Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.

Nasal metastases from neuroblastoma-a rare entity: Two case reports.

BACKGROUND: Neuroblastoma (NB) is one of the most common malignancies in children. Metastasis in NB is not uncommon. However, nasal metastases are rare. Here, we reported two pediatric cases of nasal metastases. CASE SUMMARY: Case 1 was a 3-year-old boy without a history of NB. Case 2 was a 10-year-old girl who had a history of NB for 6 years. Both of them presented with symptoms of nasal and sinus masses such as epistaxis or discharge from the nose. The radiologic imaging results revealed masses in the nasal cavity or nasopharynx in both cases and a mass in the right adrenal gland of case 1. The pathologic examination of biopsy samples of their nasal masses revealed "small round blue-cell tumor" along with abundant vascular fibrous septa. The tumor cells expressed synaptophysin, cluster of differentiation 56, chromogranin A, paired like homeobox protein 2B and a very high Ki67 index in both case but were negative for vimentin, desmin, leucocyte common antigen and cytokeratin. Myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification was detected in both cases. Finally, the two cases were diagnosed as nasal metastases from NB based on the clinical and pathologic findings. The two patients affected by NB were > 18 mo old, the primary tumor location was adrenal gland, and they presented with multiple metastases. CONCLUSION: It is difficult to differentiate between metastatic NB in the nose and olfactory neuroblastoma in the absence of a history of NB. Paired like homeobox protein 2B can play an important role in the diagnosis and differential diagnosis of this disease.

A case report of targeted therapy with apatinib in a patient with advanced gastric cancer and high serum level of alpha-fetoprotein.

BACKGROUND: Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma, and the detection of serum AFP is currently the principle method for the diagnosis of hepatocellular carcinoma. The prevalence of gastric cancer (GC) with high level of serum AFP is extremely rare, but has unique clinical features. CASE SUMMARY: We herein present a rare case with GC and high level of serum AFP. A 64-year-old Chinese female underwent gastrectomy was diagnosed as gastric adenocarcinoma and the pathological stage was T1bN0M0, IA. With the progression of disease, the tumor widely metastasized and the serum AFP level increased progressively with the highest level of 3396 ng/mL. She successively entered into 3 lines palliative systematic chemotherapy and fourth-line targeted therapy of apatinib, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Although previous studies suggested that the prognosis of this special type of GC was poor, this patient lived for 22 months after tumor transfer. Apatinib kept her progression-free survival for 5 months, and the overall survival was 4.5 years. CONCLUSION: So, we speculate that maybe we can focus apatinib on serum AFP elevated GC patients.

Atypical teratoid/rhabdoid tumours: clinicopathological characteristics, prognostic factors and outcomes of 22 children from 2010 to 2015 in China.

Atypical teratoid/rhabdoid tumours (AT/RTs) are rare, highly malignant tumours of the central nervous system (CNS) with poor prognosis that usually affect young children. The aim of this study was to assess the clinicopathological features and prognostic factors of AT/RTs. Here, we describe the clinicopathological and immunohistochemical characteristics, along with the treatments and outcomes, of 22 patients with AT/RTs treated in our hospital from 2010 to 2015. Morphologically, cytoplasmic vacuoles, the most common characteristic in our cases, were observed in 68% of the cases. Similarly, vesicular nuclei were detected in 68% of the cases. However, rhabdoid cells were found in only 59.1% of the cases and were not observed in 40.9% of the cases. Immunohistochemical analysis revealed loss of nuclear INI1 expression in all 22 cases. Age, surgical resection and adjuvant therapy, but not tumour location, were associated with AT/RTs patient prognosis. Our results showed that cells with cytoplasmic vacuoles or with vesicular nuclei are more common than rhabdoid cells in patients with AT/RTs and that a lack of INI1 protein expression is the most useful marker for the differential diagnosis of AT/RTs. Young age is a negative prognostic factor, whereas gross total surgical resection and adjuvant therapy are positive prognostic factors for AT/RT patients.

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies.

Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer.

Cancer-associated fibroblasts (CAFs) are important components of various types of tumors, including gastric cancer (GC). During tumorigenesis and progression, CAFs play critical roles in tumor invasion and metastasis via a series of functions including extracellular matrix deposition, angiogenesis, metabolism reprogramming and chemoresistance. However, the mechanism of the interaction between gastric cancer cells and CAFs remains largely unknown. MicroRNAs (miRNAs) are a class of non-coding small RNA molecules, and their expression in CAFs not only regulates the expression of a number of target genes but also plays an essential role in the communication between tumor cells and CAFs. In this review, we provide an overview of recent studies on CAF miRNAs in GC and the relevant signaling pathways in gastrointestinal tumors. Focusing the attention on these signaling pathways may help us better understand their role in tumor invasion and metastasis and identify new molecular targets for therapeutic strategies.

Extranodal follicular dendritic cell sarcoma: A clinicopathological report of four cases and a literature review.

The aim of the present study was to characterize the clinicopathological features of follicular dendritic cell sarcoma (FDCS), and to report the experience of the Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (Shanghai, China) with this entity. The clinicopathological findings of four cases that had recently been encountered and 142 previously reported cases in the English literature were evaluated. The current tumors were found in two male and two female patients, aged 49-76 years old, who exhibited a mean tumor size of 8.7 cm. Three of the four cases were misdiagnosed during the initial diagnosis and one experienced intra-abdominal recurrence six months after the first diagnosis. Assessment of all 142 cases in the literature revealed a mild female predominance. The tumors exhibited a mean tumor size of ~7.0 cm. Histologically, the tumors were composed of plump spindle- or oval-shaped cells that exhibited eosinophilic cytoplasm and were arranged in sheets, storiform patterns or whorls. Immunohistochemically, the neoplastic cells expressed at least one of the FDC markers. Among the 130 cases with follow-up data, the overall recurrence, metastasis and mortality rates were 49.2% (64 cases), 21.5% (28 cases), and 13.8% (18 cases), respectively. FDCS can appear deceptively similar to other soft-tissue tumors, even poorly-differentiated carcinomas. A correct diagnosis requires a high degree of suspicion and immunohistochemical evaluation.

Effects of the fibroblast activation protein on the invasion and migration of gastric cancer.

OBJECTIVE: Cancer-associated fibroblasts (CAFs) are one of the most important components of tumor microenvironment. CAFs are believed to play an important role in tumor invasion and metastasis. Recently, fibroblast activation protein (FAP), a type II integral membrane glycoprotein belonging to the serine protease family, has emerged as a specific marker of CAFs. FAP was overexpressed in stromal fibroblasts of solid malignancies, however, the role of FAP on the process of invasion and metastasis of gastric carcinomas is still unknown. METHODS: Expression of FAP level was detected by immunohistochemistry in 60 gastric cancer surgical specimens (28 with omentum metastasis and 32 without), 20 normal human gastric tissues and omentum of 10 nonneoplastic gastric diseases. Fibroblasts were isolated from patient's tissues in the distal normal zones and tumor zones respectively, which were correspondingly designated as normal zone fibroblasts (NFs) and cancer-associated fibroblasts (CAFs). To explore the effects of FAP on NFs or CAFs, fibroblasts were co-cultured with human gastric cancer cell line MGC-803 cells. The ability of invasion and migration of MGC-803 cells was evaluated after transfecting FAP siRNA into CAFs of gastric carcinomas. RESULTS: We investigated the level of expression of FAP in surgical specimens, and found overexpressed in CAFs and non-expressed in NFs. Expression of FAP level in CAFs is significantly associated with Lauren classification,the degree of differentiation, depth of tumor invasion and TNM stage, but it is not correlated to age and gender in gastric carcinoma patients. There was positive correlation between the FAP level with metastasis to the omentum(p < 0.05, R(2) = 0.2736, p < 0.05, R(2) = 0.1479). In addition, the invasion and migration abilities of MGC-803 cells were significantly increased when cells were co-cultured with CAFs. On the other hand, invasion and migration abilities were significantly decreased by 46.9 and 50.3%, respectively, after knocking down FAP in CAFs.Further, NFs did not have appreciable effect on the invasion and migration of MGC-803 cells. CONCLUSIONS: Our findings showed that FAP was overexpressed in CAFs of gastric carcinomas, and siRNA-mediated knock down of FAP significantly suppressed invasion and migration of MGC-803 cells. FAP may be an important regulator in the invasion and migration of gastric cancer and may provide a novel therapeutic target in gastric carcinomas.

