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1.
Cell Rep Methods ; 4(7): 100802, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38964316

RESUMO

PAX3/7 fusion-negative rhabdomyosarcoma (FN-RMS) is a childhood mesodermal lineage malignancy with a poor prognosis for metastatic or relapsed cases. Limited understanding of advanced FN-RMS is partially attributed to the absence of sequential invasion and dissemination events and the challenge in studying cell behavior, using, for example, non-invasive intravital microscopy (IVM), in currently used xenograft models. Here, we developed an orthotopic tongue xenograft model of FN-RMS to study cell behavior and the molecular basis of invasion and metastasis using IVM. FN-RMS cells are retained in the tongue and invade locally into muscle mysial spaces and vascular lumen, with evidence of hematogenous dissemination to the lungs and lymphatic dissemination to lymph nodes. Using IVM of tongue xenografts reveals shifts in cellular phenotype, migration to blood and lymphatic vessels, and lymphatic intravasation. Insight from this model into tumor invasion and metastasis at the tissue, cellular, and subcellular level can guide new therapeutic avenues for advanced FN-RMS.


Assuntos
Invasividade Neoplásica , Rabdomiossarcoma , Neoplasias da Língua , Animais , Rabdomiossarcoma/patologia , Rabdomiossarcoma/secundário , Humanos , Camundongos , Neoplasias da Língua/patologia , Linhagem Celular Tumoral , Metástase Neoplásica/patologia , Xenoenxertos , Língua/patologia , Movimento Celular
2.
Clin Exp Med ; 24(1): 156, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003350

RESUMO

Tumor-associated macrophages (TAMs) represent one of the most abundant tumor-infiltrating stromal cells, and their normal function in tumor microenvironment (TME) is to suppress tumor cells by producing cytokines which trigger both direct cell cytotoxicity and antibody-mediated immune response. However, upon prolonged exposure to TME, the classical function of these so-called M1-type TAMs can be converted to another type, "M2-type," which are recruited by tumor cells so that they promote tumor growth and metastasis. This is the reason why the accumulation of TAMs in TME is correlated with poor prognosis in cancer patients. Both M1- and M2-types have high degree of plasticity, and M2-type cells can be reprogrammed to M1-type for therapeutic purposes. This characteristic introduces TAMs as promising target for developing novel cancer treatments. In addition, inhibition of M2-type cells and blocking their recruitment in TME, as well as their depletion by inducing apoptosis, are other approaches for effective immunotherapy of cancer. In this review, we summarize the potential of TAMs to be targeted for cancer immunotherapy and provide an up-to-date about novel strategies for targeting TAMs.


Assuntos
Imunoterapia , Neoplasias , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Microambiente Tumoral/imunologia , Imunoterapia/métodos , Animais
3.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000413

RESUMO

Our study aims to address the methodological challenges frequently encountered in RNA-Seq data analysis within cancer studies. Specifically, it enhances the identification of key genes involved in axillary lymph node metastasis (ALNM) in breast cancer. We employ Generalized Linear Models with Quasi-Likelihood (GLMQLs) to manage the inherently discrete and overdispersed nature of RNA-Seq data, marking a significant improvement over conventional methods such as the t-test, which assumes a normal distribution and equal variances across samples. We utilize the Trimmed Mean of M-values (TMMs) method for normalization to address library-specific compositional differences effectively. Our study focuses on a distinct cohort of 104 untreated patients from the TCGA Breast Invasive Carcinoma (BRCA) dataset to maintain an untainted genetic profile, thereby providing more accurate insights into the genetic underpinnings of lymph node metastasis. This strategic selection paves the way for developing early intervention strategies and targeted therapies. Our analysis is exclusively dedicated to protein-coding genes, enriched by the Magnitude Altitude Scoring (MAS) system, which rigorously identifies key genes that could serve as predictors in developing an ALNM predictive model. Our novel approach has pinpointed several genes significantly linked to ALNM in breast cancer, offering vital insights into the molecular dynamics of cancer development and metastasis. These genes, including ERBB2, CCNA1, FOXC2, LEFTY2, VTN, ACKR3, and PTGS2, are involved in key processes like apoptosis, epithelial-mesenchymal transition, angiogenesis, response to hypoxia, and KRAS signaling pathways, which are crucial for tumor virulence and the spread of metastases. Moreover, the approach has also emphasized the importance of the small proline-rich protein family (SPRR), including SPRR2B, SPRR2E, and SPRR2D, recognized for their significant involvement in cancer-related pathways and their potential as therapeutic targets. Important transcripts such as H3C10, H1-2, PADI4, and others have been highlighted as critical in modulating the chromatin structure and gene expression, fundamental for the progression and spread of cancer.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metástase Linfática/genética , Feminino , RNA-Seq/métodos , Perfilação da Expressão Gênica/métodos , Linfonodos/patologia , Axila , Biomarcadores Tumorais/genética , Análise de Sequência de RNA/métodos
4.
Cancer Invest ; : 1-11, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007916

