Tumor Metastatic Potential Research Articles

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS."

Cadherin-11 increases tumor cell proliferation and metastatic potential via Wnt pathway activation.

During epithelial-mesenchymal transition (EMT) in cancer progression, tumor cells switch cadherin profile from E-cadherin to cadherin-11 (CDH11), which is accompanied by increased invasiveness and metastatic activity. However, the mechanism through which CDH11 may affect tumor growth and metastasis remains elusive. Here, we report that CDH11 was highly expressed in multiple human tumors and was localized on the membrane, in the cytoplasm and, surprisingly, also in the nucleus. Interestingly, β-catenin remained bound to carboxy-terminal fragments (CTFs) of CDH11, the products of CDH11 cleavage, and co-localized with CTFs in the nucleus in the majority of breast cancer samples. Binding of β-catenin to CTFs preserved β-catenin activity, whereas inhibiting CDH11 cleavage led to β-catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidate a previously unknown role of CDH11, which serves to stabilize β-catenin in the cytoplasm and facilitates its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential.

MiRNA-mRNA integrative analysis reveals epigenetically regulated and prognostic miR-103a with a role in migration and invasion of carboplatin-resistant ovarian cancer cells that acquired mesenchymal-like phenotype

BackgroundDNA methylation, histone modifications, and miRNAs affect ovarian cancer (OC) progression and therapy response. PurposeIdentification of epigenetically downregulated miRNAs in drug-resistant OC cell lines with a possible role in drug resistance and/or drug-induced mesenchymal-like phenotype. MethodsMiRNA profiling was performed on parental and carboplatin-resistant OC cells, MES-OV and MES-OV CBP. RT-qPCR validation, epigenetic modulation and other CBP-resistant OC cell lines were used to select miRNAs of interest. The integration of miRNA-predicted target genes and differentially expressed genes (DEGs), pathway and functional analysis were used for forecasting their biological role. Data mining was performed to determine their possible prognostic and predictive values. ResultsMiRNA profiling revealed 48 downregulated miRNAs in OC cells whose drug sensitivity and metastatic potential were impacted by epigenetic modulators. Of the fourteen selected, nine were validated as changed, and seven of these restored their expression upon treatment with epigenetic inhibitors. Only three had similar expression patterns in other OC cell lines. MiRNA-mRNA integrative analysis resulted in 56 target DEGs. Pathway analysis revealed that these genes are involved in cell adhesion, migration, and invasion. The functional analysis confirmed the role of miR-103a–3p, miR-17–5p and miR-107 in cell invasion, while data mining showed their prognostic and predictive values. Only miR-103a–3p was epigenetically regulated at the constitutive level. ConclusionHigh throughput miRNA and cDNA profiling coupled with pathway analysis and data mining delivered evidence for miRNAs which can be epigenetically regulated in drug-resistant, mesenchymal-like OC cells as possible markers to combat therapy-induced short overall survival and tumor metastatic potential.

Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Retrospective, Monocentric Cohort Study

Smooth muscle tumors of unknown malignant potential (STUMP) represent a group of heterogeneous uterine neoplasms showing worrisome histological features, raising concerns for a malignant behavior, but do not satisfy the diagnostic criteria for leiomyosarcoma. The existing literature remains scarce due to its rarity; therefore, there is no consensus regarding diagnostic criteria, malignant potential, treatment of choice, and follow-up. The authors report their case series to analyze the heterogeneous features of this poorly understood neoplasm. A retrospective, monocentric cohort study of all patients who underwent surgery diagnosed with STUMP at the Garibaldi-Nesima Hospital in Catania from February 2018 to August 2021 was conducted. Each patient’s age at diagnosis, symptoms, surgical treatment, tumor features, postoperative management, and follow-up were recorded. Nine STUMP cases were included. All patients reported menometrorrhagia and pelvic pain. In all women, the tumor lesion was single and intramural, and the mean diameter was 7.5 cm. Four women underwent laparotomic conservative surgery. The mean postoperative follow-up time was 36 months, and recurrences were observed in two patients. In conclusion, STUMP cases should be systematically discussed by tumor boards, pathologists with good expertise in gynecological diseases should examine the histological samples, and close surveillance is mandatory because of the possibility of recurrence or metastasis.

Co-expression of galectin-3 and vimentin in triple negative breast cancer cells promotes tumor progression, metastasis and survival.

