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Liver fibrosis is the only way for various chronic liver diseases to develop into liver cirrhosis and is a reversible pathological state. However, how to prevent or reverse the development and progression of liver fibrosis is still an important scientific problem to be solved in clinical practice. As an important cell fate determinant, Numb has been shown to be closely associated with the development of many diseases. In the fibrotic environment, different subtypes of Numb protein are translated due to the selective shear action of the Numb gene, which have different regulatory effects on the activation of different signaling pathways and the differentiation of liver stem cells. At present, there are few reports on the role of Numb protein subtypes in liver fibrosis. This article reviews the regulatory effect of different Numb protein subtypes on the Notch, Hedgehog, and P53 signaling pathways and liver stem cells and elaborates on their potential application prospects in the treatment of liver fibrosis.
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Liver fibrosis is the response of the body to wound repair, and it is the only way for various chronic liver diseases to develop into liver cirrhosis. At present, there is still no chemical or biological drugs for blocking or reversing liver fibrosis. Liver fibrosis has a complex pathogenesis, which involves the TGF-β/Smad, Notch, Wnt, and Hedgehog signaling pathways. However, how to use simple methods to solve this complex issue remains a key scientific problem in the treatment field. As a critical determinant for cell fate, Numb is involved in the regulation of various signaling pathways such as Notch, Wnt, and Hedgehog, but its role in anti-fibrosis has not been taken seriously. This article reviews the potential value of Numb in anti-fibrosis.
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Liver cancer is one of the most common malignant tumors in China, ranking fifth in malignant tumors and the third in tumor-related deaths. As a membrane-related protein, the asymmetric distribution of cell fate determinant Numb plays a key role in cell differentiation. Research reports that Numb may be closely associated to the occurrence and development of tumors. Recently, scholars have gradually valued its important role in liver cancer. This article briefly reviews the structure of Numb molecule, relationship between Numb and tumorigenesis, the molecular mechanism of Numb-regulated tumors, and the role of Numb in the development of liver cancer.
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Objective To study the effect of Numb gene on cell cycle and proliferation in human renal carcinoma cells and its related mechanism. Methods Renal carcinoma cells Caki-1 were taken as research objects, and the Numb-ORF plasmid transfected cells, negative control group and blank control group were set respectively. The expression levels of Numb and cyclin D1 were detected by real-time PCR and Western blot. The cell cycle was analyzed respectively by flow cytometry. Cell proliferation was assessed by comparing with absorbance at 490 nm using a micro-plate reader. Results Compared to the negative control group (5.05±0.45) and blank control group (5.13±0.31), the △Ct value of Numb in the Numb-ORF group (1.92±0.39) was significantly lower. The protein levels in the Numb-ORF group, the negative control group and the blank control group were 6.67±0.83, 3.08±0.47, 2.85±0.36, respectively (P = 0.00). Meanwhile, the △Ct value of cyclin D1 in the Numb-ORF group (6.20±0.87) was higher than that in the negative control group (4.35±0.51) and the blank control group (4.56±0.31) (P = 0.02), and the protein level in the Numb-ORF group (5.85±0.72) was lower than that in the negative control group (10.04±0.83) and the blank control group (11.88±1.26) (P = 0.00). The ratio of G0/G1 cells in the Numb-ORF group was (54.29±4.15) %, the negative control group was (38.69±2.60) % and the blank control group was (41.28±1.29) % (P = 0.00). In proliferation assay, compared with the negative control group (0.93±0.10) and the blank control group (1.02±0.06), the A value at 24 h in the Numb-ORF group (0.67±0.07) was significantly reduced (P = 0.00). Conclusion Numb gene could increase the cell percentage in G0/G1 phase and inhibit proliferation of renal carcinoma cells via down-regulating the expression of cyclin D1.
