Solitary plasmacytoma of the left rib misdiagnosed as angina pectoris: A case report.

BACKGROUND: Solitary plasmacytoma in the left rib is rare and can cause chest discomfort such as chest pain and tightness, and its clinical manifestations are not typical, so it is often misdiagnosed. We report a case of left costal plasmacytoma misdiagnosed as angina pectoris. We also review the literature and provide suggestions as to how to avoid misdiagnosis. CASE SUMMARY: A 77-year-old man with a history of intermittent chest tightness for 3 years presented with pain in the left chest for 1 wk and was admitted to hospital. The cardiologists initially diagnosed angina pectoris but the findings of coronary angiography were not consistent with the symptoms. Computed tomography showed that the left eighth rib mass was accompanied by bone destruction. The patient was transferred to our department for further treatment. Preoperative biopsy indicated that the lesion was possibly malignant, and elective surgery was performed to remove the lesion. The size of the tumor was about 4 cm. The tumor was spindle-shaped and protruded into the pleural cavity, without invading the lungs. Postoperative pathology confirmed that the left rib lesion was plasmacytoma. After 14 mo follow-up, the patient died of systemic metastasis. CONCLUSION: Left rib solitary plasmacytoma is a rare disease confined to a specific rib and can cause local pain. Attention should be paid to the differential diagnosis of angina pectoris to avoid misdiagnosis.

Interrelationship of Gut Microbiota, Obesity, Body Composition and Insulin Resistance in Asians with Type 2 Diabetes Mellitus.

Metabolic syndrome (MS) has been an important health issue in the world, and insulin resistance (IR) is one of the characteristics of MS, increasing the risk for the onset and poor prognosis of type 2 diabetes mellitus (T2D). However, the interactional effect of obesity or abnormal body composition on the correlation between gut microbiota and IR in T2D patients is not well-explored. This cross-sectional study used a body composition monitor to evaluate lean tissue mass and fat tissue mass. IR was calculated using homeostatic model assessment-insulin resistance (HOMA-IR). Eight pairs of 16S rRNA gene primers specific to Firmicutes, Bacteroidetes, Clostridium leptum group, Faecalibacteriumprausnitzii, B acteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli were utilized to measure their abundance by qPCR. One hundred and fifty-four T2D patients were enrolled and stratified by the median HOMA-IR (2.5) and body mass index (BMI) of 25 kg/m2. A lower abundance of A. muciniphila was found in T2D patients with high HOMA-IR and BMI respectively. HOMA-IR and BMI had a synergistic effect on the reduction of the abundance of A. muciniphila. After adjusting metabolic factors, the low abundance of A. muciniphila significantly increased the risk for greater severity of IR. Furthermore, the negative correlation between A. muciniphila and IR was only found in T2D patients with high lean tissue. In conclusion, decreased abundance of fecal A. muciniphila enhanced the severity of IR in Asians with T2D, especially those having lean mass, and this significant relationship was independent of obesity.

Prophenoloxidase-Mediated Ex Vivo Immunity to Delay Fungal Infection after Insect Ecdysis.

Skin immunity protects animals from airborne pathogen infection. Unlike mammals, arthropods, including insects, undergo periodic ecdysis to grow and develop. Newly molted insects emerge with unsclerotized thin cuticles but successfully escape pathogenic infections during the post-molt period. Here we show that prophenoloxidases (PPOs) in molting fluids remain bioactive on the integument and impede fungal infection after ecdysis. We found that the purified plasma PPOs or recombinant PPOs could effectively bind to fungal spores (conidia) by targeting the cell wall components chitin and ß-1,3-glucan. Pretreatment of the spores of the fungal pathogen Beauveria bassiana with PPOs increased spore hydrophilicity and reduced spore adhesion activity, resulting in a significant decrease in virulence as compared with mock infection. We also identified a spore-secreted protease BPS8, a member of peptidase S8 family of protease that degrade PPOs at high levels to benefit fungal infection, but which at lower doses activate PPOs to inhibit spore germination after melanization. These data indicate that insects have evolved a distinct strategy of ex vivo immunity to survive pathogen infections after ecdysis using PPOs in molting fluids retained on the underdeveloped and tender integument of newly molted insects for protection against airborne fungal infection.

