RESUMEN

LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential. METHODS: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology. The changes in mitochondrial dynamics were observed through fluorescent imaging, while Western blot analysis was used to examine key autophagy and apoptosis markers. RESULTS: LAH significantly inhibited mitochondrial complex I activity, inducing ATP depletion and a compensatory increase in glycolysis. This disruption caused mitochondrial fragmentation, a trigger for autophagy, as shown by increased LC3-II expression and mTOR suppression. Apoptosis was also confirmed through the cleavage of caspase-3, contributing to reduced cancer cell viability. CONCLUSIONS: LAH's anticancer effects in CRC cells are driven by its disruption of mitochondrial function, triggering both autophagy and apoptosis. These findings highlight its potential as a therapeutic compound for further exploration in cancer treatment.

Asunto(s)

Apoptosis , Autofagia , Proliferación Celular , Neoplasias Colorrectales , Mitocondrias , Humanos , Autofagia/efectos de los fármacos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Acetogeninas/farmacología , Transducción de Señal/efectos de los fármacos , Glucólisis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos

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Robotic colectomy has been associated with comparable or improved short-term morbidity and mortality when compared to laparoscopic colectomy, including shorter length of stay. In this study, we sought to understand oncologic advantages for robotic as compared to laparoscopic colectomy in colon cancer. We analyzed the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) participant user files for all elective colon cancer cases from 1/2016 through 12/2021 performed with minimally invasive surgical techniques (robotic and laparoscopic). We calculated relative risks (RR) through Poisson Regression models and treatment effect coefficients by propensity-score match, after adjusting for age, BMI, ASA scores, mechanical and antibiotic bowel preparation, emergency surgery, race, gender, smoking status, hypertension and diabetes mellitus. Analyzed outcomes included rate of chemotherapy initiation within 90 days of surgery, number of harvested lymph nodes, any occurrence of intraoperative or postoperative blood transfusion, and the need for ostomy. During the study period, 44,745 patients underwent minimally invasive colectomy for colon cancer; 39,614 in the laparoscopic cohort and 7,831 in the robotic cohort. After adjusting for confounders, robotic colectomy was associated with a significant increase in the likelihood for initating chemotherapy within 90 days (RR 1.98, 95% CI {1.86-2.10}, p < 0.001). The robotic-treated patients had a significantly more lymph nodes harvested, a significant decrease in the need for intraperative or postoperative blood transfusion (RR 0.64, 95% CI {0.57-0.71}, p < 0.001) and a significant reduction in the need for ostomy formation (RR 0.26, 95% CI {0.22-0.30}, p < 0.001). As a retrospective and non-randomized study, residual bias and confouding variables are likely to exist. The study is also subject to coding incompleteness and inaccuracies. We also do not have additional context on potential factors that might influence time to chemotherapy. In addition, there is no information on surgeon or hospital volume, which can be associated with outcomes. Robotic colectomy for colon cancer was associated with significant improvement in the rate of chemotherapy initiation within 90 days, a significant reduction in need for blood transfusions, and a lower likelihood of receiving an ostomy when compared to laparoscopic colectomy procedures. The data reveal substantial short-term gains in oncologic outcomes for colon cancer performed with robotic techniques.

Asunto(s)

Colectomía , Neoplasias del Colon , Laparoscopía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Colectomía/métodos , Neoplasias del Colon/cirugía , Laparoscopía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Puntaje de Propensión , Tiempo de Internación/estadística & datos numéricos

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Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential ß-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/ß-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.

Asunto(s)

Neoplasias del Colon , Sinergismo Farmacológico , Fluorouracilo , Taurina , Taurina/farmacología , Animales , Fluorouracilo/farmacología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Ratas , Masculino , Modelos Animales de Enfermedad , Adenocarcinoma/tratamiento farmacológico , 1,2-Dimetilhidrazina , Ratas Wistar , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología

RESUMEN

This research identified the bioactive compounds and antioxidant capacity of the extractable (EP) and non-extractable (NEP) polyphenol fractions of berrycactus (BC). Additionally, the effects of BC and its residue (BCR) on preventing AOM/DSS-induced early colon carcinogenesis were evaluated in vivo. Male Sprague Dawley rats were randomly assigned to six groups (n = 12/group): healthy control (C), AOM/DSS, BC, BCR, BC+AOM/DSS, and BCR+AOM/DSS. NEP was obtained through acid hydrolysis using H2SO4 and HCl (1 M or 4 M). The HCl-NEP fraction exhibited the highest total phenolic and flavonoid content, while condensed tannins were more abundant in the H2SO4-NEP fraction. A total of 33 polyphenols were identified by UPLC-QTOF-MSE in both EP and NEP, some of which were novel to BC. Both NEP hydrolysates demonstrated significant total antioxidant capacity (TEAC), with HCl-NEP exhibiting the highest ORAC values. The BC+AOM/DSS and BCR+AOM/DSS groups exhibited fewer aberrant crypt foci (p < 0.05), reduced colonic epithelial injury, and presented lower fecal ß-glucuronidase activity, when compared to AOM/DSS group. No differences in butyric acid concentrations were observed between groups. This study presents novel bioactive compounds in EP and NEP from BC that contribute to chemopreventive effects in early colon carcinogenesis, while reducing fecal ß-glucuronidase activity and preserving colonic mucosal integrity.

RESUMEN

Polyploid Giant Cancer Cells (PGCCs) have been recognized as tumor cells that are resistant to anticancer therapies. However, it remains unclear whether their presence in the bloodstream can be consistently detected and utilized as a clinical marker to guide therapeutic anticancer regimens. To address these questions, we conducted a retrospective study involving 228 patients diagnosed with six different types of carcinomas (colon, gastric, NSCLC, breast, anal canal, kidney), with the majority of them (70%) being non-metastatic. Employing a highly sensitive liquid biopsy approach, ISET®, and cytopathological readout, we isolated and detected circulating PGCCs in the patients' blood samples. PGCCs were identified in 46 (20.18%) out of 228 patients, including in 14.47% of 152 non-metastatic and 29.85% of 67 metastatic cases. Patients were subsequently monitored for a mean follow up period of 44.74 months (95%CI: 33.39-55.79 months). Remarkably, the presence of circulating PGCCs emerged as a statistically significant indicator of poor overall survival. Our findings suggest that circulating PGCCs hold promise as a reliable prognostic indicator. They underscore the importance of further extensive investigations into the role of circulating PGCCs as a prognostic marker and the development of anti-PGCC therapeutic strategies to improve cancer management and patient survival.

Asunto(s)

Biomarcadores de Tumor , Células Gigantes , Células Neoplásicas Circulantes , Poliploidía , Humanos , Femenino , Masculino , Pronóstico , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Anciano , Células Neoplásicas Circulantes/patología , Células Neoplásicas Circulantes/metabolismo , Células Gigantes/patología , Estudios Retrospectivos , Adulto , Neoplasias/sangre , Neoplasias/patología , Neoplasias/diagnóstico , Carcinoma/sangre , Carcinoma/patología , Carcinoma/diagnóstico , Anciano de 80 o más Años

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Background and Objectives: Colon cancer (CC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like matted nodes (lymph node conglomerates), are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of matted nodes in CC. Materials and Methods: From a retrospective analysis of 502 CC consecutive cases treated with colectomy (2005-2018), we identified 255 (50.8%) cases with lymph node metastasis (our study group), which were categorized into two groups: (1) lymph node metastasis alone (n = 208), and (2) lymph node metastasis with matted nodes (n = 47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for patients with matted nodes was 47.7%, compared to 60% without (p = 0.096); however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and adjuvant chemotherapy use as independent factors contributing to survival. Conclusions: This study underscores matted nodes as potential prognostic indicators in CC, emphasizing their association with higher pN stage and reduced survival. Although the patients with matted nodes showed lower survival, this figure did not search statistical significance, but a tendency was detected, which necessitates precise further research, which is essential for validating these findings and integrating matted nodes into the broader context of colorectal cancer management.