Tetra-kis(µ-4-methoxy-benzoato)bis-[(4-methoxy-benzoato)(1,10-phenan-throline)terbium(III)].

In the title dinuclear complex, [Tb(2)(C(8)H(7)O(3))(6)(C(12)H(8)N(2))(2)], each Tb(III) ion is eight-coordinated by two N atoms from a 1,10-phenanthroline ligand and six O atoms from the carboxyl-ate groups of five 4-methoxy-benzoate ligands in a distorted square-anti-prismatic geometry. All six 4-methoxy-benzoate ligands act in a bidentate mode, two coordinating to one Tb center each and the other four bridging two Tb centers [Tb⋯Tb separation = 4.3144 (6) Å]. In the crystal, inter-molecular π-π inter-actions between the aromatic rings of 1,10-phenanthroline and 4-methoxy-benzoate ligands [centroid-centroid distance = 3.742 (9) Å] link two mol-ecules into a centrosymmetric dimer. Weak inter-molecular C-H⋯O hydrogen bonds help to consolidate the crystal packing.

[Emitting characteristics and carrier composite regions variety of the blend of terbium complex and poly-n-vinylcarbazole].

A new rare earth complex TbGd(BA)6(bipy)2 was synthesized, which was used as an emitting material in electroluminescence. By doping with poly-N-vinylcarbazole (PVK), the stability and conductivity of terbium complex were improved. The photoluminescence of PVK, terbium complex and their blend indicated that energy transfer from PVK to terbium complex occurred. In the present paper, single-, double- and multi-layer devices were fabricated. In the double-layer devices, holes and electrons were recombined at the interface of emitting layer (EML) and electron transporting layer (ETL). With increasing the thickness of Alq3, especially at highly electric field, carrier composite region transferred closely to ETL. However, in multi-layer devices, carrier composite region was restricted at the interface of emitting layer and holes blocking layer (HBL) due to high HOMO level of BCP. Enhancing electric field, emission from terbium complex was getting saturation gradually and weak emission from PVK was observed. From the optimized multi-layer device, bright and green emission from terbium complex was obtained with the highest EL brightness of the device of 213 cd x m(-2) at 13.5 V.

[Effects of PBD on the electroluminescence (EL) of Tb complex doped PVK system].

Electroluminescent (EL) properties of the terbium complex [Tb(m-MBA)3 phen]2 x 2H2O doped PVK system were investigated. Two kinds of devices with the structures of ITO/PVK: Tb complex/PBD/LiF/Al and ITO/PVK: Tb complex: PBD/PBD/LiF/Al were fabricated. PBD emission appears in the EL spectra of ITO/PVK: Tb complex/PBD/LiF/Al in comparison with ITO/PVK: Tb complex: PBD/PBD/LiF/Al. The reason is that PBD acts as a hole blocking material in the emitting layer (PVK: Tb complex: PBD) and thus the combination of excitons mostly occur within this layer. The energy of terbium complex emission comes from two different ways, namely energy transfer and direct combination of carriers. By altering the doping weight ratio of PBD, a set of devices were fabricated with the configuration of ITO/PVK: Tb complex: PBD/PBD/LiF/Al. Both the efficiency and brightness of these devices decrease with the rising of the PBD doping weight ratios. The efficiency of the carriers trapping may decrease with the rising of PBD doping ratios, for PBD may block the hoping of hole or electron between the PVK chains, causing a decrease in the brightness and efficiency. The PBD doping ratios have little effect on the efficiency of Förester energy transfer based on our synthesis.

