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1. The therapeutic potential of targeting hyaluronic acid to prevent peritoneal metastatic dissemination in colorectal cancer

Author

Soliman, Faris

Abstract

Background Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body and is particularly found in abundance coating the mesothelial cells of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion to the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1. Methods Expression of HA-dependent and HA-independent adhesion molecules was examined in CRC using tissue microarray datasets and matched to clinicopathological data. In vitro peritoneal modelling tested CRC cellular adhesion when treated with either a small peptide competitive binding HA-inhibitor (HAi) or excess exogenous HA. Further in vitro testing assessed CRC ability to aggregate and survive when in suspension, evaluating the ability of cells both to survive and to aggregate at fixed time points. An in vivo Xenograft peritoneal model was used, using three groups of CD1 nude mice injected with CRC cells both intraperitoneally (IP) and subcutaneously to monitor tumour growth. Treatment groups received either a further IP injection of HAi or HA continuously for 5 days for the first week of treatment and biweekly for the remaining three weeks and compared to a control. (PPL: PE9445FC2). Results Tissue microarray data demonstrated a significant increase in RNA expression of the three HA-dependent adhesion molecules CD44 (p=<0.0001), RHAMM (p=0.0004) and ICAM-1 (p=<0.0001) in CRC. Whereas, in non-HA-dependent adhesion molecules showed eithersignificant downregulation or no expression difference. In vitro adhesion assays saw significantly reduced cellular adhesion of HT115, HRT-18 and Caco-2 cell lines when treated with either HAi or excess exogenous HA in peritoneal mimicking plate coated models. Free-floating CRC cells in suspension demonstrated, firstly, significantly decreased viability at 24-hours when compared to controls (HAi p=0.0040, HA312ug/ml p= 0.0039 and HA624ug/ml p= 0.0019). Secondly, treatment groups exhibited reduced aggregation when compared to controls (HAi p=0.0015, HA312ug/ml p=0.0027 and HA624ug/ml p=0.0017). In vivo experimentation demonstrated no difference in weight or subcutaneous tumour size growth between groups. However, a significant reduction in the number of PM was seen for both treatment groups, compared to controls (HAi p=0.0094, HA p=0.0009). Interestingly, there was no significant difference in average peritoneal tumour nodule size between the groups compared to controls (HAi p=0.7976, HA p=0.4536). Conclusions Expression of HA-dependent adhesion molecules is increased in CRC. Targeting HAdependent adhesion potentially affects CRC cells' ability to survive in the peritoneal environment and may have a potential therapeutic use in treatment or prevention of PM in CRC. Further in vitro and in vivo modelling is needed.

