Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence

Metastasis-associated processes are the predominant instigator of fatalities linked to cancer,wherein the pivotal role of circulating tumor cells lies in the resurgence of malignant growth.In recent epochs,exosomes,constituents of the extracellular vesicle cohort,have garnered attention within the field of tumor theranostics owing to their inherent attributes encompassing biocompatibility,modifiability,payload capacity,stability,and therapeutic suitability.Nonetheless,the rudimentary functionalities and limited efficacy of unmodified exosomes curtail their prospective utility.In an effort to surmount these shortcomings,intricate methodologies amalgamating nanotechnology with genetic manipulation,chemotherapy,immunotherapy,and optical intervention present themselves as enhanced avenues to surveil and intercede in tumor metastasis and relapse.This review delves into the manifold techniques currently employed to engineer exosomes,with a specific focus on elucidating the interplay between exosomes and the metastatic cascade,alongside the implementation of tailored exosomes in abating tumor metastasis and recurrence.This review not only advances comprehension of the evolving landscape within this domain but also steers the trajectory of forthcoming investigations.

Recurrence of Poorly Differenciated Cervical Cancer by Single Splenic Metastasis: Case Report and Literature Review

Background: The incidence of cervical cancer in Belgium is 11.1 per 100,000. With the introduction of cervical cytology screening and more recently anti-HPV vaccination, this rate has been decreasing for almost 20 years. Despite this, some patients are missed by the screening and prevention system and cervical cancer is still diagnosed at an advanced stage. Recurrences by splenic metastases are rare and are most often found at autopsy. Case Study: We describe the case of a 41-year-old caucasian patient with a single splenic recurrence after radiotherapy, chemotherapy, brachytherapy, and surgery for a poorly differentiated adenocarcinoma of the cervix grade 3 at an initial stage IIB according to FIGO. This recurrence happens 3 years after the initial treatment. After monitoring this asymptomatic lesion, the size increase results in laparoscopic splenectomy. Histology demonstrates a splenic metastasis recurrence of adenocarcinoma of endocervical origin. Conclusion: The spleen is a rare metastatic site in cervical cancer. Splenectomy followed by chemotherapy is the therapy most often found in the literature, which is however poor in this regard.

Solitary extraovarian primary peritoneal carcinoma with direct invasion into the liver,diaphragm and lung without peritoneal dissemination or distant metastasis

To the Editor:Extraovarian primary peritoneal carcinoma(EOPPC)is an uncommon malignancy with many similarities to epithelial ovarian carcinoma in histological,clinical,and etiological aspects[1].This phenomenon is explained by their common embryonal origin,in which both develop from the coelomic epithelium in the early embryological stage.Despite their similarities,the incidence of EOPPC is significantly lower than that of epithelial ovarian carcinoma(6.78 cases per million vs.120.5 cases per million)[1].

Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis

BACKGROUND The regulatory effects of KIF26B on gastric cancer(GC)have been confirmed,but the specific mechanism still needs further exploration.Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancerassociated fibroblasts(CAFs),and CAFs promote macrophage M2 polarization and affect cancers’progression.AIM To investigate the regulatory functions of KIF26B on immune and metastasis of GC.METHODS We analyzed genes’mRNA levels by quantitative real-time polymerase chain reaction.Expression levels of target proteins were detected by immunohistochemistry,ELISA,and Western blotting.We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC.The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining.Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability.Tube formation assay was used for detecting angiogenesis.M2-polarized macrophages were estimated by immunofluorescence and flow cytometry.RESULTS KIF26B was significantly overexpressed in cells and tissues of GC,and the higher expression of KIF26B was related to GC metastasis and prognosis.According to in vivo experiments,KIF26B promoted tumor formation and metastasis of GC.KIF26B expression was positively associated with CAFs’degree of infiltration.Moreover,CAFs could regulate M2-type polarization of macrophages,affecting GC cells’migration,angiogenesis,invasion,and epithelial-mesenchymal transition process.CONCLUSION KIF26B regulated M2 polarization of macrophage through activating CAFs,regulating the occurrence and metastasis of GC.

