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Objective: Chondrosarcoma (CHS) is resistant to conventional chemotherapy and radiotherapy and currently lacks effective treatment options when in advanced stages. Accordingly, this research investigated the mechanism of RNF2/CBX7 in CHS to drive the development of molecularly targeted drugs for CHS. Methods: RNF2 and CBX7 levels were detected in CHS cells and tissues. RNF2 and CBX7 expression was modulated through cell transfection to examine their effects on cell proliferation, apoptosis, migration, and angiogenesis. The correlation between RNF2 and CBX7 levels was determined, and the ubiquitination level of CBX7 was tested. Protein synthesis was blocked in RNF2-knockdown/overexpressing cells with CHX to assess the effect of RNF2 on CBX7 stability. JJ012 cells transfected with LV-sh-RNF2 were subcutaneously injected into nu/nu nude mice to ascertain the action of RNF2 in the growth and metastasis of CHS. Results: RNF2 was highly expressed in CHS cells and tissues. RNF2 knockdown curbed CHS cell proliferation, migration, and angiogenesis while promoting apoptosis. RNF2 knockdown in JJ012 cells upregulated CBX7 protein levels and reduced CBX7 ubiquitination, whilst RNF2 had no effect on CBX7 mRNA expression. CBX7 knockdown partially nullified the repressing effects of RNF2 knockdown on CHS cell proliferation, migration, and angiogenesis, and CBX7 overexpression partially abolished the promotional effects of RNF2 overexpression. LV-sh-RNF2 prominently restricted tumor growth and weight and declined lung metastatic nodules and Ki-67-positive cells in mice. Conclusion: RNF2 fosters CHS progression by elevating CBX7 degradation via the ubiquitination pathway. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a summary of the publication about the DESTINY-Lung01 study, which was published in the New England Journal of Medicine in September 2021. The DESTINY-Lung01 study includes 181 adults with metastatic non-small-cell lung cancer (NSCLC) that could not be treated with surgery and who have had previous standard anticancer treatment. The publication includes information and results about 91 of the 181 study participants. These 91 participants had HER2-mutant NSCLC. Researchers wanted to learn if the drug trastuzumab deruxtecan (T-DXd) could help treat participants with HER2-mutant NSCLC. At the time of this publication, this study is ongoing. What are the key takeaways? Results from the study showed that 55% of participants responded to treatment with T-DXd. The median length of time participants continued to respond to T-DXd was 9.3 months. After receiving T-DXd, 92% of participants had disease control. After receiving T-DXd, half of the participants lived for at least 17.8 months. After receiving T-DXd, half of the participants lived for 8.2 months before their cancer got worse. During the study, 97% of participants had drug-related adverse events, with nausea being the most common. There were 20% of participants with serious drug-related adverse events. What were the main conclusions reported by the researchers? Based on these results, T-DXd could be a treatment option for people with HER2-mutant NSCLC that has been previously treated. Clinical Trial Registration:NCT03505710 (DESTINY-Lung01) (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Background: With the advancement of cancer treatment, appropriate treatment for musculoskeletal problems is becoming more important as it extends the patient's lifespan and improves the quality of life. In surgical treatment for metastatic spine tumors (MST), various efforts are being considered to obtain a good prognosis. The purposes of this study are to analyze prognostic factors for postoperative ambulation and perioperative complications in patients surgically treated for MST with neurologic symptoms. Methods: Seventy five cases of patients who underwent surgery for MST with neurologic symptoms were enrolled between December 2016 and January 2023. Postoperative ambulatory function and medical complications were assessed for each patient in this study. The endpoint of ambulatory function was defined as the best function among entire periods of follow-up outpatient visits. We defined the improvement of ambulatory function as improvement in Eastern Cooperative Oncology Group (ECOG) scale. For complications, we applied complication classification system for orthopaedic surgery. Perioperative complications were defined as those requiring changes of treatment compared with routine postoperative treatment during patient's admission. Confirmed complications included expire, delirium, urinary tract infection (UTI), pneumonia, sepsis, bacteremia, acute kidney injury (AKI), chylothorax. Prognostic factors were collected and analyzed for relationship by logistic regression. Results: Of the 75 cases, postoperatively 42 (56%) cases of patients were improved in Nurick grade, 36 (48%) cases of patients in ECOG performance. And 21 (28%) cases of patients were treated in intensive care unit (ICU) and 15 (20%) cases of patients suffered from major perioperative complications. Regression analysis showed that clinical factors such as ECOG, psoas muscle index (PMI) and prognostic nutritional index (PNI) were related to the improvement of ambulatory function and incidence of perioperative complications. On multivariate analysis, improvement of ambulatory function was associated with PMI (p = 0.014) and incidence of perioperative complications was associated with PNI (p = 0.045). Conclusions: Preoperative nutritional status and sarcopenia are related factors in the outcome of surgical treatment for MST, and preoperative efforts to improve these may be a way to obtain better clinical results. [ABSTRACT FROM AUTHOR]

Metastasis and recurrence are the main challenges in cancer treatment. Among various therapeutic approaches, immunotherapy holds promise for preventing metastasis and recurrence. In this study, we evaluated the efficacy of treating primary cancer and blocking metastasis and recurrence with photo-immunotherapeutic nanoparticles, which were synthesized using two types of charged polysaccharides. Codium fragile polysaccharide (CFP), which exhibits immune-stimulating properties and carries a negative charge, was combined with positively charged chitosan to synthesize nanoparticles. Additionally, indocyanine green (ICG), a photosensitizer, was loaded inside these particles and was referred to as chitosan-CFP-ICG (CC-ICG). Murine colon cancer cells (CT-26) internalized CC-ICG, and subsequent 808-nanometer laser irradiation promoted apoptotic/necrotic cell death. Moreover, intratumoral injection of CC-ICG, with 808-nanometer laser irradiation eliminated CT-26 tumors in mice. Rechallenged lung metastases of CT-26 cancer were inhibited by dendritic cell activation-mediated cytotoxic T lymphocyte stimulation in mice cured by CC-ICG. These results demonstrated that CC-ICG is a natural tumor therapeutic with the potential to treat primary tumors and suppress metastasis and recurrence. [ABSTRACT FROM AUTHOR]

