MiR-15b-5p Promotes Growth and Metastasis of Renal Clear Cell Carcinoma / MiR-15b-5p Promueve el Crecimiento y la Metástasis del Carcinoma Renal de Células Claras

SUMMARY: We investigated the expression and clinical significance of miR-15b-5p in clear cell renal cell carcinoma (RCC) through bioinformatics analysis and experimental verification. The differentially expressed miRNAs were screened in the GEO database. Venn diagram showed that there were 5 up-regulated miRNAs (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p, and has-miR-193a-3p) and only 1 down-regulated miRNA (has-miR-532-3p) that were commonly expressed between GSE189331 and GSE16441 datasets. This was further confirmed in TCGA. Further analysis showed that the has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p, and has-miR-15b-5p were closely related to tumor invasion, distant metastasis and survival probability. The expression of miR-15b-5p in ccRCC tissues was significantly higher than that in adjacent normal kidney tissues (P0.05). Following inhibition of miR-15b-5p expression, RCC cells had attenuated proliferation, increased apoptosis, and attenuated migration and invasion. has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC. miR-15b-5p is highly expressed in cancer tissues of ccRCC patients. It may promote proliferation, inhibit apoptosis and enhance cell migration and invasion of RCC cells. The has-miR-15b-5p-WEE1, has-miR-15b-5p-EIF4E, and has-miR-15b-5p-PPP2R1B may be three potential regulatory pathways in ccRCC.

Investigamos la expresión y la importancia clínica de miR-15b-5p en el carcinoma de células renales (CCR) de células claras mediante análisis bioinformático y verificación experimental. Los miARN expresados diferencialmente se examinaron en la base de datos GEO. El diagrama de Venn mostró que había 5 miARN regulados positivamente (has-miR-210, has-miR-142-3p, has-miR-142-5p, has-miR-15b-5p y has-miR-193a-3p). ) y solo 1 miARN regulado negativamente (has-miR-532-3p) que se expresaron comúnmente entre los conjuntos de datos GSE189331 y GSE16441. Esto fue confirmado aún más en TCGA. Un análisis más detallado mostró que has-miR-193a-3p, has-miR-142-3p, has- miR-142-5p y has-miR-15b-5p estaban estrechamente relacionados con la invasión tumoral, la metástasis a distancia y la probabilidad de supervivencia. La expresión de miR-15b-5p en tejidos ccRCC fue significativamente mayor que la de los tejidos renales normales adyacentes (P 0,05). Tras la inhibición de la expresión de miR-15b-5p, las células RCC tuvieron una proliferación atenuada, un aumento de la apoptosis y una migración e invasión atenuadas. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E, has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC. miR-15b-5p se expresa altamente en tejidos cancerosos de pacientes con ccRCC. Puede promover la proliferación, inhibir la apoptosis y mejorar la migración celular y la invasión de células RCC. has-miR-15b-5p-WEE1, has- miR-15b-5p-EIF4E y has-miR-15b-5p-PPP2R1B pueden ser tres posibles vías reguladoras en ccRCC.

Peritumoral infiltration of local anesthetic before surgery in early breast cancer: a comment

This is a comment on a study recently published about peritumoral infiltration of local anesthetic before surgery in early breast cancer. Previously, animal models and a randomized study for stage IV breast cancer patients inferred that the removal of the primary tumor resulted in increased growth factors and worse distant disease control. Therefore, breast cancer surgery might not be a strictly local intervention. In this new randomized study, the intervention was a peritumoral infiltration of local anesthetic ­ lidocaine 0.5% in the six tumor margins, as an attempt to limit the systemic repercussions of surgery. Although the adjuvant treatment available for the study seems outdated, leading us to question the external validation, limited resources may have increased the power of surgery. Unknown mechanisms during surgery can change the patient's journey, and it is our duty to look at surgical studies with due seriousness

Hemicraniectomía endonasal por estesioneuroblastoma: informe de un caso / Endonasal hemicraniectomy by esthesioneuroblastoma: report of a case

