Global and Latest Hotspots of Female Genital Plastic Surgery in the Past 20 Years: A Bibliometric and Visualized Review.

BACKGROUND: An increasing number of surgical and nonsurgical interventions are available in the field of female genital plastic surgery. The rate of female genital plastic surgery has increased by nearly 220 percent over the past 5 years. Despite several studies on the topic, no relevant bibliometric analysis has been conducted. METHODS: We searched the Web of Science Core Collection for articles related to female genital plastic surgery. CiteSpace 6.1.R2 (Drexel University, USA) and VOSviewer 1.6.10.0 (Leiden University, the Netherlands) were used, and national distribution, institutions, journals, authors, and key words were analyzed and calculated. RESULTS: From 2003 to 2022, 1299 papers in the field of female genital plastic surgery were retrieved. There were more articles produced in the United States, and there were also two institutions in the Netherlands that were highly productive. A wide and close relationship has been established between researchers and institutions conducting female genital plastic surgery. Professor Bouman MB published the most articles on female genital plastic surgery in the Journal of Sexual Medicine. Female genital plastic surgery dominated the top 10 references with the highest local citation score. There were four clusters of key words with the most citations, and the most recently trending key words were "vaginal agenesis," "transgender," and "congenital adrenal hyperplasia." CONCLUSIONS: The purpose of this article is to provide a summary of the current research status focusing on female genital plastic surgery. It is hoped that more efforts will be made to promote the development of female genital plastic surgery in the future.

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

EphB6 deficiency in intestinal neurons promotes tumor growth in colorectal cancer by neurotransmitter GABA signaling.

EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons. But how EphB6 is involved in functions of intestinal neurons has not been known. In our study, we constructed a mouse xenograft model of CRC by injecting CMT93 cells into the rectum of EphB6-deficient mice. We found that the deletion of EphB6 in mice promoted tumor growth of CMT93 cells in a xenograft model of CRC, which was independent of changes in the gut microbiota. Interestingly, inhibition of intestinal neurons by injecting botulinum toxin A into rectum of EphB6-deficient mice could eliminate the promotive effect of EphB6 deficiency on tumor growth in the xenograft model of CRC. Mechanically, the deletion of EphB6 in mice promoted the tumor growth in CRC by increasing GABA in the tumor microenvironment. Furthermore, EphB6 deficiency in mice increased the expression of synaptosomal-associated protein 25 in the intestinal myenteric plexus, which mediated the release of GABA. Our study concluded that EphB6 knockout in mice promotes tumor growth of CMT93 cells in a xenograft model of CRC by modulating GABA release. Our study found a new regulating mechanism of EphB6 on the tumor progression in CRC that is dependent on intestinal neurons.

Global Analyses and Latest Research Hot Spots of Adipose-Derived Stem Cells in Fat Grafting: A Bibliometric and Visualized Review.

BACKGROUND: Fat grafting is one of the most effective treatments for soft tissue restoration and augmentation. Adipose-derived stem cells (ASCs) supplementation is one of the foremost concerns to improve its efficiency. There have been several studies aiming at adipose-derived mesenchymal stem cells in fat grafting, but no relevant bibliometric research has conducted. METHODS: Articles about fat grafting and ASCs were retrieved in Web of Science Core Collection (WoSCC). Using VOSviewer 1.6.10.0 (Leiden University, the Netherlands) and CiteSpace 6.1.R2 (Drexel University, USA), the information of national distribution, institutions, journals, authors and keywords were evaluated and calculated. RESULTS: A total of 1166 papers in the field of ASCs in fat grafting were retrieved from 2002 to 2021. The USA produced the most articles, and the top 2 productive institutions were all from the USA. Researchers and institutions conducting ASCs in fat grafting research have shown a widespread and close connection. Plastic and Reconstructive Surgery published the most article on ASCs in fat grafting, and professor Rubin Peter is the most productive author. The top 10 references with the highest LCS mainly focused on applying ASCs to assist fat transplantation in plastic surgery. The most cited keywords formed 4 clusters, and "mesenchymal stem," "mesenchymal stromal cell," "stromal vascular fraction" and "long term" were the most recently trending keywords. CONCLUSIONS: This article provides a summary of the current research status focusing on fat grafting and ASCs. More efforts will be made to promote the application of ASCs in fat grafting. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Radiographic Assessment of Aseptic Loosening of Tumor-Type Knee Prosthesis in Distal Femur.