Published
2021

2. Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

Author

Abe, Tomoyuki, Abu Hilal, Moh'd, Achalandabaso Boira, Maria del Mar, Adham, Mustapha, Adam, Mohamed, Ahmad, Maryam, Al-Sarireh, Bilal, Albiol, Maite, Alhaboob, Nassir, Alseidi, Adnan, Ammar, Houssem, Anand, Akshay, Andersson, Bodil, Antonakis, Pantelis, Araya, Veronica, Ashley, Stanley W., Atanasov, Georgi, Ausania, Fabio, Balestri, Ricardo, Banerjee, Abhirup, Banerjee, Sudeep, Banting, Simon, Barauskas, Giedrius, Bartsch, Fabian, Belli, Andrea, Beretta, Simona, Berrevoet, Frederik, Bhandari, Ramesh Singh, Blanco Fernandez, Gerardo, Bolm, Louisa, Bonal, Mathieu, Bozkurt, Emre, Braat, Andries E., Bradshaw, Luke, Bramis, Konstantinos, Branes, Alejandro, Burdine, Lyle, Byrne, Matthew, Caceres, Maria, Castro Santiago, Maria Jesus, Chan, Benjamin, Chong, Lynn, Çoker, Ahmet, Conde Rodriguez, Maria, Croagh, Daniel, Crutchley, Alyn, Cutolo, Carmen, D'Hondt, Mathieu, D'Souza, Daniel, Daams, Freek, Dalla Valle, Raffaele, Davide, José, de Bellis, Mario, de Boer, Marieke, de Meyere, Celine, de Reuver, Philip, Dixon, Matthew, Dorovinis, Panagiotis, Echeverría Bauer, Gabriela, Eduarda, Maria, Eker, Hasan, Erdmann, Joris, Erkan, Mert, Felekouras, Evangelos, Felli, Emanuele, Fernandes, Eduardo, Figueroa Rivera, Eduardo, Fulop, Andras, Galun, Daniel, Gerhards, Michael, Ghorbani, Poya, Giannone, Fabio, Gil, Luis, Giorgakis, Emmanouil, Giuffrida, Mario, Giuliante, Felice, Gkekas, Ioannis, Gomez Bravo, Miguel, Groot Koerkamp, Bas, Guevara, Oscar, Guglielmi, Alfredo, Gulla, Aiste, Gupta, Rahul, Gupta, Amit, Gutiérrez, Marta, Hafeez Bhatti, Abu Bakar, Hagendoorn, Jeroen, Hajee, Zain, Hakeem, Abdul Rahman, Hamid, Hytham, Hassen, Sayed, Heinrich, Stefan, Higuchi, Ryota, Hoffman, Daniel, Holroyd, David, Hughes, Daniel, Ivanecz, Arpad, Iype, Satheesh, Jaen Torrejimeno, Isabel, Joglekar, Shantanu, Jones, Robert, Kaczirek, Klaus, Kanhere, Harsh, Kausar, Ambareen, Kee, Zhanyi, Keilson, Jessica, Kleef, Jorg, Klose, Johannes, Knowles, Brett, Koong, Jun Kit, Kumar, Nagappan, Kunnuru, Supreeth, Lakhey, Paleswan Joshi, Laurenzi, Andrea, Lee, Yeong Sing, Leon, Felipe, Leow, Voon Meng, Lequeu, Jean-Baptiste, Lesurtel, Mickael, Lo, Elisabeth, Löb, Stefan, Lockie, Elizabeth, Lodge, Peter, López Garnica, Dolores, Lopez Lopez, Victor, Lundgren, Linda, Machairas, Nikolaos, Maharjan, Dhiresh, Malde, Deep, Martel, Guillaume, Martin, Julie, Mazzola, Michele, Mehrabi, Arianeb, Memeo, Ricardo, Milana, Flavio, Molina, George, Monette, Leah, Morgul, Haluk, Moris, Dimitrios, Morsi-Yeroyannis, Antonios, Mowbray, Nicholas, Mulita, Francesk, Muttillo, Edoardo Maria, Nandasena, Malith, Nashidengo, Pueya Rashid, Nickkholgh, Arash, Noel, Colin Byron, Ohtsuka, Masayuki, Ozolins, Arturs, Pandanaboyana, Sanjay, Pararas, Nikolaos, Parente, Alessandro, Peng, June, Perfecto Valero, Arkaitz, Perinel, Julie, Perivoliotis, Konstatinos, Perra, Teresa, Pessaux, Patrick, Petruch, Natalie, Piccolo, Gaetano, Piros, Laszlo, Porcu, Alberto, Prabakaran, Viswakumar, Prasad, Raj, Prieto Calvo, Mikel, Primavesi, Florian, Pueyo Periz, Eva Maria, Quaglia, Alberto, Ramia Angel, Jose M., Rammohan, Ashwin, Razionale, Francesco, Robles Campos, Ricardo, Roy, Manas, Rozwadowski, Sophie, Ruffolo, Luis, Ruiz, Natalia, Ruzzenante, Andrea, Saadat, Lily, Said, Mohamed Amine, Saladino, Edoardo, Saliba, Gabriel, Sandstrom, Per, Schena, Carlo Alberto, Scholer, Anthony, Schwarz, Christoph, Serafini, Lorenzo, Serrano, Pablo E., Sharma, Deepak, Sheen, Aali, Siddagangaiah, Vishwanath, Silva, Michael, Singh, Saurabh, Siriwardena, Ajith, Skalski, Michal, Smig, Mante, Soliman, Faris, Sonkar, Abhinav Arun, Sousa Silva, Donzília, Sparrelid, Ernesto, Srinivasan, Parthi, Sternby Eilard, Malin, Strobel, Oliver, Stupan, Urban, Suarez-Munoz, Miguel Angel, Subramaniam, Manisekar, Sugiura, Teiichi, Sutcliffe, Robert, Swank, Hilko, Taylor, Lillian, Thapa, Prabin Bikram, The, Catherine, Thepbunchonchai, Asara, Thieu, Caman, Tiwari, Navneet, Torzilli, Guido, Tovikkai, Chutwichai, Trotovsek, Blaz, Tsaramanidis, Savvas, Tsoulfas, Georgios, Uesaka, Katsuhiko, Umar, Garzali, Urbani, Lucio, Vailas, Michail, van Dam, Ronald, van de Boezem, Peter, van Laarhoven, Stijn, Vanagas, Tomas, Van Dooren, Mike, Viennet, Manon, Vigano, Luca, Vijayashanker, Aarathi, Villodre, Celia, Wakai, Toshifumi, Workneh, Aklile, Xu, Li, Yamamoto, Masakazu, Yang, Zhiying, Young, Robert, Zivanovic, Marko, Balakrishnan, Anita, Barmpounakis, Petros, Demiris, Nikolaos, Jah, Asif, Spiers, Harry V.M., Talukder, Shibojit, Martin, Jack L., Gibbs, Paul, Harper, Simon J.F., Huguet, Emmanuel L., Kosmoliaptsis, Vasilis, Liau, Siong S., Praseedom, Raaj K., Basu, Bristi, de Aretxabala, Xavier, Lendoire, Javier, Maithel, Shishir, Serrablo, Alejandro, and Adsay, Volkan

