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Sample records for advanced tumour stages

  1. Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma.

    PubMed

    Wirsing, Anna M; Rikardsen, Oddveig G; Steigen, Sonja E; Uhlin-Hansen, Lars; Hadler-Olsen, Elin

    2016-02-01

    Staging of oral squamous cell carcinoma is based on the tumour-node-metastasis (TNM) system, which has been deemed insufficient for prognostic purposes. Hence, better prognostic tools are needed to reflect the biological diversity of these cancers. Previously, high numbers of specialized blood vessels called high-endothelial venules have been reported to be associated with prolonged survival in patients with breast cancer. In this study, we analysed the prognostic value and morphological characteristics of tumour-associated high-endothelial venules in oral cancer. The presence of tumour-associated high-endothelial venules was evaluated by immunohistochemistry in 75 patients with oral squamous cell carcinoma and analysed with correlation to clinicopathological parameters, patients' survival and vessel morphology. Ten of the samples were analysed at multiple levels to evaluate intratumoural heterogeneity. The presence of tumour-associated high-endothelial venules was found to be associated with lower disease-specific death in multivariate regression analyses (P = 0.002). High-endothelial venules were present in all (n = 53) T1-T2 tumours, but only in two thirds (n = 14) of the T3-T4 tumours. The morphology of high-endothelial venules was heterogeneous and correlated with lymphocyte density. High-endothelial venules were found to be distributed homogeneously within the tumours. We found the presence of tumour-associated high-endothelial venules to be an easy-to-use, robust, and independent positive prognostic factor for patients with oral cancer. Absence of these vessels in advanced-stage tumours might identify patients with more aggressive disease. Evaluating the presence of tumour-associated high-endothelial venules might help to tailor the treatment of oral cancer patients to their individual needs. PMID:26383526

  2. Thoracic Wall Reconstruction in Advanced Breast Tumours

    PubMed Central

    Daigeler, A.; Harati, K.; Goertz, O.; Hirsch, T.; Behr, B.; Lehnhardt, M.; Kolbenschlag, J.

    2014-01-01

    In advanced mammary tumours, extensive resections, sometimes involving sections of the thoracic wall, are often necessary. Plastic surgery reconstruction procedures offer sufficient opportunities to cover even large thoracic wall defects. Pedicled flaps from the torso but also free flap-plasties enable, through secure defect closure, the removal of large, ulcerated, painful or bleeding tumours with moderate donor site morbidity. The impact of thoracic wall resection on the respiratory mechanism can be easily compensated for and patientsʼ quality of life in the palliative stage of disease can often be improved. PMID:24976636

  3. Preoperative carcinoembryonic antigen is related to tumour stage and long-term survival in colorectal cancer.

    PubMed Central

    Chapman, M. A.; Buckley, D.; Henson, D. B.; Armitage, N. C.

    1998-01-01

    Evidence as to the value of preoperative carcinoembryonic antigen (CEA) in guiding treatment for patients with colorectal cancer is conflicting. The aim of this prospective study was to investigate the value of preoperative CEA in predicting tumour factors of proven prognostic value and long-term survival in patients undergoing surgery for colorectal cancer. Preoperative serum CEA, tumour ploidy, stage and grade were ascertained in 277 patients undergoing colorectal cancer surgery. This cohort of patients were followed up for a minimum of 5 years, or until death, in a dedicated colorectal clinic. Patients with an elevated CEA had a 5 year survival of 39%. This increased to 57% if the CEA was normal (P=0.001). The proportion of patients with a raised CEA increased with a more advanced tumour stage (P < 0.000001) and a poorly differentiated tumour grade (P < 0.005). Once stage had been controlled for, CEA was not a predictor of survival. No relationship between tumour ploidy and CEA was found. In conclusion, a raised preoperative serum CEA is likely to be associated with advanced tumour stage and poor long-term survival, compared with patients with a normal value. PMID:9823977

  4. Oncolytic virotherapy for advanced liver tumours

    PubMed Central

    Chang, Ju-Fang; Chen, Pei-Jer; Sze, Daniel Y; Reid, Tony; Bartlett, David; Kirn, David H; Liu, Ta-Chiang

    2009-01-01

    Primary and metastatic neoplasms of the liver account for more than a million deaths per year worldwide. Despite decades of research, effective novel therapies for these cancers are urgently needed. Oncolytic virotherapeutics represent a novel class of pharmacophore that holds promise for the treatment of hepatic neoplasms. Cancer-specific replication is followed by oncolysis, virus spreading and infection of adjacent cancer cells. This process is then repeated. Virotherapeutics target multiple genetic pathways involved in carcino-genesis, and demonstrate activity against apoptosis-resistant tumour cells. This platform can also exploit the advantage of multiple intrinsic anti-cancer therapeutic mechanisms, combining direct viral oncolysis with therapeutic transgene expression. Recent advances in pre-clinical and clinical studies are revealing the potential of this unique therapeutic class, in particular for liver cancers. This review summarizes the available data on applying oncolytic virotherapeutics to hepatic neoplasms to date, and discusses the challenges and future directions for virotherapy. PMID:19175689

  5. Role of Staging in Patients with Small Intestinal Neuroendocrine Tumours.

    PubMed

    Clift, Ashley Kieran; Faiz, Omar; Al-Nahhas, Adil; Bockisch, Andreas; Liedke, Marc Olaf; Schloericke, Erik; Wasan, Harpreet; Martin, John; Ziprin, Paul; Moorthy, Krishna; Frilling, Andrea

    2016-01-01

    Small bowel neuroendocrine tumours are the commonest malignancy arising in the small intestine and have substantially increased in incidence in recent decades. Patients with small bowel neuroendocrine tumours commonly develop lymph node and/or distant metastases. Here, we examine the role of staging in 84 surgically treated patients with small bowel neuroendocrine tumours, comparing diagnostic information yielded from morphological, functional and endoscopic modalities. Furthermore, we correlate pre-operative staging with intra-operative findings in a sub-cohort of 20 patients. The vast majority of patients had been histologically confirmed to have low-grade (Ki-67 <2%) disease; however, lymph node and distant metastases were observed in 74 (88.1%) and 51 (60.7%) of patients at presentation, respectively. Liver metastases were evident in 48 (57.1%) patients, with solely peritoneal and bone metastases observed in 2 (2.4%) and 1 (1.2%) patients, respectively. Forty patients (47.6%) received multimodal treatment. In our sub-cohort analysis, pre-operative imaging understaged disease in 14/20 (70%) when compared with intra-operative findings. In patients with multifocal primary tumours and miliary liver metastases, no imaging modality was able to detect entire disease spread. Overall, presently available imaging modalities heavily underestimate disease stage, with meticulous intra-operative abdominal examination being superior to any imaging technology. Multimodal treatment has an important role in prolonging survival. PMID:26394880

  6. One-stage laparoscopic procedure for a patient with bilateral colorectal tumours and renal carcinoma

    PubMed Central

    FAZZIN, M.; DELLACHIESA, L.; RESTA, G.; BANDI, M.; MARINO, S.; ANANIA, G.

    2013-01-01

    Summary: We describe a case of a patient with synchronous bilateral colorectal tumours and renal carcinoma who underwent one-stage laparoscopic surgery procedure with right transperitoneal nefrectomy, right hemicolectomy and sigmoidectomy. One-stage laparoscopic procedure can be used safely and successfully for a patient with multiple primary tumours. PMID:23660167

  7. Fibre intake and incident colorectal cancer depending on fibre source, sex, tumour location and Tumour, Node, Metastasis stage.

    PubMed

    Vulcan, Alexandra; Brändstedt, Jenny; Manjer, Jonas; Jirström, Karin; Ohlsson, Bodil; Ericson, Ulrika

    2015-09-28

    Studies on fibre intake and incident colorectal cancer (CRC) indicate inverse associations. Differences by tumour stage have not been examined. We examined associations between fibre intake and its sources, and incidental CRC. Separate analyses were carried out on the basis of sex, tumour location and the Tumour, Node, Metastasis (TNM) classification. The Malmö Diet and Cancer Study is a population-based cohort study, including individuals aged 45-74 years. Dietary data were collected through a modified diet history method. The TNM classification was obtained from pathology/clinical records and re-evaluated. Among 27 931 individuals (60% women), we found 728 incident CRC cases during 428 924 person-years of follow-up. Fibre intake was inversely associated with CRC risk (P(trend) = 0.026). Concerning colon cancer, we observed borderline interaction between fibre intake and sex (P = 0.052) and significant protective association restricted to women (P(trend) = 0.013). Intake of fruits and berries was inversely associated with colon cancer in women (P(trend) = 0.022). We also observed significant interactions between intakes of fibre (P = 0.048) and vegetables (P = 0.039) and sex on rectal cancer, but no significant associations were seen between intake of fibre, or its sources, in either of the sexes. Except for inverse associations between intake of fibre-rich cereal products and N0- and M0-tumours, we did not observe significant associations with different TNM stages. Our findings suggest different associations between fibre intake and CRC depending on sex, tumour site and fibre source. High fibre intake, especially from fruits and berries, may, above all, prevent tumour development in the colon in women. No clear differences by TNM classification were detected. PMID:26281852

  8. Advanced two-stage incinerator

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    The Institute of Gas Technology (IGT) is developing an advanced incinerator that combines the fluidized-bed agglomeration/incineration and cyclonic combustion/incineration technologies that have been developed separately at IGT over many years. This combination results in a unique and extremely flexible incinerator for solid, sludge, liquid, and gaseous wastes. This system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes would be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)), whereas solid inorganic contaminants would be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. This technology is different from other existing technologies because of its agglomeration and encapsulation capability and its flexibility with respect to the types wastes it can handle. Both the fluidized-bed as well as the cyclonic incineration technologies have been fully developed and tested separately at pilot scales. 12 refs., 4 figs., 4 tabs.

  9. Nuclear medicine in the detection, staging and treatment of gastrointestinal carcinoid tumours.

    PubMed

    Oberg, Kjell; Eriksson, Barbro

    2005-06-01

    Carcinoid tumours belong to the family of neuroendocrine tumours with a capacity to take up and concentrate amines and precursors as well as peptides, and can thereby be detected by nuclear medicine techniques. These rare tumours are difficult to diagnose at earlier stages because of small size and multiplicity. Computed tomography (CT) and magnetic resonance imaging (MRI) are mostly of benefit for detection of larger primary tumours (1-3 cm) and liver and lymph-node metastases. A majority of carcinoid tumours express somatostatin receptors, particularly receptor type 2, and thus somatostatin receptor scintigraphy (SRS) can be used for detection and staging of carcinoid tumours. The detection rate of carcinoid tumours has been reported to be somewhere between 80 and 100% in different studies. The scintigraphy gives a good staging of the disease and detection of unexpected tumour sites, which were not determined by conventional imaging. This method also indicates content of somatostatin receptors, which might indicate efficacy of treatment with octreotide or other somatostatin analogues. Another new non-invasive technique for detection of carcinoid tumours is positron emission tomography (PET). The biological substance for study can be labelled for radioactive imaging with radionuclears, such as (11)C, (15)O and (18)F, with emission of positrons. More than 95% of patients studied displayed high tracer uptake from PET with (11)C-5HTP (5-hydroxytryptophan), which is significantly higher compared to both computer tomography and somatostatin receptor scintigraphy. MIBG has been used for decades to visualize carcinoid tumours, because MIBG is concentrated in the endocrine cells. It was initially developed to detect phaeochromocytomas of the adrenal with reported high sensitivity (87%) and specificity as high as 99%. The method can be used when other methods fail to localize carcinoid tumours and particularly when treatment with (131)I-MIBG is being considered. Tumour

  10. Surgical management of stage T1 renal tumours at Canadian academic centres

    PubMed Central

    Lavallée, Luke T.; Tanguay, Simon; Jewett, Michael A.; Wood, Lori; Kapoor, Anil; Rendon, Ricardo A.; Moore, Ronald B.; Lacombe, Louis; Kawakami, Jun; Pautler, Stephen E.; Drachenberg, Darrel E.; Black, Peter C.; Lattouf, Jean-Baptiste; Morash, Christopher; Cagiannos, Ilias; Liu, Zhihui; Breau, Rodney H.

    2015-01-01

    Introduction: The proportion of patients with stage 1 renal tumours receiving partial nephrectomy is considered a quality of care indicator. The objective of this study was to characterize surgical practice patterns at Canadian academic institutions for the treatment of these tumours. Methods: The Canadian Kidney Cancer Information System (CKCis) is a multicentre collaboration of 13 academic institutions in Canada. All patients with pathologic stage T1 renal tumours in CKCis were identified. Descriptive statistics were performed to characterize practice patterns over time. Associations between patient, tumour, and treatment factors with the use of partial nephrectomy were determined. Results: From 1988 to April 2014, 1453 patients with pathologic stage 1 renal tumours were entered in the CKCis database. Of these, 977 (67%) patients had pT1a tumours; of these, 765 (78%) received partial nephrectomy. Of the total number of patients (1453), 476 (33%) had pT1b tumours; of these, 204 (43%) received partial nephrectomy. The use of partial nephrectomy increased over time from 60% to 90% for pT1a tumours and 20% to 60% for pT1b tumours. Stage pT1b (relative risk [RR] 0.56, 95% confidence interval [CI] 0.50–0.63) and minimally invasive surgical approach (RR 0.78, 95% CI 0.73–0.84 for pT1a and RR 0.23, 95% CI 0.17–0.30 for pT1b) were associated with decreased use of partial nephrectomy. Most patient factors including age, gender, body mass index, hypertension, and renal function were not significantly associated with use of partial nephrectomy (p > 0.05). Conclusion: Almost all pT1a and most pT1b renal tumours managed surgically at academic centres in Canada receive partial nephrectomy. The use of partial versus radical nephrectomy appears to occur independently of patient age and comorbid status, which may indicate that urologists are performing partial nephrectomy whenever technically feasible based on tumour factors. Although the ideal proportion patients receiving

  11. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study

    PubMed Central

    Phan, Alexandria T; Halperin, Daniel M; Chan, Jennifer A; Fogelman, David R; Hess, Kenneth R; Malinowski, Paige; Regan, Eileen; Ng, Chaan S; Yao, James C; Kulke, Matthew H

    2015-01-01

    Summary Background Treatment options for advanced, well-differentiated neuroendocrine tumours (NETs) remain scarce. Pazopanib is an orally bioavailable, small molecule, multitargeted kinase inhibitor that inhibits VEGF receptors 1, 2, and 3. We did a study of the efficacy of pazopanib with depot octreotide in patients with advanced NETs. Methods We did a parallel cohort study of patients with metastatic or locally advanced grade 1–2 carcinoid tumours or pancreatic NETs, by use of a single-group, two-stage design. Patients received pazopanib 800 mg orally once per day and octreotide at their preprotocol dosage. The primary endpoint was the proportion of patients achieving an objective response, as assessed by investigators, by intention-to-treat analysis. This study is registered with ClinicalTrials.gov, identifier NCT00454363, and was completed in March, 2014. Findings Between April 12, 2007, and July 2, 2009, we enrolled 52 patients, including 32 individuals with pancreatic NETs and 20 individuals with carcinoid tumours. Seven (21.9%, 95% CI 11.0–38.8) of 32 patients with pancreatic NETs achieved an objective response. We detected no responses in the first stage of the cohort with carcinoid tumours, and we terminated accrual at 20 patients. Toxic effects included one patient with grade 4 hypertriglyceridaemia and one with grade 4 thrombosis, with the most common grade three events being aminotransferase increases and neutropenia, each of which happened in 3 patients. In all 52 patients, the most frequently observed toxic effects were fatigue (39 [75%]), nausea (33 [63%]), diarrhoea (33 [63%]), and hypertension (28 [54%]). Interpretation Treatment with pazopanib is associated with tumour response for patients with pancreatic NETs, but not for carcinoid tumours; a randomised controlled phase 3 study to assess pazopanib in advanced pancreatic NETs is warranted. Funding US National Cancer Institute of the National Institutes of Health. PMID:25956795

  12. [The ultrastructure of mixed mammary gland tumours in bitches. III. The early stages of the myoepithelial proliferation (author's transl)].

    PubMed

    von Bomhard, D; von Sandersleben, J

    1975-08-12

    The early stages of myoepithelial proliferation in 14 mixed canine mammary tumours were studied by light- and electron microscopy. Two different early stages can be distinguished: 1. Proliferations inside the basal lamina with partial maintenance of the organoid pattern. 2. Proliferations with a break through the basal lamina and transposition of tumour cells into the surrounding connective tissue. The intracytoplasmic fibrillae of myoepithelial tumour cells are striped periodically and thicker than those of normal myothelia. It is suggested that the amorphous as well as the fibrous intercellular substance in the early stages is derived from the described myoepithelial tumour cells. PMID:169622

  13. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    PubMed Central

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  14. The cholesterol-binding protein NPC2 restrains recruitment of stromal macrophage-lineage cells to early-stage lung tumours.

    PubMed

    Kamata, Tamihiro; Jin, Hong; Giblett, Susan; Patel, Bipin; Patel, Falguni; Foster, Charles; Pritchard, Catrin

    2015-09-01

    The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during pre-cancerous development. In this model, we have found that immature macrophage-lineage cells (IMCs) producing PDGFA, TGFβ and CC chemokines are recruited to the stroma of premalignant lung adenomas through CC chemokine receptor 1 (CCR1)-dependent mechanisms. Stromal IMCs promote proliferation and transcriptional alterations suggestive of epithelial-mesenchymal transition in isolated premalignant lung tumour cells ex vivo, and are required for the maintenance of early-stage lung tumours in vivo. Furthermore, we have found that IMC recruitment to the microenvironment is restrained by the cholesterol-binding protein, Niemann-Pick type C2 (NPC2). Studies on isolated cells ex vivo confirm that NPC2 is secreted from tumour cells and is taken up by IMCs wherein it suppresses secretion of the CCR1 ligand CC chemokine 6 (CCL6), at least in part by facilitating its lysosomal degradation. Together, these findings show that NPC2 secreted by premalignant lung tumours suppresses IMC recruitment to the microenvironment in a paracrine manner, thus identifying a novel target for the development of chemopreventive strategies in lung cancer. PMID:26183450

  15. Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study

    PubMed Central

    Board, R E; Ellison, G; Orr, M C M; Kemsley, K R; McWalter, G; Blockley, L Y; Dearden, S P; Morris, C; Ranson, M; Cantarini, M V; Dive, C; Hughes, A

    2009-01-01

    Background: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. Methods: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. Results: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. Conclusions: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection. PMID:19861964

  16. Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review.

    PubMed

    Chau, I; Casciano, R; Willet, J; Wang, X; Yao, J C

    2013-11-01

    Neuroendocrine tumours (NET) are often diagnosed at an advanced stage when the prognosis is poor for patients, who often experience diminished quality of life (QoL). As new treatments for NET become available, it is important to characterise the associated outcomes, costs and QoL. A comprehensive search was performed to systematically review available data in advanced NET regarding cost of illness/resource utilisation, economic studies/health technology assessment and QoL. Four rounds of sequential review narrowed the search results to 22 relevant studies. Most focused on surgical procedures and diagnostic tools and contained limited information on the costs and consequences of medical therapies. Multiple tools are used to assess health-related QoL in NET, but few analyses have been conducted to assess the comparative impact of available treatment alternatives on QoL. Limitations include English language and the focus on advanced NET; ongoing terminology and classification changes prevented pooled statistical analyses. This systematic review suggests a lack of comparative economic and outcomes data associated with NET treatments. Further research on disease costs, resource utilisation and QoL for patients with advanced NET is warranted. PMID:23895457

  17. Quality of life, resource utilisation and health economics assessment in advanced neuroendocrine tumours: a systematic review

    PubMed Central

    Chau, I; Casciano, R; Willet, J; Wang, X; Yao, JC

    2013-01-01

    Neuroendocrine tumours (NET) are often diagnosed at an advanced stage when the prognosis is poor for patients, who often experience diminished quality of life (QoL). As new treatments for NET become available, it is important to characterise the associated outcomes, costs and QoL. A comprehensive search was performed to systematically review available data in advanced NET regarding cost of illness/resource utilisation, economic studies/health technology assessment and QoL. Four rounds of sequential review narrowed the search results to 22 relevant studies. Most focused on surgical procedures and diagnostic tools and contained limited information on the costs and consequences of medical therapies. Multiple tools are used to assess health-related QoL in NET, but few analyses have been conducted to assess the comparative impact of available treatment alternatives on QoL. Limitations include English language and the focus on advanced NET; ongoing terminology and classification changes prevented pooled statistical analyses. This systematic review suggests a lack of comparative economic and outcomes data associated with NET treatments. Further research on disease costs, resource utilisation and QoL for patients with advanced NET is warranted. PMID:23895457

  18. Management of asymptomatic primary tumours in stage IV colorectal cancer: Review of outcomes

    PubMed Central

    Wilkinson, Kate Jessica; Chua, Wei; Ng, Weng; Roohullah, Aflah

    2015-01-01

    AIM: To compare outcomes for patients presenting with stage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection (PTR) plus palliative chemotherapy vs primary chemotherapy up-front. METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primary-tumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1b stage and non-use of modern chemotherapy agents. CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated. PMID:26691885

  19. Can advanced-stage ovarian cancer be cured?

    PubMed

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  20. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    PubMed

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (p<0.01) reduction of the incidence and number of skin papillomas, precancerous skin lesions, along with significant (p<0.01) elevation of phase II detoxifying enzymes (GST, Catalase and SOD) and inhibition of lipid peroxidation in liver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

  1. Spinal cord tumours: advances in genetics and their implications for treatment

    PubMed Central

    Zadnik, Patricia L.; Gokaslan, Ziya L.; Burger, Peter C.; Bettegowda, Chetan

    2014-01-01

    Tumours of the spinal cord, although rare, are associated with high morbidity. Surgical resection remains the primary treatment for patients with this disease, and offers the best chance for cure. Such surgical procedures, however, carry substantial risks such as worsening of neurological deficit, paralysis and death. New therapeutic avenues for spinal cord tumours are needed, but genetic studies of the molecular mechanisms governing tumourigenesis in the spinal cord are limited by the scarcity of high-quality human tumour samples. Many spinal cord tumours have intracranial counterparts that have been extensively studied, but emerging data show that the tumours are genetically and biologically distinct. The differences between brain and spine tumours make extrapolation of data from one to the other difficult. In this Review, we describe the demographics, genetics and current treatment approaches for the most commonly encountered spinal cord tumours—namely, ependymomas, astrocytomas, haemangioblastomas and meningiomas. We highlight advances in understanding of the biological basis of these lesions, and explain how the latest progress in genetics and beyond are being translated to improve patient care. PMID:23528542

  2. Targeted Therapies for Advanced Ewing Sarcoma Family of Tumours

    PubMed Central

    Jiang, Yunyun; Ludwig, Joseph; Janku, Filip

    2015-01-01

    The prognosis of adolescent and young adult patients battling metastatic Ewing Sarcoma Family of Tumours (ESFT) remains less than 30% despite the development of systemic therapies. In the era of personalized medicine, novel molecular targets have been tested in preclinical or clinical settings in ESFT. In this review, we focus on early clinical and translational research that identified multiple molecular targets, including IGF-1R; mTOR; tyrosine kinase inhibitors; EWS-FLI1-related targets, and others. Overall, novel targeted therapies demonstrated modest efficacy; however pronounced and durable antineoplastic responses have been observed in small subsets of treated patients, for example with IGF-1R antibodies. Identifying outcome-predicting biomarkers and overcoming treatment resistance remain major challenges. Due to the rarity of ESFT, multi-institutional collaboration efforts of clinicians, basic and translational scientists are needed in order to understand biology of therapeutic response or resistance, which can lead to development of novel therapeutic methods and improved patient outcomes. PMID:25869102

  3. Regional variations in cancer survival: Impact of tumour stage, socioeconomic status, comorbidity and type of treatment in Norway.

    PubMed

    Skyrud, Katrine Damgaard; Bray, Freddie; Eriksen, Morten Tandberg; Nilssen, Yngvar; Møller, Bjørn

    2016-05-01

    Cancer survival varies by place of residence, but it remains uncertain whether this reflects differences in tumour, patient and treatment characteristics (including tumour stage, indicators of socioeconomic status (SES), comorbidity and information on received surgery and radiotherapy) or possibly regional differences in the quality of delivered health care. National population-based data from the Cancer Registry of Norway were used to identify cancer patients diagnosed in 2002-2011 (n = 258,675). We investigated survival from any type of cancer (all cancer sites combined), as well as for the six most common cancers. The effect of adjusting for prognostic factors on regional variations in cancer survival was examined by calculating the mean deviation, defined by the mean absolute deviation of the relative excess risks across health services regions. For prostate cancer, the mean deviation across regions was 1.78 when adjusting for age and sex only, but decreased to 1.27 after further adjustment for tumour stage. For breast cancer, the corresponding mean deviations were 1.34 and 1.27. Additional adjustment for other prognostic factors did not materially change the regional variation in any of the other sites. Adjustment for tumour stage explained most of the regional variations in prostate cancer survival, but had little impact for other sites. Unexplained regional variations after adjusting for tumour stage, SES indicators, comorbidity and type of treatment in Norway may be related to regional inequalities in the quality of cancer care. PMID:26679150

  4. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation.

    PubMed

    Andreasen, E B; Nielsen, O L; Tranholm, M; Knudsen, T; Kristensen, A T

    2016-06-01

    Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC). PMID:24674618

  5. Treatment of Advanced Tumours of Head and Neck with Fast Neutrons

    PubMed Central

    Catterall, Mary; Vonberg, D. D.

    1974-01-01

    Fast neutrons interact with matter in a different way from x and gamma rays. They have been used at Hammersmith Hospital for the past four years in the treatment of advanced tumours in several sites of the body, and the results of this treatment in the first 100 cases of tumours of the head and neck are described here. Altogether 62 patients who had been referred for fast neutron therapy because it was thought that no other treatment would be effective experienced complete regression of the tumours, and only two recurred. Tumours of the buccal cavity and salivary glands responded particularly well and the relief of pain and ulceration was striking. Side effects were not serious and did not differ from those seen with supervoltage radiation, apart from the reaction of the skin. Follow-up was short, however, owing to deaths from metastases, and out of 76 patients treated more than one year previously only 30 survived. Cases which have not metastasized must therefore be treated so that the effects on tumours and adjacent normal tissues can be observed for several years after treatment. The results obtained so far indicate that it is now justifiable to use neutrons in such cases. ImagesFIG. 2FIG. 3 PMID:4210570

  6. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

    PubMed Central

    Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

    2014-01-01

    Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

  7. Treatment of advanced-stage Hodgkin lymphoma.

    PubMed

    Vassilakopoulos, Theodoros P; Johnson, Peter W M

    2016-07-01

    There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this. PMID:27496308

  8. Advance statement of consent from patients with primary CNS tumours to organ donation and elective ventilation.

    PubMed

    Patel, Umang Jash

    2013-03-01

    A deficit in the number of organs available for transplantation persists even with an increase in donation rates. One possible choice of donor for organs that appears under-referred and/or unaccepted is patients with primary brain tumours. In spite of advances in the treatment of high-grade primary central nervous system (CNS) tumours, the prognosis remains dire. A working group on organs from donors with primary CNS tumours showed that the risk of transmission is small and outweighs the benefits of waiting for a normal donor, in survival and organ life-years, with caveats. This paper explores the possibility that, if information on organ donation were made available to patients and their families with knowledge of their inevitable fate, perhaps some will choose to donate. It would be explained that to achieve this, elective ventilation would be performed in their final moments. This would obviate the consent question because of an advance statement. It is accepted that these are sensitive matters and there will be logistic issues. This will need discussion with the public and other professionals, but it could increase the number of donors and can be extrapolated to encompass other primary CNS tumours. PMID:23303178

  9. Advanced two-stage compressor program design of inlet stage

    NASA Technical Reports Server (NTRS)

    Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

    1973-01-01

    The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

  10. Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.

    PubMed

    Pencavel, Tim D; Wilkinson, Michelle J; Mansfield, David C; Khan, Aadil A; Seth, Rohit; Karapanagiotou, Eleni M; Roulstone, Victoria; Aguilar, Richard J; Chen, Nanhai G; Szalay, Aladar A; Hayes, Andrew J; Harrington, Kevin J

    2015-02-15

    Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells. An orthotopic model of advanced extremity sarcoma was used to evaluate survival of animals after ILP with combinations of TNF-α, melphalan and GLV-1h68. We investigated the efficiency of viral tumour delivery by ILP compared to intravenous therapy, the locoregional and systemic biodistribution of virus after ILP, and the effect of mode of administration on antibody response. The combination of melphalan and GLV-1h68 was synergistic in vitro. The addition of virus to standard ILP regimens was well tolerated and demonstrated superior tumour targeting compared to intravenous administration. Triple therapy (melphalan/TNF-α/GLV-1h68) resulted in increased tumour growth delay and enhanced survival compared to other treatment regimens. Live virus was recovered in large amounts from perfused regions, but in smaller amounts from systemic organs. The addition of oncolytic vaccinia virus to existing TNF-α/melphalan-based ILP strategies results in survival advantage in an immunocompetent rat model of advanced extremity sarcoma. Virus administered by ILP has superior tumour targeting compared to intravenous delivery. Further evaluation and clinical translation of this approach is warranted. PMID:24978211

  11. The seventh tumour-node-metastasis staging system for lung cancer: Sequel or prequel?

    PubMed

    van Meerbeeck, Jan P; Janssens, Annelies

    2013-09-01

    Anatomical cancer extent is an important predictor of prognosis and determines treatment choices. In non-small-cell lung cancer (NSCLC) the tumour-node-metastasis (TNM) classification developed by Pierre Denoix replaced in 1968 the Veterans Administration Lung cancer Group (VALG) classification, which was still in use for small-cell lung cancer (SCLC). Clifton Mountain suggested several improvements based on a database of mostly surgically treated United States (US) patients from a limited number of centres. This database was pivotal for a uniform reporting of lung cancer extent by the American Joint Committee of Cancer (AJCC) and the International Union against Cancer (IUCC), but it suffered increasingly from obsolete diagnostic and staging procedures and did not reflect new treatment modalities. Moreover, its findings were not externally validated in large Japanese and European databases, resulting in persisting controversies which could not be solved with the available database. The use of different mediastinal lymph-node maps in Japan, the (US) and Europe facilitated neither the exchange nor the comparison of treatment results. Peter Goldstraw, a United Kingdom (UK) thoracic surgeon, started the process of updating the sixth version in 1996 and brought it to a good end 10 years later. His goals were to improve the TNM system in lung cancer by addressing the ongoing controversies, to validate the modifications and additional descriptors, to validate the TNM for use in staging SCLC and carcinoid tumours, to propose a new uniform lymph-node map and to investigate the prognostic value of non-anatomical factors. A staging committee was formed within the International Association for the Study of Lung Cancer (IASLC) - which supervised the collection of the retrospective data from >100,000 patients with lung cancer - treated throughout the world between 1990 and 2000, analyse them with the help of solid statistics and validate externally with the Surveillance

  12. Optical diagnostics of tumour cells at different stages of pathology development

    SciTech Connect

    Shcheglova, L S; Maryakhina, V S; Abramova, L L

    2013-11-30

    The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 – 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions. (optical methods in biology and medicine)

  13. Optical diagnostics of tumour cells at different stages of pathology development

    NASA Astrophysics Data System (ADS)

    Shcheglova, L. S.; Abramova, L. L.; Maryakhina, V. S.

    2013-11-01

    The differences in optical and biophysical properties between the cells of mammary gland tumour extracted from tumours of different diameter are described. It is shown that the spectral and spectrokinetic properties of fluorescent probes in the cells extracted from the tumours 1 - 3 cm in diameter are essentially different. Thus, the extinction coefficient of rhodamine 6G gradually increases with the pathology development. At the same time the rate of interaction of the triplet states of molecular probes with the oxygen, diluted in the tumour cells cytoplasm, decreases with the growth of the tumour capsule diameter. The observed regularities can be due to the changes in the cell structure, biochemical and biophysical properties. The reported data may be useful for developing optical methods of diagnostics of biotissue pathological conditions.

  14. A model to predict survival following pancreaticoduodenectomy for malignancy based on tumour site, stage and lymph node ratio☆

    PubMed Central

    Dasari, Bobby V.M.; Roberts, Keith J.; Hodson, James; Stevens, Lewis; Smith, Andrew M.; Hubscher, Stefan G.; Isaac, John; Muiesan, Paolo; Sutcliffe, Robert P.; Marudanayagam, Ravi; Mirza, Darius F.

