Metastasizing pleomorphic adenoma of the parotid gland: A common tumour with a very unusual presentation / Metástasis de adenoma pleomorfo de la glándula parótida: un tumor frecuente con una presentación muy poco habitual

Metastasizing pleomorphic adenoma is recognized as a subtype of pleomorphic adenoma in WHO classification 5th edition of salivary glands. The controversy pertaining to the entity is the benign features of the disease even at a metastatic site. We present a rare case of left recurrent pre-auricular swelling in a young male reported as metastasizing pleomorphic adenoma. A nineteen-year-old male presented with left preauricular swelling seven years ago which was diagnosed as pleomorphic adenoma and underwent complete excision of tumour. The tumour recurred twice – two and five years after the surgery. At the second recurrence, the level II neck dissection showed multiple encapsulated deposits of pleomorphic adenoma having similar morphology in the cervical soft tissue with no features of high-grade transformation. (AU)

La metástasis de adenoma pleomorfo está reconocida como un subtipo de adenoma pleomorfo según la clasificación de tumores de las glándulas salivales de la Organización Mundial de la Salud (OMS), 5ª edición. La controversia sobre la entidad se refiere a las características benignas de la enfermedad, incluso en lugares de metástasis. Presentamos un raro caso, en un varón de 19 años, de inflamación preauricular izquierda recurrente que se comunica como una metástasis de adenoma pleomorfo. El paciente presentó inflamación preauricular izquierda hace siete años, que se diagnosticó como adenoma pleomorfo, y se sometió a una resección completa del tumor, el cual presentó dos recidivas, dos y cinco años después de la cirugía. En la segunda recidiva, la resección a nivel II del cuello mostró múltiples depósitos encapsulados de adenoma pleomorfo de morfología similar en el tejido blando cervical, sin características de transformación de alto grado. (AU)

Extraskeletal myxoid chondrosarcoma metastasis to a Meckel's diverticulum adenocarcinoma / Metástasis de condrosarcoma mixoide extraesquelético a un adenocarcinoma de divertículo de Meckel

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature. (AU)

El condrosarcoma mixoide extraesquelético es un tumor de tejidos blandos poco frecuente, con una elevada tasa de recurrencia y metástasis a distancia y una respuesta limitada a la quimioterapia. El divertículo de Meckel es la anomalía congénita más frecuente y se asocia a un riesgo considerable de transformación maligna. En este caso clínico describimos a una paciente de 50 años con antecedentes de condrosarcoma mixoide extraesquelético de miembro inferior y metástasis en el antebrazo que acudió al servicio de urgencias por dolor abdominal. La exploración reveló un vólvulo cecal. Se descubrió incidentalmente una lesión en el tercio medio del íleon, que se extirpó durante la intervención quirúrgica. El examen patológico reveló un adenocarcinoma de divertículo de Meckel, afectado por metástasis de condrosarcoma mixoide extraesquelético. La resección fue completa; sin embargo, la paciente presentaba enfermedad pulmonar metastásica difusa y falleció ocho meses después debido a la progresión de la enfermedad. Este mecanismo de metástasis entre tumores está descrito en otras localizaciones, pero en lo que respecta al divertículo de Meckel, se trata de una situación única en la literatura. (AU)

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma.

Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally, we explored the impact of FAK degradation on HCC metastasis through wound healing experiments, transwell invasion experiments, and a xenograft tumor model. The expression of proteins related to epithelial-mesenchymal transition (EMT) was measured to elucidate the underlying mechanisms. The results showed that FAK PROTAC can degrade FAK, inhibit the migration and invasion of HCC cells in vitro, and notably decrease the lung metastasis of HCC in vivo. Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited. Consequently, degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis, holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Stressed out neutrophils drive metastasis.

Stress hormones can contribute to cancer progression, but how immune cells play a role in this process is unclear. In a recent study in Cancer Cell, He et al. showed that glucocorticoids potentiate metastasis by skewing neutrophils toward pro-tumorigenic functions.

