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Solid Tumours (solid + tumour)
Selected AbstractsDrug-eluting bead therapy in primary and metastatic disease of the liverHPB, Issue 7 2009Stewart Carter Abstract Background:, Drug-eluting bead transarterial chemoembolization (DEB-TACE) is a novel therapy for the treatment of hypervascuarized tumours. Through the intra-arterial delivery of microspheres, DEB-TACE allows for embolization as well as local release of chemotherapy in the treatment of hepatic malignancy, providing an alternative therapeutic option in unresectable tumours. Its role as an adjunct to surgical resection or radiofrequency ablation (RFA) is less clear. The purpose of this review is to summarize recent studies investigating DEB-TACE in order to better define safety, efficacy and outcomes associated with its use. Methods:, A systematic review of all published articles and trials identified nine clinical trials and 23 abstracts. These were reviewed for tumour histology, stage of treatment, delivery technique, outcome at follow-up, complications and mortality rates. Results:, Publications involved treatment of hepatocellular carcinoma (HCC), metastatic colorectal carcinoma (MCRC), metastatic neuroendocrine (MNE) disease and cholangiocarcinoma (CCA). Using Response Evaluation Criteria in Solid Tumours (RECIST) or European Association for the Study of the Liver (EASL) criteria, studies treating HCC reported complete response (CR) rates of 5% (5/101) at 1 month, 9% (8/91) at 4 months, 14% (19/138) at 6 months and 25% (2/8) at 10 months. Partial response (PR) was reported as 58% (76/131) at 1 month, 50% (67/119) at 4 months, 57% (62/108) at 6,7 months and 63% (5/8) at 10 months. Studies involving MCRC, CCA and MNE disease were less valuable in terms of response rate because there is a lack of comparative data. The most common procedure-associated complications included fever (46,72%), nausea and vomiting (42,47%), abdominal pain (44,80%) and liver abscess (2,3%). Rather than reporting individual symptoms, two studies reported rates of post-embolic syndrome (PES), consisting of fever, abdominal pain, and nausea and vomiting, at 82% (75/91). Six of eight studies reported length of hospital stay, which averaged 2.3 days per procedure. Mortality was reported as occurring in 10 of 456 (2%) procedures, or 10 of 214 (5%) patients. Conclusions:, Drug-eluting bead TACE is becoming more widely utilized in primary and liver-dominant metastatic disease of the liver. Outcomes of success must be expanded beyond response rates because these are not a reliable surrogate for progression-free survival or overall survival. Ongoing clinical trials will further clarify the optimal timing and strategy of this technology. [source] Long-term results of patients with malignant carcinoid syndrome receiving octreotide LARALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009C. TOUMPANAKIS Summary Background, Octreotide LAR is an established treatment for malignant carcinoid syndrome. However, studies with large number of patients and long follow-up are lacking. Aim, To present long-terms results with octreotide LAR, assessing duration of clinical and objective response and treatment tolerance, in a large, homogeneous cohort of patients with malignant carcinoid syndrome. Methods, A total of 108 patients with metastatic midgut neuroendocrine tumours were included in this 8-year study. Clinical evaluation was based on a symptom score. Radiological assessment was based on RECIST (Response Evaluation Criteria In Solid Tumours) criteria. Results, Of the 108 patients, 24% had a sustained symptomatic response. In the remaining patients, loss of symptomatic response with the initial dose was noted within 3-60 months. In 17% of them, symptoms were controlled by just an increase of octreotide LAR dose, whilst the other patients required additional treatment. Overall, in 45.3% of patients, symptoms were well controlled during the study period with only octreotide LAR, and no additional treatment was required. No significant adverse effects were noted. Conclusions, Octreotide LAR treatment provides a sustained symptomatic response in about half of the patients with malignant carcinoid syndrome and contributes to disease stabilization for a longer period than previously described. [source] Factors affecting outcomes of prenatally-diagnosed tumoursPRENATAL DIAGNOSIS, Issue 5 2002K. L. Chan Abstract Objective The outcomes of prenatally-diagnosed tumours affect obstetrical management and parental decisions. The present study reviews the factors affecting outcomes for fetuses with prenatally-diagnosed tumours. Methods Medical records of all fetuses referred to our institutions with antenatally-diagnosed tumours were reviewed for the type and location of the tumours, results of treatment and/or causes of death. Results From January 1994 to May 2001, there were 15 fetuses with antenatally- diagnosed tumours: mesoblastic nephroma (MN) (n=2); neuroblastoma (NB) (n=2); cystic hygroma (CH) (n=3); intracranial germ cell tumour (IGCT) (n=2); sacrococcygeal teratoma (SCT) (n=3) and haemangioma (liver, n=2; limb, n=1). One mother had termination of pregnancy for her fetal SCT. Three mothers had Caesarean section for large fetal heads (CH, n=2; IGCT, n=1). Three fetuses died; two with IGCT and one with SCT, who died of heart failure. Two newborns with CH needed emergency intubation and, later, one of them had tracheostomy. One baby had cardiac failure resulting from a lower limb haemangioma and needed drug therapy. All