Publications by authors named "David Lawson Morris"

Background: The CEA/PCI ratio, which evaluates tumour marker and burden, has been demonstrated as a prognosticator for patients with colorectal cancer with peritoneal carcinomatosis. The aim of this study was to compare the CEA/PCI ratio with the Modified Colorectal Peritoneal Score (mCOREP) for overall survival (OS) and recurrence free survival (RFS). There is no literature currently comparing both markers for RFS.

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Pseudomyxoma peritonei is a rare peritoneal malignancy characterized by the progressive accumulation of mucinous material and tumour within the abdomen and pelvis. Percutaneous drainage of mucin may be a non-surgical option for relief of symptoms; however, it remains difficult due to the high viscosity of mucin, with numerous case reports reporting difficulty removing material through medium-bore catheters alone. BromAc is a therapy currently undergoing development which dissolves mucinous tumour masses and allows for extraction.

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Importance: Studies on the prognostic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in pseudomyxoma peritonei (PMP) are currently not available.

Objectives: To evaluate outcomes after cytoreductive surgery (CRS) and HIPEC compared with CRS alone in patients with PMP.

Design, Setting, And Participants: This cohort study analyzed data from the Peritoneal Surface Oncology Group International (PSOGI) registry, including 1924 patients with histologically confirmed PMP due to an appendiceal mucinous neoplasm.

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Current systemic dosages of chemotherapeutic drugs such as gemcitabine, 5-FU, cisplatin, doxorubicin are administered every 7 days over 4 cycles due to systemic toxicity. An increase in potency of the drugs will result in dosage reduction with more frequent administration and efficacy increase. Hence, we investigated how the drugs potency can be increased by combining with bromelain and N-acetylcysteine.

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Ovarian cancer is a lethal disease since treated patients often die from relapse. Resistance to current treatment regime involving doxorubicin and gemcitabine is well known. Hence, we set forth to develop a more effective therapy by combining current treatment drugs with monepantel, an antihelminth drug with proven anticancer effect.

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Pancreatic cancer is the fourth highest cause of cancer mortality in the world. It has very low survival rates owing to late diagnosis resulting from the absence of accurate diagnostic tools and effective therapies. Hence, there is a pressing need to develop new diagnostic and therapeutic tools.

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Poor aqueous solubility of anticancer drug, albendazole (ABZ), prevents parenteral application. Here, we demonstrate how to increase the aqueous solubility of ABZ to 6- 8 mg/ml using sulfobutylether - β-cyclodextrin (SBE-β-CD) or Hydroxypropyl- β-cyclodextrin (HP- β-CD) by manipulation of complexation parameters such as the physical state of ABZ (ionized in acetic acid), the concentration of ionised ABZ, agitation time and temperature. Solubility was first examined with suspension of excess ABZ powder in cyclodextrin (CD) solutions at pH (2.

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Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient's treatment protocol and outcome.

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Background: Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored.

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Compared to current treatment for pseudomyxoma peritonei (PMP), the extraction of solubilised mucin through peritoneal catheter can be minimally invasive. However, mucin has variable appearance that may influence mucolysis. Hence, we investigated the mucolysis of 36 mucin samples with a novel agent.

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Background: Our recent study on a panel of human ovarian cancer cells revealed that SKOV-3 cells barely express the Sprouty isoform 1 (Spry1) while 1A9 cells maintain it at a level similar to normal ovarian cells. Here we investigated the functional outcomes of induced alterations in the expression of Spry1 in the two cell lines in vitro.

Methods: Using the Spry1 specific plasmid and siRNA, the expression of Spry1 was induced and conversely silenced in SKOV-3 and 1A9 cells, respectively.

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Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1-2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction.

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Sprouty proteins are evolutionarily conserved modulators of MAPK/ERK pathway. Through interacting with an increasing number of effectors, mediators, and regulators with ultimate influence on multiple targets within or beyond ERK, Sprouty orchestrates a complex, multilayered regulatory system and mediates a crosstalk among different signaling pathways for a coordinated cellular response. As such, Sprouty has been implicated in various developmental and physiological processes.

