Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary* ; Carcinoma, Hepatocellular/therapy* ; Humans ; Liver Neoplasms/therapy* ; Prognosis

Objective: To explore the effects of circTNPO1 on the proliferation and metastasis of osteosarcoma (OS) by sponging miR-338-3p. Methods: The expression of circTNPO1 on osteoblasts and multiple OS cell lines were detected by qRT-PCR. CircTNPO1 stable knockdown 143B cell line was constructed by sh-circTNPO1. Cell count kit 8 (CCK-8) assay and wound healing assay were applied to evaluate the proliferation and metastasis of this cell. Luciferase reporter assay was used to explore the binding between circTNPO1 and miR-338-3p. In xenograft tumor model, miR-338-3p inhibitor or its control was injected into the circTNPO1 knockdown tumors. The weight and size of the tumors were evaluated and Ki-67 expression was detected by immunohistochemistry. Results: The RNA expression of circTNPO1 in OS cell lines U2OS, HOS, MG63, 143B, ZOS and ZOSM were 2.73±0.27, 3.18±0.54, 4.33±0.52, 5.75±0.65, 4.50±0.49 and 3.96±0.35, respectively, higher than 1.00±0.09 in hFOB1.19 (P<0.001). CCK-8 assay revealed that after 48 h and 72 h, the absorbance of sh-circTNPO1 #1 was 0.81±0.05 and 1.09±0.06, while sh-circTNPO1 #2 143B cells was 0.84±0.04 and 1.2±0.04, which were sharply reduced compared with the control (1.00±0.06 and 1.49±0.06, P<0.001); after 48 h and 72 h, the absorbance of 143B cells transfected with circTNPO1 #1 and miR-338-3p (0.92±0.06 and 1.32±0.07) were higher than those of cells transfected with sh-circTNPO1 cells and miR NC (0.92±0.06 and 1.32±0.07, P<0.050). Wound healing assay demonstrated that the 24 hour-migration rates of sh-circTNPO1 #1 and sh-circTNPO1 #2 cells were (24.43±2.15)% and (39.70±4.20)% respectively, which were significantly lower than that of the control [(56.51±3.27)%, P<0.010]; the migration rates of sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor were (26.70±2.21)% and (46.10±5.71)%, with a significant difference (P<0.005). In xenograft tumor model, the weight and size of tumors in control, sh-circTNPO1 #1+ miR NC and sh-circTNPO1 #1+ miR-338-3p inhibitor mice were (458.80±158.10) mg, (262.50±82.09) mg, (395.40±137.60) mg and (593.00±228.40) mm(2,) (203.30±144.20) mm(2,) (488.60±208.60) mm(2,) respectively. Compared with control, sh-circTNPO1 tumors were significantly smaller (P<0.01). Injection with miR-338-3p inhibitor significantly reversed both the weight and size of tumors (P<0.05). Conclusion: CircTNPO1 promotes the proliferation and metastasis of OS by sponging miR-338-3p, which could be a new target for OS treatments.
Animals ; Bone Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Ki-67 Antigen/metabolism* ; Mice ; MicroRNAs/metabolism* ; Osteosarcoma/secondary* ; RNA, Circular/metabolism* ; Sincalide/metabolism*

With the extension of survival period and the improvement of imaging technology, the incidence of bone metastasis from colorectal cancer gradually increases. Therefore, the early diagnosis and treatment of bone metastasis should not be neglected while the primary lesion was controlled.Currently, the available evidence for bone metastasis from colorectal cancer is very limited. In this article, the Chinese Society of Colorectal Cancer organized multi-disciplinary experts to integrate the relevant studies worldwide and combine with clinical practice, focused on the issues and controversies about clinical characteristics, diagnosis and treatment, and follow-up of bone metastatic patients with colorectal cancer.After discussion and voting, Chinese expert consensus on multidisciplinary treatment of bone metastasis from colorectal cancer (2020 version) was formed. This consensus could provide clinicians with more detailed multidisciplinary treatment strategies for bone metastasis from colorectal cancer.
Asian Continental Ancestry Group ; Bone Neoplasms ; pathology ; secondary ; therapy ; China ; Colonic Neoplasms ; diagnosis ; therapy ; Colorectal Neoplasms ; diagnosis ; therapy ; Consensus ; Humans ; Interdisciplinary Communication ; Patient Care Team ; Practice Guidelines as Topic ; Treatment Outcome