Lack of druggable targets and complex expression heterogeneity of known targets is common among TNBC subtypes. An enhanced expression of galectin-3 in TNBCs has already been documented. We have observed a tumor progression-dependent galectin-3 expression in TNBCs compared to adjacent epithelium and non TNBCs. To unravel the association of galectin- 3 in tumor progression, aggressiveness and drug resistance in TNBC patients. Galectin-3 expression in 489 breast cancer tissues was correlated with clinicopathological features and the results were validated in cell lines and mouse model by silencing galectin-3 using shRNA and the proteins were profiled by western blot and qRT-PCR. Protein interaction was analyzed by GFP Trap and Mass spectrometry. Galectin-3 expression correlated with tumor stage in TNBC and a lower galectin-3 expression was associated with poor patient survival. The positive correlation between galectin-3, vimentin and CD44 expression, pinpoints galectin-3 contribution to epithelial to mesenchymal transition, drug resistance and stemness. Vimentin was found as an interacting partner of galectin-3. Duplexing of galecin-3 and vimentin in patient samples revealed the presence of tumor cells co-expressing both galectin-3 and vimentin. In vitro studies also showed its role in tumor cell survival and metastatic potential, elementary for tumor progression. In vivo studies further confirmed its metastatic potential. Tumor progression dependent expression pattern of galectin 3 was found to indicate prognosis. Co-expression of galectin-3 and vimentin in tumor cells promotes tumor dissemination, survival and its metastatic capability in TNBCs.

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo.

Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state-of-the-art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta-analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.

Quantitative MR texture analysis for the differentiation of uterine smooth muscle tumors with high signal intensity on T2-weighted imaging.

The purpose of this study was to distinguish leiomyosarcomas/smooth muscle tumors of uncertain malignant potential (STUMP) from leiomyomas with high signal intensity (SI) on T2-weighted imaging (T2WI) using quantitative MR texture analysis combined with patient characteristics and visual assessment. Thirty-one leiomyomas, 2 STUMPs, and 6 leiomyosarcomas showing high SI on T2WI were included. First, we searched for differences in patient characteristics and visual assessment between leiomyomas and leiomyosarcomas/STUMPs. We also compared the MR texture on T2WI and the apparent diffusion coefficient (ADC) to identify differences between leiomyomas and leiomyosarcomas/STUMPs. In the univariate analysis, significant differences between leiomyomas and leiomyosarcomas/STUMPs were observed in age, menopausal status, margin, hemorrhage, long diameter, T2-variance, T2-volume, ADC-variance, ADC-entropy, ADC-uniformity, ADC-90th and 95th percentile values, and ADC-volume (P < .05, respectively). There were significantly more postmenopausal patients with leiomyosarcomas/STUMPs than with leiomyomas, and leiomyosarcomas/STUMPs had more irregular margins, more frequent presence of hemorrhage and exhibited larger tumor diameters, T2-volume, T2-variance, ADC-volume, ADC-variance, ADC-entropy, and higher ADC-90th and 95th percentile values but lower ADC-uniformity. Multivariate analyses revealed that the independent differentiators were menopausal status, hemorrhage and ADC-entropy (P < .05, respectively). The area under the curve obtained by combining the 3 items was 0.980. The best cutoff value for ADC-entropy was 9.625 (sensitivity: 100%, specificity: 58%). The combination of menopausal status, hemorrhage, and ADC-entropy can help accurately distinguish leiomyosarcomas/STUMPs from leiomyomas with high SI on T2WI; however, external validation in a larger population is required because of the small sample size of our study.

The relationship between telomerase reverse transcriptase promoter rs2853669 allele C accompanied by C228T and the grade of thyroid malignancy.

91 Background: Two-point mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) gene are considered molecular indicators of adverse thyroid tumor biology. The regulatory single nucleotide polymorphism rs2853669 (TrSNP) is located near these TERT promoter mutations and its association with the grade of various cancers has been recently reported. To clarify whether the TrSNP can be a clinically useful molecular marker, we analyzed the relationship of the TrSNP with tumor growth and malignant potential in papillary thyroid cancer and follicular tumors. Methods: DNA was extracted from blood and FFPE specimens of 218 patients with thyroid tumors (133 papillary and 85 follicular), and TrSNP, C228T, and C250T were analyzed. BRAFV600E and NRAS Q61R mutations were also analyzed. The association of these genotypes and mutations with clinicopathological parameters were investigated. Results: The C allele of TrSNP from blood and FFPE specimens were validated with 97.3% concordance, so the C allele of TrSNP from blood samples were used in this study. Univariate analysis of 133 papillary carcinomas for clinicopathologic features showed that the C allele of TrSNP significantly correlated with tumor size as did the C228T mutation (p&lt;0.05, p&lt;0.001). Co-expression of the TrSNP and C228T were significantly corelated with tumor size, extrathyroidal invasion and lymph nodal metastasis (p&lt;0.01, p&lt;0.05). Eighty-five follicular tumors (19 follicular carcinomas and 66 follicular adenomas) were examined. Univariate analysis showed no significant association between the C allele of TrSNP, C228T, or C250T and tumor size. Multivariate analysis demonstrated the C allele TrSNP and C228T were significantly frequent in follicular carcinoma (p&lt;0.05, p&lt;0.001) and therefore were considered a risk factor for malignancy. Conclusions: This study demonstrates that the C-allele of the TrSNP is an indicator of tumor growth of papillary carcinoma and co-expression of the TrSNP and C228T relate tumor progression and malignant grade. These genetic features are expected to be a useful molecular marker for differential diagnosis of benign and malignant tumors and for determining treatment strategies.