    2016-01-01

    Background Site of tumour origin, lymph node metastases and lymph node ratio (LNR) are identified as important factors determining prognosis in patients undergoing pancreaticoduodenectomy (PD). This study hypothesised that a prognostic index to predict survival could be developed through statistical modelling based on these pathological variables. Methods Patients who underwent PD between 2004 and 2013 were included. Univariable and multivariable (Cox regression) analyses were performed to identify predictors of survival, and a prognostic index was derived. The prognostic index was then validated using an external patient cohort. Results A total of 567 patients who underwent PD were used as a derivation cohort. Tumour site (p < 0.001), tumour size (p = 0.002), T-stage (p < 0.001), vascular involvement (p = 0.002), number of positive nodes (p < 0.001) and LNR (p < 0.001) were significantly associated with survival in univariable analysis. LNR (p < 0.001), tumour site (p < 0.001), T-stage (p = 0.007) remained significant predictors of survival in multivariable analysis, and were combined to derive a prognostic index. The accuracy of the prognostic index was assessed both on the original cohort, and a validation set of 194 patients from another institutional prospective database. The AUROC scores for predicting the overall survival at 3 years were 0.77 in the derivation cohort and 0.74 in the validation cohort. Conclusion The Pancreaticoduodenectomy Prognostic Index is a validated clinico-pathological model based on tumour site, T-stage and LNR to predict long-term survival following PD. PMID:27037202

  15. Treatment of advanced solid tumours with NSAIDs: Correlation of quantitative monitoring of circulating tumour cells and positron emission tomography-computed tomography imaging

    PubMed Central

    Willecke-Hochmuth, Regina; Pachmann, Katharina; Drevs, Joachim

    2016-01-01

    The detection and characterisation of tumour-derived circulating epithelial tumor cells (CETCs) or circulating tumor cells (CTCs) have been a main focus of basic oncological research over previous years. Numerous studies in the past decade have shown that CTCs are a promising tool for the estimation of the risk for metastatic relapse. The present observational study describes treatment results using tumour imaging and the quantification of CTCs. A group of 14 patients with advanced carcinomas was followed during their anticancer treatments. CTC numbers were serially detected and treatment success was estimated by positron emission tomography-computed tomography. A connection was found between tumour remission and a decreasing CTC count in 83%, a connection between stable disease and stable CTC numbers in 78% and a connection between progressive disease (PD) and an increase in CTC count in 50% of cases. In the patients with PD, an incomplete response was observed affecting the CTCs, but not the solid region of the tumour. As a result of this study, it may be concluded that patients with solid tumours benefit from serial quantification of CTCs in addition to imaging, as this combination of techniques provides a more sensitive result than imaging alone. PMID:27588120

  16. New clinical advances in immunotherapy for the treatment of solid tumours

    PubMed Central

    Zavala, Valentina A; Kalergis, Alexis M

    2015-01-01

    Advances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anti-cancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients. PMID:25826229

  17. Hepatic intra-arterial chemotherapy in patients with advanced primary liver tumours

    PubMed Central

    Spada, Francesca; Fazio, Nicola; Bonomo, Guido; Monfardini, Lorenzo; Vigna, Paolo Della; Radice, Davide; Boselli, Sabrina; Orsi, Franco

    2012-01-01

    Background: Primary liver tumours (PLTs) are currently a major health problem worldwide. The study’s aim was to investigate the feasibility, toxicity, and activity of hepatic intra-arterial chemotherapy (HIAC) in patients with advanced PLTs. Methods: We retrospectively analysed 43 patients with advanced unresectable PLT, who were consecutively treated. HIAC with 5-fluorouracil, cisplatin, and mitomycin-C was administered through a radiologically positioned temporary percutaneous catheter every six weeks until tumour progression or unacceptable toxicity was reached. Results: Partial response was observed in 26% and stable disease in 41% of patients. The median overall survival was 12.3 months. Manageable catheter-related complications occurred in 23% of patients. The grade 3–4 toxicities included neutropenia, thrombocytopenia, and transaminitis. There were no toxic deaths. Conclusion: The results of this retrospective study show that HIAC is feasible, active, and manageable in patients with PLTs. The treatment could be studied in selected patients with advanced progressive HCC/BTC being treated with or ineligible for sorafenib/cisplatin plus gemcitabine. PMID:23226162

  18. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  19. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  20. Vincristine-induced polyneuropathy in a child with stage I Wilms’ tumour presenting with unilateral abducens nerve palsy

    PubMed Central

    Panjawatanan, Panadeekarn; Charoenkwan, Pimlak; Katanyuwong, Kamornwan; Choeyprasert, Worawut

    2014-01-01

    A 4-year-old boy presented with right esotropia while receiving vincristine and dactinomycin for stage I Wilms’ tumour according to the National Wilms Tumour Study-5 protocol. On examination, he had isolated limitation of his right lateral gaze. CT of the brain and cerebrospinal fluid examination were normal. A nerve conduction velocity study which was performed on the peripheral nerves revealed predominant motor polyneuropathy compatible with axonal loss involving the upper limbs. The patient had received a cumulative vincristine dose of 17 mg/m2 before developing esotropia. Vincristine-induced abducens nerve mononeuropathy and subclinical motor polyneuropathy was suspected. Unilateral esotropia markedly improved after the discontinuation of vincristine and a short course of oral pyridoxine treatment. PMID:24966267

  1. Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study

    PubMed Central

    Trillsch, F; Mahner, S; Vettorazzi, E; Woelber, L; Reuss, A; Baumann, K; Keyver-Paik, M-D; Canzler, U; Wollschlaeger, K; Forner, D; Pfisterer, J; Schroeder, W; Muenstedt, K; Richter, B; Fotopoulou, C; Schmalfeldt, B; Burges, A; Ewald-Riegler, N; de Gregorio, N; Hilpert, F; Fehm, T; Meier, W; Hillemanns, P; Hanker, L; Hasenburg, A; Strauss, H-G; Hellriegel, M; Wimberger, P; Kommoss, S; Kommoss, F; Hauptmann, S; du Bois, A

    2015-01-01

    Background: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). Results: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. Conclusion: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed. PMID:25562434

  2. Phase I study of afatinib combined with nintedanib in patients with advanced solid tumours

    PubMed Central

    Bahleda, Rastislav; Hollebecque, Antoine; Varga, Andrea; Gazzah, Anas; Massard, Christophe; Deutsch, Eric; Amellal, Nadia; Farace, Françoise; Ould-Kaci, Mahmoud; Roux, Flavien; Marzin, Kristell; Soria, Jean-Charles

    2015-01-01

    Background: This Phase I study evaluated continuous- and intermittent-dosing (every other week) of afatinib plus nintedanib in patients with advanced solid tumours. Methods: In the dose-escalation phase (n=45), maximum tolerated doses (MTDs) were determined for continuous/intermittent afatinib 10, 20, 30 or 40 mg once daily plus continuous nintedanib 150 or 200 mg twice daily. Secondary objectives included safety and efficacy. Clinical activity of continuous afatinib plus nintedanib at the MTD was further evaluated in an expansion phase (n=25). Results: The most frequent dose-limiting toxicities were diarrhoea (11%) and transaminase elevations (7%). Maximum tolerated doses were afatinib 30 mg continuously plus nintedanib 150 mg, and afatinib 40 mg intermittently plus nintedanib 150 mg. Treatment-related adverse events (mostly Grade ⩽3) included diarrhoea (98%), asthenia (64%), nausea (62%) and vomiting (60%). In the dose-escalation phase, two patients had partial responses (PRs) and 27 (60%) had stable disease (SD). In the expansion phase, one complete response and three PRs were observed (all non-small cell lung cancer), with SD in 13 (52%) patients. No pharmacokinetic interactions were observed. Conclusions: MTDs of continuous or intermittent afatinib plus nintedanib demonstrated a manageable safety profile with proactive management of diarrhoea. Antitumour activity was observed in patients with solid tumours. PMID:26512876

  3. NM23-H1 immunostaining is inversely associated with tumour staging but not overall survival or disease recurrence in colorectal carcinomas.

    PubMed Central

    Cheah, P. Y.; Cao, X.; Eu, K. W.; Seow-Choen, F.

    1998-01-01

    The NM23-H1 gene product has been recently identified as a potential metastasis suppressor. Studies on breast carcinomas have shown an inverse correlation between NM23-H1 status and stage of carcinogenesis and overall survival. However, in colorectal cancer, conflicting data have been reported. This study aimed to investigate whether NM23-H1 immunostaining is correlated with tumour stage, overall survival, disease recurrence, tumour differentiation, age and sex in colorectal carcinomas for the Singapore population using chi-square analysis. The staining was performed on 141 paraffin-embedded surgical specimens collected between 1991 and 1992 using a monoclonal anti-NM23-H1 antibody. Follow-up of patients was until time of death or for 5 years. There was a very significant inverse association between tumour staging and NM23-H1 status (P = 0.0004). However, NM23-H1 expression was not significantly correlated to overall 5-year survival, disease recurrence, tumour differentiation, age or sex. Thus, although NM23-H1 may be involved in suppressing metastasis, NM23-H1 immunohistochemistry has no prognostic value in colorectal cancer. This is the first report of a significant inverse association of NM23-H1 status with tumour staging in colorectal cancer which showed no correlation with overall survival or disease recurrence. Our result thus cautions against the practice of equating an inverse relation of genetic markers with tumour staging to survival or disease recurrence. Images Figure 1 PMID:9569056

  4. Accuracy of MRI in Prediction of Tumour Thickness and Nodal Stage in Oral Tongue and Gingivobuccal Cancer With Clinical Correlation and Staging

    PubMed Central

    Parihar, Pratap Singh; Parihar, Akhilesh; Goel, Ashok Kumar; Waghwani, Kapil; Gupta, Richa; Bhutekar, Umesh

    2016-01-01

    Introduction Squamous cell carcinoma of lower gingivo-buccal complex and tongue are the most common cancer in the Indian sub-continent. The value of imaging in the staging of Oral Squamous Cell Carcinoma (OSCC) is in judging operability, assessment of the prognostic characteristics and dimensions of the primary tumour, depth of tumour invasion, the presence of cervical metastasis and detection of bone infiltration. Aim This study evaluated squamous cell carcinomas of the oral cavity (tongue and gingivo-buccal complex) on the basis of their appearance, soft tissue extent, depth of tumour invasion and staging. Further, this study assessed the accuracy of MRI in the detection of cervical lymph nodal metastasis on the basis of ADC values on diffusion weighted MR sequence. Materials and Methods T1- and T2-weighted MR, diffusion-weighted sequences and post contrast T1W sequences were performed in various planes on biopsy proven squamous cell carcinomas (61 cases) involving tongue and/or gingivo-buccal region. Depth of tumour invasion was calculated on axial images of post contrast T1W images. The Apparent Diffusion Coefficient (ADC) was measured by using two b factors (500 and 1000 s/mm2). MRI findings were compared clinically and histopathologically. Results Average depth of invasion calculated on MRI was 8.47mm and by histopathology was 6.85mm. Pearson’s correlation coefficient was 0.988. Shrinkage factor was 0.8. A 71% of patients with depth of invasion greater than 9mm showed evidence of cervical lymph nodal metastasis at one or another levels. Cut-off value to discriminate between malignant and benign lymph nodes was 1.038 x10-3 mm2/s in the present study. Conclusion Depth of tumour invasion in oral malignancies can be measured reliably on MRI which helps in predicting cervical lymph node metastasis. Benign or malignant cervical lymph nodes can be differentiated on diffusion-weighted imaging of MRI on the basis of their ADC values. PMID:27504375

  5. The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer.

    PubMed

    Adams, M; Navabi, H; Croston, D; Coleman, S; Tabi, Z; Clayton, A; Jasani, B; Mason, M D

    2005-03-18

    A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here. PMID:15755631

  6. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  7. [Drug therapy for neuroendocrine tumours].

    PubMed

    Tóth, Miklós

    2013-09-29

    The author aims to review the established medical treatment options of neuroendocrine tumours, which have expanded greatly in recent years and present the most important aspects to be considered in planning patients' management. Medical treatment is usually considered in advanced stages of these tumours, as well as in cases of hormone overproduction. Somatostatin analogues have been known to be effective in alleviating hormone excess syndromes, especially carcinoid syndrome for the past 25 years. There is a convincing evidence that the somatostatin analogue octreotide is useful as an antitumor agent, at least in well-differentiated small intestinal neuroendocrine tumours and probably also in those of pancreatic origin. Interferons may be also used and the indications for their use may be almost the same. Optimal patient selection is mandatory for the use of cytotoxic chemotherapy. Streptozotocin- and, recently, temozolomide-based chemotherapies should be considered in progressive phases of well differentiated (G1/G2) pancreatic neuroendocrine tumours. A cisplatin-etoposide combination is the first choice for the treatment of G3 neuroendocrine carcinomas of any origin. Recently, the mammalian target of rapamycin inhibitor everolimus and the combined tyrosine kinase inhibitor sunitinib were registered for the treatment of G1/G2 pancreatic neuroendocrine tumours. The most recent drug treatment recommendations and therapeutic algorithms to improve systemic therapy in patients with neuroendocrine tumours are summarized and novel drug candidates with particular potential for future management of these tumours are outlined. PMID:24058101

  8. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading

    PubMed Central

    Pityński, Kazimierz; Banas, Tomasz; Pietrus, Milosz; Milian-Ciesielska, Katarzyna; Ludwin, Artur; Okon, Krzysztof

    2015-01-01

    Background: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated. Methods: SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients. Results: The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R2 = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index. Conclusions: There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages. PMID:26339387

  9. In Silico Modelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

    PubMed Central

    Marcu, Loredana G.; Harriss-Phillips, Wendy M.

    2012-01-01

    Mathematical and stochastic computer (in silico) models of tumour growth and treatment response of the past and current eras are presented, outlining the aims of the models, model methodology, the key parameters used to describe the tumour system, and treatment modality applied, as well as reported outcomes from simulations. Fractionated radiotherapy, chemotherapy, and combined therapies are reviewed, providing a comprehensive overview of the modelling literature for current modellers and radiobiologists to ignite the interest of other computational scientists and health professionals of the ever evolving and clinically relevant field of tumour modelling. PMID:22852024

  10. Tumour infiltrating lymphocytes in squamous cell carcinoma of the oro- and hypopharynx: prognostic impact may depend on type of treatment and stage of disease.

    PubMed

    Distel, Luitpold V; Fickenscher, Rainer; Dietel, Katrin; Hung, Alexander; Iro, Heiner; Zenk, Johannes; Nkenke, Emeka; Büttner, Maike; Niedobitek, Gerald; Grabenbauer, Gerhard G

    2009-10-01

    he purpose of this study was to evaluate the prognostic influence of various subtypes of tumour infiltrating lymphocytes (TIL) in head and neck cancer, in particular the potential influence of regulatory T cells (Treg) in relation to different treatment modalities was addressed. A total of 115 patients with squamous cell carcinoma of the oro- and hypopharynx were selected. A low-risk group of 62 patients with early disease was treated by primary surgery followed by external radiotherapy. A high-risk group of 53 inoperable patients with advanced disease was treated by primary radiochemotherapy. Two-hundred and forty biopsy samples were evaluated by use of the tissue-micro-array technique employing the following markers: CD3, CD4, CD8, CD20, CD68, FOXP3, Granzyme B. In the low-risk group high CD20+ infiltration was associated with a significantly better NED-survival rate (p=0.02). Contrary, among high-risk patients low CD20+ counts indicated significantly better survival (p=0.03). Additionally, in the low-risk group higher numbers of intraepithelial CD8+ TIL (>66.6 per thousand) led to improved NED-survival of 95% vs. 52% (p=0.005). The impact of TIL on prognosis in patients with head and neck cancer may be affected by type of treatment and stage of disease. This finding will influence future studies on the role of TIL in human cancers. PMID:19576838

  11. Advanced technologies for rocket single-stage-to-orbit vehicles

    NASA Technical Reports Server (NTRS)

    Wilhite, Alan W.; Bush, Lance B.; Cruz, Christopher I.; Lepsch, Roger A.; Morris, W. Douglas; Stanley, Douglas O.; Wurster, Kathryn E.

    1991-01-01

    A single-stage-to-orbit vertical takeoff/horizontal landing rocket vehicle was studied to determine the benefits of advanced technology. Advanced technologies that were included in the study were variable mixture ratio oxygen/hydrogen rocket engines and materials, structures, and subsystem technologies currently being developed in the National Aero-Space Plane Program. The application of advanced technology results in an 85 percent reduction in vehicle dry weight. With advanced materials, an external thermal protection system, like the Space Shuttle tiles, was not required. Compared to an all-airbreathing horizontal takeoff/horizontal landing vehicle using the same advanced technologies and mission requirements, the rocket vehicle is lighter in dry weight and has fewer subsystems. To increase reliability and safety, operational features were included in the rocket vehicle-robust subsystems, 5 percent additional margin, no slush hydrogen, fail-operational with an engine out, and a crew escape module. The resulting vehicle grew in dry weight and was still lower in dry weight than the airbreathing vehicle.

  12. Advanced Low-Noise Research Fan Stage Design

    NASA Technical Reports Server (NTRS)

    Neubert, Robert; Bock, Larry; Malmborg, Eric; Owen-Peer, William

    1997-01-01

    This report describes the design of the Advanced Low-Noise Research Fan stage. The fan is a variable pitch design, which is designed at the cruise pitch condition. Relative to the cruise setting, the blade is closed at takeoff and opened for reverse thrust operation. The fan stage is a split flow design with fan exit guide vanes (FEGVs) and core stators. The fan stage design is combined with a nacelle and engine core duct to form a powered fan/nacelle subscale model. This model is intended for use in combined aerodynamic, acoustic, and structural testing in a wind tunnel. The fan has an outer diameter of 22 in. and a hub-to-tip of 0.426 in., which allows the use of existing NASA fan and cowl force balance and rig drive systems. The design parameters were selected to permit valid acoustic and aerodynamic comparisons with the Pratt & Whitney (P&W) 17- and 22-in. rigs previously tested under NASA contract. The fan stage design is described in detail. The results of the design axisymmetric and Navier-Stokes aerodynamic analysis are presented at the critical design conditions. The structural analysis of the fan rotor and attachment is included. The blade and attachment are predicted to have adequate low-cycle fatigue life and an acceptable operating range without resonant stress or flutter. The stage was acoustically designed with airfoil counts in the FEGV and core stator to minimize noise. A fan/FEGV tone analysis developed separately under NASA contract was used to determine the optimum airfoil counts. The fan stage was matched to the existing nacelle, designed under the previous P&W low-noise contract, to form a fan/nacelle model for wind tunnel testing. It is an axisymmetric nacelle for convenience in testing and analysis. Previous testing confirmed that the nacelle performed as required at various aircraft operating conditions.

  13. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  14. Treatment results in advanced stage Hodgkin's lymphoma: A retrospective study

    PubMed Central

    Jain, H; Sengar, M; Nair, R; Menon, H; Laskar, S; Shet, T; Gujral, S; Sridhar, E

    2015-01-01

    Background: Hodgkin's lymphoma displays distinct epidemiological attributes in Asian population thus making it relevant to study whether there are any differences in treatment outcomes too when treated with current standard of care. Aim: To evaluate the treatment outcomes of de-novo advanced stage HL in adults. Materials and Methods: This retrospective study included de-novo advanced stage HL patients (≥15 years) registered at our center from January 2004 to December 2007. Treatment outcomes were measured in terms of response rates, overall survival (OS) and progression-free survival (PFS). Overall and PFS were calculated with Kaplan-Meier methodology and Cox-proportional hazards model was used for multivariate analysis to identify prognostic factors. Results: There were 125 patients (males 77%) who received minimum one cycle of chemotherapy with median age of 32 years (Range 15-65 years). Stage IV disease was seen in (46 patients) 37%; 75% (94 patients) patients had B symptoms. International prognostic score (IPS) ≤4 was seen in 95/112 (85%) patients. ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy was given to 94%. Radiation to residual/bulky sites was given to 36% (45 patients). Response data was available for 112 patients; complete response in 76%; partial response in 10 % and progressive disease in 3 patients. Nineteen deaths (progressive disease-7, toxicity-8, unrelated cause-4) were observed. At median follow-up of 28 months, estimated 5-year OS and PFS were 60% and 58%, respectively. On multivariate analysis, IPS and response to treatment were significant factors for both OS and PFS. Conclusions: The treatment outcomes in this study are comparable with the published literature with limited follow-up data. PMID:25766339

  15. Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy

    PubMed Central

    Lamarca, Angela; Rigby, Christina; McNamara, Mairéad G; Hubner, Richard A; Valle, Juan W

    2016-01-01

    AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient’s morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PMID

  16. MRI Helps Depict Clinically Undetectable Risk Factors in Advanced Stage Retinoblastomas

    PubMed Central

    Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

    2015-01-01

    SUMMARY This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. PMID:25924174

  17. Advanced Therapies For End-Stage Heart Failure

    PubMed Central

    Katz, Jason N; Waters, Sarah B; Hollis, Ian B; Chang, Patricia P

    2015-01-01

    Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantation and mechanical circulatory support, as well inotropic agents for the short-term. Despite a growing armamentarium of resources, the clinician must carefully weigh the risks and benefits of each therapy to develop an optimal treatment strategy. While cardiac transplantation remains the only true “cure” for end-stage disease, this resource is limited and the demand continues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior to transplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularly for the non-operative pa-tient, intravenous inotropes can be utilized for symptom control. Regardless of the treatments considered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualized care. While survival is important, most patients covet quality of life above all outcomes. An often overlooked component is the patient’s control over the dying process. It is vital that clinicians make goals-of-care discussions a priority when seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitates these difficult conversations to ensure that all patient needs are ultimately met. PMID:24251460

  18. Surgical techniques for advanced stage pelvic organ prolapse.

    PubMed

    Brown, Douglas N; Strauchon, Christopher; Gonzalez, Hector; Gruber, Daniel

    2016-02-01

    Pelvic organ prolapse is an extremely common condition, with approximately 12% of women requiring surgical correction over their lifetime. This manuscript reviews the most recent literature regarding the comparative efficacy of various surgical repair techniques in the treatment of advanced stage pelvic organ prolapse. Uterosacral ligament suspension has similar anatomic and subjective outcomes when compared to sacrospinous ligament fixation at 12 months and is considered to be equally effective. The use of transvaginal mesh has been shown to be superior to native tissue vaginal repairs with respect to anatomic outcomes but at the cost of a higher complication rate. Minimally invasive sacrocolpopexy appears to be equivalent to abdominal sacrocolpopexy (ASC). Robot-assisted sacrocolpopexy (RSC) and laparoscopic sacrocolpopexy (LSC) appear as effective as abdominal sacrocolpopexy, however, prospective studies of comparing long-term outcomes of ASC, LSC, and RSC in relation to health care costs is paramount in the near future. Surgical correction of advanced pelvic organ prolapse can be accomplished via a variety of proven techniques. Selection of the correct surgical approach is a complex decision process and involves a multitude of factors. When deciding on the most suitable surgical intervention, the chosen route must be individualized for each patient taking into account the specific risks and benefits of each procedure. PMID:26448444

  19. Advances in the study of transmissible respiratory tumours in small ruminants.

    PubMed

    Monot, M; Archer, F; Gomes, M; Mornex, J-F; Leroux, C

    2015-12-14

    Sheep and goats are widely infected by oncogenic retroviruses, namely Jaagsiekte Sheep RetroVirus (JSRV) and Enzootic Nasal Tumour Virus (ENTV). Under field conditions, these viruses induce transformation of differentiated epithelial cells in the lungs for Jaagsiekte Sheep RetroVirus or the nasal cavities for Enzootic Nasal Tumour Virus. As in other vertebrates, a family of endogenous retroviruses named endogenous Jaagsiekte Sheep RetroVirus (enJSRV) and closely related to exogenous Jaagsiekte Sheep RetroVirus is present in domestic and wild small ruminants. Interestingly, Jaagsiekte Sheep RetroVirus and Enzootic Nasal Tumour Virus are able to promote cell transformation, leading to cancer through their envelope glycoproteins. In vitro, it has been demonstrated that the envelope is able to deregulate some of the important signaling pathways that control cell proliferation. The role of the retroviral envelope in cell transformation has attracted considerable attention in the past years, but it appears to be highly dependent of the nature and origin of the cells used. Aside from its health impact in animals, it has been reported for many years that the Jaagsiekte Sheep RetroVirus-induced lung cancer is analogous to a rare, peculiar form of lung adenocarcinoma in humans, namely lepidic pulmonary adenocarcinoma. The implication of a retrovirus related to Jaagsiekte Sheep RetroVirus is still controversial and under investigation, but the identification of an infectious agent associated with the development of lepidic pulmonary adenocarcinomas might help us to understand cancer development. This review explores the mechanisms of induction of respiratory cancers in small ruminants and the possible link between retrovirus and lepidic pulmonary adenocarcinomas in humans. PMID:26340900

  20. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  1. Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours.

    PubMed Central

    Planting, A. S.; van der Burg, M. E.; de Boer-Dennert, M.; Stoter, G.; Verweij, J.

    1993-01-01

    Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies. PMID:8398709

  2. Should noncurative resection of the primary tumour be performed in patients with stage iv colorectal cancer? A systematic review and meta-analysis

    PubMed Central

    Ahmed, S.; Shahid, R.K.; Leis, A.; Haider, K.; Kanthan, S.; Reeder, B.; Pahwa, P.

    2013-01-01

    Purpose Surgical resection of the primary tumour in patients with advanced colorectal cancer (crc) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (qol). Methods Reports in the central, medline, and embase databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle–Ottawa Scale. Data were collected and synthesized per protocol. Results From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10–30.7 months) in the resection group and 11.4 months (range: 3–22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (ci): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% ci: 0% to 9.7%) and 25.9% (95%ci: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% ci: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 ci: 15.4% to 39.9%). No study provided qol data. Conclusions Although this review supports primary tumour resection in advanced crc, the results have significant biases. Randomized trials

  3. Downregulation of transforming growth factor β (TGFβ) and latent TGFβ binding protein (LTBP)-4 expression in late stage canine mammary tumours.

    PubMed

    Klopfleisch, R; Schütze, M; Gruber, A D

    2010-12-01

    Although canine mammary tumours (CMT) are the most common malignant tumours in bitches the pathogenesis is far from understood. To analyse the role of the transforming growth factor β (TGFβ) family in the carcinogenesis of CMT, relative mRNA and protein expression of TGFβ-1, -2 and -3, TGFβ receptor (TGFβR)-1 and -3, latent TGFβ-binding protein (LTBP)-1, -3 and -4, and oestrogen receptor α in CMT were quantified. mRNA expression concentrations were measured in laser-microdissected tissue samples of mammary adenomas, carcinomas and their lymph node metastases and normalised to the non-neoplastic mammary gland of the same dog. Carcinomas and metastases had significantly decreased expression levels of TGFβ-3, TGFβR-3 and LTBP-4, but increased LTBP-1 expression when compared to non-neoplastic glands or adenomas. Decreased TGFβ and LTBP-4 expression were confirmed immunohistochemically. The data suggested that loss of TGFβ-3 and LTBP-4 may have growth-stimulatory effects in late-stage tumours, and loss of their expression, together with reduced TGFβR-3 expression, may be associated with increased proliferative activity of CMT similar to findings in human breast cancer. PMID:19836277

  4. Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

    PubMed Central

    Litchfield, Kevin; Sultana, Razvan; Renwick, Anthony; Dudakia, Darshna; Seal, Sheila; Ramsay, Emma; Powell, Silvana; Elliott, Anna; Warren-Perry, Margaret; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Stratton, Michael R.; Easton, Douglas F.; Bishop, D. Timothy; Huddart, Robert A.; Rahman, Nazneen; Turnbull, Clare; Pugh, J.; Linger, R.; Marke, J.; Hughes, D.; Pernet, D.; Hall, P.; Easton, D.F.; Berchuck, A.; Eeles, R.; Chenevix-Trench, G.; Dennis, J.; Dunning, A.M.; Lee, A.; Dicks, E.; Easton, D.F.; Benitez, J.; Gonzalez-Neira, A.; Simard, J.; Tessier, D.C.; Bacot, F.; Vincent, D.; LaBoissière, S.; Robidoux, F.; Bojesen, S.E.; Nielsen, S.F.; Nordestgaard, B.G.; Cunningham, J.M.; Windebank, S.A.; Hilker, C.A.; Meyer, J.

    2015-01-01

    Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06–1.27; P = 1.2 × 10−9]. PMID:25281660

  5. Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25.

    PubMed

    Litchfield, Kevin; Sultana, Razvan; Renwick, Anthony; Dudakia, Darshna; Seal, Sheila; Ramsay, Emma; Powell, Silvana; Elliott, Anna; Warren-Perry, Margaret; Eeles, Rosalind; Peto, Julian; Kote-Jarai, Zsofia; Muir, Kenneth; Nsengimana, Jeremie; Stratton, Michael R; Easton, Douglas F; Bishop, D Timothy; Huddart, Robert A; Rahman, Nazneen; Turnbull, Clare

    2015-02-15

    Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10(-9)]. PMID:25281660

  6. Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: a Children's Oncology Group Report.

    PubMed

    Galardy, Paul J; Hochberg, Jessica; Perkins, Sherrie L; Harrison, Lauren; Goldman, Stanton; Cairo, Mitchell S

    2013-11-01

    Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III-IV, bone marrow(+) and/or central nervous system(+) mature B-NHL received hydration and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well-tolerated and there were no grade III-IV toxicities probably or directly related to rasburicase. Patients with an initial lactate dehydrogenase ≥2× upper limit of normal had a significantly elevated uric acid level (P = 0·005), increased incidence of TLS (P-0·005) and lower glomerular filtration rate (GFR; P < 0·001). Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS, respectively. Furthermore, there was a significant improvement in estimated GFR from Day 0 to Day 7 following rasburicase (P = 0·0007) and only 1·3% of patients required new onset renal assisted support after rasburicase administration. A TLS strategy incorporating rasburicase prior to cytoreductive chemotherapy proved safe and effective in preventing new onset renal failure and was associated with a significant improvement in GFR. PMID:24032600

  7. Combination cancer immunotherapies tailored to the tumour microenvironment.

    PubMed

    Smyth, Mark J; Ngiow, Shin Foong; Ribas, Antoni; Teng, Michele W L

    2016-03-01

    Evidence suggests that cancer immunotherapy will be a major part of the combination treatment plan for many patients with many cancer types in the near future. There are many types of immune processes involving different antitumour and tumour-promoting leucocytes, and tumour cells use many strategies to evade the immune response. The tumour microenvironment can help determine which immune suppressive pathways become activated to restrain antitumour immunity. This includes immune checkpoint receptors on effector T-cells and myeloid cells, and release of inhibitory cytokines and metabolites. Therapeutic approaches that target these pathways, particularly immune-checkpoint receptors, can induce durable antitumour responses in patients with advanced-stage cancers, including melanoma. Nevertheless, many patients do not have a good response to monotherapy approaches and alternative strategies are required to achieve optimal therapeutic benefit. These strategies include eliminating the bulk of tumour cells to provoke tumour-antigen release and antigen-presenting cell (APC) function, using adjuvants to enhance APC function, and using agents that enhance effector-cell activity. In this Review, we discuss the stratification of the tumour microenvironment according to tumour-infiltrating lymphocytes and PD-L1 expression in the tumour, and how this stratification enables the design of optimal combination cancer therapies tailored to target different tumour microenvironments. PMID:26598942

  8. Loss of ATRX and DAXX expression identifies poor prognosis for smooth muscle tumours of uncertain malignant potential and early stage uterine leiomyosarcoma.

    PubMed

    Slatter, Tania L; Hsia, Howard; Samaranayaka, Ari; Sykes, Peter; Clow, William Bill; Devenish, Celia J; Sutton, Tim; Royds, Janice A; Pc, Philip; Cheung, Annie N; Hung, Noelyn Anne

    2015-04-01

    Uterine smooth muscle tumours of uncertain malignant potential (STUMP) are diagnostically and clinically challenging. The alternative lengthening of telomeres (ALT) telomere maintenance mechanism is associated with poor survival in soft tissue leiomyosarcoma. Time to first recurrence and survival were known for 18 STUMP and 43 leiomyosarcomata (LMS). These were screened for ALT telomere maintenance by the presence of ALT-associated PML bodies (APBs) and for changes associated with the ALT phenotype, namely aberrant p53 expression, isocitrate dehydrogenase 1 mutation (R132H substitution) expression, mutant ATRX (αthalassemia/mental retardation syndrome X-linked) expression and mutant DAXX (death-domain-associated protein) expression by immunohistochemistry (IHC). Overexpression of p16(INK4A) was examined immunohistologically in a subset of cases. Many of the tumours associated with death or recurrence demonstrated APBs commensurate with ALT telomere maintenance. However, all uterine STUMP (4/4), and vaginal STUMP (2/2) patients, and almost all LMS patients (88.4%, 23/26, including 90% (9/10) of stage 1 LMS cases), who had died of disease or who had recurrent disease, displayed loss of ATRX or DAXX expression. Loss of ATRX or DAXX expression identified poor prognosis (95% CI 2.1 to 40.8, p < 0.003), in the LMS group. Thus, loss of ATRX or DAXX expression in uterine smooth muscle tumours identifies a clinically aggressive molecular subtype of early stage LMS and when histopathological features are problematic such as in STUMP. As ATRX and DAXX IHC is readily performed in diagnostic laboratories these are potentially useful for routine histopathological classification and management. PMID:27499896

  9. Anti-tumour strategies aiming to target tumour-associated macrophages

    PubMed Central

    Tang, Xiaoqiang; Mo, Chunfen; Wang, Yongsheng; Wei, Dandan; Xiao, Hengyi

    2013-01-01

    Tumour-associated macrophages (TAMs) represent a predominant population of inflammatory cells that present in solid tumours. TAMs are mostly characterized as alternatively activated M2-like macrophages and are known to orchestrate nearly all stages of tumour progression. Experimental investigations indicate that TAMs contribute to drug-resistance and radio-protective effects, and clinical evidence shows that an elevated number of TAMs and their M2 profile are correlated with therapy failure and poor prognosis in cancer patients. Recently, many studies on TAM-targeted strategies have made significant progress and some pilot works have achieved encouraging results. Among these, connections between some anti-tumour drugs and their influence on TAMs have been suggested. In this review, we will summarize recent advances in TAM-targeted strategies for tumour therapy. Based on the proposed mechanisms, those strategies are grouped into four categories: (i) inhibiting macrophage recruitment; (ii) suppressing TAM survival; (iii) enhancing M1-like tumoricidal activity of TAMs; (iv) blocking M2-like tumour-promoting activity of TAMs. It is desired that further attention be drawn to this research field and more effort be made to promote TAM-targeted tumour therapy. PMID:23113570

  10. Staged off-pump coronary artery bypass grafting and radical nephrectomy in a patient with multivessel coronary artery disease and a renal tumour

    PubMed Central

    Cetin, Erdem; Ozyuksel, Arda; Akay, Ferruh

    2014-01-01

    Coronary artery diseases and neoplastic disorders are the leading causes of morbidity and mortality in the elderly. Recently, controversial approaches have been raised about the treatment of cases with concomitant occurrence of coronary artery diseases and malignancies. The detrimental effects of cardiopulmonary bypass on neoplastic cells are always a challenge for such cases. We present a case of a large renal tumour associated with a recently symptomatic coronary artery disease which was successfully treated with staged off-pump coronary artery bypass grafting followed by radical nephrectomy. In such patients, off-pump revascularisation is favourable in order to decrease the risk of cancer spreading when compared to traditional on-pump cases. In our opinion, staged off-pump coronary arterial revascularisation followed by definitive surgical treatment for the malignancy is a safe and effective treatment modality in patients with coronary artery disease and oncological diseases. PMID:24962482

  11. Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours

    PubMed Central

    Millward, M; Underhill, C; Lobb, S; McBurnie, J; Meech, S J; Gomez-Navarro, J; Marshall, M A; Huang, B; Mather, C B

    2013-01-01

    Background: Tremelimumab, a fully human cytotoxic T-lymphocyte antigen 4 monoclonal antibody, and PF-3512676, a Toll-like receptor-9 agonist, are targeted immune modulators that elicit durable single-agent antitumour activity in advanced cancer. Methods: To determine the maximum tolerated dose (MTD) of these agents combined during this phase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg−1) every 12 weeks plus subcutaneous PF-3512676 (0.05, 0.10, or 0.15 mg kg−1) weekly. Primary end points were safety and tolerability; secondary end points included pharmacokinetics and antitumour activity. Results: Twenty-one patients with stage IV melanoma (n=17) or advanced solid tumours (n=4) were enrolled. Injection-site reactions (n=21; 100%), influenza-like illness (n=18; 86%), and diarrhoea (n=13; 62%) were the most common treatment-related adverse events (TAEs). Grade ⩾3 TAEs were reported (n=7; 33%). Dose-limiting toxicities (prespecified 6-week observation) occurred in one of the six patients in the 10 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort (grade 3 hypothalamopituitary disorder) and two of the six patients in the 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 cohort (grade 3 diarrhoea). Consequently, 15 mg kg−1 tremelimumab plus 0.05 mg kg−1 PF-3512676 exceeded the MTD. Two melanoma patients achieved durable (⩾170 days) partial response. No human antihuman antibody responses to tremelimumab were observed. Conclusion: Weekly PF-3512676 (⩽0.15 mg kg−1) plus tremelimumab (⩽10 mg kg−1 every 12 weeks) was tolerable. PMID:23652314

  12. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  13. Advanced two-stage incineration: Research and development

    SciTech Connect

    Rehmat, A.; Khinkis, M.

    1991-01-01

    IGT is currently developing a two-stage fluidized-bed/cyclonic agglomerating incineration system that is based on combining the fluidized-bed agglomeration/incineration and cyclonic combustion technologies, both of which have been developed individually at IGT over many years. This combination has resulted in a unique and extremely flexible incinerator for solid, liquid, and gaseous wastes. The system can operate over a wide range of conditions in the first stage, from low temperature (desorption) to high temperature (agglomeration), including gasification of high-Btu wastes. In the combined system, solid, liquid, and gaseous organic wastes are expected to be easily and efficiently destroyed (>99.99% destruction and removal efficiency (DRE)) while solid inorganic contaminants are expected to be contained within a glassy matrix, rendering them benign and suitable for disposal in an ordinary landfill. The development of the two-stage incinerator is a culmination of extensive research and development efforts on each stage of the incinerator. A variety of data obtained for both stages includes agglomeration of ash, incineration and reclamation of used blast grit and foundry sand, partial combustion of carbonaceous fuels, in-situ desulfurization, combustion of low-Btu gases, incineration of industrial wastewater, and incineration of carbon tetrachloride.

  14. Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer

    PubMed Central

    Melosky, B.; Agulnik, J.; Albadine, R.; Banerji, S.; Bebb, D.G.; Bethune, D.; Blais, N.; Butts, C.; Cheema, P.; Cheung, P.; Cohen, V.; Deschenes, J.; Ionescu, D.N.; Juergens, R.; Kamel-Reid, S.; Laurie, S.A.; Liu, G.; Morzycki, W.; Tsao, M.S.; Xu, Z.; Hirsh, V.

    2016-01-01

    Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348

  15. Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

    PubMed

    Melosky, B; Agulnik, J; Albadine, R; Banerji, S; Bebb, D G; Bethune, D; Blais, N; Butts, C; Cheema, P; Cheung, P; Cohen, V; Deschenes, J; Ionescu, D N; Juergens, R; Kamel-Reid, S; Laurie, S A; Liu, G; Morzycki, W; Tsao, M S; Xu, Z; Hirsh, V

    2016-06-01

    Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348

  16. Post-chemotherapy surgery in advanced non-seminomatous germ-cell testicular tumours: the significance of histology with particular reference to differentiated (mature) teratoma.

    PubMed Central

    Tait, D.; Peckham, M. J.; Hendry, W. F.; Goldstraw, P.