Cancer detection and inflammation monitoring during photothermal therapy (PTT) enable timely cancer intervention and precise inflammation control, advancing to address inflammation‐related tumor recurrence and metastasis associated with PTT. This can be achieved through real‐time monitoring biomarker for cancer and inflammation, like hypochlorous acid (HOCl), a highly reactive oxygen species (hROS) in body with elevated levels in inflammation. Here, a HOCl‐responsive theranostic nanoprobe is introduced, AuNRs@SiO2‐CAA for ratiometric photoacoustic (PA) cancer detection and inflammation monitoring during PTT. AuNRs@SiO2‐CAA emits PA signals at 680 and 820 nm, with only PA680 undergoing changes in the presence of HOCl, enabling precise HOCl imaging via recording changes of ratiometric PA signals (PA680/PA820). AuNRs@SiO2‐CAA exhibits high selectivity and sensitivity, with a detection limit of 0.34 µM for ratiometric PA imaging of HOCl. In vivo, it effectively detects tumor, drives PTT, and monitors inflammation during PTT by sensing HOCl. The successful development of AuNRs@SiO2‐CAA offers a novel theranostic nanoprobe system for cancer diagnosis, poised to enhance PTT through precise inflammation control. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion In the assessment of breast cancer using 18‐F FDG PET/CT, the incremental clinical benefit in performing a true whole‐body PET/CT (with a field of view (FOV) from the vertex to the toes) over a limited whole‐body PET/CT (with a FOV from the base of skull to the mid‐thighs) is uncertain.Two hundred and one studies of 120 patients who underwent staging or restaging true whole body 18F‐FDG PET/CT for breast cancer were retrospectively identified. Any abnormal hypermetabolic or structural focus outside the limited FOV was recorded and characterised, and referenced with the patient's known disease status and any symptomatology.A total of 18 (9.0%) studies had FDG avid and/or structural abnormalities detected outside the limited whole‐body FOV which were identified as malignant. Seventeen out of 18 (94.4%) were skeletal and of these, 15/17 (88.2%) were located within the lower limbs. In three cases, there were de novo findings but identified in the presence of interval progression of other metastases within the limited whole‐body FOV. None of these additional findings is known to have resulted in a change to staging or clinical management.In the assessment of breast cancer, a true whole‐body PET/CT can reveal metastases outside the limited whole‐body FOV, but these are unlikely to be encountered in isolation and therefore may have little bearing on clinical stage or management. Ultimately, while the choice of FOV should still be based on the individual patient situation, routine utilisation of the true whole‐body FOV in the asymptomatic patient may not be necessary. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, with high incidence and poor prognosis. Revealing mechanisms of ESCC progression and developing new therapeutic targets remains crucial. The aim of this study was to elucidate the molecular mechanism of miR‐30c‐5p in regulating the malignant progression of ESCC. Methods: TCGA, GEO, and other datasets were used to analyze the differential expression of miR‐30c‐5p in ESCC and adjacent tissues, and its impact on prognosis. Then the effects of miR‐30c‐5p on the proliferation, migration, and invasion of TE‐1 and Eca9706 cells were investigated through proliferation experiments, transwell and wounding healing assays. The regulatory mechanism of miR‐30c‐5p on the PI3K/AKT signaling pathway and its interaction in cancer progression were investigated through Western blots, dual‐luciferase reporter assay, and rescue experiments. Results: miR‐30c‐5p was significantly downregulated in ESCC tissue and represented a poor prognosis. miR‐30c‐5p mimic significantly inhibited the proliferation, migration, and invasion ability of ESCC, while miR‐30c‐5p inhibitor significantly promoted tumor cell progression. Through bioinformatic analysis and experimental results, miR‐30c‐5p interacted directly with PIK3CA mRNA and inhibited subsequent signaling pathway activation. PIK3CA activator could eliminate the inhibitory effects of miR‐30c‐5p mimic on the progression of ESCC, while PIK3CA inhibitors could rescue the promoting effect of miR‐30c‐5p inhibitor group cells. Conclusions: In summary, we found that miR‐30c‐5p inhibited the proliferation, invasion and migration of ESCC by inhibiting PI3K/AKT signaling pathway for the first time, and this study is expected to provide a novel insight and potential therapeutic target for managing ESCC. [ABSTRACT FROM AUTHOR]

Purpose: This study compared survival and metastasis occurrence between colorectal neuroendocrine neoplasms (cNEN) and colorectal adenocarcinoma with neuroendocrine differentiation (cNED) and further explored their prognostic factors and treatment indicators. Methods: Patients diagnosed as cNEN and cNED in West China Hospital from January 2009 to December 2020 were enrolled. The diagnosis and metastasis rates were calculated. Univariate and multivariate Cox analyses were conducted for progression-free survival (PFS) in cNEN surgical patients, and generalized linear regression was used for metastatic disease. Result: The study enrolled 435 patients, including 257 neuroendocrine tumors (NET), 52 neuroendocrine carcinomas (NEC), 29 mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), and 97 NED patients, of whom 202 received local resection, and 233 received radical resection. Metastasis rates were higher in MiNEN and NEC groups compared to other groups (NED: 28.9%, MiNEN: 58.6%, NEC: 65.4%, NET: 8.6%, p < 0.001). The liver is the main metastatic site in cNEN, whereas cNED metastasized to various sites. For NEC and MiNEN patients, colon location (p = 0.002) and T stage > 2 (p = 0.040) were associated with disease progression separately. Independent risk factors for metastatic NET included tumor grade G2/G3 (p < 0.001), colon location (p = 0.001), size ≥ 1 cm (p = 0.005), and CK20 partial positive (p < 0.001). Conclusion: cNEN show high metastatic capacity and are challenging to diagnose. More aggressive treatment and follow-up strategies are necessary for those patients. NET tumor grade higher than G2, size larger than 1 cm, or located in the colon should be managed with radical surgery. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Contralateral axillary lymph node metastasis (CAM) is a rare clinical condition in patients with breast cancer (BC). CAM can be either a locoregional event or a distant metastasis. Molecular application for clonal evolution in BC has not been reported in CAM cases.We studied six patients with CAM with clinical, pathological and/or molecular evidence of distant metastasis; those patients had poor outcomes.Two cases with molecular analysis of paired primary and CAM established clonal evolution of the CAM with its corresponding primary with additional molecular alteration, increased tumour mutation burden, and copy number variations (CNVs) in the CAMs. Four cases containing alterations from genes potentially modulate chromatin organization, supporting chromatin and subsequent transcriptional signature changes are essential in CAM. Molecular analysis is critical to establish the connection between CAM and its primary counterpart. Distant CAM shows clonal evolution compared with its corresponding primary with additional molecular alterations, increased mutation burden and/or copy number variations.CAM should be evaluated individually and handled in a personalized fashion. Evidence of a true metastatic CAM can be supported by distant metastasis to other organs, specific morphological features and/or clonal evolution. [ABSTRACT FROM AUTHOR]

