Search

Fine-needle aspiration (FNA) cytology is a rapid, inexpensive, and uncomplicated method. However, its role in the assessment of soft tissue lesions (STL) remains controversial, and its ability to guide surgical treatment remains unclear. This study investigated the positive predictive value (PPV) of FNA for detecting malignancy and its guiding role in the surgical treatment of STL.We retrospectively reviewed 514 patients with STL who underwent preoperative FNA and surgical resection between March 2015 and August 2021. Imaging assessments confirmed that radical surgery was possible. The FNA results were compared with the final postoperative histopathology.Of the 514 patients with STL, 496 (mean age, 48.9 years; range, 21-91 years) were eligible for analysis, the male to female ratio was 111:100. According to the 496 FNA results, 90 (18.2%) were positive for malignancy, 84 (16.9%) were suspicious for malignancy, 80 (16.1%) were spindle cell present, and 242 (48.8%) were negative for malignant cells. Compared with postoperative histopathology, FNA correctly detected all 90 malignant lesions and 203 of the 242 benign lesions. A total of 39 false-negative results were obtained. FNA showed an accuracy of 88.3%, sensitivity of 69.8%, specificity of 100%, negative predictive value (NPV) of 83.9%, and PPV of 100%. In the other seven validation cohorts (n = 1157), FNA had a consistently high PPV, with values all more than 93%.Our results demonstrate that FNA has a high PPV for detecting malignancy. For patients with resectable lesions and malignant FNA, the core needle biopsy (CNB) step can be omitted with multidisciplinary evaluation, and subsequent radical surgery can be performed.

PDF file - 223KB

Purpose: MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis.Experimental Design: We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored.Results: We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3′ untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a–induced suppression of gastric cancer cell migration and invasion.Conclusions:miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis. Clin Cancer Res; 17(24); 7574–83. ©2011 AACR.

Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid tumors, including melanomas, to identify potential drug targets. However, the association between clinical outcomes and the molecular alterations has not yet been fully clarified.A total of 108 patients with melanoma were included in this study, 95 of whom had both sequencing data and clinical outcomes were collected. We analyzed the genetic alterations of 108 malignant melanoma patients using the OncoCare panel, which covers 559 genes.A model was also established to predict side effects through a combination analysis of clinical data and somatic variants, yielding an area under the receiver operating characteristic curve (AUROC) score of 0.8. We also identified epidermal growth factor receptor (EGFR) mutation was excellent predictor for progression-free survival (PFS) for patient who received immunotherapy (log-rank P=0.01), while tumor mutation burden (TMB) was found to not be significantly associated with PFS (log-rank P=0.87). Combining clinical features with genetic analysis, we found that patients carrying both DNA POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate.Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.

Purpose Our study aimed to describe the clinical features of undifferentiated pleomorphic sarcoma (UPS) and identify the predictors of poor outcomes. Patients and methods The clinicopathological variables and treatment strategies of 100 UPS patients who underwent surgical resections at a single institution between November 2004 and July 2016 were reviewed. Kaplan-Meier and Cox regression method were conducted for survival analysis. Results The median follow-up time was 94 months (range, 1.5-154 months). R0 resection was applied for 72 cases, and the median tumor size was 5.75cm (range, 1-30cm). Tumor grades of 45 patients were intermediate grade (G2), and 54 patients were with advanced stage (stage III/IV). Twenty-seven patients presented with tumors involving important structures, in which the nerve was the most frequently invaded structure (n=12). During the follow-up, 40 patients suffered from postoperative local recurrence, and distant metastasis was observed in 25 patients which mainly metastasized to the lung (n=14). The 5-year OS rate, 5-year LRFS rate, and 5-year MFS rate was 53%, 55%, and 70%, respectively. Multivariate analysis revealed that tumor presentation, tumor size, and important structures involved (p=0.033, p=0.004, and p=0.033, respectively) were independent prognostic factors associated with OS. Meanwhile, age, resection quality and tumor grade were independent prognostic factors for LRFS (p=0.033, p=0.045, and p=0.007, respectively) and tumor depth was significantly associated with MFS (p=0.050) in multivariate analysis. Conclusion Primary treatment of UPS should be conducted by experts in large sarcoma center. Wide surgical margin provides sufficient control of the disease recurrence.