    1984-01-01

    Of a total of 307 patients treated with chemotherapy for advanced non-seminomatous germ-cell testicular tumours between 1976 and 1983, 73 (23.8%) had masses excised after treatment. Resected tissue showed residual malignancy in 16 (22%), fibrosis and necrosis in 25 (34%) and differentiated (mature teratoma) in 32 (44%). Of the 16 patients with tumour only 7 (44%) are alive and disease-free compared with 21/25 (84%) and 27/32 (84%) for fibrosis/necrosis and differentiated teratoma respectively. In addition to histological evidence of residual tumour, elevated serum markers at the time of surgery and/or incomplete excision of residual masses were adverse prognostic features. Of 12 patients with differentiated teratoma or fibrosis who had incomplete resections or densely adherent masses excised with difficulty, 7 subsequently relapsed. The majority of differentiated teratoma patients (75%) had evidence of differentiation in their primary tumours; 88% showed cystic change in metastases and almost one-third showed an increase in the size of metastases during chemotherapy. The data suggest that post-chemotherapy surgery may have a therapeutic as well as a diagnostic role and that complete excision of residual disease should be attempted even if resection at one site has shown either fibrosis or differentiated teratoma. The significance of these findings in relation to treatment induced differentiation is discussed. PMID:6093838

  17. Staging laparoscopy improves treatment decision-making for advanced gastric cancer

    PubMed Central

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-01-01

    AIM: To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). METHODS: Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ2 test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. RESULTS: Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. CONCLUSION: Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy. PMID:26855545

  18. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

    PubMed

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2). Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m(2) b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m(2) and 1,500 mg/m(2). At 1,500 mg/m(2), one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m(2) b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  19. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours

    PubMed Central

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m2, and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m2. Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m2 b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m2 and 1,500 mg/m2. At 1,500 mg/m2, one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m2 b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  20. Exprimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions.

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency for large gas turbine engines. Under ERA, the highly loaded core compressor technology program attempts to realize the fuel burn reduction goal by increasing overall pressure ratio of the compressor to increase thermal efficiency of the engine. Study engines with overall pressure ratio of 60 to 70 are now being investigated. This means that the high pressure compressor would have to almost double in pressure ratio while keeping a high level of efficiency. NASA and GE teamed to address this challenge by testing the first two stages of an advanced GE compressor designed to meet the requirements of a very high pressure ratio core compressor. Previous test experience of a compressor which included these front two stages indicated a performance deficit relative to design intent. Therefore, the current rig was designed to run in 1-stage and 2-stage configurations in two separate tests to assess whether the bow shock of the second rotor interacting with the upstream stage contributed to the unpredicted performance deficit, or if the culprit was due to interaction of rotor 1 and stator 1. Thus, the goal was to fully understand the stage 1 performance under isolated and multi-stage conditions, and additionally to provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to understand fluid dynamics loss source mechanisms due to rotor shock interaction and endwall losses. This paper will present the description of the compressor test article and its measured performance and operability, for both the single stage and two stage configurations. We focus the paper on measurements at 97% corrected speed with design intent vane setting angles.

  1. The Critical Technologies and Applications on Advanced Upper Stage Vehicles

    NASA Astrophysics Data System (ADS)

    Qi, Feng; Wang, Guo-hui

    2016-07-01

    Upper Stage Vehicle(USV) is a kind of independent one-stop-into-space launching vehicles. In this article, different new-conception USVs are mentioned and out of them, on basis of the possibility in future application, laser propelling USV and nuclear-thermal propelling USV are selected and discussed in technical details, especially in critical technologies and recent relative technical improvements about new propelling methods within these two kinds. Furthermore, laser propelled USV and nuclear-thermal propelled USV both seem to have important roles to play in future space exploring projects. And several possible applications of the two kinds of USVs emphasized above are carried out at the end of this piece of article.

  2. Experimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency of large gas turbine engines. Under ERA the task for a High Pressure Ratio Core Technology program calls for a higher overall pressure ratio of 60 to 70. This mean that the HPC would have to almost double in pressure ratio and keep its high level of efficiency. The challenge is how to match the corrected mass flow rate of the front two supersonic high reaction and high corrected tip speed stages with a total pressure ratio of 3.5. NASA and GE teamed to address this challenge by using the initial geometry of an advanced GE compressor design to meet the requirements of the first 2 stages of the very high pressure ratio core compressor. The rig was configured to run as a 2 stage machine, with Strut and IGV, Rotor 1 and Stator 1 run as independent tests which were then followed by adding the second stage. The goal is to fully understand the stage performances under isolated and multi-stage conditions and fully understand any differences and provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to isolate fluid dynamics loss source mechanisms due to interaction and endwalls. The paper will present the description of the compressor test article, its predicted performance and operability, and the experimental results for both the single stage and two stage configurations. We focus the detailed measurements on 97 and 100 of design speed at 3 vane setting angles.

  3. Advanced MRI and staging of multiple sclerosis lesions.

    PubMed

    Absinta, Martina; Sati, Pascal; Reich, Daniel S

    2016-06-01

    Over the past few decades, MRI-based visualization of demyelinated CNS lesions has become pivotal to the diagnosis and monitoring of multiple sclerosis (MS). In this Review, we outline current efforts to correlate imaging findings with the pathology of lesion development in MS, and the pitfalls that are being encountered in this research. Multimodal imaging at high and ultra-high magnetic field strengths is yielding biologically relevant insights into the pathophysiology of blood-brain barrier dynamics and both active and chronic inflammation, as well as mechanisms of lesion healing and remyelination. Here, we parallel the results in humans with advances in imaging of a primate model of MS - experimental autoimmune encephalomyelitis (EAE) in the common marmoset - in which demyelinated lesions resemble their human counterparts far more closely than do EAE lesions in the rodent. This approach holds promise for the identification of innovative biological markers, and for next-generation clinical trials that will focus more on tissue protection and repair. PMID:27125632

  4. Bronchial involvement in advanced stage lymphangioleiomyomatosis: histopathologic and molecular analyses.

    PubMed

    Hayashi, Takuo; Kumasaka, Toshio; Mitani, Keiko; Okada, Yoshinori; Kondo, Takashi; Date, Hiroshi; Chen, Fengshi; Oto, Takahiro; Miyoshi, Shinichiro; Shiraishi, Takeshi; Iwasaki, Akinori; Hara, Kieko; Saito, Tsuyoshi; Ando, Katsutoshi; Kobayashi, Etsuko; Gunji-Niitsu, Yoko; Kunogi, Makiko; Takahashi, Kazuhisa; Yao, Takashi; Seyama, Kuniaki

    2016-04-01

    Lymphangioleiomyomatosis (LAM), a rare progressive disease that almost exclusively affects women, is characterized by pulmonary cysts and neoplastic proliferation of smooth muscle-like cells (LAM cells). Airflow obstruction is a physiologic consequence that is commonly observed in LAM and has been attributed to narrowing of peripheral airways. However, histopathologic examinations of the entire airway have been precluded by the limited availability of such specimens. Here, we used explanted lung tissues from 30 LAM patients for a thorough histologic analysis with a special emphasis on the bronchi. We found bronchial involvement by LAM cells and lymphatics in all patients examined. Furthermore, a moderate to severe degree of chronic inflammation (73%), goblet cell hyperplasia (97%), squamous cell metaplasia (83%) of the epithelium, and thickening of basal lamina (93%) were identified in the bronchi. Because LAM cells are transformed by the functional loss of the TSC genes leading to a hyperactivated mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, we confirmed the expression of phospho-p70S6K, phospho-S6, phospho-4E-BP1, and vascular endothelial growth factor (VEGF)-D in LAM cells from all of the patients examined. In contrast, no protein expression of hypoxia-inducible factor 1α, a downstream molecule indicative of mTORC1 activation and leading to VEGF production, was detected in any patient. Our study indicates that late-stage LAM patients commonly have bronchi involved by the proliferation of both LAM cells and lymphatics and that chronic inflammation complicated their disease. Furthermore, the up-regulation of hypoxia-inducible factor 1α, a common event in mTORC1-driven tumor cells, does not occur in LAM cells and plays no role in VEGF-D expression in LAM cells. PMID:26997436

  5. Diminished production of interleukin-6 in chronic lymphocytic leukaemia (B-CLL) cells from patients at advanced stages of disease. Tampere CLL Group.

    PubMed

    Hulkkonen, J; Vilpo, J; Vilpo, L; Hurme, M

    1998-03-01

    The production of the cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in B-CLL cells from 24 patients at different stages of chronic lymphocytic B-cell leukaemia (B-CLL) was investigated in vitro. In the majority of these cases, low spontaneous IL-6 production was measured. Mitogenic stimulation with phorbol 12-myristate 13-acetate (PMA) or PMA plus interleukin-2 (IL-2) resulted in a tremendous increase in TNF-alpha and IL-6 production in cells representing early stage (Binet A) disease. In contrast, very little, if any, production took place in cells from patients with advanced stage (Binet C) B-CLL. The results from stage B patients were intermediate. The most remarkable difference was recorded in PMA-stimulated (1 ng/ml) IL-6 production. In stimulated 72 h cultures, IL-6 concentrations were 1280 +/- 1080 pg/ml for Binet A (n = 11), 757 +/- 597 pg/ml for Binet B (n = 8) and 46.0 +/- 84.0 pg/ml for Binet C (n = 5). The differences in IL-6 production between stage C v B and stage C v A were both statistically significant (P=0.025). Similar effects, but to a lesser extent, were observed in TNF-alpha production. These results suggest that the varying capacity to produce IL-6 and TNF-alpha may play a role in B-CLL progression and in clinical manifestations of the disease. PMID:9504629

  6. Inhibitory Effects of Gymnema (Gymnema sylvestre) Leaves on Tumour Promotion in Two-Stage Mouse Skin Carcinogenesis

    PubMed Central

    Yasukawa, Ken; Okuda, Sakiko; Nobushi, Yasuhito

    2014-01-01

    Ethanol extracts of gymnema (Gymnema sylvestre) leaves exhibited marked antitumour-promoting activity in an in vivo two-stage carcinogenesis test in mice using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. From the active fraction of the ethanol extract of the gymnema leaves, three triterpenoids were isolated and identified. These compounds were evaluated for their inhibitory effects on TPA-induced inflammation (1 µg/ear) in mice. The tested compounds showed marked anti-inflammatory effects, with a 50% inhibitory dose of 50–555 nmol/ear. PMID:24734106

  7. Inhibitory Effects of Gymnema (Gymnema sylvestre) Leaves on Tumour Promotion in Two-Stage Mouse Skin Carcinogenesis.

    PubMed

    Yasukawa, Ken; Okuda, Sakiko; Nobushi, Yasuhito

    2014-01-01

    Ethanol extracts of gymnema (Gymnema sylvestre) leaves exhibited marked antitumour-promoting activity in an in vivo two-stage carcinogenesis test in mice using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. From the active fraction of the ethanol extract of the gymnema leaves, three triterpenoids were isolated and identified. These compounds were evaluated for their inhibitory effects on TPA-induced inflammation (1 µg/ear) in mice. The tested compounds showed marked anti-inflammatory effects, with a 50% inhibitory dose of 50-555 nmol/ear. PMID:24734106

  8. Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

    PubMed Central

    Leung, Dilys; Gould, Jodee A.; Jobling, Tom; Fuller, Peter J.

    2016-01-01

    Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ∼80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets. PMID:26893359

  9. Gastrointestinal stromal tumour.

    PubMed

    Joensuu, Heikki; Hohenberger, Peter; Corless, Christopher L

    2013-09-14

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine and rarely elsewhere in the abdomen. They can occur at any age, the median age being 60-65 years, and typically cause bleeding, anaemia, and pain. GISTs have variable malignant potential, ranging from small lesions with a benign behaviour to fatal sarcomas. Most tumours stain positively for the mast/stem cell growth factor receptor KIT and anoctamin 1 and harbour a kinase-activating mutation in either KIT or PDGFRA. Tumours without such mutations could have alterations in genes of the succinate dehydrogenase complex or in BRAF, or rarely RAS family genes. About 60% of patients are cured by surgery. Adjuvant treatment with imatinib is recommended for patients with a substantial risk of recurrence, if the tumour has an imatinib-sensitive mutation. Tyrosine kinase inhibitors substantially improve survival in advanced disease, but secondary drug resistance is common. PMID:23623056

  10. An Unusual Cause of Subacute Headache in a Patient Undergoing Chemotherapy for Advanced Testicular Nonseminomatous Germ Cell Tumour

    PubMed Central

    Porfiri, Emilio

    2016-01-01

    Testicular (germ cell) cancer is a model of a chemocurable malignancy and tends to have a favourable prognosis even in advanced stages due to exquisite sensitivity to platinum-based chemotherapy. However, both acute and longer-term toxicities of multiagent chemotherapy remain significant as causes of morbidity, very occasionally mortality, and impaired quality-of-life. Here, we report a case of acute cerebral venous sinus thrombosis occurring within 10 days of chemotherapy initiation in a young patient without comorbidities, whose only predisposing factors were malignancy, chemotherapy, and perhaps mild dehydration. The clinical presentation was also unusual with headache of moderate severity only without focal or global neurologic deficits. We suspect that cisplatin may have had direct vasculotoxic effects. The patient recovered fully after short-duration anticoagulation but oncologists must remain aware of unusual and unpredictable complications of cytotoxic treatment. PMID:27200199

  11. [Advances in Surgical Treatment of Early Stage Non-small Cell Lung Cancer].

    PubMed

    Hu, Jian; Bao, Feichao

    2016-06-20

    Lung cancer is the leading cause of cancer-related deaths worldwide, computed tomography screening has made the disease spectrum of lung cancer shift from the previously predominating central local advanced squamous cell carcinoma to early stage lung adenocarcinoma represented by solitary pulmonary nodule, ground-glass opacity (GGO) and sub-centimeter nodule. This paper reviewed the recent proceeding in the surgical management of early stage lung cancer. PMID:27335305

  12. Aggressive local therapy combined with systemic chemotherapy provides long-term control in grade II stage 2 canine mast cell tumour: 21 cases (1999–2012)*

    PubMed Central

    Lejeune, A.; Skorupski, K.; Frazier, S.; Vanhaezebrouck, I.; Rebhun, R. B.; Reilly, C. M.; Rodriguez, C. O.

    2016-01-01

    This retrospective case series evaluates the outcome of 21 dogs with grade II stage 2 mast cell tumour (MCT) treated with adequate local therapy and adjuvant systemic chemotherapy (prednisone, vinblastine and CCNU). The median survival for all dogs was 1359 days (range, 188–2340). Median disease-free interval was 2120 days (149–2325 days). Dogs treated with surgery and chemotherapy had shorter survival (median, 1103 days; 188–2010 days) than those that underwent surgery, radiation therapy and chemotherapy as part of their treatment (median, 2056 days; 300–2340 days). Two patients had local recurrence in the radiation field and four patients had de novo MCT. Distant metastasis was not observed in any dogs. The results of this study suggest that, in the presence of loco-regional lymph node metastasis in grade II MCT, the use of prednisone, vinblastine and CCNU after adequate local-regional therapy can provide a median survival in excess of 40 months. PMID:23721492

  13. Testicular germ cell tumours.

    PubMed

    Rajpert-De Meyts, Ewa; McGlynn, Katherine A; Okamoto, Keisei; Jewett, Michael A S; Bokemeyer, Carsten

    2016-04-23

    Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors. PMID:26651223

  14. Influence of tumour condition on the macrophage activity in Candida albicans infection.

    PubMed

    Venturini, J; de Camargo, M R; Félix, M C; Vilani-Moreno, F R; de Arruda, M S P

    2009-07-01

    To better understand the interactions between opportunistic fungi and their hosts, we investigated hydrogen peroxide (H2O2), nitric oxide and TNF-alpha production by peritoneal macrophages from Ehrlich tumour-bearing mice (TBM) during microbial infections. For this purpose, TBM at days 7, 14 and 21 of tumour progression were inoculated intraperitoneally with C. albicans and evaluated after 24 and 72 h. We observed that TBM showed significant increases in H2O2, TNF-alpha levels and fungal clearance at day 7 after C. albicans infection. However, as the tumour advanced, there was a progressive decline in the release of H2O2 and TNF-alpha that was paired with the dissemination of C. albicans. These results demonstrate that protective macrophage activities against Candida albicans are limited to the initial stages of tumour growth; continued solid tumour growth weakened the macrophage response and as a consequence, weakened the host's susceptibility to opportunistic infections. PMID:19522762

  15. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  16. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  17. Advanced Development Program for a 625 lbf thrust engine for Ares First Stage Roll Control System

    NASA Technical Reports Server (NTRS)

    Dawson, Matt; Chenevert, Blake; Brewster, Gerry; Frei, Tom; Bullard, Brad; Fuller, Ray

    2009-01-01

    NASA's new Ares Launch Vehicle will require twelve thrusters to provide roll control of the vehicle during the first stage firing. All twelve roll control thrusters will be located at the inter-stage segment that separates the solid rocket booster first stage from the second stage. NASA selected a mono propellant hydrazine solution and as a result awarded Aerojet-General a contract in 2007 for an advanced development program for an MR-80- series 625 Ibf vacuum thrust monopropellant hydrazine thruster. This thruster has heritage dating back to the 1976 Viking Landers and most recently for the 2011 Mars Science Laboratory. Prior to the Ares application, the MR-80-series thrusters had been equipped with throttle valves and not typically operated in pulse mode. The primary objective of the advanced development program was to increase the technology readiness level and retire major technical risks for the future flight qualification test program. Aerojet built on their heritage MR-80 rocket engine designs to achieve the design and performance requirements. Significant improvements to cost and lead-time were achieved by applying Design for Manufacturing and Assembly (DFMA) principles. AerojetGeneral has completed Preliminary and Critical Design Reviews, followed by two successful rocket engine development test programs. The test programs included qualification random vibration and firing lite that significantly exceed the flight qualification requirements. This paper discusses the advanced development program and the demonstrated capability of the MR-80C engine. Y;

  18. Reusable launch vehicles, enabling technology for the development of advanced upper stages and payloads

    SciTech Connect

    Metzger, John D.

    1998-01-15

    In the near future there will be classes of upper stages and payloads that will require initial operation at a high-earth orbit to reduce the probability of an inadvertent reentry that could result in a detrimental impact on humans and the biosphere. A nuclear propulsion system, such as was being developed under the Space Nuclear Thermal Propulsion (SNTP) Program, is an example of such a potential payload. This paper uses the results of a reusable launch vehicle (RLV) study to demonstrate the potential importance of a Reusable Launch Vehicle (RLV) to test and implement an advanced upper stage (AUS) or payload in a safe orbit and in a cost effective and reliable manner. The RLV is a horizontal takeoff and horizontal landing (HTHL), two-stage-to-orbit (TSTO) vehicle. The results of the study shows that an HTHL is cost effective because it implements airplane-like operation, infrastructure, and flight operations. The first stage of the TSTO is powered by Rocket-Based-Combined-Cycle (RBCC) engines, the second stage is powered by a LOX/LH rocket engine. The TSTO is used since it most effectively utilizes the capability of the RBCC engine. The analysis uses the NASA code POST (Program to Optimize Simulated Trajectories) to determine trajectories and weight in high-earth orbit for AUS/advanced payloads. Cost and reliability of an RLV versus current generation expandable launch vehicles are presented.

  19. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. PMID:26175519

  20. Statins augment efficacy of EGFR-TKIs in patients with advanced-stage non-small cell lung cancer harbouring KRAS mutation.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Topolcan, Ondrej

    2015-08-01

    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) represent novel effective agents approved for the treatment of patients with advanced-stage NSCLC. KRAS mutations have been reported as a negative prognostic and predictive factor in patients with NSCLC treated with EGFR-TKIs. Several studies have recently shown that statins can block tumour cell growth, invasion and metastatic potential. We analysed clinical data of 67 patients with locally advanced (IIIB) or metastatic stage (IV) NSCLC harbouring Kirsten rat sarcoma viral oncogene (KRAS) mutation treated with erlotinib or gefitinib. Twelve patients were treated with combination of EGFR-TKI and statin and 55 patients were treated with EGFR-TKI alone. Comparison of patients' survival (progression-free survival (PFS) and overall survival (OS)) according to the treatment used was performed using the Gehan-Wilcoxon test. The median of PFS and OS for patients treated with EGFR-TKI alone was 1.0 and 5.4 months compared to 2.0 and 14.0 months for patients treated with combination of EGFR-TKI and statin (p = 0.025, p = 0.130). In conclusion, the study results suggest significant improvement of PFS for patients treated with combination of statin and EGFR-TKI, and the difference in OS was not significant. PMID:25702091

  1. An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers.

    PubMed

    Xie, Maobin; Fan, Dejun; Chen, Yufeng; Zhao, Zheng; He, Xiaowen; Li, Gang; Chen, Aizheng; Wu, Xiaojian; Li, Jiashen; Li, Zhi; Hunt, John A; Li, Yi; Lan, Ping

    2016-10-01

    The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 μg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 μg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy. PMID:27376557

  2. Phase I study and preclinical efficacy evaluation of the mTOR inhibitor sirolimus plus gemcitabine in patients with advanced solid tumours

    PubMed Central

    Martin-Liberal, J; Gil-Martín, M; Sáinz-Jaspeado, M; Gonzalo, N; Rigo, R; Colom, H; Muñoz, C; Tirado, O M; García del Muro, X

    2014-01-01

    Background: We conducted a phase I study in patients with advanced solid tumours to identify the recommended dose, assess pharmacokinetics (PK), pharmacodynamic activity and preclinical antitumour efficacy of the combination of sirolimus and gemcitabine. Methods: Nineteen patients were treated with sirolimus 2 or 5 mg daily and gemcitabine 800 or 1000 mg m−2 on days 1 and 8. Dose escalation depended on dose-limiting toxicity (DLT) rate during the first 3-week period. Paired skin biopsies were evaluated for phosphorylated S6 (pS6) as marker of mTOR (mammalian target of rapamycin) inhibition. Pharmacokinetics and preclinical evaluation of efficacy using two different sarcoma cell lines and leiomyosarcoma xenografts were also conducted. Results: Three DLTs were observed: grade 3 transaminitis, grade 3 thrombocytopenia and grade 4 thrombocytopenia. Common treatment-related adverse events included anaemia, neutropenia, thrombocytopenia and transaminitis. Pharmacodynamic analyses demonstrated mTOR inhibition with sirolimus 5 mg and PK showed no influence of sirolimus concentrations on gemcitabine clearance. In vitro and in vivo studies suggested mTOR pathway hyperactivation by gemcitabine that was reversed by sirolimus. Tumour growth in leiomyosarcoma xenografts was dramatically inhibited by the treatment. Conclusions: Recommended dose was sirolimus 5 mg per 24 h plus gemcitabine 800 mg m−2. Antitumour activity in preclinical sarcoma models and mTOR signalling inhibition were observed. A phase II study is currently ongoing. PMID:25003665

  3. Stages of Change for the Component Behaviors of Advance Care Planning

    PubMed Central

    Fried, Terri R.; Redding, Colleen; Robbins, Mark; Paiva, Andrea; O’Leary, John R.; Iannone, Lynne

    2010-01-01

    Objectives 1) To develop stages of change measures for advance care planning (ACP), conceptualized as a group of interrelated but separate behaviors. 2) To use these measures to characterize older persons’ engagement in and factors associated with readiness to participate in ACP. Design Observational cohort study. Setting Community. Participants Persons age ≥ 65 recruited from physician offices and a senior center. Measurements Stages of change for six ACP behaviors: completion of a living will and health care proxy, communication with loved ones regarding use of life-sustaining treatments and quantity versus quality of life (QOL), and communication with physicians about these same issues. Results Readiness to participate in ACP varied widely across behaviors. Whereas between approximately 50–60% of participants were in the action or maintenance stage for communicating with loved ones and completing a living will, 40% were in the precontemplation stage for communicating with loved ones about quantity versus QOL, and 70–75% were in the precontemplation stage for communicating with physicians. Participants were frequently in different stages for the different behaviors. Relatively few sociodemographic, health, or psychosocial factors were associated with stages of change for completing a living will, but a broader range of factors was associated with stages of change for communication with loved ones about quantity versus QOL. Conclusion Older persons show a range of readiness to engage in different aspects of ACP. Individualized assessment and interventions targeted to stage of behavior change for each component of ACP may be an effective strategy to increase participation in ACP. PMID:21143441

  4. The experience of living with advanced-stage cancer: a thematic synthesis of the literature.

    PubMed

    García-Rueda, N; Carvajal Valcárcel, A; Saracíbar-Razquin, M; Arantzamendi Solabarrieta, M

    2016-07-01

    The aim of the study was to understand the experience of people living with advanced-stage cancer through literature. The search included The Cochrane Library, PubMed, PsycInfo, CINAHL and Cuiden. Thirteen studies were included. A qualitative meta-synthesis was conducted. One thread emerged from the thematic synthesis: the desire to live as normally as possible, despite being aware of the proximity of death. Three themes also emerged: "a process that is unique" with its four sub-themes; "support network" and "health context," each of them having two sub-themes. This study concludes that living with advanced-stage cancer is a unique and complex process which has both positive and negative aspects. The review provides a comprehensive view of the experience, which considers the importance of the support network and the health context in which the person lives. In this study, "normalcy" is the adjustment to the new reality and living as closely as possible to the way one lived before the disease, while developing a new relationship with being finite and death. A better understanding of the experience of living with advanced-stage cancer will help health professionals to identify the needs of the patients in order to plan individual, high-quality care. PMID:27297131

  5. Physical Activity in Patients With Advanced-Stage Cancer: A Systematic Review of the Literature

    PubMed Central

    Albrecht, Tara A.; Taylor, Ann Gill

    2014-01-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  6. Current approaches to the treatment of advanced-stage Hodgkin's disease.

    PubMed Central

    Rusthoven, J J

    1986-01-01

    Combination chemotherapy (CT) has been the mainstay of treatment of advanced-stage Hodgkin's disease since the late 1960s. Although treatment with MOPP (nitrogen mustard, vincristine sulfate [Oncovin], procarbazine and prednisone) has resulted in long-term disease-free survival rates exceeding 50%, newer approaches have been studied to improve on this success rate and to reduce the toxic effects associated with MOPP. Prognostic factors have now been defined that identify patients who may require more aggressive treatment; they include age greater than 40 years, presence of B symptoms and more advanced (especially extranodal) disease. A small number of patients with pathological stage III disease may still be successfully treated with extensive radiotherapy (RT) alone. Among patients with advanced-stage disease, significantly better therapeutic results are being obtained with newer treatment approaches than with MOPP, particularly in patients with factors that predict a poor outcome. These newer approaches include combination CT plus RT, alternating cycles of two non-cross-resistant CT regimens and hybrid regimens, which combine agents from two different CT regimens in one cycle. The prognosis of patients who suffer relapse after combination CT remains poor, even with newer drug regimens. The newer treatment approaches may well lead to better cure rates and fewer short-term and long-term toxic effects. PMID:2427176

  7. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives. PMID:22641322

  8. Treatment of Children with Advanced-Stage Lymphoblastic Lymphoma with Pegaspargase

    PubMed Central

    Yu-tong, Zhang; Li-hua, FENG; Xiao-dan, Zhong; Li-zhe, Wang; Jian, Chang

    2014-01-01

    Objective: To evaluate the feasibility of Pegaspargase instead of L-asparaginase to treat children with advanced-stage lymphoblastic lymphoma (LBL) on the Berlin-Frankfurt-Munster (BFM)-95 protocol. Methods: Fifty-four newly diagnosed patients with stage III or IV LBL and without any treatment were enrolled in this study. Pegaspargase took place of L-asparaginase in BFM-95. The complications and treatment responses of patients treated on the BFM-95 protocol and modified BFM-95 protocol were then evaluated respectively. Findings : For LBL patients treated with BFM-95 protocol or modified BFM-95 protocol, the complete response, event-free survival, overall survival were similar. Stage 4 myelosuppression was the most common complication in both groups. Besides that, among 31 patients receiving modified BFM-95 protocol, coagulation defects were the most common complication. In contrast, anaphylactic reaction was the most common complication in the other 23 patients receiving BFM-95 protocol. Conclusion: Modified BFM-95 protocol is available to children with advanced-stage LBL with an equal outcome and enhances its compliance and decreases the incidence of anaphylactic reaction, compared to BFM-95 protocol. Coagulation defects are the major complication and tolerable in modified one. PMID:25793049

  9. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    PubMed

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways. PMID:16953241

  10. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  11. Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

    NASA Technical Reports Server (NTRS)

    Seiler, James; Brasfield, Fred; Cannon, Scott

    2008-01-01

    Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

  12. Two-stage, low noise advanced technology fan. 5: Acoustic final report

    NASA Technical Reports Server (NTRS)

    Sofrin, T. G.; Riloff, N., Jr.

    1975-01-01

    The NASA Q2S(quiet two-stage) fan is a 0.836m (32.9 in.) diameter model of the STF 433 engine fan, selected in a 1972 study for an Advanced Technology Transport (ATT) airplane. Noise-control features include: low tip speed, moderate stage pressure rise, large blade-vane spacings, no inlet guide vanes, and optimum blade and vane numbers. Tests were run on the baseline Q2S fan with standard inlet and discharge ducts. Further tests were made of a translating centerbody sonic inlet device and treated discharge ducts. Results were scaled to JT8D and JT3D engine fan size for comparison with current two-stage fans, and were also scaled to STF 433 fan size to compare calculated ATT flyover noise with FAR 36 limits. Baseline Q2S results scaled to JT8D and JT3D engine fan sizes showed substantial noise reductions. Calculated unsuppressed baseline ATT flyovers averaged about 2.5 EPNdB below FAR 36 limits. Using measured sonic inlet results, scaled baseline Q2S fan results, and calculated attenuations for a 1975 technology duct liner, projected flyover noise calculations for the ATT averaged about FAR 36 limits minus 10 EPNdB. Advances in suppression technology required to meet the 1985 goal of FAR 36 limits minus 20 EPNdB are discussed.

  13. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    NASA Astrophysics Data System (ADS)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  14. Advanced Strategies for End-Stage Heart Failure: Combining Regenerative Approaches with LVAD, a New Horizon?

    PubMed Central

    Tseng, Cheyenne C. S.; Ramjankhan, Faiz Z.; de Jonge, Nicolaas; Chamuleau, Steven A. J.

    2015-01-01

    Despite the improved treatment of cardiovascular diseases, the population with end-stage heart failure (HF) is progressively growing. The scarcity of the gold standard therapy, heart transplantation, demands novel therapeutic approaches. For patients awaiting transplantation, ventricular-assist devices have been of great benefit on survival. To allow explantation of the assist device and obviate heart transplantation, sufficient and durable myocardial recovery is necessary. However, explant rates so far are low. Combining mechanical circulatory support with regenerative therapies such as cell (-based) therapy and biomaterials might give rise to improved long-term results. Although synergistic effects are suggested with mechanical support and stem cell therapy, evidence in both preclinical and clinical setting is lacking. This review focuses on advanced and innovative strategies for the treatment of end-stage HF and furthermore appraises clinical experience with combined strategies. PMID:25905105

  15. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  16. Recent advances in renal transplantation: antibody-mediated rejection takes center stage

    PubMed Central

    Chen, Chien Chia; Sicard, Antoine; Rabeyrin, Maud; Morelon, Emmanuel; Dubois, Valérie

    2015-01-01

    Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. This review provides an overview of the current knowledge of antibody-mediated rejection and discusses future interesting research directions. PMID:26097724

  17. P08: Somatostatin analogs plus prednisone in aggressive histotype and advanced stage of thymic epithelial tumors

    PubMed Central

    Ottaviano, Margaret; Damiano, Vincenzo; Nappi, Lucia; Rescigno, Pasquale; Marino, Mirella; Del Vecchio, Silvana; Tucci, Irene; von Arx, Claudia; Palumbo, Giuliano; Palmieri, Giovannella

    2015-01-01

    Background Thymic epithelial tumors (TETs) are rare neoplasms characterized by histological variability and different expression at the molecular level. Several biological agents have been evaluated in TETs in small phase II trials. Efficacy of octreotide/lanreotide with or without prednisone in TETs OctreoScan positive has been widely demonstrated in thymoma, but no clearly in thymic carcinoma. Methods Twelve patients (five men, seven women; median age 47 years; range, 27–70 years) with advanced stage disease according to the Masaoka-Koga staging system (seven with IVa stage; five with IVb stage), and aggressive histotype according to WHO classification, revised by central review (two B2/B3; five B3; one B3/thymic carcinoma; four thymic carcinoma) were enrolled in this monocentric referral study. All the patients showed a progressive disease according to RECIST 1.1 criteria to previous conventional chemotherapeutic regimens platinum or not platinum-based. All the patients performed OctreoScan. The schedule includes administration of long-acting analog octreotide (30 mg/every 28 days intramuscularly) plus prednisone 0.2 mg/kg/day until progression of disease was documented. Overall response rate and toxicity were evaluated. Results The median time to progression was 6 months (range, 3–24 months), the overall response rate was 74.9%, particularly three patients (25%) obtained stable disease; four patients (33.3%) partial response; two patients (16.6%) complete response; three patients (25%) progression disease. One patient with Good Syndrome interrupted treatment after 6 months for infection disease. One patient has been lost to follow-up after 24 months of treatment. One patient died after progression disease for PRCA. Treatment was generally well tolerated with acceptable toxicity: no symptomatic cholelithiasis (one patient), grade 1 diarrhea (two patients) hyperglycemia (one patient). One patient with thymic carcinoma and IVB stage had PS improvement from 2

  18. Selecting the best strategy of treatment in newly diagnosed advanced-stage ovarian cancer patients

    PubMed Central

    Minig, Lucas; Zorrero, Cristina; Iserte, Pablo Padilla; Poveda, Andres

    2015-01-01

    Although it is assumed that the combination of chemotherapy and radical surgery should be indicated in all newly diagnosed advanced-stage ovarian cancer patients, one of the main raised questions is how to select the best strategy of initial treatment in this group of patients, neoadjuvant chemotherapy followed by interval debulking surgery or primary debulking surgery followed by adjuvant chemotherapy. The selection criteria to offer one strategy over the other as well as a stepwise patient selection for initial treatment are described. Selecting the best strategy of treatment in newly diagnosed advanced stage ovarian cancer patients is a multifactorial and multidisciplinary decision. Several factors should be taken into consideration: (1) the disease factor, related to the extension and localization of the disease as well as tumor biology; (2) the patient factor, associated with patient age, poor performance status, and co-morbidities; and (3) institutional infrastructure factor, related to the lack of prolonged operative time, an appropriate surgical armamentarium, as well as well-equipped intensive care units with well-trained personnel. PMID:26713279

  19. Nonlinear modelling of cancer: bridging the gap between cells and tumours

    NASA Astrophysics Data System (ADS)

    Lowengrub, J. S.; Frieboes, H. B.; Jin, F.; Chuang, Y.-L.; Li, X.; Macklin, P.; Wise, S. M.; Cristini, V.