Development and validation of a nomogram model for predicting the risk of gallstone recurrence after gallbladder-preserving surgery

Background:The high incidence of gallstone recurrence was a major concern for laparoscopic gallbladderpreserving surgery.This study aimed to investigate the risk factors for gallstone recurrence after gallbladder-preserving surgery and to establish an individualized nomogram model to predict the risk of gallstone recurrence.Methods:The clinicopathological and follow-up data of 183 patients who were initially diagnosed with gallstones and treated with gallbladder-preserving surgery at our hospital from January 2012 to January 2019 were retrospectively collected.The independent predictive factors for gallstone recurrence following gallbladder-preserving surgery were identified by multivariate logistic regression analysis.A nomogram model for the prediction of gallstone recurrence was constructed based on the selected variables.The C-index,receiver operating characteristic(ROC)curve and calibration curve were used to evaluate the predictive power of the nomogram model for gallstone recurrence.Results:During the follow-up period,a total of 65 patients experienced gallstone recurrence,and the recurrence rate was 35.5%.Multivariate logistic regression analysis revealed that the course of gallstones>2 years[odds ratio(OR)=2.567,95%confidence interval(CI):1.270-5.187,P=0.009],symptomatic gallstones(OR=2.589,95%CI:1.059-6.329,P=0.037),multiple gallstones(OR=2.436,95%CI:1.133-5.237,P=0.023),history of acute cholecystitis(OR=2.778,95%CI:1.178-6.549,P=0.020)and a greasy diet(OR=2.319,95%CI:1.186-4.535,P=0.014)were independent risk factors for gallstone recurrence after gallbladder-preserving surgery.A nomogram model for predicting the recurrence of gallstones was established based on the above five variables.The results showed that the C-index of the nomogram model was 0.692,suggesting it was valuable to predict gallstone recurrence.Moreover,the calibration curve showed good consistency between the predicted probability and actual probability.Conclusions:The nomogram model for the prediction of gallstone recurrence might help clinicians develop a proper treatment strategy for patients with gallstones.Gallbladder-preserving surgery should be cautiously considered for patients with high recurrence risks.

Dual-wavelength pumped latticed Fermi-Pasta-Ulam recurrences in nonlinear Schrödinger equation

We show that the nonlinear stage of the dual-wavelength pumped modulation instability(MI)in nonlinear Schrödinger equation(NLSE)can be effectively analyzed by mode truncation methods.The resulting complicated heteroclinic structure of instability unveils all possible dynamic trajectories of nonlinear waves.Significantly,the latticed-Fermi-Pasta-Ulam recurrences on the modulated-wave background in NLSE are also investigated and their dynamic trajectories run along the Hamiltonian contours of the heteroclinic structure.It is demonstrated that there has much richer dynamic behavior,in contrast to the nonlinear waves reported before.This novel nonlinear wave promises to inject new vitality into the study of MI.

Cholera Recurrence within Benin Littoral County: Analysis of Epidemics from 2008, 2016 to 2023

Introduction: Cholera is an acute diarrheal infection caused by the bacillus Vibrio cholerae, which can be fatal in a few hours if left untreated. It rages in endemic-epidemic mode in several countries, including Benin. Despite being the economic capital, the largest city in Benin and the most urbanized municipality in the country, the Littoral County, confounded with the city of Cotonou, is subject to recurrent epidemics. This paper aims to analyze successive cholera epidemics with a view of highlighting the factors contributing to this recurrence. Methods: A secondary analysis was done of the cholera-related databases of the County health office from 2016 to 2023, and its Situation Report No. 79 of December 7th, 2016, to describe the 2016 epidemic. Database data were analyzed in Excel. Results: Similarly to 2008, the 2016 cholera epidemic in Cotonou, which recorded 519 cases and 07 deaths, i.e. a case-fatality rate of 1.35%, spread to the town and six neighboring municipalities. The municipality of So-Ava, home to the index case, had the highest overall attack rate. The two epidemics share the same period of severity. Both epidemic and endemic cases are concentrated in the first seven boroughs of Cotonou, located on the lagoon shore, with low levels of hygiene and sanitation and a poor supply of drinking water. Conclusion: Low levels of hygiene, sanitation and drinking water supply all play a part in the recurrence of cholera epidemics. Sanitation work. Undertaken by the Beninese government is a ray of hope for improving this situation. Meanwhile, public awareness of hygiene measures must continue.

Microbiota in colorectal cancer related to liver metastasis

The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Game-changing insights on vertebral skeletal stem cells in bone metastasis and therapeutic horizons

Greenblatt and his team have unveiled vertebral skeletal stem cells(vSSCs)as a critical player in the landscape of bone metastasis.This commentary delves into the transformative discoveries surrounding vSSCs,emphasizing their distinct role in bone metastasis compared to other stem cell lineages.We illuminate the unique properties and functions of vSSCs,which may account for the elevated susceptibility of vertebral bones to metastatic invasion.Furthermore,we explore the exciting therapeutic horizons opened by this newfound understanding.These include potential interventions targeting vSSCs,modulation of associated signaling pathways,and broader implications for the treatment and management of bone metastasis.By shedding light on these game-changing insights,we hope to pave the way for novel strategies that could revolutionize the prognosis and treatment landscape for cancer patients with metastatic bone disease.

Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis:A case report

BACKGROUND According to the latest report,colorectal cancer is still one of the most prevalent cancers,with the third highest incidence and mortality worldwide.Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory,especially for mismatch repair proficient(pMMR)rectal cancer,which leads to poor prognosis and recurrence.CASE SUMMARY We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes,including the left supraclavicular lymph node,before treatment in a 70-year-old man.He received full courses of chemoradiotherapy(CRT)followed by 4 cycles of programmed death 1 inhibitor Tislelizumab,and a pathologic complete response(pCR)was achieved,and the lesion of the left supraclavicular lymph node also disappeared.CONCLUSION pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

NUDT5 promotes the growth,metastasis,and Warburg effect of IDH wild-type glioblastoma multiforme cells by upregulating TRIM47

Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM patients.RT-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM cells.LN-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with NUDT5.ECAR assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related indexes.Co-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and TRIM47.Results:GEPIA database showed that NUDT5 expression was significantly increased in GBM patients.Inhibiting the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM cells.Moreover,TRIM47 was highly expressed in GBM cells and interacted with NUDT5.Overexpression of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM cells.Conclusions:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating TRIM47.Both NUDT5 and TRIM47 can be used as targets for GMB treatment.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Risk factors,prognostic factors,and nomograms for distant metastasis in patients with diagnosed duodenal cancer:A population-based study

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM,potentially enhancing clinical decision-making.

Early gastric cancer recurrence after endoscopic submucosal dissection:Not to be ignored!

This editorial comments on the article“Efficacy of multi-slice spiral computed tomography in evaluating gastric cancer recurrence after endoscopic submucosal dissection”.We focus on the importance of paying more attention to postendoscopic submucosal dissection(ESD)gastric cancer recurrence in patients with early gastric cancer(EGC)and how to manage it effectively.ESD has been a wellknown treatment and the mainstay for EGC,with the advantages of less invasion and fewer complications when compared with traditional surgical procedures.Despite a lower local recurrence rate after ESD,the problem of postoperative recurrence in patients with EGC has become increasingly non-ignorable with the global popularization of ESD technology and the increasing number of post-ESD patients.

Leveraging machine learning for early recurrence prediction in hepatocellular carcinoma:A step towards precision medicine

The high rate of early recurrence in hepatocellular carcinoma(HCC)post curative surgical intervention poses a substantial clinical hurdle,impacting patient outcomes and complicating postoperative management.The advent of machine learning provides a unique opportunity to harness vast datasets,identifying subtle patterns and factors that elude conventional prognostic methods.Machine learning models,equipped with the ability to analyse intricate relationships within datasets,have shown promise in predicting outcomes in various medical disciplines.In the context of HCC,the application of machine learning to predict early recurrence holds potential for personalized postoperative care strategies.This editorial comments on the study carried out exploring the merits and efficacy of random survival forests(RSF)in identifying significant risk factors for recurrence,stratifying patients at low and high risk of HCC recurrence and comparing this to traditional COX proportional hazard models(CPH).In doing so,the study demonstrated that the RSF models are superior to traditional CPH models in predicting recurrence of HCC and represent a giant leap towards precision medicine.

Low skeletal muscle mass and high visceral adiposity are associated with recurrence of acute cholecystitis after conservative management:A propensity score-matched cohort study

Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.

Fifty-five cases of hepatic alveolar echinococcosis combined with lymph node metastasis:A retrospective study

BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ2=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.

Adenocarcinoma of sigmoid colon with metastasis to an ovarian mature teratoma: A case report

BACKGROUND Colorectal cancer ranks third in global cancer-related mortality,often due to metastases to liver and lungs.Ovarian metastases are less common,accounting for 3.6%to 7.4%of cases.In contrast,mature ovarian teratomas are frequently benign.Tumor-to-tumor metastasis is a rare phenomenon,with a limited number of documented cases.Three cases of mature ovarian teratomas metastasizing from different cancers have been reported.This report focuses on a case of tumor-totumor metastasis from sigmoid colon adenocarcinoma to a mature ovarian teratoma.CASE SUMMARY A 41-year-old Taiwan residents woman with no known systemic diseases presented with lower back pain,which led to imaging revealing malignant lesions in the spine,pelvis,liver,and multiple lung metastases.She was diagnosed with sigmoid colon adenocarcinoma with metastases to the liver,lung,bone,and a left ovarian teratoma.Treatment involved radiotherapy and chemotherapy,resulting in regression of the primary tumor and stable lung and liver lesions.Due to abdominal symptoms,she underwent exploratory surgery,unveiling a mature teratoma in the left ovary with signs of metastatic adenocarcinoma.CONCLUSION Consider resecting mature ovarian teratomas with concurrent colorectal adenocarcinoma to prevent tumor-to-tumor metastasis.

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.