BACKGROUND: The purpose of this study is to compare the survival time of non-small cell lung cancer (NSCLC) patients with different organ metastasis. Among all cancers, the morbidity and mortality of lung cancer is the highest worldwide, which may caused by local recurrence and distant metastasis, and the location of metastasis may predict the prognosis of patients. METHODS: A total of 117,542 patients with NSCLC diagnosed between 2010 and 2014 were enrolled from Surveillance, Epidemiology, and End Result (SEER) databases, and the relationship between distant metastasis and survival time was retrospectively analyzed. RESULTS: Of all the 117,542 patients diagnosed with non-small cell lung cancer, 42,071 (35.8%) patients had different degrees of distant metastasis during their medical history, including 26,932 single organ metastases and 15,139 multiple organ metastases, accounting for 64.0% and 36.0% of the metastatic patients respectively. Compared with patients with no metastasis, whose median survival time was 21 months, the median survival time of patients with metastases was 7 months (lung), 6 months (brain), 5 months (bone), 4 months (liver), and 3 months (multiple organ) respectively, and the difference was significant (P<0.001, except liver vs multiple organ P=0.650); Most patients with NSCLC (88.4%) eventually died of lung cancer. CONCLUSIONS Distant metastasis of NSCLC patients indicates poor prognosis. In NSCLC patients with single organ metastasis, the prognosis of lung metastasis is the best, and liver metastasis is the worst, and multiple organ metastasis is worse than single organ metastasis.
Aged ; Aged, 80 and over ; Bone Neoplasms ; mortality ; secondary ; Brain Neoplasms ; mortality ; secondary ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; Female ; Humans ; Liver Neoplasms ; mortality ; secondary ; Lung Neoplasms ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies

Objective To investigate the expression and regulation of programmed cell death protein 1 (PD1), B lymphocyte and T lymphocyte attenuator (BTLA) in peripheral blood of patients with non-small cell lung cancer (NSCLC); to examine the correlation of the mRNA levels between PD and BTLA in NSCLC. Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8⁺ T cells and γδ⁺ T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals. We compared the expression of PD1 and BTLA on the surfaces of γδ⁺ T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid. The correlations of PD1 and BTLA, as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform. Results The frequency of PD1 on the surfaces of CD8⁺ T cells was significantly higher than that of the γδT cells in both healthy controls (t=2.324, P=0.024) and NSCLC patients（t=2.498, P=0.015). The frequency of PD1 on CD8⁺ T cells, rather than on γδ⁺ T cells, was significantly upregulated in advanced NSCLC patients compared with that in healthy controls (t=4.829, P<0.001). The PD1⁺ BTLA⁺γδT cells of the healthy controls were significantly lower than that of the NSCLC patients (t=2.422, P=0.0185). No differences in percentage of PD1⁺γδ⁺ and BTLA⁺γδ⁺ T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment. PD1 was positively correlated with BTLA in both lung adenocarcinoma (r=0.54; P<0.05) and lung squamous cell carcinoma (r=0.78; P<0.05). Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8⁺ T cells and γδT cells in advanced NSCLC, suggesting that these molecules were involved in regulating the inactivation of CD8⁺ T cells and γδ⁺ T cells, immune escape and tumor invasion.
Bone Neoplasms/secondary* ; CD8-Positive T-Lymphocytes ; Carcinoma, Non-Small-Cell Lung/immunology* ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Ligands ; Lung Neoplasms/immunology* ; Lymphocyte Subsets/immunology* ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/metabolism* ; RNA, Messenger/metabolism* ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, Immunologic/metabolism*

