- Role of LKB1 in migration and invasion of Cr(VI)-transformed human bronchial epithelial Beas-2B cells. [Journal Article]
- ADAnticancer Drugs 2018 May 18
- Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epith...
Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells. The mechanism underlying its carcinogenicity is unclear in terms of how it facilitates metastases. Cr(VI) compounds are reported to briefly promote cell migration in a concentration-dependent manner and oncogene liver kinase B1 (LKB1) was reduced in Cr(VI)-transformed cells. Overexpression of LKB1 in Beas-2B-Cr [Cr(VI) malignantly transformed Beas-2B cells] suppressed cell migration and invasion and inactivated FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, which contribute to cell migration and invasion. Silencing LKB1 with siRNA promoted migration and invasion, and activated these downstream proteins. Long-term exposure to Cr(VI) enhanced the migration and invasiveness of Beas-2B cells and reduced the expression of LKB1, while activating these proteins as mentioned above. Data suggest that LKB1 may regulate downstream proteins such as FAK, Src, MMP-2, GSK3β, β-catenin, and HEF1, and affect the migration and invasiveness of Beas-2B-Cr cells.
- Early onset of diffuse melanosis cutis under pembrolizumab therapy illustrates the limitations of anti-PD-1 checkpoint inhibitors. [Journal Article]
- MRMelanoma Res 2018 May 17
- Anti-PD-1 targeted immunotherapies have revolutionized the treatment of advanced melanoma and other tumor entities, and long disease-free intervals have been reported in responding patients. However,...
Anti-PD-1 targeted immunotherapies have revolutionized the treatment of advanced melanoma and other tumor entities, and long disease-free intervals have been reported in responding patients. However, a considerable number of patients still progress rapidly after the start of anti-PD-1 antibodies. Here, we document two patients, 78 and 85-year old, who suffered from advanced BRAF-V600 wild-type melanoma and received pembrolizumab 2 mg/kg every 3 weeks as the first systemic treatment. After only one, respectively, two infusions of pembrolizumab, both patients developed melanuria and diffuse melanosis cutis (DMC) on sun-exposed areas of their skin. Both also had liver metastases, which have been reported to be associated with DMC before. Pembrolizumab was stopped because of rapid tumor progression and both patients died within 2 months after manifestation of DMC. We conclude that DMC is a condition that may be a negative predictor of response to anti-PD-1 treatment. With respect to the very short survival, which is even shorter than that reported after conventional therapies, it needs to be evaluated whether immunotherapy may be a (relative) contraindication in DMC patients when another treatment option, that is targeted therapy, is available.
- iPhone-imaged and cell-powered electrophoresis titration chip for the alkaline phosphatase assay in serum by the moving reaction boundary. [Journal Article]
- LCLab Chip 2018 May 21
- As a vital enzyme, alkaline phosphatase (ALP) has great clinical significance in diagnoses of bone or liver cancer, bone metastases, rickets, and extrahepatic biliary obstruction. However, there is s...
As a vital enzyme, alkaline phosphatase (ALP) has great clinical significance in diagnoses of bone or liver cancer, bone metastases, rickets, and extrahepatic biliary obstruction. However, there is still no really portable chip for the ALP assay in blood. Herein, a simple electrophoresis titration (ET) model was developed for ALP detection via a moving reaction boundary (MRB). In the model, ALP catalyzed the dephosphorylation of a 4-methylumbelliferyl phosphate disodium salt (4-MUP) substrate in the cathode well to 4-methylumbelliferone ([4-MU]-) with a negative charge and blue fluorescence under UV excitation. After the catalysis, an electric field was used between the cathode and the anode. Under the electric field, [4-MU]- moved into the channel and neutralized the acidic Tris-HCl buffer, resulting in the quenching of [4-MU]- and creating a MRB. The ET system just had an ET chip, a lithium cell, a UV LED and an iPhone used as a recorder, having no traditional expensive power supply and fluorescence detector. The relevant method was developed, and a series of experiments were conducted via the ET chip. The experiments showed: (i) a MRB could be formed between the [4-MU]- base and the acidic buffer, and the MRB motion had a linear relationship with the ALP activity, validating the ET model; (ii) the ET run was not impacted by many interferences, implying good selectivity; and (iii) the ET chip could be used for portable detection within 10 min, implying an on-site and rapid analysis. In addition, the ET method had a relatively good sensitivity (0.1 U L-1), linearity (V = 0.033A + 3.87, R2 = 0.9980), stability (RSD 2.4-6.8%) and recoveries (101-105%). Finally, the ET method was successfully used for ALP assays in real serum samples. All the results implied that the developed method was simple, rapid and low-cost, and had potential for POCT clinical ALP assays.
- [Is preoperative systemic chemotherapy recommended for resectable colorectal liver metastases? Oncosurgical aspects]. [Journal Article]
- OHOrv Hetil 2018; 159(21):823-830
- Surgical resection is still the only curative treatment for colorectal liver metastases, but this is one part of a complex therapy. Nowadays a patient with colorectal liver metastasis is not treated ...
Surgical resection is still the only curative treatment for colorectal liver metastases, but this is one part of a complex therapy. Nowadays a patient with colorectal liver metastasis is not treated only by a surgeon or by an oncologist or even only by an invasive radiologist. Collective decisions, complement treatments give the only chance to treat these patients for longer time. Patients with colorectal liver metastases could be regarded as patients with chronic disease. Specially interesting are the various treatment options of resectable colorectal liver metastases. The efficiency and necessity of preoperative chemotherapy are still a hot spot in the treatment of resectable liver metastases. In this study, we try to summarize the international and local experiences and the current evidence of the use of preoperative chemotherapy in the treatment of colorectal liver metastases. Orv Hetil. 2018; 159(21): 823-830.
- Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases. [Journal Article]
- IJInt J Surg Case Rep 2018 May 16; 48:26-29
- CONCLUSIONS: Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes.Liver resection for metastases of tracheal ACC may contribute to long survival.
- Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7. [Journal Article]
- BBBiochem Biophys Res Commun 2018 May 16
- Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule o...
Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients. Loss- and gain-of-function assays demonstrated that SPOP inhibited HCC cell migration and invasion in vitro. Mechanisitically, co-immunoprecipitation and ubiquitination assays revealed that SPOP recognized and bound SENP7 and promoted its degradation via ubiquitin-dependent proteolysis. Analysis of immunohistochemistry showed that vimentin expression was correlated negatively with SPOP and positively with SENP7. These results implied that increased degradation of SENP7 by overexpression of SPOP decreased vimentin levels, which in turn attenuated HCC cell metastasis. Moreover, in vivo assays showed that SPOP overexpression also significantly suppressed liver and lung metastases. In summary, SPOP inhibits HCC cell metastasis via ubiquitin-dependent SENP7 proteolysis and may thus serve as a new opinion for the prevention of HCC metastasis.
- Application of Cu-64 NODAGA-PSMA PET in Prostate Cancer. [Journal Article]
- ATAdv Ther 2018 May 17
- CONCLUSIONS: 64Cu NODAGA-PSMA PET is a promising imaging tool in the detection of residual disease in patients with recurrent or primary progressive prostate cancer. Furthermore, the increased tracer uptake over time indicates in vivo stability of the diagnostic radiopharmaceutical.
- Site-specific expression of amine oxidases in breast cancer metastases. [Journal Article]
- TBTumour Biol 2018; 40(5):1010428318776822
- We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 12...
We aimed to evaluate the expression of amine oxidase-related proteins in metastatic breast cancer tissue and determine its clinical implication. A tissue microarray was constructed from a total of 126 metastatic breast tumors (31 bone metastases (24.6%), 36 brain metastases (28.6%), 11 liver metastases (8.7%), and 48 lung metastases (38.1%)). Immunohistochemical staining for amine oxidase-related proteins (lysyl oxidase, diamine oxidase, and monoamine oxidase A and B) was performed. In metastatic breast cancer tissue, lysyl oxidase ( p = 0.001), tumoral diamine oxidase ( p = 0.003), stromal diamine oxidase ( p = 0.047), and stromal monoamine oxidase B ( p = 0.002) were differentially expressed in different metastatic sites. Bone metastases showed low expression of lysyl oxidase, tumoral diamine oxidase, and stromal diamine oxidase. We observed high expression of lysyl oxidase in brain metastases, tumoral diamine oxidase in liver metastases, stromal diamine oxidase in lung metastases, and stromal monoamine oxidase B in bone metastases. Lysyl oxidase positivity was associated with progesterone receptor negativity ( p = 0.001), and monoamine oxidase A positivity was associated with human epidermal growth factor receptor-2 negativity ( p = 0.003) and the luminal A subtype ( p = 0.003). On univariate analysis shorter overall survival was associated with stromal diamine oxidase negativity ( p = 0.008), especially in lung metastases ( p = 0.025), and stromal monoamine oxidase B positivity ( p < 0.001). Stromal monoamine oxidase B positivity was an independent prognostic factor for shorter overall survival in multivariate Cox analysis (hazard ratio, 4.069; 95% confidence interval, 1.649-10.04; p = 0.002). Finally, in metastatic breast cancer, amine oxidase-related proteins were differentially expressed in a manner specific to metastatic site, and stromal monoamine oxidase B expression was correlated with prognosis.
- [Prognostic analysis and clinicopathological features of 20 patients with appendiceal neuroendocrine neoplasms]. [Journal Article]
- ZWZhonghua Wei Chang Wai Ke Za Zhi 2018 May 25; 21(5):564-568
- CONCLUSIONS: Most a-NEN patients have no typical symptoms, and the main complaint at consultation is acute right lower quadrant abdominal pain. Prognosis is poor for patients with age >50 years, MANEC pathology grade and metastasis.
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- Gadofosveset-enhanced magnetic resonance imaging as a problem-solving tool for diagnosing colorectal liver metastases: a case report. [Journal Article]
- QIQuant Imaging Med Surg 2018; 8(3):360-363
- Due to significant improvements in morbidity and mortality, surgery with curative intent is now the standard of care for patients with colorectal liver metastases who are surgical candidates. As a re...
Due to significant improvements in morbidity and mortality, surgery with curative intent is now the standard of care for patients with colorectal liver metastases who are surgical candidates. As a result, highly accurate preoperative per-lesion diagnosis is crucial. However, in some instances, this remains limited with standard techniques, including magnetic resonance imaging (MRI) with conventional contrast agents. Delayed retention of contrast of fibrotic liver metastases on MRI with extracellular contrast agents may mimic the late retention of contrast in hemangiomas and represent a diagnostic pitfall that limits diagnosis. Early preliminary work suggests that this imaging pitfall may not be seen on MRI with intravascular contrast agents (e.g., gadofosveset). This case report describes a surgical patient with colorectal liver metastases where gadofosveset-enhanced liver MRI was helpful in determining patient management.