Background The objective of this retrospective study was to evaluate the prognostic value of various factors in clear cell sarcoma patients after radical surgery. Methods Forty-two clear cell sarcoma patients from August 2006 to March 2018 were included in the study. Curves of disease-free survival and overall survival were calculated using the Kaplan–Meier method, and univariate and multivariate analyses of various prognostic factors were performed using a Cox proportional hazard regression model. Laboratory test of peripheral blood was recorded before surgery. The optimal cutoff value of systemic inflammatory markers was defined by receiver-operating curve analysis. Results The 5-year DFS and 5-year OS rate were 22% and 46%, respectively. The median DFS and OS times were 12 and 41.5 months, respectively. In univariate analysis, there was a significant association between shorter DFS and tumor size larger than 5 cm (p = 0.0043), positive surgical margin (p = 0.0233), and the neutrophil-to-lymphocyte ratio (NLR) higher than 2.73 (p = 0.0009). Furthermore, we observed a significant association between shorter OS and tumor size larger than 5 cm (p = 0.0075), positive surgical margin (p = 0.0101), NLR higher than 2.73 (p = 0.0126), the platelet-to-lymphocyte ratio (PLR) higher than 103.89 (p = 0.0147) and the lymphocyte-to-monocyte ratio (LMR) lower than 4.2 (p = 0.0445). A multivariate analysis demonstrated that the surgical margin (p = 0.013) and NLR (p = 0.001) were significantly associated with DFS. Tumor size (p = 0.010) and NLR (p = 0.013) were independent prognostic factors for OS. Conclusions This study had the second largest sample around the world and preoperative NLR may be a useful prognostic factor in CCS patients after radical surgery.

Background/aim Undifferentiated pleomorphic sarcomas (UPSs) are difficult to treat, with a high recurrence rate. However, the genetic and molecular characterization of recurrent UPS has not been identified. Patients and methods In this study, we investigated the pathogenic and targetable genetic alterations in 16 paired locally pre-recurrent and post-recurrent UPS cases by targeted next-generation sequencing (466 genes). Results Sequence variations were most frequently found in TP53 (66%), ATRX (34%), and RB1 (28%). In addition, for the first time, recurrent IL7R gene amplification (19%) and KMT2C gene mutation (16%) were detected in UPS. Interestingly, genetic alterations varied with tumor relapse. Importantly, targetable driver variants were found in recurrent UPS. Mutated genes were correlated with the cell cycle, PI3K/mTOR and RAS/MAPK signaling pathways. TMB was also found to be increased after tumor recurrence (4.6 vs. 7.5 mutations/MB, p=0.0343). Conclusion Routine use of targeted next-generation sequencing for recurrent UPS can facilitate timely therapeutic decision-making.

Background/aim Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal neoplasm characterized by chromosomal instability. The aim of this study was to identify fusion events involved in UPS. Materials and methods Transcriptome sequencing was performed to search for new fusion genes in 19 UPS samples, including two paired recurrent (R) and re-recurrent (RR) samples. Results A total of 66 fusion genes were detected. Among them, 10 novel fusion genes were further confirmed by reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing. Retinoblastoma (RB1) fusions (2 cases) were the most recurrent fusion genes. The gene fusions RB1-RNASEH2B, RB1-FGF14-AS1, and E2F6-FKBP4 were correlated with the Rb/E2F pathway. Pseudogenes were involved in the formation of the gene fusions CIC-DUX4L8 and EIF2AK4-ANXA2P2. Importantly, targetable gene fusions (PDGFRA-MACROD2 and NCOR1-MAP2K1) were detected in UPS. Conclusion Screening for the presence of fusion transcripts will provide vital clues to the understanding of genetic alterations and the finding of new targeted therapies for UPS.

Goodlad et al. [1] reported that 95 of 236 cases had inappropriate margin resection, and incomplete resection of the primary tumor was identified in 56 (59%) after re-resection, including 29/55 in the lower extremities, 16/25 in the upper extremities, 7/10 in the trunk and 4/5 in the head and neck, and remnants can be seen with naked eyes in 31 cases. Chardrasekar et al. [2] reported that 2201 cases of STS were admitted from Apr 1982 to Dec 2005, among which, 402 (18%) were unplanned resections, and 363 were studied; 316 underwent re-resection, and 188 (59%) showed residual tumor. The phenomenon of unplanned resection is seen throughout the world [3, 4].

Chondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.

Sarcomas are located on the superficial aspect of the skin or deep fascia, which is largely uninvolved. It is a tumor nodule type with the maximum diameter less than 5 cm (equivalent to stages I and IIA of the UICC staging), and its wound can be closed without repair or via simple method after re-resection. It is a true surface malignancy, including sarcomas, skin malignancies, and other types of malignancies.

Background: The present study was designed to explore the underlying role of hypoxia-inducible factor 1&alpha, (HIF-1&alpha, ) in reactive oxygen species (ROS) formation and apoptosis in osteosarcoma (OS) cells induced by hypoxia. Methods: In OS cells, ROS accumulated and apoptosis increased within 24 h after exposure to low HIF-1&alpha, expression levels. A co-expression analysis showed that HIF was positively correlated with Forkhead box class O1 (FoxO1) expression and negatively correlated with CYP-related genes from the National Center for Biotechnology Information&rsquo, s Gene Expression Omnibus (NCBI GEO) datasets. Hypoxia also considerably increased HIF-1&alpha, and FoxO1 expression. Moreover, the promoter region of FoxO1 was directly regulated by HIF-1&alpha, We inhibited HIF-1&alpha, via siRNA and found that the ROS accumulation and apoptosis induced by hypoxia in OS cells decreased. In this study, a murine xenograft model of BALB-c nude mice was adopted to test tumour growth and measure the efficacy of 2-ME + As2O3 treatment. Results: Ad interim knockdown of HIF-1&alpha, also inhibited manganese-dependent superoxide dismutase (MnSOD), catalase and sestrin 3 (Sesn3) expression in OS cells. Furthermore, hypoxia-induced ROS formation and apoptosis in OS cells were associated with CYP450 protein interference and were ablated by HIF-1&alpha, silencing via siRNA. Conclusions: Our data reveal that HIF-1&alpha, inhibits ROS accumulation by directly regulating FoxO1 in OS cells, which induces MnSOD, catalase and Sesn3 interference, thus resulting in anti-oxidation effects. The combination of an HIF-1&alpha, inhibitor (2-mercaptoethanol,2-ME) and ROS inducer (arsenous oxide, As2O3) can prohibit proliferation and migration and promote apoptosis in MG63 cells in vitro while inhibiting tumour growth in vivo.

Skin cutaneous melanoma (SCM) is a common malignant tumor of the skin and its pathogenesis still needs to be studied. In this work, we constructed a co-expression network and screened for hub genes by weighted gene co-expression network analysis (WGCNA) using the GSE98394 dataset. The relationship between the mRNA expression of hub genes and the prognosis of patients with melanoma was validated by Gene Expression Profiling Interactive Analysis (GEPIA) database. Furthermore, immunohistochemistry in the Human Protein Atlas was used to validate hub genes and grayscale analysis was performed using ImageJ software. It was found that the yellow module was most significantly associated with the difference between common nevus and SCM, and 13 genes whose expression correlation &gt, 0.9 were candidate hub genes. The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of SCM. STK26 (P = 0.0024) and KCNT2 (P &lt, 0.0001) were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future.

Background: Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). Methods: We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. Results: We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. Conclusions: The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Malignant melanoma (MM) remains the leading cause of skin cancer related death, which has very poor prognosis because of locoregional recurrence and distant metastasis. DEPDC1B (DEP domain-containing protein 1B), has been proved to be associated with some types of malignant tumors. However, the role of DEPDC1B in MM is still unknown. In this study, the expression levels of DEPDC1B in MM tissues were detected by IHC. DEPDC1B knockdown cell lines were constructed, evaluated by Western blot and qRT-PCR, and also used for construction of mice xenograft models. Cell proliferation and apoptosis were investigated by MTT, colony formation assay and flow cytometry, respectively. The results indicated significantly up-regulated expression of DEPDC1B in tumor tissues. Moreover, knockdown of DEPDC1B could inhibit cell proliferation while inducing cell apoptosis. The in vivo study demonstrated the significant suppression of tumor growth by knockdown of DEPDC1B. Finally, the results of antibody array proved the up-regulation of pro-apoptotic proteins and the down-regulation of anti-apoptotic proteins by DEPDC1B knockdown. Therefore, it could be concluded that DEPDC1B was involved in the development and progression of MM, which may act as promotor for MM and could be a potential therapeutic target.

