Blockade of CaV3 calcium channels and induction of G0/G1 cell cycle arrest in colon cancer cells by gossypol.

BACKGROUND AND PURPOSE: Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. EXPERIMENTAL APPROACH: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. KEY RESULTS: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. CONCLUSION AND IMPLICATIONS: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.

Learning curve and safety of the implementation of laparoscopic complete mesocolic excision with intracorporeal anastomosis for right-sided colon cancer: results from a propensity score-matched study.

BACKGROUND: Retrospective studies and randomized controlled trials support the safety of laparoscopic complete mesocolic excision (CME) for the treatment of right-sided colon cancer (RSCC). Few studies, however, examine the learning curve of this operation and its impact on safety during an implementation period. We aim to evaluate the learning curve and safety of the implementation of laparoscopic CME with intracorporeal anastomosis for RSCC. METHODS: Consecutive patients undergoing a laparoscopic right colectomy with intracorporeal anastomosis for RSCC between January 2016 and June 2023 were included. Clinical, perioperative, and histopathological variables were collected. Correlation and cumulative sum (CUSUM) analyses between the operating time and case number were performed. Breakpoints of the learning curve were estimated using the broken-line model. CME and conventional laparoscopic right colectomy outcomes were compared after propensity score matching (PSM). RESULTS: Two hundred and ninety patients underwent laparoscopic right colectomy during study period. One hundred and eight met inclusion criteria. After PSM, 56 non-CME and 28 CME patients were compared. CME group had a non-statistically significant tendency to a longer operating time (201 versus 195 min; p = 0.657) and a shorter hospital stay (3 versus 4 days; p = 0.279). No significant differences were found in total complication rates or their profile. Correlation analysis identified a significant trend toward operating time reduction with increasing case numbers (Pearson correlation coefficient = - 0.624; p = 0.001). According to the CUSUM analysis, an institutional learning curve was deemed completed after 13 cases and the broken-line model identified three phases: learning (1-6 cases), consolidation (7-13 cases), and mastery (after 13 cases). CONCLUSION: The learning curve of laparoscopic CME for RSCC can be achieved after 13 cases in centers with experience in advanced laparoscopic surgery and surgeons with familiarity with this technique. Its implementation within this setting seems to be as safe as performing a conventional right colectomy.

Digested galactoglucomannan mitigates oxidative stress in human cells, restores gut bacterial diversity, and provides chemopreventive protection against colon cancer in rats.

Galactoglucomannan (GGM) is the predominant hemicellulose in coniferous trees, such as Norway spruce, and has been used as a multipurpose emulsifier in the food industry. In vitro digestion with a cellular antioxidant activity assay was performed to determine the bioaccessibility and antioxidant activity of phenolic compounds, and the behaviour of GGM on in vivo experimental assay against induced colon cancer. The results showed that digestion decreased the bioaccessibility and antioxidant capacity of phenolic compounds. Cellular analysis did not support these findings once an antioxidant effect was observed in human cell lines. GGM attenuated the initiation and progression of colon cancer, by reducing the foci of aberrant crypts in rats, and modified the intestinal bacterial microbiota (disrupting the balance between Firmicutes and Bacteroidetes phyla). Thus, GGM provided chemopreventive protection against the development of colon cancer and acted as an intracellular antioxidant agent.

Uncovering Metabolic Alterations in HCT-116 Colon Cancer Cells upon Exposure to Bamboo Leaf Extract Obtained from Guadua incana Londoño.

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

SEOM-GEMCAD-TTD clinical guidelines for the adjuvant treatment of colon cancer (2023).

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer.

Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.

Genotoxic and antiproliferative properties of Endopleura uchi bark aqueous extract.

The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella/microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC50 = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.

Intracorporeal anastomosis could be associated with a higher lymph node yield in right colon cancer surgery: Results of the ICA-LATAM study, a retrospective, multicentre, comparative analysis in Latin America.