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The purpose of this study is to report a rare case of mandibular adenocarcinoma that was diagnosed due to metastasis from the prostate. Numb chin syndrome (NCS), which was associated with this case, is also discussed. Computed tomography (CT) and an intraoral incisional biopsy of the left mandibular area were performed. Urology consultation, hormone therapy, chemotherapy and follow-up radiographic images were administered. Histological examination of the incised specimen revealed moderately differentiated adenocarcinoma. The Gleason score was 8 (primary 4/secondary 4). Immunohistochemical features and radiographic results confirmed the diagnosis of metastasis from prostate adenocarcinoma, moderately differentiated. The patient's prostate-specific antigen (PSA) level was very high. After hormone treatment, the patient's PSA levels dropped gradually. Seventeen months later, in May 2015, the PSA level was elevated. The 18-month follow-up CT image indicated that the patient's condition was aggravated. Docetaxel chemotherapy was started in June 2015 (18 months later), and the sixth cycle of the therapy is in progress. Oral metastases that originate from prostate adenocarcinoma are rare and can induce various periosteal reactions. Hormone therapy, chemotherapy and close follow-up could be additional, appropriate treatment, and were applied in this case. Finally, NCS is a valuable indicator of metastatic disease in the mandible.
Subject(s)
Adenocarcinoma , Biopsy , Chin , Diagnosis , Drug Therapy , Follow-Up Studies , Mandible , Neoplasm Grading , Neoplasm Metastasis , Prostate , Prostate-Specific Antigen , UrologyABSTRACT
Objective To study the effect of Numb gene overexpression on invasion and migration in human renal cell carcinoma cells and its related mechanism. Methods The Numb-ORF plasmid was transfected into renal cell carcinoma cells 786-O, set the negative control and blank control. The expression of Numb and matrix metalloproteinase-9 (MMP-9) was detected by real-time PCR and western blot. Then abilities of cells invasion and migration were measured respectively by transwell assay and scratch-wound-healing assay. Results Compared to negative control (2.51±0.27) and blank control (2.87±0.21), Numb expression in Numb-ORF group (36.13 ±8.33) was significantly higher (P= 0.00). Meanwhile, MMP-9 level in Numb-ORF group was decreased: Numb-ORF group was 2.36±0.29, negative control was 8.73±0.91, blank control was 8.99±0.78 (P=0.00). In scratch-wound-healing assay,the repair ratio of 12 h was as follow: Numb-ORF group was 0.53 ±0.06, negative control was 0.73 ±0.09, blank control was 0.75 ±0.08 (P= 0.02). In transwell assay, the number of invasion cells in Numb-ORF group was 31.40±5.96, less than negative control (126.93±13.61) and blank control (131.87 ±15.42) (P= 0.00). Conclusion Overexpression of Numb significantly decreases abilities of invasion and migration in 786-O cells, and the suppressive effect may be due to the down-regulation of MMP-9 expression in human renal cell carcinoma.
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Objective To detect the expressions of Numb and α-catenin in the gastric cancer and matched normal gastric mucosa,and to analyze their relationship with clinicopathological factors of gastric cancer and explore their roles in gastric carcinogenesis and progression.Methods Immunohistochemical method was used to detect the expressions of Numb and α-catenin in 109 cases of tumor specimens and 97 cases of matched normal gastric mucosa.The correlations between Numb,α-catenin and clinicopathological factors were analyzed.Results The positive rates of Numb and α-catenin in gastric cancer were significantly lower than those in normal gastric mucosa (60.6％ ∶ 100.0％,x2 =48.361,P =0.000;76.1％ ∶ 100.0％,x2 =26.480,P=0.000).The expression of Numb protein was correlated with Lauren type (x2 =17.018,P =0.000) and tubular adenocarcinoma differentiation (x2 =17.586,P =0.000).The expression of α-catenin protein was correlated with Borrmann type (x2 =6.700,P =0.035),Lauren type (x2 =11.098,P =0.001),tubular adenocarcinoma differentiation (x2 =8.203,P =0.017) and lymph node metastasis (x2 =6.402,P =0.011).The expressions of Numb and α-catenin were statistically correlated in 109 cases of gastric cancer (rk =0.184,P =0.028).Conclusion Compared with normal gastric mucosa,both Numb and α-catenin expressions are down-regulated and the two expressions are correlated in gastric cancer.Numb and α-catenin may be involved in the regulation of histological differentiation of gastric cancer by certain passages,Numb protein may be adjusted by α-catenin pathway which is involved in Wnt-β-catenin pathway,and thus plays an important role in promoting cell proliferation,invasion and metastasis in human gastric cancer.