Background Soft tissue sarcomas are rare neoplasms that can occur in the thoracic wall, abdominal wall, extremities, and inguinal region. Wide local resection, with precise histological margin control, results in large skin defects that are challenging to close. Various repair procedures, such as vertical rectus abdominis flaps (VRAM), latissimus dorsi flaps, and tensor fascia lata (TFL) flaps are used to cover broad thoracic wall defects. Although the cosmetic reconstruction results of using these flaps are often excellent, each has significant drawbacks. The external oblique musculocutaneous flap is a simple and safe surgical procedure for covering thoracic wall defects. Objective This study aimed to retrospectively assess the safety and technique of using the external oblique musculocutaneous flap to cover large thoracic wall defects after radical excision of locally advanced sarcomas in 20 patients at a single institution. Method From January 2006 to December 2016, 20 Chinese patients with large advanced sarcomas on their trunks received wide local resection, with precise histological negative margins. The external oblique musculocutaneous flap, mobilized from the ipsilateral abdominal wall, was harvested to cover broad thoracic wall defects. Results Among the 20 sarcoma patients (12 females and 8 males, ranging in age from 25 to 73 years), there were five patients with primary tumors and 15 patients with recurrent tumors. The median tumor diameter was approximately 15.3 cm. After excising the lesion, the median time to cover the defect with the external oblique myocutaneous flap was 66 min. The average blood loss when harvesting the flap was approximately 48 mL. For the 20 patients in our cohort, the external oblique flap achieved closure of defects measuring an average area of 256 cm[2]. No other flaps or reconstruction techniques were used to cover the large defects in this study. There were no deaths directly related to the flap reconstruction procedures. Conclusion The external oblique musculocutaneous flap was a safe and reliable method of covering broad thoracic wall defects after radical tumor excision.

Background External oblique myocutaneous flap (EOMF) has been used successfully for many years in reconstructive plastic surgery, its function is mainly concentrated in the restoration of chest wall defects following breast cancer resection. However, for the lower abdominal wall or groin defects after malignant tumor resection, reconstruction with EOMF is little reported. In this study, we report our experience with EOMF downward transposition to repair the defects. Methods 12 patients with malignant diseases in the lower abdominal wall or groin underwent aggressive tumor resection, the defects were reconstructed immediately with EOMF. Patient characteristics, details of operation and postoperative complications were described. Results 12 patients received radical resection, the defect size ranged from 140 to 588 cm2. Ipsilateral or bilateral EOMF was utilized to repair the defects. The EOMF had good quality skin and soft tissue to cover the defects, postoperatively, four patients developed seroma, two patients had distal tip necrosis, but no serious complications occurred, the wound of donor site healed well, no abdominal hernia was found. Conclusion Our study provides a new and alternative approach to reconstruct large defects with EOMF downward transposition after malignant tumor resection in the lower abdominal wall or groin. J. Surg. Oncol. 2014; 110:930–934. © 2014 Wiley Periodicals, Inc.