OBJECTIVE: To measure the full-length anteroposterior and lateral radiographs of lower limbs after the resection of a tumor in the distal femur and tumor-type knee prosthesis replacement and to analyze the factors leading to aseptic loosening of the prosthesis. METHODS: A total of 26 cases of tumor-type knee prosthesis replacement or revision due to the distal femoral tumor at our hospital from January 2007 to December 2019 were retrospectively analyzed. The patients were divided into the loosening and unloosening groups depending on whether aseptic loosening occurred after surgery. Full-length anteroposterior and lateral radiographs of lower limbs were used to measure bone resection length, length of prosthesis, distance of proximal apex of the medullary stem of the femoral prosthesis from the maximum arc of the anterior femoral arch, diameter of the medullary stem, etc. Data were analyzed, and the risk factors for aseptic loosening of the prosthesis were explored. RESULTS: The ratio of the prosthetic length to the femoral length (63.72 ± 5.21) and the ratio of the femoral medullary stem diameter to the femoral diameter (26.03 ± 8.45) were smaller in the loosening group than in the unloosening group. The difference was statistically significant (p < 0.05). The distance between the apex of the medullary stem and the maximum arc of the anterior femoral arch was significantly shorter in the loosening group (3.47 ± 2.96) than in the unloosening group, and the difference was statistically significant (p < 0.05). The measurement of the lower limb alignment showed significant differences between the loosening and unloosening groups in terms of HKAA, mLDFA, and distance between the lower limb alignment and the center of the knee joint (p < 0.05). The logistic regression analysis showed that less than 30% ratio between the medullary stem diameter and the femoral diameter, less than 3 cm distance between the apex of the medullary stem and the maximum curvature of the anterior arch of the femur, distance between the lower limb alignment and the center of the knee joint, and presence of varus knee and valgus knee after the surgery were the risk factors for aseptic loosening of the prosthesis. CONCLUSIONS: The diameter of the femoral medullary stem of the prosthesis, the apex position of the prosthetic stem, and the lower limb alignment are the risk factors for aseptic loosening of the prosthesis.

[Characteristics of BTEX and Health Risk Assessment During Typical Pollution Episodes in Summer and Winter in Tianjin Urban Area].

Real-time BTEX(including benzene, toluene, ethylbenzene, m-, p-, and o-xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10-9 and 4.83×10-9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.

Destination Joint Spacers: A Similar Infection-Relief Rate But Higher Complication Rate Compared with Two-Stage Revision.

OBJECTIVE: To evaluated the clinical outcomes of periprosthetic joint infection (PJI) patients with destination joint spacer compared with that of two-stage revision. METHODS: From January 2006 to December 2017, data of PJI patients who underwent implantation with antibiotic-impregnated cement spacers in our center due to chronic PJI were collected retrospectively. The diagnosis of PJI was based on the American Society for Musculoskeletal Infection (MSIS) criteria for PJI. One of the following must be met for diagnosis of PJI: a sinus tract communicating with the prosthesis; a pathogenis isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; four of the following six criteria exist: (i) elevated ESR and CRP; (ii) elevate dsynovial fluid white blood cell (WBC) count; (iii) elevated synovial fluid neutrophil percentage (PMN%); (iv) presence of purulence in the affected joint; (v) isolation of a microorganism in one periprosthetic tissue or fluid culture; (vi) more than five neutrophilsper high-power fields in five high-power fields observed from histological analysis of periprosthetic tissue at ×400 magnification. Age, sex, body mass index (BMI), and laboratory test results were recorded. All patients were followed up regularly after surgery, the infection-relief rates were recorded, Harris hip score (HHS) and knee society score (KSS) were used for functional evaluation, a Doppler ultrasonography of the lower limb veins was performed for complication evaluation. The infection-relief rates and complications were compared between destination joint spacer group and two-stage revision group. RESULTS: A total of 62 patients who were diagnosed with chronic PJI were enrolled, with an age of 65.13 ± 9.94 (39-88) years. There were 21 cases in the destination joint spacer group and 41 cases in the temporary spacer group, namely, two-stage revision group (reimplantation of prosthesis after infection relief). The Charlson comorbidity index (CCI) in the destination joint spacer group was higher than that in the temporary spacer group, and this might be the primary reason for joint spacer retainment. As for infection-relief rate, there were three cases of recurrent infection (14.29%) in the destination joint spacer group and four cases of recurrent infection (9.76%) in the two-stage revision group, there were no significant differences with regard to infection-relief rate. Moreover, there two patients who suffered from spacer fractures, three cases of dislocation, one case of a periarticular fracture, and three cases of deep venous thrombosis in destination joint spacer group, while there was only one case of periprosthetic hip joint fracture, one case of dislocation, and one patient suffered from deep venous thrombosis of the lower extremity in two-stage revision. The incidence of complications in the destination joint spacer group was higher than that of two-stage revision. CONCLUSIONS: In summary, the present work showed that a destination joint spacer might be provided as a last resort for certain PJI patients due to similar infection-relief rate compared with two-stage revision.