Published
2023
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6. Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

Author

Balakrishnan, Anita, primary, Barmpounakis, Petros, additional, Demiris, Nikolaos, additional, Jah, Asif, additional, Spiers, Harry V.M., additional, Talukder, Shibojit, additional, Martin, Jack L., additional, Gibbs, Paul, additional, Harper, Simon J.F., additional, Huguet, Emmanuel L., additional, Kosmoliaptsis, Vasilis, additional, Liau, Siong S., additional, Praseedom, Raaj K., additional, Basu, Bristi, additional, de Aretxabala, Xavier, additional, Lendoire, Javier, additional, Maithel, Shishir, additional, Branes, Alejandro, additional, Andersson, Bodil, additional, Serrablo, Alejandro, additional, Adsay, Volkan, additional, Abe, Tomoyuki, additional, Abu Hilal, Moh'd, additional, Achalandabaso Boira, Maria del Mar, additional, Adham, Mustapha, additional, Adam, Mohamed, additional, Ahmad, Maryam, additional, Al-Sarireh, Bilal, additional, Albiol, Maite, additional, Alhaboob, Nassir, additional, Alseidi, Adnan, additional, Ammar, Houssem, additional, Anand, Akshay, additional, Antonakis, Pantelis, additional, Araya, Veronica, additional, Ashley, Stanley W., additional, Atanasov, Georgi, additional, Ausania, Fabio, additional, Balestri, Ricardo, additional, Banerjee, Abhirup, additional, Banerjee, Sudeep, additional, Banting, Simon, additional, Barauskas, Giedrius, additional, Bartsch, Fabian, additional, Belli, Andrea, additional, Beretta, Simona, additional, Berrevoet, Frederik, additional, Bhandari, Ramesh Singh, additional, Blanco Fernandez, Gerardo, additional, Bolm, Louisa, additional, Bonal, Mathieu, additional, Bozkurt, Emre, additional, Braat, Andries E., additional, Bradshaw, Luke, additional, Bramis, Konstantinos, additional, Burdine, Lyle, additional, Byrne, Matthew, additional, Caceres, Maria, additional, Castro Santiago, Maria Jesus, additional, Chan, Benjamin, additional, Chong, Lynn, additional, Çoker, Ahmet, additional, Conde Rodriguez, Maria, additional, Croagh, Daniel, additional, Crutchley, Alyn, additional, Cutolo, Carmen, additional, D'Hondt, Mathieu, additional, D'Souza, Daniel, additional, Daams, Freek, additional, Dalla Valle, Raffaele, additional, Davide, José, additional, de Bellis, Mario, additional, de Boer, Marieke, additional, de Meyere, Celine, additional, de Reuver, Philip, additional, Dixon, Matthew, additional, Dorovinis, Panagiotis, additional, Echeverría Bauer, Gabriela, additional, Eduarda, Maria, additional, Eker, Hasan, additional, Erdmann, Joris, additional, Erkan, Mert, additional, Felekouras, Evangelos, additional, Felli, Emanuele, additional, Fernandes, Eduardo, additional, Figueroa Rivera, Eduardo, additional, Fulop, Andras, additional, Galun, Daniel, additional, Gerhards, Michael, additional, Ghorbani, Poya, additional, Giannone, Fabio, additional, Gil, Luis, additional, Giorgakis, Emmanouil, additional, Giuffrida, Mario, additional, Giuliante, Felice, additional, Gkekas, Ioannis, additional, Gomez Bravo, Miguel, additional, Groot Koerkamp, Bas, additional, Guevara, Oscar, additional, Guglielmi, Alfredo, additional, Gulla, Aiste, additional, Gupta, Rahul, additional, Gupta, Amit, additional, Gutiérrez, Marta, additional, Hafeez Bhatti, Abu Bakar, additional, Hagendoorn, Jeroen, additional, Hajee, Zain, additional, Hakeem, Abdul Rahman, additional, Hamid, Hytham, additional, Hassen, Sayed, additional, Heinrich, Stefan, additional, Higuchi, Ryota, additional, Hoffman, Daniel, additional, Holroyd, David, additional, Hughes, Daniel, additional, Ivanecz, Arpad, additional, Iype, Satheesh, additional, Jaen Torrejimeno, Isabel, additional, Joglekar, Shantanu, additional, Jones, Robert, additional, Kaczirek, Klaus, additional, Kanhere, Harsh, additional, Kausar, Ambareen, additional, Kee, Zhanyi, additional, Keilson, Jessica, additional, Kleef, Jorg, additional, Klose, Johannes, additional, Knowles, Brett, additional, Koong, Jun