solid tumours (MN, NB, SCT) of the live births had no recurrence after surgery with or without adjuvant chemotherapy. Conclusion Prenatally-diagnosed tumours without any other associated abnormality cause morbidity and mortality because of their location and vascularity. Solid tumours are relatively benign. Copyright © 2002 John Wiley & Sons, Ltd. [source] Pharmacokinetics of alizapride in children receiving chemotherapy for solid tumourFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2001Elisabeth Rey The purpose of the present study was to determine the pharmacokinetics of alizapride to optimize its use in children aged 1 month to 15 years old who were receiving chemotherapy. Seventeen children were given a single 4 mg/kg alizapride infusion prior to the administration of cytostatic drugs. Blood and urine samples were collected within 10 h after onset of the infusion. Kinetic parameters were calculated and showed a decrease in plasma clearance expressed per unit of body weight with age. The current data suggest that dosage expressed per unit of body weight should be higher in children than in adults and higher in infants than in children. [source] The oral health needs of children after treatment for a solid tumour or lymphomaINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2010ALISON HUTTON Background., With increasing survival rates for childhood cancer, late effects are of growing importance. Oral health is central to general health, level of nutrition, quality of life, and is significant in the holistic care of children during cancer therapy. Hypothesis., The oral health needs of children treated for solid tumours/lymphoma will be greater than the general population, groups will differ according to tumour and treatment. Design., One hundred and twenty patients, 0,17 years, under follow-up from 01/07/06 to 07/02/07 were investigated for caries, opacities, microdontia, and gingivitis. Analysis was performed with stratification according to tumour and treatment. Comparisons made with the UK 2003 Child Dental Health Survey. Results., The neuroblastoma group and high-dose chemotherapy with stem-cell rescue (HDCSCR) therapy group had increased caries of the primary teeth. Chi-squared analysis revealed a statistically significant relationship (P < 0.03) between the age at receipt of chemotherapy (<3.5 years) and the presence of microdont teeth. Conclusion., Oral health care is important for all patients particularly those with a neuroblastoma, or who received HDCSCR. Patients should be advised about the possibility of microdontia in the permanent dentition following chemotherapy under 3.5 years. [source] Gynaecological presentation of retroperitoneal tumoursBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2000Andrew J. Spillane Fellow (Surgical Oncology) Objective To illustrate the problems associated with mistaken pre-operative diagnosis following gynaecological presentation of patients with retroperitoneal tumours. Design A case series of five referrals. Results Non-gynaecological tumours were not suspected in each case and hence there was a failure to undertake further pre-operative investigation and referral to a specialised soft tissue sarcoma service. This resulted in four of the patients having an unnecessary laparotomy with an inappropriate transperitoneal biopsy undertaken when the retroperitoneal tumour was discovered. The mistaken diagnosis of ovarian malignancy lead to increased morbidity, compromise of potential for a long disease free interval and/or possibly lessened the chance of cure in each case. Conclusions Misinterpretation of clinical signs and an over-reliance on ultrasound diagnosis were the commonest causes of inappropriate management of these patients. Gynaecologists should consider more frequently the other, less common differential diagnoses of a pelvic mass. This is especially true in circumstances with a predominantly solid tumour, where there are clinical signs of vascular or rectal displacement, or where there is ultrasound evidence of ureteric obstruction. The more frequent utilisation of a computerised tomography scan with intravenous and oral contrast with referral before inappropriate transperitoneal biopsy are recommended as complete en bloc surgical excision at the first laparotomy is the treatment of choice in virtually all primary retroperitoneal tumours. [source] Granular cell tumour of the lacrimal glandACTA OPHTHALMOLOGICA, Issue 2009SL VON HOLSTEIN Purpose To report the clinical and histopathological characteristics of a patient with a granular cell tumour (GCT) of the lacrimal gland. Methods Surgical excision and histological examination. Results A 38-year old male presented with a painful swelling located temporally in the right upper eyelid. Clinical examination revealed proptosis and displacement of the right eye and a tumour was palpated at the site of the lacrimal gland. MRI scan revealed a solid tumour in the lacrimal fossa. The tumour was excised. Microscopically the tumour was composed of tumour cells with coarsely granular cytoplasm. The tumour cells were arranged in clusters and ribbons separated by collagen bundles and no necrosis or mitosis were present. The granules were PAS positive, diastase resistant and the tumour cells expressed focal staining for S100. Electron microscopy showed numerous secondary lysosomes. The diagnosis is consistent with a GCT. Conclusion This case presents for the first time a GCT of the lacrimal gland. [source] Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunityCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006R. Kim