Psoralen attenuates bleomycin-induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7th to 21st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM-induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM-induced expression of α-smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor-ß1, interleukin-1ß, and tumor necrosis factor-α in the lungs of BLM-stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM-induced murine model.

FGF2/FGFR1 regulates autophagy in FGFR1-amplified non-small cell lung cancer cells.

BACKGROUND: Autophagy is a conserved catabolic process to degrade cellular organelles. The role of autophagy in cancer development is complex. Amplification of fibroblast growth factor receptor 1 (FGFR1) is one of the most frequent targets in lung squamous cell carcinoma (SQCC). Whether fibroblast growth factor 2 (FGF2)/FGFR1 contributes to the regulation of autophagy remains elusive. METHODS: Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3), formation of GFP-LC3 puncta, and monodansylcadaverine (MDC) staining. The effect of autophagy inhibition on cell survival was assessed by cell viability and apoptosis assays. RESULTS: We elucidated that FGFR1 activation suppressed autophagy. Pharmacological or genetic inhibition of FGFR1 by AZD4547 or FGFR1 short hairpin RNA (shRNA) induced autophagy in FGFR1-amplified non-small cell lung cancer (NSCLC) cells, H1581 and H520 cells. Mechanistic study revealed that the induction of autophagy by FGFR1 inhibition was mediated through inhibiting the ERK/MAPK pathway not by AKT pathway, accompanied by upregulation of beclin-1. Furthermore, activation of ERK/MAPK by transfection with a constitutively active MEK1 (caMEK1) construct or knockdown of beclin-1 by RNAi could attenuate autophagy induced by FGFR1 inhibition. Beclin-1 expression was inversely correlated with MEK1 phosphorylation. Inhibition of autophagy by beclin-1 silencing could enhance apoptosis after AZD4547 treatment in H1581 and H520 cells. High levels of LC3B mRNA was a marker of poor prognosis in NSCLC patients. CONCLUSIONS: Simultaneously inhibiting FGFR1 and autophagy could enhance cell death which should be further explored in vivo.

XBP1-LOX Axis is critical in ER stress-induced growth of lung adenocarcinoma in 3D culture.

Rapid growth of tumor cells needs to consume large amounts of oxygen and glucose, due to lack of blood supply within the tumor, cells live in an environment that lack of oxygen and nutrients. This environment results in endoplasmic reticulum (ER) stress and activates the UPR (unfolded protein response). More and more evidence suggests UPR provides a growth signal pathway required for tumor growth. In the present study, we investigated the relationship between XBP1, one transcription factor in UPR, and the expression of LOX. We found that ER stress induces high expression of XBP1, one transcription factor in UPR, in both 2D culture and 3D culture; but only promotes growth of lung adenocarcinoma cells in in vitro 3D culture other than 2D culture. In 3D culture, we further showed that knockdown XBP1 expression can block Tm/Tg-induced cell growth. LOX genes may be key downstream effector of XBP1. Knockdown LOX expression can partially block XBP1-induced cell growth. Then we showed XBP1 suppressed by RNA interference (RNAi) can reduce the expression of LOX. For the first time, it is being shown that XBP1 can regulate the expression of LOX to promote cell growth.

17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway.