Background: Roburic acid (ROB) is a newly discovered tetracyclic triterpene acid extracted from oak galls, which has anti-inflammatory effects, but the mechanism of its anticancer effect is not clear. Our study focuses on exploring the potential mechanism of action of ROB in the treatment of lung cancer using a combination of network pharmacological prediction, molecular docking technique and experimental validation. Methods: A network pharmacology approach was used to screen the protein targets of ROB and lung cancer, and PPI network analysis and enrichment analysis were performed on the intersecting genes. The tissue and organ distribution of the targets was also evaluated based on the BioGPS database. To ensure the reliability of the network pharmacology prediction results, we proceeded to use molecular docking technique to determine the relationship between drugs and targets. Finally, in vitro experiments with cell lines were performed to further reveal the potential mechanism of ROB for the treatment of lung cancer. Results: A total of 83 potential targets of ROB in lung cancer were collected and further screened by using Cytoscape software, and 7 targets of PTGS2, CYP19A1, PTGS1, AR, CYP17A1, PTGES and SRD5A1 were obtained as hub genes and 7 hub targets had good binding energy with ROB. GO and KEGG analysis showed that ROB treatment of lung cancer mainly involves Arachidonic acid metabolism, Notch signaling pathway, cancer pathway and PPAR signaling pathway. The results of in vitro experiments indicated that ROB may inhibit the proliferation and metastasis of lung cancer cells and activate the PPARg signaling pathway, as well as induce cellular autophagy. Conclusions: The results of this study comprehensively elucidated the potential targets and molecular mechanisms of ROB for the treatment of lung cancer, providing new ideas for further lung cancer therapy. [ABSTRACT FROM AUTHOR]

Background: The status of sentinel lymph nodes is crucial for prognosis and treatment decisions in breast cancer patients. This study aimed to evaluate the predictive value of combined methylene blue and indocyanine green for sentinel lymph node metastasis in breast cancer. Methods: This prospective cohort study enrolled 90 clinically node-negative breast cancer patients. Methylene blue and indocyanine green were injected locally before surgery. Sentinel lymph nodes were grouped based on fluorescence intensity and methylene blue staining. A binary logistic regression model was established using 285 lymph node groups to predict metastatic risk. Results: A total of 475 lymph nodes were identified, with 33 being metastatic. The metastatic risk reached 70% for partially blue-stained and weakly fluorescent lymph nodes between 1-2 cm. The model revealed associations between lymph node size, dye staining patterns, and metastatic risks (P<0.05). The AUC of the ROC curve was 0.855. Conclusions: The staining pattern of combined methylene blue and indocyanine green could predict risks of sentinel lymph node metastasis and facilitate rapid intraoperative identification of high-risk lymph nodes. [ABSTRACT FROM AUTHOR]

Background: Extraskeletal mesenchymal chondrosarcoma (ESMC), an uncommon and highly aggressive form of chondrosarcoma, is characterized by its mesenchymal origin and absence of skeletal involvement. Only a few cases of primary ESMC with metastasis to the pancreas have been reported so far. In this study, we present a case of ESMC in the left thigh with a solitary pancreatic metastasis in a 45-year-old woman. Additionally, we provide a thorough overview of ESMC, encompassing its entire clinical progression and radiographic observations. Furthermore, we reviewed all thirteen cases of pancreatic metastasis, including this present case, analyzing patient attributes, clinical management, and prognosis. Case presentation: A 45-year-old woman has had a painless mass in her left thigh for one year. X-ray, computed tomography (CT), andmagnetic resonance imaging of the left thigh were performed. Positron emission tomography-CT imaging showed a high accumulation in the left thigh tumor and the pancreatic neck lesion. A diagnosis of extraskeletal chondrosarcoma with pancreatic metastasis was determined based on the radiological examinations. A final diagnosis of ESMC was confirmed by histopathological and immunohistochemical examinations after surgical resection. The patient presentedmetastasis in the lung, right groin, and tail of the pancreas successively, and mostly received complete surgical excision during a 39-month follow-up with postoperative chemotherapy. Conclusion: We present a highly uncommon case of ESMC spreading to the pancreas and highlight the importance of recognizing the distinctive imaging features of ESMC for diagnosis and prognosis assessment. [ABSTRACT FROM AUTHOR]

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F] NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0-20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%-34% for non-tumour bone in each dose level. [ABSTRACT FROM AUTHOR]

Background: The liver is a frequent location of metastatic disease in various malignant tumor entities. Computed tomography (CT) is the most frequently employed modality for initial diagnosis. However, liver metastases may only be delineated vaguely on CT. Calculating radiomics features in feature maps can unravel textures not visible to the human eye on a standard CT reconstruction (SCTR). This study aimed to investigate the comparative diagnostic accuracy of radiomics feature maps and SCTR for liver metastases. Materials and methods: Forty-seven patients with hepatic metastatic colorectal cancer were retrospectively enrolled. Whole-liver maps of original radiomics features were generated. A representative feature was selected for each feature class based on the visualization of example lesions from five patients. These maps and the conventional CT image data were viewed and evaluated by four readers in terms of liver parenchyma, number of lesions, visual contrast of lesions and diagnostic confidence. T-tests and chi²-tests were performed with a significance cut off of p<0.05 to compare the feature maps with SCRT, and the data were visualized as boxplots. Results: Regarding the number of lesions detected, SCTR showed superior performance compared to radiomics maps. However, the feature map for firstorder RootMeanSquared was ranked superior in terms of very high visual contrast in 57.4% of cases, compared to 41.0% in standard reconstructions (p < 0.001). All other radiomics maps ranked significantly lower in visual contrast when compared to SCTR. For diagnostic confidence, firstorder RootMeanSquared reached very high ratings in 47.9% of cases, compared to 62.8% for SCTR (p < 0.001). The conventional CT images showed superior results in all categories for the other features investigated. Conclusion: The application of firstorder RootMeanSquared feature maps may help visualize faintly demarcated liver lesions by increasing visual contrast. However, reading of SCTR remains necessary for diagnostic confidence. [ABSTRACT FROM AUTHOR]

A 75‐year‐old female was diagnosed with a type 0‐I, moderately differentiated, early gastric carcinoma on the posterior wall of the middle gastric body during esophagogastroduodenoscopy (EGD). Several small whitish structures, referred to as white globe appearances (WGAs), were noted on the oral side outside the demarcation line of the cancerous protrusion. Although this area was flat without cancerous mucosal changes on the surface, subepithelial cancer extension was suspected. The histopathology of the resected specimen revealed that the carcinoma with submucosal invasion had significant lymphatic invasion with submucosal lateral extent along lymphatic vessels. In some areas, the carcinoma within the lymphatic vessels regressed from the submucosal layer towards the mucosal lamina propria, penetrating the muscularis mucosas. The intralymphatic carcinoma reaching just beneath the epithelium was considered to manifest WGA features during endoscopy. [ABSTRACT FROM AUTHOR]

Introduction: Cetuximab, used to treat head and neck squamous cell carcinoma and metastatic colorectal cancer, can cause severe infusion reactions. Case presentation: We report an 87-year-old East Asian woman with stage IV ileocecal signet ring cell carcinoma who experienced severe allergic reactions to cetuximab despite pre-treatment. A dose escalation method, involving weekly incremental doses with comprehensive pre-treatment and close monitoring, was employed, successfully reducing allergic reactions and allowing safe administration. Conclusion: This approach demonstrates a viable alternative for patients with hypersensitivity to cetuximab, warranting further research for personalized treatment optimization. [ABSTRACT FROM AUTHOR]