Summary Dendritic cells play a crucial role in initiating tumour immunity as well as in the immune response for invading foreign pathogens such as bacteria and viruses. For bacterial and viral infections, the immature dendritic cells (iDCs) residing in peripheral tissues are efficiently activated and matured by pathogen signals for performing the immune response. In contrast, for self-antigens, the naive T cells are not activated by iDCs but proceed to anergy/deletion, and the generation of regulatory T cells for immune tolerance. The induction of immune response and tolerance is regulated strictly by iDCs as the sensor for homeostasis of immune response in the host. Despite the identification of some tumour antigens, tumour immunity is not provoked successfully. Even though there are some critical obstacles to inhibit effective tumour immunity, tumour cells are able to exploit the functional roles of iDCs for tumour progression, which are induced by tumour-derived soluble factors such as vascular endothelial growth factor (VEGF) and functionally modulated in the microenvironment. The iDCs still remain as the critical target for provoking tumour immunity. In this review, the functional roles of tumour-associated iDCs and the strategy for targeting iDCs in effective tumour immunity for the cancer patient are discussed. [source] Blueberry muffin rash as a presentation of alveolar cell rhabdomyosarcoma in a neonateACTA PAEDIATRICA, Issue 1 2000SV Godambe Soft tissue sarcomas of childhood continue to present problems with pathologic diagnosis, staging and treatment. Rhabdomyosarcoma, the most common soft tissue sarcoma, represents 4,8% of all malignant solid tumours in children. We report a case of congenital alveolar rhabdomyosarcoma who presented with "blueberry muffin"-like rash. A full-term female infant was noted at birth to have multiple skin lesions resembling blueberry muffin rash and an abdominal mass in the left iliac fossa, which appeared to be fixed to the posterior abdominal wall. There was no enlargement of liver and spleen, but her para-aortic lymph nodes were enlarged. Biopsy from the mass confirmed the diagnosis of alveolar cell rhabdomyosarcoma. Molecular investigation for the t (2:13) translocation was negative. The infant received chemotherapy but died within 1 mo of diagnosis. [source] Once-weekly epoetin beta therapy in patients with solid tumours and chemotherapy-induced anaemia: a randomized, double-blind, dose-finding studyEUROPEAN JOURNAL OF CANCER CARE, Issue 6 2008P. HERAS md, phd Anaemia is common in patients receiving chemotherapy, causing symptoms that have a major impact on quality of life (QoL). Epoetin beta rapidly increases haemoglobin (Hb) levels and improves QoL in anaemic patients with a variety of tumours. This was a randomized, double-blind, parallel-group, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy. Adult patients with anaemia (Hb < 11 g/dL) were randomized to receive epoetin beta 30 000 IU or 20 000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Haemoglobin levels, transfusion need and QoL [Functional Assesment of Cancer Therapy-fatigue (FACT-F) subscale score] were assessed at regular intervals. Fifty patients were randomized; 30 patients received epoetin beta 30 000 IU once weekly and 20 received 20 000 IU once weekly. Mean (± SD) increase in Hb from baseline to week 12 was 1.75 ± 2.15 g/dL in the 30 000 IU group (P = 0.008 vs. baseline) and 1.04 ± 1.75 g/dL in the 20 000 IU group (non-significant). Haemoglobin response (increase in Hb ,2 g/dL from baseline) was observed in 78.3% of patients receiving epoetin beta 30 000 IU and 66.7% receiving epoetin beta 20 000 IU. Improvements in FACT-F subscale score were significantly (P < 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regiments were well tolerated and there were no dose-dependant adverse events. Epoetin beta 30 000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours. [source] Oxidative stress as a multiple effector in Fanconi anaemia clinical phenotypeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005Giovanni Pagano Abstract:, Fanconi anaemia (FA) is a genetic disease characterised by bone marrow failure with excess risk of myelogenous leukaemia and solid tumours. A widely accepted notion in FA research invokes a deficiency of response to DNA damage as the fundamental basis of the ,crosslinker sensitivity' observed in this disorder. However, such an isolated defect cannot readily account for the full cellular and clinical phenotype, which includes a number of other abnormalities, such as malformations, endocrinopathies, and typical skin spots. An extensive body of evidence pointing toward an involvement of oxidative stress in the FA phenotype includes the following: (i) In vitro and ex vivo abnormalities in a number of redox status endpoints; (ii) the functions of several FA proteins in protecting cells from oxidative stress; (iii) redox-related toxicity mechanisms of the xenobiotics evoking excess toxicity in FA cells. The clinical features in FA and the in vivo abnormalities of redox parameters are here reconsidered in view of the pleiotropic clinical phenotype and known biochemical and molecular links to an in vivo prooxidant state, which causes oxidative damage to biomolecules, resulting in an excessive number of acquired abnormalities that may overwhelm the cellular repair capacity rather than a primary deficiency in DNA repair. FA may thus represent a unique model disease in testing the integration between