RESUMO

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

5.
Skeletal Radiol ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007948

RESUMO

Metastatic disease and myeloma present unique diagnostic challenges due to their multifocal nature. Accurate detection and staging are critical for determining appropriate treatment. Bone scintigraphy, skeletal radiographs and CT have long been the mainstay for the assessment of these diseases, but have limitations, including reduced sensitivity and radiation exposure. Whole-body MRI has emerged as a highly sensitive and radiation-free alternative imaging modality. Initially developed for skeletal screening, it has extended tumor screening to all organs, providing morphological and physiological information on tumor tissue. Along with PET/CT, whole-body MRI is now accepted for staging and response assessment in many malignancies. It is the first choice in an ever increasing number of cancers (such as myeloma, lobular breast cancer, advanced prostate cancer, myxoid liposarcoma, bone sarcoma, …). It has also been validated as the method of choice for cancer screening in patients with a predisposition to cancer and for staging cancers observed during pregnancy. The current and future challenges for WB-MRI are its availability facing this number of indications, and its acceptance by patients, radiologists and health authorities. Guidelines have been developed to optimize image acquisition and reading, assessment of lesion response to treatment, and to adapt examination designs to specific cancers. The implementation of 3D acquisition, Dixon method, and deep learning-based image optimization further improve the diagnostic performance of the technique and reduce examination durations. Whole-body MRI screening is feasible in less than 30 min. This article reviews validated indications, recent developments, growing acceptance, and future perspectives of whole-body MRI.

6.
Int J Biol Macromol ; 275(Pt 1): 133582, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955301

RESUMO

Inulin as a natural polysaccharide regulates intestinal microorganisms, and improves the immune and gastrointestinal function. In order to explore the effect of inulin on pulmonary metastasis of colon cancer, we set up a CT26 injected pulmonary metastatic model. The results showed that inulin used alone did not improve pulmonary metastasis of colon cancer, while inulin combined with rifaximin significantly prolonged the survival time of mice, and inhibited pulmonary metastasis compared with model and inulin groups. Inulin treatment increased the abundance of harmful bacteria such as Proteobacteria and Actinobacteria, while combined treatment decreased their abundance and increased the abundance of beneficial bacteria containing Firmicutes and Eubacterium which belonged to the bile acid-related bacteria. The combination treatment decreased the content of primary bile acids and secondary bile acids in the feces of mice, especial for DCA and LCA which were the agonists of TGR5. Furthermore, the combination treatment reduced the mRNA expression of the TGR5, cyclin dependent kinase 4, cyclin 1 and CDK2, increased the mRNA expression of p21 in the lung, down-regulated the level of NF-κB p65, and up-regulated the level of TNF-α compared with the model group. The above may be the reason for the better use of the combination treatment.

7.
Avicenna J Med ; 14(2): 75-109, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38957158

RESUMO

Background Renal cancer metastasis to oral region is very rare. Studies have been published analyzing the cases of metastatic tumors to the oral cavity by many researchers. Very few research studies have been conducted till date to analyze the renal cancer metastasis as the sole primary source to the oral soft tissues. The goal of this study was to examine the published cases of oral soft tissue metastasis from renal cell carcinoma as the only primary source from 1911 to 2022. Materials and Methods An electronic search of the published literature was performed without publication year limitation in PubMed/Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research Gate databases, using mesh keywords like ("Renal cancer," or "Renal carcinoma" or "Renal cell cancer" or "Renal cell carcinoma"), and ("Metastasis" or "Metastases"), and ("Oral soft tissues" or "Tongue" or "Palate" or "Tonsil" or "Buccal mucosa" or "Salivary glands"). We also searched related journals manually and the reference lists. Results Our research revealed a total of 226 relevant articles with 250 patients. Parotid glands and tongue were the most common sites of metastasis. 23% patients died with a survival time of 10 days to 4 years. Conclusions Oral soft tissue metastasis from renal cell carcinoma has a bad prognosis. More cases need to be published in order to raise awareness of these lesions.