A recruiting protein of geranylgeranyl diphosphate synthase controls metabolic flux toward chlorophyll biosynthesis in rice.

In plants, geranylgeranyl diphosphate (GGPP) is produced by plastidic GGPP synthase (GGPPS) and serves as a precursor for vital metabolic branches, including chlorophyll, carotenoid, and gibberellin biosynthesis. However, molecular mechanisms regulating GGPP allocation among these biosynthetic pathways localized in the same subcellular compartment are largely unknown. We found that rice contains only one functionally active GGPPS, OsGGPPS1, in chloroplasts. A functionally active homodimeric enzyme composed of two OsGGPPS1 subunits is located in the stroma. In thylakoid membranes, however, the GGPPS activity resides in a heterodimeric enzyme composed of one OsGGPPS1 subunit and GGPPS recruiting protein (OsGRP). OsGRP is structurally most similar to members of the geranyl diphosphate synthase small subunit type II subfamily. In contrast to members of this subfamily, OsGRP enhances OsGGPPS1 catalytic efficiency and specificity of GGPP production on interaction with OsGGPPS1. Structural biology and protein interaction analyses demonstrate that affinity between OsGRP and OsGGPPS1 is stronger than between two OsGGPPS1 molecules in homodimers. OsGRP determines OsGGPPS1 suborganellar localization and directs it to a large protein complex in thylakoid membranes, consisting of geranylgeranyl reductase (OsGGR), light-harvesting-like protein 3 (OsLIL3), protochlorophyllide oxidoreductase (OsPORB), and chlorophyll synthase (OsCHLG). Taken together, genetic and biochemical analyses suggest OsGRP functions in recruiting OsGGPPS1 from the stroma toward thylakoid membranes, thus providing a mechanism to control GGPP flux toward chlorophyll biosynthesis.

Characterization of cyclophilin D in freshwater pearl mussel (Hyriopsis schlegelii).

Cyclophilin D (referred to as HsCypD) was obtained from the freshwater pearl mussel (Hyriopsis schlegelii). The full-length cDNA was 2 671 bp, encoding a protein consisting of 367 amino acids. HsCypD was determined to be a hydrophilic intracellular protein with 10 phosphorylation sites and four tetratricopeptide repeat (TPR) domains, but no signal peptide. The core sequence region YKGCIFHRIIKDFMVQGG is highly conserved in vertebrates and invertebrates. Phylogenetic tree analysis indicated that CypD from all species had a common origin, and HsCypD had the closest phylogenetic relationship with CypD from Lottia gigantea. The constitutive mRNA expression levels of HsCypD exhibited tissue-specific patterns, with the highest level detected in the intestines, followed by the gonads, and the lowest expression found in the hemocytes.

Rb deficiency accelerates progression of carcinoma of the urinary bladder in vivo and in vitro through inhibiting autophagy and apoptosis.

Urinary bladder cancer is known as a common cancer diagnosed across the world and results in significant mortality and morbidity rates among patients. The retinoblastoma (Rb) protein, as a main tumor suppressor, controls cellular responses to potentially oncogenic stimulation. Rb phosphorylation could disrupt E2F complex formation, resulting in diverse transcription factor dysfunction. In our study, we investigated how Rb is involved in controlling urinary bladder cancer progression. The results indicate that Rb expression is reduced in mice with urinary bladder tumor, and its suppression leads to urinary bladder cancer progression in vivo and in vitro. Rb mutation directly results in tumor size with lower survival rate in vivo. Rb knockdown in vitro promoted bladder tumor cell proliferation, migration and invasion. Interestingly, Rb knockout and knockdown result in autophagy and apoptosis inhibition via suppressing p53 and caspase-3 signaling pathways, enhancing bladder cancer development in vitro and in vivo. These findings reveal that Rb deficiency accelerated urinary bladder cancer progression, exposing an important role of Rb in suppressing urinary bladder cancer for treatment in the future.

Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways.

Human bladder cancer is a common genitourinary malignant cancer worldwide. However, new therapeutic strategies are required to overcome its stagnated survival rate. Triterpene glycoside Actein (ACT), extracted from the herb black cohosh, suppresses the growth of human breast cancer cells. Our study attempted to explore the role of ACT in human bladder cancer cell growth and to reveal the underlying molecular mechanisms. We found that ACT significantly impeded the bladder cancer cell proliferation via induction of G2/M cycle arrest. Additionally, ACT administration triggered autophagy and apoptosis in bladder cancer cells, proved by the autophagosome formation, LC3B-II accumulation, improved cleavage of Caspases/poly (ADP-ribose) polymerase (PARP). Furthermore, reduction of reactive oxygen species (ROS) and p-c-Jun N-terminal kinase (JNK) could markedly reverse ACT-induced autophagy and apoptosis. In contrast, AKT and mammalian target of rapamycin (mTOR) were greatly de-phosphorylated by ACT, while suppressing AKT and mTOR activity could enhance the effects of ACT on apoptosis and autophagy induction. In vivo, ACT reduced the tumor growth with little toxicity. Taken together, our findings indicated that ACT suppressed cell proliferation, induced autophagy and apoptosis through promoting ROS/JNK activation, and blunting AKT pathway in human bladder cancer, which indicated that ACT might be an effective candidate against human bladder cancer in future.

Rb knockdown accelerates bladder cancer progression through E2F3 activation.

Bladder cancer is one of the most common cancers diagnosed in the world and leads to significant mortality and morbidity among affected patients. The retinoblastoma (Rb) protein is a main tumor suppressor, controlling cellular responses to potentially oncogenic stimulation. E2F3 was invariably disrupted in different human cancers for its central role in the control of cellular proliferation. Here, we investigated how Rb is integrated to control bladder cancer progression through E2F3 and p53 regulation. The results exhibit that Rb expression is lower in patients with bladder tumor, while E2F3 level is high. Rb knockdown enhanced bladder tumor cell proliferation and migration, aggravated with p53 silence. Interestingly, Rb silence results in E2F3, Myc and mTOR signaling pathway activation, contributing to bladder cancer cell proliferation and apoptosis suppression mainly through caspase-3 inhibition in vitro and in vivo. Immunohistochemical analysis revealed that Rb is highly expressed in normal bladder cells, but was repressed in tumor tissues of the bladder completely, suggesting a possible role of Rb as a tumor suppressor.

Antioxidant activity and growth inhibition of human colon cancer cells by crude and purified fucoidan preparations extracted from Sargassum cristaefolium.

Fucose-containing sulfated polysaccharides, also termed "fucoidans", which are known to possess antioxidant, anticoagulant, anticancer, antiviral, and immunomodulating properties, are normally isolated from brown algae via various extraction techniques. In the present study, two methods (SC1 and SC2) for isolation of fucoidan from Sargassum cristaefolium were compared, with regard to the extraction yields, antioxidant activity, and inhibition of growth of human colon cancer cells exhibited by the respective extracts. SC1 and SC2 differ in the number of extraction steps and concentration of ethanol used, as well as the obtained sulfated polysaccharide extracts, namely, crude fucoidan preparation (CFP) and purified fucoidan preparation (PFP), respectively. Thin layer chromatography, Fourier transform infrared analysis, and measurements of fucose and sulfate contents revealed that the extracts were fucoidan. There was a higher extraction yield for CFP, which contained less fucose and sulfate but more uronic acid, and had weaker antioxidant activity and inhibition of growth in human colon cancer cells. In contrast, there was a lower extraction yield for PFP, which contained more fucose and sulfate but less uronic acid, and had stronger antioxidant activity and inhibition of growth in human colon cancer cells. Thus, since the difference in bioactive activities between CFP and PFP was not remarkable, the high extraction yield of SC1 might be favored as a method in industrial usage for extracting fucoidan.

