Association between psoas major muscle mass and CPET performance and long-term survival following major colorectal surgery: A retrospective cohort study.

OBJECTIVES: To evaluate whether computed tomography (CT)-derived psoas major muscle measurements could predict preoperative cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery and to compare predictive performance of psoas muscle measurements using 2D approach and 3D approach. METHODS: A retrospective cohort study compliant with STROCSS standards was conducted. Consecutive patients undergoing major colorectal surgery between January 2011 and January 2017 following CPET as part of their preoperative assessment were included. Regression analyses were modelled to investigate association between the CT-derived psoas major muscle mass variables [total psoas muscle area (TPMA), total psoas muscle volume (TPMV) and psoas muscle index (PMI)] and CPET performance and mortality (1-year and 5-year). Discriminative performances of the variables were evaluated using Receiver Operating Characteristic (ROC) curve analysis. RESULTS: A total of 457 eligible patients were included. The median TPMA and TPMV were 21 â€‹cm2 (IQR: 15-27) and 274 â€‹cm3 (IQR: 201-362), respectively. The median PMI measured via 2D and 3D approaches were 7 â€‹cm2/m2 (IQR: 6-9) and 99 â€‹cm3/m2 (IQR: 76-120), respectively. The risks of 1-year and 5-year mortality were 7.4% and 27.1%, respectively. Regression analyses showed TPMA, TPMV, and PMI can predict preoperative CPET performance and long-term mortality. However, ROC curve analyses showed no significant difference in predictive performance amongst TPMA, TPMV, and PMI. CONCLUSION: Radiologically-measured psoas muscle mass variables may predict preoperative CPET performance and may be helpful with informing more objective selection of patients for preoperative CPET and prehabilitation.

Identifying critical gaps in research to advance global surgery by 2030: a systematic mapping review.

Progress on surgical system strengthening has been slow due to a disconnect between evidence generation and the information required for effective policymaking. This systematic mapping review sought to assess critical research gaps in the field of global surgery guided by the World Health Organisation Health Systems building block framework, analysis of authorship and funding patterns, and an exploration of emerging research partnership networks. Literature was systematically mapped to identify, screen, and synthesize results of publications in the global surgery field between 2015 and March 2022. We searched four databases and included literature published in seven languages. A social network analysis determined the network attributes of research institutions and their transient relationships in shaping the global surgery research agenda. We identified 2,298 relevant studies out of 92,720 unique articles searched. Research output increased from 453 in 2015-16 to 552 in 2021-22, largely due to literature on Covid-19 impacts on surgery. Sub-Saharan Africa (792/2298) and South Asia (331/2298) were the most studied regions, although high-income countries represented a disproportionate number of first (42%) and last (43%) authors. Service delivery received the most attention, including the surgical burden and quality and safety of services, followed by capacity-building efforts in low- and middle-income countries. Critical research in economics and financing, essential infrastructure and supplies, and surgical leadership necessary to guide policy decisions at the country level were lacking. Global surgical systems remain largely under-researched. Knowledge diffusion requires an emphasis on developing sustainable research partnerships and capacity across low- and middle-income countries. A renewed focus must be given to equipping countries with tools for effective decision-making to enhance investments in high-quality surgical services.

EPLIN, a Putative Tumour Suppressor in Colorectal Cancer, Implications in Drug Resistance.

Colorectal cancer is a serious threat to human health. Poor prognosis and frequently reported drug resistance urges research into novel biomarkers and mechanisms to aid in the understanding of the development and progression of colorectal cancer and to optimise therapeutic strategies. In the current study, we investigated the roles of a putative tumour suppressor, EPLIN, in colorectal cancer. Our clinical colorectal cancer cohort and online databases revealed a downregulation of EPLIN in colorectal cancer tissues compared with normal tissues. The reduced expression of EPLIN was associated with poor clinical outcomes of patients. In vitro cellular function assays showed that EPLIN elicited an inhibitory effect on cellular growth, adhesion, migration and invasion. Utilising a protein microarray on protein samples from normal and tumour patient tissues suggested HSP60, Her2 and other signalling events were novel potential interacting partners of EPLIN. It was further revealed that EPLIN and HSP60 were negative regulators of Her2 in colorectal cancer cells. The clinical cohort also demonstrated that expression of HSP60 and Her2 affected clinical outcomes, but most interestingly the combination of EPLIN, HSP60 and Her2 was able to identify patients with the most unfavourable clinical outcome by independently predicting patient overall survival and disease free survival. Furthermore, EPLIN and HSP60 exhibited potential to regulate cellular response to chemotherapeutic and EGFR/Her2 targeted therapeutic agents. In conclusion, EPLIN is an important prognostic factor for patients with colon cancer and reduced EPLIN in CRC contributes to aggressive traits of CRC cells and their responses to chemotherapeutic drugs. Collectively, EPLIN is a pivotal factor for the development and progression of colorectal cancer and has important clinical and therapeutic values in this cancer type.