Bone is one of the most metastatic sites of advanced malignant tumors. With the continuous improvement of diagnosis and treatment of malignant tumors, the survival time of patients is prolonged and incidence of bone metastases also increases. Lung cancer is the leading cause of cancer-related mortality worldwide. It is estimated that the incidence of bone metastases in patients advanced lung cancer is about 30%-40%. The traditional diagnosis of bone metastases in lung cancer is based on clinical symptoms, X ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathology. Recently, a large number of exploratory studies have reported blood biomarkers as indicators of bone metastasis screening and efficacy evaluation. In this review, we summarize the progress of biomarkers in diagnosis of bone metastases of lung cancer.
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Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; metabolism ; physiopathology ; secondary ; Humans ; Lung Neoplasms ; pathology ; Osteogenesis

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths, patients with non-small cell lung cancer (NSCLC) usually have distant metastases, such as bone metastasis, brain metastasis, and lung metastasis. The purpose of this study was to explore the risk factors for bone metastasis in NSCLC patients. METHODS: A total of 176 cases of NSCLC were selected from May 2009 to May 2011, and patients were divided into two groups, namely the bone metastasis group and non-bone metastasis group. The general clinicopathological data of the two groups and analyzing the independent risk factors of bone metastasis were compared. RESULTS: In the general clinicopathological data of NSCLC patients. The thrombus or not and tumor-node-metastasis (TNM) stage were closely related to the occurrence of bone metastasis, and were statistically significant (all P<0.01). Prothrombin time, activated partial thromboplastin time, Fibrinogen, thrombin time, blood platelet, D-Dimer and alkaline phosphatase have significantly difference between the two groups (all P<0.05). Logistic regression analysis showed that fibrinogen, activated partial thromboplast in time, alkaline phosphatase, T4 phase, N3 phase and d-dimer were independent risk factors for bone metastasis in NSCLC patients. CONCLUSIONS Fibrinogen, alkaline phosphatase, T3, N2 stage and D-Dimer is the independent risk factors of bone metastases in patients with NSCLC.
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Aged ; Bone Neoplasms ; diagnosis ; secondary ; Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Risk Factors

BACKGROUND: Small cell lung cancer (SCLC) is highly malignant and prone to bone marrow metastasis in early stage, but its related reports are limited. This study analyzed the clinical feature, laboratory examination, treatment and prognosis of SCLC patients with bone marrow metastasis. METHODS: The clinical data of 26 SCLC patients with bone marrow metastasis were analyzed retrospectively. Prognostic factors were evaluated. RESULTS: The median age of 26 patients was 57 years and the median time from diagnosis of SCLC to confirmed bone marrow metastases was 8 d. Most patients (96.2%) were accompanied by other organ metastases. The most common laboratory abnormalities were elevated lactate dehydrogenase in 19 cases (73.1%), thrombocytopenia and elevated alkaline phosphatase respectively in 11 cases (42.3%) and anemia in 7 cases (26.9%). Twenty patients had received chemotherapy and the remaining 6 patients had not. Of this group, 16 patients received at least 2 cycles of chemotherapy after the diagnosis of bone marrow metastasis. The median survival time was 15.7 wk (0.1 wk-82.9 wk) after diagnosis of bone marrow metastasis. The survival of patients with chemotherapy was significantly better than that of those without chemotherapy (χ²=33.768, P<0.001). Multivariate analysis showed that no chemotherapy was independent poor prognostic factors (P<0.05). CONCLUSIONS The SCLC patients with bone marrow metastasis have short survival, whereas chemotherapy can extend the survival of patients.
Aged ; Bone Marrow ; pathology ; Bone Marrow Neoplasms ; mortality ; pathology ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Small Cell Lung Carcinoma ; pathology

