Small nodules (≤ 6 mm in diameter) of multiple primary lung cancers: prevalence and management.

BACKGROUND: Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth. METHODS: This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. RESULTS: There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08-1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94-6.30) predicted small nodule interval growth. CONCLUSION: We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.

Ordered mesoporous silica cubic particles decorated with silver nanoparticles: a highly active and recyclable heterogeneous catalyst for the reduction of 4-nitrophenol.

In this work, using a modified Stöber process, we synthesized ordered mesoporous silica cubic particles (OMS-C) and prepared a nanocatalyst (Ag-OMS-C) based on OMS-C with a high surface area via an in situ auto-reduction strategy. The as-prepared Ag-OMS-C nanocomposites demonstrated open mesopores (3.51 nm), a large specific surface area (540 m2 g-1) and a high pore volume (0.88 cm3 g-1). The catalytic reduction of 4-nitrophenol (4-NP) over the Ag-OMS-C nanocatalyst was almost complete within 150 s without stirring and the rate constant k (30 × 10-3 s-1) is much higher than those of other substrate-supported Ag nanocatalysts. Moreover, the Ag-OMS-C nanocomposites hold a stable catalytic efficiency over five reaction cycles. The results indicate that the Ag-OMS-C nanocatalyst exhibited high catalytic activity and good reusability toward the reduction of 4-NP, which might be attributed to the large specific surface area, the pore structure of the nanocatalyst, as well as the synergistic effect between OMS-C and AgNPs.

Fluorescent assay for alkaline phosphatase activity based on graphene oxide integrating with λ exonuclease.

A novel fluorescence turn-on strategy for the alkaline phosphatase (ALP) assay is developed based on the preferential binding of graphene oxide (GO) to single-stranded DNA (ssDNA) over double-stranded DNA (dsDNA) coupled with λ exonuclease (λ exo) cleavage. Specifically, in the absence of ALP, the substrate-dsDNA constructed by one oligonucleotide with a fluorophore at the 3'-end (F-DNA) and its complementary sequence modified with a 5'-phosphoryl termini (p-DNA), is promptly cleaved by λ exo, and the resulting F-DNA is adsorbed on GO surface, allowing fluorescence quenching. Whereas the introduction of ALP leads to the hydrolysis of the P-DNA, and the yielding 5'-hydroxyl end product hampers the λ exo cleavage, inducing significant fluorescence enhancement due to the weak binding of dsDNA with GO. Under the optimized conditions, the approach exhibits high sensitivity and specificity to ALP with a detection limit of 0.19 U/L, and the determination of ALP in spiked human serum samples has also been realized. Notably, this new approach not only provides a novel and sensitive platform for the ALP activity detection but also promotes the exploitation of the GO-based biosensing for the detection of the protein with no specific binding element, and thus extending the GO-based sensing applications into a new field.

A fluorescent aptasensor using double-stranded DNA/graphene oxide as the indicator probe.

We developed a fluorescent aptasensor based on the making use of double-stranded DNA (dsDNA)/graphene oxide (GO) as the signal probe and the activities of exonuclease I (Exo I). This method takes advantage of the stronger affinity of the aptamer to its target rather than to its complementary sequence (competitor), and the different interaction intensity of dsDNA, mononucleotides with GO. Specifically, in the absence of target, the competitor hybridizes with the aptamer, preventing the digestion of the competitor by Exo I, and thus the formed dsDNA is adsorbed on GO surface, allowing fluorescence quenching. When the target is introduced, the aptamer preferentially binds with its target. Thereby, the corresponding nuclease reaction takes place, and slight fluorescence change is obtained after the introduction of GO due to the weak affinity of the generated mononucleotides to GO. Adenosine (AD) was chosen as a model system and tested in detail. Under the optimized conditions, smaller dissociation constant (Kd, 311.0 µM) and lower detection limit (LOD, 3.1 µM) were obtained in contrast with traditional dye-labeled aptamer/GO based platform (Kd=688.8 µM, LOD=21.2 µM). Satisfying results were still obtained in the evaluation of the specificity and the detection of AD in human serum, making it a promising tool for the diagnosis of AD-relevant diseases. Moreover, we demonstrated the effect of the competitor on the LOD, and the results reveal that the sensitivity could be enhanced by using the rational competitor. The present design not only constructs a label-free aptamer based platform but also extends the application of dsDNA/GO complex in biochemical and biomedical studies.

Efficient labeling in vitro with non-ionic gadolinium magnetic resonance imaging contrast agent and fluorescent transfection agent in bone marrow stromal cells of neonatal rats.