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design.

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+CD25hiFoxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Surprisingly, both immunogenic peptides and those recognised by Tregs clustered in the same HLA-DR transcending epitope-rich hotspots within the 5T4 protein. Similarly, regions of low Th1-cell immunogenicity also did not contain peptides capable of stimulating Tregs, further supporting the notion that Treg and Th1 cells recognise the same peptides. Understanding the rules which govern the balance of Th1 and Treg cells responding to a given peptide specificity is, therefore, of fundamental importance to designing strategies for manipulating the balance in favour of Th1 cells, and thus the most effective anti-cancer T cell responses.

EPLIN: a fundamental actin regulator in cancer metastasis?

Treatment of malignant disease is of paramount importance in modern medicine. In 2012, it was estimated that 162,000 people died from cancer in the UK which illustrates a fundamental problem. Traditional treatments for cancer have various drawbacks, and this creates a considerable need for specific, molecular targets to overcome cancer spread. Epithelial protein lost in neoplasm (EPLIN) is an actin-associated molecule which has been implicated in the development and progression of various cancers including breast, prostate, oesophageal and lung where EPLIN expression is frequently lost as the cancer progresses. EPLIN is important in the regulation of actin dynamics and has multiple associations at epithelial cells junctions. Thus, EPLIN loss in cancer may have significant effects on cancer cell migration and invasion, increasing metastatic potential. Overexpression of EPLIN has proved to be an effective tool for manipulating cancerous traits such as reducing cell growth and cell motility and rendering cells less invasive illustrating the therapeutic potential of EPLIN. Here, we review the current state of knowledge of EPLIN, highlighting EPLIN involvement in regulating cytoskeletal dynamics, signalling pathways and implications in cancer and metastasis.

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes.

BACKGROUND/AIMS: Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, currently treated empirically with immunosuppression. PG is a good target for gene therapy since the skin is easily accessible. This study used the FDA-approved vector Lipofectamine® 2000 to investigate in vitro transfection of skin keratinocytes. The aim was to determine an optimum transfection protocol, including the effect of drugs currently used to treat PG on the efficiency of gene transfer, since gene therapy is unlikely to be used as monotherapy. METHODS: Cells of the HaCaT line were transfected with the lacZ reporter gene, and transgene expression was measured after a given time period. Conditions tested were: relative concentrations of DNA and Lipofectamine®, time from transfection to measurement of expression, pH, and exposure to clinically relevant drugs (hydrocortisone, methotrexate, infliximab). RESULTS: The greatest levels of ß-galactosidase expression were observed using a DNA:Lipofectamine® ratio of 1:5 (µg/µl) on day 3 after transfection, using culture medium at pH 7, and in the presence of hydrocortisone. Transfection efficiency was reduced by the presence of methotrexate and not significantly affected by infliximab. CONCLUSION: Gene therapy is a potential future strategy for the management of PG; this study is a step towards the development of a topical gene-based agent.

WISP-2 in human gastric cancer and its potential metastatic suppressor role in gastric cancer cells mediated by JNK and PLC-γ pathways.