AIM: The aim of this work was to compare lymph node (LN) yield in patients operated on for right colon cancer (RCC) using a laparoscopic approach between those receiving an intracorporeal (ICA) or extracorporeal anastomosis (ECA). METHOD: This is a retrospective multicentre study involving patients operated on for RCC in nine tertiary referral centres in Latin America during a 2-year period. The main comparative outcome between groups was the number of LNs harvested between groups. RESULTS: The study included 416 patients, 261 (62.7%) in the ECA group and 155 (37.3%) in the ICA group. Patients in the ECA group were elderly (66 vs. 61 years, p < 0.001). Patients receiving an ICA achieved a significantly higher LN yield than those receiving an ECA (24 vs. 18, p < 0.001). This group also had a lower percentage of patients achieving a substandard LN yield (<12 LNs) (10% vs. 24.8%, p = 0.001) and more patients achieving a high number of harvested LNs (>32 LNs) (15.5% vs. 8.3%, p = 0.039). In the multivariate analysis, ICA was independently related to the primary outcome (LN yield) (OR 3.28, p = 0.027, 95% CI 1.14-9.38). CONCLUSION: In this retrospective study, patients operated on for RCC who received an ICA achieved a higher LN yield. Further studies are needed to reconfirm these findings, and also to find an explanation for these results.

Decoding the Versatile Landscape of Autophagic Protein VMP1 in Cancer: A Comprehensive Review across Tissue Types and Regulatory Mechanisms.

Autophagy, a catabolic process orchestrating the degradation of proteins and organelles within lysosomes, is pivotal for maintaining cellular homeostasis. However, its dual role in cancer involves preventing malignant transformation while fostering progression and therapy resistance. Vacuole Membrane Protein 1 (VMP1) is an essential autophagic protein whose expression, per se, triggers autophagy, being present in the whole autophagic flux. In pancreatic cancer, VMP1-whose expression is linked to the Kirsten Rat Sarcoma Virus (KRAS) oncogene-significantly contributes to disease promotion, progression, and chemotherapy resistance. This investigation extends to breast cancer, colon cancer, hepatocellular carcinoma, and more, highlighting VMP1's nuanced nature, contingent on specific tissue contexts. The examination of VMP1's interactions with micro-ribonucleic acids (miRNAs), including miR-21, miR-210, and miR-124, enhances our understanding of its regulatory network in cancer. Additionally, this article discusses VMP1 gene fusions, especially with ribosomal protein S6 kinase B1 (RPS6KB1), shedding light on potential implications for tumor malignancy. By deciphering the molecular mechanisms linking VMP1 to cancer progression, this exploration paves the way for innovative therapeutic strategies to disrupt these pathways and potentially improve treatment outcomes.

Anticancer Potential and Safety Profile of ß-Lapachone In Vitro.

Ipê is a plant of the Bignoniaceae family. Among the compounds extracted from this tree, lapachol is notable because its structural modification allows the production of ß-lapachone, which has anticancer properties. The objective of this work was to test this hypothesis at a cellular level in vitro and assess its potential safety for use. The following tests were performed: MTT cell viability assay, apoptotic index determination, comet assay, and micronucleus test. The results showed that ß-lapachone had a high cytotoxic capacity for all cell lines tested: ACP02 (gastric adenocarcinoma cells), MCF7 (breast carcinoma cells), HCT116 (colon cancer cells) and HEPG2 (hepatocellular carcinoma cells). Regarding genotoxicity, the exposure of cells to sublethal doses of ß-lapachone induced DNA damage (assessed by the comet assay) and nuclear abnormalities, such as nucleoplasmic bridges and nuclear buds (assessed by the micronucleus test). All tested cell lines responded similarly to ß-lapachone, except for ACP02 cells, which were relatively resistant to the cytotoxic effects of the compound in the MTT test. Our results collectively indicate that although ß-lapachone showed antiproliferative activity against cancer cell lines, it also caused harmful effects in these cells, suggesting that the use of ß-lapachone in treating cancer should be carried out with caution.

Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage.

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.

Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells.

Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified (SALL1-4), and SALL2 is the family's most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.

Ionizable Lipid Nanoparticle-Mediated TRAIL mRNA Delivery in the Tumor Microenvironment to Inhibit Colon Cancer Progression.

Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1-7 (Ang(1-7)) to reduce vascular compression and deposition of extracellular matrix in mice. Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1-7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization. Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.