Asunto(s)

Adenocarcinoma , Neoplasias del Colon , Metástasis Linfática , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Persona de Mediana Edad , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Ganglios Linfáticos/patología , México/epidemiología , Pronóstico , Análisis de Supervivencia , Adulto , Colectomía/estadística & datos numéricos , Colectomía/métodos , Anciano de 80 o más Años , Estadificación de Neoplasias

RESUMEN

Colorectal cancer is one of the predominant tumors in the world, primarily generated by a progression from polyp to cancer which can last several years, giving a great opportunity to the scientific community for its prevention by screening programs that can be done with invasive and non-invasive tests. In this issue, Lopes et al show us an excellent review of screening, its options, its advantages and disadvantages.

RESUMEN

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.

Asunto(s)

Anastomosis Quirúrgica , Colectomía , Neoplasias del Colon , Laparoscopía , Curva de Aprendizaje , Mesocolon , Tempo Operativo , Puntaje de Propensión , Humanos , Laparoscopía/métodos , Laparoscopía/educación , Colectomía/métodos , Colectomía/educación , Masculino , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Femenino , Mesocolon/cirugía , Anastomosis Quirúrgica/métodos , Anastomosis Quirúrgica/educación , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Tiempo de Internación/estadística & datos numéricos

RESUMEN

OBJECTIVE: To examine the impact of a combined craniocaudal approach on pain and complications during laparoscopic D3 lymph node dissection in clients diagnosed with right colon cancer (RCC). METHODS: 100 RCC patients were divided into Group A and Group B. Both groups underwent laparoscopic D3 lymph node dissection, with Group A undergoing an intermediate approach and Group B undergoing a combined head and tail approach. Two groups of patients' perioperative (surgical time, intraoperative blood loss, number of lymph node dissection) indicators, postoperative recovery (postoperative exhaust time, postoperative hospital stay, drainage tube removal time) indicators, perioperative pain level (VAS scores 1, 3, and 5 days following surgery), and incidence of complications (vascular injury, intestinal obstruction, anastomotic bleeding, incision infection), and the therapeutic efficacy [CEA, CA19-9] indicators were compared. RESULTS: Clients in the B team had substantially shorter operating times and considerably fewer intraoperative hemorrhage than those in the A team. The VAS grades of clients in the B team were considerably lower than those in the A team the day following surgery. Clients in the B team experienced vascular injury at a substantially lower rate than those in the A team. The overall incidence rate of problems did not differ statistically significantly between the A team and the B team. Following therapy, teams A and B's CEA and CA19-9 levels were considerably lower than those of the same team prior to therapy. CONCLUSION: Combined craniocaudal technique can significantly reduce intraoperative bleeding, postoperative pain, and the risk of sequelae from vascular injuries.

RESUMEN

Colorectal cancer (CRC) is a significant global health concern. Prognostication of CRC traditionally relies on the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) TNM staging classifications, yet clinical outcomes often vary independently of stage. Despite similarities, rectal and colon cancers are distinct in their diagnostic methodologies and treatments, with MRI and CT scans primarily used for staging rectal and colon cancers, respectively. This paper examines the challenges in accurately assessing prognostic factors of colon cancer such as primary tumor extramural extension, retroperitoneal surgical margin (RSM) involvement, extramural vessel invasion (EMVI), and lymph node metastases through preoperative CT and MRI. It highlights the importance of these factors in risk stratification, treatment decisions, and surgical planning for colon cancer patients. Advancements in imaging techniques are crucial for improving clinical management and optimizing patient outcomes, underscoring the necessity for ongoing research to refine diagnostic methods and incorporate novel findings into practice.

Asunto(s)

Neoplasias del Colon , Imagen por Resonancia Magnética , Estadificación de Neoplasias , Tomografía Computarizada por Rayos X , Humanos , Imagen por Resonancia Magnética/métodos , Pronóstico , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/patología , Invasividad Neoplásica , Metástasis Linfática/diagnóstico por imagen