El estesioneuroblastoma es una neoplasia maligna que se origina del epitelio olfatorio. El tratamiento se establece de acuerdo con su extensión y el grado histológico de atipia y puede incluir cirugía, cirugía más radioterapia o más radioquimioterapia. Se han utilizado diferentes abordajes quirúrgicos que incluyeron incisiones faciales y craneotomía pero, con la mayor experiencia adquirida en cirugía endoscópica de senos paranasales y el trabajo en equipo con el neurocirujano, se han desarrollado técnicas endonasales que posibilitan realizar resecciones oncológicas en pacientes seleccionados, con menos morbilidad, internación breve y sin comprometer el control local de la enfermedad. Describimos el caso clínico de una paciente con un estesioneuroblastoma con invasión intracraneal, que fue tratada con éxito mediante una hemicraniectomía endonasal preservando el bulbo olfatorio contralateral. (AU)

Esthesioneuroblastoma is a malignant neoplasm that originates from the olfactory epithelium. Treatment is established according to its extension and the histological degree of atypia and may include surgery, surgery more radiotherapy or more chemoradiation therapy. Different surgical approaches have been used, including facial incisions and craniotomy, but with the greater experience acquired with endoscopic sinus surgery and teamwork with the neurosurgeon, endonasal techniques have been developed that make it possible to perform oncological resections in selected patients, with less morbidity, brief hospitalization and without compromising local control of the disease. We describe the clinical case of a patient with an esthesioneuroblastoma with intracranial invasion who was successfully treated by endonasal hemicraniectomy preserving the contralateral olfactory bulb. (AU)

Estadiaje ganglionar en el adenocarcinoma gástrico / Lymph node stage in gastric adenocarcinoma

Resumen Objetivos: El sistema linfático del estómago es complejo y multidireccional, siendo difícil predecir el patrón de diseminación linfática en el adenocarcinoma (ADC) gástrico. Los objetivos de este trabajo son determinar si el analizar los grupos ganglionares de la pieza quirúrgica por separado tiene implicaciones en el estadiaje, además estudiar la afectación de diferentes grupos ganglionares. Materials y Método: Estudio observacional retrospectivo de pacientes intervenidos de gastrectomía y linfadenectomía con intención curativa por ADC en un hospital de referencia (2017-2021).,_Se han comparado aquellos pacientes cuya pieza quirúrgica se estudió en su totalidad (grupo A) con aquellos en los que se separaron los grupos ganglionares para su análisis (grupo B). En el grupo B, se ha analizado la afectación ganglionar de diferentes grupos ganglionares en base a la localización tumoral y el estadio pT. Resultados: Se incluyeron 150 pacientes. La media de ganglios analizados fue significativamente mayor cuando se separaron los grupos ganglionares (grupo B) (24,01 respecto a 20,49). La afectación ganglionar fue del 45,8%, 58,3% y 55,5% en los tumores de tercio superior, medio e inferior respectivamente, y los grupos difirieron en base a la localización tumoral. El riesgo de afectación ganglionar fue significativamente mayor y hubo más grupos ganglionares perigástricos afectos cuanto mayor era el estadio pT. Conclusiones: Separar los grupos ganglionares previo a su análisis aumenta el número de ganglios analizados mejorando el estadiaje ganglionar. Existen diferentes rutas de drenaje linfático dependiendo de la localización tumoral y la afectación ganglionar aumenta de forma paralela al estadio pT.

Objectives: The lymphatic system of the stomach is complex and multidirectional, making it difficult to predict the pattern of lymphatic spread in gastric adenocarcinoma (GAC). The aim of this paper is to determine if analyzing the lymph node groups of the surgical specimen separately has implications in the pathological staging, as well as to study the involvement rate of different lymph node groups. Material and Method: Retrospective observational study of patients who underwent curative intent gastrectomy and lymphadenectomy for GAC in a reference hospital (2017-2021). Those patients whose surgical specimen was studied as a whole (group A) were compared with those in whom the lymph node groups were separated by surgeons before analysis (group B). In group B, the involvement of different lymph node groups was analyzed based on tumor location and pT stage. Results: 150 patients were included. The mean number of lymph nodes analyzed was significantly higher when the lymph node groups were separately analyzed (group B) (24.01 compared to 20.49). Lymph node involvement was 45.8%, 58.3%, and 55.5% in tumors of the upper, middle, and lower third, respectively, and the involved groups differed depending on the tumor location. The higher the pT stage was, the risk of lymph node involvement was significantly higher and there were more perigastric lymph node groups affected. Conclusions: Separating lymph node groups prior to their analysis increases the number of lymph nodes analyzed and therefore improves lymph node staging. There are different lymphatic drainage routes depending on the tumor location and lymph node involvement increases in parallel with the pT stage.