the acquisition of macromolecular damage as a result of oxidative stress and the ability of the mammalian cell to respond effectively to such damage. [source] Antibiotic prophylaxis in chemotherapy-induced neutropenia: time to reconsiderHEMATOLOGICAL ONCOLOGY, Issue 3 2006Nangi Lo Abstract The use of antibiotic prophylaxis in neutropenic patients remains controversial. The main arguments against prophylaxis are the lack of survival benefit and the risk of inducing antibiotic resistance. At present, clinical guidelines advise against routine use of antibiotic prophylaxis and current practice is to commence broad-spectrum antibiotics at the onset of fever in the neutropenic patient. However hospitalization, investigations and treatment all impact on resources as well as affecting patient quality of life, often resulting in chemotherapy delays and dose reductions. The benefits of prophylactic antibiotics have been emphasized by two major double-blind, placebo controlled trials with levofloxacin with very significant reductions in all infection-related events. Furthermore, the meta-analysis confirms a survival advantage and this is greatest with the use of fluoroquinolones. These benefits must be weighed against the problem of emerging antibiotic resistance. It has been shown that antibiotic prophylaxis does induce resistant organisms, but some studies have shown that the impact on clinical outcomes may not be as great as expected. Current evidence supports antibiotic prophylaxis with fluoroquinolones in acute leukaemia and high-dose chemotherapy patients, commencing at the same time as chemotherapy. Febrile episodes are much commoner with the first cycle in patients with solid tumours or lymphoma having moderately myelosuppressive chemotherapy, and these patients should be offered prophylaxis for at least the first cycle of chemotherapy. Further work is ongoing to facilitate the selection of patients with the greatest chance of benefit so that prophylaxis can be used efficiently. Copyright © 2006 John Wiley & Sons, Ltd. [source] Adult thymus transplantation with allogeneic intra-bone marrow,bone marrow transplantation from same donor induces high thymopoiesis, mild graft-versus-host reaction and strong graft-versus-tumour effectsIMMUNOLOGY, Issue 4 2009Takashi Miyake Summary Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow,bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4+ FoxP3+ regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8+ T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR. [source] Study on VNTR polymorphism of gene IL-1RA in 19 Chinese populationsINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2010J. Jiang Summary Earlier studies suggested that a variable number tandem repeat (VNTR) polymorphism in intron 2 of the interleukin-1 receptor antagonist (IL-1RA) gene might be associated with some chronic inflammatory diseases, autoimmune diseases and solid tumours. To study the distribution of this polymorphism in China, 1352 samples were collected from 19 widely distributed Chinese populations. PCR was used to genotype the VNTR. The overall frequencies of allele 1 and allele 2 were 0.913 and 0.064 respectively. The frequency of the allele 2 was significantly different between the northeastern and the northwestern populations. Moreover, the allele frequencies at this locus in three Chinese Han populations were different from that in minority populations. When compared with other populations worldwide, the frequencies of the two alleles in China were not significantly different from those in the Asian and Pacific Islands. However, the prevalence of allele 1 in China was significantly higher, and the prevalence of allele 2 was significantly lower, than those in American and European Caucasians, and the pairwise Fst values reinforced this observation. The differences of the allele frequencies between different regions and within the same region showed that geography and race have important roles in the population differentiation for the IL-1RA gene. In summary, our results provide a valuable reference for population genetic information and future disease association studies in Chinese populations. [source] High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic abilityJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Alysha K. Croker Abstract Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) for expression of prospective CSC markers CD44/CD24 and CD133, and for functional activity of aldehyde dehydrogenase (ALDH), an enzyme involved in stem cell self-protection. We then used fluorescence-activated cell sorting and functional assays to characterize differences in malignant/metastatic behaviour in vitro (proliferation, colony-forming ability, adhesion, migration, invasion) and in vivo (tumorigenicity and metastasis). Sub-populations of cells demonstrating stem-cell-like characteristics (high expression of CSC markers and/or high ALDH) were identified in all cell lines except MCF-7. When isolated and compared to ALDHlowCD44low/, cells, ALDHhiCD44+CD24, (MDA-MB-231) and ALDHhiCD44+CD133+ (MDA-MB-468) cells demonstrated increased growth (P < 0.05), colony formation (P < 0.05), adhesion (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). Furthermore, following tail vein or mammary fat pad injection of NOD/SCID/IL2, receptor null mice, ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells showed enhanced tumorigenicity and metastasis relative to ALDHlowCD44low/, cells (P < 0.05). These novel results suggest that stem-like ALDHhiCD44+CD24, and