The large tumour suppressor 1 (LATS1) signalling network has been proved to be an essential regulator within the cell, participating in multiple cellular phenotypes. However, it is unclear concerning the clinical significance of LATS1 and the regulatory mechanisms of 17-Allylamino-17- demethoxygeldanamycin (17-AAG) in lung adenocarcinoma (LAC). The aim of the present study was to investigate the correlation of LATS1 and yes-associated protein (YAP) expression with clinicopathological characteristics in LAC patients, and the effects of 17-AAG on biological behaviours of LAC cells. Subcutaneous LAC tumour models were further established to observe the tumour growth in nude mice. The results showed that the positive expression of LATS1 was significantly lowered (26.7% versus 68.0%, P < 0.001), while that of YAP was elevated (76.0% versus 56.0%, P = 0.03) in LAC tissues compared to the adjacent non-cancerous tissues; LAST1 expression was negatively correlated with YAP expression (r = 0.432, P < 0.001) and lymphatic invasion of the tumour (P = 0.015). In addition, 17-AAG inhibited proliferation and invasion, and induced cell apoptosis and cycle arrest in LAC cells together with increased expression of E-cadherin and p-LATS1, and decreased expression of YAP and connective tissue growth factor. Tumour volumes and weight were much smaller in 17-AAG-treated groups than those in untreated group (P < 0.01). Taken together, our findings indicate that decreased expression of LATS1 is associated with lymphatic invasion of LAC, and 17-AAG suppresses growth and invasion of LAC cells via regulation of the LATS1/YAP pathway in vitro and in vivo, suggesting that we may provide a promising therapeutic strategy for the treatment of human LAC.

FBXL5-mediated degradation of single-stranded DNA-binding protein hSSB1 controls DNA damage response.

Human single-strand (ss) DNA binding proteins 1 (hSSB1) has been shown to participate in DNA damage response and maintenance of genome stability by regulating the initiation of ATM-dependent signaling. ATM phosphorylates hSSB1 and prevents hSSB1 from ubiquitin-proteasome-mediated degradation. However, the E3 ligase that targets hSSB1 for destruction is still unknown. Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation. Furthermore, cells overexpression of Fbxl5 abrogated the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets and exhibited increased radiosensitivity, chemosensitivity and defective checkpoint activation after genotoxic stress stimuli. Moreover, the protein levels of hSSB1 and Fbxl5 showed an inverse correlation in lung cancer cells lines and clinical lung cancer samples. Therefore, Fbxl5 may negatively modulate hSSB1 to regulate DNA damage response, implicating Fbxl5 as a novel, promising therapeutic target for lung cancers.

Prognostic significance of the extent of lymph node involvement in stage II-N1 non-small cell lung cancer.

BACKGROUND: The non-small cell lung cancer (NSCLC) staging system (published in 2009 in the seventh edition of the cancer staging manuals of the Union for International Cancer Control and American Joint Commission on Cancer) did not include any changes to current N descriptors for NSCLC. However, the prognostic significance of the extent of lymph node (LN) involvement (including the LN zones involved [hilar/interlobar or peripheral], cancer-involved LN ratios [LNRs], and the number of involved LNs) remains unknown. The aim of this report is to evaluate the extent of LN involvement and other prognostic factors in predicting outcome after definitive surgery among Chinese patients with stage II-N1 NSCLC. METHODS: We retrospectively reviewed the clinicopathologic characteristics of 206 patients with stage II (T1a-T2bN1M0) NSCLC who had undergone complete surgical resection at Shanghai Chest Hospital from June 1999 to June 2009. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier statistical analysis. Stratified and Cox regression analyses were used to evaluate the relationship between the LN involvement and survival. RESULTS: Peripheral zone LN involvement, cancer-involved LNR, smaller tumor size, and squamous cell carcinoma were shown to be statistically significant indicators of higher OS and DFS by univariate analyses. Visceral pleural involvement was also shown to share a statistically significant relationship with DFS by univariate analyses. Multivariate analyses showed that tumor size and zone of LN involvement were significant predictors of OS. CONCLUSIONS: Zone of N1 LN, LN ratios, and tumor size were found to provide independent prognostic information in patients with stage II NSCLC. This information may be used to stratify patients into groups by risk for recurrence.

Clinical analysis of postoperative venous thromboembolism risk factors in lung cancer patients.

