First case report of a novel KIF13A-ALK fusion in a lung adenocarcinoma patient and response to alectinib with a 4-year follow-up.

The prevalence of Anaplastic Lymphoma Kinase gene (ALK) fusion is about 5% among patients with lung adenocarcinoma, underscoring the importance of pinpointing distinct fusion variants for optimizing treatment approaches. This is the first reported case of a 74-year-old female with stage IV lung adenocarcinoma, featuring a novel Kinesin Family Member 13A (KIF13A)-ALK fusion, identified via next-generation sequencing (NGS) and confirmed with fluorescence in situ hybridization (FISH). Initially undergoing chemotherapy and then crizotinib, she achieved a partial response (PR) before progressing with multiple bone metastases. However, subsequent treatment with alectinib as a third-line option yielded positive results. A stable disease state persisted for an impressive 31 months of progression-free survival (PFS), accompanied by minimal toxicity symptoms. Up until now, a remarkable near 4-year span of overall survival (OS) has been consistently observed and monitored. This report of a KIF13A-ALK fusion case benefit significantly from alectinib with extensive follow-up. The case diversifies the array of ALK fusion partners and holds clinical relevance in refining therapeutic choices for KIF13A-ALK fusion-associated lung cancer.

Comparative Analysis on the Effect of Surface Reflectance for Laser 3D Scanner Calibrator.

The calibrator is one of the most important factors in the calibration of various laser 3D scanning instruments. The requirements for the diffuse reflection surface are emphasized in many national standards. In this study, spherical calibrator and plane calibrator comparative measurement experiments were carried out. The black ceramic standard sphere, white ceramic standard sphere, metal standard sphere, metal standard plane, and white ceramic standard plane were used to test the laser 3D scanner. In the spherical calibrator comparative measurement experiments, the results indicate that the RMS of the white ceramic spherical calibrator with a reflectance of approximately 60% is 10 times that of the metal spherical calibrator with the reflectance of approximately 15%, and the RMS of the black ceramic spherical calibrator with reflectance of approximately 11% is of the same order as the metal spherical calibrator. In the plane calibrators comparative measurement experiments, the RMS of the flatness measurement is 0.077 mm for the metal plane calibrator with a reflectance of 15%, and 2.915 mm for ceramic plane calibrator with a reflectance of 60%. The results show that when the optimal measurement distance and incident angle are selected, the reflectance of the calibrator has a great effect on the measurement results, regardless of the outlines or profiles. Based on the experiments, it is recommended to use the spherical calibrator or the standard plane with a reflectance of around 18% as the standard, which can obtain reasonable results. In addition, it is necessary to clearly provide the material category and surface reflectance information of the standard when calibrating the scanner according to the measurement standard.

Identification of novel transcription factor-microRNA-mRNA co-regulatory networks in pulmonary large-cell neuroendocrine carcinoma.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare neuroendocrine neoplasm. Previous studies have shown that microRNAs (miRNAs) are widely involved in tumor regulation through targeting critical genes. However, it is unclear which miRNAs play vital roles in the pathogenesis of LCNEC, and how they interact with transcription factors (TFs) to regulate cancer-related genes. METHODS: To determine the novel TF-miRNA-target gene feed-forward loop (FFL) model of LCNEC, we integrated multi-omics data from Gene Expression Omnibus (GEO), Transcriptional Regulatory Relationships Unraveled by Sentence-Based Text Mining (TRRUST), Transcriptional Regulatory Element Database (TRED), and The experimentally validated microRNA-target interactions database (miRTarBase database). First, expression profile datasets for mRNAs (GSE1037) and miRNAs (GSE19945) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. The target genes of the FFL were obtained from the miRTarBase database, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed on the target genes. Then, we screened for key miRNAs in the FFL and performed gene regulatory network analysis based on key miRNAs. Finally, the TF-miRNA-target gene FFLs were constructed by the hypergeometric test. RESULTS: A total of 343 DEGs and 60 DEMs were identified in LCNEC tissues compared to normal tissues, including 210 down-regulated and 133 up-regulated genes, and 29 down-regulated and 31 up-regulated miRNAs. Finally, the regulatory network of TF-miRNA-target gene was established. The key regulatory network modules included ETS1-miR195-CD36, TAOK1-miR7-1-3P-GRIA1, E2F3-miR195-CD36, and TEAD1-miR30A-CTHRC1. CONCLUSIONS: We constructed the TF-miRNA-target gene regulatory network, which is helpful for understanding the complex LCNEC regulatory mechanisms.

[Radioactive seed implantation for the treatment of mediastinal malignant tumors and lymph node metastases in 43 cases].