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Objective To study the effect of Numb overexpression on invasion and migration in human bladder cancer cell line T24,and its related mechanism.Methods In June 2013,the plasmids including Numb-ORF plasmid and its blank vector pCMV6-Entry were transfected into T24 cells,and set the blank control as usual.The expressions of Numb and MMP-9 (Matrix metalloproteinase-9) were detected by Real-Time PCR and Western Blot.Then T24 cell invasion and migration were measured respectively by Transwell assay and Scratch Wound Healing Assay.Results Compared to negative control group,which transfected with blank-vector plasmid and untransfected group,Numb expression level in Numb-ORF group was significantly higher (P＜0.01).Meanwhile,MMP-9 level in Numb-ORF group was decreased,△ CT-value as follows:Numb-ORF group was 8.423±0.202,negative control group was 7.294±0.138,untransfected group was 7.220±0.118 (P＜0.01).In Scratch Wound Healing Assay,the repair ratio of Numb-ORF group was less than negative control group and untransfected group.The repair ratio in 12 hours as follow:Numb-ORF group was 0.525±0.037,negative control group was 0.693±0.034,untransfected group was 0.701 ±0.038(P=0.004).In Transwell assay,the number of invasion cells in Numb-ORF group was 12.6±3.2,less than in control group (130.8±9.2) and untransfected group (132.2± 10.6) (P＜0.05).Conclusions Overexpression of Numb by transfection significantly decreases the capability of T24 cell invasion and migration.This suppressed effect may be due to the down-regulation of MMP-9 expression in human bladder cancer.
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Numb,one of the important cell fate determinants,plays a key role in regulation of nerve system development,and it is closely related to the occurrence of tumors.It is proven that Numb is implicated in the processes of occurrence,invasion and metastasis of tumors through regulating the way of cell division,cell polarity,epithelial-mesenchymal transitions and several signal pathways,e.g.,Notch,Hh,p53.The expression levels of Numb in cells are related to the malignant degree and prognosis of tumors.It is vital to explore the role of Numb in tumors for treating tumors at the standpoint of Numb.
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Numb chin syndrome is a sensory neuropathy of the inferior alveolar branch of the trigeminal nerve, characterized by unilateral numbness of the chin, the lower lip and the buccal and gingival mucosa. We report a girl with acute lymphoblastic leukemia of B-cell type who initially presented with numb chin syndrome resulting from skull base infiltration.
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Objective To investigate the expression of Notchl and NUMB in gastric cancer and explore the relationship between two genes and clinicopathologic features. Methods The mRNA and protein expressions of Notchl and NUMB in the gastric cancer tissues and normal gastric tissues were determined by realtime PCR and Western blotting. Results The mRNA expression of Notchl in gastric cancer tissues was 1.67times that of Notchl in normal gastric tissues. The increase of the mRNA expression of Notchl was correlated with tumor differentiation and lymph node metastatis of the patients ( P < 0. 05 ). The mRNA expression of NUMB in gastric cancer tissues was 0.597 times that of Notchl in normal tissues. The decrease of the mRNA expression of NUMB was correlated with tumor differentiation of the patients (P < 0.05). The expression of Notchl was negatively correlated to that of NUMB ( r = - 0.459, P < 0.05 ). The protein expression of Notchl in gastric cancer tissues was (0. 348 ±0. 133) , which was significantly higher than (0. 208 ±0. 140) in normal gastric tissues (P < 0.05 ). The protein expression of NUMB in gastric cancer tissues was (0.490 ±0.440), which was significantly lower than 0.746 ±0.390 in normal gastric tissues (P<0.05).Conclusion Up-regulation of Notchl and down-regulation of NUMB may play an important role in the occurrence and development of gastric cancer.