RESUMEN

Introduction: The anastomotic leak (AL) is one of the most feared complications of colorectal surgery, since it is associated with a high rate of morbidity, mortality, length of hospital stay and cost of care. Our aim was to determine the risk factors associated with anastomosis leak in colorectal cancer patients who underwent surgical resection with anastomosis. Methods: A multicentre observational, analytical, retrospective and case-control study was carried out. For each case, two controls were included from three national hospitals from Lima, Peru during the period 2021-2022. To determine the degree of association, multivariate logistic regression model was carried out. Results: A total of 360 patients were included, 120 from each hospital. The mean age of the population was 68.03 ± 14.21 years old. The majority were 65 years old or older (66.1%), 52.8% were female, and 63.3% had clinical stage III. The 40% of the patients had albumin levels lower than 3.5 g/dL. Regarding the surgery, 96.4% were elective, 68.9% underwent open approach, and 80.8% had an operative time of more than 180 minutes. Most of them had right colon cancer (50.8%). In the multivariate analysis, a significant association was found with the age variable (OR = 2.48; 95%CI:1.24-4.97), clinical tumour level (OR = 2.71; 95%CI:1.34-5.48), American Society of Anesthesiologists (ASA) Score (OR = 3.23; 95%CI:1.10-9.50), preoperative serum albumin (OR = 22.2; 95%CI:11.5-42.9). Conclusion: The most important independent risk factors associated with AL among patients with colorectal cancer were pre-operative such as lower preoperative serum albumin levels, followed by a higher ASA Score, clinical-stage III-IV, and an age ≥65 years old.

RESUMEN

This study aimed to assess the use of colorectal cancer (CRC) tests for prevention and early detection, alongside exploring the associated barriers to these tests. A stratified national survey was conducted in Chile, involving 1893 respondents (with a 2.3% error margin and 95% confidence interval). Logistic and multinomial regression analyses were employed to examine variations in test utilization likelihood and barrier. We found that the key determinants for undergoing CRC tests included age, health status, possession of private health insurance, and attainment of postgraduate education. Notably, 18% and 29% of respondents covered by public and private insurance, respectively, cited personal prevention as the primary motivation for test uptake. The principal obstacle identified was lack of knowledge, mentioned by 65% of respondents, while 29% and 19% of the publicly and privately insured respectively highlighted lack of access as a barrier. The results of this study provide valuable insights into factors influencing CRC screening, aiming to inform public health policies for expanding national coverage beyond diagnosis and treatment to encompass preventive measures.

Asunto(s)

Neoplasias Colorrectales , Seguro de Salud , Humanos , Chile/epidemiología , Detección Precoz del Cáncer , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Cobertura del Seguro

RESUMEN

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.

Asunto(s)

Neoplasias del Colon , Citostáticos , Humanos , Citostáticos/farmacología , Mitógenos/farmacología , Transducción de Señal , Proteínas Mitocondriales/metabolismo , Proliferación Celular , Proteínas Portadoras/metabolismo

RESUMEN

Colorectal cancer (CRC) is the third most common neoplasia in the world. Its mortality rate is high due to the lack of specific and effective treatments, metastasis, and resistance to chemotherapy, among other factors. The natural products in cancer are a primary source of bioactive molecules. In this research, we evaluated the antitumor activity of an acetogenin (ACG), laherradurin (LH), isolated from the Mexican medicinal plant Annona macroprophyllata Donn.Sm. in a CRC murine model. The CRC was induced by azoxymethane-dextran sulfate sodium (AOM/DSS) in Balb/c mice and treated for 21 days with LH or cisplatin. This study shows for the first time the antitumor activity of LH in an AOM/DSS CRC model. The acetogenin diminished the number and size of tumors compared with cisplatin; the histologic studies revealed a recovery of the colon tissue, and the blood toxicity data pointed to less damage in animals treated with LH. The TUNEL assay indicated cell death by apoptosis, and the in vitro studies exhibited that LH inhibited cell migration in HCT116 cells. Our study provides strong evidence of a possible anticancer agent for CRC.