Prótesis colónicas en el tratamiento paliativo del cáncer colónico. Nuestra evaluación tras 10 años de experiencia / Self-expanding metal stents in the palliative treatmentof coloncancer. Results of 10 years of experience

Introducción: la colocación de prótesis metálicas autoexpansibles (PAE) por vía endoscópica surge como opción terapéutica para la obstrucción colónica neoplásica en dos situaciones: como tratamiento paliativo y como puente a la cirugía curativa. Este procedimiento evita cirugías en dos tiempos y disminuye la probabilidad de colostomía definitiva y sus complicaciones con el consecuente deterioro de la calidad de vida. Objetivo: comunicar nuestra experiencia en la colocación de PAE para el tratamiento paliativo de la obstrucción colorrectal neoplásica. Diseño: retrospectivo, longitudinal, descriptivo y observacional. Material y métodos: se incluyeron todos los pacientes a quienes el mismo grupo de endoscopistas les colocó PAE con intención paliativa por cáncer colorrectal avanzado entre agosto de 2008 y diciembre de 2019. Fueron analizadas las variables demográficas y clínicas, el éxito técnico y clínico, las complicaciones tempranas y tardías y la supervivencia. Resultados: se colocó PAE en 54 pacientes. La media de edad fue 71 años. El 85% de las lesiones se localizó en el colon izquierdo. En el 57% de los pacientes se realizó en forma ambulatoria. El éxito técnico y clínico fue del 92 y 90%, respectivamente y la supervivencia media de 209 días. La tasa de complicaciones fue del 29,6%, incluyendo un 14,8% de obstrucción y un 5,6% de migración. La mortalidad tardía atribuible al procedimiento fue del 5,6%, ocasionada por 3 perforaciones tardías: 2 abiertas y 1 microperforación con formación de absceso localizado. Conclusiones: la colocación de PAE como tratamiento paliativo de la obstrucción neoplásica colónica es factible, eficaz y segura. Permitió el manejo ambulatorio o con internación breve y la realimentación temprana, mejorando las condiciones para afrontar un eventual tratamiento quimioterápico paliativo. Las mayoría de las complicaciones fueron tardías y resueltas endoscópicamente en forma ambulatoria. (AU)

Introduction: endoscopic placement of self-expanding metal stents (SEMS) emerges as a therapeutic option for neoplastic obstruction of the colon in two situations: as palliative treatment and as a bridge to curative surgery. This procedure avoids two-stage surgeries and reduces the probability of permanent colostomy and its complications with the consequent deterioration in quality of life. Objective: to report our experience in the placement of SEMS as palliative treatment in neoplastic colorectal obstruction. Design: retrospective, longitudinal, descriptive and observational study. Methods: all patients in whom the same group of endoscopists performed SEMS placement with palliative intent for advanced colorectal cancer between August 2008 and December 2019 were analyzed. Data collected were demographic and clinical variables, technical and clinical success, early and late complications, and survival. Results: SEMS were placed in 54 patients. The average age was 71 years. Eighty-five percent were left-sided tumors. In 57% of the patients the procedure was performed on an outpatient basis. Technical and clinical success was 92 and 90%, respectively, and median survival was 209 days. The complication rate was 29.6%, including 14.8% obstruction and 5.6% migration. Late mortality attributable to the procedure was 5.6%, caused by 3 late perforations: 2 open and 1 microperforation with localized abscess formation. Conclusions: The placement of SEMS as a palliative treatment for neoplastic colonic obstruction is feasible, effective and safe. It allowed outpa-tient management or brief hospitalization and early refeeding, improving the conditions to face an eventual palliative chemotherapy treatment. Most complications were late and resolved endoscopically on an outpatient basis. (AU)

La profesora Raquel Pérez González y el signo de la muela de cangrejo / Professor Raquel Pérez González and crab claw sign

La Dra. Raquel Pérez González, más conocida entre colegas, alumnos y compañeros de trabajo por "la profe Raquel", obtuvo el título de Medicina en el año 1976. Comenzó por vía directa la residencia de Radiología y obtuvo el título de especialista de primer grado en 1979. Se convirtió así, el Hospital Militar Central "Dr. Carlos J. Finlay", en la cuna de su formación profesional y en años posteriores, en la casa que la vio crecer, especialmente como maestra de numerosas generaciones de radiólogos e imagenólogos. Hoy reposan en el jardín del Departamento de Imagenología, parte de sus cenizas, custodiadas por el amor que fue capaz de cultivar. En el 2016, una paciente femenina de 60 años de edad, acudió a la consulta de gastroenterología, con dolor abdominal difuso. La radiografía de abdomen simple, anteroposterior, en posición acostado mostró, una imagen en "muela de cangrejo", visible al tomar el aire dentro del hemicolon transverso izquierdo, como contraste, el cual bordea por ese lado parcialmente, una opacidad de partes blandas, que se extiende desde el mesogastrio, hasta la fosa ilíaca derecha, donde se observa el signo del menisco. Los estudios de imágenes realizados, evidenciaron signos radiológicos típicos de invaginación por causa tumoral maligna. En varias ocasiones, la profesora Raquel utilizó la imagen de este caso, como pregunta en exámenes de promoción de residentes. La publicación de este caso constituye un homenaje a quien será siempre un paradigma de docente.

