVID-19をめぐる現状と課題

新型コロナウイルス感染症（以下，COVID-19）の対応に際して，緊急事態宣言発出後，筆者らが関与する教育関係，福祉関係，医療関係の最前線での実践現場においては，これまでの実践内容にない対応を求められた。本論文では，筆者らが関与している教育関係，福祉関係，医療関係の最前線での実践現場についての現状と課題を把握していくことを目的とした。現状として，実践現場での感染症予防対策以外にも教材作成や労務上の対応が求められており，課題として，児童・生徒，利用者の心のケアや実践者自身のバーンアウトへの対応必要性も示唆された。After the state of emergency, about the measures against the novel coronavirus (COVID-19), at educational field, medical front and welfare site in which we are involved, we have demanded to change the way of working. The purpose of this article is to understand the current situations and issues in the front line on educational, medical and welfare fields. We found that we required creating the teaching material for on-line and deal with labor in addition to measures to prevent the spread of COVID-19. We also suggested the need to do the mental health care for students and users and prevent working people from burnout

Teacher's kept : teaching practice's embroidery and tangles of research lines

Orientador: Guilherme do Val Toledo PradoDissertação (mestrado profissional) - Universidade Estadual de Campinas, Faculdade de EducaçãoResumo: Esta dissertação é a pesquisa narrativa de uma professora sobre sua própria prática a partir da questão "quais perguntas surgem ao organizar os guardados no inventário e como, na busca por respondê-las, são construídos conhecimentos da prática profissional?". A metodologia de pesquisa narrativa orienta esta pesquisa, fazendo com que os caminhos, as perguntas, as inquietações que vão surgindo durante a pesquisa sejam narradas de modo a dar a ver como se deu o percurso de construção de conhecimentos. Os materiais usados nesta pesquisa são os guardados de professora e de estudante que são inventariados. O processo de inventariar é narrado e, com isso, a professora-pesquisadora se vê em meio a muitas perguntas de sua prática. Essas questões são agrupadas e respondidas em quatro momentos, que são chamados de emaranhados de linhas, e que dialogam com temas como a formação continuada de professoras e professores, a escrita narrativa do cotidiano escolar, as experiências em sala de aula e a prática docente em um contexto escolar que tem como plano de fundo o trabalho com o material apostilado. A aproximação destes temas com os estudos bakhtinianos permite a ampliação dos sentidos ao que vai sendo narrado e pesquisado ajudando, assim, na construção considerações de pesquisa que dizem respeito à escrita narrativa como possibilidade da professora-pesquisadora se colocar distante do que pesquisa e vive com as estudantes e os estudantes para, dessa maneira, poder ter outros entendimentos da sua prática e da pesquisa. Além disso, é possível oferecer conselhos da prática docente que dialogam com os temas que são trazidos pelas perguntas reveladas com o inventário e mostram entendimentos possíveis para uma prática única, singular e irrepetível da professora-pesquisadora. Nesta pesquisa narrativa, portanto, a professora-pesquisadora entende que a partir do ato narrativo é possível recuperar saberes, experiências e memórias que se revelam em seu guardados inventariados e que ajudam a produzir saberes transgredientes a sua prática docenteAbstract: This dissertation is the narrative research of a teacher about her own practice based on the question "what questions arise when organizing those formation and teaching materials kept in the inventory and how, in the search for answering them, are knowledge of professional practice constructed?". The narrative research methodology guides this research, making the paths, the questions, the concerns that arise during the research be narrated in order to show how the knowledge construction path took place. The materials used in this research are those stored by teacher and student that are inventoried. The inventorying process is narrated and, with this, the teacher-researcher finds herself amidst many questions of her practice. These questions are grouped and answered in four moments, which are called tangles of lines, and which dialogue with topics such as the continuing education of teachers, the narrative writing of everyday school life, classroom experiences and teaching practice in a school context that has as a background the work with the handout material. The approximation of these themes with the Bakhtinian studies allows the expansion of meanings to what is being narrated and researched, thus helping in the construction of research considerations that relate to narrative writing as a possibility for the teacher-researcher to place herself far from what she researches and lives with students so that she can have other understandings of her practice and research. In addition, it is possible to offer advices on teaching practice that dialogue with the themes that are brought up by the questions revealed with the inventory and show possible understandings for a unique, singular and unrepeatable practice of the teacher-researcher. In this narrative research, therefore, the teacher-researcher understands that from the narrative act it is possible to recover knowledge, experiences and memories that are revealed in her inventoried materials and that help to produce knowledge that is transgressive to her teaching practiceMestradoEducação EscolarMestra em Educação Escola

