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Background Gastro-Intestinal Stromal tumours (GISTs) are rare neoplasms of mesenchymal origin that arise in the GI tract and account for approximately 0.1-3% of all GI tumours. The aim of this study was to determine whether the mode of clinical presentation of GISTs has an effect on outcome. Methods Consecutive 143 patients diagnosed with GISTs were identified from the regional network database (median age 67 (21-88) years, 85 male). Data were collected on presenting symptoms, tumour, treatment undertaken, and the primary outcome measure was survival. Results The commonest GIST anatomical sites were stomach (69.9%), small bowel (13.3%), and colon (4.9%). Commonest symptoms were abdominal pain (30.0%), dyspepsia (11.8%), and anaemia (11.1%). Symptomatic presentations were associated with older age (p = 0.056) and higher mitotic index (>5 per 50HPF, p = 0.045). On univariable analysis the factors associated with cumulative 10-year survival were age (p = 0.076), the presence of symptoms (78.1% vs. 96.4%, p = 0.028), mitotic index (p = 0.011), and modified National Institutes of Health (NIH) prognostic index (p = 0.010), but not deprivation index, anatomical site or GIST diameter. Symptomatic patients aged over 60 years with mitotic index >5 per 50 HPF had the poorest 10-year survival at 63.6% (HR 2.577, 95%CI 1.132-5.867). On multivariable analysis, NIH index (HR 4.283, 95%CI 1.395-13.149, p = 0.011) and age (HR1.061, 95%CI 1.006-1.118, p = 0.029) were independently associated with 10-year survival. Conclusions Age, symptoms, and NIH criteria represent the most important prognostic biomarkers in patients diagnosed with GISTs.

Aberrant expression of nephroblastoma overexpressed (NOV) has been evident\ud in certain malignancies. In the current study, we aim to investigate the role played by\ud NOV in colorectal cancer (CRC). NOV expression was determined in a cohort of 359 CRC\ud tissues and 174 normal colorectal tissues. Its impact on CRC cells was investigated\ud using in vitro NOV knockdown and overexpression models. NOV transcripts were\ud reduced in the CRC tumours compared with the paired adjacent normal colorectal\ud tissues (p < 0.01) and was associated with distant metastases. NOV knockdown\ud resulted in increased cell proliferation and invasion of RKO cells, whilst an opposite\ud effect was seen in the HT115 NOV over expressing cells. A positive association\ud between Caspase-3/-8 and NOV was seen in NOV knockdown and overexpression\ud cell lines which contributed to the survival of serum deprived CRC cells. Further\ud investigation showed that NOV regulated proliferation, survival and invasion through\ud the JNK pathway. NOV knockdown in RKO cells reduced the responsiveness to\ud 5-Fluorouracil treatment, whilst overexpression in HT115 cells exhibited a contrasting\ud effect. Taken together, NOV is reduced in CRC tumours and this is associated with\ud disease progression. NOV inhibits the proliferation and invasion of CRC cells in vitro.\ud Inhibition of proliferation is mediated by a regulation of Caspase-3/-8, via the JNK\ud pathway, which has potential for predicting and preventing chemoresistance.

The downstream of tyrosine kinase 7 (DOK7) is an adaptor protein mediating signalling transduction between receptors and intracellular downstream molecules. Reduced expression of DOK7 has been observed in breast cancer. The present study aimed to investigate the role played by DOK7 in lung cancer. The expression of DOK7 at both mRNA and protein levels was evaluated in human lung cancer. A reduced expression of DOK7 transcripts was seen in lung cancers compared with normal lung tissues. Kaplan-Meier analyses showed that the reduced expression of DOK7 was associated with poorer overall survival and progression-free survival of patients with lung cancer. A further western blot analysis revealed a predominant expression of DOK7 isoform 1 (DOK7V1) in normal lung tissues, which was reduced in lung cancer. Forced overexpression of DOK7V1 in lung cancer cell lines, A549 and H3122 resulted in a decrease of in vitro cell proliferation and migration, while adhesion to extracellular matrix was enhanced following the expression. In conclusion, DOK7 was reduced in lung cancer and reduced DOK7 expression was associated with poorer survival. DOK7 isoform 1 plays an inhibitory role on the proliferation and migration of lung cancer cells in which Akt pathway may be involved.

Phospholipase C (PLC) regulates a number of\ud cellular behaviours including cell motility, cell transformation,\ud differentiation and cell growth. PLC plays a regulatory\ud role in cancer cells partly by acting as signalling intermediates\ud for cytokines such as EGF and interleukins. The current\ud study examined the expression of the PLC isozymes in human\ud breast cancer and corresponding clinical relevance. Transcript\ud levels of human PLC-α, -β1, -δ, -ε, and -γ1 in human breast\ud cancer tissues were quantitatively determined by real-time\ud PCR. Immunochemical staining was performed for PLC-δ.\ud The clinical relevance was analysed with clinic pathological\ud information. Mammary tissues widely expressed PLC-α, -β1,\ud -δ, -ε, and -γ1. Significantly high levels of PLC -β1 and -ε\ud were seen in breast cancer tissues in comparison with normal\ud mammary gland tissues. PLC-γ1 however, showed marginally\ud low levels in tumour tissues. No significant difference was\ud seen in the expression of the PLC isozymes in tumours with\ud lymph node metastases. Moderately and poorly differentiated\ud breast tumours (grade 2 and grade 3) had significantly higher\ud levels of PLC-γ1, compared with well differentiated tumours.\ud High levels of PLC-δ were significantly correlated with a\ud shorter disease-free survival. The altered expression of other\ud isozymes had no correlation with the survival. It is concluded\ud that mammary tissues differentially expressed PLC isozymes.\ud These isozymes have certain implications in the disease development\ud and progression, with PLC-δ showing a significant\ud correlation with shorter disease-free survival.