There is documented sex disparity in cutaneous melanoma incidence and mortality, increasing disproportionately with age and in the male sex. However, the underlying mechanisms remain unclear. While biological sex differences and inherent immune response variability have been assessed in tumor cells, the role of the tumor-surrounding microenvironment, contextually in aging, has been overlooked. Here, we show that skin fibroblasts undergo age-mediated, sex-dependent changes in their proliferation, senescence, ROS levels, and stress response. We find that aged male fibroblasts selectively drive an invasive, therapy-resistant phenotype in melanoma cells and promote metastasis in aged male mice by increasing AXL expression. Intrinsic aging in male fibroblasts mediated by EZH2 decline increases BMP2 secretion, which in turn drives the slower-cycling, highly invasive, and therapy-resistant melanoma cell phenotype, characteristic of the aged male TME. Inhibition of BMP2 activity blocks the emergence of invasive phenotypes and sensitizes melanoma cells to BRAF/MEK inhibition. [Display omitted] • Skin fibroblasts show age- and sex-specific changes in proliferation and stress response • Male fibroblasts age faster due to elevated ROS levels • BMP2 is secreted in the aged male dermal microenvironment • BMP2 promotes slow-cycling, invasive, targeted therapy-resistant melanoma tumors Aging-driven and sex-dependent molecular changes in skin fibroblasts drive the emergence of invasive and therapy-resistant melanomas in male mice. [ABSTRACT FROM AUTHOR]

ABSTRACT Nodal metastasis is a negative prognostic factor in dogs with mast cell tumours (MCTs), thus early detection enables more informed decision‐making and provides valuable prognostic information. The aim of this study is to assess the concordance between histopathologic findings of LNs and cytology and flow cytometry (FC), respectively, and to evaluate the ability of FC to differentiate between metastatic (HN2–HN3) and non‐metastatic (HN0–HN1) LNs. Overall, 117 LNs from 64 dogs with first occurring MCTs were submitted for cytology, histology and FC. LNs were cytologically and histologically classified according to Krick and Weishaar systems, respectively. Using FC, mast cells (MCs) were identified as IgE+ CD117+ CD5− CD21− cells and quantified as a percentage. When compared with histologic classification, cytology showed an accuracy of 88.2% in distinguishing between metastatic and non‐metastatic LNs but did not detect 25.3% of metastatic cases. FC revealed an increase in the median percentages of MCs across histologic classes, progressing from HN0 to HN3. ROC curves pinpointed 0.3% as the optimal cut‐off for distinguishing between metastatic and non‐metastatic LNs, with an accuracy of 84.3%. A 1.1% cut‐off proved valuable in identifying HN3 LNs. The combined interpretation of cytology and FC increased accuracy to 92.2%. An algorithm for guiding the combined interpretation of cytology and FC is suggested based on these findings. In conclusion, FC proves beneficial in enhancing the early detection of metastatic LNs, particularly when utilised alongside cytology. Histopathology remains essential for confirmation, enabling the discrimination of HN classes or, in doubtful cases, for the detection or exclusion of nodal metastases. [ABSTRACT FROM AUTHOR]

Introduction: Neutrophil extracellular traps (NETs) are complex structures released by activated neutrophils that may modulate different steps of the metastatic cascade. The aim of our study was to investigate how NETs can modulate the adhesion properties of cancer cells and whether cell exposure to NETs can activate the epithelial-to-mesenchymal transition (EMT) program thus enhancing the migratory and invasive properties of tumor cells. Materials and methods: Different cancer cell lines were subjected to a solidphase adhesion assay using NET-coated plates with or without the addition of antibodies against α5β1 or CCDC25 receptor. After 1-4 h of incubation, adherent cells were expressed as the percentage of total cell number. To test EMT occurrence, cells were treated with NETs for up to 48 h and then the levels of E-cadherin, vimentin, Snail, Slug, Zeb 1 and Twist 1 along with levels of Notch 1 and cleaved Notch 1 were determined by western blotting. Untreated and NETtreated cells were subjected to migration assays using 24-multiwell plates with transwell and FBS as chemoattractant. Results: Cancer cell adhesion to NET-coated plates varied between 30% and 92.7% and was significantly higher than that obtained in uncoated plates. The addition of antibodies against α5β1 or CCDC25 caused a strong reduction of cell adhesion to NETs. The prolonged exposure of EGFR-driven cancer cell lines to NETs caused the activation of the EMT program through the upregulation and cleavage of Notch 1 and was confirmed by the enhanced expression of EMT markers. The consequent loss of the epithelial phenotype induced a strong reduction of the expression of the oncogene driver. Cell migration was significantly enhanced in NET-treated cells as compared to untreated cells. Discussion: Our findings reveal the dynamic role of NETs that may provide a DNA and fibronectin rich environment for binding of many cancer cells at distant sites where the prolonged exposure to NETs triggers the EMT through the activation of Notch 1 signaling pathway with the subsequent enhancement of migratory and invasive properties of cancer cells. Furthermore, our findings provide an example of how an immune/inflammatory microenvironment may directly modulate the sensitivity of cancer cells to oncogene targeted agents. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) provides essential conditions for the occurrence, invasion, and spread of cancer cells. Initial research has uncovered immunosuppressive properties of the TME, which include low oxygen levels (hypoxia), acidic conditions (low pH), increased interstitial pressure, heightened permeability of tumor vasculature, and an inflammatory microenvironment. The presence of various immunosuppressive components leads to immune evasion and affects immunotherapy efficacy. This indicates the potential value of targeting the TME in cancer immunotherapy. Therefore, TME remodeling has become an effective method for enhancing host immune responses against tumors. In this study, we elaborate on the characteristics and composition of the TME and how it weakens immune surveillance and summarize targeted therapeutic strategies for regulating the TME. [ABSTRACT FROM AUTHOR]

Most studies on CTCs have focused on isolating cells that express EpCAM. In this study, we emphasize the presence of EpCAM-negative and EpCAMlow CTCs, in addition to EpCAMhigh CTCs, in early BC. We evaluated stem cell markers (CD44/CD24 and CD133) and EMT markers (N-cadherin) in each subpopulation. Our findings indicate that all stemness variants were present in both EpCAMhigh and EpCAM-negative CTCs, whereas only one variant of stemness (nonCD44+CD24−/CD133+) was observed among EpCAMlow CTCs. Nearly all EpCAMhigh CTCs were represented by CD133+ stem cells. Notably, the hybrid EMT phenotype was more prevalent among EpCAM-negative CTCs. scRNA-seq of isolated CTCs and primary tumor partially confirmed this pattern. Therefore, further investigation is imperative to elucidate the prognostic significance of EpCAM-negative and EpCAMlow CTCs. [ABSTRACT FROM AUTHOR]