ALDHhiCD44+CD133+ cells may be important mediators of breast cancer metastasis. [source] Anaplastic lymphoma kinase proteins in growth control and cancerJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2004K. Pulford The normal functions of full-length anaplastic lymphoma kinase (ALK) remain to be completely elucidated. Although considered to be important in neural development, recent studies in Drosophila also highlight a role for ALK in gut muscle differentiation. Indeed, the Drosophila model offers a future arena for the study of ALK, its ligands and signalling cascades. The discovery of activated fusion forms of the ALK tyrosine kinase in anaplastic large cell lymphoma (ALCL) has dramatically improved our understanding of the pathogenesis of these lymphomas and enhanced the pathological diagnosis of this subtype of non-Hodgkin's lymphoma (NHL). Likewise, the realisation that a high percentage of inflammatory myofibroblastic tumours express activated-ALK fusion proteins has clarified the causation of these mesenchymal neoplasms and provided for their easier discrimination from other mesenchymal-derived inflammatory myofibroblastic tumour (IMT) mimics. Recent reports of ALK expression in a range of carcinoma-derived cell lines together with its apparent role as a receptor for PTN and MK, both of which have been implicated in tumourigenesis, raise the possibility that ALK-mediated signalling could play a role in the development and/or progression of a number of common solid tumours. The therapeutic targeting of ALK may prove to have efficacy in the treatment of many of these neoplasms. © 2004 Wiley-Liss, Inc. [source] Tumour and dendrimers: a review on drug delivery aspectsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2008Abhinav Agarwal Tumour is a morbid state, characterized by spontaneous outgrowth of an abnormal mass of cells. The evolution of tumours is random, disorganized, a condition of numerous mutations. The properties are biased and incompletely comprehended. It is a malignant or benign condition that encompasses its own rules of morphogenesis, an immortal state that elucidates different physiology. It is a pathological crisis that still haunts the minds of scientists, physicians and patients, a complete cure of which is still a dream to be realized. The unpredictable microenvironment of cancerous cells in all of its existing forms i.e. leukaemic cells, solid tumours and sarcomas is well documented. This phenomenon expressed by cancerous sites in the body poses various obstacles towards drug efficacy. Thus, it has become necessary to address briefly the issues relating to tumour physiology, its vasculature and angiogenesis. The information could provide insight towards the development of tumour-targeted drug delivery. The salient features regarding these have been discussed. [source] Vehicles for oligonucleotide delivery to tumoursJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2002Crispin R. Dass The vasculature of a tumour provides the most effective route by which neoplastic cells may be reached and eradicated by drugs. The fact that a tumour's vasculature is relatively more permeable than healthy host tissue should enable selective delivery of drugs to tumour tissue. Such delivery is relevant to carrier-mediated delivery of genetic medicine to tumours. This review discusses the potential of delivering therapeutic oligonucleotides (ONs) to tumours using cationic liposomes and cyclodextrins (CyDs), and the major hindrances posed by the tumour itself on such delivery. Cationic liposomes are generally 100,200 nm in diameter, whereas CyDs typically span 1.5 nm across. Cationic liposomes have been used for the introduction of nucleic acids into mammalian cells for more than a decade. CyD molecules are routinely used as agents that engender cholesterol efflux from lipid-laden cells, thus having an efficacious potential in the management of atherosclerosis. A recent trend is to employ these oligosaccharide molecules for delivering nucleic acids in cells both in-vitro and in-vivo. Comparisons are made with other ON delivery agents, such as porphyrin derivatives (< 1 nm), branched chain dendrimers (, 10 nm), polyethylenimine polymers (, 10 nm), nanoparticles (20,1000 nm) and microspheres (> 1 ,m), in the context of delivery to solid tumours. A discourse on how the chemical and physical properties of these carriers may affect the uptake of ONs into cells, particularly in-vivo, forms a major basis of this review. [source] Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with adenocarcinoma of prostate and transitional cell carcinoma of urinary bladderJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2005K Hussein ABSTRACT Association of Sweet's syndrome (SS) with solid tumours is found in about 15% of all malignancy-associated cases, but an association with two malignancies occurring in the same patient has been rarely reported. In the present report, we describe an 82-year-old male with SS in association with adenocarcinoma of the prostate and transitional cell carcinoma of the urinary bladder. [source] Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesisJOURNAL OF VIRAL HEPATITIS, Issue 4 2003K. Miyaji Summary. Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN- , in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas. [source] Glomerulosclerosis: A paraneoplastic phenomenon?NEPHROLOGY, Issue 6 2004Case Report SUMMARY: Glomerulosclerosis is not classically considered a paraneoplastic glomerular lesion. Focal and segmental glomerulosclerosis (FSGS) has rarely been reported in association with solid tumours. We report three cases of FSGS and an additional case of collapsing glomerulosclerosis in patients presenting with nephrotic syndrome and malignancy. [source] Factors affecting outcomes of prenatally-diagnosed tumoursPRENATAL DIAGNOSIS, Issue 5 2002K. L. Chan Abstract Objective The outcomes of prenatally-diagnosed tumours affect obstetrical management and parental decisions. The present study reviews the factors affecting outcomes for fetuses with prenatally-diagnosed tumours. Methods Medical records of all fetuses referred to our institutions with antenatally-diagnosed tumours were reviewed for the type and location of the tumours, results of treatment and/or causes of death. Results From January 1994 to May 2001, there were 15 fetuses with antenatally- diagnosed tumours: mesoblastic nephroma (MN) (n=2); neuroblastoma (NB) (n=2); cystic hygroma (CH) (n=3); intracranial germ cell tumour (IGCT) (n=2); sacrococcygeal teratoma (SCT) (n=3) and haemangioma (liver, n=2; limb, n=1). One mother had termination of pregnancy for her fetal SCT. Three mothers had Caesarean section for large fetal heads (CH, n=2; IGCT, n=1). Three fetuses died; two with IGCT and one with SCT, who died of heart failure. Two newborns with CH needed emergency intubation and, later, one of them had tracheostomy. One baby had cardiac failure resulting from a lower limb haemangioma and needed drug therapy. All solid tumours (MN, NB, SCT) of the live births had no recurrence after surgery with or without adjuvant chemotherapy. Conclusion Prenatally-diagnosed tumours without any other associated abnormality cause morbidity and mortality because of their location and vascularity. Solid tumours are relatively benign. Copyright © 2002 John Wiley & Sons, Ltd. [source] Angiogenesis and Interstitial Pressure in a Rat Tumour ModelANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005H. Hünigen Introduction and Aim:, Angiogenesis, the formation of new blood vessels, is a crucial process in physiological and pathological growth. Pathological angiogenesis is responsible for growth and metastasis of solid tumours, and, when blocked, improves prognosis. As a result of the angiogenic cascade in solid tumours an irregular, leaky capillary network develops. The aim of the present study was to define malignant tumours' vascular characteristics and reveal functional anatomy by quantification of the microvasculature and interstitial pressure (IP) in relation to tumour fluid dynamics as visualized by contrast enhanced magnetic resonance imaging (MRI). Material and Methods:, Dynamic MRI and measurement of the IP was performed in 21 rats implanted with colon carcinomas subcutaneously. Angiogenesis was studied by morphometry of the capillaries, and immunolocalization of the angiogenic factor VEGF and VEGF-Receptor 2. Results and Conclusions:, Histology, immunohistochemistry and MRI confirmed concentric arrangement of 4 tumour zones. The tumour margin included loose connective tissue with abundant mononuclear cells. Many large microvessels were seen in this most intensely vascularized zone. IP measurement in this zone was adjusted to the zero level. Diameter of the peripheral zone of vital cells measured 1.3 mm. Capillaries were smaller and sparse. Dynamic MRI revealed peripheral washout of the contrast agent in this zone. After an initial increase of the signal intensity a hypo-intense rim was formed within a few minutes. The intermediate region was characterized by islands of vital tumour cells containing 3% capillaries (hot spots). The innermost area, the necrotic zone, took 35% of the total tumour area with less than 0.5% vessels. The IP increased from the periphery to the centre. VEGF and VEGF-receptor 2 was found in the vessels of the tumour margin and vital tumour cells of the peripheral zone. From this can be concluded that the peripheral washout phenomenon seems to be correlated with elevated interstitial pressure and increased capillary density and therefore may be a reliable sign of malignancy. [source] Platinum pharmacokinetics in sulphur-crested cockatoos (Cacatua galerita) following single-dose cisplatin infusionAUSTRALIAN VETERINARY JOURNAL, Issue 6 2000LJ FILIPPICH Objective To determine the pharmacokinetics of platinum (Pt) in cockatoos. Design A pharmacokinetic study of Pt, following a single IV infusion of cisplatin, was done in six healthy sulphur-crested cockatoos (Cacatua galerita). Procedure Birds were hydrated for 1 h before and 2 h after a 1-h cisplatin infusion (1 mg/kg, IV). Serial blood samples were collected for 96 h after initiation of the infusion and urine was collected for 2 h during the hydration period after cisplatin administration. Tissue samples from 10 organs were obtained at necropsy, 96 h after cisplatin infusion. Total Pt and filterable Pt in plasma, urinary Pt and tissue Pt concentrations were assayed by inductively coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was performed on the plasma and urine data. Results For total Pt and filterable Pt, the respective mean systemic clearances were 0.373 and 0.699 L/kg hourly, the steady state volumes of distribution were 4.19 and 0.356 L/kg, and the mean residence times were 111 and 0.512 h. Total plasma Pt displayed a bi-exponential decay profile with average half-lives of 0.398 and 79.0 h, while filterable Pt had a monoexponential decay with mean half-life of 0.413 h. The renal clearance during the 2-h postinfusion period was 0.167 L/kg hourly. The kidneys had the highest Pt accumulation (4.54 u.g/g DM). Conclusions and Clinical Relevance Cisplatin infusion in cockatoos was well tolerated and Pt plasma concentrations were similar to those measured during treatment of solid tumours in human patients. Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of Pt in the cockatoo shares some features with the kinetics reported previously in rodents, dogs and human beings. [source] Prognostic significance of erythropoietin expression in human renal cell carcinomaBJU INTERNATIONAL, Issue 2 2007Agniezka Michael OBJECTIVES To investigate, in a retrospective study, the expression of erythropoietin (Epo) in human renal cell carcinoma (RCC) and its correlation with overall survival, as Epo (an haematopoietic cytokine that regulates the production of red blood cells), with its receptor, was recently localized in non-haematopoietic tissues, e.g. liver, uterus, central nervous system, vascular endothelial cells and solid tumours. PATIENTS AND METHODS We used data from 113 patients who had radical nephrectomy for RCC between 1990 and 2000, taking sections from formalin-fixed and paraffin wax-embedded tissue blocks. The association between Epo staining and the patients' characteristics was assessed by either chi-squared tests (for categorical variables) or two-sample independent t -tests (for continuous variables). RESULTS Tissue from 37 patients (33%) was positive for cytoplasmic Epo expression; 76 (67%) samples were negative. Univariate hazard ratio analysis confirmed that those with positive Epo staining were more than twice as likely to die as those with negative staining (hazard ratio 2.34, 95% confidence interval 1.27,4.3). CONCLUSION This study shows that the expression of Epo in RCC is adversely associated with overall survival. This is the first report of such an association, and might be explained by the loss of Von Hippel-Lindau protein function in clear cell RCC. The expression of Epo might have potential use in clinical trials when stratifying high-risk patients for adjuvant therapy after nephrectomy. [source] Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole positron emission tomographyBJU INTERNATIONAL, Issue 4 2005Nathan Lawrentschuk OBJECTIVE To assess renal tumours for hypoxic regions using 18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET), a recognized noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma (RCC) can be potentially cured with nephrectomy but recurrence develops in most patients, who then respond poorly to treatments such as chemotherapy, and hypoxia is known to confer resistance to radiotherapy and chemotherapy in many solid tumours. PATIENTS AND METHODS In all, 17 patients had 18F-FMISO PET scans before nephrectomy for presumed RCC. Specimens were examined histologically, and immunohistochemistry was used to compare the microvessel density (MVD) as an indicator of angiogenesis in the tumour and normal parenchyma, in 15 patients. Tumour oxygenation was measured invasively in three patients using a polarographic oxygen sensor probe. RESULTS Of the 15 patients with histological results, 11 had RCC and four had other tumours. Although there was a trend there was no statistically significant (P = 0.14) difference in the maximum standardized uptake value (SUVmax) when comparing the region of the kidney involved with RCC; the mean (95% confidence interval) SUVmax in the tumours was 1.3 (0.15), whilst that in the normal contralateral kidney was 1.1 (0.22). The MVD was greater in RCC, at 13.7 (3.1) mean vessels per high-power field than in normal tissue, at 6.9 (1.9). Hypoxia as measured polarographically was detected in three RCCs (median pO2 9.6 mmHg) compared to normal parenchyma at 37.6 mmHg. CONCLUSIONS Although 18F-FMISO scans showed significant uptake in other solid tumours, there was only mild 18F-FMISO uptake in the present RCCs. The invasive measurements indicated that there was hypoxia in RCC, but the median pO2 did not fall below 9.5 mmHg. Further direct studies of renal tumour oxygenation combined with therapies directed towards hypoxia may allow a better understanding of the relationship between 18F-FMISO results and the biological significance of hypoxia in RCC. [source] Variability in the pharmacokinetics of intravenous busulphan given as a single daily dose to paediatric blood or marrow transplant recipientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008Christa E. Nath WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The pharmacokinetics of oral busulphan given four times daily has been extensively studied. , Large inter- and intravariability in oral busulphan exposure has led to attempts at pharmacokinetic monitoring. , However, there have been limitations in the pharmacokinetic analysis due to inadequate characterization of the elimination phase in a 6-h dosing interval, due to late absorption in some patients. , Intravenous (i.v.) busulphan is a relatively new administration method and there have been relatively few studies on the pharmacokinetics of i.v. busulphan, especially when given as a single daily dose. WHAT THIS STUDY ADDS , Inter- and intrapatient variability in i.v. busulphan pharmacokinetics is comparable to that previously observed with oral busulphan, suggesting that pharmacokinetic monitoring is advisable. , Children with immune deficiencies, in particular, have widely variable exposure. AIM To examine inter- and intrapatient variability in the pharmacokinetics of intravenous (i.v.) busulphan given as a single daily dose to children with malignant (n = 19) and nonmalignant (n = 21) disease. METHODS