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Case Presentation: A 60-year-old female presented to the emergency department with unilateral eye pain and vision loss. Point-of-care ultrasound (POCUS) was performed, which demonstrated ocular metastatic lesions of breast cancer.Discussion: Ocular metastasis is rare, clinically challenging, and may present with a wide range of ophthalmic symptoms. However, POCUS may safely and rapidly identify metastatic lesions to direct further care.

The key challenge in cancer treatment is prevention of metastatic disease which is therapeutically resistant and carries poor prognoses necessitating efficacious prophylactic approaches that prevent metastasis and recurrence. It is previously demonstrated that cowpea mosaic virus (CPMV) induces durable antitumor responses when used in situ, i.e., intratumoral injection. As a new direction, it is showed that CPMV demonstrates widespread effectiveness as an immunoprophylactic agent - potent efficacy is demonstrated in four metastatic models of colon, ovarian, melanoma, and breast cancer. Systemic administration of CPMV stimulates the innate immune system, enabling attack of cancer cells; processing of the cancer cells and associated antigens leads to systemic, durable, and adaptive antitumor immunity. Overall, CPMV demonstrated broad efficacy as an immunoprophylactic agent in the rejection of metastatic cancer.

Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs.

Engrailed-1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain- and loss-of-function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.

Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fueled by the tumor cell's ability to "secrete-and-sense" growth factors (GFs); this translates into cell survival and proliferation that is self-sustained by autocrine/paracrine secretion. A Golgi-localized circuitry comprised of two GTPase switches has recently been implicated in the orchestration of growth signaling autonomy. Using breast cancer cells that are either endowed or impaired (by gene editing) in their ability to assemble the circuitry for growth signaling autonomy, here we define the transcriptome, proteome, and phenome of such an autonomous state, and unravel its role during cancer progression. We show that autonomy is associated with enhanced molecular programs for stemness, proliferation, and epithelial-mesenchymal plasticity. Autonomy is both necessary and sufficient for anchorage-independent GF-restricted proliferation and resistance to anticancer drugs and is required for metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated, with a surprising degree of specificity, with self-sustained epidermal growth factor receptor (EGFR)/ErbB signaling. Derivation of a gene expression signature for autonomy revealed that growth signaling autonomy is uniquely induced in circulating tumor cells (CTCs), the harshest phase in the life of tumor cells when it is deprived of biologically available epidermal growth factor (EGF). We also show that autonomy in CTCs tracks therapeutic response and prognosticates outcome. These data support a role for growth signaling autonomy in multiple processes essential for the blood-borne dissemination of human breast cancer.

Electronic cigarettes (e-cigarettes) are thought to pose low risk of cancer because the components of e-cigarette liquid are not carcinogens. We analyzed the effects of the two major components, PG/VG and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine. Whole body exposure of mice to PG/VG and nicotine rendered animals more susceptible to developing tumors with high frequencies of infiltrating proinflammatory macrophages expressing IL-6 and TNFα. Moreover, tumor-infiltrating and circulating T cells in e-cigarette exposed mice showed increased levels of immune checkpoints including CTLA4 and PD-1. Treatment with anti-CTLA4 antibody was able to abrogate metastasis with no detrimental effects on its ability to induce tumor regression in exposed mice. These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab.

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

Being implicated in bone metastasis development, bone sialoprotein (BSP) expression is upregulated in patients with cancer. While BSP regulates cancer cell adhesion to the extracellular matrix, to the best of our knowledge, the specific adhesive molecular interactions in metastatic bone disease remain unclear. The present study aimed to improve the understanding of the arginine-glycine-aspartic acid (RGD) sequence of BSP and the integrin receptors αvβ3 and αvβ5 in BSP-mediated cancer cell adhesion. Human breast cancer (MDA-MB-231), prostate cancer (PC-3) and non-small cell lung cancer (NSCLC; NCI-H460) cell lines were cultured on BSP-coated plates. Adhesion assays with varying BSP concentrations were performed to evaluate the effect of exogenous glycine-arginine-glycine-aspartic acid-serine-proline (GRGDSP) peptide and anti-integrin anti-bodies on the attachment of cancer cells to BSP. Cell attachment was assessed using the alamarBlue® assay. The present results indicated that BSP supported the adhesion of cancer cells. The RGD counterpart GRGDSP peptide reduced the attachment of all tested cancer cell lines to BSP by ≤98.4%. Experiments with anti-integrin antibodies demonstrated differences among integrin receptors and cancer cell types. The αvβ5 antibody decreased NSCLC cell adhesion to BSP by 84.3%, while the αvβ3 antibody decreased adhesion by 14%. The αvβ3 anti-body decreased PC-3 cell adhesion to BSP by 46.4%, while the αvβ5 antibody decreased adhesion by 9.5%. Adhesion of MDA-MB-231 cells to BSP was inhibited by 54.7% with αvβ5 antibody. The present results demonstrated that BSP-induced cancer cell adhesion occurs through the binding of the RGD sequence of BSP to the cell integrin receptors αvβ3 and αvβ5. Differences between cancer types were found regarding the mediation via αvβ3 or αvβ5 receptors. The present findings may explain why certain cancer cells preferentially spread to the bone tissue, suggesting that targeting the RGD-integrin binding interaction could be a promising novel cancer treatment option. [ABSTRACT FROM AUTHOR]