8.
Front Oncol ; 14: 1395159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957322

RESUMO

Background: The performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC. Methods: We searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities. Results: Fourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89-0.94), 0.79 (95% CI 0.72-0.85), and 0.90 (95% CI 0.86-0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists. Discussion: In conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

9.
Front Immunol ; 15: 1379056, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957472

RESUMO

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. Materials and methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Results: A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Conclusion: Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.


Assuntos
Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Idoso , Estudos Retrospectivos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Neoplasias Ósseas/secundário , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Resultado do Tratamento
10.
Cureus ; 16(7): e63665, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957515

RESUMO

Lung cancer metastasizing to the colon is exceedingly rare and can present similarly to colorectal cancer. It is crucial to conduct further evaluations using immunohistochemical (IHC) stains and genomic testing to differentiate between the two and provide appropriate treatment without delay. Lung cancer generally has a poor prognosis, especially in cases with distant metastases. Although gastrointestinal (GI) metastases from lung cancer have been reported, cases of lung cancer manifesting as colon metastasis are extremely rare, with only a few instances documented.

11.
Ann Gastroenterol Surg ; 8(4): 631-638, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957561

RESUMO

Background: This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods: We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (-) groups, respectively. Propensity score-matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results: In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3-year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (-) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3-year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (-) groups, respectively. Conclusion: LLND would lead to comparable local control in the pLLNM (+) and (-) groups if the clinicopathological characteristics except for LLNM are similar.

12.
Ann Gastroenterol Surg ; 8(4): 553-565, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957562

RESUMO

By presenting the most up-to-date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up-to-date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence-based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

13.
Ann Gastroenterol Surg ; 8(4): 681-690, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38957555

RESUMO

Background: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. Patients and method: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. Results: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. Conclusions: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

14.
J Cancer Res Clin Oncol ; 150(7): 333, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955827

RESUMO

OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.


Assuntos
Quimioembolização Terapêutica , Neoplasias Hepáticas , Relaxina , Animais , Quimioembolização Terapêutica/métodos , Coelhos , Relaxina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Doxorrubicina/administração & dosagem , Humanos , Terapia Combinada , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Metástase Neoplásica
15.
Sci Rep ; 14(1): 15258, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956127

RESUMO

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites.


Assuntos
Neoplasias Oculares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Oculares/patologia , Neoplasias Oculares/terapia , Neoplasias Oculares/mortalidade , Neoplasias Oculares/secundário , Idoso , Estudos Retrospectivos , Adulto , Resultado do Tratamento , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/mortalidade , Idoso de 80 Anos ou mais , Metástase Neoplásica
16.
Sci Rep ; 14(1): 15173, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956143

RESUMO

Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5'-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis.


Assuntos
Biomarcadores Tumorais , Antígeno Ca-125 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/sangue , Masculino , Feminino , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Antígeno Ca-125/sangue , Prognóstico , Idoso , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Metástase Neoplásica , Estudos Retrospectivos , Adulto
17.
J Transl Med ; 22(1): 621, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961395

RESUMO

BACKGROUND: The tumor microenvironment is profoundly heterogeneous particularly when comparing sites of metastases. Establishing the extent of this heterogeneity may provide guidance on how best to design lipid-based drug delivery systems to treat metastatic disease. Building on our previous research, the current study employs a murine model of metastatic cancer to explore the distribution of ~ 100 nm liposomes. METHODS: Female NCr nude mice were inoculated with a fluorescently labeled, Her2/neu-positive, trastuzumab-resistant breast cancer cell line, JIMT-1mkate, either in the mammary fat pad to create an orthotopic tumor (OT), or via intracardiac injection (IC) to establish tumors throughout the body. Animals were dosed with fluorescent and radio-labeled liposomes. In vivo and ex vivo fluorescent imaging was used to track liposome distribution over a period of 48 h. Liposome distribution in orthotopic tumors was compared to sites of tumor growth that arose following IC injection. RESULTS: A significant amount of inter-vessel heterogeneity for DiR distribution was observed, with most tumor blood vessels showing little to no presence of the DiR-labelled liposomes. Further, there was limited extravascular distribution of DiR liposomes in the perivascular regions around DiR-positive vessels. While all OT tumors contained at least some DiR-positive vessels, many metastases had very little or none. Despite the apparent limited distribution of liposomes within metastases, two liposomal drug formulations, Irinophore C and Doxil, showed similar efficacy for both the OT and IC JIMT-1mkate models. CONCLUSION: These findings suggest that liposomal formulations achieve therapeutic benefits through mechanisms that extend beyond the enhanced permeability and retention effect.