BACKGROUND: It has recently been shown that WISP proteins (Wnt-inducted secreted proteins), a group of intra- and extra-cellular regulatory proteins, have been implicated in the initiation and progression of a variety of tumour types including colorectal and breast cancer. However, the role of WISP proteins in gastric cancer (GC) cells and their clinical implications have not yet been elucidated. METHODS: The expression of WISP molecules in a cohort of GC patients was analysed using real-time quantitative PCR and immunohistochemistry. The expression of a panel of recognised epithelial-mesenchymal transition (EMT) markers was quantified using Q-PCR in paired tumour and normal tissues. WISP-2 knockdown (kd) sublines using ribozyme transgenes were created in the GC cell lines AGS and HGC27. Subsequently, several biological functions, including cell growth, adhesion, migration and invasion, were studied. Potential pathways for the interaction of EMT, extracellular matrix and MMP were evaluated. RESULTS: Overexpression of WISP-2 was detected in GC and significantly correlated with early tumour node-metastasis staging, differentiation status and positively correlated with overall survival and disease-free survival of the patients. WISP-2 expression was inversely correlated with that of Twist and Slug in paired samples. Kd of WISP-2 expression promoted the proliferation, migration and invasion of GC cells. WISP-2 suppressed GC cell metastasis through reversing EMT and suppressing the expression and activity of MMP9 and MMP2 via JNK and ERK. Cell motility analysis indicated that WISP-2 kd contributed to GC cells' motility and can be attenuated by PLC-γ and JNK small inhibitors. CONCLUSIONS: Increased expression of WISP-2 in GC is positively correlated with favourable clinical features and the survival of patients with GC and is a negative regulator of growth, migration and invasion in GC cells. These findings suggest that WISP-2 is a potential tumour suppressor in GC.

Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer.

BACKGROUND: Kiss-1 and Kiss-1R have been suggested as a novel pair of metastasis suppressors for several human solid tumours, however, their role in colorectal cancer remains largely unknown. Therefore, the aim of this study was to investigate the role and signal transduction of Kiss-1 and Kiss-1R in colorectal cancer. METHODS: Ribozyme transgenes were used to knockdown high expression of Kiss-1 and Kiss-1R in HT115 and HRT18 cells. The stabilized transfected cells were then used to deduce the influence of Kiss-1 and Kiss-1R on the function of colorectal cancer cells by in vitro assays and ECIS assay. The effect of Kiss-1 on MMPs related to tumour metastasis was also deleted by zymography. The mRNA and protein expression of Kiss-1 and Kiss-1R, and their correlation to the clinical outcome in human colorectal cancer were investigated using real-time PCR and IHC respectively. RESULTS: Knocking down Kiss-1 resulted in increased invasion and migration of colorectal cancer cells. Kisspeptin-10 decreased cellular migration of colorectal cancer cells and required ERK signaling as shown during the ECIS based analyses. Reduction of MMP-9 was caused by Kisspeptin-10 and ERK inhibitor, shown by zymography. In human colorectal cancer tissues, the mRNA expression level of Kiss-1 had a negative correlation with Dukes staging, TNM staging, tumour size and lymph node involvement. Reduction of Kiss-1R was also linked to poor prognosis for the patients. CONCLUSIONS: The present study has presented evidence that Kiss-1 may be a putative metastasis suppressor molecule in human colorectal cancer.

Can sugar taxes be used for financing surgical systems in Nigeria? A mixed-methods political economy analysis.

This study determined the feasibility of investing revenues raised through Nigeria's sugar-sweetened beverage (SSB) tax of 10 Naira/l to support the implementation of the National, Surgical, Obstetrics, Anaesthesia and Nursing Plan, which aims to strengthen access to surgical care in the country. We conducted a mixed-methods political economy analysis. This included a modelling exercise to predict the revenues from Nigeria's SSB tax based on its current tax rate over a period of 5 years, and for several scenarios such as a 20% ad valorem tax recommended by the World Health Organization. We performed a gap analysis to explore the differences between fiscal space provided by the tax and the implementation cost of the surgical plan. We conducted qualitative interviews with key stakeholders and performed thematic analyses to identify opportunities and barriers for financing surgery through tax revenues. At its current rate, the SSB tax policy has the potential to generate 35 914 111 USD in year 1, and 189 992 739 USD over 5 years. Compared with the 5-year adjusted surgical plan cost of 20 billion USD, the tax accounts for ∼1% of the investment required. There is a substantial scope for further increases in the tax rate in Nigeria, yielding potential revenues of up to 107 663 315 USD, annually. Despite an existing momentum to improve surgical care, there is no impetus to earmark sugar tax revenues for surgery. Primary healthcare and the prevention and treatment of non-communicable diseases present as the most favoured investment areas. Consensus within the medical community on importance of primary healthcare, along the recent government transition in Nigeria, offers a policy window for promoting a higher SSB tax rate and an adoption of other sin taxes to generate earmarked funds for the healthcare system. Evidence-based advocacy is necessary to promote the benefits from investing into surgery.

Expression of ALCAM in Clinical Colon Cancer and Relationship With Patients' Treatment Responses.