Tumores renales múltiples y hereditarios. Revisión por y para radiólogos / Multiple and hereditary renal tumors: A review for radiologists

El 80% de los carcinomas renales (CR) se diagnostican incidentalmente por imagen. Se aceptan un 2-4% de multifocalidad «esporádica» y un 5-8% de síndromes hereditarios, probablemente con infraestimación. Multifocalidad, edad joven, historia familiar, datos sindrómicos y ciertas histologías hacen sospechar un síndrome hereditario. Debe estudiarse individualmente cada tumor y multidisciplinarmente al paciente, con estrategias terapéuticas conservadoras de nefronas y un abordaje diagnóstico radioprotector. Se revisan los datos relevantes para el radiólogo en los síndromes de von Hippel-Lindau, translocación de cromosoma-3, mutación de proteína-1 asociada a BRCA, CR asociado a déficit en succinato-deshidrogenasa, PTEN, CR papilar hereditario, cáncer papilar tiroideo-CR papilar, leiomiomatosis hereditaria y CR, Birt-Hogg-Dubé, complejo esclerosis tuberosa, Lynch, translocación Xp11.2/fusión TFE3, rasgo de células falciformes, mutación DICER1, hiperparatoridismo y tumor mandibular hereditario, así como los principales síndromes de predisposición al tumor de Wilms.(AU)

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of “sporadic” multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended. Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of “non-hereditary” familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.(AU)

Impact of biliary stents in the performance of the EUS-guided tissue acquisition: A systematic review and meta-analysis / Impacto de los stents biliares en el rendimiento de la adquisición de biopsias guiadas por ecoendoscopia: una revisión sistemática y metanálisis

Introduction and aim: Pancreatobiliary tumours are challenging to diagnose exclusively by imaging methods. Although the optimum moment for carrying out the EUS is not well defined, it has been suggested that the presence of biliary stents may interfere with the proper staging of tumours and the acquisition of samples. We performed a meta-analysis to evaluate the impact of biliary stents on EUS-guided tissue acquisition yield. Material and methods: We conducted a systematic review in different databases, such as PubMed, Cochrane, Medline, and OVID Database. A search was made of all studies published up to February 2022. Results: Eight studies were analyzed. A total of 3185 patients were included. The mean age was 66.9±2.7 years; 55.4% were male gender. Overall, 1761 patients (55.3%) underwent EUS guided tissue acquisition (EUS-TA) with stents in situ, whereas 1424 patients (44.7%) underwent EUS-TA without stents. The technical success was similar in both groups (EUS-TA with stents: 88% vs EUS-TA without stents: 88%, OR=0.92 [95% CI 0.55–1.56]). The type of stent, the needle size and the number of the passes were similar in both groups. Conclusions: EUS-TA has similar diagnostic performance and technical success in patients with or without stents. The type of stent (SEMS or plastic) does not seem to influence the diagnostic performance of EUS-TA. Future prospectives and RCT studies are needed to strengthen these conclusions. (AU)

Introducción y objetivo: Los tumores pancreatobiliares son lesiones difíciles de diagnosticar exclusivamente por métodos de imagen. Aunque no está bien definido el momento óptimo para la realización de la ecoendoscopia (EUS), se ha demostrado que la presencia de stents biliares puede interferir en la correcta estadificación de los tumores y la toma de muestras. Realizamos un metanálisis para evaluar el impacto de los stents biliares en el rendimiento de la adquisición de tejido guiada por EUS. Material y métodos: Realizamos una revisión sistemática en diferentes bases de datos, como PubMed, Cochrane, Medline y OVID Database. Se realizó una búsqueda de todos los estudios publicados hasta febrero de 2022. Resultados: Se analizaron 8 estudios. Se incluyeron un total de 3.185 pacientes. La media de edad fue de 66,9±2,7 años; el 55,4% fueron pacientes de sexo masculino. En total, 1.761 pacientes (55,3%) se sometieron a biopsias guiadas por EUS con stents in situ, mientras que 1.424 pacientes (44,7%) se sometieron a dichas biopsias sin stents. El éxito técnico fue similar en ambos grupos (EUS con stents: 88% vs. EUS sin stents: 88%, OR=0,92 [IC 95% 0,55-1,56]). El tipo de stent, el tamaño de la aguja y el número de pases fueron similares en ambos grupos. Conclusiones: La biopsia por EUS tiene un rendimiento diagnóstico y un éxito técnico similares en pacientes con o sin stents. El tipo de stent (SEMS o plástico) no parece influir en el rendimiento diagnóstico de la adquisición de tejido guiada por EUS. Se necesitan futuros estudios prospectivos y estudios aleatorizados controlados para fortalecer estas conclusiones. (AU)