Metamorphic Effect of Angiogenic Switch in Tumor Development: Conundrum of Tumor Angiogenesis Toward Progression and Metastatic Potential.

Our understanding of angiogenesis has significantly expanded over the past five decades. More recently, research has focused on this process at a more molecular level, looking at it through the signaling pathways that activate it and its non-direct downstream effects. This review discusses current findings in molecular angiogenesis, focusing on its impact on the immune system. Moreover, the impairment of this process in cancer progression and metastasis is highlighted, and current anti-angiogenic treatments and their effects on tumor growth are discussed.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Comprehensive Multidisciplinary Update.

Background and Objectives: The uterine smooth muscle tumors of uncertain malignant potential (STUMP) are tumors with pathological characteristics similar to leiomyosarcoma, but that do not satisfy histological criteria for leiomyoma. These are problematic lesions with intermediate morphologic features; thus, diagnosis and treatment are difficult. This narrative review aims to review data in the literature about STUMPs, particularly focusing on management and therapeutic options and strategies for women who desire to preserve fertility. Material and Methods: authors searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed and Scopus databases, from 2000 to March 2023. Pertinent articles were obtained in full-text format and screened for additional references. Only articles in English language were included. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: The median age was 43 years old. Symptoms are similar to those of leiomyomas, with a mean diameter of 8.0 cm. Total hysterectomy with or without bilateral salpingo-oophorectomy is the standard care for women if fertility desire is satisfied. Myomectomy alone can be considered for young patients. Although these tumors have not a high malignant potential, several studies described recurrence and metastases. Conclusions: STUMPs are complex uterine smooth muscle tumors, with a rare but reasoned clinical-diagnostic management. Considering the high clinical and histological complexity of these tumors, high level of expertise is mandatory.

The new histological system for the diagnosis of adrenocortical cancer.

Adrenocortical cancer (ACC) is a rare malignant tumor that originates in the adrenal cortex. Despite extensive molecular-genetic, pathomorphological, and clinical research, assessing the malignant potential of adrenal neoplasms in clinical practice remains a daunting task in histological diagnosis. Although the Weiss score is the most prevalent method for diagnosing ACC, its limitations necessitate additional algorithms for specific histological variants. Unequal diagnostic value, subjectivity in evaluation, and interpretation challenges contribute to a gray zone where the reliable assessment of a tumor's malignant potential is unattainable. In this study, we introduce a universal mathematical model for the differential diagnosis of all morphological types of ACC in adults. This model was developed by analyzing a retrospective sample of data from 143 patients who underwent histological and immunohistochemical examinations of surgically removed adrenal neoplasms. Statistical analysis was carried out on Python 3.1 in the Google Colab environment. The cutting point was chosen according to Youden's index. Scikit-learn 1.0.2 was used for building the multidimensional model for Python. Logistical regression analysis was executed with L1-regularization, which is an effective method for extracting the most significant features of the model. The new system we have developed is a diagnostically meaningful set of indicators that takes into account a smaller number of criteria from the currently used Weiss scale. To validate the obtained model, we divided the initial sample set into training and test sets in a 9:1 ratio, respectively. The diagnostic algorithm is highly accurate [overall accuracy 100% (95% CI: 96%-100%)]. Our method involves determining eight diagnostically significant indicators that enable the calculation of ACC development probability using specified formulas. This approach may potentially enhance diagnostic precision and facilitate improved clinical outcomes in ACC management.

5hmC Immunohistochemistry: A Predictor of TERT Promoter Mutational Status in Follicular Thyroid Carcinoma?