BACKGROUND AND OBJECTIVE: The locations of mediastinal malignant tumor lesions are deep and occult, and are close to the pericardium, trachea, or major vessels. Therefore, the possibility of surgical resection is slim, and cryoablation and thermal ablation are restricted. In current study, image and life quality data were compared before and after 125I seeding therapy to investigate its safety and clinical effects. METHODS: From July 2010 to July 2011, a 43-patient follow-up of pathologically confirmed cancers, including 21 cases of primary mediastinal squamous lung cancer, 9 cases of primary esophagus cancer, and 13 cases of lymph node metastases were completed. Among these, 18 cases presented with tracheal stenosis >50%, 9 cases had esophageal obstruction, and 9 cases had superior vena cava reflux disorder. Each lesion was implanted with 10 to 60 pieces of 125I particles, with an average of 30.79±14.23. CT data at 2, 4, 6, and 12 months after therapy were obtained to evaluate the local lesion outcome. The quality of life of the patients as well as survival data was also recorded. RESULTS: The overall success rate of the operation was 100%. The longest time of follow-up was 12 months. At 6 months, 37 patients were alive, and the half-year survival rate was 85.0%. In terms of local lesions, 30 cases of PR and 7 cases of NC were found. The clinical effective rate was 81.08%, and the clinical beneficial rate was 100%. At 12 months after therapy, 31 patients were alive, and the one-year survival rate was 60.5%. In terms of local lesions, 16 cases of CR, 7 cases of PR, 2 cases of NC, and 6 cases of PD were found. The clinical effective rate was 74.19%, and the clinical beneficial rate was 80.65%. The KPS score increased after the treatment (P=0.000). Three cases of pneumothorax presented after treatment, and no severe complications, such as vessel, trachea, recurrent laryngeal nerve, or pericardiocentesis injuries, were found. CONCLUSIONS: Radiation seed implantation in mediastinal malignant tumors is a relatively safe technique with high success rate, considerable efficacy, and clear clinical value in advanced cancer treatment.

Non-mitogenic acidic fibroblast growth factor reduces intestinal dysfunction induced by ischemia and reperfusion injury in rats.

BACKGROUND: Acidic fibroblast growth factor (aFGF) has potentially therapeutic uses in some diseases, but the mitogenic activity of aFGF has been found to contribute to several human pathologies, so the extensive applications of wild-type aFGF have been limited. The purpose of the present study was to explore the effects and mechanisms of wild-type (aFGF) and non-mitogenic aFGF on gut ischemia-reperfusion injury in rats. METHODS: Rat intestinal ischemia-reperfusion injury (I/R) was produced by clamping the superior mesenteric artery (SMA) for 45 min followed by reperfusion. One hundred and fourteen rats were randomly divided into four groups: sham operation (group C, n = 6), intestinal I/R + 0.1 mL saline (group S, n = 36), intestinal I/R + 4 microg/0.1 mL wild-type aFGF (group W, n = 36) and intestinal I/R + 4 microg/0.1 mL modified aFGF (i.e. non-mitogenic aFGF; group M, n = 36). According to different periods after reperfusion, groups S, W and M were further divided into 0.5-, 1-, 2-, 6-, 12- and 24-h subgroups. The contents of D-lactate and nitrite/nitrate were determined, the changes of intestinal histology were analyzed, the protein expressions of caspase-3, extracellular signal-regulated kinase (ERK)1/2, and p38 were detected by western blot, and apoptotic cells were examined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUDP-biotin nick end labeling (TUNEL) assay at 0.5, 1, 2, 6, 12 and 24 h after I/R, respectively. RESULTS: Compared with rats in group S, intestinal histological damage, apoptotic index, d-lactate content and nitrite/nitrate level all decreased significantly in group W and group M rats. However, there was no difference between rats treated with wild-type aFGF and those with non-mitogenic aFGF. The protein expression of caspase-3, ERK1/2, and p38 in saline-treated rats was higher than those in aFGF-treated rats. CONCLUSIONS: Both types of aFGF had protective effects on gut I/R and there was no significant difference between the two aFGF. The protective effects of aFGF may come from the non-mitogenic activity rather than the mitogenic activity of aFGF in tissue repair, indicating a potentially clinical use for the non-mitogenic effects of aFGF in preventing visceral organ injury triggered by I/R injury in the future.

Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages.

Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were co-cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.

[Cellular phenotype conversion induced by co-culture of human mesenchymal stem cells cocultured with human sweat gland cells].

OBJECTIVE: To investigate the cellular phenotype conversion during human mesenchymal stem cells (hMSCs) cocultured with injured human sweat gland cells (hSGCs) in vitro. METHODS: HMSCs and hSGCs were isolated and cultured and expanded respectively. The antigens expression of hMSCs and hSGCs were detected by two-steps immunocytochemistry. HMSCs were labeled with BrdU. The hSGCs were heat-shocked at 47 degrees C for 40 min when they reached 70% confluency, then cooled for 1-2 h at 37 degrees C and (1 - 2) x 10(5) BrdU-labeled hMSCs were added before incubation for up to 2 weeks. The cocultures were observed by phase contrast microscopy and detected by double-staining immunocytochemistry using CEA and BrdU as primary antibodies. RESULTS: The cultured hMSCs and hSGCs were clonogenic growth. HMSCs were positive for anti-CD44 and anti-CD105 staining and negative for anti-CD34 and anti-CEA staining. HSGCs express CK7, CK18, CK19 and CEA. The positive rate of BrdU labeled-hMSCs was 90%. The majority of hSGCs lost cell-cell contact after heat-shock. 2 weeks after cocultured, some cocultured cells were positive for both anti-CEA and anti-BrdU staining and some cocultures had more than two nuclei which stained with two different colors by double-staining immunocytochemistry. Statistic results showed 1%-5% of the hMSCs added to the coculture system were recovered as double-staining cells expressing BrdU and CEA while only 0.01%-0.05% cells stained with two different colors in nuclei. The multi-nucleated cells were wide and flatten. CONCLUSION: HMSCs could differentiate into hSGCs in vitro under injured microenvironment. The mechanisms of which may be that hMSCs differentiate into hSGCs directly or by cell fusion, even nucleus fusion.