BACKGROUND AND OBJECTIVES: The objective of this study is to explore clinical risk factors for venous thromboembolism (VTE) in postoperative lung cancer patients in order to provide a basis for the prevention and treatment of postoperative VTE. METHODS: A total of 1,001 lung cancer patients were retrospectively analyzed. Each patient was confirmed with surgical pathology diagnosis and had a complete clinical and follow-up record. VTE was identified in a combination of spiral computed tomography (CT), pulmonary angiography, and color Doppler ultrasound. We used life table method to create an occurrence frequency curve of thrombosis. We also searched for high risk factors for postoperative VTE with Cox multivariate regression model and created frequency curves of thrombosis against different risk factors using Kaplan-Meier method. RESULTS: As of July 31, 2011, the median follow-up time is 25.73 ± 0.11 months (19.23-31.37). The cumulative frequency of VTE among 1,001 lung cancer patients is 2%, 3%, 4%, 5%, and 5.3% over 1, 3, 6, 12, and 30 months after the surgery. COX regression analysis showed that the hazard ratio of VTE occurrence in patients with incomplete resection relative to ones with complete resection is 9.867 (95% CI: 5.275-18.459, P = 0.000). And the hazard ratio of VTE occurrence is 3.472 (95% CI: 1.761-6.845, P = 0.000) in patients with anti-angiogenesis treatment compared to patients without such treatment. The hazard ratio of VTE occurrence is 2.808 (95% CI: 1.439-5.479, P = 0.002) in patients with EGFR-TKI treatment relative to patients without the treatment, and 7.520 (95% CI: 3.968-14.250, P = 0.000) in patients with an increase in D-dimer level relative to normal ones CONCLUSIONS: The highest incidence of VTE is within 1 month after lung cancer surgery. High risk factors for VTE include incomplete surgical resection, postoperative use of anti-angiogenesis drugs, EGFR-TKI application and an increase in preoperative D-dimer level.

[Clinical significance of C-reactive protein in patients with stage I non-small cell lung cancer].

OBJECTIVE: The aim of this study was to investigate the association between preoperative C-reactive protein (CRP) level and pathologic features in patients with stage I non-small cell lung cancer (NSCLC), and also to analyze if CRP provides prognostic information for NSCLC patients. METHODS: The clinicopathological data of 105 patients with stage I NSCLC, who underwent pulmonary resection in Shanghai Chest hospital from Mar 1999 to Jul 2004, were retrospectively reviewed. The association between preoperative CRP levels and several clinical variables was analyzed by chi square test. Logistic regression analysis was used for multivariate analysis. Kaplan-Meier method and Cox multivariate regression model was used to examine the prognostic significance of the covariates on survival. RESULTS: Among the 105 cases, 69 had CRP at normal level (≤ 5 mg/L) and 36 at increased level (> 5 mg/L). The patients who were male (P < 0.001), smoking (P = 0.002), with squamous cell carcinoma (P < 0.001), poor differentiation (P < 0.001), tumor size larger than 3 cm (P < 0.001) had a higher serum CRP level. The maxmal tumor diameter (P = 0.037) was an independent risk factor for preoperative serum CRP level elevation. The five-year survival rate and five-year disease free survival rate of the higher CRP group were lower than that in the normal CRP group (55.6% vs. 79.7%, P < 0.05, and 41.7%vs. 68.1%, P < 0.05, respectively). Cox regression analysis demonstrated that the CRP level had effect on overall survival (P = 0.009) and disease free survival (P = 0.019). CONCLUSIONS: Our findings indicate that the maximal tumor diameter is an independent risk factor for preoperative serum CRP level elevation. The overall survival, disease free survival, five-year survival rate and five-year disease free survival rate of the higher CRP group are lower than that in the normal CRP group.

A cost-effectiveness analysis of docetaxel versus pemetrexed in second-line chemotherapy for stage IIIb or IV non-small cell lung cancer in China.