The discovery of embryonic stem cell (ESC) mediating tumoricidal activity revealed the intimate relationship between ESCs and tumor cells, but the functional role of ESCs in tumor progression is poorly understood. To further investigate tumor cell and ESC interactions, we co-cultured mouse ESCs with mouse pancreatic cancer Pan02 cells or mouse melanoma B16-F10 cells in Transwell, and found that tumor cell invasion was significantly inhibited by ESCs. Application of ESCs to tumor-bearing mice resulted in significant inhibition of tumor metastasis in vivo. RNA-Seq analyses of tumor cell and ESC co-cultures identified TP53 and related signalling as major pathways involved in ESC-mediated inhibition of tumor cell invasion and metastasis, which indicated the potential clinical application of ESCs to treat cancer. [ABSTRACT FROM AUTHOR]

Background: There has been significant improvement in treating metastatic non–small-cell lung cancer (mNSCLC) over the past 2 decades. The aim of this study is to describe the use of tyrosine kinase inhibitors (TKIs) in Qatar. This study focuses on the objective response rate (ORR) and reported adverse drug events (ADEs) of TKIs used for the management of patients with mNSCLC. Methods: This is a descriptive retrospective cohort study. All non–small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations who received TKIs between 2015 and 2019 in Qatar were included. The TKIs used during this period include EGFR inhibitors such as afatinib, erlotinib, gefitinib, and osimertinib and ALK inhibitors such as alectinib and crizotinib. The response on each TKI was identified by reporting the ORR (as the sum of the complete response [CR] and the partial response [PR]), in addition stable disease (SD) and disease progression (DP) were reported. While ADEs were reported using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE). Results: A total of 63 patients were included, of which 36 cases (57.1%) expressed EGFR mutation, and 27 patients (42.9%) expressed ALK rearrangement. The ORR in EGFR inhibitors was as follows: osimertinib 40%, gefitinib 33%, afatinib 22%, and erlotinib 18%. However, the response to the ALK-targeted therapy was 43% with alectinib and 40% with crizotinib. A total of 112 ADEs were reported. They were distributed as 63.4% (71 of 112) with the anti-EGFR and 36.6% (41 of 112) ADEs with the ALK inhibitors. In the anti-EGFR group, the most common types of ADEs were dermatological toxicity 30%, whereas, in the anti-ALK group, gastrointestinal toxicity was the most common (29%). Conclusions: The EGFR-targeted and ALK-targeted therapies appear to have acceptable clinical response rate and safety profile in our population. Close and frequent monitoring of adverse events is advised to ensure a good quality of life and prevent serious complications. [ABSTRACT FROM AUTHOR]

Fluorogens with aggregation‐induced emission (AIEgens) are promising agents for two‐photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post‐regulation strategy to optimize AIEgens' photophysical properties. Herein, a general and efficient post‐regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two‐photon absorption cross‐section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single‐cell resolution. Furthermore, the TPF imaging quality is improved by the self‐supervised denoising algorithm. The proposed binary molecular post‐regulation strategy opened a new avenue to efficiently boost the AIEgens' photophysical properties and consequently TPF imaging quality. [ABSTRACT FROM AUTHOR]

Introduction: Treatment with topotecan is standard-of-care therapy for relapsed small-cell lung cancer (SCLC). Both oral and intravenous administrations of topotecan have been extensively researched and are found to be equally effective with less adverse events in the oral group. Case Presentation: We report a case of a patient with SCLC, who had previously received oral topotecan, with radiological stable disease with no changes in tumor or metastasis diameter size after two administrations. Subsequently, this patient received intravenous topotecan instead of oral due to supply difficulties. After one administration of intravenous topotecan, we saw significant disease regression. Conclusion: This is to our knowledge the first reported case of better response of intravenous topotecan than oral topotecan. Multiple extrinsic (e.g., food, medication) factors were investigated but could not deliver an explanation. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound-guided drainage of loculated malignancy-related ascites has been reported in limited case series with success in achieving symptomatic relief. In this case report, we detail the successful drainage of a loculated paragastric ascites with insertion of a lumen-apposing metal stent (LAMS) in a patient diagnosed with metastatic ovarian cancer. Plain language summary: Draining fluid buildup using a specialized stent: a case study in cancer treatment This article discusses a specific procedure used to drain fluid buildup caused by cancer. The procedure involves using a special type of stent placed with the help of an ultrasound device. The case study shows how this method successfully relieved symptoms in a patient with advanced ovarian cancer. [ABSTRACT FROM AUTHOR]

Metastatic colorectal cancer continues to have a high fatality rate, with approximately only 14% of patients surviving more than 5 years. To improve the survival rate of these patients, the development of new therapeutic drugs is a priority. In this study, we investigated the effects of Oroxylin A on the metastasis of human colorectal cancer cells and its potential molecular mechanism. This study utilised CCK8 assay, transwell assay, flow cytometry, western blot analysis, molecular docking, HE staining, immunofluorescence staining, and xenograft models. The proliferation, migration, and invasion of colon cancer cells were effectively suppressed by Oroxylin A in a dose-dependent manner. Oroxylin A has the potential to inhibit the process of epithelial‒mesenchymal transition (EMT) by upregulating the expression of E-cadherin, a marker associated with epithelial cells, while downregulating the levels of N-cadherin, Snail, vimentin, and slug, which are markers associated with mesenchymal cells. In addition, 200 mg/kg of Oroxylin A inhibited the growth of colorectal tumours. Molecular docking technology revealed that Oroxylin A can bind to TGFβ and inhibit the activation of the TGFβ-smad signalling pathway. The overexpression of TGFβ weakened the inhibitory effect of Oroxylin A on the proliferation, migration, and invasion of human colorectal cancer cells, as well as the promoting effect on apoptosis. Oroxylin A inhibited the activation of the TGF-smad signalling pathway and the EMT process, thereby suppressing the migration and invasion of human colorectal cancer cells. [ABSTRACT FROM AUTHOR]

The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have indicated that ψ-modified small RNAs play crucial roles in tumor metastasis. However, the ψ-modified small RNAs during metastasis of PTC are still unclear. Methods: We compared the pseudouridine synthase 7 (PUS7) alteration between metastatic and non-metastatic PTCs, and investigated its correlation with clinicopathological features. Additionally, we employed a small RNA ψ modification microarray to examine the small RNA ψ modification profile in both metastatic and non-metastatic PTCs, as well as paired paracancerous tissues. The key molecule involved in ψ modification, pre-miR-8082, was identified and found to regulate the expression of CD47. Experiments in vitro were conducted to further investigate the function of PUS7 and CD47 in PTC. Results: Our results demonstrated that PUS7 was down-regulated in PTC and was closely associated with metastasis. Moreover, the ψ modification of pre-miR-8082 was found to be decreased, resulting in down-expression of pre-miR-8082 and miR-8082, leading to the loss of the inhibitory effect on CD47, thereby promoting tumor migration. Conclusions: Our study demonstrates that PUS7 promotes the inhibition of CD47 and inhibits metastasis of PTC cells by regulating the ψ modification of pre-miR-8082. These results suggest that PUS7 and ψ pre-miR-8082 may serve as potential targets and diagnostic markers for PTC metastasis. [ABSTRACT FROM AUTHOR]