Busulphan (120 mg m,2, 130 mg m,2 or 3.2 mg kg,1) was administered over median 2.1 h. Blood samples (4,10) were collected after the first dose, busulphan concentrations were measured and pharmacokinetic parameters, including clearance (CL) and area under the concentration,time curve (AUC), were determined using the Kinetica software (Innaphase). Interpatient variability was assessed as percent coefficient of variation (% CV). Intrapatient variability was assessed by calculating percent differences between observed full dose AUC and AUC predicted from an initial 65 mg m,2 dose in 13 children who had busulphan pharmacokinetic monitoring. RESULTS Clearance of i.v. busulphan in 40 children was 4.78 ± 2.93 l h,1 (% CV 61%), 0.23 ± 0.08 l h,1 kg,1 (% CV 35%) and 5.79 ± 1.59 l h,1 m,2 (% CV 27%). Age correlated significantly (p < 0.001) with CL (l h,1) and CL (l h,1 kg,1), but not with CL (l h,1 m,2). AUC normalized to the 130 mg m,2 dose ranged from 14.1 to 56.3 mg l,1.h (% CV 37%) and also did not correlate with age. Interpatient variability in CL (l h,1 m,2) was highest in six children with immune deficiencies (60%) and lowest in seven children with solid tumours (14%). Intrapatient variability was <13% for nine (of 13) children, but between 20 and 44% for four children. CONCLUSIONS There is considerable inter- and intrapatient variability in i.v. busulphan CL (l h,1 m,2) and exposure that is unrelated to age, especially in children with immune deficiencies. These results suggest that monitoring of i.v. busulphan pharmacokinetics is required. [source] High plasma proteasome levels are detected in patients with metastatic malignant melanomaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005P-E. Stoebner Summary Background, Proteasomes, nonlysosomal proteolytic structures, are implicated in cell growth and differentiation. An abnormal expression has been described in haematopoietic malignancies and in some solid tumours. Objectives, To study the plasma proteasome levels in patients with malignant melanoma (MM) using an enzyme-linked immunosorbent assay (ELISA) technique, and to compare them with the values obtained in a normal population and in patients with severe psoriasis or chronic idiopathic urticaria (CIU). Methods, Plasma proteasome level was measured using a sandwich ELISA test in normal donors (n = 14), and in patients with stage I/II (n = 13), stage III (n = 6) and stage IV (n = 10) MM, severe psoriasis (n = 13) and CIU (n = 6). Tissue proteasome expression was also detected by immunohistology using a monoclonal antibody in paraffin-embedded samples of normal tissue, psoriasis skin and MM. Results, In normal donors, mean ± SEM plasma proteasome concentration was 2138 ± 221 ng mL,1. Patients with stages III and IV MM exhibited a significantly higher value (3373 ± 470 ng mL,1 and 8931 ± 1232 ng mL,1, respectively). Values in patients with stage I/II MM and CIU were not significantly different from those in normal volunteers. Patients with severe psoriasis also exhibited increased values (3398 ± 374 ng mL,1) but to a lesser extent than in patients with stage IV MM. There was a significant correlation of proteasome levels with serum lactate dehydrogenase in the MM group. Tissue expression as demonstrated by immunohistochemistry paralleled these findings. The strongest expression was seen on MM slides and to a lesser extent in psoriasis samples, the weakest expression being observed in normal skin. Conclusions, Proteasomes are strongly expressed in cutaneous MM; high levels of circulating proteasomes are detected in patients with metastatic MM with a high melanoma burden, and at a lesser extent in psoriatic patients, which suggests proteasomes represent a marker more of nonspecific inflammation than of early cancer. [source] CD4+CD25+FoxP3+ regulatory T cells are increased whilst CD3+CD4,CD8,,,TCR+ Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burdenBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Feyler Summary Increased levels of naturally occurring regulatory T cells (TReg cells) have been found in a variety of solid tumours and haematological malignancies. In multiple myeloma (MM), evidence suggests that TReg cells are increased though controversy exists with regards to their function and no relationship to disease stage and treatment has been demonstrated. Here, we demonstrate significantly elevated levels of functional CD4+CD25+FoxP3+ TReg cells in a large cohort of patients with MM as well as monoclonal gammopathy of uncertain significance (MGUS) in comparison to age-matched, healthy controls. The frequency of Double Negative TReg cells was also evaluated, demonstrating that these cells were reduced in patients with MM. Furthermore, a characteristic profile of immunomodulatory cytokines in the peripheral blood and bone marrow of patients with MM and MGUS was demonstrated, compared with healthy controls. This data adds further evidence to the understanding of the role of TReg cell subsets in tumour immunology and the fundamentals of the host/tumour immune conflict. [source] Serum pleiotrophin levels are elevated in multiple myeloma patients and correlate with disease statusBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Howard S. Yeh Summary Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P < 0·0001). Serum levels of this protein significantly increased during progression of disease, and decreased during response to anti-MM therapy (P < 0·001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients. [source] | ||||||||||||||||||||||||||||||||||