e22551 Background: Epithelioid sarcoma (ES) is a rare high grade soft tissue sarcoma with high incidence of lymph node involvement and distant metastasis. It is widely recognized that ES is not sensitive to chemotherapy and radiation, surgical treatment is the only curative option for localized diseases. Tyrosine kinase inhibitors (TKIs) has been proven to be effective in sarcomas, here we report the experience of Apatinib in 8 advanced ES cases. Methods: ES patients treated in Fudan University Shanghai Cancer Center from Dec, 2016 to Aug, 2018 were accrued retrospectively. Those with locally advanced diseases or distant metastasis were treated with orally Apatinib 500mg, daily use for at least 2 months. Assessment of efficacy and side effects were recorded every 2 months and patients were then treated according to reponses to Apatinib. Results: There were 8 patients with locally advanced or late stage ES in a total 20 ES patients during the study period. There were 6 males and 2 females with median age of 55 years (20-73). 3 of the 8 were classical type and 5 were proximal type. 7 of the 8 patients were locally advanced and 1 was with lung metastasis at diagnosis. 4 of the 8 had a partial response to Apatinib and one patient has a downstaged ES which was surgically removed. The other 4 had a stable disease to Apatinib but 2 were not able to tolerate side effects and stopped at first evaluation, the other 2 remains progression free. Main side effects included skin rash, hypertension and diarrhea. Hypertension was the only Grade 3-4 side effect. With median follow-up of 12 months, 6 remains progression free, the 2 patients who didn’t tolerate side effects and stopped Apatinib developed lung metastasis. Conclusions: Apatinib has unproven but promising effect in ES, TKI is an option especially for those not sensitive to cytotoxic agents and radiation.

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC.

Purpose: MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis. Experimental Design: We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored. Results: We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3′ untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a–induced suppression of gastric cancer cell migration and invasion. Conclusions: miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis. Clin Cancer Res; 17(24); 7574–83. ©2011 AACR.

Fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism, located in the FGFR4 gene exon 9, was reported to be associated with malignant tumors prognosis; however, there has been no relevant research for gastric cancer. The purpose of this study was to investigate the clinical significance of FGFR4 Gly388Arg polymorphism as well as the mRNA expression of FGFR4 in patients with gastric cancer. The mRNA expression of FGFR4 in 103 gastric cancer tissues and corresponding normal tissues were measured by reverse transcription polymerase chain reaction (PCR) and real-time quantitative PCR. PCR-restriction fragment length polymorphism analysis was performed to detect the FGFR4 Gly388Arg in 103 gastric cancer tissues. In 57.3% of patients, homozygous or heterozygous Arg388 allele was present. FGFR4 expressions in mRNA levels were higher in gastric cancer tissues compared with those in relevant normal tissues. However, there is no significantly statistical difference compared with mRNA expression of FGFR4 in different genotypes. Associations between FGFR4 Gly388Arg polymorphism and overall survival exist in patients with gastric cancer (P = 0.046).The FGFR4 Arg allele (hazard risk (HR), 2.324; 95% confidence interval (CI), 1.054–4.125; P = 0.037) and TNM stage (HR, 5.516; 95% CI 3.658–7.409; P = 0.005) were independent prognostic factors in patients with gastric cancer. Based on this study, FGFR4 Arg388 genotype—a marker for gastric cancer progression—may predict prognosis of gastric cancer.

Objective: The purpose of this study was to detect the presence of cancer stem-like cells with bronchioalveolar stem cells (BASCs) properties and investigate the clinicopathological role of expression of OCT4 as well as the correlation with clinical outcomes in adenocarcinoma of the lung. Methods: Specimens of 112 cases of Stage IB –I IIA lung adenocarcinoma after radical surgery were collected from June 1999 to June 2002. The putative cancer stem cells in tumor sections were visualized immunofluorescently by using the antibodies against three bronchioalveolar stem cells markers: surfactant protein C (SPC), Clara cell secretary protein (CCSP) and Octamer-4 (OCT4). Cancer stem-like cells with bronchioalveolar stem cell properties in human lung adenocarcinoma were subdivided into two phenotypes: OCT4 þ BASC (SPC þ CCSP þ OCT4 þ ) and OCT4 2 BASC (SPC þ CCSP þ OCT4 2 ). Results: Cancer cells with CCSP þ SPC þ BASC phenotype were detected in 107 cases, 80 cases with OCT4 þ BASC phenotype (SPC þ CCSP þ OCT4 þ ) and 27 cases with SPC þ CCSP þ OCT4 2 . There was a correlation between differentiation and OCT4 expression (P ¼ 0.047). The pattern of survival curves shows the expected trend of decreasing survival with increasing stage at diagnosis (P ¼ 0.015) and with OCT4 þ BASC expression (P ¼ 0.019). Multivariate Cox’s analysis reveals that pathological stages of TNM (P ¼ 0.008) and bronchioalveolar stem cells phenotypes (P ¼ 0.015) are the independent prognostic factors. Conclusions: The cancer cells with bronchioalveolar stem cells phenotype are detectable in adenocarcinoma of the lung and the expression of self-renewal regulatory gene OCT4 in these cells indicated the worse clinical outcomes.