Comparativa de los métodos de evComparativa de los métodos de evaluación de la reserva de yodo corporal previamente a la realización de tratamiento con radioyodoaluación de la reserva de yodo corporal previamente a la realización de tratamiento con radioyodo / Comparison of Body Iodine Pool Assessment Methods Before Radioiodine Therapy

Introducción y objetivos: El tratamiento con yodo radiactivo (RAIT) se recomienda para reducir el riesgo de recurrencia y de metástasis en personas con cáncer diferenciado de tiroides (CDT) de riesgo intermedio-alto. En la preparación para la RAIT, la estimulación de la tirotropina y la reducción en la reserva corporal de yodo son elementos importantes para contribuir al éxito de la terapia. Para ello, se pide a los pacientes que reduzcan la ingesta de este mineral antes de la RAIT, y puede evaluarse su reserva corporal midiendo su excreción por la orina (yoduria) antes del tratamiento. El objetivo de nuestro estudio ha sido comparar los métodos utilizados para medir la reserva de yodo corporal en la evaluación de la eficacia de la dieta con bajo contenido en yodo (RID) aplicada a la preparación del paciente para la RAIT. Pacientes y métodos: Suspendieron la levotiroxina tres semanas antes de la RAIT y fueron controlados con una RID durante las dos semanas previas a la realización del tratamiento 80 pacientes con CDT. Tras dos semanas de RID, en todos se llevó a cabo una recolección de orina de 24h el día previo a la fecha de administración de la RAIT. Los sujetos finalizaron dicha recolección en la mañana de la fecha de RAIT y suministraron una muestra puntual de orina. Se calculó la excreción estimada de creatinina en orina de 24 horas de los pacientes. La estimación de la excreción urinaria de yodo o yoduria (UIE) de 24 horas oras se determinó a partir del índice yodo/creatinina (I/C) obtenido en la muestra de orina puntual de los individuos. Se compararon los resultados de la yoduria de 24 horas, la concentración de yodo en la muestra puntual de orina, el cociente I/C en la muestra puntual de orina y la estimación de la yoduria de 24 horas en los pacientes. Resultados: En 99%, la eficacia de la RID fue suficiente según la yoduria de 24 horas obtenida previamente a la RAIT...(AU)

Introduction and Objectives: Radioactive iodine therapy (RAIT) is recommended to reduce the risk of recurrence and metastasis in patients with intermediate-high risk differentiated thyroid cancer (DTC). In preparation for RAIT, stimulation of thyroid-stimulating hormone and reduction of body iodine pool are important for treatment success. For this purpose, patients are asked to reduce their iodine intake before RAIT, and the body iodine pool can be evaluated by measuring iodine excretion in urine before treatment. The aim of our study is to compare the methods used to measure the body iodine pool in the evaluation of the restricted iodine diet (RID) effectiveness applied in the RAIT preparation. Patients and methods: Eighty DTC patients discontinued levothyroxine three weeks before RAIT and followed up with a RID two weeks before treatment. After two weeks of RID, all patients collected their 24-hour urine the day before the RAIT date. Patients completed 24-hour urine samples on the morning of the RAIT date and also provided a spot urine sample. The estimated 24-hour creatinine excretion of the patients was calculated. Estimated 24-hour urinary iodine excretion (UIE) was calculated using the spot urine iodine/creatinine (I/C) ratio of the patients. 24-hour UIE, iodine concentration in spot urine, I/C ratios in spot urine and estimated 24-hour UIE of the patients were analyzed by comparing with each other. Results: In 99% of the patients, RID efficiency was sufficient according to 24-hour UIE before RAIT. The mean 24-hour UIE was 48.81 micrograms/day (mcg/day) in 24-hour urine samples taken from the patients to evaluate the body iodine pool. The patients’ iodine concentrations in spot urine, I/C ratios in spot urine, and estimated 24-hour UIE were all statistically significantly lower than actual 24-hour UIE, which was the reference method (p: 0.026 vs <0.001 vs 0.041)..... (AU)

The interaction of platelet-related factors with tumor cells promotes tumor metastasis.

Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.

Ovarian tumor cell-derived JAGGED2 promotes omental metastasis through stimulating the Notch signaling pathway in the mesothelial cells.

The primary site of metastasis for epithelial ovarian cancer (EOC) is the peritoneum, and it occurs through a multistep process that begins with adhesive contacts between cancer cells and mesothelial cells. Despite evidence that Notch signaling has a role in ovarian cancer, it is unclear how exactly it contributes to ovarian cancer omental metastasis, as well as the cellular dynamics and intrinsic pathways that drive this tropism. Here we show that tumor cells produced the Notch ligand Jagged2 is a clinically and functionally critical mediator of ovarian cancer omental metastasis by activating the Notch signaling in single-layered omental mesothelial cells. In turn, Jagged2 promotes tumor growth and therapeutic resistance by stimulating IL-6 release from mesothelial cells. Additionally, Jagged2 is a potent downstream mediator of the omental metastasis cytokine TGF-ß that is released during omental destruction. Importantly, therapeutic inhibition of Jagged2-mediated omental metastasis was significantly improved by directly disrupting the Notch pathway in omental mesothelial cells. These findings highlight the key role of Jagged2 to the functional interplay between the TGF-ß and the Notch signaling pathways during the metastatic process of ovarian cancer cells to the omentum and identify the Notch signaling molecule as a precision therapeutic target for ovarian cancer metastasis.

Cell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition.

The binding of therapeutic antagonists to their receptors often fail to translate into adequate manipulation of downstream pathways. To fix this 'bug', here we report a strategy that stitches cell surface 'patches' to promote receptor clustering, thereby synchronizing subsequent mechano-transduction. The "patches" are sewn with two interactable nanothreads. In sequence, Nanothread-1 strings together adjacent receptors while presenting decoy receptors. Nanothread-2 then targets these decoys multivalently, intertwining with Nanothread-1 into a coiled-coil supramolecular network. This stepwise actuation clusters an extensive vicinity of receptors, integrating mechano-transduction to disrupt signal transmission. When applied to antagonize chemokine receptors CXCR4 expressed in metastatic breast cancer of female mice, this strategy elicits and consolidates multiple events, including interception of metastatic cascade, reversal of immunosuppression, and potentiation of photodynamic immunotherapy, reducing the metastatic burden. Collectively, our work provides a generalizable tool to spatially rearrange cell-surface receptors to improve therapeutic outcomes.

Comparative efficacy and safety of anti-PD-1 therapies used in metastatic colorectal cancer: a systematic review and network meta-analysis

Objective: Systemic studies on anti-PD-1 therapy in patients with metastatic colorectal cancer (mCRC) with microsatellite instability or mismatch repair defects are lacking. We aimed to summarize the evidence regarding the efficacy and safety of pembrolizumab, nivolumab, ipilimumab, and tislelizumab in mCRC. Methods: Network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, eligible publications from PubMed, EMBASE, Web of Science, and Cochrane Library from 2016 to April 2023 were identified through a systematic literature review. Literature screening and data extraction were performed according to established criteria. The quality of the literature was evaluated using the Cochrane risk of bias tool, and statistical analysis was performed using Revman5.4 and R language. The main outcome indicators, DCR, ORR, PFS, and OS, were used to evaluate the effectiveness of the drugs, and the main outcome indicators AE and SAE were used to evaluate the safety of each program. Results: Fifteen studies with a sample size of 798 patients were included. In terms of effectiveness, the disease control rate DCR of PD-1 inhibitors was 0.727[95% CI:0.654-0.794]; objective response rate ORR was 0.448[95% CI:0.382-0.514]; and the 1-year progression-free survival rate was 0.551[95% CI:0.458-0.642]. The 1-year overall survival rate was 0.790[95% CI:0.705-0.865]. The adverse events associated with anti-PD-1 were 0.567[95% CI:0.344-0.778] in terms of safety. The total incidence of grade 3 or higher adverse events was 0.241[95% CI:0.174-0.313]. In the subgroup analysis results, the incidence of DCR in the nivolumab + ipilimumab group was 0.826[95% CI:0.780-0.869], the ORR was 0.512[95% CI:0.377-0.647], and the PFS was 0.668[95% CI:0.516-0.804]. The incidence of AE was 0.319 [95% CI:0.039-0.700] and SAE was 0.294 [95% CI:0.171-0.433]... (AU)