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Introduction: There is increasing evidence to suggest that cancer-associated inflammation is associated with poorer long-term outcomes. Various markers have been studied over the past decade in an attempt to improve selection of patients for surgery. This meta-analysis explored the association between the neutrophil-lymphocyte ratio and prognosis following curative-intent surgery for solid tumours.

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Background: Bromelain is a pineapple stem extract with a variety of therapeutic benefits arising from interaction with a number of different biological processes. Several preclinical studies and anecdotal clinical observations have reported the anticancer properties of bromelain. In the present study, we investigated the cytotoxic effects of bromelain in four human cancer cell lines of gastrointestinal origin and the mechanisms involved.

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Bromelain is a mixture of proteolytic enzymes that is capable of hydrolyzing glycosidic linkages in glycoprotein. Glycoprotein's are ubiquitously distributed throughout the body and serve a variety of physiologic functions. Faulty glycosylation of proteins may lead to cancer.

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Background: Malignant peritoneal mesothelioma (MPM) is a rare and fatal cancer. Females are found to survive longer than males after treatment, suggesting a possible involvement of hormonal factors. Estradiol is involved in cellular proliferation of a number of cancers and acts mainly through oestrogen receptors (ERs).

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Objectives: To evaluate the effect of minocycline on the expression of cytokines and growth factors responsible for malignant ascite formation.

Methods: In vitro, cells obtained from malignant ascites were pre-treated with minocycline (0-100 μmol/L) and exposed briefly to hypoxia. In vivo, female nude mice bearing OVCAR-3 tumors were treated orally in drinking water with minocycline for 4 weeks.

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Sprouty (Spry) proteins, modulators of receptor tyrosine kinase signaling pathways, have been shown to be deregulated in a variety of pathological conditions including cancer. In the present study we investigated the expression of Spry1 and Spry2 isoforms in a panel of human ovarian cancer cell lines in vitro. Our western blot analysis showed nonuniform patterns of Spry expression in the cancer cells, none of which conformed to the pattern observed in the normal ovarian epithelial cells employed as the control.

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The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis.

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Background: Surgical resection of pulmonary metastases from renal cell carcinoma (RCC) has been demonstrated in recent studies to produce good long-term survival outcomes. Radiofrequency ablation (RFA) may offer an alternative treatment option for this group of patients, especially for those who are unable to have surgery.

Methods: Nine patients had a total of 23 pulmonary metastases treated with percutaneous RFA under fluoro-computed tomography (CT) guidance.

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Vascular endothelial growth factor (VEGF) is the key molecule mediating tumor growth and malignant ascites formation. We recently reported that, in an end stage OVCAR-3 xenograft model, albendazole (ABZ) suppresses ascites formation, but not tumor growth. Hence, in the present study, we assessed the effect of ABZ on in vitro OVCAR-3 cell proliferation plus in vivo tumor growth, however, initiating ABZ treatment at mid stage (3 weeks post cell inoculation) rather than end stage disease.

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Purpose: Angiogenesis and vessel hyperpermeability are the two factors leading to the formation of ascites. Vascular endothelial growth factor (VEGF) plays a pivotal role in malignant ascites formation. We have recently shown that albendazole inhibits peritoneal growth of human colorectal cancer cells (HT-29).

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Radiofrequency ablation (RFA) is a relatively new technique that has been investigated for the treatment of lung tumors. We evaluated for the first time the in vivo use of saline infusion during radiofrequency ablation of sheep lung. We performed RFA on 5 sheep using open and closed chest RFA and the RITA starburst XL and Xli probes using saline infusion with the Xli probe.

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Pad burns during or after radiofrequency ablation (RFA) are a skin complication probably underreported in the literature. We report on 4 severe pad burns, deep second and third degree, in 3 patients undergoing radiofrequency ablation of liver malignancies, 1 percutaneously and the other 2 after laparotomy. All burns occurred at the leading edge or at the corner of the pads attached to the patients' thighs.

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