Metastasis occurs in nearly 50% of cases of adult soft-tissue sarcoma (ASTS), leading to a dismal prognosis, with a 2-year survival rate of ~30%. Consequently, a prognostic model that incorporates metastatic characteristics may be instrumental in predicting survival time and in crafting optimal personalized therapeutic strategies for patients with ASTS. In the present study, a prognostic prediction model for ASTS was developed by examining genes that are differentially expressed between non-metastatic and metastatic patients in the Gene Expression Omnibus dataset. The prognostic model, which includes five featured genes [actin γ2 (ACTG2), apolipoprotein D, coatomer protein complex subunit γ2 imprinted transcript 1, collagen type VI α6 chain and osteomodulin], was further validated in patients with ASTS from the Cancer Genome Atlas dataset. Based on these five-gene signatures, patients were categorized into high- and low-risk groups. Functional and pathway analyses revealed disparities in stemness, extracellular matrix and cell adhesion-related pathways between the two risk groups, particularly noting the activation of the PI3K-Akt pathway in high-risk cases. Analysis of immune infiltration also revealed variations in immune microenvironment changes between the two risk groups. Immunohistochemical staining substantiated the prognostic significance of these gene signatures in a specific sarcoma subtype. Additionally, wound-healing and Transwell assays demonstrated that inhibition of ACTG2 by shRNAs curbed cell migration and invasion in a sarcoma HOS cell line, underscoring its role in sarcoma metastasis. In conclusion, the present study successfully developed and validated a metastasis-based prognosis prediction model. This model not only reliably forecasts the survival of patients with ASTS, but also may pave the way for further investigation into the processes underlying sarcoma metastasis, ultimately aiding in the design of tailored therapeutic regimens. [ABSTRACT FROM AUTHOR]

Low-grade appendiceal mucinous neoplasm (LAMN) is a tumor that primarily originates from the appendix and belongs to the family of appendiceal mucinous neoplasms (AMNs). In 50% of female patients, AMNs (particularly LAMNs) have a tendency to metastasize to organs in the genital tract, where the neoplasm can mimic the features of primary ovarian mucinous cancer (POMC). The present case report reviewed the difficulties in differentiating between these two types of tumors. In the present case report, a 61-year-old female patient was admitted to the Second Department of Gynecological Surgery and Gynecological Oncology, University Clinical Hospital no. 4 at Lublin Medical University (Lublin, Poland) with the diagnosis of a right ovarian mass. After performing ultrasound and computed tomography (CT) scans and laboratory analysis, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy and resection of the Douglas peritoneum. Notably, the postoperative pathological assessment revealed LAMN with metastases to the right ovary and omentum. Immunohistochemically, cytokeratin 20 and caudal type homeobox 2 both stained positively, whereas paired box gene 8 stained negatively. After surgery, the patient received the recommended hyperthermic intraperitoneal chemotherapy at the Department of Surgical Oncology at Lublin Medical University. After 1 year, a CT scan was performed, which indicated no evidence of recurrent disease. In conclusion, observations from the present case report suggest that gynecologists should be conscious of the possibility of malignancies of gastrointestinal origin in cases of ovarian tumors instead of making direct assumptions of POMC. If the mucinous mass involves the base of the appendix or if there is a suspicion of positive margins, then cytoreductive surgery and right-sided hemicolectomy must be performed. In addition, identifying the origin of mucinous tumors in the right ovary and/or the appendix requires the histopathological examination of a panel of markers using immunohistochemistry. [ABSTRACT FROM AUTHOR]