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Painful ophthalmoplegia (PO) and concomitant numb chin syndrome (NCS) is a very rare event. There are a few reports in the literature about PO and concomitant NCS that have preceded the diagnosis of a malignancy. In this report, we describe a patient with diffuse large B cell lymphoma who presented with PO and concomitant NCS as the initial symptom of the disease.
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Humans , Chin , Lymphoma , Lymphoma, B-Cell , OphthalmoplegiaABSTRACT
Numbness of the lower lip, the skin of the chin, or the gingiva of the lower anterior teeth secondary to various dental diseases is a common manifestation that is largely underappreciated. The association of numb chin syndrome (NCS) with serious disease like metastatic malignancy and systemic conditions is frequent enough to warrant a search for these possible etiologies. In this paper we report a case of NCS that occurred secondary to malignant disease; we discuss our findings with special emphasis on metastatic malignancies leading to NCS, when the survival is only for a few months.
Subject(s)
Chin/innervation , Cranial Nerve Neoplasms/complications , Humans , Hypesthesia/etiology , Lymphoma, Non-Hodgkin/complications , Male , Mandibular Neoplasms/complications , Mandibular Neoplasms/secondary , Mandibular Nerve , Middle Aged , SyndromeABSTRACT
Objective To explore the effect of Numb on tubular epithelial-to-mesenchymal transition (EMT) in rat proximal epithelial cells. Methods NRK52E cells were treated with different concentrations of recombinant human transforming growth factor-β1 (TGF-β1) (0, 1, 5, 10, 15, 20 μg/L) for 48 h or 10 μg/L TGF-β1 for different times (0, 24, 48, 72 h) in vitro. The expressions of E-cadherin, a-smooth muscle actin(α-SMA) and Numb in NRK 52E cells were detected by RT-PCR, Western blot and immunofluorescence staining. Meanwhile Numb siRNA oligo was transfected into NRK 52E cells with lipofectamine before TGF-β1 treatment, then Western blot was applied to detect the protein expression of E-cadherin, α-SMA and Numb in NRK52E cells. Results TGF-β1 could induce EMT in NRK52E cells in dose- and time-dependent manner. During the progress of TGF-β1-induced EMT, the protein expression of Numb in 5, 10, 15, 20 μg/L group was 1.33 folds (P=0.024), 1.39 folds (P=0.035), 1.45 folds (P=0.025), 1.51 folds (P=0.000) respectively as compared to 0 μg/L group. Likewise, the protein and mRNA expression of Numb in 24 h, 48 h, 72 h group was 1.48 folds (P=0.046) and 1.56 folds (P=0.012), 1.54 folds (P=0.011) and 1.82 folds (P=0.008), 1.79 folds (P=0.028) and 1.82 folds (P=0.002) respectively as compared to 0 h group. Moreover, large amount of Numb was accumulated in the cytoplasm. Down-regulation of Numb expression by siRNA transfection did not influence the basal expression of E-cadherin and α-SMA in NRK 52E cells, but attenuated the progression of EMT in NRK52E cells induced by TGF-β1. The up-regulation of α-SMA protein was reduced to 18.1% (P=0.004) while the down-regulation of E-cadherin protein was reversed to 2.19 folds (P=0.004). Conclusion Numb can promote EMT in rat proximal epithelial cells.
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Numb chin syndrome is a rare clinical manifestation, characterized by focal sensory loss and paresthesia of the chin. It is more often associated with cancer than with benign disorders, and can be the first manifestation of a cancer. A 60-year-old man presented with focal numbness of right chin and gingiva for 10 days. Chest computed tomography showed a 3 cm sized mass on the distal left main-stem bronchus. Squamous cell carcinoma was diagnosed on bronchoscopic biopsy. However, bony metastasis of mandible was not evident on reontgenogram, CT scan, bone scintigram and positron emission tomography. Despite the chemotherapy with three cycles of paclitaxel and cisplatinum, the cancer was progressed and pain on the right chin was developed 4 months .later. Bone scintigram showed multiple bony metastasis including mandible. Here we report this case with a brief review of the appropriate literature.