Dermatofibrosarcoma protuberans (DFSP) is a rare, plaque-like tumor of the cutaneous tissue occurring more on the trunk than the extremities and neck. More than 95% of DFSP present anomalies on the 17q22 and 22q13 chromosomal regions leading to the fusion of COL1A1 and PDGFB genes. Surgery is the optimal treatment for DFSP, but less effective in locally advanced or metastatic patients, as is the case with chemotherapy and radiotherapy. The aim of this study was to assess retrospectively the therapeutic activity and safety of imatinib on 22 Chinese patients with locally inoperative or metastatic DFSP at a single institution. In the collected data of 367 Chinese patients with DFSP, we analyzed retrospectively 22 patients with locally advanced or metastatic DFSP, all of whom received imatinib therapy at 1 center from January 2009 to October 2014. Patients were administered with imatinib at an initial dose of 400 mg and escalated to 800 mg daily after they developed imatinib resistance. The median follow-up time was 36 months, and the median treatment time was 15 months. The results showed that 10 locally advanced DFSP patients and 12 metastatic DFSP patients received imatinib therapy. Apart from 1 patient who developed primary imatinib resistance, 15 patients achieved partial remission (PR), and 6 patients achieved stable disease (SD). Both fibrosarcomatous DFSP and classic DFSP patients demonstrated similar response to imatinib. Median PFS was estimated to be 19 months. Median overall survival (OS) has not been reached, and estimated 1- and 3-year OS rates were 95.5% (21/22) and 77.3% (17/22), respectively. Four out of 10 patients with primarily unresectable DFSP received complete surgical resection after neoadjuvant treatment of imatinib. Imatinib therapy is well tolerated with a safety profile and is the therapy of choice in locally inoperative or metastatic DFSP. Neoadjuvant treatment of locally advanced or metastatic DFSP with imatinib improves surgical outcomes and may facilitate resection of difficult tumors.

In a survey of endophytic fungal biodiversity, an antimicrobial endophytic isolate zjwcf069 was obtained from twigs of Forsythia viridissima, Zhejiang Province, Southeast China. Zjwcf069 was then identified as Pezicula sp. through combination of morphological and phylogenetic analysis based on ITS-rDNA. Zjwcf069 here represented the first endophytic fungus in Pezicula isolated from host F. viridissima. From the fermentation broth, four compounds were obtained through silica gel column chromatography and Sephadex LH-20 under the guide of bioassay. Their structures were elucidated by spectroscopic analysis as mellein (1), ramulosin (2), butanedioic acid (3), and 4-methoxy-1(3H)-isobenzofuranone (4). Compound 4 here stood for the very first time as natural product from microbes. In vitro antifungal assay showed that compound 1 displayed growth inhibition against 9 plant pathogenic fungi, especially Botrytis cinerea and Fulvia fulva with EC50 values below 50 μg/mL. Endophytic fungi in medicinal plants were good resources for bioactive secondary metabolites.

External oblique myocutaneous flap (EOMF) has been used successfully for many years in reconstructive plastic surgery, its function is mainly concentrated in the restoration of chest wall defects following breast cancer resection. However, for the lower abdominal wall or groin defects after malignant tumor resection, reconstruction with EOMF is little reported. In this study, we report our experience with EOMF downward transposition to repair the defects.12 patients with malignant diseases in the lower abdominal wall or groin underwent aggressive tumor resection, the defects were reconstructed immediately with EOMF. Patient characteristics, details of operation and postoperative complications were described.12 patients received radical resection, the defect size ranged from 140 to 588 cm(2) . Ipsilateral or bilateral EOMF was utilized to repair the defects. The EOMF had good quality skin and soft tissue to cover the defects, postoperatively, four patients developed seroma, two patients had distal tip necrosis, but no serious complications occurred, the wound of donor site healed well, no abdominal hernia was found.Our study provides a new and alternative approach to reconstruct large defects with EOMF downward transposition after malignant tumor resection in the lower abdominal wall or groin.