Kit, additional, Kumar, Nagappan, additional, Kunnuru, Supreeth, additional, Lakhey, Paleswan Joshi, additional, Laurenzi, Andrea, additional, Lee, Yeong Sing, additional, Leon, Felipe, additional, Leow, Voon Meng, additional, Lequeu, Jean-Baptiste, additional, Lesurtel, Mickael, additional, Lo, Elisabeth, additional, Löb, Stefan, additional, Lockie, Elizabeth, additional, Lodge, Peter, additional, López Garnica, Dolores, additional, Lopez Lopez, Victor, additional, Lundgren, Linda, additional, Machairas, Nikolaos, additional, Maharjan, Dhiresh, additional, Malde, Deep, additional, Martel, Guillaume, additional, Martin, Julie, additional, Mazzola, Michele, additional, Mehrabi, Arianeb, additional, Memeo, Ricardo, additional, Milana, Flavio, additional, Molina, George, additional, Monette, Leah, additional, Morgul, Haluk, additional, Moris, Dimitrios, additional, Morsi-Yeroyannis, Antonios, additional, Mowbray, Nicholas, additional, Mulita, Francesk, additional, Muttillo, Edoardo Maria, additional, Nandasena, Malith, additional, Nashidengo, Pueya Rashid, additional, Nickkholgh, Arash, additional, Noel, Colin Byron, additional, Ohtsuka, Masayuki, additional, Ozolins, Arturs, additional, Pandanaboyana, Sanjay, additional, Pararas, Nikolaos, additional, Parente, Alessandro, additional, Peng, June, additional, Perfecto Valero, Arkaitz, additional, Perinel, Julie, additional, Perivoliotis, Konstatinos, additional, Perra, Teresa, additional, Pessaux, Patrick, additional, Petruch, Natalie, additional, Piccolo, Gaetano, additional, Piros, Laszlo, additional, Porcu, Alberto, additional, Prabakaran, Viswakumar, additional, Prasad, Raj, additional, Prieto Calvo, Mikel, additional, Primavesi, Florian, additional, Pueyo Periz, Eva Maria, additional, Quaglia, Alberto, additional, Ramia Angel, Jose M., additional, Rammohan, Ashwin, additional, Razionale, Francesco, additional, Robles Campos, Ricardo, additional, Roy, Manas, additional, Rozwadowski, Sophie, additional, Ruffolo, Luis, additional, Ruiz, Natalia, additional, Ruzzenante, Andrea, additional, Saadat, Lily, additional, Said, Mohamed Amine, additional, Saladino, Edoardo, additional, Saliba, Gabriel, additional, Sandstrom, Per, additional, Schena, Carlo Alberto, additional, Scholer, Anthony, additional, Schwarz, Christoph, additional, Serafini, Lorenzo, additional, Serrano, Pablo E., additional, Sharma, Deepak, additional, Sheen, Aali, additional, Siddagangaiah, Vishwanath, additional, Silva, Michael, additional, Singh, Saurabh, additional, Siriwardena, Ajith, additional, Skalski, Michal, additional, Smig, Mante, additional, Soliman, Faris, additional, Sonkar, Abhinav Arun, additional, Sousa Silva, Donzília, additional, Sparrelid, Ernesto, additional, Srinivasan, Parthi, additional, Sternby Eilard, Malin, additional, Strobel, Oliver, additional, Stupan, Urban, additional, Suarez-Munoz, Miguel Angel, additional, Subramaniam, Manisekar, additional, Sugiura, Teiichi, additional, Sutcliffe, Robert, additional, Swank, Hilko, additional, Taylor, Lillian, additional, Thapa, Prabin Bikram, additional, The, Catherine, additional, Thepbunchonchai, Asara, additional, Thieu, Caman, additional, Tiwari, Navneet, additional, Torzilli, Guido, additional, Tovikkai, Chutwichai, additional, Trotovsek, Blaz, additional, Tsaramanidis, Savvas, additional, Tsoulfas, Georgios, additional, Uesaka, Katsuhiko, additional, Umar, Garzali, additional, Urbani, Lucio, additional, Vailas, Michail, additional, van Dam, Ronald, additional, van de Boezem, Peter, additional, van Laarhoven, Stijn, additional, Vanagas, Tomas, additional, Van Dooren, Mike, additional, Viennet, Manon, additional, Vigano, Luca, additional, Vijayashanker, Aarathi, additional, Villodre, Celia, additional, Wakai, Toshifumi, additional, Workneh, Aklile, additional, Xu, Li, additional, Yamamoto, Masakazu, additional, Yang, Zhiying, additional, Young, Robert, additional, and Zivanovic, Marko, additional

