-
EMBO Reports Mar 2020lncRNAs actively regulate gene expression. They contribute to chromosomal interactions at close or distant genomic regions, which, in turn, regulate transcription [1]....
lncRNAs actively regulate gene expression. They contribute to chromosomal interactions at close or distant genomic regions, which, in turn, regulate transcription [1]. Ariel et al [2] reveal in a recent study a new molecular mechanism of the Arabidopsis lncRNA APOLO. The authors extend previously reported functions of APOLO in cis-regulation of chromosomal looping and transcription of its neighbor gene to a set of distant genes involved in auxin-induced molecular pathways controlling lateral root development. Noteworthy, APOLO recognition of multiple trans-modulated targets occurs through a novel mechanism involving R-loop formation.
Topics: Arabidopsis; Arabidopsis Proteins; DNA; Indoleacetic Acids; R-Loop Structures; RNA, Long Noncoding
PubMed: 32078233
DOI: 10.15252/embr.202050107 -
Frontiers in Bioscience (Landmark... Aug 2022Recent findings from multimodal imaging studies point to macrostructural pathological changes in areas significantly distant from the epicenter of spinal cord injury,... (Review)
Review
Recent findings from multimodal imaging studies point to macrostructural pathological changes in areas significantly distant from the epicenter of spinal cord injury, both in the spinal cord and in the brain. Studies are being performed to determine cellular and molecular mechanisms of these shifts, which are currently poorly understood. Research has demonstrated that the pathological process in the remote area is multifaceted. This process involves astrocytes and microglia, which contribute to the degeneration of nerve fibers passing from and through the immediate impact area, as well as participate in reciprocal activation. As a result, there is accompanying synaptic loss in areas remote to the spinal cord injury location. Reactive astrocytes produce chondroitin sulfate proteoglycans that inhibit axon growth and damage cells. However, neuronal death in the remote area remains controversial. The area of primary injury is the source of numerous neurotoxic molecules that release into the cerebrospinal fluid. It is assumed that these molecules, primarily matrix metalloproteinases, disrupt the blood-spinal cord barrier, which leads to tissue infiltration by macrophage precursors in the remote area. Activated macrophages secrete pro-inflammatory cytokines and matrix metalloproteinases, which, in turn, induce astrocytes and microglia towards a pro-inflammatory phenotype. In addition, reactive microglia, together with astrocytes, secrete numerous pro-inflammatory and neurotoxic molecules that activate inflammatory signaling pathways, consequently exacerbating synaptic depletion and neurological deterioration. It appears likely that the interplay between chronic inflammation and neurodegeneration is a pivotal characteristic of the pathological process in the spinal cord areas distant from the epicenter of the lesion. Pathological changes in the distant areas should be the object of research as potential therapeutic targets.
Topics: Chondroitin Sulfate Proteoglycans; Humans; Macrophages; Microglia; Spinal Cord; Spinal Cord Injuries
PubMed: 36042182
DOI: 10.31083/j.fbl2708235 -
Frontiers in Endocrinology 2022To evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during...
BACKGROUND
To evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up.
METHODS
Thyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed.
RESULTS
Among 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022).
CONCLUSIONS
A small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.
Topics: Adenocarcinoma, Follicular; Carcinoma, Papillary; Female; Humans; Male; Middle Aged; Prognosis; Thyroid Neoplasms; Thyroidectomy
PubMed: 35837311
DOI: 10.3389/fendo.2022.923182 -
World Journal of Gastroenterology Aug 2020The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures...
BACKGROUND
The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.
AIM
To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.
METHODS
Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations ( 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States).
RESULTS
Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe ( 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size ( 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe ( 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III ( 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III.
CONCLUSION
Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation.