    2010-01-01

    Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of

  20. Nonlinear modelling of cancer: bridging the gap between cells and tumours

    PubMed Central

    Lowengrub, J S; Frieboes, H B; Jin, F; Chuang, Y-L; Li, X; Macklin, P; Wise, S M; Cristini, V

    2010-01-01

    Despite major scientific, medical and technological advances over the last few decades, a cure for cancer remains elusive. The disease initiation is complex, and including initiation and avascular growth, onset of hypoxia and acidosis due to accumulation of cells beyond normal physiological conditions, inducement of angiogenesis from the surrounding vasculature, tumour vascularization and further growth, and invasion of surrounding tissue and metastasis. Although the focus historically has been to study these events through experimental and clinical observations, mathematical modelling and simulation that enable analysis at multiple time and spatial scales have also complemented these efforts. Here, we provide an overview of this multiscale modelling focusing on the growth phase of tumours and bypassing the initial stage of tumourigenesis. While we briefly review discrete modelling, our focus is on the continuum approach. We limit the scope further by considering models of tumour progression that do not distinguish tumour cells by their age. We also do not consider immune system interactions nor do we describe models of therapy. We do discuss hybrid-modelling frameworks, where the tumour tissue is modelled using both discrete (cell-scale) and continuum (tumour-scale) elements, thus connecting the micrometre to the centimetre tumour scale. We review recent examples that incorporate experimental data into model parameters. We show that recent mathematical modelling predicts that transport limitations of cell nutrients, oxygen and growth factors may result in cell death that leads to morphological instability, providing a mechanism for invasion via tumour fingering and fragmentation. These conditions induce selection pressure for cell survivability, and may lead to additional genetic mutations. Mathematical modelling further shows that parameters that control the tumour mass shape also control its ability to invade. Thus, tumour morphology may serve as a predictor of

  1. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    PubMed Central

    Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash

    2016-01-01

    Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID:26820579

  2. Strain elastography features of epidermoid tumours in superficial soft tissue: differences from other benign soft-tissue tumours and malignant tumours

    PubMed Central

    Park, H J; Lee, S M; Kim, W T; Lee, S; Ahn, K S

    2015-01-01

    Objective: We evaluated ultrasonographic features of superficial epidermoid tumour with a focus on strain elastography (SE) features that will help in the differential diagnosis of epidermoid tumour from other benign and malignant soft-tissue tumours. Methods: We retrospectively evaluated ultrasonographic and SE data of 103 surgically confirmed superficial soft-tissue tumours and tumour-like lesions: 29 cases of epidermoid tumour, 46 cases of other benign tumours and 28 cases of malignant tumour. SE and B-mode imaging were performed at the same time. SE characteristics were assigned into four grades (1–4) according to their elasticity. Interobserver agreement for the four SE scores between the two radiologists was analysed using kappa statistics. We classified each SE finding as a hard lesion (SE Score 3–4) or soft lesion (SE Score 1–2) and compared these findings using the χ2 test to identify whether a significant difference in mass hardness existed among epidermoid tumour, other benign tumour and malignant tumour. Results: Overall interobserver agreement according to the four SE scores was moderate (κ = 0.540), and overall agreement for the hardness [soft (Score 1–2) or hard (Score 3–4)] was almost perfect (κ = 0.825). Malignant tumours showed higher SE scores (3–4, hard nature) than did epidermoid tumour or other benign soft-tissue tumours. There were no differences in SE score between epidermoid tumour and other benign tumours. Conclusion: Superficial epidermoid tumour exhibits a softer nature than does malignant tumour but does not have a different SE pattern from other benign tumours. Advances in knowledge: SE features of epidermoid tumour might be helpful in differentiating from other benign and malignant tumours. PMID:25827206

  3. Two-stage, low noise advanced technology fan. Volume 2: Aerodynamic data

    NASA Technical Reports Server (NTRS)

    Harley, K. G.; Odegard, P. A.

    1975-01-01

    Aerodynamic data from static tests of a two-stage advanced technology fan designed to minimize noise are presented. Fan design conditions include delivery of 209.1kg/sec/sq m (42.85 lbm/sec/sq ft) specific corrected flow at an overall pressure ratio of 1.9 and an adiabatic efficiency of 85.3 percent. The 0.836m (2.74ft) diameter first stage rotor has a hub/tip ratio of 0.4 and 365.8m/sec (1200ft/sec) design tip speed. In addition to the moderate tip speed and pressure rise per stage, other noise control design features involve widely spaced blade rows and proper selection of blade-vane ratios. Aerodynamic data are presented for tests with unifrom and with hub and tip radially distorted inlet flow. Aerodynamic data are also presented for tests of this fan with acoustic treatments, including acoustically treated casing walls, a flowpath exit acoustic ring, and a translating centerbody sonic inlet device. A complete tabulation of the overall performance data, the blade element data, and the power spectral density information relating to turbulence levels generated by the sonic inlet obtained during these tests is included. For vol. 1, see N74-33789.

  4. Advanced stages of PD: interventional therapies and related patient-centered care.

    PubMed

    Krüger, Rejko; Hilker, Rüdiger; Winkler, Christian; Lorrain, Michael; Hahne, Matthias; Redecker, Christoph; Lingor, Paul; Jost, Wolfgang H

    2016-01-01

    During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany. PMID:26138439

  5. Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182780 in women with advanced breast cancer.

    PubMed Central

    Howell, A.; DeFriend, D. J.; Robertson, J. F.; Blamey, R. W.; Anderson, L.; Anderson, E.; Sutcliffe, F. A.; Walton, P.

    1996-01-01

    We have assessed the pharmacokinetics, pharmacological and anti-tumour effects of the specific steroidal anti-oestrogen ICI 182780 in 19 patients with advanced breast cancer resistant to tamoxifen. The agent was administered as a monthly depot intramuscular injection. Peak levels of ICI 182780 occurred a median of 8-9 days after dosing and then declined but were above the projected therapeutic threshold at day 28. Cmax during the first month was 10.5 ng/ml-1 and during the sixth month was 12.6 ng ml-1. The AUCs were 140.5 and 206.8 ng day ml-1 on the first and sixth month of dosing respectively, suggesting some drug accumulation. Luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels rose after withdrawal of tamoxifen and then plateaued, suggesting no effect of ICI 182780 on the pituitary-hypothalamic axis. There were no significant changes in serum levels of prolactin, sex hormone-binding globulin (SHBG) or lipids. Side-effects were infrequent. Hot-flushes and sweats were not induced and there was no apparent effect of treatment upon the endometrium or vagina. Thirteen (69%) patients responded (seven had partial responses and six showed "no change' responses) to ICI 182780, after progression on tamoxifen, for a median duration of 25 months. Thus ICI 182780, given by monthly depot injection, and at the drug levels described, is an active second-line anti-oestrogen without apparent negative effects on the liver, brain or genital tract and warrants further evaluation in patients with advanced breast cancer. PMID:8688341

  6. Advanced stage ovarian juvenile granuloza cell tumor causing acute abdomen: a case report.

    PubMed

    Bedir, Recep; Mürtezaoğlu, Afşin Rahman; Calapoğlu, Ahmet Salih; Şehitoğlu, İbrahim; Yurdakul, Cüneyt

    2014-09-01

    Ovary juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors that are most commonly encountered in prepubertal girls. These tumors can be of the adult type (95%) and juvenile type (5%). The main causes of complaint are abdominal distention and abdominal pain. Definitive diagnosis is confirmed by histopathologal and immunohistochemical examinations. A 10-year old girl presented with massive abdominal distention, acute abdomen findings and ascites. Abdominopelvic magnetic resonance imaging showed masses with multiple cysts and solid components in the left ovary. Tumor markers were normal, but serum estradiol level was elevated. The patient underwent mass resection with left salpingo-oophorectomy and total omentectomy. Final histopathological diagnosis was JGCT. We herein reporte an extremely rare case of advanced stage JGCT causing massive ascites and acute abdomen. PMID:25204485

  7. Advanced glycation end-products and skin autofluorescence in end-stage renal disease: a review.

    PubMed

    Arsov, Stefan; Graaff, Reindert; van Oeveren, Wim; Stegmayr, Bernd; Sikole, Aleksandar; Rakhorst, Gerhard; Smit, Andries J

    2014-01-01

    Chronic kidney disease (CKD), especially in its end stage, is marked by extremely high cardiovascular rates of morbidity and mortality; hemodialysis patients have a five-fold shorter life expectancy than healthy subjects of the same age. In CKD the metabolic products that accumulate in the body are so-called uremic toxins. These include advanced glycation end-products (AGE). AGE levels are markedly increased in CKD patients not only because of impaired excretion but also because of increased production. AGE formation has initially been described as a non-enzymatic reaction between proteins and glucose in the so-called Maillard reaction, but they are also more rapidly formed during oxidative stress and subsequent formation of reactive carbonyl compounds like (methyl)glyoxal. AGE accumulate in tissue where they cross-link with proteins, e.g., collagen, inducing tissue stiffening of blood vessels and skin. They may also interact with receptor of AGE (RAGE) and other receptors, which lead to activation of intracellular transduction mechanisms resulting in cytokine release and further tissue damage in CKD. The accumulation of AGE in the skin can be measured non-invasively using autofluorescence. The skin autofluorescence is a strong marker of cardiovascular mortality in CKD. The focus of this review is on the role of tissue and plasma AGE, and of skin autofluorescence as a proxy of tissue AGE accumulation, in the increase in cardiovascular disease in end stage renal disease (ESRD). This review will also present the possibility of reducing the AGE accumulation in ESRD patients using the following five methods: 1) use of low AGE peritoneal dialysis solutions; 2) use of advanced hemodialysis techniques; 3) use of AGE reducing drugs; 4) optimizing the nutrition of hemodialysis patients; and 5) renal transplantation. PMID:23612551

  8. Up-regulation of stromal versican expression in advanced stage serous ovarian cancer

    PubMed Central

    Ghosh, Sue; Albitar, Lina; LeBaron, Richard; Welch, William R.; Samimi, Goli; Birrer, Michael J.; Berkowitz, Ross S.; Mok, Samuel C.

    2010-01-01

    Objective The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n= 56) were done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression free survival and platinum resistance. PMID:20619446

  9. Single stage, low noise advanced technology fan. Volume 3: Acoustic design

    NASA Technical Reports Server (NTRS)

    Kazin, S. B.; Mishler, R. B.

    1976-01-01

    The acoustic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec (1,650 ft/sec). The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise is accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels (20 EPNdB) below current Federal Air Regulation noise standards for a full-scale fan at the takeoff, cutback, and approach conditions. Predicted unsuppressed and suppressed fore and aft maximum perceived noise levels indicate that the cutback condition is the most critical with respect to the goal, which is probably unattainable for that condition. This is also true for aft radiated noise in the approach condition.

  10. Single stage, low noise, advanced technology fan. Volume 1: Aerodynamic design

    NASA Technical Reports Server (NTRS)

    Sullivan, T. J.; Younghans, J. L.; Little, D. R.

    1976-01-01

    The aerodynamic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec 11,650 ft/sec). The fan and booster components are designed in a scale model flow size convenient for testing with existing facility and vehicle hardware. The design corrected flow per unit annulus area at the fan face is 215 kg/sec sq m (44.0 lb m/sec sq ft) with a hub-tip ratio of 0.38 at the leading edge of the fan rotor. This results in an inlet corrected airflow of 117.9 kg/sec (259.9 lb m/sec) for the selected rotor tip diameter if 90.37 cm (35.58 in.). The variable geometry inlet is designed utilizing a combination of high throat Mach number and acoustic treatment in the inlet diffuser for noise suppression (hybrid inlet). A variable fan exhaust nozzle was assumed in conjunction with the variable inlet throat area to limit the required area change of the inlet throat at approach and hence limit the overall diffusion and inlet length. The fan exit duct design was primarily influenced by acoustic requirements, including length of suppressor wall treatment; length, thickness and position on a duct splitter for additional suppressor treatment; and duct surface Mach numbers.

  11. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  12. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  13. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease. PMID:25247398

  14. Cognitive benefits of memantine in Alzheimer's 5XFAD model mice decline during advanced disease stages.

    PubMed

    Devi, Latha; Ohno, Masuo

    2016-05-01

    Memantine, a noncompetitive NMDA receptor antagonist with neuroprotective properties, has been used for the treatment of Alzheimer's disease (AD). Administration of memantine to various transgenic AD mice has been reported to improve cognitive deficits, very often completely back to normal wild-type control levels. However, such great benefits of memantine in preclinical studies do not translate into clinical results of this drug, showing only marginal and transient efficacy in moderate to severe AD. To further address in vivo efficacy, we compared the effects of memantine at different disease stages in 5XFAD mice, one of the rapid-onset and most aggressive amyloid models. Specifically, we administered memantine once daily for 30days to 5XFAD mice, which showed moderate (6-7months of age) and robust (12-15months) β-amyloid (Aβ) accumulation. Treatments with memantine (10mg/kg, i.p.) reversed memory impairments in the younger 5XFAD mice, as tested by the contextual fear conditioning and spontaneous alternation Y-maze paradigms. Memantine had no effects on soluble Aβ oligomer or total Aβ42 levels in 5XFAD mouse brains. In contrast, subchronic treatments with memantine showed no behavioral benefits in the older 5XFAD group, which exhibited more profound memory deficits concomitant with highly increased concentrations of Aβ as compared with those of the younger 5XFAD group. Since subchronic memantine at the higher dose (30mg/kg) impaired memory performances in wild-type controls, we further tested acute administration of 50mg/kg memantine, which was reported to enhance hippocampal adult neurogenesis and memory function. However, this treatment also failed to rescue memory deficits in 12-15-month-old 5XFAD mice. Collectively, our results demonstrate that cognitive benefits of memantine independent of Aβ reductions were no longer observed in the 5XFAD Alzheimer mouse model during advanced stages, which may be reflective of the limited efficacy of memantine in

  15. Perioperative Outcomes of Robotic Assisted Laparoscopic Surgery Versus Conventional Laparoscopy Surgery for Advanced-Stage Endometriosis

    PubMed Central

    Sirota, Ido

    2014-01-01

    Background and Objectives: To determine perioperative outcome differences in patients undergoing robotic-assisted laparoscopic surgery (RALS) versus conventional laparoscopic surgery (CLS) for advanced-stage endometriosis. Methods: This retrospective cohort study at a minimally invasive gynecologic surgery center at 2 academically affiliated, urban, nonprofit hospitals included all patients treated by either robotic-assisted or conventional laparoscopic surgery for stage III or IV endometriosis (American Society for Reproductive Medicine criteria) between July 2009 and October 2012 by 1 surgeon experienced in both techniques. The main outcome measures were extent of surgery, estimated blood loss, operating room time, intraoperative and postoperative complications, and length of stay, with medians for continuous measures and distributions for categorical measures, stratified by body mass index values. Robotically assisted laparoscopy and conventional laparoscopy were then compared by use of the Wilcoxon rank sum, χ2, or Fisher exact test, as appropriate. Results: Among 86 conventional laparoscopic and 32 robotically assisted cases, the latter had a higher body mass index (27.36 kg/m2 [range, 23.90–34.09 kg/m2] versus 24.53 kg/m2 [range, 22.27–26.96 kg/m2]; P < .0079) and operating room time (250.50 minutes [range, 176–328.50 minutes] versus 173.50 minutes [range, 123–237 minutes]; P < .0005) than did conventional laparoscopy patients. After body mass index stratification, obese patients varied in operating room time (282.5 minutes [range, 224–342 minutes] for robotic-assisted laparoscopy versus 174 minutes [range, 130–270 minutes] for conventional laparoscopy; P < .05). No other significant differences were noted between the robotic-assisted and conventional laparoscopy groups. Conclusion: Despite a higher operating room time, robotic-assisted laparoscopy appears to be a safe minimally invasive approach for patients, with all other perioperative

  16. Influence of various operating conditions on advanced PFBC with staged combustion

    SciTech Connect

    Moersch, O.; Nagel, H.; Spliethoff, H.; Hein, K.R.G.

    1999-07-01

    The development of PFBC towards advanced or second generation PFBC focuses on an increase of temperature at the gas turbine inlet to bring forth a substantial improvement of the turbine itself and the overall system performance. Most of such advanced systems described in literature include a carbonizer for partial conversion of coal producing a low calorific pressurized syngas and a PFBC burning the remaining char. After hot gas clean-up the syngas and the O{sub 2}-rich fuel gas from the PFBC are led to the combustion chamber of the gas turbine. In the proposed staged combustion concept (PFBC-SC), which also aims at raising the temperatures at the gas turbine inlet, coal is burned substoichiometrically in a pressurized fluidized bed producing a low calorific gas. After hot gas clean-up the gas undergoes post-combustion with pressurized air and enters the gas turbine at approximately 1,450 K. The advantages of PFBC-SC over APFBC as described above are the lower investment costs and the simpler process, because no separate gasifier including hot gas cleaning device is needed. At the IVD's 50 kWth PFBC test facility, experimental investigations were done into substoichiometrical combustion with regard to composition of the produced gas, carbon-conversion and afterburner temperature. The results of the experiments which were carried out at various temperatures (1,073--1,200 K), pressures (1--13 bar), air ratios (0.5--0.9) and with different coals were compared with chemical equilibrium calculations. In contrast to the operating pressure the heating value of the syngas ({ge}CO, H{sub 2}, CH{sub 4}) could be increased significantly with increasing temperatures. Due to the better gasification behavior of subbituminous coal compared with bituminous coal almost equilibrium conditions were achieved. At high pressures and temperatures (13 bar/1,173 K) the carbon conversion rate 97.5% at all air ratios.

  17. HLA-G Expression and Role in Advanced-Stage Classical Hodgkin Lymphoma

    PubMed Central

    Caocci, G.; Greco, M.; Fanni, D.; Senes, G.; Littera, R.; Lai, S.; Risso, P.; Carcassi, C.; Faa, G.; La Nasa, G.

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  18. Short-term morbidity in transdiaphragmatic cardiophrenic lymph node resection for advanced stage gynecologic cancer.

    PubMed

    LaFargue, C J; Sawyer, B T; Bristow, R E

    2016-08-01

    Ovarian cancer is commonly diagnosed at an advanced stage, with disease involving the upper abdomen. The finding of enlarged cardiophrenic lymph nodes (CPLNs) on pre-operative imaging often indicates the presence of malignant spread to the mediastinum. Surgical resection of CPLN through a transdiaphragmatic approach can help to achieve cytoreduction to no gross residual. A retrospective chart review was conducted on all patients who underwent transdiaphragmatic cardiophrenic lymph node resection from 8/1/11 through 2/1/15. All relevant pre-, intra-, and post-operative characteristics and findings were recorded. A brief description of the surgical technique is included for reference. Eleven patients were identified who had undergone transdiaphragmatic resection of cardiophrenic lymph nodes. Malignancy was identified in 18/21 (86%) of total lymph nodes submitted. The median number of post-operative days was 7. The overall post-operative morbidity associated with CPLN resection was low, with the most common finding being a small pleural effusion present on chest x-ray between POD# 3-5 (55%). Transdiaphragmatic CPLN resection is a feasible procedure with relatively minor short-term post-operative morbidities that can be used to achieve cytoreduction to no gross residual disease. PMID:27354998

  19. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer.

    PubMed

    Loggers, Elizabeth Trice; Buist, Diana S M; Gold, Laura S; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D; Sullivan, Sean D; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08-2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17-2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  20. Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

    PubMed Central

    Buist, Diana S. M.; Gold, Laura S.; Zeliadt, Steven; Hunter Merrill, Rachel; Etzioni, Ruth; Ramsey, Scott D.; Sullivan, Sean D.; Kessler, Larry

    2016-01-01

    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and p = 0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and p = 0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively. PMID:27525122

  1. Evaluation of mean platelet volume, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma

    PubMed Central

    Yavuzcan, Ali; Çağlar, Mete; Üstün, Yusuf; Dilbaz, Serdar; Özdemir, İsmail; Yıldız, Elif; Özkara, Atilla; Kumru, Selahattin

    2013-01-01

    Objective We compared the preoperative values of mean platelet volume (MPV) and peripheral systemic inflammatory response (SIR) markers (neutrophil/lymphocyte ratio and platelet/lymphocyte ratio) between patients with advanced-stage (stage 3/4) endometriosis having endometrioma (OMA) and patients with a non-neoplastic adnexal mass other than endometrioma (non-OMA). Material and Methods Patients who underwent operations with the pre-diagnosis of infertility or adnexal mass and who underwent laparoscopic tubal ligation were included. Results Haemoglobin levels, leucocyte count, platelet count, neutrophil count and lymphocyte count were not significantly different between patients with advanced stage endometriosis having OMA, patients with non-OMA and patients in the control group (p=0.970, p=0.902, p=0.373, p=0.501 and p=0.463, respectively). Patients with stage 3/4 endometriosis having OMA, patients with non-OMA and control patients were also not significantly different in terms of MPV (p=0.836), neutrophil/lymphocyte ratio (NLR) (p=0.555) and platelet/lymphocyte ratio (PLR) (p=0.358). Preoperative cancer antigen 125 (Ca-125) levels were significantly higher in patients with OMA (p=0.006). Mean size of the OMAs was significantly lower than non-OMAs (p=0.000). Conclusion It is very important to determine advanced stage endometriosis and OMAs during preoperative evaluation in order to inform patients and plan an appropriate surgical approach. We demonstrate that MPV, NLR and PLR values are not useful for this purpose in patients with advanced stage endometriosis that are proven to develop severe inflammation at either the cellular or molecular level. PMID:24592108

  2. Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications.

    PubMed

    Boiocchi, Leonardo; Gianelli, Umberto; Iurlo, Alessandra; Fend, Falko; Bonzheim, Irina; Cattaneo, Daniele; Knowles, Daniel M; Orazi, Attilio

    2015-11-01

    Polycythemia vera in 20-30% of cases progresses towards post-polycythemic myelofibrosis, an advanced phase characterized by decreased red blood cells counts and increasing splenomegaly with extramedullary hematopoiesis. There is evidence that the presence of neutrophilic leukocytosis at polycythemia vera disease outset is associated with an increased risk of recurrent thrombosis. However, its clinical significance when developing later in the course of the disease is not well defined. Over a period of 8 years we identified from the files of two reference centers 10 patients (7M/3F, median age: 68 years) who developed persistent absolute leukocytosis ≥ 13 × 10⁹/l (median: 25.1 × 10⁹/l; range: 16.1-89.7 × 10⁹/l) at or around the time of diagnosis of post-polycythemic myelofibrosis (median interval from diagnosis:0 months; range: -6/31) and persisted for a median period of 13 months. Peripheral blood smears showed numerous neutrophils without dysplastic features and, in four, ≥ 10% immature myeloid precursors. In five cases, corresponding marrow specimens obtained at or immediately after the onset of leukocytosis showed a markedly increased myeloid:erythroid ratio due to granulocytic proliferation. No change in JAK2 and BCR-ABL1 status or cytogenetic evolution was associated with the development of leukocytosis. The mutational status of CSF3R, SETBP1, and SRSF2, genes associated with other chronic myeloid neoplasms where neutrophilic leukocytosis occurs, was investigated but all cases showed wild-type only alleles. Four patients died after developing leukocytosis and one experienced worsening disease. Compared with a control group of post-polycythemic myelofibrosis patients (n=23) who never developed persistent leukocytosis, patients with leukocytosis showed higher white blood cells counts and a shorter overall survival. This is the first study describing the development of significant neutrophilic leukocytosis during advanced stages of polycythemia vera

  3. Solid rocket technology advancement for Space Tug and IUS applications. [Interim Upper Stage

    NASA Technical Reports Server (NTRS)

    Ascher, W.; Bailey, R. L.; Behm, J. W.; Gin, W.

    1975-01-01

    Two-burn restartable solid propellant rocket motors for the kick stage (auxiliary stage) of the Shuttle Tug, or Interim Upper Stage, are described, with details on features and test results of the ignition and quench (thrust termination) systems and procedures, fabrication of propellant and insulation, explosion hazards of propellants, and comparative data on present and future motor design. These rocket motor systems are designed for upper stage augmentation of launch vehicles and possible service in Shuttle-launched outer planet spacecraft.

  4. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib: an international, multicentre, prospective, randomised, placebo-controlled phase 3 trial (GRID)

    PubMed Central

    Demetri, George D; Reichardt, Peter; Kang, Yoon-Koo; Blay, Jean-Yves; Rutkowski, Piotr; Gelderblom, Hans; Hohenberger, Peter; Leahy, Michael; von Mehren, Margaret; Joensuu, Heikki; Badalamenti, Giuseppe; Blackstein, Martin; Cesne, Axel Le; Schöffski, Patrick; Maki, Robert G; Bauer, Sebastian; Nguyen, Binh Bui; Xu, Jianming; Nishida, Toshirou; Chung, John; Kappeler, Christian; Kuss, Iris; Laurent, Dirk; Casali, Paolo

    2013-01-01

    Summary Background To date, only two agents, imatinib and sunitinib, have shown clinical benefit in patients with gastrointestinal stromal tumours (GISTs), but almost all metastatic GISTs eventually develop resistance to these agents, resulting in fatal disease progression. This phase 3 trial assessed efficacy and safety of regorafenib in patients with metastatic and/or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods Patients were randomised 2:1 to receive either regorafenib 160 mg orally daily or placebo, plus best supportive care in both arms, for the first 3 weeks of each 4-week cycle. The primary endpoint was progression-free survival (PFS). Upon disease progression, patients on placebo could cross over to regorafenib. Secondary endpoints included overall survival (OS), objective response rate, disease control rate (DCR: rate of durable stable disease lasting for ≥12 weeks plus complete or partial responses), and safety. This trial is registered at ClinicalTrials.gov (NCT01271712). Results From January to August 2011, 240 patients were screened at 57 centres in 17 countries, and 199 patients were randomised to receive regorafenib (n=133) or matching placebo (n=66). Median PFS per independent blinded central review was 4·8 months and 0·9 months, respectively (hazard ratio [HR] 0·27, 95% confidence interval [CI] 0·19–0·39; p<0·0001). Following progression, 56/66 patients (84·8%) on placebo crossed over to regorafenib, resulting in no significant difference in OS between study arms (HR 0·77, 95% CI 0·42–1·41; p=0·199). A best response of partial response or stable disease was observed in 101/133 patients (75·9%) on regorafenib and 23/66 patients (34·8%) on placebo. DCR was 52·6% (70/133 patients) and 9·1% (6/66 patients), respectively. Drug-related adverse events were reported in 130 (98·5%) of 132 regorafenib patients and 45 (68·2%) of 66 placebo patients. The most common grade ≥3 regorafenib

  5. HLA-G expression and role in advanced-stage classical Hodgkin lymphoma.

    PubMed

    Caocci, G; Greco, M; Fanni, D; Senes, G; Littera, R; Lai, S; Risso, P; Carcassi, C; Faa, G; La Nasa, G

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  6. Inhibitory effect of euphol, a triterpene alcohol from the roots of Euphorbia kansui, on tumour promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

    PubMed

    Yasukawa, K; Akihisa, T; Yoshida, Z Y; Takido, M

    2000-01-01

    The anti-inflammatory activity of euphol, twelve other triterpene alcohols and sitosterol-beta-D-glucopyranoside, isolated from the dichloromethane extract of the roots of Euphorbia kansui, has been evaluated in mice with inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA (1.7 nmol; 1.0 microg/ear) was dissolved in acetone and 10 microL delivered to the inner and outer surfaces of the right ear of ICR mice. A triterpene alcohol, sterol glucoside or vehicle (20 microL; chloroform-methanol 1:1), was applied topically approximately 30 min before each TPA treatment. The ear thickness was measured before treatment and then oedema was measured 6 h after TPA treatment. For the two-stage carcinogenesis experiment, initiation was accomplished by administration of a single topical application of 7,12-dimethylbenz[a]anthracene (DMBA; 195 nmol; 50 microg/mouse) to the shaved backs of mice. Promotion was with 1.7 nmol (1.0 microg) TPA, applied twice weekly to the same shaved area, begun one week after the initiation. Euphol (2.0 micromol; 853 microg), or its vehicle (acetone-dimethylsulphoxide, 9:1; 100 microL), was applied topically 30 min before each TPA treatment. The number and diameter of skin tumours were measured every other week for 20 weeks. All the compounds were found to possess marked inhibitory activity and their 50% inhibitory dose for TPA-induced inflammation was 0.2-1.0 mg/ear. Topical application of euphol (2.0 micromol; 853 microg/mouse) markedly suppressed the tumour-promoting effect of TPA (1.7 nmol; 1.0 microg/mouse) in mouse skin initiated with DMBA. PMID:10716613

  7. Low-Noise Potential of Advanced Fan Stage Stator Vane Designs Verified in NASA Lewis Wind Tunnel Test

    NASA Technical Reports Server (NTRS)

    Hughes, Christopher E.

    1999-01-01

    With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

  8. Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

  9. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma.

    PubMed

    Ried, Michael; Marx, Alexander; Götz, Andrea; Hamer, Okka; Schalke, Berthold; Hofmann, Hans-Stefan

    2016-06-01

    In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC. PMID:26670806

  10. Peculiarities of hyperlipidaemia in tumour patients.

    PubMed Central

    Dilman, V. M.; Berstein, L. M.; Ostroumova, M. N.; Tsyrlina, Y. V.; Golubev, A. G.

    1981-01-01

    The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer). PMID:7248149

  11. Method and apparatus for advanced staged combustion utilizing forced internal recirculation

    DOEpatents

    Rabovitser, Iosif K.; Knight, Richard A.; Cygan, David F.; Nester, Serguei; Abbasi, Hamid A.

    2003-12-16

    A method and apparatus for combustion of a fuel in which a first-stage fuel and a first-stage oxidant are introduced into a combustion chamber and ignited, forming a primary combustion zone. At least about 5% of the total heat output produced by combustion of the first-stage fuel and the first-stage oxidant is removed from the primary combustion zone, forming cooled first-stage combustion products. A portion of the cooled first-stage combustion products from a downstream region of the primary combustion zone is recirculated to an upstream region of primary combustion zone. A second-stage fuel is introduced into the combustion chamber downstream of the primary combustion zone and ignited, forming a secondary combustion zone. At least about 5% of the heat from the secondary combustion zone is removed. In accordance with one embodiment, a third-stage oxidant is introduced into the combustion chamber downstream of the secondary combustion zone, forming a tertiary combustion zone.

  12. Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets

    PubMed Central

    Yoshihara, Kosuke; Tajima, Atsushi; Yahata, Tetsuro; Kodama, Shoji; Fujiwara, Hiroyuki; Suzuki, Mitsuaki; Onishi, Yoshitaka; Hatae, Masayuki; Sueyoshi, Kazunobu; Fujiwara, Hisaya; Kudo, Yoshiki; Kotera, Kohei; Masuzaki, Hideaki; Tashiro, Hironori; Katabuchi, Hidetaka; Inoue, Ituro; Tanaka, Kenichi

    2010-01-01

    Background Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. Methodology/Principal Findings Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). Conclusions/Significance The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID:20300634

  13. Effect of zoledronic acid on disseminated tumour cells in women with locally advanced breast cancer: an open label, randomised, phase 2 trial

    PubMed Central

    Aft, Rebecca; Naughton, Michael; Trinkaus, Kathryn; Watson, Mark; Ylagan, Lourdes; Chavez-MacGregor, Mariana; Zhai, Jing; Kuo, Sacha; Shannon, William; Diemer, Kathryn; Herrmann, Virginia; Dietz, Jill; Ali, Amjad; Ellis, Matthew; Weiss, Peter; Eberlein, Timothy; Ma, Cynthia; Fracasso, Paula M; Zoberi, Imran; Taylor, Marie; Gillanders, William; Pluard, Timothy; Mortimer, Joanne; Weilbaecher, Katherine

    2013-01-01

    Summary Background Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer. The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells (DTCs) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer. Methods Patients were recruited for this open-label, phase 2 randomised trial between March 17, 2003, and May 19, 2006, at a single centre. Eligible patients had clinical stage II–III (≥T2 and/or ≥N1) newly diagnosed breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, and normal cardiac, renal, and liver function. 120 women were randomly assigned, using allocation concealment, to receive 4 mg zoledronic acid intravenously every 3 weeks (n=60), or no zoledronic acid (n=60), for 1 year concomitant with four cycles of neoadjuvant epirubicin (75 mg/m²) plus docetaxel (75 mg/m²) and two cycles of adjuvant epirubicin plus docetaxel. The primary endpoint was the number of patients with detectable DTCs at 3 months. Final analysis was done 1 year after the last patient was enrolled. Analyses were done for all patients with available data at 3 months. This study is registered with ClinicalTrials.gov, number NCT00242203. Findings Of the 120 patients initially enrolled, one withdrew after signing consent and one patient’s baseline bone marrow was not available. Both of these patients were in the control group. At 3 months, 109 bone-marrow samples were available for analysis. In the zoledronic acid group, bone marrow was not collected from one patient because of disease progression, one patient was taken off study because of severe diarrhoea, and two patients had not consented at the time of surgery. In the control group, bone marrow was not collected from two patients because of disease progression, one patient withdrew consent, and three patients were not consented at the time of surgery. At baseline

  14. Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

    PubMed Central

    Achille, A.; Baron, A.; Zamboni, G.; Di Pace, C.; Orlandini, S.; Scarpa, A.

    1998-01-01

    During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9862579

  15. Antenatally detected solid tumour of kidney

    PubMed Central

    Panda, Shasanka Shekhar; Mandelia, Ankur; Gupta, Devendra Kumar; Singh, Amit

    2014-01-01

    Congenital renal tumours are rare and usually benign. Polyhydramnios is the most common mode of presentation. Although most cases have been diagnosed postnatally, with advances in imaging technology, an increasing number of cases are being detected on antenatal scans. We describe a case of solid tumour of kidney detected in the second trimester of pregnancy and managed by surgery in the postnatal period. PMID:24526198

  16. Incidence, detection, and tumour stage of breast cancer in a cohort of Italian women with negative screening mammography report recommending early (short-interval) rescreen

    PubMed Central

    2010-01-01

    Background Although poorly described in the literature, the practice of early (short-interval) rescreen after a negative screening mammogram is controversial due to its financial and psychological burden and because it is of no proven benefit. Methods The present study targeted an Italian 2-yearly screening programme (Emilia-Romagna Region, 1997-2002). An electronic dataset of 647,876 eligible negative mammography records from 376,257 women aged 50-69 years was record-linked with the regional breast cancer registry. The statistical analysis addressed the following research questions: (1) the prevalence of recommendation for early (<24 months) rescreen (RES) among negative mammography reports; (2) factors associated with the likelihood of a women receiving RES; and (3) whether women receiving RES and women receiving standard negative reports differed in terms of proportional incidence of interval breast cancer, recall rate at the next rescreen, detection rate of breast cancer at the next rescreen and the odds of having late-stage breast cancer during the interscreening interval and at the next rescreen. Results RES was used in eight out of 13 screening centres, where it was found in 4171 out of 313,320 negative reports (average rate 1.33%; range 0.05%-4.33%). Reports with RES were more likely for women aged 50-59 years versus older women (odds ratio (OR) 1.33; 95% CI 1.25-1.42), for the first versus subsequent screening rounds (OR 1.91; 95% CI 1.79-2.04) and with a centre-specific recall rate below the average of 6.2% (OR 1.41; 95% CI 1.32-1.50). RES predicted a 3.51-fold (95% CI 0.94-9.29) greater proportional incidence of first-year interval cancers, a 1.90-fold (95% CI 1.62-2.22) greater recall rate at the next screen, a 1.72-fold (95% CI 1.01-2.74) greater detection rate of cancer at the next screen and a non-significantly decreased risk of late disease stage (OR 0.59; 95% CI 0.23-1.53). Conclusion The prevalence of RES was in line with the maximum standard

  17. Changes in inflorescence protein during advanced stages of floret development in Buchloe dactyloides (Poaceae).

    PubMed

    Zhou, Y-J; Xue, J-G; Wang, X-G; Zhang, X-Q

    2012-01-01

    Buffalograss, Buchloe dactyloides, is a dioecious species native to the Great Plains of North America. The florets at the early stages of development possess both gynoecium and androecium organ primordia but later become unisexual. Very little is known about the proteomic changes that occur when the florets change from hermaphroditism to unisexuality. We compared the protein composition of florets at the hermaphroditic stage with that at the unisexual stage. The development stage of the floret was determined by stereomicroscopic observation. Two-dimensional gel electrophoresis was used to separate the proteins extracted from female and male inflorescences. Stage- specific protein maps, with an average of about 400 spots per map, were analyzed with the protein analysis software. Eighteen spots were found to be differentially expressed between the hermaphrodite and unisexual stages. Of these, 12 were present at both stages but with a different expression value. Four specific spots appeared at the hermaphrodite stage and disappeared at the unisexual stage. Two specific protein spots were associated with female and male floret differentiation. One appears to be associated with contabescence in the female floret and the final protein appears to lead to the abortion of gynoecium in the male floret. The MALDI TOF/TOF technique was used for peptide mass fingerprinting of the differentially expressed proteins and the MASCOT software was used to search the protein database. However, only two protein spots were identified from the database. These were aldolase1 and Os05g0574400 (similar to malate dehydrogenase). This type of proteomic study can help to identify novel protein products and determine the mechanisms involved in the floral sex differentiation process in buffalo grass. PMID:22930428

  18. Transurethral resection and degeneration of bladder tumour

    PubMed Central

    Li, Aihua; Fang, Wei; Zhang, Feng; Li, Weiwu; Lu, Honghai; Liu, Sikuan; Wang, Hui; Zhang, Binghui

    2013-01-01

    Introduction: We evaluate the efficacy and safety of transurethral resection and degeneration of bladder tumour (TURD-Bt). Methods: In total, 56 patients with bladder tumour were treated by TURD-Bt. The results in these patients were compared with 32 patients treated by current transurethral resection of bladder tumour (TUR-Bt). Patients with or without disease progressive factors were respectively compared between the 2 groups. The factors included recurrent tumour, multiple tumours, tumour ≥3 cm in diameter, clinical stage T2, histological grade 3, adenocarcinoma, and ureteral obstruction or hydronephrosis. Results: Follow-up time was 48.55 ± 23.74 months in TURD-Bt group and 56.28 ± 17.61 months in the TUR-Bt group (p > 0.05). In patients without progressive factors, no tumour recurrence was found and overall survival was 14 (100%) in the TURD-Bt group; 3 (37.50%) patients had recurrence and overall survival was 5 (62.5%) in the TUR-Bt group. In patients with progressive factors, 8 (19.05%) patients had tumour recurrence, overall survival was 32 (76.19%) and cancer death was 3 (7.14%) in TURD-Bt group; 18 (75.00%) patients had tumour recurrence (p < 0.05), overall survival was 12 (50.00%) (p < 0.01) and cancer death was 8 (33.33%) (p < 0.05) in TUR-Bt group. No significant complication was found in TURD-Bt group. Conclusion: This study suggests that complete resection and degeneration of bladder tumour can be expected by TURD-Bt. The surgical procedure is safe and efficacious, and could be predictable and controllable before and during surgery. We would conclude that for bladder cancers without lymph node metastasis and distal metastasis, TURD-Bt could be performed to replace radical TUR-Bt and preserve the bladder. PMID:24475002

  19. Brain and spinal tumour.

    PubMed

    Goh, C H; Lu, Y Y; Lau, B L; Oy, J; Lee, H K; Liew, D; Wong, A

    2014-12-01

    This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning. PMID:25934956

  20. Modeling of an advanced concept of a double stage Hall effect thruster

    SciTech Connect

    Garrigues, L.; Boniface, C.; Hagelaar, G. J. M.; Boeuf, J. P.