Low-dose cisplatin exposure and SNAIL, Vimentin, E-cadherin expression in HEPG2 cell line / Exposición a dosis bajas de cisplatino y expresión de SNAIL, Vimentina, E-cadherina en línea celular HEPG2

Cisplatin, the first platinum compound approved for cancer treatment, is widely used in the treatment of various cancers including hepatocellular carcinoma (HCC). HCC incidence rates rise globally. Epithelial mesenchymal transition (EMT) is implicated in cancer invasion and metastasis, which are associated with increased mortality. Cisplatin dose might influence cancer invasion and metastatic behavior of the cells. The aim of the study was to investigate the effect of low-dose cisplatin treatment on EMT- related changes in HepG2 cells. Following treatment with 4 µM cisplatin, HepG2 cells were evaluated morphologically. Gene expression of E-cadherin, Vimentin, Snail1 was assessed by quantitative PCR. Immunofluorescence analyses of NA-K ATPase were performed. Although the low-dose cisplatin treated cells exhibited a more stretched morphology, no statistical difference was detected in gene expression of E-cadherin, Vimentin, Snail1 and immunofluorescence of NA-K ATPase. Findings on low-dose cisplatin effects in HepG2 might contribute to the knowledge of antineoplastic inefficacy by further understanding the molecular mechanisms of drug action.

El cisplatino, el primer compuesto de platino aprobado para el tratamiento del cáncer, es ampliamente utilizado en el tratamiento de varios tipos de cáncer, incluido el carcinoma hepatocelular (CHC). Las tasas de incidencia de CHC aumentan a nivel mundial. La transición mesenquimal epitelial (EMT) está implicada en la invasión del cáncer y la metástasis, que se asocian con un aumento de la mortalidad. La dosis de cisplatino podría influir en la invasión del cáncer y el comportamiento metastásico de las células. El objetivo del estudio fue investigar el efecto del tratamiento con dosis bajas de cisplatino en los cambios relacionados con la EMT en las células HepG2. Tras el tratamiento con cisplatino de 4 µM, se evaluaron morfológicamente las células HepG2. La expresión génica de E-cadherina, vimentina, caracol1 se evaluó mediante PCR cuantitativa. Se realizaron análisis de inmunofluorescencia de NA-K ATPasa . Aunque las células tratadas con cisplatino en dosis bajas exhibieron una morfología más estirada, no se detectaron diferencias estadísticas en la expresión génica de E-cadherina, vimentina, Snail1 e inmunofluorescencia de NA-K ATPasa. Los hallazgos sobre los efectos del cisplatino en dosis bajas en HepG2 podrían contribuir al conocimiento de la ineficacia antineoplásica al comprender mejor los mecanismos moleculares de la acción del fármaco.

Diagnosis of advanced disease in cases of colorectal cancer in a developing country

Objectives Colorectal cancer (CRC) is the second leading cause of cancer death in the world, with survival correlated with the extension of the disease at diagnosis. In many low-/middle-income countries, the incidence of CRC is increasing rapidly, while decreasing rates are observed in high-income countries. We evaluated the anatomopathological profile of 390 patients diagnosed with CRC who underwent surgical resection, over a six-year period, in the state of Paraíba, northeastern Brazil. Results Adenocarcinomas accounted for 98% of the cases of primary colorectal tumors, and 53.8% occurred in female patients. The average age of the sample was 63.5 years, with 81.8% of individuals older than 50 years of age and 6.4% under 40 years of age. The most frequent location was the distal colon; pT3 status was found in 71% of patients, and pT4 status, in 14.4%. Angiolymphatic and lymph-node involvements were found in 48.7% and 46.9% of the cases respectively. Distant metastasis was observed in 9.2% of the patients. Advanced disease was diagnosed in almost half of the patients (48.1%). The women in the sample had poorly-differentiated adenocarcinomas (p=0.043). Patients under 60 years of age had a higher rate of lymph-node metastasis (p=0.044). Tumor budding was present in 27.2% of the cases, and it was associated with the female gender, themucinous histological type, and the depth of invasion (pT3 and pT4). Conclusions We conclude that the diagnosis of advanced disease in CRC is still a reality, with a high occurrence of aggressive prognostic factors, which results in a worse prognosis. (AU)

