Increased expression of musashi 1 on breast cancer cells has implication to understand dormancy and survival in bone marrow.

Breast cancer (BC) stem cells (CSCs) resist treatment and can exist as dormant cells in tissues such as the bone marrow (BM). Years before clinical diagnosis, BC cells (BCCs) could migrate from the primary site where the BM niche cells facilitate dedifferentiation into CSCs. Additionally, dedifferentiation could occur by cell autonomous methods. Here we studied the role of Msi 1, a RNA-binding protein, Musashi I (Msi 1). We also analyzed its relationship with the T-cell inhibitory molecule programmed death-ligand 1 (PD-L1) in CSCs. PD-L1 is an immune checkpoint that is a target in immune therapy for cancers. Msi 1 can support BCC growth through stabilization of oncogenic transcripts and modulation of stem cell-related gene expression. We reported on a role for Msi 1 to maintain CSCs. This seemed to occur by the differentiation of CSCs to more matured BCCs. This correlated with increased transition from cycling quiescence and reduced expression of stem cell-linked genes. CSCs co-expressed Msi 1 and PD-L1. Msi 1 knockdown led to a significant decrease in CSCs with undetectable PD-L1. This study has implications for Msi 1 as a therapeutic target, in combination with immune checkpoint inhibitor. Such treatment could also prevent dedifferentiation of breast cancer to CSCs, and to reverse tumor dormancy. The proposed combined treatment might be appropriate for other solid tumors.

Pilot Study Exploring the Feasibility of Incorporating Radiation Oncology Into Pre-existing Early Pathway Programs for Diverse Premedical Students.

PURPOSE: Many medical schools in the United States have affiliated pathway, preparatory, and/or prematriculation programs that enroll a high percentage of students historically underrepresented in medicine (URiM). The purpose of this pilot study was to better characterize exposures to radiation oncology (RO) among students in these programs and determine the feasibility of incorporating a radiation oncologist within their pre-existing format if nonexistent. METHODS AND MATERIALS: During the summers of 2021 and 2022, a radiation oncologist gave a presentation about basic principles of cancer care to 18 unique student groups in 12 premedical programs affiliated with 8 medical schools. Participating students were asked to complete an anonymous postpresentation questionnaire. Descriptive statistics are reported. RESULTS: A total of 467 students attended the presentations, and 241 completed the questionnaire (response rate 52.0%). The majority of participants reported being female (63.5%), URiM (66.4%), and low income (57.3%). Students were less likely to report previous teaching from a radiation oncologist (11.2%) than a surgical (17.0%) or medical oncologist (18.3%). Prior clinical shadowing with a radiation oncologist (2.9%) was also less likely than shadowing a surgical oncologist (5.0%), medical oncologist (6.6%), or any other physician (53.1%). Students were also less likely to previously believe that radiation could cure cancer (65.8%) compared with surgery (74.9%) or chemotherapy (89.3%). After the presentation, 168 students (69.7%) were more interested in a career in RO, and 211 students (87.6%) responded that the presentation was either quite or extremely valuable (median Likert-type score, 5; interquartile range, 4-5). CONCLUSIONS: Many of the students in premedical programs lack prior exposure to RO or knowledge of multidisciplinary cancer care, which was ameliorated by a simple yet effective presentation across a variety of different types of programs in this study. Longitudinal assessment of different types of educational initiatives and students' ultimate career trajectory will help optimize future RO initiatives among premedical URiM students.

Anestesia total intravenosa en cirugía oncológica de mama / Total intravenous anesthesia in breast oncology surgery

Introducción: La anestesia total intravenosa se caracteriza por estabilidad hemodinámica, profundidad anestésica, recuperación rápida y predecible, menor cantidad de medicamentos y menor toxicidad. Objetivo: Describir los resultados de la anestesia total intravenosa en cirugía oncológica de mama. Método: Se realizó un estudio descriptivo, longitudinal en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, entre enero de 2016 a diciembre 2016, en 100 pacientes a las que se les administró anestesia total intravenosa con midazolam y fentanilo para proceder quirúrgico oncológico de mama. En ellas se determinó la repercusión hemodinámica, el nivel de sedación, analgesia, la recuperación y complicaciones. Resultados: La media de la edad de las pacientes fue 58,99 ± 12,5 años. De las pacientes en estudio 92 por ciento no presentó signos clínicos de superficialidad. Solo 21 pacientes presentaron complicaciones. Las variaciones de la tensión arterial fueron las más frecuentes (16 por ciento), seguidas de la bradicardia o taquicardia en solo cuatro casos. De forma inmediata se recuperó 74 por ciento de los casos y 26 por ciento restante lo hizo de manera mediata. El nivel de sedación fue adecuado en 50 por ciento y excesivo en 4 por ciento. Del total de los casos, 99 por ciento experimentaron respuesta analgésica sin dolor. Conclusiones: Los resultados del uso de anestesia total intravenosa fueron buenos, con adecuada respuesta analgésica y escasas complicaciones(AU)

Introduction: Total intravenous anesthesia is characterized by hemodynamic stability, anesthetic depth, rapid and predictable recovery, less medication and less toxicity. Objective: To describe the outcomes of total intravenous anesthesia in breast cancer surgery. Method: A descriptive, longitudinal study was carried out in Hermanos Ameijeiras Clinical-Surgical Hospital, from January 2016 to December 2016, in 100 patients who were administered total intravenous anesthesia with midazolam and fentanyl for breast oncology surgery. The patients were determined hemodynamic repercussion, the level of sedation, analgesia, recovery and complications. Results: The mean age of the patients was 58.99±12.5 years. Among the patients under study, 92 percent did not present clinical signs of superficiality. Only 21 patients presented complications. Variations in blood pressure were the most frequent (16 percent), followed by bradycardia or tachycardia in only four cases. Immediately, 74 percent of the cases were recovered and the remaining 26 percent did so timely. The level of sedation was adequate in 50 percent and excessive in 4 percent. Among the total number of cases, 99 percent experienced analgesic response without pain. Conclusions: The outcomes of total intravenous anesthesia usage were good, with adequate analgesic response and few complications(AU)

Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo.

There is increasing evidence to suggest that the Wnt signaling pathway plays a critical role in the pathogenesis of myeloma bone disease. In the present study, we determined whether increasing Wnt signaling within the bone marrow microenvironment in myeloma counteracts development of osteolytic bone disease. C57BL/KaLwRij mice were inoculated intravenously with murine 5TGM1 myeloma cells, resulting in tumor growth in bone and development of myeloma bone disease. Lithium chloride (LiCl) treatment activated Wnt signaling in osteoblasts, inhibited myeloma bone disease, and decreased tumor burden in bone, but increased tumor growth when 5TGM1 cells were inoculated subcutaneously. Abrogation of beta-catenin activity and disruption of Wnt signaling in 5TGM1 cells by stable overexpression of a dominant-negative TCF4 prevented the LiCl-induced increase in subcutaneous growth but had no effect on LiCl-induced reduction in tumor burden within bone or on osteolysis in myeloma-bearing mice. Together, these data highlight the importance of the local microenvironment in the effect of Wnt signaling on the development of myeloma bone disease and demonstrate that, despite a direct effect to increase tumor growth at extraosseous sites, increasing Wnt signaling in the bone marrow microenvironment can prevent the development of myeloma bone disease and inhibit myeloma growth within bone in vivo.