    2008-11-15

    We present a study of the principle and operation of a two-stage Hall effect thruster, the SPT-MAG, using a two-dimensional quasineutral hybrid model coupled with a Monte Carlo simulation of electron transport. The purpose of the two-stage design is the separation of ion production and acceleration in two separate chambers, the ionization stage and the acceleration stage, with separate control of acceleration voltage and total ionization. The originality of the SPT-MAG lies in the magnetic field configuration in the ionization chamber. Electrons are confined by this magnetic field while ions are supposed to be trapped in the electric potential well supposedly resulting from the magnetic configuration, and guided toward the acceleration stage. The acceleration stage is similar to the channel of a conventional Hall effect thruster. The purpose of this paper is to clarify the physics of the SPT-MAG and to understand the formation of the positive ion trap in the ionization chamber. Using a hybrid model and a Monte Carlo simulation we show that under typical operating conditions most of the ionization in the chamber is due to high energy electrons accelerated in the channel and entering the chamber rather than to electrons accelerated by the voltage applied in the ionization chamber. We also raise the question of the possible role of an additional emissive cathode inside the ionization chamber. The model predicts that an electric potential well guiding the ions to the channel entrance forms in the chamber only if the intermediate electrode inside the chamber is an emissive cathode (which is not the case in recent configurations used for this thruster)

  1. Transoral Laser Microsurgery (TLM) ± Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

    PubMed Central

    Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H.

    2013-01-01

    Objectives/Hypothesis Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) ± adjuvant therapy. Study Design Analysis of prospectively assembled data pertaining to the above-described patient cohort. Methods Patients treated with TLM for AJCC stage III or IV oropharyngeal cancer at Washington University School of Medicine from 1996 to 2006 were followed for a minimum of 2 years. Recurrence, survival, functional, and human papilloma virus data were analyzed. Results Eighty-four patients met inclusion criteria. Mean follow-up was 52.6 months. Overall AJCC stages were: III 15% and IV 85%. T stages were T1–2, 74%; T3–4, 26%. Eighty-three patients underwent neck dissection, 50 received adjuvant radiotherapy, and 28 received adjuvant chemoradiotherapy. Overall survival at 2 and 5 years was 94% and 88%, respectively. Disease-specific survival at 2 and 5 years was 96% and 92%, respectively. Six patients recurred (7%): locally (one), regionally (four), and distant (five). T stage, positive margins, and p16 status significantly impacted survival. The addition of adjuvant chemo-therapy in high-risk patients did not significantly impact survival. Five patients (6%) had major surgical complications, but without mortality. Eighty-one percent of patients had acceptable swallowing function at last follow-up. Immediately postoperatively, 17% required G-tubes, which dropped to 3.4% of living patients at 3 years. Conclusions In this population, our findings validate TLM ± adjuvant therapy as a highly effective strategy for survival, locoregional control, and swallowing recovery in AJCC stage III and IV oropharyngeal cancer. Our finding also show that p16 positivity improves survival. PMID:19572271

  2. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer

    PubMed Central

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-01-01

    Abstract It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis. Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective. Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85–4.23 and OR 1.52, 95% CI 1.09–2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61–1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69–6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87–3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups. This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  3. [34 epibulbar malignant tumours (author's transl)].

    PubMed

    Schwartzenberg, T; Vancea, P P; Dobrescu, G

    1979-02-01

    Based on a study of 34 cases, the authors make therapeutical and diagnostical references concerning the epibulbar malignant tumours. These were met with a frequency of 10% of the total amount of the malignant tumours of the visual apparatus. The most frequent setting were at the level of the bulbar conjunctiva and of the sclero-corneal limb, especially in front of the opening of the palpebral slit and in the temporal area. The histological examination of the tumours pointed out the following morphological types; epitheliomas (61%), especially spino-cellular, malignant melanomas (32%) and sarcomas (6%). The therapeutical attitude was the surgical one -- the accurate extirpation -- in the limited tumours, followed by radiotherapy when neoplasic lesions were found at the limit of section. In the invaded tumours, the exenteration of the orbit was performed followed by radiotherapy. On the terms of such a therapeutical conduct, the distant prognosis proved to be dependent on two factors: a. The early diagnosis, that is the stage of the therapeutical action. It is insisted upon the importance of the signs of malignization of some benign tumors: papillomas or naevi. b. The nature and origin of the tumour: the secondary tumours are more severe from the beginning. PMID:444115

  4. Phase congruency map driven brain tumour segmentation

    NASA Astrophysics Data System (ADS)

    Szilágyi, Tünde; Brady, Michael; Berényi, Ervin

    2015-03-01

    Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.

  5. Multivisceral resection of pancreatic neuroendocrine tumours: a report of two cases

    PubMed Central

    2011-01-01

    Pancreatic neuroendocrine tumours (pNETs) are rare and surgical resection offers the only possibility of cure for localised disease. The role of surgery in the setting of locally advanced and metastatic disease is more controversial. Emerging data suggests that synchronous surgical resection of pancreas and liver may be associated with increased survival. We report two cases of synchronous, one stage multivisceral resections for pNET and associated reconstruction. We highlight the technical issues involved in such extensive resections and demonstrate that one stage multivisceral operations can be achieved safely. PMID:21859472

  6. Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma

    PubMed Central

    Goyal, Lipika; Govindan, Aparna; Sheth, Rahul A.; Nardi, Valentina; Blaszkowsky, Lawrence S.; Faris, Jason E.; Clark, Jeffrey W.; Ryan, David P.; Kwak, Eunice L.; Allen, Jill N.; Murphy, Janet E.; Saha, Supriya K.; Hong, Theodore S.; Wo, Jennifer Y.; Ferrone, Cristina R.; Tanabe, Kenneth K.; Chong, Dawn Q.; Deshpande, Vikram; Borger, Darrell R.; Iafrate, A. John; Bardeesy, Nabeel; Zheng, Hui

    2015-01-01

    Background. Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. Methods. Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. Results. Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. Conclusion. The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. Implications for Practice: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with

  7. Radiofrequency Ablation in the Management of Advanced Stage Thymomas: A Case Report on a Novel Multidisciplinary Therapeutic Approach

    PubMed Central

    Pala, Carlo; Versace, Renato

    2014-01-01

    We describe in this report a case of successful radiofrequency ablation of an unresectable stage III-type B3 thymoma, and we discuss the role of this novel approach in the management of patients with advanced stage thymoma. The patient, a 59-year-old Caucasian male underwent neoadjuvant chemotherapy with only a slight reduction of the mass. Subsequently, an explorative sternotomy and debulking were performed; before closing the thorax, radiofrequency ablation of the residual tumor was carried out and a partial necrosis of the mass was achieved. A further percutaneous radiofrequency ablation was performed subsequently, obtaining complete necrosis of the lesion. Successively, the patient underwent adjuvant radiotherapy. As a result of this multidisciplinary treatment, complete and stable response was obtained. It is hard to say which of the single treatments had the major impact on cure; nevertheless, the results obtained suggest that radiofrequency ablation must be taken into account for the treatment of advanced stage thymomas, and its effectiveness must be further assessed in future studies. PMID:25574416

  8. Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis.

    PubMed

    Xing, Katharine H; Connors, Joseph M; Lai, Anky; Al-Mansour, Mubarak; Sehn, Laurie H; Villa, Diego; Klasa, Richard; Shenkier, Tamara; Gascoyne, Randy D; Skinnider, Brian; Savage, Kerry J

    2014-06-01

    Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL. PMID:24713929

  9. A heartrending burden of gynaecological cancers in advance stage at nuclear institute of medicine and radiotherapy Jamshoro Sindh

    PubMed Central

    Bibi, Seema; Ashfaque, Sanober; Laghari, Naeem Ahmed

    2016-01-01

    Objectives: In Pakistan gynaecological cancers are among the leading causes of women’s morbidity and mortality posing huge financial burden on families, communities and state. Due to lack of national cancer registry exact facts and figures are unknown therefore this study was planned to find out prevalence, age, site and stage of presentation of gynaecological cancers at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro. Methods: A retrospective, cross sectional study was conducted from 1st January 2011 to 31st December 2011 at NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data was entered on predesigned performa and results were analyzed manually. Results: Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering from gynaecological cancer making it third most common cancer. Ovary was commonest site followed by cervix and uterus. More than 60% cases presented in advanced stage, mostly during 4th and 5th decade of life. Conclusion: Gynecological cancer was among top three cancers at one of the busiest public sector cancer institute in Sindh province and significant number presented in advance stage making treatment difficult and expensive. There is urgent need for development and implementation of an effective health policy regarding cancer prevention and treatment. PMID:27022358

  10. [Treatment of pain in advanced-stage intra-abdominal neoplasms].

    PubMed

    Polati, E; Finco, G; Rigo, V; Gottin, L; Pinaroli, A M; Iacono, C; Mangiante, G; Serio, G; Ischia, S

    1993-01-01

    Different types of pain are present in far advanced intra-abdominal cancer, sometimes in the same site too. An accurate semeiological analysis of pain is important because different types of pain often differently respond to the available therapeutical tools. In this paper the results and the complications of the most important methods of pain management in far advanced intra-abdominal cancer are examined. Analysis of the data reveals that the association of more methods, pharmacological and non, should be a rule rather than the exception. PMID:7923502

  11. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  12. Management of advanced primary urethral carcinomas.

    PubMed

    Dayyani, Farshid; Hoffman, Karen; Eifel, Patricia; Guo, Charles; Vikram, Raghu; Pagliaro, Lance C; Pettaway, Curtis

    2014-07-01

    Primary urethral carcinoma (PUC) is a rare malignancy accounting for <1% of genitourinary cancers, with a predilection for men and African-Americans. The sites and histology of urethral carcinoma vary by gender and anatomical location. Squamous cell carcinoma is most common among both genders but adenocarcinomas are noted in 15-35% of cases among women. Obstructive or irritative symptoms and haematuria are common modes of presentation. Clinical evaluation includes cystourethroscopy with biopsy and examination under anaesthesia. Magnetic resonance imaging provides a highly effective method to image the primary tumour while defıning the potential involvement of surrounding structures. Most tumours are localised, with regional metastases to nodal sites seen in up to 30% of cases in both genders, while distant metastases at presentation are rare (0-6%), but occur in up to 40% of cases with recurrent disease. Among men, the two most important prognostic factors are disease location and stage. Low-stage tumours (T1-2) and tumours involving the fossa navicularis or the penile urethra have a better prognosis than higher stage tumours (>T2 or N+) and lesions involving the bulbomembranous urethra. In women, in addition to stage and location, the size of the tumour has also prognostic implications. While surgery and radiation therapy (RT) are of benefit in early stage disease, advanced stage PUC requires multimodal treatment strategies to optimise local control and survival. These include induction chemotherapy followed by surgery or RT and concurrent chemoradiation with or without surgery. The latter strategy has been used successfully to treat other human papillomavirus-related cancers of the vagina, cervix and anus and may be of value in achieving organ preservation. Given the rarity of PUC, prospective multi-institutional studies are needed to better define the optimal treatment approach for this disease entity. PMID:24447439

  13. Localization of a breast cancer tumour-suppressor gene to a 3-cM interval within chromosomal region 16q22.

    PubMed

    Iida, A; Isobe, R; Yoshimoto, M; Kasumi, F; Nakamura, Y; Emi, M

    1997-01-01

    Allelic losses on chromosome 16q in tumour cells are frequent in a variety of malignancies, suggesting the presence of one or more tumour-suppressor genes in the region. Among 210 sporadic breast cancers we examined using 15 microsatellite markers on the long arm of chromosome 16, heterozygosity for at least one locus was lost in 141 (67%). Detailed deletion mapping revealed two distinct commonly deleted regions. One region was defined as a 3-cM interval flanked by markers D16S512 and D16S515 at 16q22; the second consisted of a 9.5-cM interval flanked by markers D16S498 and D16S303 at q24.3. Allelic loss on 16q was observed frequently in small tumours, tumours without lymph node metastasis and tumours of the non-invasive histological type as well as in tumours of more advanced phenotype, suggesting that inactivation of one of at least two tumour-suppressor genes on 16q plays a role in early stage breast carcinogenesis. PMID:9010036

  14. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

    PubMed

    Barrington, Sally F; Kirkwood, Amy A; Franceschetto, Antonella; Fulham, Michael J; Roberts, Thomas H; Almquist, Helén; Brun, Eva; Hjorthaug, Karin; Viney, Zaid N; Pike, Lucy C; Federico, Massimo; Luminari, Stefano; Radford, John; Trotman, Judith; Fosså, Alexander; Berkahn, Leanne; Molin, Daniel; D'Amore, Francesco; Sinclair, Donald A; Smith, Paul; O'Doherty, Michael J; Stevens, Lindsey; Johnson, Peter W

    2016-03-24

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice. PMID:26747247

  15. Stage IB2 adenosquamous cervical cancer diagnosed at 19-weeks' gestation.

    PubMed

    Peculis, Luiza D; Ius, Yvette; Campion, Michael; Friedlander, Michael; Hacker, Neville

    2015-02-01

    Neoadjuvant chemotherapy (NACT) for advanced cervical cancer in pregnancy has been shown to increase operability and be effective against spread of disease. In all reported cases of advanced disease, residual tumour has been found at surgery following NACT. We present a case of a 27-year old diagnosed with stage IB2 adenosquamous cervical carcinoma at 19-weeks' gestation who was treated with NACT. Following caesarean section and radical hysterectomy, histopathology showed no evidence of residual tumour in the cervix and negative pelvic lymph nodes. PMID:25470742

  16. [Clinical types of thoracic cancer. Mediastinal tumours].

    PubMed

    Lemarié, E

    2006-11-01

    Mediastinal germ cell tumours (teratomas, seminomas, and non-seminomatous malignant germ cell tumours) are a heterogeneous group of benign and malignant neoplasms. The standard treatment of mediastinal non-seminomatous malignant germ cell tumours is four cycles of chemotherapy followed by surgical resection of the residual mass. Small localized mediastinal seminomas may be treated with primary resection followed by radiotherapy. In patients with locally advanced disease, the preferred treatment is systemic chemotherapy followed by surgical resection of any residual disease. Thymomas can be locally invasive and associated with parathymic syndromes. Complete surgical excision is attempted in most cases of thymoma. Radiation therapy is usually recommended for invasive or incompletely excised tumours. Invasive thymoma is chemosensitive. PMID:17268355

  17. The conjoint use of music therapy and reflexology with hospitalized advanced stage cancer patients and their families.

    PubMed

    Magill, Lucanne; Berenson, Susan

    2008-09-01

    Advanced stage cancer patients experience debilitating physical symptoms as well as profound emotional and spiritual struggles. Advanced disease is accompanied by multiple changes and losses for the patient and the family. Palliative care focuses on the relief of overall suffering of patients and families, including symptom control, psychosocial support, and the meeting of spiritual needs. Music therapy and reflexology are complementary therapies that can soothe and provide comfort. When used conjointly, they provide a multifaceted experience that can aid in the reduction of anxiety, pain, and isolation; facilitate communication between patients, family members, and staff; and provide the potential for a more peaceful dying experience for all involved. This article addresses the benefits of the combined use of music therapy and reflexology. Two case studies are presented to illustrate the application and benefits of this dual approach for patients and their families regarding adjustment to the end of life in the presence of anxiety and cognitive impairment. PMID:18662423

  18. Tumours of the lung

    PubMed Central

    Stünzi, H.; Head, K. W.; Nielsen, S. W.

    1974-01-01

    Lung tumours are not common in domestic animals; there has not been the increase in epidermoid carcinomas and anaplastic small-cell carcinomas that has occurred in man this century. Adenocarcinoma is the most common type in animals. The biological behaviour of each type of tumour in animals seems to be much the same as in man. The tumours are described histologically, the main categories being: epidermoid carcinoma, anaplastic carcinoma, adenocarcinoma, combined epidermoid and adenocarcinoma, carcinoid tumours, bronchial gland tumours, benign tumours, and sarcomas. ImagesFig. 13Fig. 14Fig. 15Fig. 16Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:4371738

  19. [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

    PubMed Central

    Baum, Richard P.; Kluge, Andreas W.; Kulkarni, Harshad; Schorr-Neufing, Ulrike; Niepsch, Karin; Bitterlich, Norman; van Echteld, Cees J.A.

    2016-01-01

    Purpose: To characterise efficacy and safety of 177Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with 177Lu-DOTATOC were analysed retrospectively. Subjects were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion: 177Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with

  20. Two stage low noise advanced technology fan. 1: Aerodynamic, structural, and acoustic design

    NASA Technical Reports Server (NTRS)

    Messenger, H. E.; Ruschak, J. T.; Sofrin, T. G.

    1974-01-01

    A two-stage fan was designed to reduce noise 20 db below current requirements. The first-stage rotor has a design tip speed of 365.8 m/sec and a hub/tip ratio of 0.4. The fan was designed to deliver a pressure ratio of 1.9 with an adiabatic efficiency of 85.3 percent at a specific inlet corrected flow of 209.2kg/sec/sq m. Noise reduction devices include acoustically treated casing walls, a flowpath exit acoustic splitter, a translating centerbody sonic inlet device, widely spaced blade rows, and the proper ratio of blades and vanes. Multiple-circular-arc rotor airfoils, resettable stators, split outer casings, and capability to go to close blade-row spacing are also included.

  1. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    PubMed

    Yüksel, Özgür Haki; Verit, Ayhan; Ürkmez, Ahmet

    2015-06-01

    In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival. PMID:26150029

  2. Xenobiotic-metabolizing enzymes in canine mammary tumours.

    PubMed

    Kumaraguruparan, R; Subapriya, R; Balachandran, C; Manohar, B Murali; Thangadurai, A; Nagini, S

    2006-09-01

    Mammary tumours are the most common neoplasms in female dogs. The present study was designed to evaluate the relationship between different clinical stages with activities of phase I and phase II carcinogen-metabolizing enzymes in canine mammary tumours. The levels of cytochrome P450 and cytochrome b5 and the activities of glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in tumour tissues of 25 bitches was estimated. Enhanced levels of cytochrome P450 and b5 and phase II enzyme activities were observed in tumour tissues compared to the corresponding uninvolved adjacent tissues. The magnitude of the changes in phase I and phase II enzyme status was, however, more pronounced in stages I and II compared to stages III and IV. The results suggest that the balance between phase I carcinogen activation and phase II detoxification systems may play an important role in canine mammary tumour development. PMID:16014333

  3. Technology requirements for advanced earth-orbital transportation systems: Summary report. [single stage to orbit vehicles

    NASA Technical Reports Server (NTRS)

    Haefeli, R. C.; Littler, E. G.; Hurley, J. B.; Winter, M. G.

    1977-01-01

    Areas of advanced technology that are either critical or offer significant benefits to the development of future Earth-orbit transportation systems were identified. Technology assessment was based on the application of these technologies to fully reusable, single-state-to-orbit (SSTO) vehicle concepts with horizontal landing capability. Study guidelines included mission requirements similar to space shuttle, an operational capability beginning in 1995, and main propulsion to be advanced hydrogen-fueled rocket engines. The technical and economic feasibility of this class of SSTO concepts were evaluated as well as the comparative features of three operational take-off modes, which were vertical boost, horizontal sled launch, and horizontal take-off with subsequent inflight fueling. Projections of both normal and accelerated technology growth were made. Figures of merit were derived to provide relative rankings of technology areas. The influence of selected accelerated areas on vehicle design and program costs was analyzed by developing near-optimum point designs.

  4. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  5. Advances in the management of metastatic non-seminomatous germ cell tumours during the cisplatin era: a single-institution experience.

    PubMed Central

    Gerl, A.; Clemm, C.; Schmeller, N.; Hartenstein, R.; Lamerz, R.; Wilmanns, W.

    1996-01-01

    Long-term outcome was reviewed in 266 consecutive patients with metastatic non-seminomatous germ cell tumours treated at a single institution. The overall 3 year survival was 77%, and 3 year progression-free survival was 71%. Multivariate analysis identified the following clinical features as independent prognostic factors: the presence of liver, bone or brain metastasis, serum human chorionic gonadotropin > or = 10000 U l-1 and/or alpha-fetoprotein > or = 1000 ng ml-1, a mediastinal mass > 5 cm and the presence of 20 or more lung metastases. Age was not of prognostic significance. Patients without any of the above poor-risk factors had a 3 year survival of 91% regardless of etoposide- or vinblastine-containing chemotherapy compared with 61% for the remaining patients. However, etoposide-containing protocols led to significantly improved survival in patients with at least one poor risk factor. After 612 patient-years of observation no case of secondary leukaemia was observed among 119 surviving patients who had received etoposide as part of their treatment. With a median follow-up of 93 months, five patients developed a second germ cell tumour, two patients nongerm cell malignancies. Fourteen patients relapsed after a disease-free interval of more than 2 years, and nine patients died more than 5 years after commencement of treatment underscoring the need to report long-term results. There is some evidence that cumulative experience translates into improved survival and cure rates for patients with poor-risk metastatic disease. PMID:8883418

  6. Long-term outcome of patients with advanced-stage cutaneous T cell lymphoma treated with gemcitabine.

    PubMed

    Pellegrini, Cinzia; Stefoni, Vittorio; Casadei, Beatrice; Maglie, Roberto; Argnani, Lisa; Zinzani, Pier Luigi

    2014-11-01

    The choice of treatment for cutaneous T cell lymphoma (CTCL) is often determined by institutional experience, particularly as there is a paucity of data from phase III trials and a lack of consensus concerning treatment of the advanced stages. Among the several second-line and experimental drugs, gemcitabine could be considered one of the most suitable options for pretreated CTCL. Since it is difficult to find in literature the long-term outcome regarding the efficacy of a single-agent drug in pretreated patients and, in particular, in rare diseases such as CTCL, a retrospective observational study was conducted with the aim of evaluating the long-term outcome of CTCL patients treated with gemcitabine. Twenty-five patients with at least one therapy (range 1-8) performed prior to gemcitabine were found. After gemcitabine treatment, the overall response was 48 % with a 20 % of complete responses. At 15 years, the estimated overall survival is 47 %, progression-free survival 8.8 %, and disease-free survival 40 % (median reached at 2.9 years). All patients received at least three cycles and no grade 3-4 hematological adverse events occurred. At the latest follow-up, two patients are still in continuous complete response. This long-term update on the role of gemcitabine as a single agent in pretreated advanced-stage CTCL confirms this monotherapy as effective and safe. PMID:24908331

  7. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours

    PubMed Central

    Mahalingam, D; Wilding, G; Denmeade, S; Sarantopoulas, J; Cosgrove, D; Cetnar, J; Azad, N; Bruce, J; Kurman, M; Allgood, V E; Carducci, M

    2016-01-01

    Background: Mipsagargin (G-202; (8-O-(12-aminododecanoyl)-8-O-debutanoyl thapsigargin)-Asp-γ-Glu-γ-Glu-γ-GluGluOH)) is a novel thapsigargin-based targeted prodrug that is activated by PSMA-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. We evaluated the safety of mipsagargin in patients with advanced solid tumours and established a recommended phase II dosing (RP2D) regimen. Methods: Patients with advanced solid tumours received mipsagargin by intravenous infusion on days 1, 2 and 3 of 28-day cycles and were allowed to continue participation in the absence of disease progression or unacceptable toxicity. The dosing began at 1.2 mg m−2 and was escalated using a modified Fibonacci schema to determine maximally tolerated dose (MTD) with an expansion cohort at the RP2D. Plasma was analysed for mipsagargin pharmacokinetics and response was assessed using RECIST criteria. Results: A total of 44 patients were treated at doses ranging from 1.2 to 88 mg m−2, including 28 patients in the dose escalation phase and 16 patients in an expansion cohort. One dose-limiting toxicity (DLT; Grade 3 rash) was observed in the dose escalation portion of the study. At 88 mg m−2, observations of Grade 2 infusion-related reaction (IRR, 2 patients) and Grade 2 creatinine elevation (1 patient) led to declaration of 66.8 mg m−2 as the recommended phase II dose (RP2D). Across the study, the most common treatment-related adverse events (AEs) were fatigue, rash, nausea, pyrexia and IRR. Two patients developed treatment-related Grade 3 acute renal failure that was reversible during the treatment-free portion of the cycle. To help ameliorate the IRR and creatinine elevations, a RP2D of 40 mg m−2 on day 1 and 66.8 mg m−2 on days 2 and 3 with prophylactic premedications and hydration on each

  8. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    PubMed Central

    Tsili, Athina C; Argyropoulou, Maria I

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography (CT) is considered the examination of choice for the detection and staging of RCC. Multidetector CT (MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and three-dimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment. PMID:26120380

  9. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  10. Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

    PubMed Central

    Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

    2010-01-01

    Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

  11. Design and development of an advanced two-stage centrifugal compressor

    NASA Astrophysics Data System (ADS)

    Palmer, D. L.; Waterman, W. F.

    1995-04-01

    This paper describes the aeromechanical design and development of a 3.3 kg/s (7.3 lb/sec), 14:1 pressure ratio two-stage centrifugal compressor, which is used in the T800-LHT-800 helicopter engine. The design employs highly nonradial, splitter bladed impellers with swept leading edges and compact vaned diffusers to achieve high performance in a small and robust configuration. The development effort quantified the effects of impeller diffusion and passive inducer shroud bleed on surge margin as well as the effects of impeller loading on tip clearance sensitivity and the impact of sand erosion and shroud roughness on performance. The developed compressor exceeded its performance objectives with a minimum of 23 percent surge margin without variable geometry. The compressor provides a high-performance, rugged, low-cost configuration ideally suited for helicopter applications.

  12. Design and development of an advanced two-stage centrifugal compressor

    SciTech Connect

    Palmer, D.L.; Waterman, W.F.

    1995-04-01

    Small turboshaft engines require high-pressure-ratio, high-efficiency compressors to provide low engine fuel consumption. This paper describes the aeromechanical design and development of a 3.3 kg/s (7.3 lb/sec), 14:1 pressure ratio two-stage centrifugal compressor, which is used in the T800-LHT-800 helicopter engine. The design employs highly nonradial, splitter bladed impellers with swept leading edges and compact vaned diffusers to achieve high performance in a small and robust configuration. The development effort quantified the effects of impeller diffusion and passive inducer shroud bleed on surge margin as well as the effects of impeller loading on tip clearance sensitivity and the impact of sand erosion and shroud roughness on performance. The developed compressor exceeded its performance objectives with a minimum of 23% surge margin without variable geometry. The compressor provides a high-performance, rugged, low-cost configuration ideally suited for helicopter applications.

  13. Staged Penetrating Sclerokeratoplasty and Penetrating Keratoplasty for Management of Advanced Acquired Anterior Staphyloma

    PubMed Central

    de la Torre-Gonzalez, Enrique; de León Ascencio, Carolina Ponce

    2011-01-01

    Herein we describe a staged surgical technique consisting of penetrating sclerokeratoplasty (PSKP) followed by penetrating keratoplasty (PKP) and present its clinical course and complications over two years of follow-up. A 23-year-old man presented with cosmetically unacceptable protrusion of the globe corresponding to the cornea and sclera. PSKP was performed transplanting a full-thickness beveled 13 mm corneoscleral tectonic graft. Hypotony developed subsequently and was successfully managed medically, however corneal graft failure occurred. After 15 months, a 7.5 mm PKP was performed for optical reasons, which subsequently remained clear with a healthy epithelium. In this particular case, cosmetic, tectonic, therapeutic, and optical requirements were met. PSKP is a surgical procedure which entails a high rate of complications but may be the only alternative when the main goal of intervention is restoration of the globe in complicated cases such as our patient. PMID:22454726

  14. Tumour ablation: technical aspects

    PubMed Central

    Bodner, Gerd; Bale, Reto

    2009-01-01

    Abstract Image-guided percutaneous radiofrequency ablation (RFA) is a minimally invasive, relatively low-risk procedure for tumour treatment. Local recurrence and survival rates depend on the rate of complete ablation of the entire tumour including a sufficient margin of surrounding healthy tissue. Currently a variety of different RFA devices are available. The interventionalist must be able to predict the configuration and extent of the resulting ablation necrosis. Accurate planning and execution of RFA according to the size and geometry of the tumour is essential. In order to minimize complications, individualized treatment strategies may be necessary for tumours close to vital structures. This review examines the state-of-the art of different device technologies, approaches, and treatment strategies for percutaneous RFA of liver tumours. PMID:19965296

  15. Interventions for the treatment of borderline ovarian tumours

    PubMed Central

    Faluyi, Olusola; Mackean, Melanie; Gourley, Charlie; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background The safety of conservative surgery and the benefit of additional interventions after surgery for borderline ovarian tumours are unknown. Objectives To evaluate the benefits and harm of different treatment modalities offered for borderline ovarian tumours. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register to 2009, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE and EMBASE to 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) that compared different interventions in adult women diagnosed with borderline ovarian tumours of any histological variant. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intraperitoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral

  16. Soft Tissue Tumours of the Retroperitoneum

    PubMed Central

    Van Roggen, J. Frans Graadt

    2000-01-01

    Purpose. This review summarizes the more prevalent soft tissue tumours arising in the retroperitoneum and highlights some recent fundamental and diagnostic developments relevant to mesenchymal tumours. Discussion. The retroperitoneum is an underestimated site for benign and malignant neoplastic disease, and represents the second most common site of origin of primary malignant soft tissue tumours (sarcomas) after the deep tissues of the lower extremity. In contrast to the predominance of benign soft tissue lesions over malignant sarcomas elsewhere, retroperitoneal mesenchymal lesions are far more likely to be malignant. The differential diagnosis is primarily with the more common lymphoproliferative and parenchymatous epithelial lesions arising in this area, and with metastatic disease from known or unknown primary sites elsewhere.The most prevalent mesenchymal tumours at this site are of a lipomatous, myogenic or neural nature.Their generally late clinical presentation and poorly accessible location provides numerous clinical challenges; optimal radiological imaging and a properly performed biopsy are essential cogs in the management route. Histopathological diagnosis may be complicated, but has been aided by developments in the fields of immunohistochemistry and tumour (cyto)genetics. Despite significant advances in oncological management protocols, the prognosis remains generally less favourable than for similar tumours at more accessible sites. PMID:18521430

  17. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  18. Rocket-Induced Magnetohydrodynamic Ejector: A Single-Stage-to-Orbit Advanced Propulsion Concept

    NASA Technical Reports Server (NTRS)

    Cole, John; Campbell, Jonathan; Robertson, Anthony

    1995-01-01

    During the atmospheric boost phase of a rocket trajectory, magnetohydrodynamic (MHD) principles can be utilized to augment the thrust by several hundred percent without the input of additional energy. The concept is an MHD implementation of a thermodynamic ejector. Some ejector history is described and some test data showing the impressive thrust augmentation capabilities of thermodynamic ejectors are provided. A momentum and energy balance is used to derive the equations to predict the MHD ejector performance. Results of these equations are compared with the test data and then applied to a specific performance example. The rocket-induced MHD ejector (RIME) engine is described and a status of the technology and availability of the engine components is provided. A top level vehicle sizing analysis is performed by scaling existing MHD designs to the required flight vehicle levels. The vehicle can achieve orbit using conservative technology. Modest improvements are suggested using recently developed technologies, such as superconducting magnets, which can improve predicted performance well beyond those expected for current single-stage-to-orbit (SSTO) designs.

  19. Latest research and clinical treatment of advanced-stage epithelial ovarian cancer

    PubMed Central

    Coleman, Robert L.; Monk, Bradley J.; Sood, Anil K.; Herzog, Thomas J.

    2013-01-01

    The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free and overall survival, although the cure rates have only modestly been affected. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, armamentarium growth offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial ‘ovarian’ cancer and introduces the direction and early results of clinical investigation. PMID:23381004

  20. Trousseau’s syndrome in a patient with advanced stage gastric cancer

    PubMed Central

    Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

    2015-01-01

    Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau’s syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered. PMID:26379411

  1. Advanced transportation system studies technical area 3: Alternate propulsion system concepts. SSME upper stage use

    NASA Technical Reports Server (NTRS)

    Strangeland, Eric; Levak, Daniel

    1993-01-01

    The main objective was to determine viable methods for starting the Space Shuttle Main Engine (SSME) in an altitude environment and restarting it in an orbit environment with minimum changes in utilization of the engine system or hardware. The study concluded that the use of the SSME in an upper stage is feasible with minimal changes to the engine systems. The altitude start case requires only a change in the valve sequencing during start and reorificing of the ASI lines. Inlet pressures can be moderately low at 40 psia for the LOX and 32 psia for the H2. The orbital restart case adds the need to recirculate propellant and thermal control paint (to keep the turbomachinery inlets cold to minimize the tank pressures needed), and the need to heat two small components (to maintain acceptable mixture ratios during the early part of the start). These actions allow start anytime after approximately 120 minutes. Earlier starts (approximately one hour) are also possible but would require additional component heating for mixture ratio control during the early portion of the start sequence.

  2. Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson's disease.