RESUMEN

BACKGROUND: The current challenge in clinical cancer treatment is chemoresistance. Colon cells have inherently higher xenobiotic transporters expression and hence can attain resistance rapidly. Increased levels of TGF-ß2 expression in patients have been attributed to cancer progression, aggressiveness, and resistance. To investigate resistance progression, we treated doxorubicin (dox) to HT-29 colon adenocarcinoma cells in the presence or absence of TGF-ß2 ligand. METHODS: After 1, 3-, and 7-day treatment, we investigated cell proliferation, viability, and cytotoxicity by MTT, trypan blue staining, and lactate dehydrogenase enzyme release. The mechanism of cell death was elucidated by hoechst33342 and propidium iodide dual staining and apoptosis assay. The development of resistance was detected by rhodamine123 efflux and P-glycoprotein (P-gp)/MDR1 antibody staining through fluorimetry and flow cytometry. The colony formation ability of the cells was also elucidated. RESULTS: Inhibition of cell proliferation was noted after day 1, while a significant reduction in viability and a significant increase in lactate dehydrogenase release was detected after day 3. Reduction of intracellular rhodamine123 levels was detected after day 3 and was significantly lower in dox with TGF-ß2 treatment compared to dox alone. Increased surface P-gp levels after days 3 and 7 were observed in the treated groups. Hoechst33342/propidium iodide staining and apoptosis assay indicated non-apoptotic cell death. The cells treated with TGF-ß2 had higher colony formation ability. CONCLUSIONS: TGF-ß2 expression might play a significant role in the development of chemoresistance to doxorubicin in Duke's type B colon adenocarcinoma cell line, HT-29.

Asunto(s)

Adenocarcinoma , Antibióticos Antineoplásicos , Apoptosis , Proliferación Celular , Neoplasias del Colon , Doxorrubicina , Resistencia a Antineoplásicos , Factor de Crecimiento Transformador beta2 , Humanos , Doxorrubicina/farmacología , Adenocarcinoma/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Factor de Crecimiento Transformador beta2/metabolismo , Antibióticos Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Células HT29 , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Neoplasias del Colon , Entrenamiento de Intervalos de Alta Intensidad , Condicionamiento Físico Animal , Masculino , Ratones , Animales , Obesidad/metabolismo , Peso Corporal , Neoplasias del Colon/terapia , Microambiente Tumoral

RESUMEN

PURPOSE: To identify the relevant factors affecting the prognosis and survival time of colon cancer and construct a survival prediction model. METHODS: Data on postoperative stage I-III colon cancer patients were obtained from the Surveillance, Epidemiology, and End Results database. We used R project to analyze the data. Univariate and multivariate Cox regression analyses were performed for independent factors correlated with overall survival from colon cancer. The C-index was used to screen the factors that had the greatest influence in overall survival after surgery in colon cancer patients. Receiver operating characteristic (ROC) curve was made according to the Risk score and calculated to validate the predictive accuracy of the model. In addition, we used decision curve analysis (DCA) to evaluate the clinical benefits and utility of the nomogram. We created a model survival curve to determine the difference in prognosis between patients in the low-risk group and those in the high-risk group. RESULTS: Univariate and multifactor COX analyses showed that the race, Grade, tumor size, N-stage and T-stage were independent risk factors affecting survival time of patients. The analysis of ROC and DCA showed the nomogram prediction model constructed based on the above indicators has good predictive effects. CONCLUSION: Overall, the nomogram constructed in this study has good predictive effects. It can provide a reference for future clinicians to evaluate the prognosis of colon cancer patients.

Asunto(s)

Neoplasias del Colon , Nomogramas , Humanos , Pronóstico , Neoplasias del Colon/cirugía , Bases de Datos Factuales , Análisis Multivariante

RESUMEN

AIM: To assess the value of a prehabilitation program adapted to the current COVID-19 pandemic using a teleprehabilitation modality in a public Latin American hospital. METHODS: The medical records of candidates for elective colorectal cancer surgery (CRC) and who completed a teleprehabiltation program were analyzed. Sociodemographic, clinical, and functional variables were analyzed, such as cardiorespiratory capacity with the sit-to-stand test (STST), independence in activities of daily living with the Barthel index, balance with the five-times STST (FSTST) and fatigue with Brief Inventory Fatigue (BFI). The feasibility of the program was analyzed in terms of recruitment, retention, user satisfaction, and reporting of adverse events. RESULTS: Of 107 people recruited, 57 completed the program (54%, 68.78 ± 12.36 years). There was a significant difference in the BFI, FSTST, and STS 1-min scores after the intervention (p < .01), with an effect size (Cliff's delta) that varied between -.13 and .21. There were no differences in the Barthel index score. In relation to the viability of the program, 99% of patients referred for surgery could be recruited into the program, with 53% retention. Regarding user satisfaction with the program, seven items (77.7%) were rated as "very satisfied," and two items (22.3%) as "satisfied." No adverse events were recorded. CONCLUSION: The structured prehabilitation program adapted to teleprehabilitation for CRC candidates for surgery was effective in optimizing functional results prior to surgery and was feasible to implement in a public hospital with limited resources during the COVID-19 pandemic.