Published
2023
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12. Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Author

Cai, Shuo, primary, Sun, Zhiwei, additional, Sun, Ping-Hui, additional, Gao, Xiangyu, additional, Ji, Ke, additional, Tian, Xiuyun, additional, Ji, Jiafu, additional, Hao, Chunyi, additional, Soliman, Faris, additional, Liu, Chang, additional, Al‑Sarireh, Bilal, additional, Griffiths, Paul, additional, Hiscox, Stephen, additional, Jiang, Wen, additional, and Ye, Lin, additional

Published
2021
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21. Variations in the management of significant polyps and early colorectal cancer: results from a multicentre observational study of 383 patients.

Author

Dattani, M., Crane, S., Battersby, N. J., Di Fabio, F., Saunders, B. P., Dolwani, S., Rutter, M. D., Moran, B. J., Suggett, Nigel, Goussous, Ghaleb, Edwards, David, Tayyab, Muhammad, McKaig, Brian, Subramanian, Thejasvi, Karandikar, Sharad, Wild, John Benjamin, Osborne, Martin, Ward, Stephen, McCullough, Peter, and Soliman, Faris

Subjects
COLON cancer, COLON polyps, COLON surgery, EARLY detection of cancer, POLYPECTOMY
Abstract

Aim: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. Method: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. Results: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non‐BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08–5.82), P = 0.03]. Conclusion: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non‐BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes. [ABSTRACT FROM AUTHOR]

Published
2018
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23. OBITUARIES.