Arenobufagin inhibits lung metastasis of colorectal cancer by targeting c-MYC/Nrf2 axis.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. Metastasis is the most common cause of death in patients with CRC. Arenobufagin is an active component of bufadienolides, extracted from toad skin and parotid venom. Arenobufagin reportedly inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in various cancers. However, the mechanism through which arenobufagin inhibits CRC metastasis remains unclear. PURPOSE: This study aimed to elucidate the molecular mechanisms by which arenobufagin inhibits CRC metastasis. METHODS: Wound-healing and transwell assays were used to assess the migration and invasion of CRC cells. The expression of nuclear factor erythroid-2-related factor 2 (Nrf2) in the CRC tissues was assessed using immunohistochemistry. The protein expression levels of c-MYC and Nrf2 were detected by immunoblotting. A mouse model of lung metastasis was used to study the effects of arenobufagin on CRC lung metastasis in vivo. RESULTS: Arenobufagin observably inhibited the migration and invasion of CRC cells by downregulating c-MYC and inactivating the Nrf2 signaling pathway. Pretreatment with the Nrf2 inhibitor brusatol markedly enhanced arenobufagin-mediated inhibition of migration and invasion, whereas pretreatment with the Nrf2 agonist tert­butylhydroquinone significantly attenuated arenobufagin-mediated inhibition of migration and invasion of CRC cells. Furthermore, Nrf2 knockdown with short hairpin RNA enhanced the arenobufagin-induced inhibition of the migration and invasion of CRC cells. Importantly, c-MYC acts as an upstream modulator of Nrf2 in CRC cells. c-MYC knockdown markedly enhanced arenobufagin-mediated inhibition of the Nrf2 signaling pathway, cell migration, and invasion. Arenobufagin inhibited CRC lung metastasis in vivo. Together, these findings provide evidence that interruption of the c-MYC/Nrf2 signaling pathway is crucial for arenobufagin-inhibited cell metastasis in CRC. CONCLUSIONS: Collectively, our findings show that arenobufagin could be used as a potential anticancer agent against CRC metastasis. The arenobufagin-targeted c-MYC/Nrf2 signaling pathway may be a novel chemotherapeutic strategy for treating CRC.

Molecular perspectives on systemic priming and concomitant immunity in colorectal carcinoma.

The progression of metastasis, a complex systemic disease, is facilitated by interactions between tumor cells and their isolated microenvironments. Over the past few decades, researchers have investigated the metastatic spread of cancer extensively, identifying multiple stages in the process, such as intravasation, extravasation, tumor latency, and the development of micrometastasis and macrometastasis. The premetastatic niche is established in target organs by the accumulation of aberrant immune cells and extracellular matrix proteins. The "seed and soil" idea, which has become widely known and accepted, is being used to this day to guide cancer studies. Changes in the local and systemic immune systems have a major impact on whether an infection spreads or not. The belief that the immune response may play a role in slowing tumor growth and may be beneficial against the metastatic disease underpins the responsiveness shown in the immunological landscape of metastasis. Various hypotheses on the phylogenesis of metastases have been proposed in the past. The primary tumor's secreting factors shape the intratumoral microenvironment and the immune landscape, allowing this progress to be made. Therefore, it is evident that among disseminated tumor cells, there are distinct phenotypes that either carry budding for metastasis or have the ability to obtain this potential or in systemic priming through contact with substantial metastatic niches that have implications for medicinal chemistry. Concurrent immunity signals that the main tumor induces an immune response that may not be strong enough to eradicate the tumor. Immunotherapy's success with some cancer patients shows that it is possible to effectively destroy even advanced-stage tumors by modifying the microenvironment and tumor-immune cell interactions. This review focuses on the metastasome in colorectal carcinoma and the therapeutic implications of site-specific metastasis, systemic priming, tumor spread, and the relationship between the immune system and metastasis.