Telomerase reverse transcriptase (TERT) gene aberrancies correlate to adverse prognosis in follicular thyroid carcinoma (FTC). As loss of 5-hydroxymethylcytosine (5hmC) has been associated with TERT promoter mutations in papillary thyroid carcinoma, this study sought to analyze the levels of 5hmC in a cohort of follicular thyroid tumors with available TERT data. A total of 29 tumors (26 FTCs, 2 follicular thyroid tumors of uncertain malignant potential, and 1 oncocytic thyroid carcinoma) with known TERT promoter mutational status and TERT gene expression were assessed for 5hmC immunoreactivity using two antibodies (clones RM236 and 4D9.) Slides were analyzed using a semiquantitative scoring system. Of the 10 tumor cases with aberrant TERT, only 1 scored negative with both antibodies (1/10; 10%), whereas the remaining 9 cases (9/10; 90%) exhibited some positivity for at least one antibody. Of the 19 TERT wild-type tumors, no case was scored negative using RM236, and 2 cases (2/19; 11%) using 4D9. The differences between TERT promoter mutated and wild-type groups were non-significant. The sensitivity and specificity for 5hmC immunohistochemistry (IHC) to detect mutated cases were 10% and 100% (RM236) and 20% and 89% (4D9). Therefore, 5hmC IHC is not a sensitive marker for detecting TERT promoter mutations in follicular thyroid tumors.

Экспрессионные микрочипы: возможности применения в клинической онкологии

INTRODUCTION: Molecular oncology is currently undergoing a fairly rapid development due to the emergence of new technologies and modernization of already known methods. These technologies allow not only to update and clarify the understanding of the molecular genetic nature of tumors, but also to develop new directions for the therapy and the course of cancer diseases. The prerequisite for this scientific direction was the decoding of the human genome, as a result of which most human genes have been identified and mapped by now. Microarray technology has been since the late 1980s and has been rapidly developing since then. In a short time, biological microarrays have evolved into an independent field of analysis, including both the study of fundamental problems of molecular biology and molecular evolution, and practical applications in medicine, pharmacology, forensic expertise. AIM: To demonstrate the potential of the microarray expression assay method in clinical oncology, to describe the history of elaboration, evolution, the principle of the method and possibilities of application of expression microarrays at the current stage of clinical oncology development. MATERIALS AND METHODS: The study was carried out at Ryazan State Medical University. The review included sources found in PubMed, Google Scholar, and eLibrary using the query ‘expression microarrays’ and ‘molecular genetic technologies in oncology’. A total, of 126,455 results were found for the query ‘expression microarrays’ in PubMed and Google Scholar. Thirty-five articles were selected, after a relativity analysis of the sources. A total, of 613 results were found in the eLibrary system for the query ‘molecular genetic technology in oncology’, and 15 articles were selected. Thus, 49 articles were included in the final version. CONCLUSION: The advent of microarray technology marked a new stage in molecular genetic analysis. This method allows simultaneous analysis of hundreds of transcription products and even the entire transcriptome, which together with the data on functions of tumor proteins already opens wide horizons for the use of this technology in clinic. Accumulated data allow to see a wide perspective in this method in terms of analysis of expression profile, metastatic potential of tumors, differential diagnosis between different types of malignant neoplasia, and thus individualize the treatment approach for each individual patient. In our opinion, expression profile analysis is an area promising for further, even more detailed study and discussion within the framework of clinical oncology.

The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.

Selenium (Se) and manganese (Mn) are essential micronutrients that are important elements of cell metabolism. They are involved in the composition of enzyme systems and regulate enzyme activity. Disturbances in the homeostasis of these micronutrients affect the development of many diseases and carcinogenesis, which can be linked to increased levels of oxidative stress and impaired antioxidant properties of many enzymes. Selenium has a very important function in maintaining immune-endocrine, metabolic and cellular homeostasis. Manganese, on the other hand, is important in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activity. We review the role of selenium and manganese and their effects on tumor growth, metastasis potential and remodeling of the microenvironment. We also describe their role as potential biomarkers in the diagnosis and the potential for the use of Se- and Mn-containing compounds in composition for the treatment of cancer of the reproductive organs.

Cystic Clear Cell Renal Cell Carcinoma: A Morphological and Molecular Reappraisal.

A wide variety of renal neoplasms can have cystic areas. These can occur for different reasons: some tumors have an intrinsic cystic architecture, while others exhibit pseudocystic degeneration of necrotic foci or they have cystically dilated renal tubules constrained by stromal neoplastic cells. Clear cell renal cell carcinoma (CCRCC), either solid or cystic, is the most frequent type of renal cancer. While pseudocysts are found in high-grade aggressive CCRCC, cystic growth is associated with low-grade indolent cases. The latter also form through a cyst-dependent molecular pathway, and they are more frequent in patients suffering from VHL disease. The differential diagnosis of multilocular cystic renal neoplasm of low malignant potential and clear cell papillary renal cell tumor can be especially hard and requires a focused macroscopical and microscopical pathological analysis. As every class of renal tumor includes cystic forms, knowledge of the criteria required for a differential diagnosis is mandatory.