[The emission mechanisms of two kinds of Tb complexes doped in PVK system].

Two kinds of new rare earth complexes Tb(p-MBA)3phen (sample I) and Tb(p-ClBA)3 phen (sample II) were synthesized, and photoluminescence (PL) and electroluminescence (EL) characteristics of the terbium complex and PVK blended system were investigated. As to the sample I , the emission of PVK was completely restrained in the EL spectra of the blended film; while in the PL spectra, obvious emission of PVK appeared besides the emission of Tb3+. But as to the sample II, only the green emission from Tb3+ can be observed in both PL and EL spectra of the doping system. So there are two processes that occur in sample I, one is the incomplete Förster energy transfer process from PVK to the Tb complex, and the other is the car rier charge trapping process. The main mechanism of sample II is the energy transfer process.

[Studies on luminescence properties of seven ternary complexes of terbium with 1,10-phenanthroline and benzoic acid and its derivatives].

Seven ternary complexes of Tb(III) were synthesized with benzoic acid (BA), o-, m-, p-methylbenzoic acid (o-MBA, m-MBA, p-MBA), and o-, m-, p-methoxybenzoic acid (o-MOBA, m-MOBA, p-MOBA) as the first ligand, and 1,10-phenanthroline (phen) as the second ligand. The content of C, H and N were measured by using a Flash-EA model 1112 elemental analyzer. Excitation and luminescence spectra of the title solid complexes were recorded by using a Hitachi F-4500 fluorescence spectrophotometer at room temperature. The effects of different varieties and different positions of replacing benzoic acid as the first ligand on fluorescence properties of the ternary complexes of terbium were discussed. The results indicated that the intensity of 5D4-->7F6 (489 nm) and 5D4-->7F5 (545 nm) of substituting benzoic acid complexes was stronger than benzoic acid. Three ternary complexes of Tb(III) with o-, m-, p-methylbenzoic acid showed emission intensity in the consecution: Tb(o-MBA)3 phenTb(m-MOBA)3phen x H2O>Tb(p-MOBA)3 phen.

[Electroluminescent device based on rare earth terbium complex].

Rare earth complex TbY(m-MBA)6 (phen)2.2H20 have been synthesized, which were used as emitting materials in electroluminescence. Single-layer devices and bilayer devices with Alq as electron transmission layer have been fabricated. The electroluminescent properties of the devices were studied. The electroluminescent mechanism of the devices was proposed by measuring and analyzing the emission and the excitation spectra of the emissive layer. Y3+ may play the role to promote the energy transfer from ligand to Tb3+ and the possible energy transfer process of the device was preliminarily discussed.

[Electroluminescent device based on terbium complex].

Rare earth complex Tb(BA)3phen has been synthesized, which is used as an emitting material in electroluminescence. The properties of monolayer device with the rate of 1000 r x min(-1) and the impure concentration of 1:5 are the best. And the highest brightness of this device reached 26.8 cd x cm(-2) at a fixed bias of 21 V. Bright green emission can be obtained from the optimized double-layer device and the highest EL brightness of the device reaches 322cd x m(-2) at the voltage of 22 V.

[Emission mechanism in the Tb complex doped PVK system].

Excitation and photoluminescence (PL) spectra of the mixture terbium complex and PVK were investigated. The excitation spectrum of Tb complex dispersed PVK film is very similar to that of the pure PVK film, indicting that energy transfer occurs from PVK to Tb complex. For the overlap between the excitation spectrum of Tb complex dispersed PVK film and the PL spectrum of PVK film is very little, the ratio of occurrence for Förester energy transfer is very little. The emission of Tb3+ mainly comes from the excited ligand, which comes from the ligand capture of electron-hole pairs. In the electroluminescence (EL) spectra, the emission of PVK is completely restrained and only emission of Tb3+ is occured, which origins from the different mechanism in comparison with photoluminescence.