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet‐derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element‐binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC‐mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC‐induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Ectopic thyroid tissue along the line of descent of thyroid from foramen caecum along thyroglossal duct to the normal anatomic location in neck has been reported. Ectopic thyroid tissue in adrenal gland (ETTAG) is rarely encountered and very few cases have been reported in literature. The most common differential diagnosis to be considered when thyroid follicles are noted in adrenal gland are metastasis from a thyroid malignancy or a teratoma or an ectopic thyroid tissue in adrenal gland. We present a case of an adrenal incidentaloma in a young pregnant female which was diagnosed to be ectopic thyroid tissue in adrenal gland. The review of literature of similar cases of this rare embryological aberrance is discussed. To our knowledge, only 16 such cases have been documented in literature and our case is the first one from Indian subcontinent and the largest documented with respect to size. [ABSTRACT FROM AUTHOR]

The medicinal plant Cannabis sativa L. (C. sativa) is currently being extensively studied to determine the full extent of its therapeutic pharmacological potential. Δ9-tetrahydocannabinol (THC) and cannabidiol (CBD) are the most thoroughly investigated compounds. We aimed to explore the anticancer activity of cannabinoids mixture isolated from the Lebanese C. sativa plant in ratios comparable to the local medicinal plant, to elucidate its mechanism of action in breast cancer cells in vitro. Cells were subjected to cytotoxicity assay, cell cycle analysis, Annexin V/PI dual staining, cell death ELISA, immunofluorescence, in addition to western blot analysis of apoptotic and autophagy markers. We further evaluated the anti-metastatic effect of cannabinoids on MDA-MB-231 using the scratch wound-healing, trans-well migration and invasion assays. Our results revealed the promising therapeutic benefits of CBD/THC on inhibiting the growth of breast cancer cells by promoting cellular fragmentation, phosphatidylserine translocation to the outer membrane leaflet and DNA fragmentation in both cell lines while inhibiting the motility of the triple negative breast cancer cells. In our study, CBD/THC mixture was found to exhibit a pro-apoptotic activity via the activation of the mitochondrial apoptotic pathway, independent from ROS production while also suggesting the activation of a caspase-dependent apoptotic pathway. Even though autophagy was altered upon exposure to the cannabinoid mixture, our data suggested that it is not the mechanism responsible of inducing cell death. In conclusion, our study demonstrates the promising therapeutic benefits of CBD and THC isolated from the Lebanese C. sativa plant on breast cancer cells in vitro. [ABSTRACT FROM AUTHOR]

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]

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]

Background: Although de novo metastatic breast cancer (dnMBC) is acknowledged as a heterogeneous disease, the current staging systems do not distinguish between patients within the M1 or stage IV category. This study aimed to refine the M1 category and prognostic staging for dnMBC to enhance prognosis prediction and guide the choice of locoregional treatment. Methods: We selected patients with dnMBC from the SEER database (2010–2019), grouping them into training (N = 8048) and internal validation (N = 3450) cohorts randomly at a 7:3 ratio. An independent external validation cohort (N = 660) was enrolled from dnMBC patients (2010–2023) treated in three hospitals. Nomogram‐based risk stratification was employed to refine the M1 category and prognostic stage, incorporating T/N stage, histologic grade, subtypes, and the location and number of metastatic sites. Both internal and external validation sets were used for validation analyses. Results: Brain, liver, or lung involvement and multiple metastases were independent prognostic factors for overall survival (OS). The nomogram‐based stratification effectively divided M1 stage into three groups: M1a (bone‐only involvement), M1b (liver or lung involvement only, with or without bone metastases), and M1c (brain metastasis or involvement of both liver and lung, regardless of other metastatic sites). Only subtype and M1 stage were included to define the final prognostic stage. Significant differences in OS were observed across M1 and prognostic subgroups. Patients with the M1c stage benefited less from primary tumor surgery in comparison with M1a stage. Conclusion: Subdivision of the M1 and prognostic stage could serve as a supplement to the current staging guidelines for dnMBC and guide locoregional treatment. [ABSTRACT FROM AUTHOR]

Radiotherapy is a crucial component in the holistic management of breast cancer, with approximately 60% of individuals diagnosed with breast cancer requiring this treatment. As the survival rate of individuals with breast cancer has significantly increased, there is a growing focus on the long‐term well‐being of patients. Proton therapy (PT) is a new and rapidly developing radiotherapy method. In comparison with conventional photon therapy, PT offers the benefits of decreased radiation toxicity and increased dosage in the designated region. This can extend patients' lifespan and enhance their overall well‐being. The present analysis examines the function of PT in diminishing the harmful effects of radiation in cases of breast cancer, while also providing a brief overview of the future potential and obstacles associated with PT for breast cancer. [ABSTRACT FROM AUTHOR]

Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual‐level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127–5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391–7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675–11.099) were significantly associated with overall survival. For non‐SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087–0.651) and combined therapy (HR, 0.133; 95% CI, 0.017–0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new‐generation tyrosine kinase inhibitors (TKIs) are preferred. [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]

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]

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]

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]

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]