Carcinoma papilar tiroideo con invasión locorregional: reporte de caso / Papillary thyroid crcinoma with locoregional invasion: case report

El cáncer diferenciado de tiroides incluye el tipo papilar y folicular que representan más del 80% de los casos y tienen un excelente pronóstico. Existen varios subtipos histológicos y las variantes foliculares son probablemente las más comunes. La incidencia de cáncer papilar variante folicular ha ido en aumento. En un reporte de un solo centro, cerca del 40% de los cánceres papilares eran variantes foliculares1. El subtipo infiltrativo de la variante folicular presenta sectores que invaden el parénquima tiroideo no neoplásico y carece de una cápsula tumoral bien definida. Tiene un comportamiento biológico y un perfil molecular que es más similar al tumor papilar clásico2. Existen características clínicas y patológicas asociadas con riesgo más alto de recurrencia tumoral y mortalidad; entre ellos se describen el tamaño del tumor primario y la presencia de invasión de tejidos blandos3. En la invasión de estructuras adyacentes, los sitios más comprometidos incluyen los músculos pretiroideos, el nervio laríngeo recurrente, el esófago, la faringe, laringe y la tráquea. Además, puede haber otras estructuras involucradas como: la vena yugular interna, la arteria carótida y los nervios vago, frénico y espinal4. El compromiso de los ganglios linfáticos y la incidencia de metástasis ganglionares en adultos depende de la extensión de la cirugía. Entre los que se realizan una disección radical modificada del cuello, hasta el 80% tienen metástasis en los ganglios linfáticos y el 50% de ellas son microscópicas5. Clínicamente los tumores localmente avanzados cursan con disfonía, disfagia, disnea, tos o hemoptisis, pero la ausencia de síntomas no descarta la invasión local. Según las guías de la American Thyroid Association6 son variables de mal pronóstico: la edad del paciente, el tamaño del tumor primario, la extensión extra tiroidea y la resección quirúrgica incompleta.

Differentiated thyroid cancer includes papillary and follicular types that represent more than 80% of cases and have an excellent prognosis. There are several histologic subtypes, and follicular variants are probably the most common. The incidence of papillary follicular variant cancer has been increasing. In a singlecenter report, about 40% of papillary cancers were follicular variants1. The infiltrative subtype of the follicular variant presents sectors that invade the non-neoplastic thyroid parenchyma and lacks a well-defined tumor capsule. It has a biological behavior and a molecular profile that is more similar to the classic papillary tumor2. There are clinical and pathological characteristics associated with a higher risk of tumor recurrence and mortality; These include the size of the primary tumor and the presence of soft tissue invasion3. In the invasion of adjacent structures, the most compromised sites include the pre-thyroid muscles, the recurrent laryngeal nerve, the esophagus, the pharynx, larynx and trachea. In addition, there may be other structures involved such as: the internal jugular vein, the carotid artery and the vagus, phrenic and spinal nerves4. The involvement of the lymph nodes and the incidence of lymph node metastases in adults depends on the extent of the surgery. Among those who undergo a modified radical neck dissection, up to 80% have lymph node metastases and 50% of them are microscopic5. Clinically locally advanced tumors present with dysphonia, dysphagia, dyspnea, cough, or hemoptysis, but the absence of symptoms does not rule out local invasion. According to the American Thyroid Association guidelines6, there are variables with a poor prognosis: the age of the patient, the size of the primary tumor, the extra-thyroid extension, and incomplete surgical resection.