    PubMed

    Viana, Sofia D; Valero, Jorge; Rodrigues-Santos, Paulo; Couceiro, Patrícia; Silva, Andréa M; Carvalho, Félix; Ali, Syed F; Fontes-Ribeiro, Carlos A; Pereira, Frederico C

    2016-08-01

    Convincing evidence indicates that advanced glycation end-products and danger-associated protein S100B play a role in Parkinson's disease (PD). These agents operate through the receptor for advanced glycation end-products (RAGE), which displays distinct isoforms playing protective/deleterious effects. However, the nature of RAGE variants has been overlooked in PD studies. Hence, we attempted to characterize RAGE regulation in early stages of PD striatal pathology. A neurotoxin-based rodent model of PD was used in this study, through administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6 mice. Animals were killed 6 h post-MPTP to assess S100B/RAGE contents (RT-qPCR, ELISA) and RAGE isoform density (WB) and cellular distribution (immunohistochemistry). Dopaminergic and gliotic status were also mapped (HPLC-ED, WB, immunohistochemistry). At this preliminary stage of MPTP-induced PD in mice, RAGE inhibitory isoforms were increased whereas full-length RAGE was not affected. This putative cytoprotective RAGE phenotype paired an inflammatory and pro-oxidant setting fueling DAergic denervation. Increased RAGE inhibitory variants occur in astrocytes showing higher S100B density but no overt signs of hypertrophy or NF-κB activation, a canonical effector of RAGE. These findings expand our understanding of the toxic effect of MPTP on striatum and offer first in vivo evidence of RAGE being a responder in early stages of astrogliosis dynamics, supporting a protective rather tissue-destructive phenotype of RAGE in the initial phase of PD degeneration. These data lay the groundwork for future studies on the relevance of astrocytic RAGE in DAergic neuroprotection strategies. We report increased antagonistic RAGE variants paralleling S100B up-regulation in early stages of MPTP-induced astrogliosis dynamics . We propose that selective RAGE regulation reflects a self-protective mechanism to maintain low levels of RAGE ligands , preventing long

  3. Resection of the primary tumour versus no resection prior to systemic therapy in patients with colon cancer and synchronous unresectable metastases (UICC stage IV): SYNCHRONOUS - a randomised controlled multicentre trial (ISRCTN30964555)

    PubMed Central

    2012-01-01

    Background Currently, it remains unclear, if patients with colon cancer and synchronous unresectable metastases who present without severe symptoms should undergo resection of the primary tumour prior to systemic chemotherapy. Resection of the primary tumour may be associated with significant morbidity and delays the beginning of chemotherapy. However, it may prevent local symptoms and may, moreover, prolong survival as has been demonstrated in patients with metastatic renal cell carcinoma. It is the aim of the present randomised controlled trial to evaluate the efficacy of primary tumour resection prior to systemic chemotherapy to prolong survival in patients with newly diagnosed colon cancer who are not amenable to curative therapy. Methods/design The SYNCHRONOUS trial is a multicentre, randomised, controlled, superiority trial with a two-group parallel design. Colon cancer patients with synchronous unresectable metastases are eligible for inclusion. Exclusion criteria are primary tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy and history of another primary cancer. Resection of the primary tumour as well as systemic chemotherapy is provided according to the standards of the participating institution. The primary endpoint is overall survival that is assessed with a minimum follow-up of 36 months. Furthermore, it is the objective of the trial to assess the safety of both treatment strategies as well as quality of life. Discussion The SYNCHRONOUS trial is a multicentre, randomised, controlled trial to assess the efficacy and safety of primary tumour resection before beginning of systemic chemotherapy in patients with metastatic colon cancer not amenable to curative therapy. Trial registration ISRCTN30964555 PMID:22480173

  4. Limited Genomic Heterogeneity of Circulating Melanoma Cells in Advanced Stage Patients

    PubMed Central

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Ed; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-01-01

    Purpose Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design Blood samples from 40 metastatic melanoma patients and 10 normal blood donors (NBD) were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAb) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification (WGA) and copy number variation (CNV) analysis. Results Based on CSPG4 expression and nuclear size, 1 to 250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5 to 371.5 CMCs/ml). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this population may contribute to develop effective therapeutic strategies. PMID:25574741

  5. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    NASA Astrophysics Data System (ADS)

    Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S.; Kolatkar, Anand; Kendall, Jude T.; Flores, Edna; Topp, Zheng; Samlowski, Wolfram E.; McClay, Edward; Bethel, Kelly; Ferrone, Soldano; Hicks, James; Kuhn, Peter

    2015-02-01

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1-250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5-371.5 CMCs ml-1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma.

  6. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

    PubMed

    Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D

    2016-10-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  7. Initial Staging of Locally Advanced Rectal Cancer and Regional Lymph Nodes

    PubMed Central

    Cerny, Milena; Dunet, Vincent; Prior, John Olivier; Hahnloser, Dieter; Wagner, Anna Dorothea; Meuli, Reto Antoine; Schmidt, Sabine

    2016-01-01

    Purpose The aim of the study was to compare diffusion-weighted MRI (DW-MRI) parameters with 18F-FDG PET/CT in primary locally advanced rectal cancer (LARC). Methods From October 2012 to September 2014, 24 patients with histologically confirmed and untreated LARC (T3–T4) prospectively underwent a pelvic 1.5-T DW-MRI (b = 0 s/mm2, b = 600 s/mm2) and a whole-body 18F-FDG PET/CT, before neoadjuvant therapy. The 2 examinations were performed on the same day. Two readers measured 18F-FDG SUVmax and SUVmean of the rectal tumor and of the pathological regional lymph nodes on PET/CT and compared these with minimum and mean values of the ADC (ADCmin and ADCmean) on maps generated from DW-MRI. The diagnostic performance of ADC values in identifying pathological lymph nodes was also assessed. Results Regarding tumors (n = 24), we found a significant negative correlation between SUVmean and corresponding ADCmean values (ρ = −0.61, P = 0.0017) and between ADCmin and SUVmax (ρ = −0.66, P = 0.0005). Regarding the lymph nodes (n = 63), there was a significant negative correlation between ADCmean and SUVmean values (ρ = −0.38, P = 0.0021), but not between ADCmin and SUVmax values (ρ = −0.11, P = 0.41). Neither ADCmean nor ADCmin values helped distinguish pathological from benign lymph nodes (AUC of 0.24 [confidence interval, 0.10–0.38] and 0.41 [confidence interval, 0.22–0.60], respectively). Conclusions The correlations between ADCmean and SUVmean suggest an association between tumor cellularity and metabolic activity in untreated LARC and in regional lymph nodes. However, compared with 18F-FDG PET/CT, ADC values are not reliable for identifying pathological lymph nodes. PMID:26828149

  8. The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

    SciTech Connect

    Orman, Amber; Koru-Sengul, Tulay; Miao, Feng; Markoe, Arnold; Panoff, Joseph E.

    2014-12-01

    Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

  9. Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

    PubMed

    Shi, Wei-hong; Wu, Qing-quan; Li, Su-qing; Yang, Tong-xin; Liu, Zi-hao; Tong, Yu-suo; Tuo, Lei; Wang, Shan; Cao, Xiu-Feng

    2015-04-01

    Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC. PMID:25731728

  10. Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE).

    PubMed

    Chhatre, Sumedha; Bruce Malkowicz, Stanley; Sanford Schwartz, J; Jayadevappa, Ravishankar

    2015-08-01

    The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non-Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non-Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non-Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID:26266389

  11. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, March 1--May 31, 1995

    SciTech Connect

    Abbasian, J.

    1995-12-31

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors. In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen, calcium sulfide and calcium carbonate will be determined by conducting tests in a pressurized thermogravimetric analyzer unit. The sulfate tests conducted during this quarter, focused on the determination of the rate of sulfation reaction involving partially sulfided half-calcined dolomite and oxygen. The test parameters included CO{sub 2} and O{sub 2} concentrations, reaction temperature and pressure, as well as the sorbent particle size. The results obtained during this quarter suggest that the rate of sulfation reaction involving partially sulfided half-calcined dolomite and oxygen is very fast at temperatures above 850 C which rapidly increases with increasing temperature, achieving more than 85% conversion in less than a few minutes. The reaction appears to continue to completion, however, above 85% conversion, the rate of reaction appears to be low, requiring long residence time to reach complete conversion.

  12. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, December 1, 1994--February 28, 1995

    SciTech Connect

    Abbasian, J.

    1996-03-01

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen (gaseous reactant); and calcium sulfide and calcium carbonate (solid reactants), will be determined by conducting tests in a pressurized thermogravimetric analyzer (HPTGA) unit. The effects of sorbent type, sorbent particle size, reactor temperature and pressure; and O{sub 2} as well as SO{sub 2} partial pressures on the sulfation reactions rate will be determined. During this quarter, samples of the selected limestone and dolomite, sulfided in the fluidized-bed reactor during last quarter, were analyzed. The extent of sulfidation in these samples was in the range of 20 to 50%, which represent carbonizer discharge material at different operating conditions. The high pressure thermogravimetric analyzer (BPTGA) unit has been modified and a new pressure control system was installed to eliminate pressure fluctuation during the sulfation tests.

  13. Sulfur removal in advanced two stage pressurized fluidized bed combustion. Technical report, September 1--November 30, 1994

    SciTech Connect

    Abbasian, J.; Hill, A.; Wangerow, J.R.

    1994-12-31

    The objective of this study is to obtain data on the rates and the extent of sulfation reactions involving partially sulfided calcium-based sorbents, and oxygen as well as sulfur dioxide, at operating conditions closely simulating those prevailing in the second stage (combustor) of Advanced Two-Stage Pressurized Fluidized-Bed Combustors (PFBC). In these systems the CO{sub 2} partial pressure generally exceeds the equilibrium value for calcium carbonate decomposition. Therefore, calcium sulfate is produced through the reactions between SO{sub 2} and calcium carbonate as well as the reaction between calcium sulfide and oxygen. To achieve this objective, the rates of reaction involving SO{sub 2} and oxygen (gaseous reactant); and calcium sulfide and calcium carbonate (solid reactants), will be determined by conducting tests in a pressurized thermogravimetric analyzer (HPTGA) unit. The effects of sorbent type, sorbent particle size, reactor temperature and pressure; and O{sub 2} as well as SO{sub 2} partial pressures on the sulfation reactions rate will be determined. During this quarter, samples of the selected limestone and dolomite were sulfided in the fluidized-bed reactor. These tests were conducted in both calcining and non-calcining operating conditions to produce partially-sulfided sorbents containing calcium oxide and calcium carbonate, respectively. These samples which represent the carbonizer discharge material, will be used as the feed material in the sulfation tests to be conducted in the HPTGA unit during the next quarter.

  14. Endoscopic ultrasound for the characterization and staging of rectal cancer. Current state of the method. Technological advances and perspectives.

    PubMed

    Gersak, Mariana M; Badea, Radu; Graur, Florin; Hajja, Nadim Al; Furcea, Luminita; Dudea, Sorin M

    2015-06-01

    Endoscopic ultrasound is the most accurate type of examination for the assessment of rectal tumors. Over the years, the method has advanced from gray-scale examination to intravenous contrast media administration and to different types of elastography. The multimodal approach of tumors (transrectal, transvaginal) is adapted to each case. 3D ultrasound is useful for spatial representation and precise measurement of tumor formations, using CT/MR image reconstruction; color elastography is useful for tumor characterization and staging; endoscopic ultrasound using intravenous contrast agents can help study the amount of contrast agent targeted at the level of the tumor formations and contrast wash-in/wash-out time, based on the curves displayed on the device. The transvaginal approach often allows better visualization of the tumor than the transrectal approach. Performing the procedure with the rectal ampulla distended with contrast agent may be seen as an optimization of the examination methodology. All these aspects are additional methods for gray-scale endoscopic ultrasound, capable of increasing diagnostic accuracy. This paper aims at reviewing the progress of transrectal and transvaginal ultrasound, generically called endoscopic ultrasound, for rectal tumor diagnosis and staging, with emphasis on the current state of the method and its development trends. PMID:26052575

  15. Results of Two-Stage Light-Gas Gun Development Efforts and Hypervelocity Impact Tests of Advanced Thermal Protection Materials

    NASA Technical Reports Server (NTRS)

    Cornelison, C. J.; Watts, Eric T.

    1998-01-01

    Gun development efforts to increase the launching capabilities of the NASA Ames 0.5-inch two-stage light-gas gun have been investigated. A gun performance simulation code was used to guide initial parametric variations and hardware modifications, in order to increase the projectile impact velocity capability to 8 km/s, while maintaining acceptable levels of gun barrel erosion and gun component stresses. Concurrent with this facility development effort, a hypervelocity impact testing series in support of the X-33/RLV program was performed in collaboration with Rockwell International. Specifically, advanced thermal protection system materials were impacted with aluminum spheres to simulate impacts with on-orbit space debris. Materials tested included AETB-8, AETB-12, AETB-20, and SIRCA-25 tiles, tailorable advanced blanket insulation (TABI), and high temperature AFRSI (HTA). The ballistic limit for several Thermal Protection System (TPS) configurations was investigated to determine particle sizes which cause threshold TPS/structure penetration. Crater depth in tiles was measured as a function of impact particle size. The relationship between coating type and crater morphology was also explored. Data obtained during this test series was used to perform a preliminary analysis of the risks to a typical orbital vehicle from the meteoroid and space debris environment.

  16. Focal adhesion kinase: predictor of tumour response and risk factor for recurrence after neoadjuvant chemoradiation in rectal cancer.

    PubMed

    Gómez Del Pulgar, Teresa; Cebrián, Arancha; Fernández-Aceñero, Maria Jesús; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Marín-Arango, Juan Pablo; Caramés, Cristina; Vega-Bravo, Ricardo; Rodríguez-Remírez, María; Cruz-Ramos, Marlid; Manzarbeitia, Félix; García-Foncillas, Jesús

    2016-09-01

    Rectal cancer represents about 30% of colorectal cancers, being around 50% locally advanced at presentation. Chemoradiation (CRT) followed by total mesorectal excision is the standard of care for these locally advanced stages. However, it is not free of adverse effects and toxicity and the complete pathologic response rate is between 10% and 30%. This makes it extremely important to define factors that can predict response to this therapy. Focal adhesion kinase (FAK) expression has been correlated with worse prognosis in several tumours and its possible involvement in cancer radio- and chemosensitivity has been suggested; however, its role in rectal cancer has not been analysed yet. To analyse the association of FAK expression with tumour response to CRT in locally advanced rectal cancer. This study includes 73 patients with locally advanced rectal cancer receiving standard neoadjuvant CRT followed by total mesorectal excision. Focal adhesion kinase protein levels were immunohistochemically analysed in the pre-treatment biopsies of these patients and correlated with tumour response to CRT and patients survival. Low FAK expression was significantly correlated with local and distant recurrence (P = 0.013). Low FAK expression was found to be a predictive marker of tumour response to neoadjuvant therapy (P = 0.007) and patients whose tumours did not express FAK showed a strong association with lower disease-free survival (P = 0.01). Focal adhesion kinase expression predicts neoadjuvant CRT response in rectal cancer patients and it is a clinically relevant risk factor for local and distant recurrence. PMID:27171907

  17. Transport processes in tumours.

    PubMed

    Quastel, J H

    1965-12-01

    The characteristic features of transport systems controlling influx into tumour cells of nutrients and other chemicals are briefly described. Two notable features of transport of amino acids into tumour cells have been observed: extensive accumulation against a concentration gradient and equal accumulations, whether conditions are aerobic or anaerobic, provided glucose is present. This combination of features has not been observed in the majority of normal mammalian tissues so far examined. Important for considerations of chemotherapy is the ability of tumour transport carriers to transfer substances related in structure to amino acids and other nutrients. Amino acid analogues, for example, can either block transport of natural amino acids or can be transported into the cell where they may interfere with various aspects of amino acid metabolism. The study of transport carriers is essential for an understanding of tumour-host relationships and for considerations of chemotherapy. PMID:5842595

  18. Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice.

    PubMed

    Sharma, S; Khan, N; Sultana, S

    2004-02-01

    We designed the present study to investigate the role of gentisic acid in the chemopreventive activity of Hibiscus rosa sinensis extract on 7,12-dimethyl benz(a)anthracene (DMBA)/croton oil-mediated carcinogenesis in mouse skin via 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced tumour promotion response and oxidative stress. Single topical application of DMBA followed by twice weekly applications of croton oil after one week for 20 weeks resulted in 100% incidence of tumours in animals in 15 weeks. However, application of H. rosa sinensis extract 30 minutes prior to the application of croton oil twice weekly for 20 weeks caused significant reduction in the number of tumours per mouse and the percentage of tumour-bearing mice. Also, the latency period for the appearance of the first tumour was delayed on H. rosa sinensis pretreatment. A single topical application of TPA caused significant depletion in reduced glutathione (GSH) content, activities of its metabolizing and antioxidant enzymes, while malondialdehyde (MDA) formation, H2O2 content, ornithine decarboxylase (ODC) activity and DNA synthesis were significantly increased. Interestingly, pretreatment of H. rosa sinensis extract (3.5 mg and 7 mg/kg body weight) and gentisic acid (2.0 microg and 4.0 microg/0.2 ml acetone per animal) restored the levels of GSH, and its metabolizing and antioxidant enzymes (P<0.05). There was also a statistically significant reduction in MDA formation and H2O2 content (P<0.05) at both doses. Although inhibition of ODC activity by gentisic acid was not dose-dependent, thymidine incorporation in DNA (P<0.05) was dose-dependently recovered by the plant extract and its chemical constituent. We therefore propose that gentisic acid has a role in the modulatory activity of H. rosa sinensis extract. PMID:15075789

  19. Breast tumour angiogenesis

    PubMed Central

    Fox, Stephen B; Generali, Daniele G; Harris, Adrian L

    2007-01-01

    The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized. PMID:18190723

  20. [Tumours and liver transplants].

    PubMed

    Mejzlík, Vladimír; Husová, Libuše; Kuman, Milan; Štěpánková, Soňa; Ondrášek, Jiří; Němec, Petr

    2015-01-01

    Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID:26375706

  1. Mouse Models of Brain Metastasis for Unravelling Tumour Progression.

    PubMed

    Soto, Manuel Sarmiento; Sibson, Nicola R

    2016-01-01

    Secondary tumours in the brain account for 40 % of triple negative breast cancer patients, and the percentage may be higher at the time of autopsy. The use of in vivo models allow us to recapitulate the molecular mechanisms potentially used by circulating breast tumour cells to proliferate within the brain.Metastasis is a multistep process that depends on the success of several stages including cell evasion from the primary tumour, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood-brain barrier and proliferation within the brain microenvironment. Cellular adhesion molecules are key proteins involved in all of the steps in the metastatic process. Our group has developed two different in vivo models to encompass both seeding and colonisation stages of the metastatic process: (1) haematogenous dissemination of tumour cells by direct injection into the left ventricle of the heart, and (2) direct implantation of the tumour cells into the mouse brain.This chapter describes, in detail, the practical implementation of the intracerebral model, which can be used to analyse tumour proliferation within a specific area of the central nervous system and tumour-host cell interactions. We also describe the use of immunohistochemistry techniques to identify, at the molecular scale, tumour-host cell interactions, which may open new windows for brain metastasis therapy. PMID:27325270

  2. Intestine-associated antigens in ovarian tumours: an immunohistological study.

    PubMed

    De Boer, W G; Ma, J; Nayman, J

    1981-07-01

    The presence of 3 intestine-associated antigens, small intestine mucin antigen (SIMA), large intestine mucin antigen (LIMA) and carcinoembryonic antigen (CEA) was studied in the female genital tract and ovarian tumours by immunofluorescence. These antigens could not be detected in normal ovary, benign cysts of ovary, fallopian tube or endometrium, but both LIMA and CEA were present in endocervical glandular tissue. The antigenic cross-reactivity of endocervical and large bowel mucin may indicate a close embryological relationship between these organs during the cloacogenic stage. The 3 antigens could be demonstrated in mucinous tumours of the ovary but were absent in serous or mesonephroid tumours. In one of the 2 endometroid tumours CEA was the only detectable antigen. These observations confirm the presence of intestinal type of epithelium in cystic mucinous tumours of the ovary and explain the cross-reactivity of mucin of benign tumours of the ovary and mucin from colonic cancer, normal colonic mucosa and gastric mucosa as reported by earlier workers. In the process of malignant transformation the columnar epithelium of ovarian cystadenoma seems to behave in the same way as superficial gastric and gall bladder epithelium by forming inappropriate intestine-associated mucin substances. Our technique may provide a specific means for studies on the histogenesis of female genital tract tumours, particularly ovarian tumours. It can also be used in differentiating between benign and malignant variants of these tumours. PMID:7029434

  3. A Rare Case of Concomitant Maxilla and Mandible Brown Tumours, Papillary Thyroid Carcinoma, Parathyroid Adenoma, and Osteitis Fibrosa Cystica

    PubMed Central

    Nunes, Thaís Borguezan; Bologna, Sheyla Batista; Witzel, Andréa Lusvarghi; Nico, Marcello Menta Simonsen; Lourenço, Silvia Vanessa

    2016-01-01

    Objective. The brown tumour of hyperparathyroidism is a result of a metabolic disorder caused by primary hyperparathyroidism. Report. We described a case of a 37-year-old female patient presenting bimaxillary intraoral lesions and swelling in the neck. Incisional biopsy of the oral lesion was performed and histopathological examination revealed a central giant cell lesion composed by intense haemorrhagic exudate, abundant presence of giant cells, and areas with hemosiderin pigment. The patient also presented high levels of serum calcium and parathyroid hormone, hyperfunctioning parathyroid tissue, bilateral parenchymal nephropathy, and densitometry lower than expected, showing an advanced stage of osteitis fibrosa cystica. Synchronous parathyroid adenoma and papillary thyroid carcinoma were confirmed by imaging exams and histopathologically. Conclusion. The composition of all the clinical, pathological, and imaging findings led to the final diagnosis of brown tumour of hyperparathyroidism. The occurrence of parathyroid adenoma, papillary thyroid carcinoma, and brown tumours of hyperparathyroidism in their late stage (osteitis fibrosa cystica) associated with oral brown tumours involving the mandible and maxilla is extremely rare. PMID:26881146

  4. Tumour macrophages as potential targets of bisphosphonates

    PubMed Central

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  5. Tumour Angiogenesis and Angiogenic Inhibitors: A Review

    PubMed Central

    Yadav, Lalita; Puri, Naveen; Satpute, Pranali; Sharma, Vandana

    2015-01-01

    Angiogenesis is a complex process depending on the coordination of many regulators and there by activating angiogenic switch. Recent advances in understanding of angiogenic mechanism have lead to the development of several anti-angiogenic and anti-metastatic agents that use the strategy of regulation of angiogenic switch. Antiangiogenic therapy is a form of treatment not cure for cancer and represents a highly effective strategy for destroying tumour because vascular supply is the fundamental requirement for growth of tumour. Because of the quiescent nature of normal adult vasculature, angiogenic inhibitors are expected to confer a degree of specificity when compared to nonspecific modalities of chemo and radiotherapy, so it has the advantage of less toxicities, does not induce drug resistance and deliver a relatively non toxic, long term treatment of tumour. PMID:26266204

  6. Semi-automatic cone beam CT segmentation of in vivo pre-clinical subcutaneous tumours provides an efficient non-invasive alternative for tumour volume measurements

    PubMed Central

    Brodin, N P; Tang, J; Skalina, K; Quinn, TJ; Basu, I; Guha, C

    2015-01-01

    Objective: To evaluate the feasibility and accuracy of using cone beam CT (CBCT) scans obtained in radiation studies using the small-animal radiation research platform to perform semi-automatic tumour segmentation of pre-clinical tumour volumes. Methods: Volume measurements were evaluated for different anatomical tumour sites, the flank, thigh and dorsum of the hind foot, for a variety of tumour cell lines. The estimated tumour volumes from CBCT and manual calliper measurements using different volume equations were compared with the “gold standard”, measured by weighing the tumours following euthanasia and tumour resection. The correlation between tumour volumes estimated with the different methods, compared with the gold standard, was estimated by the Spearman's rank correlation coefficient, root-mean-square deviation and the coefficient of determination. Results: The semi-automatic CBCT volume segmentation performed favourably compared with manual calliper measures for flank tumours ≤2 cm3 and thigh tumours ≤1 cm3. For tumours >2 cm3 or foot tumours, the CBCT method was not able to accurately segment the tumour volumes and manual calliper measures were superior. Conclusion: We demonstrated that tumour volumes of flank and thigh tumours, obtained as a part of radiation studies using image-guided small-animal irradiators, can be estimated more efficiently and accurately using semi-automatic segmentation from CBCT scans. Advances in knowledge: This is the first study evaluating tumour volume assessment of pre-clinical subcutaneous tumours in different anatomical sites using on-board CBCT imaging. We also compared the accuracy of the CBCT method to manual calliper measures, using various volume calculation equations. PMID:25823502

  7. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer

    PubMed Central

    Russell, Samantha; Duquette, Mark; Liu, Joyce; Drapkin, Ronny; Lawler, Jack; Petrik, Jim

    2015-01-01

    Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in an orthotopic, syngeneic mouse model of advanced stage EOC. Mice were treated with 3TSR (4 mg/kg per day) alone or in combination with chemotherapy drugs delivered with maximum tolerated dose or metronomic scheduling. Pretreatment with 3TSR induced tumor regression, normalized tumor vasculature, and improved uptake of chemotherapy drugs. Combination 3TSR and metronomic chemotherapy induced the greatest tumor regression (6.2-fold reduction in size compared to PBS-treated controls) and highest survival when treatment was initiated at advanced stage. 3TSR binding to its receptor, CD36 (cluster of differentiation 36), increased binding of CD36 and SHP-1, which significantly inhibited phosphorylation of the VEGF receptor. In this study, we describe a novel treatment approach and mechanism of action with 3TSR and chemotherapy that induces regression of advanced stage EOC and significantly improves survival.—Russell, S., Duquette, M., Liu, J., Drapkin, R., Lawler, J., Petrik, J. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer. PMID:25395453

  8. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    PubMed Central

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  9. Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Defrin, Ruti; Pick, Chagi G; Giménez-Llort, Lydia

    2015-07-23

    Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia. PMID:26091881

  10. Stage-by-Stage and Parallel Flow Path Compressor Modeling for a Variable Cycle Engine, NASA Advanced Air Vehicles Program - Commercial Supersonic Technology Project - AeroServoElasticity

    NASA Technical Reports Server (NTRS)

    Kopasakis, George; Connolly, Joseph W.; Cheng, Larry

    2015-01-01

    This paper covers the development of stage-by-stage and parallel flow path compressor modeling approaches for a Variable Cycle Engine. The stage-by-stage compressor modeling approach is an extension of a technique for lumped volume dynamics and performance characteristic modeling. It was developed to improve the accuracy of axial compressor dynamics over lumped volume dynamics modeling. The stage-by-stage compressor model presented here is formulated into a parallel flow path model that includes both axial and rotational dynamics. This is done to enable the study of compressor and propulsion system dynamic performance under flow distortion conditions. The approaches utilized here are generic and should be applicable for the modeling of any axial flow compressor design accurate time domain simulations. The objective of this work is as follows. Given the parameters describing the conditions of atmospheric disturbances, and utilizing the derived formulations, directly compute the transfer function poles and zeros describing these disturbances for acoustic velocity, temperature, pressure, and density. Time domain simulations of representative atmospheric turbulence can then be developed by utilizing these computed transfer functions together with the disturbance frequencies of interest.

  11. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

    The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient. PMID:8678441

  12. Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours

    PubMed Central

    Boss, D. S.; Schwartz, G. K.; Middleton, M. R.; Amakye, D. D.; Swaisland, H.; Midgley, R. S.; Ranson, M.; Danson, S.; Calvert, H.; Plummer, R.; Morris, C.; Carvajal, R. D.; Chirieac, L. R.; Schellens, J. H. M.; Shapiro, G. I.

    2010-01-01

    Background: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. Three phase I studies assessed the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5438 when administered in different dosing schedules. Patients and methods: AZD5438 was administered four times daily, once every 7 days (study 1), for 14 consecutive days followed by 7 days of rest (study 2), or continuously (study 3), to patients with advanced solid tumours. Dose escalation proceeded until the emergence of dose-limiting toxic effects. Results: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends. Conclusions: AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies. PMID:19825886

  13. Regulatory expectations during product development for tumour vaccines.

    PubMed

    Kawakami, K; Puri, R K

    2004-01-01

    Among various approaches for the treatment of cancer, tumour vaccines stimulate the host immune response against cancer and produce local inflammation that may result in the regression of existing tumour in the body. Therapeutic tumour vaccines may generally be grouped into cellular vaccines, synthetic peptides, purified or recombinant proteins, and multi-antigen preparations including shed, or secreted antigens or cell lysates. While no tumour vaccines have been licensed by the U.S. Food and Drug Administration (FDA), a large number of products and approaches are being developed and numerous clinical trials are currently ongoing. In this article, we summarize regulatory issues associated with different types of tumour vaccines. The step-wise approach to regulatory requirements including current good manufacturing practices (cGMPs) and characterization of these vaccines at various stages of product development is discussed. PMID:15603183

  14. Tumours of the thymus

    PubMed Central

    Sellors, T. Holmes; Thackray, A. C.; Thomson, A. D.

    1967-01-01

    Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed. Images PMID:6033387

  15. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  16. Circulating tumor DNA identified by targeted sequencing in advanced-stage non-small cell lung cancer patients.

    PubMed

    Xu, Song; Lou, Feng; Wu, Yi; Sun, Da-Qiang; Zhang, Jing-Bo; Chen, Wei; Ye, Hua; Liu, Jing-Hao; Wei, Sen; Zhao, Ming-Yu; Wu, Wen-Jun; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Chen, Jun

    2016-01-28

    Non-small cell lung cancers (NSCLC) have unique mutation patterns, and some of these mutations may be used to predict prognosis or guide patient treatment. Mutation profiling before and during treatment often requires repeated tumor biopsies, which is not always possible. Recently, cell-free, circulating tumor DNA (ctDNA) isolated from blood plasma has been shown to contain genetic mutations representative of those found in the primary tumor tissue DNA (tDNA), and these samples can readily be obtained using non-invasive techniques. However, there are still no standardized methods to identify mutations in ctDNA. In the current study, we used a targeted sequencing approach with a semi-conductor based next-generation sequencing (NGS) platform to identify gene mutations in matched tDNA and ctDNA samples from 42 advanced-stage NSCLC patients from China. We identified driver mutations in matched tDNA and ctDNA in EGFR, KRAS, PIK3CA, and TP53, with an overall concordance of 76%. In conclusion, targeted sequencing of plasma ctDNA may be a feasible option for clinical monitoring of NSCLC in the near future. PMID:26582655

  17. Design and overall performance of four highly loaded, high speed inlet stages for an advanced high-pressure-ratio core compressor

    NASA Technical Reports Server (NTRS)

    Reid, L.; Moore, R. D.

    1978-01-01

    The detailed design and overall performances of four inlet stages for an advanced core compressor are presented. These four stages represent two levels of design total pressure ratio (1.82 and 2.05), two levels of rotor aspect ratio (1.19 and 1.63), and two levels of stator aspect ratio (1.26 and 1.78). The individual stages were tested over the stable operating flow range at 70, 90, and 100 percent of design speeds. The performances of the low aspect ratio configurations were substantially better than those of the high aspect ratio configurations. The two low aspect ratio configurations achieved peak efficiencies of 0.876 and 0.872 and corresponding stage efficiencies of 0.845 and 0.840. The high aspect ratio configurations achieved peak ratio efficiencies of 0.851 and 0.849 and corresponding stage efficiencies of 0.821 and 0.831.

  18. Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in patients with non-small-cell lung cancer: correlation with histological expression of ICAM-1 and tumour stage.

    PubMed Central

    Grothey, A.; Heistermann, P.; Philippou, S.; Voigtmann, R.

    1998-01-01

    The expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) seems to have an influence on the metastatic behaviour of tumour cells via immunological mechanisms. Recently, a soluble form of ICAM-1 was identified in physiological fluids. We analysed the serum levels of sICAM-1 in patients with non-small-cell lung cancer (NSCLC) and healthy individuals using a sandwich ELISA technique. Sera from 51 patients with NSCLC were tested for sICAM-1 (46 male, five female; age 38-81 years, median 64 years), 29 of whom presented with localized and 26 with metastatic disease. The control group consisted of 40 healthy individuals (20 smokers, 20 non-smokers). Immunohistochemical analysis of ICAM-1 in tumour cells was performed in 20 cases. Patients with NSCLC had significantly higher serum levels of sICAM-1 compared with healthy non-smokers (P = 0.00001) and smokers (P= 0.0328). Metastatic disease was associated with higher sICAM-1 than localized tumours (P = 0.0013). Only 11 out of 23 patients with localized NSCLC had sICAM-1 levels >300 ng ml(-1), compared with 25 out of 28 patients with metastatic disease. Histological expression of ICAM-1 was positively correlated with serum slCAM-1 (P = 0.0399). No difference was observed between histological tumour types with regard to sICAM-1 or NSCLC expression of ICAM-1. In sequential analysis (13 patients), rising sICAM-1 levels predicted a short-term fatal outcome (P = 0.0054) but, overall, sICAM-1 levels did not correlate with prognosis. In the control group, smokers showed significantly higher levels than non-smokers (P = 0.0016). In contrast to patients with NSCLC, sICAM-1 in the control group was correlated to the leucocyte count (r = 0.580, P = 0.003). In conclusion, serum levels of sICAM-1 seem to be associated with tumour burden and histological expression of ICAM-1 in patients with NSCLC. However, the (patho-) physiological role of ICAM-1 in NSCLC remains to be determined. PMID:9514061

  19. Early prognosis of metastasis risk in inflammatory breast cancer by texture analysis of tumour microscopic images.

    PubMed

    Kolarevic, Daniela; Tomasevic, Zorica; Dzodic, Radan; Kanjer, Ksenija; Vukosavljevic, Dragica Nikolic; Radulovic, Marko

    2015-10-01

    Inflammatory breast cancer (IBC) is a rare and aggressive type of locally advanced breast cancer. The purpose of this study was to determine the value of microscopic tumour histomorphology texture for prognosis of local and systemic recurrence at the time of initial IBC diagnosis. This retrospective study included a group of 52 patients selected on the basis of non-metastatic IBC diagnosis, stage IIIB. Gray-Level-Co-Occurrence-Matrix (GLCM) texture analysis was performed on digital images of primary tumour tissue sections stained with haematoxylin/eosin. Obtained values were categorized by use of both data- and outcome-based methods. All five acquired GLCM texture features significantly associated with metastasis outcome. By accuracies of 69-81% and AUCs of 0.71-0.81, prognostic performance of GLCM parameters exceeded that of standard major IBC clinical prognosticators such as tumour grade and response to induction chemotherapy. Furthermore, a composite score consisting of tumour grade, contrast and correlation as independent features resulted in further enhancement of prognostic performance by accuracy of 89%, discrimination efficiency by AUC of 0.93 and an outstanding hazard ratio of 71.6 (95%CI, 41.7-148.4). Internal validation was successfully performed by bootstrap and split-sample cross-validation, suggesting that the model is generalizable. This study indicates for the first time the potential use of primary breast tumour histology texture as a highly accurate, simple and cost-effective prognostic indicator of metastasis risk in IBC. Clinical relevance of the obtained results rests on the role of prognosis in decisions on induction chemotherapy and the resulting impact on quality of life and survival. PMID:26286863

  20. Results of an Advanced Fan Stage Operating Over a Wide Range of Speed and Bypass Ratio. Part 1; Fan Stage Design and Experimental Results

    NASA Technical Reports Server (NTRS)

    Suder, Kenneth L.; Prahst, Patricia S.; Thorp, Scott A.

    2011-01-01

    NASA s Fundamental Aeronautics Program is investigating turbine-based combined cycle (TBCC) propulsion systems for access to space because it provides the potential for aircraft-like, space-launch operations that may significantly reduce launch costs and improve safety. To this end, National Aeronautics and Space Administration (NASA) and General Electric (GE) teamed to design a Mach 4 variable cycle turbofan/ramjet engine for access to space. To enable the wide operating range of a Mach 4+ variable cycle turbofan ramjet required the development of a unique fan stage design capable of multi-point operation to accommodate variations in bypass ratio (10 ), fan speed (7 ), inlet mass flow (3.5 ), inlet pressure (8 ), and inlet temperature (3 ). In this paper, NASA has set out to characterize a TBCC engine fan stage aerodynamic performance and stability limits over a wide operating range including power-on and hypersonic-unique "windmill" operation. Herein, we will present the fan stage design, and the experimental test results of the fan stage operating from 15 to 100 percent corrected design speed. Whereas, in the companion paper, we will provide an assessment of NASA s APNASA code s ability to predict the fan stage performance and operability over a wide range of speed and bypass ratio.

  1. Radiotherapy for ocular tumours.

    PubMed

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-02-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  2. Radiotherapy for ocular tumours

    PubMed Central

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-01-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25–30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  3. Immunology of naturally transmissible tumours.

    PubMed

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  4. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  5. High serum level of C-reactive protein is associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib.