Objective: Video-assisted thoracoscopic surgical (VATS) lung biopsy is frequently used in the diagnosis of parenchymal lung disease. However, there is still debate over the need for routine use of an intercostal chest drain after this procedure. This study aimed to evaluate the necessity of positioning an intercostal chest drain as an integral part of VATS lung biopsy. Methods: Data from VATS lung biopsies performed over a 5-year period were retrospectively analysed. Patients in whom there was evidence of air leak intra-operatively following lung biopsy were excluded. Patients in whom no air leak was detected on testing were included in this study. A chest drain was inserted solely according to the surgeons’ practice. Results:This study included 175 patients. Of these, 82 patients had an intercostal chest drain positioned during the VATS procedure and 93 did not. There were no significant differences between the two groups in terms of mean (standard deviation (SD)), age (54.4 (14.9) vs 55.8 (13.5) years, p = 0.58), gender (63% vs 59% males, p = 0.56) or side of procedure (45% vs 56% right side, p = 0.22). One patient in the ‘no drain’ group developed a clinically significant pneumothorax 24 h after surgery and required a drain to be inserted. There was also no significant difference between the two groups in the incidence of radiologically detected pneumothorax immediately post-procedure (23% vs 20%, p = 0.66) or on postoperative day 1 (26% vs 20%, p = 0.63). There was no significant difference in the incidence of pneumothorax on follow-up (at 4—6 weeks) chest radiograph (10% vs 7%, p = 0.61). In all cases, the pneumothoraces were small and not clinically significant. However, there was a significant difference in the median (inter-quartile range (IQR)) length of stay between the two groups (3 (2,4) vs 2 (1,3) days, respectively, p < 0.001). Conclusions: The routine use of an intercostal chest drain after VATS lung biopsy unnecessarily increases the length of hospital stay without reduction in the incidence of pneumothorax. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Sonic Hedgehog (SHH) is a protein that is aberrantly expressed in various human tumors. SHH and its signaling molecules have been indicated as potential therapeutic targets. In the present study, we evaluated the expression of SHH transcript in human non-small cell lung cancer (NSCLC) tissues and investigated the impact of inhibiting SHH together with a traditional Chinese medicine formula, YangZheng XiaoJi (YZXJ), on the function and growth of lung cancer cells. Human NSCLC tissues had significantly higher levels of the SHH transcript compared matched normal lung tissues (n=83). TNM2 tumors and tumors with pleural invasion had higher levels than TNM1 and non-invasive tumors. High SHH levels were associated with a shorter overall survival (OS) of the patients. A SHH inhibitor, cyclopamine, and YZXJ alone or in combination had a marked inhibitory effect on cellular invasion and cellular migration of human lung cancer cells, A549 and SKMES1. YangZheng XiaoJi and its combination with cyclopamine also significantly reduced the growth of lung tumors in vivo together with a reduction of SHH and smoothened (Smo) proteins in the lung tumors. The present study provides evidence that blocking SHH by way of small inhibitor and by YangZheng XiaoJi has a profound influence on lung cancer cells as seen by in vitro invasion and cell migration and in vivo tumor growth. Together with the aberrant expression of SHH in NSCLC tumors in the patients, it is suggested that SHH is a potential target for therapies for NSCLC.

Background Hepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells. Methods Human lung cancer cells, SKMES1 and A549 were used in the study. An extract from the medicine was used. Cell migration was investigated using the EVOS and by ECIS. Cell–matrix adhesion and in vitro invasion were assessed. In vivo growth of lung cancer was tested using an in vivo xenograft tumour model and activation of the HGF receptor in lung tumours by an immunofluorescence method. Results Both lung cancer cells increased their migration in response to HGF and responded to YZXJ by reducing their speed of migration. YZXJ markedly reduced the migration and in vitro invasiveness induced by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor inhibitors on the lung cancer cells both on HGF receptor activation and on cell functions. A combination of HGF and EGF resulted in a greater increase in cell migration, which was similarly inhibited by YZXJ, and in combination with the HGF receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour growth and potentiated the effects of PHA665752 on tumour growth. It was further revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF receptor in lung tumours. Conclusion YZXJ has a significant role in reducing the migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This effect is likely attributed to the inhibition of the HGF receptor activation. These results indicate that YZXJ has a therapeutic role in lung cancer and that combined strategy with methods to block HGF and EGF should be considered. Electronic supplementary material The online version of this article (doi:10.1186/s12967-015-0639-1) contains supplementary material, which is available to authorized users.