Author

Troy, Anne, Forrest, Ewen, Sampson, Julian, Marenah, Kirsten, Swallow, Dallas, Wilkinson, John, Wilkinson, Emma, Soliman, Faris, and Walmsley, Anthony

Subjects
ANESTHESIOLOGISTS, COLLEGE teachers
Published
2021

24. The therapeutic potential of targeting hyaluronic acid to prevent peritoneal metastatic dissemination in colorectal cancer

Author

Soliman, Faris and Soliman, Faris

Abstract

Background Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body and is particularly found in abundance coating the mesothelial cells of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion to the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1. Methods Expression of HA-dependent and HA-independent adhesion molecules was examined in CRC using tissue microarray datasets and matched to clinicopathological data. In vitro peritoneal modelling tested CRC cellular adhesion when treated with either a small peptide competitive binding HA-inhibitor (HAi) or excess exogenous HA. Further in vitro testing assessed CRC ability to aggregate and survive when in suspension, evaluating the ability of cells both to survive and to aggregate at fixed time points. An in vivo Xenograft peritoneal model was used, using three groups of CD1 nude mice injected with CRC cells both intraperitoneally (IP) and subcutaneously to monitor tumour growth. Treatment groups received either a further IP injection of HAi or HA continuously for 5 days for the first week of treatment and biweekly for the remaining three weeks and compared to a control. (PPL: PE9445FC2). Results Tissue microarray data demonstrated a significant increase in RNA expression of the three HA-dependent adhesion molecules CD44 (p=<0.0001), RHAMM (p=0.0004) and ICAM-1 (p=<0.0001) in CRC. Whereas, in non-HA-dependent adhesion molecules showed eithersignificant downregulation or no expression difference. In vitro adhesion assays saw significantly reduced cellular adhesion of HT115, HRT-18 and Caco-2 cell lines when treated with either HAi or excess exogenous HA in peritoneal mimicking plate coated models. Free-floating CRC cells in suspension demonstrated, firstly, signific

25. The therapeutic potential of targeting hyaluronic acid to prevent peritoneal metastatic dissemination in colorectal cancer

Author

Soliman, Faris and Soliman, Faris

Abstract

Background Peritoneal Metastasis (PM) in Colorectal Cancer (CRC) undoubtedly remains a challenge to treat and often portends a poor prognosis for patients. Hyaluronic acid (HA) is found throughout the body and is particularly found in abundance coating the mesothelial cells of the peritoneum. Interaction of HA with HA-dependent adhesion molecules can facilitate cell adhesion to the peritoneum. HA may play a role in spread of PM in CRC in association with known HA-receptor molecules CD44, RHAMM and ICAM-1. Methods Expression of HA-dependent and HA-independent adhesion molecules was examined in CRC using tissue microarray datasets and matched to clinicopathological data. In vitro peritoneal modelling tested CRC cellular adhesion when treated with either a small peptide competitive binding HA-inhibitor (HAi) or excess exogenous HA. Further in vitro testing assessed CRC ability to aggregate and survive when in suspension, evaluating the ability of cells both to survive and to aggregate at fixed time points. An in vivo Xenograft peritoneal model was used, using three groups of CD1 nude mice injected with CRC cells both intraperitoneally (IP) and subcutaneously to monitor tumour growth. Treatment groups received either a further IP injection of HAi or HA continuously for 5 days for the first week of treatment and biweekly for the remaining three weeks and compared to a control. (PPL: PE9445FC2). Results Tissue microarray data demonstrated a significant increase in RNA expression of the three HA-dependent adhesion molecules CD44 (p=<0.0001), RHAMM (p=0.0004) and ICAM-1 (p=<0.0001) in CRC. Whereas, in non-HA-dependent adhesion molecules showed eithersignificant downregulation or no expression difference. In vitro adhesion assays saw significantly reduced cellular adhesion of HT115, HRT-18 and Caco-2 cell lines when treated with either HAi or excess exogenous HA in peritoneal mimicking plate coated models. Free-floating CRC cells in suspension demonstrated, firstly, signific

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