Quercetin-induced degradation of RhoC suppresses hepatocellular carcinoma invasion and metastasis.

BACKGROUND: Tumor metastasis and recurrence are major causes of mortality in patients with hepatocellular carcinoma (HCC) that is still lack of effective therapeutic targets and drugs. Previous reports implied that ras homolog family member C (RhoC) plays a toxic role on metastasis and proliferation of cancer. METHODS: In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real-time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient-derived xenografts (PDXs) were employed to evaluate the anti-metastasis effects of quercetin. RESULTS: Clinical relevance and in vitro experiments further confirmed the level of RhoC was positively correlated with invasion and metastasis ability of HCC. Then we uncovered that quercetin could attenuate invasion and metastasis of HCC by downregulating RhoC's level in vitro, in vivo and PDXs. Furthermore, mechanistic investigations displayed quercetin hindered the E3 ligase expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) leading to enhancement of RhoC's ubiquitination and proteasomal degradation. CONCLUSIONS: Our research has revealed the novel mechanisms quercetin regulates degradation of RhoC level by targeting SMURF2 and identified quercetin may be a potential compound for HCC therapy.

Prevention of Metastasis by Suppression of Stemness Genes Using a Combination of microRNAs.

We propose an original strategy for metastasis prevention using a combination of three microRNAs that blocks the dedifferentiation of cancer cells in a metastatic niche owing to the downregulation of stemness genes. Transcriptome microarray analysis was applied to identify the effects of a mixture of microRNAs on the pattern of differentially expressed genes in human breast cancer cell lines. Treatment of differentiated CD44- cancer cells with the microRNA mixture inhibited their ability to form mammospheres in vitro. The combination of these three microRNAs encapsulated into lipid nanoparticles prevented lung metastasis in a mouse model of spontaneous metastasis. The mixture of three microRNAs (miR-195-5p/miR-520a/miR-630) holds promise for the development of an antimetastatic therapeutic that blocks tumor cell dedifferentiation, which occurs at secondary tumor sites and determines the transition of micrometastases to macrometastases.

Tumor metastásico en tejido blando a nivel del sacro secundario a carcinoma de células claras de riñón. Reporte de caso / Metastatic tumor in soft tissue at the level of the sacrum secondary toclear cell carcinoma of the kidney. A case report

Introducción. El cáncer de riñón es la undécima neoplasia maligna más común en los Estados Unidos Mexicanos. El carcinoma de células claras de riñón (CCR) es considerado la estirpe más frecuente y representa el 2-3 % de todos los cánceres a nivel mundial. En el contexto de la enfermedad metastásica, por lo general se identifica un tumor renal primario y las metástasis se localizan en pulmón, hueso, hígado, cerebro y, raramente, en tejidos blandos. Los pacientes con metástasis a tejidos blandos no tienen síntomas en las etapas iniciales y generalmente se identifican sólo cuando las lesiones aumentan de tamaño o durante el estudio de la pieza de resección quirúrgica. Caso clínico. Se presenta el caso de una paciente en la séptima década de la vida, con una metástasis en tejidos blandos de la región sacra, de 10 años de evolución posterior a una nefrectomía secundario a CCR. Resultados. Hallazgos clínicos e imagenológicos de un tumor bien delimitado. Se realizó resección quirúrgica de la lesión, bajo anestesia regional, con extirpación completa. Conclusión. Se recomienda que los pacientes con un sitio metastásico resecable y solitario sean llevados a resección quirúrgica con márgenes libres, como fue el caso de nuestra paciente, por su fácil acceso y ser una lesión única. En el CCR, además de su tratamiento quirúrgico inicial, es indispensable una estrecha vigilancia con examen físico e imágenes transversales, para detectar la presencia de metástasis y con ello evitar tratamientos tardíos.