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare sub-type of renal cell carcinoma (RCC). It has been considered to be a kind of "indolent" tumor with low-grade fashion, weak invasive capacity and relatively favorable prognosis. However, in the current case, a 3.7 cm×2.8 cm spherical mass with contrast enhancement was found in the left kidney incidentally by computed tomography (CT) in a 60-year-old male patient. A lesion in the right humerus (2.1 cm×1.6 cm×3.1 cm) was found at the same time without any symptoms or sign of pathological fracture by magnetic resonance (MR) imaging. Further positron emission tomography (PET)/CT scan which was ordered immediately after admission suggested multiple bone destruction including skull, pelvis, sternum, right humerus and femur, left scapula, multiple vertebrae and libs. Pathological examination after radical nephrectomy and palliative resection with internal fixation of the lesion in the right humerus indicated that both renal (3.0 cm×3.0 cm×2.5 cm) and bone lesions were MTSCC with the features of high-grade ovoid epithelioid cells, cord-like spindle cells and mucinous matrix under light microscope. The diagnosis of renal MTSCC concurrent with multiple bone metastasis was made. This case report suggested the necessity of general evaluation, especially bone scan for possible distant metastasis, as MTSCC might present unexpected advanced behaviors without any orthopedic symptoms. The behavior of bone metastasis might be associated with male and elderly age. MTSCC has similar enhancement features to papillary RCC on CT scan. As results, attentions are needed to differentiate MTSCC from papillary RCC as they both tend to show lesser enhancement degrees than cortex. Rather than exhibiting a dedifferentiating appearance, the pathological characteristics of bone metastasis lesion were close to those of primary renal lesion. The reason of distant metastasis to the bone remained unclear, negative expression of cytokeratin (CK) 7 might be attributed to. Though immunotherapy, chemotherapy and target therapy could all be methods for systematic therapies, procedures to remove renal lesions and prevent skeletal related events are still highly recommended.
Adenocarcinoma, Mucinous/surgery* ; Bone Neoplasms/secondary* ; Carcinoma, Renal Cell ; Humans ; Kidney ; Kidney Neoplasms/surgery* ; Male ; Middle Aged ; Nephrectomy

OBJECTIVE: To analyze the clinical and pathological characteristics of renal cell carcinoma bone metastasis (RCC-BM) patients. METHODS: Data of RCC-BM patients from July 2003 to November 2017 were retrospectively reviewed. The patients' baseline characteristics (age, gender), tumor characteristics [specific sites of bone metastasis, time to bone metastasis (TTBM), imaging features of bone disease, coexistence of other metastasis], as well as pathological features (histological classification of primary and bone metastasis, immunohistochemical stain results) were collected. Descriptive analysis and difference analysis were used. RESULTS: A total of 113 RCC-BM patients were enrolled with the gender ratio (male:female) of 4:1, mean age of 59.39 years, and all present of osteolysis bone lesions. The common sites of bone metastasis were vertebra (46.0%) and pelvis (38.9%). Other distant metastasis sites coexisted in 28.3%, while 48.18% RCC-BM patients presented with synchronous metastasis (TTBM=0). The median TTBM for metachronous metastasis was 48 months. The majority in this cohort were determined to have primary tumor of clear cell carcinoma. After immunohistochemical examination to 104 RCC-BM patients and sub-group analysis, tendencies of higher positive rates of vascular endothelial growth factor (VEGF) was also found in synchronous group (P=0.097) while tendencies of higher positive rates of carbonic anhydrase (CA)-IX was found in the same group (P=0.100). The patients with clear cell RCC-BM had a significantly higher positive expression of epithelial growth factor receptor (EGFR, P<0.05) than those with non-clear cell RCC-BM group. CONCLUSION More male and younger patients with metastatic lesions in axial skeleton were found in this cohort. Tendencies in the expression of CA-IX and VEGF in different TTBM sub-group and EGFR in different histology-derived subgroup indicate that they might be associated with risk and prognostic factors and support further target therapies of RCC-BM.
Age Factors ; Bone Neoplasms/secondary* ; Carcinoma, Renal Cell/secondary* ; Female ; Humans ; Kidney Neoplasms/pathology* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Sex Factors ; Vascular Endothelial Growth Factor A