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR‐200c) can hamper certain steps of the invasion–metastasis cascade. However, it is still unclear whether miR‐200c expression alone is sufficient to prevent breast cancer cells from metastasis formation. Hence, we performed a xenograft mouse experiment with inducible miR‐200c expression in MDA‐MB 231 cells. The ex vivo analysis of metastatic sites in a multitude of organs, including lung, liver, brain, and spleen, revealed a dramatically reduced metastatic burden in mice with miR‐200c‐expressing tumors. A fundamental prerequisite for metastasis formation is the motility of cancer cells and, therefore, their migration. Consequently, we analyzed the effect of miR‐200c on collective‐ and single‐cell migration in vitro, utilizing MDA‐MB 231 and MCF7 cell systems with genetically modified miR‐200c expression. Analysis of collective‐cell migration revealed confluence‐dependent motility of cells with altered miR‐200c expression. Additionally, scratch assays showed an enhanced predisposition of miR‐200c‐negative cells to leave cell clusters. The in‐between stage of collective‐ and single‐cell migration was validated using transwell assays, which showed reduced migration of miR‐200c‐positive cells. Finally, to measure migration at the single‐cell level, a novel assay on dumbbell‐shaped micropatterns was performed, which revealed that miR‐200c critically determines confined cell motility. All of these results demonstrate that sole expression of miR‐200c impedes metastasis formation in vivo and migration in vitro and highlights miR‐200c as a metastasis suppressor in breast cancer. [ABSTRACT FROM AUTHOR]

γδT cells represent a group of immune cells that are understudied but whose utility has been recognized for cancer immunotherapy purposes. Recent studies have highlighted a critical role for these cells in tumor initiation, growth, and metastasis and revealed an increasingly complex biology of γδT cell subsets that is context and tissue specific. We discuss here how γδT cell subsets are regulated, their interaction with cancer and other immune cells, and the implications from these latest discoveries for people with cancer. [ABSTRACT FROM AUTHOR]

Historically, ovarian cancer (OC) was thought to metastasize by surface-to-surface spread, but recent developments have yielded a new understanding of the paths of metastatic spread. Given the histologic and molecular heterogeneity of OC, we will focus on high-grade serous carcinoma (HGSC). Here, we provide a critical and more holistic view of the evidence supporting various routes of metastasis, including peritoneal, hematogenous, lymphatic, and nerve-related. Understanding the underlying mechanisms is necessary to improve treatment strategies for this challenging disease. Historically, ovarian cancer (OC) was thought to metastasize by surface-to-surface spread, but recent developments have yielded a new understanding of the paths of metastatic spread. Given the histologic and molecular heterogeneity of OC, we will focus on high-grade serous carcinoma (HGSC). Here, we provide a critical and more holistic view of the evidence supporting various routes of metastasis, including peritoneal, hematogenous, lymphatic, and nerve related. Understanding the underlying mechanisms is necessary to improve treatment strategies for this challenging disease. [ABSTRACT FROM AUTHOR]

Aims: Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low‐grade and low‐stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes. Methods: TCGA categories include POLE‐mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification. Results: The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE‐mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low‐ and high‐stage cohorts. We demonstrate that when stratified by molecular subtype, disease‐specific survival from the time of high‐stage (stages III–IV) presentation or time of recurrence in low‐stage (stages I–II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high‐stage P = 0.02, low‐stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC. Conclusions: We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours. [ABSTRACT FROM AUTHOR]

Malignant (high-grade) gliomas are aggressive intrinsic brain tumors that diffusely infiltrate the brain parenchyma. They comprise of World Health Organization (WHO) grade III and IV gliomas. Ionizing radiation or irradiation (IR) is frequently utilized in the treatment of both primary as well as metastatic brain tumors. On the contrary, macrophages (MΦ) are the most copious infiltrating immune cells of all the different cell types colonizing glioma. MΦ at tumor milieu are referred to as tumor-associated macrophages (TAMΦ). In malignant gliomas milieu, TAMΦ are also polarized into two distinct phenotypes such as M1 TAMΦ or M2 TAMΦ, which are capable of inhibiting or promoting tumor growth, respectively. Cranial-IR such as x- and γ-IR are sufficient to induce the migration of peripherally derived MΦ into the brain parenchyma. The IR facilitate a more immunosuppressive milieu via the stimulation of efferocytosis in TAMΦ, and an upsurge of tumor cell engulfment by TAMΦ exhibited detrimental effect of the anti-tumoral immune response in glioma. The MΦ inside the tumor mass are associated with multiple phenomena that include IR resistance and enrichment of the M2 MΦ after IR is able to facilitate glioblastoma multiforme (GBM) recurrence. Reviews on the role of cranial IR-induced peripheral and brain-engrafting macrophages (BeMΦ) in glioma are lacking. Specifically, most studies on peripheral, intrinsic as well as beMΦ on IR focus on WHO grade III and IV. Thus, this review precisely focuses primary on WHO grade III as well as IV gliomas. [ABSTRACT FROM AUTHOR]

Background: Cervical squamous cell carcinoma (SCC) is the most common type of cervical carcinoma. Usually, the cancer metastasizes through lymphatic or hematogenous dissemination. However, it is uncommon for a superficial spreading of cervical cancer to reach the endometrium, fallopian tubes, and the ovaries. Objectives: In the present study, we report 15 cases of superficial spreading SCC and discuss the possible mechanism involved. Methods: We collected 15 samples diagnosed by histopathology after surgery. Immunostaining, which included P16, P63, CD138, CD34, D2-40, and Ki-67, were performed for all samples. Results: All patients were postmenopausal or perimenopausal women. The commonest clinical presentation was vaginal bleeding in 66.67%. All patients were infected with HPV 16. The endometrium was replaced by high-grade squamous intraepithelial lesion (HSIL), which involved the endometrial gland, even squeezing into the myometrium and forming SCC. Bilateral fallopian tubes and ovaries involvement was in 1/15. A total of 10/15 (66.67%) of the women had disease of stage 1B or less. All SCCs were moderately or poorly differentiated. Immunohistochemistry revealed that the tumor cells were positive for P63 and P16, with a high Ki-67 labeling index. There was CD138 positive expression in varying degrees, which was strongly and diffusely expressed in 6/15 (40.00%). Conclusion: Superficial spread of cervical cancer towards the endometrium is a rare but cognizable phenomenon, and a guideline for the management of these cases has not been established. Our present findings suggest that multiple factors may interact with each other simultaneously, contributing to this rare disease. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumor of the liver (SFTL) is an exceptionally rare mesenchymal tumor, with only 117 cases reported in the literature. While most SFTs are benign, some exhibit malignant behavior, including local recurrence and metastasis. This report presents two cases of SFTL with systemic metastases, both involving prior intracranial tumors. The first case, a 52-year-old woman, discovered a liver mass incidentally during a routine physical exam. Subsequent investigations revealed potential bone metastasis, and biopsy confirmed SFT. She received two TACE procedures, anlotinib targeted therapy, and radiotherapy for the iliac bone lesion, resulting in stable disease with reduction in lesion size. The second case, a 46-year-old man, presented with multiple liver, pelvic, and lung lesions following pelvic tumor resection, with pathology confirming SFT. He was treated with long-term anlotinib therapy, CyberKnife for hepatic, lung, and pelvic lesions, and radiofrequency ablation for hepatic lesions. Postoperative recovery was uneventful, with no tumor progression on follow-up. SFTL presents with atypical clinical and imaging features, and diagnosis requires pathological and genetic confirmation. Radical resection is preferred for solitary tumors, while comprehensive treatment, including surgery and long-term follow-up, is essential for cases with recurrence or metastasis. [ABSTRACT FROM AUTHOR]