Introduction. Kidney cancer is the eleventh most common malignancy in the United States of Mexico. Carcinoma renal cell (CRC) is considered the most frequent type and represents 2-3% of all cancers worldwide. In the setting of metastatic disease, a primary renal tumor is usually identified, and metastases are located in the lung, bone, liver, brain, and rarely in soft tissue. Patients with soft tissue metastases do not have symptoms in the initial stages and are generally found only when the lesions increase in size or during the study of the surgical resection piece. Clinical case. In this case, we report a female patient in the seventh decade of life with a soft tissue metastasis located in the sacral region, 10 years after a nephrectomy secondary to CRC. Results. Clinical and radiological findings of a well-defined tumor. Surgical resection of the lesion is performed under regional anesthesia with complete excision. Conclusions. It is recommended that patients with a resectable and solitary metastatic site be candidates for surgical resection with free margins, as was the case with our patient due to its easy access and single lesion. In CRC, in addition to its initial surgical treatment, close surveillance with physical examination and cross-sectional images is essential to monitor the presence of metastases and thus avoid late treatments.

Recent advances in micro-physiological systems for investigating tumor metastasis and organotropism.

Tumor metastasis involves complex processes that traditional 2D cultures and animal models struggle to fully replicate. Metastatic tumors undergo a multitude of transformations, including genetic diversification, adaptation to diverse microenvironments, and modified drug responses, contributing significantly to cancer-related mortality. Micro-physiological systems (MPS) technology emerges as a promising approach to emulate the metastatic process by integrating critical biochemical, biomechanical, and geometrical cues at a microscale. These systems are particularly advantageous simulating metastasis organotropism, the phenomenon where tumors exhibit a preference for metastasizing to particular organs. Organotropism is influenced by various factors, such as tumor cell characteristics, unique organ microenvironments, and organ-specific vascular conditions, all of which can be effectively examined using MPS. This review surveys the recent developments in MPS research from the past five years, with a specific focus on their applications in replicating tumor metastasis and organotropism. Furthermore, we discuss the current limitations in MPS-based studies of organotropism and propose strategies for more accurately replicating and analyzing the intricate aspects of organ-specific metastasis, which is pivotal in the development of targeted therapeutic approaches against metastatic cancers.

Neural recordings can differentiate between spontaneously metastasizing melanomas and melanomas with low metastatic potential.

Multiple studies report that melanomas are innervated tumors with sensory and sympathetic fibers where these neural fibers play crucial functional roles in tumor growth and metastasis with branch specificity. Yet there is no study which reports the direct neural recording and its pattern during in-vivo progression of the cancer. We performed daily neural recordings from male and female mice bearing orthotopic metastasizing- melanomas and melanomas with low metastatic poential, derived from B16-F10 and B16-F1 cells, respectively. Further, to explore the origins of neural activity, 6-Hydroxidopamine mediated chemical sympathectomy was performed followed by daily microneurographic recordings. We also performed the daily bioluminescent imaging to track in vivo growth of primary tumors and distant metastasis to the cranial area. Our results show that metastasizing tumors display high levels of neural activity while tumors with low metastatic potential lack it indicating that the presence of neural activity is linked to the metastasizing potential of the tumors. Moreover, the neural activity is not continuous over the tumor progression and has a sex-specific temporal patterns where males have two peaks of high neural activity while females show a single peak. The neural peak activity originated in peripheral sympathetic nerves as sympathectomy completely eliminated the peak activity in both sexes. Peak activities were highly correlated with the distant metastasis in both sexes. These results show that sympathetic neural activity is crucially involved in tumor metastasis and has sex-specific role in malignancy initiation.