BACKGROUND/AIM: Activated leukocyte cell adhesion molecule (ALCAM) plays an important role in cancer via its homotypical and heterotypical interactions with ALCAM or other proteins and can also mediate cell-cell interactions. The present study investigated the expression of ALCAM in relation to epithelial-to-mesenchymal transition (EMT) markers and its downstream signal proteins including Ezrin-Moesin-Radixin (ERM), in clinical colon cancer and in the progression of the disease. MATERIALS AND METHODS: Expression of ALCAM was determined in a clinical colon cancer cohort and assessed against the clinical pathological factors and outcome, together with the expression patterns of the ERM family and EMT markers. ALCAM protein was detected using immunohistochemistry. Cell line models, with ALCAM knock-down and over-expression, were established and used to test cells' responses to drugs. RESULTS: Tumours from patients who had distant metastasis and died of colon cancer had low levels of ALCAM. Dukes B and C tumours also had lower ALCAM expression than Dukes A tumours. Patients with high levels of ALCAM had a significantly longer overall and disease-free survival than those with lower ALCAM levels (p=0.040 and p=0.044). ALCAM is not only significantly correlated with SNAI1 and TWIST, also positively correlated with SNAI2. ALCAM enhanced the adhesiveness of colorectal cancer, an effect inhibited by both sALCAM and SRC inhibitors. Finally, high ALCAM expression rendered cells resistant, especially to 5-fluorouracil. CONCLUSION: Reduced expression of ALCAM in colon cancer is an indicator of disease progression and a poor prognostic indicator for patient's survival. However, ALCAM can enhance the adhesion ability of cancer cells and render them resistant to chemotherapy drugs.

Assessing the impact of anaesthetic and surgical task-shifting globally: a systematic literature review.

The global shortage of skilled anaesthesiologists, surgeons and obstetricians is a leading cause of high unmet surgical need. Although anaesthetic and surgical task-shifting are widely practised to mitigate this barrier, little is known about their safety and efficacy. This systematic review seeks to highlight the existing evidence on the clinical outcomes of patients operated on by non-physicians or non-specialist physicians globally. Relevant articles were identified by searching four databases (MEDLINE, EMBASE, CINAHL and Global Health) in all languages between January 2008 and February 2022. Retrieved documents were screened against pre-specified inclusion and exclusion criteria, and their qualities were appraised critically. Data were extracted by two independent reviewers and findings were synthesized narratively. In total, 40 studies have been included. Thirty-five focus on task-shifting for surgical and obstetric procedures, whereas four studies address anaesthetic task-shifting; one study covers both interventions. The majority are located in sub-Saharan Africa and the USA. Seventy-five per cent present perioperative mortality outcomes and 85% analyse morbidity measures. Evidence from low- and middle-income countries, which primarily concentrates on caesarean sections, hernia repairs and surgical male circumcisions, points to the overall safety of non-surgeons. On the other hand, the literature on surgical task-shifting in high-income countries (HICs) is limited to nine studies analysing tube thoracostomies, neurosurgical procedures, caesarean sections, male circumcisions and basal cell carcinoma excisions. Finally, only five studies pertaining to anaesthetic task-shifting across all country settings answer the research question with conflicting results, making it difficult to draw conclusions on the quality of non-physician anaesthetic care. Overall, it appears that non-specialists can safely perform high-volume, low-complexity operations. Further research is needed to understand the implications of surgical task-shifting in HICs and to better assess the performance of non-specialist anaesthesia providers. Future studies must adopt randomized study designs and include long-term outcome measures to generate high-quality evidence.

Death associated protein­3 (DAP3) and DAP3 binding cell death enhancer­1 (DELE1) in human colorectal cancer, and their impacts on clinical outcome and chemoresistance.