Although studies have been undertaken on gadolinium labeling-based molecular imaging in magnetic resonance imaging (MRI), the use of non-ionic gadolinium in the tracking of stem cells remains uncommon. To investigate the efficiency in tracking of stem cells with non-ionic gadolinium as an MRI contrast agent, a rhodamine-conjugated fluorescent reagent was used to label bone marrow stromal cells (BMSCs) of neonatal rats in vitro, and MRI scanning was undertaken. The fluorescent-conjugated cell uptake reagents were able to deliver gadodiamide into BMSCs, and cell uptake was verified using flow cytometry. In addition, the labeled stem cells with paramagnetic contrast medium remained detectable by an MRI monitor for a minimum of 28 days. The present study suggested that this method can be applied efficiently and safely for the labeling and tracking of bone marrow stromal cells in neonatal rats.

Influence of three anionic gemini surfactants with different chain lengths on the optical properties of a cationic polyfluorene.

The effects of three sulfonate gemini surfactants with different hydrophobic chain lengths (8, 10, and 12 carbon atoms) on the optical properties of a fluorene-based conjugated cationic polymer poly{[9,9-bis(6'-N,N,N-trimethylammonium)hexyl]-fluorene-phenylene} bromide (PFP) dissolved in DMSO-water solutions (4% v/v) or water were investigated, respectively. When surfactants with PFP dissolved in DMSO-water solutions (4% v/v) are incubated, a decrease in photoluminescence (PL) intensity and a red shift of emission maxima are obtained at low surfactant concentrations. Intriguingly, two different Stern-Volmer constants (KSV1 and KSV2) are obtained and analyzed in detail for the first time. Further increase in the surfactant concentration enhanced PL intensity, and distinct blue shifts of both absorption and emission maxima are observed. Importantly, the turning point between the emission quenching and enhancement is closely related to the hydrophobic chain length: the longer the chain length, the earlier the turning point appears. Simulation studies provide strong evidence to explain these phenomena. Surface tension measurements show more insight on the interactions between PFP and surfactant. On the contrary, no emission quenching is obtained at low surfactant concentrations for PFP dissolved in water.

Correlations between tumor stroma characters and dynamic enhanced MDCT findings in nodular pulmonary adenocarcinoma.

OBJECTIVE: This study aimed to evaluate correlations between tumor stroma characters and dynamic contrast-enhanced computed tomographic (CT) findings in nodular pulmonary adenocarcinoma. METHODS: Thirty-three patients with nodular pulmonary adenocarcinoma underwent dynamic contrast-enhancement CT scan before surgery. CT findings include wash-in, wash-out, and distribution of enhancement. The proportion of invasive and noninvasive stroma in tumor was calculated. RESULTS: Invasive and noninvasive stroma proportion in tumor was correlated positively with wash-in and wash-out enhancement, respectively. CONCLUSIONS: Tumor stroma proliferation may explain the pathologic basis of CT dynamic enhancement and be a useful prognostic factor of pulmonary adenocarcinoma.

Amplified fluorescent assay of potassium ions using graphene oxide and a conjugated cationic polymer.

We present a low background, highly selective and amplified fluorescent sensor for potassium ions using graphene oxide (GO) and a cationic conjugated polymer (CCP). This method takes advantage of the phenomenon that the addition of CCP cannot release the dye labeled guanine-rich DNA from the GO surface, and the conformational switch of the guanine-rich DNA from random coil to G-quadruplex induced by the target.

Amplified fluorescent sensing of DNA using graphene oxide and a conjugated cationic polymer.

We explore the interactions between a fluorescein (FAM)-labeled single-stranded DNA (P), graphene oxide (GO), and a cationic conjugated polymer, poly [(9,9-bis(6'-N,N,N-trimethylammonium)hexyl)-fluorenylene phenylene dibromide] (PFP). It is found that the fluorescence change of P-GO-PFP system is dependent on the addition order of P and PFP. When adding PFP into P/GO complex, the fluorescence resonance energy transfer (FRET) from PFP to P is inefficient. If P is added to PFP/GO complex, efficient FRET is obtained. This may be attributed to the equal binding ability for P and PFP to GO. The results of time-resolved fluorescence and fluorescence anisotropy support the different fluorescent response under different addition order of P and PFP to GO. Based on the above phenomenon, we demonstrate a method to reduce the high background signal of a traditional PFP-based DNA sensor by introducing GO. In comparison to the use of single PFP, the combination of PFP with GO-based method shows enhanced sensitivity with a detection limit as low as 40 pM for target DNA detection.

Graphene oxide based fluorescent aptasensor for adenosine deaminase detection using adenosine as the substrate.