Topics: Animals; China; Echinococcosis; Echinococcosis, Hepatic; Europe; France; Germany; Humans; Retrospective Studies
PubMed: 32848335
DOI: 10.3748/wjg.v26.i29.4302 -
Scientific Reports Apr 2021It is rare and understudied for patients with stage T1 colorectal cancer to have synchronous distant metastasis. This study was to determine the clinicopathological...
It is rare and understudied for patients with stage T1 colorectal cancer to have synchronous distant metastasis. This study was to determine the clinicopathological factors associated with distant metastasis and prognosis. T1 colorectal cancer patients diagnosed between 2010 and 2015 were obtained from the SEER database. Logistic regression was applied to determine risk factors related to distant metastasis. Cox-proportional hazard models were used to identify the prognostic factors for patients with distant metastasis. Among 21,321 patients identified, 359 (1.8%) had synchronous distant metastasis and 1807 (8.5%) had lymph node metastasis. Multivariate analysis revealed that younger age, positive serum CEA, larger tumor size, positive tumor deposit, perineural invasion, lymph node metastasis, histology of non-adenocarcinoma and poorer differentiation were significantly associated with the increased risk of synchronous distant metastasis. Older age, female, Black, positive CEA, positive lymph node metastasis, positive tumor deposit, larger tumor size, no chemotherapy, inadequate lymph node harvesting and no metastasectomy were correlated with worse survival in these patients with synchronous distant metastasis. Patients with metastasis to the liver displayed the highest rate of positive CEA. We conclude that T1 colorectal cancer patients with multiple risk factors need thorough examinations to exclude synchronous distant metastasis. Chemotherapy, adequate lymph node cleaning and metastasectomy are associated with improved survival for those patients with distant metastases. Positive serum CEA may be useful in predicting distant metastases in patients at stage T1.
Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Colorectal Neoplasms; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Risk Factors
PubMed: 33888776
DOI: 10.1038/s41598-021-87929-x -
Cancer Treatment and Research... 2022Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer that frequently compromises the lymph nodes (LN) and distal organs. We sought to describe clinical and...
INTRODUCTION
Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer that frequently compromises the lymph nodes (LN) and distal organs. We sought to describe clinical and demographic characteristics of affected patients, analyze risk factors for LN compromise, metastasis, and death, and evaluate their impact on survival.
MATERIALS AND METHODS
Patients with MCC were retrieved from the SEER database. Demographic, clinical and treatment data were analyzed. Logistic and Cox proportional hazard regression were used to analyze risk factors. Survival analysis was done with the Kaplan-Meier method.
RESULTS
A total of 2010 patients were included, among which 288 (14.33%) had distant metastases at diagnosis. LN involvement occurred in 45.8% and 20.1% of patients with and without distant metastasis, respectively. Males were more likely to present LN compromise (OR = 1.33, p<0.001). Tumors >10 mm showed a significantly higher risk for LN involvement and distant metastasis, with those >20 mm showing the highest risk (OR = 2.76 p<0.001 and OR = 8.88 p<0.001 respectively). Location of the tumor in the trunk was a protective factor for overall death (OR = 0.27), while LN compromise was a risk factor (OR = 3.12). Only history of previous malignancy significantly affected disease-specific death (OR = 0.32, p = 0.01). One-year survival was 79.7% and 38.2% for patients with regional LN disease and distant metastasis, respectively.
CONCLUSION
MCC is an aggressive cancer with high rates of LN involvement and distant metastases. Male gender and tumor size were risk factors for regional LN and metastatic disease. Tumor location in the trunk decrease the risk of overall death, while LN involvement increased it.
Topics: Humans; Male; Carcinoma, Merkel Cell; Proportional Hazards Models; Lymph Nodes; Lymph Node Excision; Skin Neoplasms
PubMed: 36446191
DOI: 10.1016/j.ctarc.2022.100665 -
PloS One 2023Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes.
BACKGROUND
Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes.
OBJECTIVE
The purpose of this study was to define factors affecting distant metastasis in patients with surgically treated HPV-positive tonsil cancer.