Death associated protein­3 (DAP3) was identified as a responsive protein to interferon­gamma­induced cell death which possibly exerts this regulation by interacting with DAP3 binding cell Death enhancer­1 (DELE1), a newly discovered mitochondrial stress protein in response to cell stress signals. Whilst DAP3 has been shown to be aberrantly expressed in several cancer types (i.e. breast cancer), little is known about the relationship between DAP3 and DELE1 in cancers. The present study examined the expression levels of both DAP3 and DELE1 in clinical colorectal cancers (CRCs), as well as their implication on chemoresistance and mechanism behind the action. Firstly, transcript levels of both DAP3 and DELE1 were quantitatively assessed in a clinical cohort of CRC (n=94). Tumour tissues had significantly higher levels of DAP3, but not DELE1 compared with normal tissues. Levels of DAP3 and DELE1 had a significant association with patient's clinical outcomes and local recurrence. DAP3 and DELE1 significantly correlated in normal colorectal tissues but not in tumour tissues. Secondly, the protein levels of DAP3 and DELE1 were evaluated in both normal and tumour colon tissues which showed that both proteins were highly aberrant in CRC tissues. In addition, both DAP3 and DELE1 at transcript and protein levels were identified as prognostic factors for patient's clinical outcomes. Furthermore, in in vitro assays, knocking down DAP3 or DELE1, and in particular both DAP3 and DELE1 together rendered the CRC cells more sensitive to chemotherapy drugs, consistent with clinical findings of the TCGA­COAD datasets. The acquisition of drug sensitivity following the genetic knockdown was independent of the mitochondrial metabolism, as neither DAP3 knockdown nor DELE1 knockdown showed a significant change. In summary, DAP3 and DELE1 are highly aberrant in CRCs, and both molecules are prognostic factors for patient's clinical outcomes and local recurrence, and are indicators for chemoresistance.

Targeting Hyaluronic Acid and Peritoneal Dissemination in Colorectal Cancer.

Peritoneal metastasis (PM) from colorectal cancer (CRC) carries a significant mortality rate for patients and treatment is challenging. The development of PM is a multistep process involving detachment, adhesion, invasion and colonization of the peritoneal cavity. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) for PM from CRC has some benefit but overall survival is poor and recurrence rates are high. Treatments to prevent the development of peritoneal metastasis could have the potential to improve CRC survival and disease-free outcomes. The ability of cancer cells to invade the peritoneum and become established as metastatic tumors is influenced by a multifactorial process. Hyaluronic acid (HA) has been shown to coat the mesothelial cells of the peritoneum and has been demonstrated to be utilized in various malignancies as part of the metastatic process in peritoneal dissemination. CD44, RHAMM (CD168) and ICAM-1 have all been shown to be binding partners for HA. Targeting HA-mediated binding may prevent adhesion to distant sites within the peritoneum through suppression of interaction of these molecules. Here we review the current literature and discuss key molecules involved with PM dissemination, with the potential to target these mechanisms in the delivery of future treatments.

Five thousand years of minimal access surgery: 1850 to 1990: Technological developments.

This is the second of a three-part series that charts the history of minimal access surgery from antiquity to current times. Although rapid developments in laparoscopic and robotic surgery have transformed surgical care over the last 30 years, our predecessors made significant advances in their time which set the principles for modern practice. Part I of this series described how ancient medical practitioners developed simple instruments, from metal or wood, for viewing body cavities. Improvements in the use of metal, glass and lighting allowed for inspection of deeper parts of the body. This second part of the series will show how advances in electrical technology allowed the development of improved lighting for endoscopy and laparoscopy along with the use of electrocautery for a wide range of therapeutic procedures.

Five thousand years of minimal access surgery: 1990-present: organisational issues and the rise of the robots.

The last 30 years have seen a revolution in the provision of minimal access surgery for many conditions, and technological advances are increasing exponentially. Many instruments are superseded by improved versions before the NHS and publicly funded health services can offer widespread coverage. Although we tend to think of minimal access surgery as a modern concept, Parts I and II of this series have shown that there is a 5000-year history to this specialty and our predecessors laid down many principles which still apply today. During the 19th and early 20th centuries, minimal access surgery was driven forward by visionary individuals, often in the face of opposition from colleagues and the medical establishment. However, in the last 30 years, innovation has been driven more in partnerships between healthcare, scientific, financial, educational and charitable organisations. There are far too many individuals involved to detail every contribution here, but this third part of the series will concentrate on some of the important themes in the development of minimal access surgery to its current status.

SIPA1 Is a Modulator of HGF/MET Induced Tumour Metastasis via the Regulation of Tight Junction-Based Cell to Cell Barrier Function.