We present a novel fluorescent aptasensor for simple and accurate detection of adenosine deaminase (ADA) activity and inhibition on the basis of graphene oxide (GO) using adenosine (AD) as the substrate. This aptasensor consists of a dye-labeled single-stranded AD specific aptamer, GO and AD. The fluorescence intensity of the dye-labeled AD specific aptamer is quenched very efficiently by GO as a result of strong π-π stacking interaction and excellent electronic transference of GO. In the presence of AD, the fluorescence of the GO-based probe is recovered since the competitive binding of AD and GO with the dye-labeled aptamer prevents the adsorption of dye-labeled aptamer on GO. When ADA was introduced to this GO-based probe solution, the fluorescence of the probe was quenched owing to ADA can convert AD into inosine which has no affinity to the dye-labeled aptamer, thus allowing quantitative investigation of ADA activity. The as-proposed sensor is highly selective and sensitive for the assay of ADA activity with a detection limit of 0.0129U/mL in clean buffer, which is more than one order of magnitude lower than the previous reports. Meanwhile, a good linear relationship with the correlation coefficient of R=0.9922 was obtained by testing 5% human serum containing a series of concentrations of ADA. Additionally, the inhibition effect of erythro-9-(2-hydroxy-3-nonyl) adenine on ADA activity was investigated in this design. The GO-based fluorescence aptasensor not only provides a simple, cost-effective and sensitive platform for the detection of ADA and its inhibitor but also shows great potential in the diagnosis of ADA-relevant diseases and drug development.

Relationship between peripheral lung cancer and the surrounding bronchi, pulmonary arteries, pulmonary veins: a multidetector CT observation.

AIM: This study aimed to investigate the relationship between peripheral lung cancer and the surrounding pulmonary vessels and bronchi using contrast-enhanced multidetector computed tomography (MDCT) and to analyze associated factors such as pathology types, stage, size, density, and location of peripheral lung cancer. MATERIALS AND METHODS: A total of 93 patients with solitary peripheral lung cancers underwent contrast-enhanced MDCT before thoracotomy were enrolled. Multiplanar reconstruction, maximal intensity projection, and volume rendering were used for demonstrating the patterns of the tumor-bronchi (Br), tumor-pulmonary artery (PA) and tumor-pulmonary vein (PV) relationship, respectively. Five subtypes were identified: Type1 (Br1, PA1 and PV1), Br, PA, or PV was erupted at the edge of nodule; Type2 (Br2, PA2, and PV2), erupted at the center of nodule; Type3 (Br3, PA3 and PV3), penetrated through the nodule; Type4, (Br4, PA4 and PV4), contacting the nodule but stretched or encased; Type5 (Br5, PA5, and PV5), contacting the nodule but smoothly compressed. RESULTS: Both bronchi and PA were interrupted in 70 (Type 1+2); both narrowed in 9 (Type 3+4). The bronchi and PA changes surrounding the lung cancer had positive relations (χ(2)=12.3918, r=0.7524, P<.01). Br1 and PA1 were more often seen in the group of solid, ≥2.0 cm, and Stage II-IV focal lesions, while Br2 and PA2, more often in the group of part-solid, non-solid, <2.0 cm, and Stage I focal lesions. PV2 was more often seen in the part-solid and non-solid focal lesions group, while PV (4+5), more often in solid focal lesions group. CONCLUSION: MDCT can demonstrate and subtype relationships among peripheral lung cancer and the bronchi, pulmonary arteries and pulmonary veins. This can be the basis for further clinical research and differential diagnosis.

[Correlation of early phase contrast enhancement of multi-detector row computed tomography to tumor stroma of nodular solid lung adenocarcinoma].

BACKGROUND & OBJECTIVE: Dynamic enhanced multi-detector row CT (MDCT) has been used in differential diagnosis of pulmonary nodules, but its mechanism was unclear yet. This study was to evaluate the correlations of early phase enhancement of MDCT to proportion and distribution of stroma in solid lung adenocarcinoma. METHODS: A total of 31 patients with lung adenocarcinoma underwent routine contrast-enhanced MDCT. All lesions were solid solitary pulmonary nodules confirmed by pathology. CT observation items included net enhancement and distribution of enhancement. Tumor morphology was observed with HE staining. About 25 fields of view of each specimen at low magnification were scanned to obtain digital data. Semi-auto segmentation software was used to calculate mean stroma proportion. RESULTS: The proportion of invasive stroma in tumors was correlated positively to CT enhancement value (r=0.483, P=0.006). Of the 31 nodules, 18 (58.1%) showed homogenous enhancement, 10 (32.3%) showed peripheral inhomogenous enhancement, 1 (3.2%) showed central inhomogenous enhancement, 1 (3.2%) showed asymmetrical inhomogenous enhancement, 1 (3.2%) showed no enhancement; 18 (58.1%) nodules showed mixed distribution of stroma, 11 (35.5%) showed peripheral distribution, 1 (3.2%) showed central distribution, 1 (3.2%) showed asymmetrical distribution. Most acinar adenocarcinomas had net enhancement of > 20 Hu, which was significantly higher than that of solid adenocarcinomas with mucin subtype (P=0.005). CONCLUSIONS: Extent and pattern of CT enhancement of solid lung adenocarcinoma nodules reflect the proliferation and distribution of stroma, respectively. It is helpful to comprehend some false negative on CT enhancement by adequately understanding of the pathologic features of different subtypes of lung adenocarcinoma.