METHODS
The present study enrolled 76 patients diagnosed with HPV-positive tonsil cancer who underwent primary surgery between January 2010 and December 2021.
RESULTS
Twelve (15.7%) patients experienced a distant failure with a median follow-up time of 43 months. Sites of distant metastasis included the lung (n = 10), liver (n = 1), and brain (n = 1). Upon multivariate analysis, an advanced T stage (odds ratio [OR]: 13.94, 95% confidence interval [CI]: 1.29-149.863, p = 0.003) and margin involvement (OR: 5.96, 95% CI: 1.33-26.76, p = 0.02) were independent predictors of distant metastases. The five-year disease-specific survival for the entire cohort was 85%. The multivariate analysis confirmed that distant metastasis (hazard ratio [HR]: 12.688, 95% CI: 3.424-47.016; p < 0.001) and margin involvement (HR: 6.243; 95% CI: 1.681-23.191; p = 0.006) were significant factors associated with the five-year disease-specific survival.
CONCLUSION
HPV-positive tonsil cancer patients with an advanced T stage and a positive surgical margin have a substantial risk of distant metastases. Distant metastasis and margin involvement are factors that affect their survival.
Topics: Humans; Tonsillar Neoplasms; Papillomavirus Infections; Neoplasm Recurrence, Local; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Prognosis; Neoplasm Staging; Neoplasm Metastasis
PubMed: 36943852
DOI: 10.1371/journal.pone.0283368 -
Cancer Medicine Jan 2024Follicular thyroid cancer (FTC) is prone to distant metastasis, and patients with distant metastasis often have poor prognosis. In this study, the impact of metastasis...
OBJECTIVES
Follicular thyroid cancer (FTC) is prone to distant metastasis, and patients with distant metastasis often have poor prognosis. In this study, the impact of metastasis and other relevant factors on the prognosis of follicular thyroid carcinoma was examined.
METHODS
This was a retrospective study. Data were obtained from Zhejiang Cancer Hospital, Sun Yat-sen University Cancer Center and Hangzhou First People's Hospital affiliated with Zhejiang University School of Medicine, from January 2009 to June 2021 for 153 FTC patients. The patients were assigned into three groups according to their distant metastasis: distant metastasis at initial diagnosis (M1), distant metastasis during follow-up (M2), and no evidence of distant metastasis over the course of the study (M0). Data were collected and summarized on clinical data, laboratory parameters, imaging features, postoperative pathologic subtypes, and metastases. The Cox proportional hazard model was used to perform the univariate and multivariate analysis. Kaplan-Meier curves were used to evaluate cancer-specific survival (CSS).
RESULTS
Based on metastasis, the patients were assigned into three groups, including 31 in the M1 group, 15 in the M2 group, and 107 in the M0 group. These individuals were followed up for an average of 5.9 years, and the group included 46 patients with distant metastasis (31 confirmed at diagnosis and 15 found during follow-up). Univariate Cox regression analysis showed that age, Hashimoto's thyroiditis (HT), surgery method, postoperative adjuvant therapy, histologic subtype, nodule size, calcification, TSH, and distant metastasis all impacted prognosis. Multivariate Cox regression analysis suggested that histologic subtype (widely invasive; HR: 7.440; 95% CI: 3.083, 17.954; p < 0.001), nodule size (≥40 mm; HR: 8.622; 95% CI: 3.181, 23.369; p < 0.001) and distant metastasis (positive; HR: 6.727; 95% CI: 2.488, 18.186; p < 0.001) were independent risk factors affecting the prognosis of follicular thyroid cancer.
CONCLUSIONS
Histologic subtype, nodule size, and distant metastasis are important risk factors for the prognosis of follicular thyroid cancer. Patients with metastatic follicular thyroid cancer have a poor prognosis, especially with metastasis at the time of initial diagnosis. As a result, this group of patients requires individualized treatment and closer follow-up.