Molecular cloning, sequence analysis, and cadmium stress-rated expression changes of BTG1 in freshwater pearl mussel (Hyriopsis schlegelii).

The B cells translocation gene 1 (BTG1) is a member of the BTG/TOB family of anti-proliferative genes, which have recently emerged as important regulators of cell growth and differentiation among verteates. Here, for the first time we cloned the full-length cDNA sequence of Hyriopsis schlegelii (Hs-BTG1), an economically important freshwater shellfish and potential indicator of environmental heavy metal pollution, for the first time. Using rapid amplification of cDNA ends (RACE) together with splicing the EST sequence from a haemocyte cDNA liary, we found that Hs-BTG1 contains a 525 bp open reading frame (ORF) encoding a 174 amino-acid polypeptide, a 306 bp 5' untranslated region (5' UTR), and a 571 bp 3' UTR with a Poly(A) tail as well as a transcription termination signal (AATAAA). Homologue searching against GenBank revealed that Hs-BTG1 was closest to Crassostrea gigas BTG1, sharing 50.57% of protein identities. Hs-BTG1 also shares some typical features of the BTG/TOB family, possessing two well-conserved A and B boxes. Clustering analysis of Hs-BTG1 and other known BTGs showed that Hs-BTG1 was also closely related to BTG1 of C. gigas from the inverteate BTG1 clade. Function prediction via homology modeling showed that both Hs-BTG1 and C. gigas BTG1 share a similar three-dimensional structure with Homo sapiens BTG1. Tissue-specific expression analysis of the Hs-BTG1 via real-time PCR showed that the transcripts were constitutively expressed, with the highest levels in the hepatopancreas and gills, and the lowest in both haemocyte and muscle tissue. Expression levels of Hs-BTG1 in hepatopancreas (2.03-fold), mantle (2.07-fold), kidney (2.2-fold) and haemocyte (2.5-fold) were enhanced by cadmium (Cd²âº) stress, suggesting that Hs-BTG1 may have played a significant role in H. schlegelii adaptation to adverse environmental conditions.

Outcomes of the patients in the respiratory care center are not associated with the seniority of the caring resident.

Although many studies show that the experience level of physicians is significantly associated with the outcomes of their patients, little evidence exists to show whether junior residents provide worse care than senior residents. This study was conducted to analyze whether the experience level of residents may affect the outcomes of patients cared for in a well-organized setting. We conducted a 7-year retrospective study utilizing statistical data from a respiratory care center (RCC) in a medical center between October 2004 and September 2011. In addition to the two medical residents who had been trained in the intensive care unit (ICU), the RCC team also included attending physicians in charge, a nurse practitioner, a case manager, a dietitian, a pharmacist, a social worker, registered respiratory therapists, and nursing staff. Weaning from mechanical ventilation was done according to an established weaning protocol. The 84 months analyzed were classified into five groups according to the levels of the two residents working in the RCC: R2 + R1, R2 + R2, R3 + R1, R3 + R2, and R3 + R3. The monthly weaning rate and mortality rate were the major outcomes, while the mean ventilator days, rate of return to the ICU, and nosocomial infection incidence rate were the minor outcomes. The groups did not differ significantly in the monthly weaning rate, mortality rate, mean ventilator days, rate of return to the ICU, or nosocomial infection incidence rate (p > 0.1). Further analysis showed no significant difference in the monthly weaning rate and mortality rate between months with a first-year resident (R1) and those with two senior residents (p > 0.2). Although the weaning rate in the RCC gradually improved over time (p < 0.001), there was no significant difference in the monthly weaning rate between the groups after adjusting for time and disease severity (p > 0.7). Thus, we concluded that in a well-organized setting, the levels (experiences) of residents did not significantly affect patient outcomes. This result may be attributed to the well-developed weaning protocol and teamwork processes in place, which avoid a large effect from any single factor and provide stable and high-quality care to the patients.

Reassessing the benefits of statins in the prevention of cardiovascular disease in diabetic patients--a systematic review and meta-analysis.