    PubMed

    Fiala, Ondrej; Pesek, Milos; Finek, Jindrich; Topolcan, Ondrej; Racek, Jaroslav; Minarik, Marek; Benesova, Lucie; Bortlicek, Zbynek; Poprach, Alexandr; Buchler, Tomas

    2015-12-01

    Erlotinib is a low molecular weight tyrosine kinase inhibitor (TKI) directed at epidermal growth factor receptor (EGFR), widely used in the treatment of locally advanced or metastatic-stage non-small cell lung cancer (NSCLC). Although introduction of EGFR-TKIs have significantly extended survival of advanced-stage NSCLC patients, their efficacy in the entire patient population is relatively low. Aside from activating EGFR mutations, no reliable biochemical or molecular predictors of response to erlotinib have been established. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in patients with advanced-stage NSCLC treated with erlotinib. We retrospectively analyzed clinical data of 595 patients with advanced-stage NSCLC (IIIB or IV) treated with erlotinib. Serum CRP was measured using an immunoturbidimetric method. High baseline levels of CRP (≥10 mg/l) were measured in 387 (65 %) patients, and normal levels (<10 mg/l) were measured in 208 (35 %) patients. The median progression-free survival (PFS) and overall survival (OS) for patients with high CRP was 1.8 and 7.7 compared to 2.8 and 14.4 months for patients with low CRP (p < 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that CRP was significantly associated with PFS and also with OS (hazard ratio (HR) = 1.57, p < 0.001, and HR = 1.63, p < 0.001, respectively). In conclusion, the results of the conducted retrospective study suggest that high baseline level of CRP was independently associated with worse outcome of patients with advanced-stage NSCLC treated with erlotinib. CRP is a commonly used biomarker which is simple and easy to detect, and thus, it is feasible for the use in the routine clinical practice. PMID:26088452

  6. Canine mammary tumours: protective effect of late ovariectomy and stimulating effect of progestins.

    PubMed

    Misdorp, W

    1988-01-01

    Ovariectomy, even when performed at an advanced age, was found to be to some extent protective against mammary tumour development in dogs. Bitches treated with progestins had a slightly higher risk for mammary tumours (all types, benign and malignant) than controls. Progestin treatment did not increase the risk of mammary cancer. Benign tumours in (treated and untreated) dogs appeared earlier than malignant ones. Progestin treatment resulted in earlier appearance of both benign and malignant tumours than in controls. The ratio solitary/multiple mammary tumours was not significantly different between treated and untreated dogs. PMID:3376408

  7. A Multi-institutional Investigation of the Prognostic Value of Lymph Nodal Yield in Advanced Stage Oral Cavity Squamous Cell Carcinoma (OCSCC)

    PubMed Central

    Jaber, James J.; Zender, Chad A.; Mehta, Vikas; Davis, Kara; Ferris, Robert L.; Lavertu, Pierre; Rezaee, Rod; Feustel, Paul J.

    2014-01-01

    Background Although existing literature provides surgical recommendations for treating occult disease (cN0) in early stage oral cavity squamous cell carcinoma, a focus on late stage OCSCC is less pervasive. Methods The records of 162 late stage OCSCC pN0 individuals that underwent primary neck dissections were reviewed. Lymph node yield (LNY) as a prognosticator was examined. Results Despite being staged pN0, patients that had a higher LNY had an improved regional/distant control rates, DFS, DSS, and OS. LNY consistently outperformed all other standard variables as being the single best prognostic factor with a tight risk ratio range (RR = 0.95–0.98) even when correcting for the number of lymph nodes examined. Conclusion The results of this study showed that lower regional recurrence rates and improved survival outcomes were seen as lymph node yield increased for advanced T-stage OCSCC pN0. This suggests that increasing lymph node yield with an extended cervical lymphadenectomy may result in lower recurrence rates and improved survival outcomes for this advanced stage group. PMID:24038739

  8. Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

    PubMed Central

    Geuna, E; Roda, D; Rafii, S; Jimenez, B; Capelan, M; Rihawi, K; Montemurro, F; Yap, T A; Kaye, S B; De Bono, J S; Molife, L R; Banerji, U

    2015-01-01

    Background: PI3K–AKT–mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients. Methods: Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups. Results: The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3–4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3–4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. Conclusions: PI3K–AKT–mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. PMID:26554652

  9. High expression of CAI2, a 9p21-embedded long non-coding RNA, contributes to advanced stage neuroblastoma

    PubMed Central

    Barnhill, Lisa M.; Williams, Richard T.; Cohen, Olga; Kim, Youngjin; Batova, Ayse; Mielke, Jenna A.; Messer, Karen; Pu, Minya; Bao, Lei; Yu, Alice L.; Diccianni, Mitchell B.

    2014-01-01

    Neuroblastoma is a pediatric cancer with significant genomic and biological heterogeneity. p16 and ARF, two important tumor suppressor genes on chromosome 9p21, are inactivated commonly in most cancers but paradoxically overexpressed in neuroblastoma. Here we report that exon γ in p16 is also part of an undescribed long non-coding RNA (lncRNA) that we have termed CAI2 (CDKN2A/ARF Intron 2 lncRNA). CAI2 is a single exon gene with a poly A signal located in but independent of the p16/ARF exon 3. CAI2 is expressed at very low levels in normal tissue but is highly expressed in most tumor cell lines with an intact 9p21 locus. Concordant expression of CAI2 with p16 and ARF in normal tissue along with the ability of CAI2 to induce p16 expression suggested that CAI2 may regulate p16 and/or ARF. In neuroblastoma cells transformed by serial passage in vitro, leading to more rapid proliferation, CAI2, p16 and ARF expression all increased dramatically. A similar relationship was also observed in primary neuroblastomas where CAI2 expression was significantly higher in advanced stage neuroblastoma, independently of MYCN amplification. Consistent with its association with high risk disease, CAI2 expression was also significantly associated with poor clinical outcomes, although this effect was reduced when adjusted for MYCN amplification. Taken together, our findings suggested that CAI2 contributes to the paradoxical overexpression of p16 in neuroblastoma, where CAI2 may offer a useful biomarker of high-risk disease. PMID:25028366

  10. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    PubMed Central

    Yuniadi, Yoga; Kusnadi, Yuyus; Sandhow, Lakshmi; Erika, Rendra; Hanafy, Dicky A.; Sardjono, Caroline; Kaligis, R. W. M.; Kasim, Manoefris; Harimurti, Ganesja M.

    2016-01-01

    Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity. PMID:27148465

  11. Impedance-Matching Hearing in Paleozoic Reptiles: Evidence of Advanced Sensory Perception at an Early Stage of Amniote Evolution

    PubMed Central

    Müller, Johannes; Tsuji, Linda A.

    2007-01-01

    Background Insights into the onset of evolutionary novelties are key to the understanding of amniote origins and diversification. The possession of an impedance-matching tympanic middle ear is characteristic of all terrestrial vertebrates with a sophisticated hearing sense and an adaptively important feature of many modern terrestrial vertebrates. Whereas tympanic ears seem to have evolved multiple times within tetrapods, especially among crown-group members such as frogs, mammals, squamates, turtles, crocodiles, and birds, the presence of true tympanic ears has never been recorded in a Paleozoic amniote, suggesting they evolved fairly recently in amniote history. Methodology/Principal Findings In the present study, we performed a morphological examination and a phylogenetic analysis of poorly known parareptiles from the Middle Permian of the Mezen River Basin in Russia. We recovered a well-supported clade that is characterized by a unique cheek morphology indicative of a tympanum stretching across large parts of the temporal region to an extent not seen in other amniotes, fossil or extant, and a braincase specialized in showing modifications clearly related to an increase in auditory function, unlike the braincase of any other Paleozoic tetrapod. In addition, we estimated the ratio of the tympanum area relative to the stapedial footplate for the basalmost taxon of the clade, which, at 23∶1, is in close correspondence to that of modern amniotes capable of efficient impedance-matching hearing. Conclusions/Significance Using modern amniotes as analogues, the possession of an impedance-matching middle ear in these parareptiles suggests unique ecological adaptations potentially related to living in dim-light environments. More importantly, our results demonstrate that already at an early stage of amniote diversification, and prior to the Permo-Triassic extinction event, the complexity of terrestrial vertebrate ecosystems had reached a level that proved advanced

  12. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  13. Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

    PubMed

    Lim, S H; Chua, W; Henderson, C; Ng, W; Shin, J-S; Chantrill, L; Asghari, R; Lee, C S; Spring, K J; de Souza, P

    2015-10-01

    Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response. PMID:26032919

  14. Contemporary methods of therapy and follow-up of neuroendocrine tumours of the gastrointestinal tract and the pancreas

    PubMed Central

    Fischbach, Jakub; Kamiński, Grzegorz; Ruchała, Marek

    2012-01-01

    The growing interest in neuroendocrine tumours is due to the dynamic growth of detection of this type of cancer. Neuroendocrine tumours (neuroendocrine neoplasms – NENs / neuroendocrine tumours – NETs) derive from glands, groups of endocrine cells and diffuse neuroendocrine system cells. Mainly they derive from the gastrointestinal tract (gastroenteropancreatic-neuroendocrine tumours – GEP-NETs). Currently the modified WHO classification from 2010 is widely used. An important element in the choice of treatment is histological maturity based on mitotic activity and on assessment of proliferation activity (Ki-67). The treatment of choice is surgery. In most cases, complete surgical removal is impossible because of the advanced staging at the time of diagnosis. In well-differentiated neoplasms where the expression of somatostatin receptors is expected, patients are qualified for somatostatin analogues therapy. Poorly differentiated lesions are qualified for chemotherapy. In the guidelines of ENETS (European Neuroendocrine Tumor Society) from 2007 the rules concerning monitoring depending on the WHO classification were specified. PMID:23788913

  15. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

    Uterine fatty tumours (UFT) are uncommon and have received little attention in the English literature. They have aroused interest as a consequence of occasional diagnostic confusion with sarcomas and the continuing unresolved dispute as to their histogenesis. Three cases of UFT are described and the pathological features of note discussed. The viewpoint that these tumours are hamartomas/choristomas is rejected. UFT most probably represent tumour metaplasia within a leiomyoma. There is no uniform accepted nomenclature for such tumours and it is suggested that they be designated "uterine fatty tumours" and subdivided into "lipoma" and "mixed lipoma/leiomyoma" (synonym lipoleiomyoma). Images PMID:7174848

  16. Glomus tumour of the stomach.

    PubMed

    Troller, Rebekka; Soll, Christopher; Breitenstein, Stefan

    2016-01-01

    Glomus tumours are benign tumours typically arising from the glomus bodies and primarily found under the fingernails or toenails. These rare neoplasms account for <2% of all soft tissue tumours and are generally not found in the gastrointestinal tract. We report a case of a 40-year-old man presenting with recurrent epigastric pain and pyrosis. Endoscopy revealed a solitary tumour in the antrum of the stomach. Fine-needle aspiration biopsy was suspicious for a gastrointestinal stroma tumour. After CT indicated the resectability of the tumour, showing neither lymphatic nor distant metastases, a laparoscopic-assisted gastric wedge resection was performed. Surprisingly, histology revealed a glomus tumour of the stomach. PMID:27343282

  17. The role of radiology in head and neck tumours in children

    PubMed Central

    McHugh, Kieran

    2010-01-01

    Abstract Head and neck malignancy is rare in children. However, distinguishing malignant tumours from the more common and numerous benign causes of neck masses in childhood is crucial as many malignant conditions have an excellent prognosis with appropriate oncological management. Ultrasound, computed tomography and magnetic resonance imaging all have crucial roles in the diagnosis of head and neck malignancy in children and there is an emerging role for positron emission tomography, particularly in the management and follow-up of lymphoma. We describe the imaging appearances of the common malignant tumours arising in the extracranial head and neck in children, focusing on lymphoma, rhabdomyosarcoma and nasopharyngeal carcinoma. The clinical presentation and radiological appearances of benign tumours in the head and neck in children may overlap with those seen in malignant disease. We describe the imaging appearances of juvenile angiofibroma, vascular abnormalities involving the extracranial head and neck and cervical teratomas. Advances in both imaging techniques and cancer staging systems, many of the latter aimed at avoiding over-treatment and treatment-related complications, will lead to an increasingly central role for imaging in childhood head and neck cancer. PMID:20199940

  18. Coping with an Advanced Stage Lung Cancer Diagnosis: Patient, Caregiver, and Provider Perspectives on the Role of the Health Care System.

    PubMed

    Islam, K M; Opoku, Samuel T; Apenteng, Bettye A; Fetrick, Ann; Ryan, June; Copur, M; Tolentino, Addison; Vaziri, Irfan; Ganti, Apar K

    2016-09-01

    Although lung cancer is the leading cause of cancer death in the USA, there have been few studies on patient-centered advanced lung cancer treatment practices. As part of a larger research study on how to use a patient-inclusive approach in late-stage lung cancer treatment, this present study describes patient, caregiver, and provider perspectives on the role of the health care system in helping patients cope with an advanced stage lung cancer diagnosis. Four focus group sessions were conducted with six to eleven participants per group for a total of 36 participants. Two focus groups were held with patients and family members/caregivers and two with physicians and nurses. A major theme that emerged concerned coping with an advanced lung cancer diagnosis, which is the subject of this paper. The patients, caregivers, and providers spoke passionately about interactions with the health care system and volunteered examples of supportive and non-supportive relationships between patients and clinicians. They advocated for better patient-provider communication practices as well as the expanded use of patient navigation and new patient orientation programs. This study contributes additional knowledge by including the perspectives of caregivers and providers who live and work closely with patients with advanced lung cancer. The findings can inform the development of comprehensive patient-centered care plans for patients living with an advanced lung cancer diagnosis. PMID:25900672

  19. First Human Treatment With Investigational rhGUS Enzyme Replacement Therapy in an Advanced Stage MPS VII Patient

    PubMed Central

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-01-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80 mmHg range, eventually approaching respiratory failure (ETCO2 of 100 mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2 mg/kg over 4 hours every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained

  20. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  1. PET Scan in Head and Neck Tumours in a Developing Country Like India: Is It a Must?

    PubMed

    Kapre, Neeti Madan; Dabholkar, Jyoti Pralhad

    2014-01-01

    To study the impact of Positron emission tomography (PET) and its incremental value in diagnosing an unknown primary tumour with secondaries in the head and neck; recurrent head and neck cancers (confirmation of suspected recurrences and re-staging); and staging of head and neck tumours. This was a prospective observational study where 60 patients of head and neck tumours under the clinical settings as described above were evaluated. Thorough clinical examination and necessary radiological and histopathological investigations were done. All patients underwent a PET scan, the results of which were correlated with histopathological examination. Sensitivities, specificities, positive and negative predictive values, false positives and false negatives of PET scan in the different indications were calculated. The study included 11 patients of unknown primary, 28 patients with suspected recurrent tumours and 21 patients where PET scan was done for initial staging. PETCT scan was able to detect the primary in 3 out of 11 patients (27.27 %) who presented with cervical metastases with an unknown primary. In 2 of the 8 patients where a primary tumour was not found, PETCT detected distant metastases. For recurrent tumours, PETCT scan showed sensitivity, specificity, positive predictive value and negative predictive value as 100, 72.72, 85 and 100 % respectively. In restaging of recurrent disease, 4 out of 28 patients were detected to have distant metastases. In 7 cases of locoregionally advanced tumors, where PETCT scan was used for pre-treatment staging, it detected distant metastases in 4 of 7 patients. In the patients with N0 neck status PETCT scan showed a sensitivity, specificity, positive predictive value and negative predictive value of 100, 66.67, 50 and 100 % respectively. PETCT scan was able to alter the plan of management in 15 out of 60 patients. Thus, in carefully selected patients PETCT scan can provide incremental information that proves invaluable in these

  2. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  3. Tumours of the kidney

    PubMed Central

    Nielsen, Svend W.; Mackey, L. J.; Misdorp, W.

    1976-01-01

    The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. ImagesFig. 5,6Fig. 7Fig. 8Fig. 1,2Fig. 3,4Fig. 16,17,18,19Fig. 9,10Fig. 11Fig. 12Fig. 13Fig. 14,15 PMID:1086154

  4. A Broadly Adaptive Array of Dose-Constraint Templates for Planning of Intensity-Modulated Radiation Therapy for Advanced T-Stage Nasopharyngeal Carcinoma

    SciTech Connect

    Chau, R.M.-C. Leung, S.-F.; Kam, M.K.-M.; Cheung, K.-Y.; Kwan, W.-H.; Yu, K.-H.; Chiu, K.-W.; Cheung, M.L.-M.; Chan, A.T.-C.

    2009-05-01

    Purpose: To develop and validate adaptive dose-constraint templates in intensity-modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal carcinoma (NPC). Method and Materials: Dose-volume histograms of clinically approved plans for 20 patients with advanced T-stage NPC were analyzed, and the pattern of distribution in relation to the degree of overlap between targets and organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT) was developed based on the degree of overlap. Another set of 10 patients with advanced T-stage NPC was selected for validation. Results of the manual arm optimization protocol and the ADCT optimization protocol were compared with respect to dose optimization time, conformity indices, multiple-dose end points, tumor control probability, and normal tissue complication probability. Results: For the ADCT protocol, average time required to achieve an acceptable plan was 9 minutes, with one optimization compared with 94 minutes with more than two optimizations of the manual arm protocol. Target coverage was similar between the manual arm and ADCT plans. A more desirable dose distribution in the region of overlap between planning target volume and OARs was achieved in the ADCT plan. Dose end points of OARs were similar between the manual arm and ADCT plans. Conclusions: With the developed ADCT, IMRT treatment planning becomes more efficient and less dependent on the planner's experience on dose optimization. The developed ADCT is applicable to a wide range of advanced T-stage NPC treatment and has the potential to be applied in a broader context to IMRT planning for other cancer sites.

  5. Advanced Stage T-Cell Non-Hodgkin lymphoma in an 11-Month-Old Infant and Related Superior Vena Cava Syndrome: Importance of Transthoracic Echocardiography.

    PubMed

    Yilmaz, Osman; Karabag, Kezban; Keskin Yildirim, Zuhal; Calik, Muhammet; Kilic, Omer

    2014-01-01

    Superior vena cava syndrome (SVCS) is rare in infants. Non-Hodgkin lymphoma is the most common cause of SVCS in children. Swelling in the face and neck are the most common clinical symptoms associated with this syndrome. However, these clinical findings are also observed in allergic diseases, which therefore often leads to misdiagnosis. Here, we reported the importance of echocardiography in diagnosing SVCS in an infant with advanced stage non-Hodgkin lymphoma. PMID:24639614

  6. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    PubMed

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients

  7. Resected tumours of the sublingual gland: 15 years' experience.

    PubMed

    Huang, Tung-Tsun; Chou, Yu-Fu; Wen, Yu-Hsuan; Chen, Peir-Rong

    2016-07-01

    Sublingual gland tumours are rare, and we have evaluated the clinical features and prognosis of patients treated at a tertiary medical centre in eastern Taiwan. We retrospectively reviewed the cases of nine patients with sublingual gland tumours that were resected from December 1993 to November 2008, four of whom were men and five women. The median (range) age at diagnosis was 52 (39-63) years. Seven had malignant tumours, of which adenoid cystic carcinoma was the most common. All patients with malignant tumours had neck dissections, and four had cervical lymph node metastases. The incidence of lymph node metastases was much higher in patients with advanced primary tumours (T1/2 compared with T3/4: one out of three compared with three out of four). All patients with malignant tumours were given adjuvant radiotherapy. There were no local failures. One patient had regional recurrence in the neck and had a successful further resection. Three patients developed distant metastases, and two died during the follow-up period. Our results suggest that radical resection with postoperative radiotherapy offers adequate local and regional control for malignant sublingual gland tumours. Neck dissection is beneficial, especially for T3/4 disease. PMID:27062437

  8. First-line systemic treatment of advanced stage non-small-cell lung cancer in Asia: consensus statement from the Asian Oncology Summit 2009.

    PubMed

    Soo, Ross A; Anderson, Benjamin O; Cho, Byoung Chul; Yang, Chih-Hsin; Liao, Meilin; Lim, Wan-Teck; Goldstraw, Peter; Mok, Tony S

    2009-11-01

    Non-small-cell lung cancer (NSCLC) is an increasing global challenge, especially in low-income countries. Most guidelines for the management of advanced-stage NSCLC have limited effect in countries with resource constraints. Following a systematic literature search, we present an overview of the management of advanced-stage NSCLC in the first-line setting, discuss resources required for systemic therapy, and provide treatment recommendations stratified to four resources levels. Treatment guidelines appropriate for different resource levels offer a realistic approach to management of advanced-stage NSCLC, by recognising the limitations of a particular health-care system. Although there are many barriers to cancer control in low-resource countries, these can be overcome by using measures that are culturally appropriate, economically feasible, and evidence-based. Initiatives include strategic planning, tobacco control, training of health-care workers, access to therapeutic agents, acquisition of information, public education, and alliances with established institutions and international organisations. PMID:19880064

  9. Clinical features of gastroenteropancreatic tumours

    PubMed Central

    Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  10. Biophysical models of tumour growth

    NASA Astrophysics Data System (ADS)

    Tracqui, P.

    2009-05-01

    Tumour growth is a multifactorial process, which has stimulated in recent decades the development of numerous models trying to figure out the mechanisms controlling solid tumours morphogenesis. While the earliest models were focusing on cell proliferation kinetics, modulated by the availability of supplied nutrients, new modelling approaches emphasize the crucial role of several biophysical processes, including local matrix remodelling, active cell migration and traction, and reshaping of host tissue vasculature. After a brief presentation of this experimental background, this review will outline a number of representative models describing, at different scales, the growth of avascular and vascularized tumours. Special attention will be paid to the formulation of tumour-host tissue interactions that selectively drive changes in tumour size and morphology, and which are notably mediated by the mechanical status and elasticity of the tumour microenvironment. Emergence of invasive behaviour through growth instabilities at the tumour-host interface will be presented considering both reaction-diffusion and mechano-cellular models. In the latter part of the review, patient-oriented implications of tumour growth modelling are outlined in the context of brain tumours. Some conceptual views of the adaptive strategies and selective barriers that govern tumour evolution are presented in conclusion as potential guidelines for the development of future models.

  11. Mathematical modelling of the Warburg effect in tumour cords.

    PubMed

    Astanin, Sergey; Preziosi, Luigi

    2009-06-21

    The model proposed here links together two approaches to describe tumours: a continuous medium to describe the movement and the mechanical properties of the tissue, and a population dynamics approach to represent internal genetic inhomogeneity and instability of the tumour. In this way one can build models which cover several stages of tumour progression. In this paper we focus on describing transition from aerobic to purely glycolytic metabolism (the Warburg effect) in tumour cords. From the mathematical point of view this model leads to a free boundary problem where domains in contact are characterized by different sets of equations. Accurate stitching of the solution was possible with a modified ghost fluid method. Growth and death of the cells and uptake of the nutrients are related through ATP production and energy costs of the cellular processes. In the framework of the bi-population model this allowed to keep the number of model parameters relatively small. PMID:19232360

  12. Functional properties of ion channels and transporters in tumour vascularization

    PubMed Central

    Fiorio Pla, Alessandra; Munaron, Luca

    2014-01-01

    Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro, such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one. PMID:24493751

  13. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

    Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria

    2014-01-01

    Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours. PMID:25654053

  14. The epidemiology of neonatal tumours. Report of an international working group.

    PubMed

    Moore, S W; Satgé, D; Sasco, A J; Zimmermann, A; Plaschkes, J

    2003-09-01

    Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular

  15. Messenger RNA (mRNA) nanoparticle tumour vaccination

    NASA Astrophysics Data System (ADS)

    Phua, Kyle K. L.; Nair, Smita K.; Leong, Kam W.

    2014-06-01

    Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a more robust immune response. Advances in the past decade have deepened our understanding of gene delivery barriers, mRNA's biological stability and immunological properties, and support the notion for engineering innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery system. In this review we will first examine the suitability of mRNA for engineering manipulations, followed by discussion of a model framework that highlights the barriers to a robust anti-tumour immunity mediated by mRNA encapsulated in nanoparticles. Finally, by consolidating existing literature on mRNA nanoparticle tumour vaccination within the context of this framework, we aim to identify bottlenecks that can be addressed by future nanoengineering research.

  16. Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

    SciTech Connect

    Salazar, Omar M. Sandhu, Taljit S.; Lattin, Paul B.; Chang, Jung H.; Lee, Choon K.; Groshko, Gayle A.; Lattin, Cheryl J.

    2008-11-01

    Purpose: To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. Methods and Materials: A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy{sub 10}). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy{sub 10}. Respiration gating was used in 46%. Results: The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. Conclusions: SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older

  17. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    SciTech Connect

    Blackstock, A. William . E-mail: ablackst@wfubmc.edu; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    2006-02-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.

  18. Time-to-Progression of NSCLC from Early to Advanced Stages: An Analysis of data from SEER Registry and a Single Institute

    PubMed Central

    Yuan, Ping; Cao, Jin Lin; Rustam, Azmat; Zhang, Chong; Yuan, Xiao Shuai; Bao, Fei Chao; Lv, Wang; Hu, Jian

    2016-01-01

    The average time required for cancers to progress through stages can be reflected in the average age of the patients diagnosed at each stage of disease. To estimate the time it takes for non-small-cell lung cancer (NSCLC) to progress through different tumor, node and metastasis (TNM) stages and sizes, we compared the mean adjusted age of 45904 NSCLC patients with different stages and tumor sizes from Surveillance, Epidemiology and End Results (SEER) cancer registry database and our institute. Multiple-linear-regression models for age were generated adjusting for various factors. Caucasian, African-American and Asian patients with stage IA cancers were on average 0.8, 1.0 and 1.38 adjusted years younger, respectively, than those with stage IIIB cancers (p < 0.001). And these with T1a cancers were on average 0.84, 0.92 and 1.21 adjusted years younger, respectively, than patients with T3 cancers (p < 0.001). Patients with tumors measuring larger than 8 cm in diameter were on average 0.85 adjusted years older than these with tumors smaller than 1 cm (p < 0.001), with Caucasian demonstrating the shortest age span (0.79 years, P < 0.001). In conclusion, the time-to-progression of NSCLC from early to advanced stages varied among ethnicities, Caucasian patients demonstrating a more rapid progression nature of tumor than their African-American and Asian counterparts. PMID:27346236

  19. Decreased expression of RNA-binding motif protein 3 correlates with tumour progression and poor prognosis in urothelial bladder cancer

    PubMed Central

    2013-01-01

    Background Low nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to be associated with poor prognosis in several cancer forms e.g. breast, ovarian, colorectal, prostate cancer and malignant melanoma. The aim of this study was to examine the prognostic impact of RBM3 expression in urinary bladder cancer. Methods Immunohistochemical RBM3 expression was examined in tumours from 343 patients with urothelial bladder cancer. Chi-square and Spearman’s correlation tests were applied to explore associations between RBM3 expression and clinicopathological characteristics. The impact of RBM3 expression on disease-specific survival (DSS), 5-year overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analysis and Cox proportional hazards modelling. Results Reduced nuclear RBM3 expression was significantly associated with more advanced tumour (T) stage (p <0.001) and high grade tumours (p=0.004). Negative RBM3 expression was associated with a significantly shorter DSS (HR=2.55; 95% CI 1.68-3.86)) and 5-year OS (HR=2.10; 95% CI 1.56-2.82), also in multivariable analysis (HR=1.65; 95% CI 1.07-2.53 for DSS and HR=1.54; 95% CI 1.13-2.10 for 5-year OS). In patients with Ta and T1 tumours expressing reduced RBM3 levels, Kaplan-Meier analysis revealed a significantly shorter PFS (p=0.048) and 5-year OS (p=0.006). Conclusion Loss of RBM3 expression is associated with clinically more aggressive tumours and an independent factor of poor prognosis in patients with urothelial bladder cancer and a potentially useful biomarker for treatment stratification and surveillance of disease progression. PMID:23565664

  20. Efficacy Comparison Between Total Laryngectomy and Nonsurgical Organ-Preservation Modalities in Treatment of Advanced Stage Laryngeal Cancer: A Meta-Analysis.

    PubMed

    Fu, Xiaoyuan; Zhou, Qi; Zhang, Xianquan

    2016-04-01

    It remains unclear whether the efficacy of nonsurgical organ-preservation modalities (NOP) in the treatment of advanced-stage laryngeal cancer was noninferiority compared with that of total laryngectomy (TL). The objective of this study was to compare the curative effects between TL and NOP in the treatment of advanced-stage laryngeal cancer through a meta-analysis.Clinical studies were retrieved from the electronic databases of PubMed, Embase, Wanfang, and Chinese National Knowledge infrastructure. A meta-analysis was performed to investigate the differences in the curative efficacy of advanced-stage laryngeal cancer between TL and the nonsurgical method. Two reviewers screened all titles and abstracts, and independently assessed all articles. All identified studies were retrospective.Sixteen retrospective studies involving 8308 patients (4478 in the TL group and 3701 in the nonsurgical group) were included in this meta-analysis. The analysis results displayed the advantage of TL for 2-year and 5-year overall survival (OS)(OR 2.79, 95% CI 1.85-4.23 and OR 1.52, 95% CI 1.09-2.14) as well as in 5-year disease-specific survival (DSS)(OR 1.79, 95% CI 1.61-1.98), but no significant difference in 2-year DSS was detected between the 2 groups (OR = 2.09,95% CI0.69-6.40). Additionally, there were no significant differences between TL and NOP for 5-year local control (LC) either (OR = 1.75, 95% CI 0.87-3.53). When we carried out subgroup analyses, the advantage of TL was especially obvious in T4 subgroups, but not in T3 subgroups.This is the first study to compare the curative effects on advanced-stage laryngeal cancer using meta-analytic methodology. Although there was a trend in favor of TL for OS and DSS, there is no clear difference in oncologic outcome between TL and NOP. Therefore, other factors such as tumor T-stage and size, lymph node metastasis, and physical condition are also important indicators for treatment choice. PMID:27057837

  1. Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

    PubMed Central

    Camargo, M Constanza; Kim, Woo-Ho; Chiaravalli, Anna Maria; Kim, Kyoung-Mee; Corvalan, Alejandro H; Matsuo, Keitaro; Yu, Jun; Sung, Joseph J Y; Herrera-Goepfert, Roberto; Meneses-Gonzalez, Fernando; Kijima, Yuko; Natsugoe, Shoji; Liao, Linda M; Lissowska, Jolanta; Kim, Sung; Hu, Nan; Gonzalez, Carlos A; Yatabe, Yashushi; Koriyama, Chihaya; Hewitt, Stephen M; Akiba, Suminori; Gulley, Margaret L; Taylor, Philip R; Rabkin, Charles S

    2015-01-01

    Background and objective About 9% of gastric carcinomas have Epstein–Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. Methods We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. Results During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Conclusions Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association. PMID:23580779

  2. Testing of polyimide second-stage rod seals for single-state applications in advanced aircraft hydraulic systems

    NASA Technical Reports Server (NTRS)

    Waterman, A. W.

    1977-01-01

    Machined polyimide second-stage rod seals were evaluated to determine their suitability for single-stage applications where full system pressure acts on the upstream side of the seal. The 6.35-cm (2.5-in.) K-section seal was tested in impulse screening tests where peak pressure was increased in 3.448-MPa (500-psi) increments each 20,000 cycles. Seal failure occurred at 37.92 MPa (5,500 psi), indicating a potential for acceptability in a 27.58-MPa (4,000-psi) system. Static pressurization for 600 sec at pressures in excess of 10.34 MPa (1,500 psi) revealed structural inadequacy of the seal cross section to resist fracture and extrusion. Endurance testing showed the seals capable of at least 65,000 1.27-cm (0.5-in.) cycles at 450 K (350 F) without leakage. It was concluded that the second-stage seals were proven to be exceptional in the 1.379-MPa (200-psi) applications for which they were designed, but polyimide material properties are not adequate for use in this design at pressure loading equivalent to that present in single-stage applications.

  3. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy.

    PubMed

    Lee, Nayoung; Zakka, Labib R; Mihm, Martin C; Schatton, Tobias

    2016-02-01

    The field of systemic cancer therapy for metastatic disease has entered an exciting era with the advent of novel immunomodulatory strategies targeting immune checkpoints. At the heart of these promising efforts are the tumour-infiltrating lymphocytes (TILs). As the reports demonstrating efficacy of modulating TIL effector function in patients with advanced stage cancer continue to accrue, it has become essential to better understand TIL immunobiology in order to further improve clinical outcome. In addition to providing an overview of the current immunotherapies available for metastatic melanoma, this review will briefly introduce the history and classification of TILs. Moreover, we will dissect the multifaceted roles of TILs in tumour-specific immunity and melanoma immune escape. The significance of TILs in melanoma prognosis and cancer immunotherapy will also be discussed, with a particular focus on their potential utility as biomarkers of patient response. The goal of personalised medicine appears to be in realistic sight, as new immunomodulatory techniques and technological innovations continue to advance the field of cancer immunotherapy. In light of recent studies highlighting the possible utility of TILs in determining therapeutic outcome, further characterisation of TIL phenotype and function has the potential to help translate individualised care into current medical practice. PMID:27020390

  4. [Epidemiology and risk factors of testicular tumours].

    PubMed

    Kozłowski, Piotr; Starosławska, Elżbieta; Szumiło, Justyna; Jankiewicz, Małgorzata; Kozłowska, Magdalena; Burdan, Franciszek

    2016-04-01

    Testicular tumours are rare neoplasms, which most commonly affects men aged 25 to 35 years. Among young adult males it is the most common cause of testicular swelling. In recent decades, the number of cases of testicular tumours has greatly increased. The most significant predisposing factors are cryptorchidism and some endocrine disorders, especially increased levels of gonadotropins and female sex hormones. Testicular trauma, inguinal hernia, extreme values of body mass index (BMI), high-calorie diet rich in dairy products as well as high social status are also regarded as risk factors. Furthermore, some chromosomal abnormalities like increased number of chromosomes 7, 8. 12, 21 and X, loss of chromosomes 4, 5, 11, 13, 18, or Y, mutation in the gene Xq27; as well as multiplied copy of the gene i(12p) are associated with tumor development. It has been proven that high testosterone levels and regular physical activity may prevent testicular tumours. Since one of the first sign the lesion is often a lump or swelling of the testis and the appearance of abnormal structure in the scrotum routine testicular self-examination seems to be important in early detection. In all suspected cases an immediate ultrasound examination of both testicles is highly recommended. It is also advised to conduct a computerized tomography (CT) and a positron emission tomography (PET) scan for staging of the tumor to select the best mode of treatment. PMID:27137819

  5. Role of tumour angiogenesis in haematological malignancies.

    PubMed

    Medinger, Michael; Passweg, Jakob

    2014-01-01

    Tumour angiogenesis plays a key role in the pathogenesis and progression of haematological malignancies. Thereby, pro- and anti-angiogenic growth factors and cytokines regulate the angiogenic process. The most important growth factor, vascular endothelial growth factor (VEGF) and its signaling through its receptors 1 and 2, is not only involved in solid tumours, but there is also emerging evidence that tumour progression in haematological malignancies also depends on the induction of new blood vessel formation. The evidence supporting this theory includes the finding of increased bone marrow microvessel density and increased levels of plasma pro-angiogenic cytokines. Leukaemia cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype. The pathophysiology of leukaemia induced angiogenesis involves both direct production of angiogenic cytokines by leukaemia cells and their interaction with bone marrow microenvironment. The inhibition of VEGF signalling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully used for the treatment of different cancer entities, and multiple new drugs are being tested. This review summarises recent advances in the basic understanding of the role of angiogenesis in haematological malignancies and the translation of such basic findings into clinical studies. PMID:25375891

  6. Imatinib treatment for gastrointestinal stromal tumour (GIST)

    PubMed Central

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734

  7. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  8. Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas.