BACKGROUND: Lung cancer is the leading cause of cancer death. SIPA1 is a mitogen induced GTPase activating protein (GAP) and may hamper cell cycle progression. SIPA1 has been shown to be involved in MET signaling and may contribute to tight junction (TJ) function and cancer metastasis. METHODS: Human lung tumour cohorts were analyzed. In vitro cell function assays were performed after knock down of SIPA1 in lung cancer cells with/without treatment. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to analyze expression of HGF (hepatocyte growth factor), MET, and their downstream markers. Immunohistochemistry (IHC) and immunofluorescence (IFC) staining were performed. RESULTS: Higher expression of SIPA1 in lung tumours was associated with a poorer prognosis. Knockdown of SIPA1 decreased invasiveness and proliferation of in vitro cell lines, and the SIPA1 knockdown cells demonstrated leaky barriers. Knockdown of SIPA1 decreased tight junction-based barrier function by downregulating MET at the protein but not the transcript level, through silencing of Grb2, SOCS, and PKCµ (Protein kinase Cµ), reducing the internalization and recycling of MET. Elevated levels of SIPA1 protein are correlated with receptor tyrosine kinases (RTKs), especially HGF/MET and TJs. The regulation of HGF on barrier function and invasion required the presence of SIPA1. CONCLUSIONS: SIPA1 plays an essential role in lung tumourigenesis and metastasis. SIPA1 may be a diagnostic and prognostic predictive biomarker. SIPA1 may also be a potential therapeutic target for non-small cell lung cancer (NSCLC) patients with aberrant MET expression and drug resistance.

NUPR1 and its potential role in cancer and pathological conditions (Review).

Nuclear protein­1 (NUPR1) is also known as Com­1 or p8. It is a protein primarily found in the nucleus of various cells, including cancer cells, and it has been found to play an important role in cell stress and stress­related apoptosis. Over the past two decades, NUPR1 has been firmly indicated to play a role in the development and progression of numerous types of cancer, as well as in a number of other pathological conditions, including pancreatitis, diabetes, neurological and inflammatory conditions. The past decade has witnessed a rapid understanding of the biological and cellular mechanisms through which NUPR1 operates on cells and the identification of new variant of the protein. Most importantly, there have been comprehensive studies on the clinical and pathological aspects of NUPR1 and its variant in multiple malignancies and identification of therapeutic methods by targeting the protein. The present review aimed to summarise the current knowledge relating to NUPR1 in human malignancies and to discuss the associated controversies and potential future prospects of this molecule.

Expression of Death Associated Proteins DAP1 and DAP3 in Human Pancreatic Cancer.

BACKGROUND: Death associated proteins (DAPs) are involved in the apoptosis of various cell types in response to interferon gamma, including cancer cells. The present study assessed both DAP1 and DAP3 in human pancreatic cancer. MATERIALS AND METHODS: DAP1 and DAP3 transcripts were quantitatively analysed in pancreatic tumour tissues and paired adjacent normal tissues using real time PCR followed by statistical analyses for their clinical implications. RESULTS: Levels of DAP3 transcripts in pancreatic cancer were markedly higher than in normal tissues, whereas DAP1 had lower levels in cancer versus normal tissues. Adenocarcinomas showed higher levels of DAP3 than other histological types. Patients with high levels of DAP3 had a significantly shorter overall survival than those with low levels (p=0.012). The status of DAP3 and lymph node involvement identified patients with poor survival (p<0.00001). CONCLUSION: DAP3 was highly expressed in pancreatic tumour tissues and was significantly associated with shorter survival.

Influence of anaesthetics on the production of cancer cell motogens, stromal cell-derived factor-1 and hepatocyte growth factor by fibroblasts.

Anaesthetics have been implicated to influence cancer cells and progression. Similarly, crosstalk between cancer cells and stromal components within the microenvironment is also an important factor driving progression. Stromal cell-derived factor-1 (SDF-1) and hepatocyte growth factor (HGF) are key chemokines/cytokines produced by fibroblasts which have been established as influential factors in cancer progression. The present study explored the capacity of anaesthetics to influence the expression of these key molecules in fibroblasts. The anaesthetics rocuronium bromide (RB), vecuronium bromide (VB), suxamethonium chloride CRS (SCC), dexmedetomidine hydrochloride (DH) and lidocaine were used to treat MRC-5 fibroblasts over a range of concentrations. Following treatment, transcript expression of SDF-1 and HGF was quantified using quantitative PCR. Treatment of MRC-5 cells with RB brought about a reduction of SDF-1 expression which was found to be significant in the 45 µg/ml treatment group. Treatment with the other anaesthetics brought about some alterations in SDF-1 expression but these were not found to be statistically significant. Treatment with the tested anaesthetics did not have any significant effect on HGF transcript expression within MRC-5 cells, although again some alterations were observed. The results indicated that anaesthetics may have an impact on the fibroblast component of the tumour microenvironment, potentially influencing SDF-1 and HGF expression which in turn could influence tumour progression.