OBJECTIVES: Despite the fact that statins have been prescribed widely, cardiovascular disease (CVD) remains the leading cause of death in diabetic patients. The aim of this study was to reassess the benefits of statins for CVD prevention in patients with diabetes mellitus. METHODS: Two independent investigators searched for prospective, randomized statin trials that investigated the power of reducing CVD in statin-treated patients. The search was performed using Pubmed, Web of Science, and CENTRAL databases. Data was extracted from eligible studies. RESULTS: A total of 7061 articles were surveyed and 22 articles were identified as eligible articles. The meta-analyses of the 22 trials showed that statin treatment was positively associated with a lowered risk of CVD in the following groups: (i) total population with pooled odds ratios (OR) of 0.791 (95 % CI: 0.74-0.846, p < 0.001), (ii) diabetic population with OR 0.792 (95% CI: 0.721-0.872, p < 0.001), and (iii) non-diabetic population with OR 0.791 (95% CI: 0.730-0.857, p < 0.001). In diabetic patients, statins were also helpful in the primary and secondary prevention of CVD, with pooled ORs of 0.757 (95% CI: 0.676 to 0.847, p < 0.001) and 0.800 (95% CI: 0.712 to 0.898, p < 0.001), respectively. However, when trials that investigated only diabetic patients (i.e., CARDS, 4D, and ASPEN) were included in the analysis, statin treatment was not found to reduce CVD significantly (OR: 0.817, 95% CI: 0.649 to 1.029, p = 0.086). Furthermore, after performing subgroup analysis, no benefit of statin treatment was found in primary prevention (OR: 0.774, 95% CI: 0.506 to 1.186, p = 0.240) or secondary prevention (OR: 0.893, 95% CI: 0.734 to 1.088, p = 0.262) of CVD in diabetic patients. CONCLUSIONS: Although our study may be limited by unmeasured confounders and heterogeneity among the studies included, the results suggest that the effects of statins in the prevention of CVD in diabetic patients are not only beneficial. More informative data are needed to verify the benefits of statins in the protection against CVD in diabetic patients.

Oxido[N-(2-oxidobenzyl-idene-κO)leucinato-κ²N,O](1,10-phenanthroline-κ²N,N')vanadium(IV).

In the title V(IV) complex, [VO(C13H15NO3)(C12H8N2)], the oxidovanadium cation is N,N'-chelated by a 1-10-phenanthroline ligand and N,O,O'-chelated by a Schiff base anion in a distorted octa-hedral geometry. Weak inter-molecular C-H⋯O hydrogen bonds occur in the crystal structure which contains solvent-accessible voids of 81 ų.

[Study on intra-gastric floating beads of naringenin].

OBJECTIVE: To prepare calcium alginate-chitosan intra-gastric floating beads of naringenin combining with the solid dispersion method and investigate the in vitro floating characteristics, entrapment efficiency and drug release property of the beads. METHODS: The solid dispersion of naringenin was prepared by the Eudragit RLPO. Sodium alginate solution mixed with the powder of the solid dispersion of naringenin and frother was slowly dripped into chitosan-calcium chloride solution added with acetic acid. Calcium alginatechitosan intra-gastric floating beads of naringenin were obtained after drying. The effects of solid dispersion on in vitro release of naringenin were investigated. RESULTS: Intra-gastric floating beads of naringenin were acquired successfully. More than 70% of the beads kept floating in artificial gastric juice in 9 h, the release ratio of naringenin during 9 h was 65%-70% and the entrapment efficiency was about 70%-80%. CONCLUSION: The sustained release of naringenin in the calcium alginate-chitosan intra-gastric floating beads could be achieved by using the solid dispersion method and it provides some ideas of intra-gastric floating preparations.

Preparation, characterization, and in vivo evaluation of mitoxantrone-loaded, folate-conjugated albumin nanoparticles.

