Novel Tumor Organoid-Based Mouse Model to Study Image Guided Radiation Therapy of Rectal Cancer After Noninvasive and Precise Endoscopic Implantation.

PURPOSE: Preoperative (neoadjuvant) radiation therapy (RT) is an essential part of multimodal rectal cancer therapy. Recently, total neoadjuvant therapy (TNT), which combines simultaneous radiochemotherapy with additional courses of chemotherapy, has emerged as an effective approach. TNT achieves a pathologic complete remission in approximately 30% of resected patients, opening avenues for treatment strategies that avoid radical organ resection. Furthermore, recent studies have demonstrated that anti-programmed cell death protein 1 immunotherapy can induce clinical complete responses in patients with specific genetic alterations. There is significant potential to enhance outcomes through intensifying, personalizing, and de-escalating treatment approaches. However, the heterogeneous response rates to RT or TNT and strategies to sensitize patients without specific genetic changes to immunotherapy remain poorly understood. METHODS AND MATERIALS: We developed a novel orthotopic mouse model of rectal cancer based on precisely defined endoscopic injections of tumor organoids that reflect tumor heterogeneity. Subsequently, we employed endoscopic- and computed tomography-guided RT and validated rectal tumor growth and response rates to therapy using small-animal magnetic resonance imaging and endoscopic follow-up. RESULTS: Rectal tumor formation was successfully induced in all mice after 2 organoid injections. Clinically relevant RT regimens with 5 × 5 Gy significantly delayed clinical signs of tumor progression and significantly improved survival. Consistent with human disease, rectal tumor progression correlated with the development of liver and lung metastases. Notably, long-term survivors after RT showed no evidence of tumor recurrence, as demonstrated by in vivo radiologic tumor staging and histopathologic examination. CONCLUSIONS: Our novel mouse model combines orthotopic tumor growth via noninvasive and precise rectal organoid injection and small-animal RT. This model holds significant promise for investigating the effect of tumor cell-intrinsic aspects, genetic alterations of the host, and exogenous factors (eg, nutrition or microbiota) on RT outcomes. Furthermore, it allows for the exploration of combination therapies involving chemotherapy, immunotherapy, or novel targeted therapies.

Microbiota and Colorectal Cancer: From Gut to Bedside.

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host's gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

[Interests and perspectives of first and last year medical students]. / Intereses y perspectiva sobre la carrera de medicina: un contraste entre estudiantes de medicina de primero y séptimo año.

BACKGROUND: The interests that motivate medical students to study this career are diverse and they may change during the seven years of study. In Chile, 22 universities offer medicine and the number of graduated students has increased by more than 50% over the last 10 years. AIM: To determine the motivational profile of medical students at admission, and at the end of their career. SUBJECTS AND METHODS: A voluntary anonymous survey was applied to 275 first and 140 seventh year medical students from one traditional public and two private schools. RESULTS: The main reason for applying to medical school was social interest (68.7%), followed by interest in science and academia. Thirty six percent of students from seventh year would not study medicine again. In the seventh year, the interest in medical care persists in 88% of students, followed by academic interests in 64%. Only 24% had research interests. Fifty nine and 57% of students projected their medical work in private and public hospital settings, respectively. Only 11% projected themselves as doing research. Sixty nine percent of students would like to receive more information about post graduate education. CONCLUSIONS: There is a low interest in research and a high percentage of seventh year students that would not apply to medicine again. Medical schools should perform a systematic analysis of students' interests to improve faulty areas.

Intereses y perspectiva sobre la carrera de medicina: un contraste entre estudiantes de medicina de primero y séptimo año / Interests and perspectives of first and last year medical students

Background: The interests that motivate medical students to study this career are diverse and they may change during the seven years of study. In Chile, 22 universities offer medicine and the number of graduated students has increased by more than 50% over the last 10 years. Aim: To determine the motivational profile of medical students at admission, and at the end of their career. Subjects and Methods: A voluntary anonymous survey was applied to 275 first and 140 seventh year medical students from one traditional public and two private schools. Results: The main reason for applying to medical school was social interest (68.7%), followed by interest in science and academia. Thirty six percent of students from seventh year would not study medicine again. In the seventh year, the interest in medical care persists in 88% of students, followed by academic interests in 64%. Only 24% had research interests. Fifty nine and 57% of students projected their medical work in private and public hospital settings, respectively. Only 11% projected themselves as doing research. Sixty nine percent of students would like to receive more information about post graduate education. Conclusions: There is a low interest in research and a high percentage of seventh year students that would not apply to medicine again. Medical schools should perform a systematic analysis of students' interests to improve faulty areas.