Recent studies have shown that microRNAs (miRNA) exhibit altered expression levels in cancers, and they may be considered as valuable prognostic biomarkers for patients with cancers. We performed this meta-analysis to provide a comprehensive evaluation of the role of miRNA-100 expression on the overall survival rate by calculating the pooled hazard ratio (HR) for overall survival (OS), which compared the high and low expression levels of miR-100 in patients of the available studies. Finally, a total of six studies dealing with various carcinomas were involved for this meta-analysis. The results indicated that lower expression of miR-100 in cancerous tissue could significantly predict poorer survival in various carcinomas with the pooled HR of 2.19 (95 % CI 1.49–3.24, P = 0.0007). In conclusion, the findings from this present meta-analysis suggest that miR-100 expression is associated with OS in cancer patients and could be a useful clinical prognostic factor for those patients.

Lung adenocarcinomas are proposed to originate from the malignant transformation of bronchioalveolar stem cells (BASC). This hypothesis, however, has not been confirmed in humans yet. In the present study, we determined to analyze the BASC properties in human lung adenocarcinoma stem cells.The human lung adenocarcinoma stem cells were obtained by flow cytometry (FCM) and induced with the sphereforming assay. The markers associated with BASC were measured by immunofluorescent staining, and their metastatic capacity was evaluated by injecting into NOD/SCID mice via tail vein.The majority of A549 and SPC-A1 human lung adenocarcinoma cells expressed the type II alveolar cell-specific marker SP-C. However, a minority of cells also expressed the bronchiolar Clara cell-specific marker CCSP and the embryonic stem cell marker OCT4, suggesting that these cells may belong to cancer stem cells with BASC properties. The CD24(+)CD221(+) human lung adenocarcinoma stem cells were purified by FCM and then subjected to the immunofluorescent staining. The results documented that these cells had the phenotype of CCSP(+)SP-C(+)OCT4(+), with the same phenotype as mouse BASC. Furthermore, the floatgrowing spheres (named pulmospheres) were developed after 2-week incubation of cancer cells in the serum-free medium containing EGF, IGF-1, and FGF-10. Again, the resultant pulmosphere cells had the phenotype of BASC. These cells were able to differentiate when incubated for two weeks in serum-containing conditions, exhibiting the loss of CCSP and OCT4 markers. Animal studies indicated that the pulmosphere cells had the highly metastatic capacity.The human lung adenocarcinoma stem cells may originate from the transformation of BASC, as their mouse counterparts. These primitive cancer cells are characterized to express the BASC markers as well as the embryonic stem cell gene OCT4.

Gastric cancer (GC) is the second leading cause of cancer-related death worldwide, with an estimated one million new cases per year. Approximately 50 % of cases occur in Eastern Asia (mainly in China). In most patients, GC is diagnosed at advanced stage frequently accompanied by extensive invasion and lymphatic metastasis, successful therapeutic strategies are limited and the mortality is high. Therefore, investigations into the molecular mechanisms involving in GC progression have major importance and may tend to develop novel avenues for targeted therapy. MicroRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer (GC) metastasis. We found that miR-148a expression was suppressed by more than 4 folds in GC compared with their corresponding non-tumorous tissues (90 paired), and the downregulated miR-148a was significantly associated with TNM stage and lymph-node metastasis. Functional assays demonstrated that overexpression of miR-148a suppressed GC cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, we found that miR-148a could target RhoA/ROCK signaling pathway through downregulating ROCK1. Overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the two sites of 3' untranslated region of ROCK1. Moreover, in GC tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited GC cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a-induced suppression of GC cell migration and invasion. Taken together, our results show that miR-148a functions as a tumor metastasis suppressor in GC, and downregulation of miR-148a contributes to GC lymph-node metastasis and progression. By understanding the function and molecular mechanism of miR-148a in GC, miR-148a may have a therapeutic potential to suppress GC metastasis. (Clin Cancer Res; 17(24); 7574-83) Download : Download full-size image Fig. 1 . miR-148a is downregulated in GC and associated with advanced clinical stage and lymph-node metastasis.