Variante células altas de cáncer papilar de tiroides: reporte de casos / Tall cell variant of papillary thyroid cancer: case report

El cáncer papilar constituye aproximadamente el 80% de todos los casos de cáncer de tiroides y el 85% de los tumores diferenciados. La variante de células altas representa el 1,3 al 12% del cáncer papilar siendo la variante agresiva más común de estos tumores. Posee un comportamiento agresivo, con mayor incidencia de invasión extratiroidea, linfovascular y metástasis a distancia, responsables de tasas de recurrencia más altas y peor pronóstico. Los casos aquí reportados reflejan las características que hacen sospechar mayor agresividad tumoral, desde el diagnóstico. Describimos dos pacientes de sexo femenino, entre 40 y 50 años, con historia de corta evolución, cuya presentación fue con síntomas de compresión locorregional y adenopatías metastásicas en cuello. Con hallazgos ecográficos e intraoperatorios de relevancia en cuanto la agresividad tumoral que hicieron sospechar la presencia de una variante agresiva del cáncer papilar. La histopatología de la variante de células altas posee una base molecular diferente respecto al papilar clásico que le confiere mayor morbi-mortalidad, constituyendo un factor de pronóstico independiente para la recurrencia. El tratamiento quirúrgico es la tiroidectomía total con vaciamiento profiláctico de los ganglios linfáticos centrales y eventualmente vaciamiento lateral de cuello según valoración preoperatoria, con posterior ablación postoperatoria de restos tiroideos mediante yodo radiactivo.

Papillary cancer constitutes approximately 80% of all thyroid cancer cases and 85% of differentiated tumors. The tall cell variant represents 1.3 to 12% of papillary cancers, being the most common aggressive variant of these tumors. It has an aggressive behavior, showing a higher incidence of extrathyroid and lymphovascular invasion and distant metastasis, responsible for higher recurrence rates and a worse prognosis. The cases reported here reflect characteristics that make us suspect tumor aggressiveness. These are female patients, between 40 and 70 years old, with a history of short evolution. They present locoregional symptoms or metastatic adenopathies, with ultrasound and intraoperative findings of relevance in terms of tumor aggressiveness that led to the suspicion of the presence of an aggressive variant of papillary cancer. The histopathology of the tall cell variant has a different molecular basis that confers its own morbidity and mortality, being an independent prognostic factor for recurrence. Total thyroidectomy is recommended with prophylactic dissection of the central lymph nodes and eventually lateral neck dissection according to preoperative evaluation followed by postoperative ablation with radioactive iodine.

Factors associated with utilization of neoadjuvant chemotherapy in charlson comorbidity zero non-metastatic muscle-invasive bladder cancer patients

ABSTRACT Background: Guideline-based best practice treatment for muscle invasive bladder cancer (MIBC) involves neoadjuvant chemotherapy followed by radical cystectomy (NACRC). Prior studies have shown that a minority of patients receive NACRC and older age and renal function are drivers of non-receipt of NACRC. This study investigates treatment rates and factors associated with not receiving NACRC in MIBC patients with lower comorbidity status most likely to be candidates for NACRC. Materials and Methods: Retrospective United States National Cancer Database analysis from 2006 to 2015 of MIBC patients with Charlson comorbidity index (CCI) of zero. Analysis of NACRC treatment trends in higher CCI patients was also performed. Results: 15.561 MIBC patients met inclusion criteria. 1.507 (9.7%) received NACRC within 9 months of diagnosis. NACRC increased over time (15.0% in 2015 compared to 3.6% in 2006). Higher NACRC was noted in females, cT3 or cT4 cancer, later year of diagnosis, and academic facility treatment. Lower utilization was noted for blacks and NACRC decreased with increasing age and CCI. Only 16.9% of patients aged 23-62 in the lowest age quartile with muscle invasive bladder cancer and CCI of 0 received NACRC. Conclusions: Although utilization is increasing, receipt of NACRC remains low even in populations most likely to be candidates. Further study should continue to elucidate barriers to utilization of NACRC.

Cervical mesonephric adenocarcinoma: A case report of a rare gynecological tumor from embryological remains of the female genital tract / Adenocarcinoma mesonéfrico cervical: Relato de caso de um tumor ginecológico raro de restos embriológicos do trato genital feminino

Abstract Introduction Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as the uterine cervix. The information about these tumors, their treatment protocol, and prognosis are scarce. Case report A 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma. After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma. She was subjected to a radical hysterectomy, which revealed International Federation of Gynecology and Obstetrics (FIGO) IB1 stage, and adjuvant radiotherapy. The follow-up showed no evidence of recurrence after 60 months. Conclusion We present the case of a woman with cervical mesonephric adenocarcinoma. When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas. Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

Endoclips as novel fiducial markers in trimodality bladder-preserving therapy of muscle-invasive bladder carcinoma: feasibility and patient outcomes

ABSTRACT Hypothesis: Endoclip can be used as fiducial marker in urology. Objective: To assess the feasibility, cost effectiveness and reliability of endoclips as novel fiducial markers in precision radiotherapy, as part of a trimodality bladder-preserving treatment (TBPT) of muscle-invasive bladder carcinoma. Materials and Methods: This retrospective study was performed at Weifang People's Hospital (Weifang, China) from January 2015 to June 2018. A total of 15 patients underwent TBPT. Endoclips were applied to healthy edges of the resected bladder wall as novel fiducial markers. Radio-sensitizing chemotherapy and routine precision radiotherapy were given. The number and position of the endoclips during radiotherapy sessions were monitored. Complications and tumor recurrence were analyzed. Results: The mean age (±standard deviation) of the patients was 67±10 years (range 46-79). There were 3 females and 12 males. Forty-nine endoclips were applied in all patients (3.3±0.8). The tumor was completely visibly resected in all patients. The number of endoclips remained the same through the planned last radiotherapy session (3.3±0.8), i.e., none were lost. All endoclips were removed after the last radiotherapy session. The average number of follow-up months was 38.9±13.2 (range 11-52). There were no procedure-related complications at discharge or follow-up. At one-year, overall recurrence-free survival was 93.3%. Two patients had recurrences at 18 months and 10 months after TBPT, respectively, and salvage radical cystectomy was performed with no further recurrences. Another patient died due to metastasis 9 months after the completion of therapy. Conclusions: Endoclips are reliable, safe and cost-effective as novel fiducial markers in precision-radiotherapy post-TBPT.

Down-regulation of HCP5 inhibits cell proliferation, migration, and invasion through regulating EPHA7 by competitively binding miR-101 in osteosarcoma

Patients with osteosarcoma (OS) usually have poor overall survival because of frequent metastasis. Long non-coding RNAs (lncRNAs) have been reported to be associated with tumorigenesis and metastasis. In this study, we investigated the expression and roles of lncRNA human histocompatibility leukocyte antigen (HLA) complex P5 (HCP5) in OS, aiming to provide a novel molecular mechanism for OS. HCP5 was up-regulated both in OS tissues and cell lines and high expression of HCP5 was associated to low survival in OS patients. Down-regulation of HCP5 inhibited cell proliferation, migration, and invasion, suggesting its carcinogenic role in OS. miR-101 was targeted by HCP5 and its expression was decreased in OS. The inhibitor of miR-101 reversed the impact of HCP5 down-regulation on cell proliferation, apoptosis, and metastasis in OS. Ephrin receptor 7 (EPHA7) was proved to be a target of miR-101 and had ability to recover the effects of miR-101 inhibitor in OS. In conclusion, lncRNA HCP5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis through depleting the expression of EPHA7 by binding to miR-101, providing a potential therapeutic strategy of HCP5 in OS.