Topics: Humans; Thyroid Neoplasms; Retrospective Studies; Adenocarcinoma, Follicular; Prognosis
PubMed: 38102879
DOI: 10.1002/cam4.6727 -
Cells Jan 2023Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key...
Identification and Validation of the Prognostic Panel in Clear Cell Renal Cell Carcinoma Based on Resting Mast Cells for Prediction of Distant Metastasis and Immunotherapy Response.
Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key tumor-infiltrating immune cells (TIICs) affecting the distant metastasis and prognosis of patients with ccRCC and to construct a relevant prognostic panel to predict immunotherapy response. Based on ccRCC bulk RNA sequencing data, resting mast cells (RMCs) were screened and verified using the CIBERSORT algorithm, survival analysis, and expression analysis. Distant metastasis-associated genes were identified using single-cell RNA sequencing data. Subsequently, a three-gene (, and ) panel with superior distant metastatic and prognostic performance was established and validated, which stratified patients into high- and low-risk groups. The high-risk group exhibited lower infiltration of RMCs, higher tumor mutation burden (TMB), and worse prognosis. Therapeutically, the high-risk group was more sensitive to anti-PD-1 and anti-CTLA-4 immunotherapy, whereas the low-risk group displayed a better response to anti-PD-L1 immunotherapy. Furthermore, two immune clusters revealing distinct immune, clinical, and prognosis heterogeneity were distinguished. Immunohistochemistry of ccRCC samples verified the expression patterns of the three key genes. Collectively, the prognostic panel based on RMCs is able to predict distant metastasis and immunotherapy response in patients with ccRCC, providing new insight for the treatment of advanced ccRCC.
Topics: Humans; Carcinoma, Renal Cell; Mast Cells; Prognosis; Immunotherapy; Carcinoma; Kidney Neoplasms; Adaptor Proteins, Signal Transducing
PubMed: 36611973
DOI: 10.3390/cells12010180 -
American Journal of Translational... 2020The distant metastasis in liposarcoma is not thoroughly investigated. Based on a large cohort, we attempted to evaluate the survival in liposarcoma patients with distant...
BACKGROUND
The distant metastasis in liposarcoma is not thoroughly investigated. Based on a large cohort, we attempted to evaluate the survival in liposarcoma patients with distant metastasis and to reveal the risk factors.
METHODS
The records of liposarcoma patients with or without distant metastasis were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2010 to 2016. Survival was calculated by the Kaplan-Meier method. Cox hazard regression was scheduled to investigate prognostic factors for liposarcoma patients with distant metastasis. Risk factors for metastasis were identified by the logistic regression analysis.
RESULTS
A total of 227 liposarcomas with distant metastasis were identified in 4,181 patients. The 5-year survival rate for patients with and without metastasis was 12.1% (95% CI: 5.0%-19.0%) and 75.4% (95% CI: 73.6%-77.2%), respectively. Age ≥60 years (HR=1.73; 95% CI: 1.11-2.69) and surgery (HR=0.26; 95% CI: 0.17-0.41) were independent prognostic factors for patients with metastasis. The annual incidence of distant metastasis was from 3.76% to 7.3%. Liposarcoma in trunk (OR=1.69; 95% CI: 1.02-2.79), myxoid type (OR=2.65; 95% CI: 1.16-6.05), grade III (OR=2.62; 95% CI: 1.17-5.88), grade IV (OR=4.07; 95% CI: 1.84-9.00), T2 stage (OR=2.71; 95% CI: 1.15-6.40), and N1 stage (OR=9.44; 95% CI: 4.63-19.26) were associated with the development of metastasis. Homogeneous and heterogeneous factors were found for patients with different metastatic organs.
CONCLUSIONS
The survival was significantly dismal in liposarcoma patients with distant metastasis. The risk and prognostic factors provide a reference to clinical screening and prevention for distant metastasis in liposarcoma.
PubMed: 32509201
DOI: No ID Found