Folic acid was covalently conjugated to bovine serum albumin nanoparticles (BSANP) to target the nanoparticles to SKOV3 cells expressing folate receptors. Mitoxantrone was incorporated into the folate-conjugated albumin nanoparticles, and the final nanoparticle size was 68 nm, as measured by a laser light scattering particle analyzer. The cytotoxic activity of mitoxantrone- loaded, folate-conjugated albumin nanoparticles (MTO-BSANP-folate), which was quantitated by (3)H-thymidine incorporation, was higher than mitoxantrone-loaded BSANP (MTO-BSANP) and MTO solution, and could be inhibited by free folic acid. MTO-BSANPfolate may be endocytosed via the folate receptor on the surface of SKOV3 cells. MTO-BSANPfolate also inhibited tumor growth better than the MTO-BSANP and MTO solution in vivo. These results indicate that folate-conjugated BSANP may have therapeutic potential as a vector for anticancer drugs in cancer chemotherapy.

Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-kappaB pathway in primary rat microglia.

AIM: To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia. METHODS: Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 microg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the content of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and monocyte chemoattractant protein (MCP-1) was measured with ELISA. Protein expression of the nuclear factor-kappaB (NF-kappaB) p65 subunit, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was detected with immunocytochemistry 1 h or 24 h after LPS treatment. RESULTS: LIG showed a concentration-dependent anti-inflammatory effect in LPS-activated microglia, without causing cytotoxicity. Pretreatment with LIG at 2.5, 5, 10, and 20 micromol/L decreased LPS-induced NO production to 75.9%, 54.4%, 43.1%, and 47.6% (P<0.05 or P< 0.01), TNF-alpha content to 86.2%, 68.3%, 40.1%, and 39.9% (P<0.01, with the exception of 86.2% for 2.5 micromol/L LIG), IL-1beta content to 31.5%, 27.7%, 0.6%, and 0% (P<0.01), and MCP-1 content to 84.4%, 50.3%, 45.1%, and 42.2% (P<0.05 or P<0.01), respectively, compared with LPS treatment alone. LIG (10 micromol/L) significantly inhibited LPS-stimulated immunoreactivity of activated NF-kappaB, COX-2, and iNOS (P<0.01 vs LPS group). CONCLUSION: LIG exerted a potent anti-inflammatory effect on microglia through inhibition of NF-kappaB pathway. The data provide direct evidence of the neuroprotective effects of LIG and the potential application of LIG for the treatment of the neuroinflammatory diseases characterized by excessive microglial activation.

Antiproliferative effect of Toona sinensis leaf extract on non-small-cell lung cancer.

Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti-LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non-small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC(50) value was observed in TSL-1-treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1-induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.

Antiproliferative and antitumorigenic activity of Toona sinensis leaf extracts in lung adenocarcinoma.

Toona sinensis is a traditional Chinese herb, and the extracts of T. sinensis leaf possess a variety of biological functions. This study attempted to test the antiproliferative effect of TSL-1 (a bioactive fraction of T. sinensis) in H441 cells (lung adenocarcinoma). The data showed that the antiproliferative effect of TSL-1 on H441 cells is prominent using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSL-1-induced apoptosis was confirmed by cell morphology, sub-G(1) peak accumulation, cleavage of poly(ADP)-ribose polymerase, and propidium iodide-annexin V double staining. Furthermore, decreased Bcl-2 accompanied by increased Bax (in western blotting) was found with TSL-1 treatment of H441 cells. TSL-1 treatment-induced G(1) arrest was concurrent with the down-regulation of protein levels of cyclin D1 and cyclin-dependent kinase 4 in H441 cells. Peroral and intraperitoneal administrations of TSL-1 were performed to evaluate the therapeutic efficacy, and peroral administration of TSL-1 was also used to elucidate the therapeutic efficacy in the H441 cell xenograft model in vivo. The data revealed that TSL-1 treatment inhibited H441 tumor growth in both therapeutic and preventive experiments. Taken together, these results demonstrate that TSL-1 possesses the capability of preventing and alleviating lung cancer proliferation in vitro and in vivo with proven nephrological and hepatic safety and has the potential to be developed as an anti-lung cancer drug.