Low miR-1273a expression predicts poor prognosis of colon cancer and facilitates tumor cell proliferation, migration, and invasion

MicroRNAs (miRNAs) have been indicated to be frequently dysregulated in various cancers and promising biomarkers for colon cancer. The present study aimed to assess the prognostic significance and biological function of miR-1273a in colon cancer. The expression levels of miR-1273a was estimated using quantitative real-time polymerase chain reaction. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1273a in patients of colon cancer. The effects of miR-1273a on cell proliferation, migration, and invasion were investigated by cell experiments. The expression of miR-1273a was downregulated in colon cancer tissues and tumor cell lines compared with the normal controls (all P<0.001). The aberrant expression of miR-1273a was associated with vascular invasion (P=0.005), differentiation (P=0.023), lymph node metastasis (P=0.021), and TNM stage (P=0.004). The patients with low miR-1273a expression had low overall survival compared with the patients with high miR-1273a expression (log-rank P=0.002). miR-1273a was detected to be an independent prognostic biomarker for patients. Furthermore, the results of cell experiments revealed that miR-1273a downregulation promoted, while miR-1273a upregulation suppressed the cell proliferation, migration, and invasion. In conclusion, all data indicated that a downregulated expression of miR-1273a predicted poor prognosis for colon cancer and enhanced tumor cell proliferation, migration, and invasion. Thus, we suggest that methods to promote miR-1273a expression may serve as novel therapeutic strategies in colon cancer.

Melittin suppresses growth and induces apoptosis of non-small-cell lung cancer cells via down-regulation of TGF-ß-mediated ERK signal pathway

The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-β expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-β overexpression (pTGF-β) abolished melittin-decreased TGF-β expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-β and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-β-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.

Effects of Arf6 downregulation on biological characteristics of human prostate cancer cells

ABSTRACT Objective To evaluate the effects of Arf6 downregulation on human prostate cancer cells. Materials and Methods The effects of Arf6 downregulation on cell proliferation, migration, invasion and apoptosis were assessed by MTT, BrdU, scratch, Transwell assays and flow cytometry respectively. AKT, p-AKT, ERK1/2, p-ERK1/2 and Rac1 protein expressions were detected by Western blot. Results Downregulating Arf6 by siRNA interference suppressed the mRNA and protein expressions of Arf6. The proliferation capacities of siRNA group at 48h, 72h, and 96h were significantly lower than those of control group (P <0.05). The migration distance of siRNA group at 18h was significantly shorter than that of control group (P <0.01). The number of cells penetrating Transwell chamber membrane significantly decreased in siRNA group compared with that of control group (P <0.01). After 24h, negative control and normal control groups had similar apoptotic rates (P >0.05) which were both significantly lower than that of siRNA group (P <0.01). After Arf6 expression was downregulated, p-ERK1/2 and Rac1 protein expressions were significantly lower than those of control group (P <0.05). Conclusion Downregulating Arf6 expression can inhibit the proliferation, migration and invasion of prostate cancer cells in vitro, which may be related to ERK1/2 phosphorylation and Rac1 downregulation.

The impact of minimal extrathyroidal extension in the recurrence of papillary thyroid cancer patients

ABSTRACT Objective We aimed to evaluate the impact of minimal extrathyroidal extension (mETE) alone on the risk of recurrence of papillary thyroid carcinoma (PTC). The impact of other factors, including multifocality, age, tumor size, and stimulated thyroglobulin (sTg) values was also assessed. Subjects and methods We retrospectively analyzed 1,108 PTC patients from a medical institution, who presented tumors ≤ 4 cm without any adverse characteristics other than mETE. Patients were classified according to their response to initial treatment 12 to 24 months after surgery as proposed by the 2015 American Thyroid Association (ATA) guideline. Statistical analysis was performed using multivariate logistic regression and receiver operating characteristic (ROC) curve. Results In the multivariate logistic regression analysis, mETE did not have an impact on the response to initial treatment (p = 0.44), similar to multifocality, age, and tumor size. Initial Tg value was the only variable associated with a poor response (p < 0.01, odds ratio = 1.303, 95% confidence interval 1.25-1.36). The ROC analysis revealed that Tg was significant (area under curve = 0.8750); the cutoff value of sTg as a predictor of poor response was 10 ng/mL (sensitivity = 72.2%, specificity = 98.5%). Conclusion For low-risk PTC presenting mETE as the only aggressive feature, the initial sTg value is essential to identify patients who may have a poor response after initial treatment and benefit from further treatment. Arch Endocrinol Metab. 2020;64(3):251-6