Clostridium difficile Colitis and Neutropenic Fever Associated with Docetaxel Chemotherapy in a Patient with Advanced Extramammary Paget’s Disease

Extramammary Paget's disease is a rare cutaneous malignant neoplasm. Previous studies indicated the efficacy of docetaxel in advanced cases. The common side effects of docetaxel are usually tolerable and seldom life-threatening. We experienced a case of severe pseudomembranous colitis and neutropenic fever that developed just after the first cycle of docetaxel chemotherapy. To the best of our knowledge, there are few reports of pseudomembranous colitis associated with docetaxel administration for skin cancers. The patient showed complete resolution of her symptoms within 2 weeks with an oral metronidazole therapy. During the second and third cycles, the patient received docetaxel safely with lower doses. The present case indicated that pseudomembranous colitis should be included in the differential diagnosis when assessing patients who develop severe diarrhea during systemic chemotherapy with docetaxel

Validation and reliability of the Japanese version of the Food Allergy Quality of Life Questionnaire–Parent Form

Background: Food allergy (FA) is a heavy burden for patients and their families and can significantly reduce the quality of life (QoL) of both. To provide adequate support, qualitative and quantitative evaluation of the parents' QoL may be helpful. The objective of this study is to develop and validate a Japanese version of the Food Allergy QoL Questionnaire–Parent Form (FAQLQ-PF-J), an internationally validated disease-specific QoL measurement of the parental burden of having a child with FA. Methods: The FAQLQ-PF and the Food Allergy Independent Measure (FAIM), an instrument to test the construct validity of the FAQLQ-PF-J, were translated into Japanese. After language validation, the questionnaires were administered to parents of FA children aged 0–12 years and those of age-matched healthy (without FA) children. Internal consistency (by Cronbach's α) and test-retest reliability were evaluated. Construct validity and discriminant validity were also examined. Results: One hundred twenty-seven parents of children with FA and 48 parents of healthy children filled out the questionnaire. The FAQLQ-PF-J showed excellent internal consistency (Cronbach's α > 0.77) and test-retest reliability. Good construct validity was demonstrated by significant correlations between the FAQLQ-PF-J and FAIM-J scores. It discriminated parents of children with FA from those without. The scores were significantly higher (lower QoL) for parents of FA children with a history of anaphylaxis than those without, for those with >6 FA-related symptoms experienced than those with less FA-related symptoms. Conclusions: The FAQLQ-PF-J is a reliable and valid measure of the parental burden of FA in children

Tumor-Associated Macrophages: Therapeutic Targets for Skin Cancer

Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are significant components of the microenvironment of solid tumors in the majority of cancers. TAMs sequentially develop from monocytes into functional macrophages. In each differentiation stage, TAMs obtain various immunosuppressive functions to maintain the tumor microenvironment (e.g., expression of immune checkpoint molecules, production of Treg-related chemokines and cytokines, production of arginase I). Although the main population of TAMs is immunosuppressive M2 macrophages, TAMs can be modulated into M1-type macrophages in each differential stage, leading to the suppression of tumor growth. Because the administration of certain drugs or stromal factors can stimulate TAMs to produce specific chemokines, leading to the recruitment of various tumor-infiltrating lymphocytes, TAMs can serve as targets for cancer immunotherapy. In this review, we discuss the differentiation, activation, and immunosuppressive function of TAMs, as well as their benefits in cancer immunotherapy