CT and MRI findings of primary hepatic giant cell tumor of soft tissue: A case report

AbstractPrimary giant cell tumor of soft tissue (GCT-ST) is a low-grade malignant tumor and uncommon cancer originating from soft tissue. Primary hepatic GCT is an extremely rare finding. Only a handful of cases have been reported in the literature. Although GCT-ST has a relatively low malignant potential tumor in the view of histology, some patients who suffered from this tumor have poor prognosis after surgery because of the aggressiveness. Thus, the early diagnosis is important, and a preoperative imaging can supply the evidence of differential diagnosis to evaluate tumor malignancy. In this study, we systematically present a rare case of 56-year-old women with chills, fever, jaundice and anorexia for 3 days. CT showed a huge and multinodular confluent lesion in the left lobe of the liver, and it had a calcification component. This tumor is characterized by fibrous components and calcification, which showed iso-intense with peripheral hypo-intense on T1WI, and mainly inhomogeneous hypo-intense on fat-suppressed T2WI. Moreover, it was mainly hypointense and peripheral linear hyperintense on DWI images with a b-value of 800 (b800) and iso-hyperintense on ADC.

A műtéti érzéstelenítés hatása a daganatkiújulásra.

Cancers cause nearly a quarter of all deaths in Hungary. The long-term success of tumor resection operations, i.e., the absence of recurrence and metastasis as well as survival, are also influenced by anesthetic methods. This was confirmed by experiments on cell cultures and animal models. Propofol and local anesthetics have been shown to reduce tumor cell viability and metastatic potential compared to inhalation anesthetics and opioids. However, studies conducted on patient groups only confirmed the advantage of propofol compared to inhalation anesthetics. Unfortunately, the epidural, additional use of local anesthetics for general anesthesia did not reduce the recurrence-free and survival time of the patients. Further clinical studies are necessary to reveal the actual effect of surgical anesthesia in each type of cancer in the future. Orv Hetil. 2023; 164(22): 843-846.

Smooth Muscle Tumors of the Uterus at MRI: Focus on Leiomyomas and FIGO Classification.

Leiomyomas are smooth muscle tumors of the uterus and are the most common uterine neoplasm. Although leiomyomas are usually asymptomatic, they can manifest with symptoms such as pain or uterine bleeding. Leiomyomas are classified on the basis of their anatomic location and morphology. Localization of leiomyomas relative to the endometrium, myometrium, and uterine serosa with use of the International Federation of Gynecology and Obstetrics (FIGO) classification system is helpful for guiding management in symptomatic patients. The FIGO system is a practical and universally accepted approach for classifying leiomyomas to guide radiologists and clinicians in deciding management. The MRI appearance of conventional leiomyomas is related to their tissue contents of smooth muscle and fibrous tissue and is well established. The MRI features of some leiomyoma subtypes and forms of degeneration also have been described. Other smooth muscle tumors of the uterus recognized in the 2020 World Health Organization classification system include intravenous leiomyomatosis, smooth muscle tumors of uncertain malignant potential, and metastasizing leiomyoma. At the far end of the spectrum are leiomyosarcomas, which are frankly malignant and therefore must be managed accordingly. Although MRI features that suggest a diagnosis of leiomyosarcoma have been proposed, these features overlap with those of some leiomyoma subtypes and degeneration. © RSNA, 2023 See the invited commentary by Fennessy and Gargiulo in this issue. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis

BackgroundBone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment.MethodsWe analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment.ResultsHere, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy.ConclusionTaken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.

A Transanal Endoscopic Ultrasound-guided Fine-needle Aspiration Biopsy for an Intrapelvic Tumor Diagnosed as Recurrence of a Smooth Muscle Tumor of Uncertain Malignant Potential Following Uterine Morcellation.

A transoral endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is a well-established tissue-sampling method. However, performing a transanal EUS-FNAB remains challenging. Uterine morcellation has emerged as a minimally invasive approach for benign tumor treatment. However, uterine myomas are heterogeneous and include malignant and indeterminate malignant cells. We herein report a rare case of intrapelvic tumor diagnosed by a transanal EUS-FNAB as a recurrence of smooth muscle tumors of uncertain malignant potential following uterine morcellation. Physicians should be aware that a previous uterine myoma resected under morcellation has the possibility of intra-abdominal recurrence. A transanal EUS-FNAB is a practical option for making a pathological diagnosis.