Introduction: The apparent diffusion coefficient (ADC) is a quantitative parameter that facilitates the detection and reliable differentiation of rectal cancer. MR differentiation between rectal carcinoma, post-radiation proctitis, and normal rectal wall with the ADC values and their comparison depending on the level of tumor markers and pathohistological characteristics of rectal carcinoma. Methods: The retrospective study performed at the Oncology Institute of Vojvodina included 300 patients, 100 each with rectal cancer, post-radiation proctitis, and normal rectum. Mean ADC values were obtained by measuring the region of interest (ROI) of the rectal wall. Results: Rectal cancer showed lower ADC values (0.665 ± 0.086 x 10-3mm2/s) compared to both post-radiation proctitis (1.648 ± 0.268 x 10-3mm2/s) and normal rectum (1.180 ± 0.110 x 10-3mm2/s) (p<0.001). No significant differences in ADC values were observed between different grades of rectal cancer (p=0.874; p>0.05), depending on the presence of metastases in the lymph nodes (p=0.357; p>0.05), different TN stage (p=0.196; p>0.05), local spread of the tumor (p=0.312; p>0.05), the presence of RAS mutation (p=0.829; p>0.05) and the value of tumor markers (p=0.923; p>0.05). ADC values below 1.013 x 10-3mm2/s with 100% sensitivity and 96% specificity indicate the presence of rectal cancer in relation to normal wall, with a positive predictive value of 96.1% and a negative of 100%. ADC values below 1.255 x 10-3mm2/s with 100% sensitivity and 95% specificity indicate rectal cancer in relation to post-radiation proctitis. ADC values above 1.339 x 10-3mm2/s with 87% sensitivity and 89% specificity indicate post-radiation proctitis in relation to normal wall. Discussion: The ADC is a useful marker in differentiating between rectal cancer, post-radiation proctitis, and normal rectal wall with high sensitivity and specificity, but it cannot be used to distinguish the histological grades of rectal cancer, nor other pathohistological parameters. [ABSTRACT FROM AUTHOR]

Esophageal cancer (EC) is among the most aggressive malignancies, ranking as the seventh most prevalent malignant tumor worldwide. Lymph node metastasis (LNM) indicates localized spread of cancer and often correlates with a poorer prognosis, emphasizing the necessity for neoadjuvant systemic therapy before surgery. However, accurate identification of LNM in EC presents challenges due to the lack of satisfactory diagnostic techniques. Imaging techniques, including ultrasound and computerized tomography scans, have low sensitivity and accuracy in assessing LNM. Additionally, the existing serological detection lacks precise biomarkers. The intricate and not fully understood molecular processes involved in LNM of EC contribute to current detective limitations. Recent research has shown potential in using various molecules, circulating tumor cells (CTCs), and changes in the microbiota to identify LNM in individuals with EC. Through summarizing potential biomarkers associated with LNM in EC and organizing the underlying mechanisms involved, this review aims to provide insights that facilitate biomarker development, enhance our understanding of the underlying mechanisms, and ultimately address the diagnostic challenges of LNM in clinical practice. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) is a pillar of cancer therapy used by more than half of all cancer patients. Clinically, RT is mostly delivered as external beam radiation therapy (EBRT). However, the scope of EBRT is limited in the metastatic setting, where all sites of disease need to be irradiated. Such a limitation is attributed to radiation-induced toxicities, for example on bone marrow and hematologic toxicities, resulting from a large EBRT field. Radiopharmaceutical therapy (RPT) has emerged as an alternative to EBRT for the irradiation of all sites of metastatic disease. While RPT can reduce tumor burden, it can also impact the immune system and anti-tumor immunity. Understanding these effects is crucial for predicting and managing treatment-related hematological toxicities and optimizing their integration with other therapeutic modalities, such as immunotherapies. Here, we review the immunomodulatory effects of α- and β-particle emitter-based RPT on various immune cell lines, such as CD8+and CD4+ T cells, natural killer (NK) cells, and regulatory T (Treg) cells. We briefly discuss Auger electron-emitter (AEE)-based RPT, and finally, we highlight the combination of RPT with immune checkpoint inhibitors, which may offer potential therapeutic synergies for patients with metastatic cancers. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prognostic significance of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) expression in patients with surgically resected osteosarcoma. Methods: CD44v6 and MMP2 expression were immunohistochemically detected in 113 primary osteosarcoma patients at our institute between 2001 and 2019. Results: Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival. An extended predictive range and improved sensitivity were observed when the combined effects of CD44v6 and MMP2 were considered. Specifically, patients with CD44v6+ and MMP2+ expression were more susceptible to lung metastasis and exhibited the poorest survival rates compared with the other groups. Conclusion: The combination of CD44v6 and MMP2 may serve as a precise prognostic indicator for predicting metastatic progression and survival outcomes in patients with osteosarcoma. Plain Language Summary The most common type of bone cancer in children, teens and young adults is osteosarcoma, which often spreads to the lungs. With proper chemotherapy and surgery, many patients can recover, but if the diagnosis and treatment process go wrong, it could have serious consequences. The most common symptoms of osteosarcoma in its early stages are pain and swelling. The pain usually comes and goes, which can be easily mistaken for growing pains, resulting in a delayed diagnosis. In patients with metastatic (cancer cells spreading from the primary site to other parts of the body) osteosarcoma, the number of metastatic sites and whether they can be completely removed through surgery are factors that affect prognosis. So, starting appropriate treatment early for patients could effectively reduce tumor spread and increase survival time. Article highlights The expression of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) exhibited a significant positive correlation in tumor tissues. A notable disparity was observed in the expression of CD44v6, CD44v6 and lung metastasis. Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival. When considering the combined expression of CD44v6 and MMP2, the double negative group for CD44v6 and MMP2 exhibited the most favorable 3-year metastasis-free survival (82.4%) and overall survival (85.7%) rates. Further multivariate analysis determined that co-expression of CD44v6 and MMP2 remained the most significant and independent prognostic factors for poor survival. The combined utilization of CD44v6 and MMP2 receiver operating characteristic analyses demonstrated a noteworthy area under the curve value of 0.817, signifying that the predictive efficacy of these two proteins exhibited an additive effect. [ABSTRACT FROM AUTHOR]