Assuntos
Antineoplásicos , Lipossomos , Camundongos Nus , Metástase Neoplásica , Animais , Linhagem Celular Tumoral , Feminino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacocinética , Antineoplásicos/administração & dosagem , Humanos , Resultado do Tratamento , Camundongos
18.
Int J Gynecol Cancer ; 34(7): 985-992, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950926

RESUMO

OBJECTIVES: To assess the diagnostic performance of ultrasonography in pre-operative assessment of lymph nodes in patients with cervical cancer, to compare the outcomes for pelvic and para-aortic regions, and to detect macrometastases and micrometastases separately. METHODS: Patients were retrospectively included if they met the following inclusion criteria: pathologically verified cervical cancer; ultrasonography performed by one of four experienced sonographers; surgical lymph node staging, at least in the pelvic region-sentinel lymph node biopsy or systematic pelvic lymphadenectomy or debulking. The final pathological examination was the reference standard. RESULTS: 390 patients met the inclusion criteria between 2009 and 2019. Pelvic node macrometastases (≥2 mm) were confirmed in 54 patients (13.8%), and micrometastases (≥0.2 mm and <2 mm) in another 21 patients (5.4%). Ultrasonography had sensitivity 72.2%, specificity 94.0%, and area under the curve (AUC) 0.831 to detect pelvic macrometastases, while sensitivity 53.3%, specificity 94.0%, and AUC 0.737 to detect both pelvic macrometastases and micrometastases (pN1). Ultrasonography failed to detect pelvic micrometastases, with sensitivity 19.2%, specificity 85.2%, and AUC 0.522. There was no significant impact of body mass index on diagnostic accuracy. Metastases in para-aortic nodes (macrometastases only) were confirmed in 16 of 71 patients who underwent para-aortic lymphadenectomy. Ultrasonography yielded sensitivity 56.3%, specificity 98.2%, and AUC 0.772 to identify para-aortic node macrometastases. CONCLUSION: Ultrasonography performed by an experienced sonographer can be considered a sufficient diagnostic tool for pre-operative assessment of lymph nodes in patients with cervical cancer, showing similar diagnostic accuracy in detection of pelvic macrometastases as reported for other imaging methods (18F-fluorodeoxyglucose positron emission tomography/CT or diffusion-weighted imaging/MRI). It had low sensitivity for detection of small-volume macrometastases (largest diameter <5 mm) and micrometastases. The accuracy of para-aortic assessment was comparable to that for pelvic lymph nodes, and assessment of the para-aortic region should be an inseparable part of the examination protocol.


Assuntos
Linfonodos , Metástase Linfática , Ultrassonografia , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Pessoa de Meia-Idade , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Metástase Linfática/diagnóstico por imagem , Idoso , Sensibilidade e Especificidade , Excisão de Linfonodo , Cuidados Pré-Operatórios/métodos , Micrometástase de Neoplasia/diagnóstico por imagem
19.
Environ Toxicol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38994737

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. However, the underlying mechanism of Suppressor of variegation 3-9 homolog 2 (SUV39H2) in NPC remains poorly understood. RT-qPCR was carried out to examine SUV39H2 and SIRT1 expression in NPC tissues and cells. Kaplan-Meier method was utilized to evaluate the association between SUV39H2 level and overall survival. The function of SUV39H2 and SIRT1 in NPC cell viability, metastasis, and apoptosis was tested through CCK-8, transwell, and flow cytometry experiments. Here, it was uncovered that SUV39H2 level was augmented in NPC tissues and cells. Moreover, SUV39H2 expedited NPC cell viability, metastasis, and inhibited apoptosis, while SIRT1 addition reversed these impacts. Besides, SUV39H2 induced H3K9me3 enhancement to repress SIRT1 transcription via binding to SIRT1 promoter. Collectively, our results demonstrated upregulated SUV39H2 aggravated NPC tumorigenesis through SIRT1, which may offer a potential therapeutic target for NPC.

20.
Oncol Rep ; 52(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38994771

RESUMO

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the scratch­wound assay experiments shown in Fig. 3C, two images appeared to overlap [specifically, the '0 h / Control' and 0 h / OP­B (5 µmol/l) data panels], albeit with different magnification and after a 180° rotation. The authors have examined their original data, and realize that an inadvertent error was made in assembling the images in the figure; specifically, the images of 5 and 10 µmol/l OP­B treatment for 0 h were both misused. The corrected version of Fig. 3, showing all the correct data for Fig. 3C, is shown on the next page. Note that these errors did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [Oncology Reports 40: 1339­1347, 2018; DOI: 10.3892/or.2018.6531].

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