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Male , Humans , Neoplasm Metastasis , Lung NeoplasmsABSTRACT
Cerebral aspergillosis is a rare condition that affects primarily the immunocompromised host. Most of cerebral aspergillosis is developed by hematogenous dissemination from extracranial foci, but aspergillosis of sino-nasal origin rarely affects the CNS. In case 1, wel symptom of tumor recurrence was unilateral numbness of the chin. A 65-year-old male was admitted because of paresthesia around the left chin and left lower lip. Neurologic examination revealed hypesthesia on the left side of chin, lower lip and buccal mucous mem-brane. Bone scan (Tc-99m MDP) showed focal hot uptakes on the left mandible and left first rib. Brain CT with bone window setting showed a focal osteolytic lesion in the bone marrow of the left mandibular canal without destruction of bone cortex. Both coronal T1 weighted image and axial T2 weighted image showed focal low signal intensities on the left ramus. The pathophysiologic mechanism could be understood by identification of the pathologic focus.
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Aged , Humans , Male , Aspergillosis , Bone Marrow , Brain , Chin , Hypesthesia , Immunocompromised Host , Lip , Mandible , Neurologic Examination , Paresthesia , Recurrence , RibsABSTRACT
The numb chin syndrome (NCS) is characterized by chin or lower lip numbness restricted to the distribution of the mental nerve (the distal trigeminal nerve). The authors report a patient whose initial symptom of tumor recurrence was unilateral numbness of the chin. A 65-year-old male was admitted because of paresthesia around the left chin and left lower lip. Neurologic examination revealed hypesthesia on the left side of chin, lower lip and buccal mucous mem-brane. Bone scan (Tc-99m MDP) showed focal hot uptakes on the left mandible and left first rib. Brain CT with bone window setting showed a focal osteolytic lesion in the bone marrow of the left mandibular canal without destruction of bone cortex. Both coronal T1 weighted image and axial T2 weighted image showed focal low signal intensities on the left ramus. The pathophysiologic mechanism could be understood by identification of the pathologic focus.
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Aged , Humans , Male , Bone Marrow , Brain , Chin , Hodgkin Disease , Hypesthesia , Lip , Mandible , Neurologic Examination , Paresthesia , Recurrence , RibsABSTRACT
The level of vitamin B1 in 20 patients with the mild and typical the "numb-unsteady" syndrome and 20 healthy persons with ages of 20-50 was quantified during 10-12/1999. The participants did use the vitamin B1 within the previous 3 weeks. The level of vitamin B1 was quantified by the high performance liquid chromatography (HPLC). The results have shown that the level of blood vitamin B1 in 100% of participants was lower than normal level. Although patients used continuously the vitamin B1 at high dose, the blood vitamin B1 has still lower than normal range and control. The level of vitamin B1, B2 and PP in the diet of both patients and control groups did not meet the wanted level
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Thiamine , HypesthesiaABSTRACT
The numb chin syndrome (NCS) is characterized by chin or lower lip numbness restricted to the distribution of mental nerve (the distal trigeminal nerve). This uncommon neuropathy may be associated with neoplastic disease and usually appeared as a late manifestation of systemic malignancy, and it is an important sign for early diagnosis and prediction of clinical course and prognosis of hematologic malignancy. The numb chin syndrome is usually associated with a poor prognosis although various therapeutic strategies led to resolution of this syndrome. We report 2 cases of numb chin syndrome ; one in acute leukemia in early course of disease before diagnosis of leukemia and the other in leptomeningeal seeding of malignant lymphoma. The therapeutic response and prognosis were poor, a patient of malignant lymphoma expired in two months and a patient of acute leukemia is alive at present but the disease was relapsed in 5 months after complete remission.