Objective: Notable progress has been made in "ferroptosis-based nano drug delivery systems (NDDSs)" over the past 11 years. Despite the ongoing absence of a comprehensive scientometric overview and up-to-date scientific mapping research, especially regarding the evolution, critical research pathways, current research landscape, central investigative themes, and future directions. Methods: Data ranging from 1 January 2012, to 30 November 2023, were obtained from the Web of Science database. A variety of advanced analytical tools were employed for detailed scientometric and visual analyses. Results: The results show that China significantly led the field, contributing 82.09% of the total publications, thereby largely shaping the research domain. Chen Yu emerged as the most productive author in this field. Notably, the journal ACS Nano had the greatest number of relevant publications. The study identified liver neoplasms, pancreatic neoplasms, gliomas, neoplasm metastases, and melanomas as the top five crucial disorders in this research area. Conclusion: This research provides a comprehensive scientometric assessment, enhancing our understanding of NDDSs focused on ferroptosis. Consequently, it enables rapid access to essential information and facilitates the extraction of novel ideas in the field of ferroptotic nanomedicine for both experienced and emerging researchers. [ABSTRACT FROM AUTHOR]

Erbin is an adapter protein that interacts with the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) in epithelial cells. Erbin plays an important role in various signaling pathways, including cell proliferation, apoptosis, and autophagy. Additionally, Erbin is implicated in the pathogenesis and progression of sepsis and various cancers, including breast cancer, acute myeloid leukemia (AML), hepatocellular carcinoma (HCC), and colorectal cancer (CRC). A recent study shows that loss of Erbin increases the release of acylcarnitine (Acar) through abolishing interaction with prothrombotic protein endothelial cell-specific adhesion molecule (ESAM), promotes mitochondrial oxidative phosphorylation in B cells, and ultimately suppresses lung metastasis of CRC. Accordingly, Erbin provides us with a new potential treatment for tumor metastasis. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most common primary intraocular tumour in adults. Local resection, radiation therapy, and enucleation are the current first-line, primary UM treatments. However, regardless of the treatment received, around 50% of UM patients will develop metastatic disease within five to 7 years. In the largest published series of unselected patients with metastatic UM (mUM), the median survival time after diagnosis of metastasis was 3.6 months, with less than 1% of patients surviving beyond 5 years. Approved drugs for treatment of mUM include systemic treatment with tebentafusp-tebn or isolated hepatic perfusion (IHP) with melphalan. However, these drugs are only available to a subset of patients and improve survival by only a few months, highlighting the urgent need for new mUM treatments. Accurately predicting which patients are at high risk for metastases is also crucial. Researchers are developing gene expression signatures in primary UM to create reliable prognostic models aimed at improving patient follow-up and treatment strategies. In this review we discuss the evidence supporting ferroptosis, a non-apoptotic form of cell death, as a potential novel treatment target and prognosticator for UM. [ABSTRACT FROM AUTHOR]

Introduction: Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. Materials and methods: This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. Results: In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. Conclusions: The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice. [ABSTRACT FROM AUTHOR]

In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer and causes high mortality worldwide. Although CRC has been studied widely, the molecular mechanism is not completely known. Eukaryotic translation elongation factor 1 delta (EEF1D) participates in the progression of various tumors, however, the effect of EEF1D on CRC remains unclear. Here, we aimed to identify the potential mechanism of EEF1D in CRC. The expression levels of EEF1D were assessed in CRC samples. Functional analysis of EEF1D in CRC was detected in vitro and in vivo. The regulatory mechanism of EEF1D was identified with RNA immunoprecipitation, RNA pull‐down assay, and proteomics analysis. Our findings confirmed that EEF1D was upregulated in human CRC tissues. Functionally, EEF1D overexpression accelerated cell proliferation and metastasis, whereas EEF1D knockdown inhibited cell proliferation and metastasis both in vitro and in vivo CRC models. Furthermore, we showed that EEF1D was upregulated by SRSF9 via binding to 3′UTR of EEF1D mRNA. EEF1D knockdown reversed the malignant phenotype induced by SRSF9 overexpression. These findings demonstrated that EEF1D promotes CRC progression, and EEF1D may be a molecular target against CRC. [ABSTRACT FROM AUTHOR]

Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis. [ABSTRACT FROM AUTHOR]

Background: Dedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated. Methods: This retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed. Results: A total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes. Conclusions: This is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted. [ABSTRACT FROM AUTHOR]

Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to analyze the clinical outcomes and malignant progression of tumors in patients who underwent reoperation for recurrent solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs). Methods: We identified 48 patients who underwent reoperation because of tumor recurrence at Tangdu Hospital between January 2010 and December 2021 and analyzed the clinical outcomes, namely, the rate of gross total resection (GTR), progression-free survival (PFS), overall survival (OS), malignant progression of tumors and radiotherapy. The survival curves for each group were plotted using the Kaplan‒Meier method and compared using log-rank tests. Results: Of the 48 patients (25 men and 23 women, mean age 49.5 ± 14.3 years), 25 experienced a second recurrence or metastasis, 15 of whom underwent a third surgery, and the remaining 10 patients who did not undergo surgery ultimately died after tumor progression. The median time (95% CI) to tumor recurrence was 40.0 (32.3–47.7) months after reoperation, with 3-, 5- and 10-year PFS rates of 54.6%, 29.5% and 14.8%, respectively. The median (95% CI) survival time was 70.0 (46.6–93.4) months, with 3-, 5- and 10-year survival rates of 67.9%, 55.1% and 36.7%, respectively. Among the 48 patients who underwent reoperation, 27 (56.3%) achieved GTR, and 21 (43.8%) achieved STR. Twelve patients in the GTR group (12/27, 44.4%) received radiotherapy after surgery, and 18 patients in the STR group (18/21, 85.7%) received radiotherapy. Of the 48 recurrent SFTs, 24 were classified as WHO grade 1, 14 were classified as WHO grade 2, and 10 were classified as WHO grade 3 based on 2021 WHO classification after the primary operation. After reoperation, 9 tumors developed malignant progression, including 4 WHO grade 1 tumors progressing to WHO grade 2 tumors, 1 WHO grade 1 tumor progressing to a WHO grade 3 tumor and 4 WHO grade 2 tumors progressing to WHO grade 3 tumors. Conclusions: GTR after reoperation was associated with better PFS and OS compared to STR. However, the PFS after the third surgery was significantly shorter than that after the second surgery, and the rate of GTR also decreased. Malignant progression may occur after second or third tumor recurrence. Furthermore, compared with WHO grade 1 SFTs, WHO grade 2 and grade 3 SFTs significantly decreased PFS, but OS did not differ among the three groups. Radiotherapy did not prolong PFS or OS in patients who underwent reoperation. [ABSTRACT FROM AUTHOR]