BACKGROUND: To study the cost-efficacy of docetaxel and pemetrexed as single agents versus platinum-based combination agents in second-line treatment of stage IIIb or IV non-small cell lung cancer (NSCLC) patients by evaluating chemotherapeutic indexes and medical costs. METHODS: Treatment responses were evaluated by progression-free survival (PFS), overall survival (OS), hematological and gastrointestinal toxicities. RESULTS: Two hundred and seven stage IIIb or IV NSCLC patients were recruited to this clinical observation retrospective study. Thirty-four subjects were treated with docetaxel (group A), 98 with platinum-based doublet chemotherapy with docetaxel (group B), 42 with pemetrexed (group C), and 33 patients with platinum-based doublet combination therapy with pemetrexed (group D). The average PFS of groups A and B was 3.28 and 4.58 months, respectively (p = 0.042). The mean PFS of groups C and D was 3.1 and 4.98 months, respectively (p = 0.017). The mean OS of these groups was 12.88, 13.17, 12.40 and 13.04 months, respectively, without significant differences. The total medical costs in these four groups amounted to USD 5,533, 7,745, 8,569 and 15,291, respectively. CONCLUSIONS: Platinum-based doublet chemotherapy with docetaxel or pemetrexed could significantly increase PFS, however, without significant OS improvement in comparison with using them as single agents. The medical expenses associated with doublet therapy were much higher than those associated with single therapy with a significant portion of the medical expenses spent on treating hematological and gastrointestinal toxicity.

The effects of cetuximab alone and in combination with endostatin on vascular endothelial growth factor and interleukin-8 expression in human lung adenocarcinoma cells.

BACKGROUND: Angiogenesis, the growth of new blood vessels, plays an important role in tumor growth and metastasis. Both cetuximab and endostatin have been found to reduce the expression of endothelial-stimulating growth factors such as vascular endothelial growth factor (VEGF) and interleukin (IL)-8. However, the effects of cetuximab alone or in combination with endostatin on human lung adenocarcinoma cell growth remain unclear. OBJECTIVE: The aim of this study was to evaluate the cellular and molecular effects of cetuximab alone and in combination with endostatin on human lung adenocarcinoma cell lines HI 299, SPC-A1, and H460 in vitro. Methods The epidermal growth factor receptor (EGFR) status of a panel of human lung adenocarcinoma cell lines was characterized using Western blot analysis. We used a modified tetrazolium salt assay to evaluate the growth-inhibitory effects of cetuximab and endostatin alone and in combination on the cell lines. We also determined the effects of these 2 drugs on VEGF and IL-8 expression using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Cells were treated for 4 days with cetuximab 12.5 µ/mL, endostatin 25 µ/mL, or cetuximab 12.5 µg/mL + endostatin 25 µg/mL. Untreated cells cultured for 4 days served as controls. RESULTS: EGFR expression in the H1299 cells was higher than in the SPC-A1 and H460 cells. Varying concentrations of cetuximab alone were associated with a significant growth-inhibitory effect on all 3 cell lines in a dose-dependent manner after 4 days of exposure compared with controls (all, P < 0.05). Compared with controls, varying concentrations of endostatin alone were not associated with significant inhibition of cell growth in any of the 3 cell lines. The inhibitory ratio of cetuximab + endostatin at varying concentrations was significantly greater than that of cetuximab alone (all, P < 0.05). On ELISA, either drug alone was associated with significant reductions in secreted VEGF and IL-8 in the HI 299, SPC-A1, and H460 cell lines (all, P < 0.05), with the exception of IL-8 concentration in the H460 cells. Mean (SD) VEGF expression with combination treatment in the H1299 and SPC-A1 cell lines (687 [21] and 629 [23] pg/mL, respectively) was significantly lower than with cetuxi-mab alone (878 [31] and 708 [20] pg/mL; both, P < 0.001); in the H460 cell line, combination treatment was not associated with a significant further reduction in VEGF expression. IL-8 concentrations with cetuximab in the H1299, SPC-A1, and H460 cell lines were 628 (20), 484 (29), and 532 (28) pg/mL, respectively, while the IL-8 concentrations with the combination treatment were 516 (20), 480 (18), and 467 (30) pg/mL. An enhanced effect of endostatin on IL-8 was observed in the H1299 and H460 cell lines (P < 0.001 and P = 0.018, respectively); however, no enhanced effect in the SPC-A1 line was observed. Similar results for VEGF and IL-8 expression were found using Western blot analysis. CONCLUSIONS: The results from this in vitro study suggest that cetuximab treatment might both inhibit human lung adenocarcinoma cell line growth and reduce the expression of VEGF and IL-8, which are the biomarkers of angiogenesis. Endostatin was not associated with inhibition of human lung adenocarcinoma cell line growth directly. Findings with the combination of cetuximab + endostatin suggest that endostatin might enhance the antiangiogenic and antitumor activity of cetuximab through an apparent effect on VEGF expression and, to a lesser degree, on IL-8 expression.

Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice.

Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone.