APOBEC mutagenesis, kataegis, chromothripsis in EGFR-mutant osimertinib-resistant lung adenocarcinomas.

BACKGROUND: Studies of targeted therapy resistance in lung cancer have primarily focused on single-gene alterations. Based on prior work implicating apolipoprotein b mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, we hypothesized that mutational signature analysis may help elucidate acquired resistance to targeted therapies. PATIENTS AND METHODS: APOBEC mutational signatures derived from an Food and Drug Administration-cleared multigene panel [Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT)] using the Signature Multivariate Analysis (SigMA) algorithm were validated against the gold standard of mutational signatures derived from whole-exome sequencing. Mutational signatures were decomposed in 3276 unique lung adenocarcinomas (LUADs), including 93 paired osimertinib-naïve and -resistant EGFR-mutant tumors. Associations between APOBEC and mechanisms of resistance to osimertinib were investigated. Whole-genome sequencing was carried out on available EGFR-mutant lung cancer samples (10 paired, 17 unpaired) to investigate large-scale genomic alterations potentially contributing to osimertinib resistance. RESULTS: APOBEC mutational signatures were more frequent in receptor tyrosine kinase (RTK)-driven lung cancers (EGFR, ALK, RET, and ROS1; 25%) compared to LUADs at large (20%, P < 0.001); across all subtypes, APOBEC mutational signatures were enriched in subclonal mutations (P < 0.001). In EGFR-mutant lung cancers, osimertinib-resistant samples more frequently displayed an APOBEC-dominant mutational signature compared to osimertinib-naïve samples (28% versus 14%, P = 0.03). Specifically, mutations detected in osimertinib-resistant tumors but not in pre-treatment samples significantly more frequently displayed an APOBEC-dominant mutational signature (44% versus 23%, P < 0.001). EGFR-mutant samples with APOBEC-dominant signatures had enrichment of large-scale genomic rearrangements (P = 0.01) and kataegis (P = 0.03) in areas of APOBEC mutagenesis. CONCLUSIONS: APOBEC mutational signatures are frequent in RTK-driven LUADs and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer. APOBEC mutational signature enrichment in subclonal mutations, private mutations acquired after osimertinib treatment, and areas of large-scale genomic rearrangements highlights a potentially fundamental role for APOBEC mutagenesis in the development of resistance to targeted therapies, which may be potentially exploited to overcome such resistance.

A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

A repeating fast radio burst associated with a persistent radio source.

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

[Fat1 inhibits cell proliferation via ERK signaling pathway in esophageal squamous cell carcinoma].

Objective: To clarify the mechanism of Fat1 on the proliferation of esophageal squamous cell carcinoma (ESCC). Methods: KYSE450 cells were transfected with Plko.1-puro-GFP-shRNA-Fat1 plasmid and real time polymerase chain reaction (PCR) was used to verify the efficiency of Fat1 knockdown. The effects of Fat1 and extracellular regulated protein kinase (ERK) pathway inhibitor U0126 on the proliferation of ESCC cells were detected by methyl thiazolyl tetrazolium (MTT). Colony formation assay was used to detect the colony formation ability. Cell cycle was detected by live cell imaging. Western blot was used to observe the level of target protein. Mouse xenograft assay was applied to detect the effect of Fat1 knockdown on KYSE450 cell tumor growth. Immunohistochemistry was used to detect the expressions of related proteins in tumor sections. Results: The efficiency of Fat1 knockdown was (77.1±6.9)% in Fat1 sh1 group and (77.7±7.1)% in Fat1sh2 group. Compared with the control group, the cell proliferation and the expression of p-ERK1/2 were significantly increased in Fat1 sh1 and Fat1sh2 group (P<0.05). After U0126 treatment, the effect of Fat1 knockdown on the proliferation of KYSE450 cells disappeared, and the expression of p-ERK1/2 in KYSE450 cells decreased to a level similar to that in the control group. The number of cell clones in the control group was (72±8), lower than (155±28) and (193±9) in the Fat1sh1 and Fat1sh2 groups, respectively (P<0.05). In KYSE450 cell, division time was shortened from 1 622±32 min in control group to 1 408±29 min in Fat1 sh1 group, the difference was statistically significant (P<0.05). Compared with the control group, the tumor volume of Fat1 knockdown group increased significantly. The tumor weight of control group and Fat1 knockdown group were (0.224±0.028) g and (1.532±0.196) g, respectively, at 4 weeks after inoculation, and the difference was statistically significant (P<0.05). Conclusion: Fat1 inhibits cell proliferation via ERK signaling in ESCC.

Carbachol alleviates myocardial injury in septic rats through PI3K/AKT signaling pathway.

OBJECTIVE: To explore the effect of carbachol on myocardial injury in septic rats, and to further study its influence on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. MATERIALS AND METHODS: A total of 48 healthy male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=16), and carbachol group (n=16). The rat model of sepsis was established via cecal ligation and puncture. Carbachol was intraperitoneally injected (10 µg/kg) immediately after operation in carbachol group, and no cecal ligation was performed in sham group. At 48 h after operation, the survival rate of rats in each group was recorded, the activity of plasma creatine kinase-MB (CK-MB) was detected, and the cardiac function in each group was determined. Moreover, the heart was isolated, and the myocardial tissues were taken to detect the apoptosis level using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) apoptosis kit. The content of inflammatory factors in myocardial tissues was determined using enzyme-linked immunosorbent assay (ELISA) kits, and the expression levels of apoptosis-related proteins and the PI3K/AKT signaling pathway-related proteins were detected via Western blotting. RESULTS: Carbachol could significantly raise the survival rate of septic rats (p<0.01), remarkably decrease the activity of CK-MB (p<0.01), markedly reduce the left ventricular internal diameter at end-systole (LVIDs), and markedly increase the left ventricular ejection fraction (LVEF, %) and left ventricular fractional shortening (LVFS, %). Besides, carbachol could evidently lower the apoptosis level of myocardial cells of septic rats (p<0.01), reduce the content of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 (p<0.01), notably decrease the expression of Caspase-3 in myocardial tissues (p<0.01), remarkably increase the expression of Bcl-2/Bax (p<0.01), and distinctly inhibit the expressions of phosphorylated (p-)PI3K, p-AKT, Nod-like receptor protein 3 (NLRP3), and Caspase-1 (p<0.01). CONCLUSIONS: Carbachol can reduce the release of inflammatory factors in myocardial cells, the expression of apoptotic proteins and the apoptosis of myocardial cells, and improve the cardiac function and survival rate of septic rats by inhibiting the PI3K/AKT signaling pathway.

[Simultaneous treatments in patients with severe carotid artery stenosis and coronary artery disease].

Objective: To implement simultaneous treatments in patients with severe carotid artery stenosis and coronary artery disease (CAD), we sought to investigate its efficacy of reducing perioperative major adverse cardiac and cerebrovascular event (MACCE). Methods: Brain-and-Heart treatment team in Peking University International Hospital performed hybrid Digital Substraction Angiography (DSA) of carotid artery and coronary artery for 37 patients meeting the group criterion from September 2017 to February 2019.Twelve patients were diagnosed and received simultaneous treatments of severe carotid artery stenosis and coronary artery disease after hybrid DSA. We conducted the retrospective study and made analysis of these patients. Results: The diagnosis rate by simultaneous treatmentsin patients with carotid artery stenosis and coronary artery disease is 59.5% (22/37), the rate of severe carotid artery stenosis or multi-vessel CAD is 77.3% (17/22).The rate of severe carotid artery stenosis with CAD is 54.5% (12/22), therate of simultaneous treatmentsis 83.3%(10/12). Nine patients post-operative symptoms release, one patient with ischemic stroke after CABG, and two patients of medical therapy with stable symptoms. Conclusion: Simultaneous treatments in patients with severe carotid artery stenosis and coronary artery disease not only reveal the positive correlation between carotid stenosis and CAD, but also accurately evaluate severity degree or rapidly formulate scheme and reduce MACCE.

[The prognostic value of the international prognostic index, the national comprehensive cancer network IPI and the age-adjusted IPI in diffuse large B cell lymphoma].

Objective: To explore the prognostic value of the international prognostic index (IPI), the national comprehensive cancer network IPI(NCCN-IPI)and the age-adjusted IPI (aa-IPI) in diffuse large B cell lymphoma. Methods: A total of 311 patients with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2003 to 2012 in Nanfang hospital were included. All patients were divided into CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) and R-CHOP (rituximab, CHOP) groups. Survival analysis was compared among IPI, NCCN-IPI and aa-IPI models. Discrimination of three different prognostic models was assessed using the Harrell's C statistic. Results: A total of 311 patients were analyzed. Among them, 128 patients were treated with CHOP regimen and other 183 patients were treated with R-CHOP regimen. In CHOP groups, both NCCN-IPI (5-year OS: 59.7% vs 26.8%, P<0.001) and aa-IPI (5-year OS: 71.0% vs 25.0%, P<0.001) showed better risk stratification for low-intermediate and high-intermediate group than the IPI (5-year OS: 47.6% vs 36.6%, P=0.003). However, in the patients treated with R-CHOP, NCCN-IPI showed better risk stratification in low, low-intermediate, high-intermediate groups (5-year OS: 96.0% vs 83.0% vs 66.5%, P=0.009). According to the Harrell's C statistic, C-index of IPI, NCCN-IPI and aa-IPI for overall survival (OS) were 0.546, 0.667, 0.698 in CHOP group and 0.611,0.654, 0.695 in R-CHOP group respectively. In patients younger than 60 years old, C-index of IPI, NCCN-IPI and aa-IPI for OS were 0.534, 0.675, 0.698 in CHOP group and 0.584, 0.648, 0.695 in R-CHOP respectively. Conclusion: The NCCN-IPI is more powerful than IPI and aa-IPI in DLBCL patients receiving R-CHOP. aa-IPI is a preferable model in predicting prognosis than IPI and NCCN-IPI in anthracycline-based chemotherapy without rituximab.

[Adenocarcinoma in a Meckel's diverticulum with multiple liver metastases and gastrointestinal hemorrhage: a case report].

Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract, affecting approximately 2% of the population. It is a true diverticulum occurring on the anti-mesenteric border of the distalileum, typically within 100 cm of the ileo-caecal valve. Neoplasms arising in Meckel's diverticula are uncommon, and those reported in the literature are mainly carcinoid tumors, followed by gastrointestinal stromal tumors (GIST) and benign leiomyomas. Adenocarcinomas are extremely rare. Tumors in Meckel's present non-specifically with gastrointestinal complaints, such as bleeding, obstruction, inflammation or perforation. The suspicion of a Meckel's tumor is often not thought of at the initial. In this article we describe a 57-year-old woman who presented with massive rectal bleeding and severe anemia, later found to be caused by a adenocarcinoma arising from Meckel's diverticulum. The tumor was unfortunately highly aggressive. Multiple liver metastases had already existed when we discovered the primary mass. Later we performed a partial resection of the ileumto cease the bleeding. Meckel's diverticulum and the tumor were resected simultaneously. The pathological diagnosis confirmed adenocarcinoma arising from the Meckel's diverticulum. The final stage was pT4NxM1, stage IV according to the Union for International Cancer Control (UICC) classification. After operation we gave the patient first-line, mFOLFOX6 chemotherapy, but it turned out to be not effective. Rapid progress of the liver metastases and suspicion of multiple lung metastasis in short time after therapy indicated a bad outcome. We believe this is the first case of adenocarcinoma in a Meckel's diverticulum to be reported in domestic literature. The diagnosis of Meckel's tumor should be considered as inpatients'acute gastrointestinal complaints; when found incidentally at laparotomy, it should be carefully examined for any gross abnormality and resection should be considered.

Research on the correlation of diabetes mellitus complicated with osteoporosis with lipid metabolism, adipokines and inflammatory factors and its regression analysis.

OBJECTIVE: To investigate the correlation of type 2 diabetes mellitus (DM) complicated with osteoporosis with lipid metabolism, adipokines and inflammatory factors, and to define the risk factors via the multivariate regression analysis. PATIENTS AND METHODS: A total of 80 patients with DM admitted into our hospital from November 2015 to November 2016 were enrolled, including 40 patients complicated with osteoporosis and 40 patients not complicated with osteoporosis. The levels of blood lipid, adipokines and inflammatory factors were compared; the correlations between bone mineral density (BMD) and total cholesterol (TC), adiponectin and tumor necrosis factor-α (TNF-α) were analyzed; and multivariate Logistic regression analysis was performed for osteoporosis, hyperlipidemia, abnormal adipokine levels and body's inflammatory response. RESULTS: The levels of serum lipid indexes, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), in patients without complicating osteoporosis were significantly lower than those in patients complicated with osteoporosis. The level of high-density lipoprotein cholesterol (HDL-C) was significantly higher than that in patients complicated with osteoporosis. The levels of adipokines, adiponectin and visfatin, in patients without complicating osteoporosis were significantly lower than those in patients complicated with osteoporosis. The levels of inflammatory factors, TNF-α, interleukin-6 (IL-6) and C-reactive protein (CRP), in patients without complicating osteoporosis were significantly lower than those in patients complicated with osteoporosis. There were negative correlations between BMD and TC, adiponectin and TNF-α. Abnormal blood lipid, abnormal adipokine levels and elevated inflammatory factor levels were independent risk factors for osteoporosis. CONCLUSIONS: Enhanced inflammatory response, abnormal blood lipid metabolism and abnormal changes in adipokines may increase the risk of osteoporosis in patients with diabetes mellitus.

[Immediate reconstruction of facial nerve defect using cable grafting of the greater auricualr nerve after parotid cancer resection].

Objective:To evaluate the feasibility of immediate reconstruction of facial nerve defect by using cable grafting of the greater auricular nerve after parotid cancer resection.Method:Clinical data of 11 patients suffering from parotid cancer was reviewed.9 cases were diagnosed as mucoepidermoid carcinoma and 2 cases were adenoid cystic carcinoma. Total parotidectomy and elective neck dissection were performed before cable grafting of the greater auricular nerve was interposed between stumps of facial nerve trunk and its branches. The facial nerve electromyogram and symmetry of mimetic musculature were evaluated. The House Brackmann (HB) grading system was used to assess the functional outcome of facial nerve rehabilitation. 8 patients received 50-65 Gy postoperative radiotherapy. The follow-up time ranged from 8 months to 36 months with the mean time of 12 months.Result:At all function oriented facial nerve reconstructed region, satisfactory orbicularis oculi muscle function in 7 patients was achieved (7/7); 5 patients obtained seeable and almost symmetric frowning (5/7); 9 patients obtained obvious nasolabial groove and satisfactory rest symmetry of the mouth corners (9/9); 4 patients got better facial nerve function restoration when it was 3 months after radiotherapy. Nine patients got HB grade Ⅱ, and 2 patients got HB grade Ⅲ facial nerve function restoration. Facial nerve electromyogram revealed weaker amplitude nerve conduction in 9 patients of HB grade Ⅱ than the conduction at its corresponding normal side.Conclusion:Cable grafting of the greater auricular nerve is a feasible candidate for the immediate reconstruction of facial nerve defect. Free nerve transplantation is probably not a contraindication for postoperative radiotherapy in the parotid region.

Serum microRNA-135a downregulation as a prognostic marker of non-small cell lung cancer.

Abnormal expression of microRNA-135a (miR-135a) is closely associated with oncogenesis. However, the relationship between serum miR-135a levels and the clinical parameters and prognosis of non-small cell lung cancer (NSCLC) remain unclear. The study aimed to investigate the clinical significance of serum miR-135a expression in patients with NSCLC. miR-135a expression was analyzed by real-time PCR and its correlation with NSCLC was determined by various statistical methods for 104 NSCLC patients and 40 healthy volunteers. The serum miR-135a level was significantly lower in NSCLC patients than in healthy control subjects (P < 0.01), and was closely related to distant metastasis (P < 0.015), lymphatic metastasis (P = 0.000), TNM (tumor node metastasis) stage (P = 0.001), and pathological stage (P = 0.021) of NSCLC. The five year overall survival was significantly lower in patients with low miR-135a expression than that in patients with high serum miR-135a levels (P = 0.010). Multivariate analysis showed that serum miR-135a level could be treated as an independent risk factor for NSCLC prognosis (P = 0.011). In conclusion, the serum miR-135a level was downregulated in NSCLC patients, and was associated with poor prognosis. Additionally, it can be used as a biomarker for NSCLC prognosis.

[Leukocyte chemotactic factor 2 associated renal amyloidosis: one case report].

Here we report a case of leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis (ALect2) in our hospital. A 68-year-old male presented with massive proteinuria, hematuria, and hypertension. The renal function was normal. Light microscopy of the renal biopsy revealed glomeruli ,interstitium and arteriole with amorphous pink acellular deposits on hematoxylin and eosin stain. The deposits were strongly stained for Congo red and presented apple green birefringence viewed with polarized light. Ultrastructural examination revealed nonbranching fibrils (diameters ranging from 8 nm to 12 nm) distributed in glomerular mesangium, subendothelia and renal interstitium. Immunohistochemistry and immunoelectron microscopy using a polyclonal anti-LECT2 antibody showed that the amyloid deposits and the fibrils were stained positively. ALect2 presented proteinuria,with or without acute/chronic renal dysfunction clinically and all compartments of the kidney were involved.

Synthesis of boronate-silica hybrid affinity monolith via a one-pot process for specific capture of glycoproteins at neutral conditions.

In this study, a boronate-silica hybrid affinity monolith was prepared for specific capture of glycoproteins at neutral pH condition. The monolith was synthesized via a facile one-pot procedure in a stainless steel column by concurrently mixing hydrolyzed alkoxysilanes tetramethoxysilane and vinyltrimethoxysilane, organic monomer 3-acrylamidophenylboronic acid and initiator 2,2'-azobisisobutyronitrile together. The polycondensation of alkoxysilanes and copolymerization of organic monomer and vinyl-silica monolith were carried out successively by reacting at different temperatures. After optimizing the preparation conditions, the resulting hybrid affinity monolith was systematically characterized and exhibited excellent affinity to both cis-diol-containing small molecules and glycoproteins at neutral and physiological pH, including adenosine, horseradish peroxidase, transferrin and ovalbumin. The binding capacity of ovalbumin on monolith was measured to be 2.5 mg g(-1) at pH 7.0. Furthermore, the hybrid affinity monolith was applied to the separation of transferrin from bovine serum sample at a physiological condition. Good repeatability was obtained and the relative standard deviations of retention time were 1.15 and 4.77 % (n = 5) for run-to-run and column-to-column, respectively.

Serum overexpression of microRNA-10b in patients with bone metastatic primary breast cancer.

OBJECTIVE: Bone metastasis is a major complication of advanced breast cancer. The present prospective case-control study investigated the involvement of microRNA (miR)-10b in the development of bone metastasis arising from primary breast carcinoma. METHODS: Serum miR-10b concentrations were determined by quantitative real-time reverse transcription-polymerase chain reaction in 122 patients with breast cancer, with or without bone metastases, and 59 age-matched healthy control subjects. RESULTS: Serum miR-10b concentrations were significantly higher in patients with bone metastases than in patients without bone metastases or control subjects. Serum miR-10b had an area under the receiver operating characteristic curve for the presence of bone metastases of 0.769, with 64.8% sensitivity and 69.5% specificity. CONCLUSION: These results suggest that serum miR-10b may be a useful biomarker for the identification of bone metastatic breast cancer.

Lung resistance protein and multidrug resistance protein in non-small cell lung cancer and their clinical significance.

This study examined lung resistance protein (LRP) and multidrug resistance protein (MRP) in lung tumour tissue from 92 patients with non-small cell lung cancer (NSCLC) and normal lung tissue from 20 patients with benign lung tumours. The rates for LRP- and MRP-positive tumours among the NSCLC cases were 54% and 59%, respectively, and their combined positive rate was 45%. These rates were significantly higher than in normal lung tissue. The rates of LRP- and MRP-positive tumours were significantly higher among cases of adenocarcinoma than in cases of squamous cell carcinoma, and in highly differentiated tumours compared with tumours of low or moderate differentiation. There was a significant association between LRP- and MRP-positive tumours and a decrease in overall survival. In conclusion, LRP and MRP play a role in multidrug resistance in NSCLC and are related to prognosis in patients with NSCLC.

Microvessel density and expression of thrombospondin-1 in non-small cell lung cancer and their correlation with clinicopathological features.

Microvessel density and thrombospondin-1 (TSP-1) expression were analysed in 42 non-small cell lung cancer (NSCLC) specimens and 40 normal lung tissue specimens using immunohistochemistry. Microvessel density was significantly higher and TSP-1 expression significantly lower in NSCLC tissue compared with normal tissue. Significantly lower levels of TSP-1 expression and higher microvessel densities were found in late-stage NSCLC compared with early-stage NSCLC, and in those with lymph node metastasis compared with those without metastasis. A statistically significant inverse correlation was observed between TSP-1 expression and microvessel density in squamous cell carcinoma but not in adenocarcinoma. These results suggest a close relationship between microvessel density and NSCLC tumour progress, and that a high expression of TSP-1 may play an important role in inhibiting tumour occurrence and development. The lack of correlation between microvessel density and TSP-1 expression in adenocarcinoma suggests that the mechanism of tumour inhibition by TSP-1 varies according to histological type.