Asunto(s)

COVID-19 , Neoplasias Colorrectales , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Actividades Cotidianas , Estudios de Factibilidad , Pandemias/prevención & control , Neoplasias Colorrectales/cirugía

RESUMEN

BACKGROUND: The COVID-19 pandemic created a backlog in colorectal cancer (CRC) screening and surveillance colonoscopies. The real impact in Argentina is not fully known. GOAL: To estimate the impact of the COVID-19 pandemic on CRC prevention by comparing the number of CRC screening and surveillance consults in a clinical decision support-tool used in Argentina before, during and after pandemic lockdown. METHODS: We analyzed data from May 2019 to December 2021 from CaPtyVa, a clinical decision support tool for CRC screening and surveillance. Queries were divided in pre-pandemic (May 2019 to March 2020), lockdown (April 2020 to December 2020), and post-lockdown (January 2021 to December 2021). The number of CRC monthly screening and surveillance visits were compared among the three periods and stratified according to CRC risk. RESULTS: Overall, 27,563 consults were analyzed of which 9035 were screening and 18,528 were surveillance. Pre-pandemic, the median number of screening consults was 346 per month (IQR25-75 280-410). There was a decrease to 156 (80-210)/month (p<0.005) during lockdown that partially recovered during post-lockdown to 230 (170-290)/month (p=0.05). Pre-pandemic, the median number of surveillance consults was 716 (560-880)/month. They decreased to 354 (190-470)/month during lockdown (p<.05) and unlike screening, completely recovered during post-lockdown to 581 (450-790)/month. CONCLUSIONS: There was a >50% decrease in the number of CRC screening and surveillance consults registered in CaPtyVa during lockdown in Argentina. Post-lockdown, surveillance consults recovered to pre-pandemic levels, but screening consults remained at 66% of pre-pandemic levels. This has implications for delays in CRC diagnoses and patient outcomes.

Asunto(s)

COVID-19 , Neoplasias Colorrectales , Sistemas de Apoyo a Decisiones Clínicas , Neoplasias , Humanos , Detección Precoz del Cáncer , COVID-19/epidemiología , Argentina/epidemiología , Control de Enfermedades Transmisibles , Pandemias/prevención & control , Estudios Retrospectivos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología

RESUMEN

PURPOSE: Metabolic reprogramming is a novel hallmark and therapeutic target of cancer. Our study aimed to establish fatty acid metabolism-associated scores based on gene signature and investigated its effects on immunotherapy in colon cancer. METHODS: Gene expression and clinical information were collected from Gene Expression Omnibus (GEO) database to identify a gene signature by non-negative matrix factorization (NMF) clustering and Cox regression analysis. Subsequently, we constructed the fatty acid metabolism score (FA-score) model by principal component analysis (PCA) and explored its relativity of prognosis and the response to immunotherapy in colon cancer. Finally, the Cancer Genome Atlas (TCGA) database was introduced and in vitro study was performed for verification. RESULTS: The FA-score-high group had a higher level of fatty acid metabolism and was associated with worse patient overall survival. Significantly, FA-score correlated closely with the biomarkers of immunotherapy, and the FA-score-high group had a poorer therapeutic efficacy of immune checkpoint blockade. In vitro experiments demonstrated that ACSL5 may be a critical metabolic regulatory target. CONCLUSIONS: Our study provided a comprehensive analysis of the heterogeneity of fatty acid metabolism in colon cancer. We highlighted the potential clinical utility of fatty acid metabolism-related genes to be biomarkers of colon cancer prognosis and targets to improve the effect of immunotherapy.

Asunto(s)

Neoplasias del Colon , Humanos , Pronóstico , Neoplasias del Colon/genética , Neoplasias del Colon/terapia , Inmunoterapia , Biomarcadores , Ácidos Grasos