Dr. Raquel Pérez González, better known among colleagues, students and co-workers as "professor Raquel", obtained her degree in Medicine in 1976. She began her Radiology residency directly and obtained the title of first-class specialist degree in 1979. Thus, the Central Military Hospital "Dr. Carlos J. Finlay" is the cradle of her professional training and in later years, in her home where she saw her grow up, especially as a teacher to numerous generations of radiologists and imaging scientists. Today, part of her ashes rest in the garden of the Imaging Department, guarded by the love that she was able to cultivate. In 2016, a 60-year-old female patient attended the gastroenterology clinic with diffuse abdominal pain. The simple, anteroposterior abdominal x-ray, in the lying position, showed a "crab claw" image, visible when breathing into the left transverse hemicolon, as contrast, which partially borders on that side, a soft tissue opacity, which extends from the mesogastrium to the right iliac fossa, where the meniscus sign is observed. The imaging studies performed showed typical radiological signs of invagination due to malignant tumor. On several occasions, Professor Raquel used the image of this case as a question in resident promotion exams. The publication of this case constitutes a tribute to someone who will always be a paradigm of a teacher.

Pre and Post-high-intensity Interval Training Delays Colon Tumor Onset in a Syngeneic Mouse Model.

BACKGROUND/AIM: High-intensity interval training (HIIT) can trigger transient anti-tumor cytotoxicity through the mobilization of natural killer cells (NK cells) and myokines. Yet, the effects of HIIT on tumor development and microenvironment are unclear. MATERIALS AND METHODS: Male C57/BL6 mice were administered either MC38 of syngeneic colon cancer cells or vehicle in a single subcutaneous injection. Before injection, the training group completed four weeks of the HIIT program (progressive swimming training, 3/week, 10-12 min, 4-6% of body weight for overload). Following injection, trained mice continued to exercise for two additional weeks. RESULTS: Pre and post-HIIT training was effective in preventing tumor onset (p=0.0065), maintaining body weight gain, and counteracting splenomegaly by 40% compared to the tumor group. However, HIIT had no impact on suppressing tumor growth, modifying final tumor volume, or significantly changing tumor proliferation (Ki-67), connective tissue content, or DNA double-strand damage detected by phospho-histone gamma-H2AX (γ-H2AX). CONCLUSION: Pre and post-HIIT program is feasible for mice carrying a subcutaneous syngeneic tumor and effective in delaying tumor burden; however, HIIT did not alter colon tumor endpoints.

Ablação térmica para o tratamento do câncer de cólon e reto com metástase hepática irressecável ou ressecável com alto risco cirúrgico / Thermal ablation for colon cancer treatment and challenge with unresectable liver metastasis or resect with high surgical risk

INTRODUÇÃO: As técnicas de ablação são usadas para destruir tumores pequenos (até 4 cm), sem removê-los com cirurgia ou para diminuir seu tamanho possibilitando a cirurgia. A ablação por radiofrequência já é utilizada no SUS para tratamento do carcinoma hepático primário localizado, em estágios I e II. PERGUNTA DE PESQUISA: Para adultos com diagnóstico de câncer de cólon e reto com metástase hepática irressecável ou ressecável com alto risco cirúrgico, o tratamento com ablação térmica (por radiofrequência ou por micro-ondas) é eficaz, efetivo, seguro, custoefetivo e viável economicamente quando comparado ao tratamento com quimioterapia? EVIDÊNCIAS CIENTÍFICAS: Identificaram-se, por busca estruturada, duas revisões sistemáticas e dois estudos primários (duas publicações de um ECR de fase 2, de 2002 a 2007, e um estudo observacional retrospectivo). Não foi identificada evidência para ablação por micro-ondas que atendesse aos critérios de elegibilidade deste PTC. No estudo observa