    PubMed

    He, Qimin; Mao, Yongrong; Wu, Jainping; Decker, Catrine; Merza, Malik; Wang, Naining; Eriksson, Staffan; Castro, Juan; Skog, Sven

    2004-10-01

    Thymidine kinase 1 (TK1), an enzyme involved in the synthesis of precursors for DNA, and thus proliferation dependent, has been suggested as a good tumour marker. We have recently developed poly/monoclonal antibodies against TK1, which proved useful for diagnostics in both serum and immunohistochemistry of cancer patients. The anti-TK1 monoclonal antibodies (mAbs) 1D11 and 1E3 were characterized by Western blot, immunoprecipitation and flow cytometry. TK1 mAbs and Ki-67 mAb were then used for immunohistochemistry staining of tumour sections from 54 patients with ductal infiltrated breast carcinoma. Results showed the relative number of patients with positively stained tumours for TK1 (mAb 1D11) and for Ki-67 (mAb MIB-1) were 47 and 41%, respectively, significantly related (p=0.007). Combination of TK1 mAbs 1D11 and 1E3 increased this number to 56%, due to detection of a significantly higher number of patients with grade 2 tumours. Patients with stage II and grade 2 tumours showed significantly higher TK1 staining when compared to stage I and grade 1. Ki-67 staining was significantly higher in stage III and grade 3. The tumours only stained for TK1 represented higher stages and grades, while tumours staining only for Ki-67 were of lower stages and grades. Combining TK1 and Ki-67 increased the number of patients with positively stained tumours to 69%. In conclusion, TK1 is a reliable marker for identification of patients with grade 2 tumours. The highest number of patients with positively stained tumours were obtained when both TK1 and Ki-67 markers were used. PMID:15375544

  9. SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

    SciTech Connect

    Qu, H; Xia, P; Yu, N

    2015-06-15

    Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dose was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.

  10. One very rare and one new tracheal tumour found by electron microscopy: glomus tumour and acinic cell tumour resembling carcinoid tumours by light microscopy.

    PubMed Central

    Heard, B E; Dewar, A; Firmin, R K; Lennox, S C

    1982-01-01

    Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract. Images PMID:6281934

  11. Metabolic reprogramming of the tumour microenvironment.

    PubMed

    Xing, Yazhi; Zhao, Shimin; Zhou, Binhua P; Mi, Jun

    2015-10-01

    Tumour cells, stromal cells and the stroma comprise the tumour microenvironment. The metabolism of both tumour cells and several types of tumour stromal cells, such as cancer-associated fibroblasts and tumour-associated macrophages, is reprogrammed. Current studies have found that stromal cells promote tumour progression and metastasis, through not only the paracrine secretion of cytokines or chemokines, but also intermediate metabolites. Here, we summarize the latest insights into the mechanism of metabolic reprogramming in cancer cells, cancer-associated fibroblasts and tumour-associated macrophages, and their potential roles in tumour progression and metastasis. PMID:26255648

  12. Alternatively spliced variants of the cell adhesion molecule CD44 and tumour progression in colorectal cancer.

    PubMed Central

    Gotley, D. C.; Fawcett, J.; Walsh, M. D.; Reeder, J. A.; Simmons, D. L.; Antalis, T. M.

    1996-01-01

    Increased expression of alternatively spliced variants of the CD44 family of cell adhesion molecules has been associated with tumour metastasis. In the present study, expression of alternatively spliced variants of CD44 and their cellular distribution have been investigated in human colonic tumours and in the corresponding normal mucosa, in addition to benign adenomatous polyps. The expression of CD44 alternatively spliced variants has been correlated with tumour progression according to Dukes' histological stage. CD44 variant expression was determined by immunohistochemisty using monoclonal antibodies directed against specific CD44 variant domains together with RT-PCR analysis of CD44 variant mRNA expression in the same tissue specimens. We demonstrate that as well as being expressed in colonic tumour cells, the full range of CD44 variants, CD44v2-v10, are widely expressed in normal colonic crypt epithelium, predominantly in the crypt base. CD44v6, the epitope which is most commonly associated with tumour progression and metastasis, was not only expressed by many benign colonic tumours, but was expressed as frequently in normal basal crypt epithelium as in malignant colonic tumour cells, and surprisingly, was even absent from some metastatic colorectal tumours. Expression of none of the CD44 variant epitopes was found to be positively correlated with tumour progression or with colorectal tumour metastasis to the liver, results which are inconsistent with a role for CD44 variants as indicators of colonic cancer progression. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:8695347

  13. Large-Scale Liquid Hydrogen Tank Rapid Chill and Fill Testing for the Advanced Shuttle Upper Stage Concept

    NASA Technical Reports Server (NTRS)

    Flachbart, R. H.; Hedayat, A.; Holt, K. A.; Sims, J.; Johnson, E. F.; Hastings, L. J.; Lak, T.

    2013-01-01

    Cryogenic upper stages in the Space Shuttle program were prohibited primarily due to a safety risk of a 'return to launch site' abort. An upper stage concept addressed this concern by proposing that the stage be launched empty and filled using shuttle external tank residuals after the atmospheric pressure could no longer sustain an explosion. However, only about 5 minutes was allowed for tank fill. Liquid hydrogen testing was conducted within a near-ambient environment using the multipurpose hydrogen test bed 638.5 ft3 (18m3) cylindrical tank with a spray bar mounted longitudinally inside. Although the tank was filled within 5 minutes, chilldown of the tank structure was incomplete, and excessive tank pressures occurred upon vent valve closure. Elevated tank wall temperatures below the liquid level were clearly characteristic of film boiling. The test results have substantial implications for on-orbit cryogen transfer since the formation of a vapor film would be much less inhibited due to the reduced gravity. However, the heavy tank walls could become an asset in normal gravity testing for on-orbit transfer, i.e., if film boiling in a nonflight weight tank can be inhibited in normal gravity, then analytical modeling anchored with the data could be applied to reduced gravity environments with increased confidence.

  14. ABCB1 in children's brain tumours.

    PubMed

    Coyle, Beth; Kessler, Maya; Sabnis, Durgagauri H; Kerr, Ian D

    2015-10-01

    Tumours of the central nervous system are the most common solid tumour, accounting for a quarter of the 1500 cases of childhood cancer diagnosed each year in the U.K. They are the most common cause of cancer-related death in children. Treatment consists of surgery followed by adjuvant chemotherapy and/or radiotherapy. Survival rates have generally increased, but many survivors suffer from radiotherapy-related neurocognitive and endocrine side effects as well as an increased risk of secondary cancer. Adjuvant chemotherapy is normally given in combination to circumvent chemoresistance, but several studies have demonstrated it to be ineffective in the absence of radiotherapy. The identification of children with drug-resistant disease at the outset could allow stratification of those that are potentially curable by chemotherapy alone. Ultimately, however, what is required is a means to overcome this drug resistance and restore the effectiveness of chemotherapy. Medulloblastomas and ependymomas account for over 30% of paediatric brain tumours. Advances in neurosurgery, adjuvant radiotherapy and chemotherapy have led to improvements in 5-year overall survival rates. There remain, however, significant numbers of medulloblastoma patients that have intrinsically drug-resistant tumours and/or present with disseminated disease. Local relapse in ependymoma is also common and has an extremely poor prognosis with only 25% of children surviving first relapse. Each of these is consistent with the acquisition of drug and radiotherapy resistance. Since the majority of chemotherapy drugs currently used to treat these patients are transport substrates for ATP-binding cassette sub-family B member 1 (ABCB1) we will address the hypothesis that ABCB1 expression underlies this drug resistance. PMID:26517917

  15. Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

    PubMed Central

    Tomasini, Pascale; Barlesi, Fabrice; Mascaux, Celine; Greillier, Laurent

    2016-01-01

    Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed’s mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing. PMID:27239238

  16. Engineered affinity proteins for tumour-targeting applications.

    PubMed

    Friedman, Mikaela; Ståhl, Stefan

    2009-05-01

    Targeting of tumour-associated antigens is an expanding treatment modality in clinical oncology as an alternative to, or in combination with, conventional treatments, such as chemotherapy, external-radiation therapy and surgery. Targeting of antigens that are unique or more highly expressed in tumours than in normal tissues can be used to increase the specificity and reduce the cytotoxic effect on normal tissues. Several targeting agents have been studied for clinical use, where monoclonal antibodies have been the ones most widely used. More than 20 monoclonal antibodies are approved for therapy today and the largest field is oncology. Advances in genetic engineering and in vitro selection technology has enabled the feasible high-throughput generation of monoclonal antibodies, antibody derivatives [e.g. scFvs, Fab molecules, dAbs (single-domain antibodies), diabodies and minibodies] and more recently also non-immunoglobulin scaffold proteins. Several of these affinity proteins have been investigated for both in vivo diagnostics and therapy. Affinity proteins in tumour-targeted therapy can affect tumour progression by altering signal transduction or by delivering a payload of toxin, drug or radionuclide. The ErbB receptor family has been extensively studied as biomarkers in tumour targeting, primarily for therapy using monoclonal antibodies. Two receptors in the ErbB family, EGFR (epidermal growth factor receptor) and HER2 (epidermal growth factor receptor 2), are overexpressed in various malignancies and associated with poor patient prognosis and are therefore interesting targets for solid tumours. In the present review, strategies are described for tumour targeting of solid tumours using affinity proteins to deliver radionuclides, either for molecular imaging or radiotherapy. Antibodies, antibody derivatives and non-immunoglobulin scaffold proteins are discussed with a certain focus on the affibody (Affibody) molecule. PMID:19341363

  17. ERCC1 protein as a guide for individualized therapy of late-stage advanced non-small cell lung cancer

    PubMed Central

    GAO, ZHIQIANG; HAN, BAOHUI; SHEN, JIE; GU, AIQIN; QI, DAJIANG; HUANG, JINSU; SHI, CHUNLEI; XIONG, LIWEN; ZHAO, YIZHUO; JIANG, LIYAN; WANG, HUIMIN; CHEN, YURONG

    2011-01-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been associated with cisplatin resistance. The objective of this study was to investigate the correlation between ERCC1 protein levels and the therapeutic effect of individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of 190 advanced NSCLC patients were included in this study. Patients were randomized into either the individualized therapy group or the standard therapy group at a ratio of 2:1. Patients in the standard therapy group were treated with either gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1 protein in lung cancer tissues of patients from the individualized therapy group was detected with immunohistochemistry. Patients with low ERCC1 levels received either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients with high levels received gemcitabine plus vinorelbine. The main outcome assessments were response rate (RR), overall survival (OS) and time to progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1-year survival rate and TTP were not statistically significant. The median survival time was 10.10 months in the standard therapy group (95% CI 8.48–11.92) and 13.59 months in the individualized therapy group (95% CI 11.86–14.74). The difference in median survival time was significantly different between these groups (P=0.036). The median survival time was longer in the individualized group compared to the standard therapy group. ERCC1 protein expression in advanced NSCLC patients, however, was not significantly correlated with RR, OS and TTP in the individualized therapy group. Therefore, this study suggests that ERCC1 protein levels should be assessed in combination with additional biomarkers to determine an optimal index for individualized therapy in advanced NSCLC patients. PMID:22977580

  18. A two stage launch vehicle for use as an advanced space transportation system for logistics support of the space station

    NASA Technical Reports Server (NTRS)

    1987-01-01

    This report describes the preliminary design specifications for an Advanced Space Transportation System consisting of a fully reusable flyback booster, an intermediate-orbit cargo vehicle, and a shuttle-type orbiter with an enlarged cargo bay. It provides a comprehensive overview of mission profile, aerodynamics, structural design, and cost analyses. These areas are related to the overall feasibility and usefullness of the proposed system.

  19. Recurrent hyperphosphatemic tumoural calcinosis

    PubMed Central

    Amit, Sonal; Agarwal, Asha; Nigam, Anand; Rao, Yashwant Kumar

    2012-01-01

    Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint. PMID:23010461

  20. Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition.

    PubMed Central

    Marti, J. H.; Thomson, D. M.

    1976-01-01

    Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated anti-tumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4-5% of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) "armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen. The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after "curative" surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence. PMID:962991

  1. Tumours of bones and joints

    PubMed Central

    Misdorp, W.; Van Der Heul, R. O.

    1976-01-01

    Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157

  2. Granulocyte colony-stimulating factor in secondary prophylaxis for advanced-stage Hodgkin lymphoma treated with ABVD chemotherapy: a cost-effectiveness analysis.

    PubMed

    Cheung, M C; Prica, A; Graczyk, J; Buckstein, R; Chan, K K W

    2016-08-01

    Granulocyte colony-stimulating factor (G-CSF) is commonly administered to patients with Hodgkin lymphoma (HL) with neutropenia. We constructed a decision-analytic model to compare the cost-effectiveness of secondary prophylaxis with G-CSF to a strategy of 'no G-CSF' in response to severe neutropenia for adults with advanced-stage HL treated with ABVD. A Canadian public health payer's perspective was considered and costs were presented in 2013 Canadian dollars. The quality-adjusted life years (QALYs) attained with the G-CSF and 'no G-CSF' strategies were 1.403 and 1.416, respectively. Costs for the strategies with and without G-CSF were $38,971 and $33,982, respectively. In the base case analysis, the 'no G-CSF' strategy was associated with cost savings and improved QALYs; therefore, 'no G-CSF' was the dominant approach. For patients with severe neutropenia during ABVD chemotherapy for advanced-stage HL, a strategy without G-CSF support is associated with improved quality-adjusted outcomes, cost savings, and is the preferred approach. PMID:26758765

  3. Single stage, low noise, advanced technology fan. Volume 5: Fan acoustics. Section 2: One-third octave data tabulations and selected narrowband traces

    NASA Technical Reports Server (NTRS)

    Jutras, R. R.

    1976-01-01

    The raw-acoustic data corrected to standard day, from acoustic tests performed on a 0.508-scale fan vehicle of a 111,300 newton thrust, full-size engine, which has application on an advanced transport aircraft, are presented. The single-stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec to achieve the desired pressure ratio in a single-stage fan with low radius ratio, and to maintain adequate stall margin. The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise was accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels. The suppression goal of FAR 36-20 was not reached, but improvements in the technology of both front and aft fan-noise suppression were realized.

  4. Advanced space engine preliminary design. [liquid hydrogen/liquid oxygen upper stage engine for space tug application

    NASA Technical Reports Server (NTRS)

    Zachary, A. T.

    1973-01-01

    Analysis and design of an optimum LO2/LH2, combustion topping cycle, 88,964 Newtons (20,000-pound) thrust, liquid rocket engine was conducted. The design selected is well suited to high-energy, upper-stage engine applications such as the Space Tug and embodies features directed toward optimization of vehicle performance. A configuration selection was conducted based on prior Air Force Contracts, and additional criteria for optimum stage performance. Following configuration selection, analyses and design of the major components and engine systems were conducted to sufficient depth to provide layout drawings suitable for subsequent detailing. In addition, engine packaging to a common interface and a retractable nozzle concept were defined. Alternative development plans and related costs were also established. The design embodies high-performance, low-weight, low NPSH requirements (saturated propellant inlet conditions at start), idle-mode operation, and autogenous pressurization. The design is the result of the significant past and current LO2/LH2 technology efforts of the NASA centers and the Air Force, as well as company-funded programs.

  5. Tumours of the urinary bladder

    PubMed Central

    Pamukcu, A. M.

    1974-01-01

    Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours. Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs—the two species most studied. They are described under the following names: papilloma, adenoma, transitional cell carcinoma (with variants), squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16 PMID:4371741

  6. Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients

    NASA Astrophysics Data System (ADS)

    Neicu, Toni; Shirato, Hiroki; Seppenwoolde, Yvette; Jiang, Steve B.

    2003-03-01

    Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than 1 cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung

  7. New approaches to targeted drug delivery to tumour cells

    NASA Astrophysics Data System (ADS)

    Severin, E. S.

    2015-01-01

    Basic approaches to the design of targeted drugs for the treatment of human malignant tumours have been considered. The stages of the development of these approaches have been described in detail and theoretically substantiated, and basic experimental results have been reported. Considerable attention is paid to the general characteristic of nanopharmacological drugs and to the description of mechanisms of cellular interactions with nanodrugs. The potentialities and limitations of application of nanodrugs for cancer therapy and treatment of other diseases have been considered. The use of nanodrugs conjugated with vector molecules seems to be the most promising trend of targeted therapy of malignant tumours. The bibliography includes 122 references.

  8. Quality Improvement Guidelines for Radiofrequency Ablation of Liver Tumours

    SciTech Connect

    Crocetti, Laura; Baere, Thierry de; Lencioni, Riccardo

    2010-02-15

    The development of image-guided percutaneous techniques for local tumour ablation has been one of the major advances in the treatment of liver malignancies. Among these methods, radiofrequency ablation (RFA) is currently established as the primary ablative modality at most institutions. RFA is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when liver transplantation or surgical resection are not suitable options [1, 2]. In addition, RFA is considered a viable alternate to surgery (1) for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer, and (2) for patients deemed ineligible for surgical resection because of extent and location of the disease or concurrent medical conditions [3]. These guidelines were written to be used in quality-improvement programs to assess RFA of HCC and liver metastases. The most important processes of care are (1) patient selection, (2) performing the procedure, and (3) monitoring the patient. The outcome measures or indicators for these processes are indications, success rates, and complication rates.

  9. Treatment of liver cancer of middle and advanced stages using ultrasound-guided percutaneous ethanol injection combined with radiofrequency ablation: A clinical analysis

    PubMed Central

    SUN, XUE; LI, RU; ZHANG, BOTAO; YANG, YUEJIE; CUI, ZHIFEI

    2016-01-01

    Liver cancer is a malignancy of the digestive system and has a high morbidity and mortality rate. Local intervention has become a viable option in identifying liver treatment. The aim of the present study was to analyze the clinical effects of treating liver cancer in middle and advanced stages using ultrasound-guided percutaneous ethanol injection (PEI) in tumors combined with radiofrequency ablation (RFA). A total of 100 patients with stage III–IV liver cancers were selected to participate in the study. Patients were divided into groups. In group A, treatment was initiated with PEI and after 1–2 weeks RFA was applied while in group B treatment was initiated with RFA and after 1–2 weeks PEI was applied. Patients in group C received PEI and RFA simultaneously. The clinical effects in the 3 groups were compared after 6-month follow ups. The volume of tumor ablation necrosis in group A was significantly greater than that in the groups B and C, while the size was significantly smaller compared to groups B and C after ablation. For group A, the complete ablation rate was significantly higher than that in groups B and C, and the differences were statistically significant (P<0.05). Liver damage indices, including raising levels of glutamic-pyruvic transaminase and total bilirubin, were significantly decreased in group A (P<0.05). The survival rate in group A was also significantly higher than in groups B and C (P<0.05). In conclusion, for patients with liver cancer in middle and advanced stages, the treatment method using PEI followed by RFA was more beneficial in terms of improving the tumor ablation rate, alleviating liver damages and increasing survival rates. PMID:26998128

  10. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  11. Distribution of Photofrin between tumour cells and tumour associated macrophages.

    PubMed Central

    Korbelik, M.; Krosl, G.; Olive, P. L.; Chaplin, D. J.

    1991-01-01

    Photofrin levels in cells derived from SCCVII tumours, excised from mice that previously received the drug, were measured using a fluorescence activated cell sorter (FACS). Concomitantly, in the same cells the FACS was used to measure fluorescein isothiocyanate (FITC) fluorescence that originated from FITC-conjugated antimouse IgG added to the cell suspension before sorting. This later measurement enabled discrimination between IgG negative tumour malignant cells and IgG positive host cells (primarily macrophages). In addition, cellular Photofrin content in 'tumour' and 'host' cells sorted by FACS was determined by chemical extraction. The measurements were performed for the time intervals 1-96 h post Photofrin administration. The data showed consistently higher Photofrin levels in the 'host cells', i.e., tumour associated macrophages (TAM), than in 'tumour' cells. On a per cell basis, at any time point studied there was a minimum of 1.7 times more Photofrin in 'host' than in 'tumour cells', while at 4-12 h postadministration, ratios of up to 3.0 times were observed. This corresponds to ratio values greater than 9, when based on Photofrin content per micrograms cell protein. PMID:1832927

  12. Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in Advanced-Stage Cervical and Vaginal Cancers

    PubMed Central

    Kunos, Charles A.; Radivoyevitch, Tomas; Waggoner, Steven; Debernardo, Robert; Zanotti, Kristine; Resnick, Kimberly; Fusco, Nancy; Adams, Ramon; Redline, Raymond; Faulhaber, Peter; Dowlati, Afshin

    2013-01-01

    Objective Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods We conducted a phase II study evaluating 3x weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m2) co-administered with 1x weekly intravenous cisplatin (40 mg/m2) and daily pelvic radiation (45 Gy) in women with stage IB2-IVB cervical (n = 22) or stage II-IV vaginal (n = 3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET/CT) and clinical examination. Results 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. Conclusions The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted. PMID:23603372

  13. Pathophysiology of tumour-induced microangiopathic haemolytic anaemia.

    PubMed

    Chalasani, Pavani; Segar, Jennifer M; Marron, Marilyn; Stopeck, Alison

    2016-01-01

    Cancer-associated microangiopathic haemolytic anaemia (CA-MAHA) is a syndrome characterised by Coombs-negative haemolytic anaemia and thrombocytopenia. It is primarily seen in advanced solid tumours and is distinct from thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome. Diagnosis is often delayed and patients have a high mortality. We present the case of CA-MAHA in a patient with metastatic breast cancer treated successfully with early initiation of chemotherapy. In addition, we report longitudinal laboratory evaluation of circulating tumour cells and microparticles and suggest a hypothesis for the mechanism behind CA-MAHA. PMID:26744538

  14. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    PubMed Central

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  15. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  16. Studies of Advanced Stages of Meditation in the Tibetan Buddhist and Vedic Traditions. I: A Comparison of General Changes

    PubMed Central

    Hankey, Alex

    2006-01-01

    This article is the first of two comparing findings of studies of advanced practitioners of Tibetan Buddhist meditation in remote regions of the Himalayas, with established results on long-term practitioners of the Transcendental Meditation programs. Many parallel levels of improvement were found, in sensory acuity, perceptual style and cognitive function, indicating stabilization of aspects of attentional awareness. Together with observed increases in EEG coherence and aspects of brain function, such changes are consistent with growth towards a state of total brain functioning, i.e. development of full mental potential. They are usually accompanied by improved health parameters. How they may be seen to be consistent with growth of enlightenment will be the subject of a second article. PMID:17173116

  17. Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study

    PubMed Central

    Li, Jun; Yang, Shengke; Hu, Junjie; Liu, Hao; Du, Feng; Yin, Jie; Liu, Sai; Li, Ci; Xing, Shasha; Yuan, Jiatian; Lv, Bo; Fan, Jun; Leng, Shusheng; Zhang, Xin; Wang, Bing

    2016-01-01

    We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients. PMID:26934317

  18. Quantifying tumour heterogeneity with CT

    PubMed Central

    Miles, Kenneth A.

    2013-01-01

    Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171

  19. Leydig cell tumours in childhood.

    PubMed

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  20. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  1. Multicellular Streaming in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Kas, Josef

    As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  2. Quantifying the Effects of Radiation on Tumour Vasculature with High-Frequency Three-Dimensional Power Doppler Ultrasound

    NASA Astrophysics Data System (ADS)

    Hupple, Clinton

    Recent evidence suggests that radiation may have a significant effect on tumour vasculature in addition to damaging tumour cell DNA. It is well established that endothelial cells are among the first cells to respond after administration of ionizing radiation in both normal and tumour tissues. It has also been suggested that microvascular dysfunction may regulate tumour response to radiotherapy at high doses. However, due to limitations in imaging the microcirculation this response is not well characterized. Advances in high-frequency ultrasound and computation methods now make it possible to acquire and analyze 3-D ultrasound data of tumour blood flow in tumour microcirculation. This thesis outlines the work done to test the hypothesis that single dose 8 Gy radiotherapy produces changes in tumour blood vessels which can be quantified using high-frequency power Doppler ultrasound. In addition, the issue of reproducibility of power Doppler measurements and the relationship between histopathology and power Doppler measurements have been examined.

  3. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  4. Imaging of skull base tumours.

    PubMed

    Thust, Stefanie Catherine; Yousry, Tarek

    2016-01-01

    The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours. PMID:27330416

  5. City tumour board Karachi: an innovative step in multidisciplinary consensus meeting and its two years audit.

    PubMed

    Asghar, Asghar Hussain; Abbasi, Ahmed Nadeem; Jamal, Abid; Haider, Ghulam; Rizvi, Sadia

    2013-12-01

    Management of cancer patients is a team work which usually comprises of surgeons, oncologists, radiologists, pathologists, psychiatrist, nutritionist and a nurse. Any patient who is suffering from any tumour needs a multimodality meeting as cancer treatment is not a single persons job. Most of the time, it is difficult to get the whole team together for a plan discussion due to their busy schedule. This problem was overcome by starting a tumour board meeting early morning of Sunday in Karachi which was named "City Tumour Board (CTB) Karachi". Its first meeting was held on Sunday March 28, 2010 and since then it takes place regularly fortnightly. Till March 2012, 44 sessions were conducted and total 264 cases were discussed. Here we present an audit of these two years. On average, in 60% of cases, tumour was up (36%) or down staged (12%) while in 52% of cases the stage remained unchanged. In 70% of cases (inclusive of above 60%), initial treatment plan was changed after discussion in the tumour board. This data signifies the importance of tumour board especially in a Pakistani setup where patient and even referring persons are not well aware of this disease and its outcome. It is advisable that every case should be discussed in tumour board before embarking on any treatment so that the best treatment plan can be given. It is also important that all relevant specialists should be present in the tumour board when planning for any treatment. PMID:24397101

  6. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma

    PubMed Central

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  7. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma.

    PubMed

    Shen, Long; Li, Honghao; Shi, Yuzhi; Wang, Dekun; Gong, Junbo; Xun, Jing; Zhou, Sifan; Xiang, Rong; Tan, Xiaoyue

    2016-01-01

    Effects of M2 tumour-associated macrophages on the pathogenesis of diffuse large B cell lymphoma (DLBCL) are still controversial. Our data showed that the number of CD163-positive M2 macrophages correlated negatively with DLBCL prognosis. Macrophage depletion by clodronate liposomes significantly suppressed tumour growth in a xenograft mouse model of DLBCL using OCI-Ly3 cells. Moreover, M2 polarization of macrophages induced legumain expression in U937 cells. Exogenous legumain promoted degradation of fibronectin and collagen I, which was abolished by administration of a legumain inhibitor RR-11a. Overexpression of legumain in Raw 264.7 cells also induced tube formation of endothelial cells in matrigel. In the xenograft mouse model of DLBCL, decreased fibronectin and collagen I, as well as increased legumain expression and angiogenesis were found at the late stage tumours compared with early stage tumours. Co-localization of legumain and fibronectin was observed in the extracellular matrix of tumour tissues. Administration of the legumain inhibitor to the xenograft DLBCL model suppressed tumour growth, angiogenesis and collagen deposition compared with the control. Taken together, our results suggest that M2 tumour-associated macrophages affect degradation of the extracellular matrix and angiogenesis via overexpression of legumain, and therefore play an active role in the progression of DLBCL. PMID:27464733

  8. Predictors of Surgery Types after Neoadjuvant Therapy for Advanced Stage Breast Cancer: Analysis from Florida Population-Based Cancer Registry (1996–2009)

    PubMed Central

    Al-Azhri, Jamila; Koru-Sengul, Tulay; Miao, Feng; Saclarides, Constantine; Byrne, Margaret M.; Avisar, Eli

    2015-01-01

    PURPOSE Despite the established guidelines for breast cancer treatment, there is still variability in surgical treatment after neoadjuvant therapy (NT) for women with large breast tumors. Our objective was to identify predictors of the type of surgical treatment: mastectomy versus breast-conserving surgery (BCS) in women with T3/T4 breast cancer who received NT. METHODS Population-based Florida Cancer Data System Registry, Florida’s Agency for Health Care Administration, and US census from 1996 to 2009 were linked for women diagnosed with T3/T4 breast cancer and received NT followed by either BCS or mastectomy. Analysis of multiple variables, such as sociodemographic characteristics (race, ethnicity, socioeconomic status, age, marital status, and urban/rural residency), tumor’s characteristics (estrogen/progesterone receptor status, histology, grade, SEER stage, and regional nodes positivity), treatment facilities (hospital volume and teaching status), patients’ comorbidities, and type of NT, was performed. RESULTS Of 1,056 patients treated with NT for T3/T4 breast cancer, 107 (10%) had BCS and 949 (90%) had mastectomy. After adjusting with extensive covariables, Hispanic patients (adjusted odds ratio (aOR) = [3.50], 95% confidence interval (CI): 1.38–8.84, P = 0.008) were more likely to have mastectomy than BCS. Compared to localized SEER stage, regional stage with direct extension (aOR = [3.24], 95% CI: 1.60–6.54, P = 0.001), regional stage with direct extension and nodes (aOR = [4.35], 95% CI: 1.72–11.03, P = 0.002), and distant stage (aOR = [4.44], 95% CI: 1.81–10.88, P = 0.001) were significantly more likely to have mastectomy than BCS. Compared to patients who received both chemotherapy and hormonal therapy, patients who received hormonal NT only (aOR = [0.29], 95% CI: 0.12–0.68, P = 0.004) were less likely to receive mastectomy. CONCLUSION Our study suggests that Hispanic ethnicity, advanced SEER stage, and type of NT are significant

  9. Advances in chemical and physical properties of electric arc furnace carbon steel slag by hot stage processing and mineral mixing.

    PubMed

    Liapis, Ioannis; Papayianni, Ioanna

    2015-01-01

    Slags are recognised as a highly efficient, cost effective tool in the metal processing industry, by minimising heat losses, reducing metal oxidation through contact with air, removing metal impurities and protecting refractories and graphite electrodes. When compared to natural aggregates for use in the construction industry, slags have higher specific weight that acts as an economic deterrent. A method of altering the specific weight of EAFC slag by hot stage processing and mineral mixing, during steel production is presented in this article. The method has minimal interference with the production process of steel, even by limited additions of appropriate minerals at high temperatures. Five minerals are examined, namely perlite, ladle furnace slag, bauxite, diatomite and olivine. Measurements of specific weight are accompanied by X-ray diffraction (XRD) and fluorescence (XRF) analysis and scanning electron microscopy spectral images. It is also shown how altering the chemical composition is expected to affect the furnace refractory lining. Additionally, the process has been repeated for the most suitable mix in gas furnace and physical properties (FI, SI, LA, PSV, AAV, volume stability) examined. Alteration of the specific weight can result in tailoring slag properties for specific applications in the construction sector. PMID:25261762

  10. In vivo response of the rat's retinal pigment epithelium to azide at advanced stages of hereditary retinal dystrophy.

    PubMed

    Ando, H; Noell, W K

    1993-01-01

    Electrophysiological properties of the retinal pigment epithelium (RPE) were studied in the rat with hereditary retinal dystrophy (rdy). Transocular potential changes evoked by intravenous bolus injections of azide and thiocyanate (SCN-) are the only available indication of RPE state when degeneration of rods is in progress. Also determined were age-dependent decrease in retinal DNA content and in counts of cones that survive after degeneration of rods. The azide response in the pigmented and albino rdy rat was already reduced at the earliest age tested (60 d) and continued to decrease till the age of 2 years. The SCN-response was similarly affected but seemed to decline faster than the azide response. The azide/SCN- response ratio was significantly increased in albino mutants, especially around the age of 400 d. At the age of 10 months and later, the azide and SCN- responses became slower than those of normals. A prolonged exposure of 1,200 1x light to dystrophic rats older than 110 did not affect the azide and SCN- responses whereas the same exposure abolishes the responses of normal rats and of the dystrophic rats at early stages. In rdy rats, the electrophysiological changes were considered to correlate with structural changes of the junctional RPE complex and with abnormal membrane enzyme distribution discovered by others. These RPE changes may contribute to the decreasing cone cell number after rod cell disappearance. PMID:8230852

  11. A comparison of patients with hepatitis B- or hepatitis C-based advanced-stage hepatocellular carcinoma.

    PubMed

    Carr, Brian I; Guerra, Vito; Steel, Jennifer L; Lu, Sheng-Nan

    2015-04-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death and has characteristic causes, epidemiology and clinical features. The leading causes include hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, and aflatoxin B1 dietary exposure, as well as combinations of these factors. Few cancers offer the opportunity to study the clinical and cancer phenotype that results from different causes, quite like HCC. Advantage was taken of a large cohort of advanced, unresectable and untransplantable HCCs to compare the phenotypes resulting from HBV-based compared with HCV-based HCC. The main findings were that HBV-based HCC patients were statistically significantly younger, had a higher percent of males, had larger maximum tumor sizes, and had higher blood alpha-fetoprotein (AFP) and albumin levels and platelet counts than HCV-based HCC patients. These differences partly reflect an earlier age of HBV infection and a lesser degree of cirrhosis-associated liver damage, as a result of the different biological consequences of chronic HBV compared with chronic HCV infection. PMID:25843735

  12. Prostate cancer as a model for tumour immunotherapy

    PubMed Central

    Drake, Charles G.

    2011-01-01

    Advances in basic immunology have led to an improved understanding of the interactions between the immune system and tumours, generating renewed interest in approaches that aim to treat cancer immunologically. As clinical and preclinical studies of tumour immunotherapy illustrate several immunological principles, a review of these data is broadly instructive and is particularly timely now that several agents are beginning to show evidence of efficacy. This is especially relevant in the case of prostate cancer, as recent approval of sipuleucel-T by the US Food and Drug Administration marks the first antigen-specific immunotherapy approved for cancer treatment. Although this Review focuses on immunotherapy for prostate cancer, the principles discussed are applicable to many tumour types, and the approaches discussed are highlighted in that context. PMID:20651745

  13. Interleukin-6 and leptin as markers of energy metabolic changes in advanced ovarian cancer patients.

    PubMed

    Macciò, Antonio; Madeddu, Clelia; Massa, Daniela; Astara, Giorgio; Farci, Daniele; Melis, Gian Benedetto; Mantovani, Giovanni

    2009-09-01

    The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint. PMID:18624749

  14. DCC constrains tumour progression via its dependence receptor activity.

    PubMed

    Castets, Marie; Broutier, Laura; Molin, Yann; Brevet, Marie; Chazot, Guillaume; Gadot, Nicolas; Paquet, Armelle; Mazelin, Laetitia; Jarrosson-Wuilleme, Loraine; Scoazec, Jean-Yves; Bernet, Agnès; Mehlen, Patrick

    2012-02-23

    The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis. PMID:22158121

  15. Pilot study of modified LMB-based therapy for children with ataxia-telangiectasia and advanced stage high grade mature b-cell malignancies

    PubMed Central

    Sandlund, J. T.; Hudson, M. M.; Kennedy, W.; Onciu, M.; Kastan, M. B.

    2014-01-01

    Children with ataxia-telangiectasia (A-T) and cancer have a poorer prognosis due in part to increased treatment-related toxicity. We piloted a curative intent approach in five children with A-T who presented with advanced stage (III, n=2; IV, n=3) B-NHL (diffuse large B-cell lymphoma, n=4; Burkitt leukemia, n=1) using a modified LMB-based protocol. Two achieved sustained CCR (one, CCR at 6 years; one, pulmonary death after 3 years in CCR). Two died from toxicity during induction and 1 failed induction with progressive disease. Novel therapeutic approaches which overcome drug resistance and are less toxic are needed for children with A-T and B-NHL. PMID:23900766

  16. Radioimmunotherapy of human tumours.

    PubMed

    Larson, Steven M; Carrasquillo, Jorge A; Cheung, Nai-Kong V; Press, Oliver W

    2015-06-01

    The eradication of cancer remains a vexing problem despite recent advances in our understanding of the molecular basis of neoplasia. One therapeutic approach that has demonstrated potential involves the selective targeting of radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Such radioimmunotherapy (RIT) permits the delivery of a high dose of therapeutic radiation to cancer cells, while minimizing the exposure of normal cells. Although this approach has been investigated for several decades, the cumulative advances in cancer biology, antibody engineering and radiochemistry in the past decade have markedly enhanced the ability of RIT to produce durable remissions of multiple cancer types. PMID:25998714

  17. A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic murine tumours.

    PubMed Central

    Franco, M.; Bustuoabad, O. D.; di Gianni, P. D.; Goldman, A.; Pasqualini, C. D.; Ruggiero, R. A.

    1996-01-01

    Resistance of tumour-bearing mice to a second tumour challenge, that is concomitant resistance, was evaluated in euthymic and nude mice using nine tumours with widely different degrees of immunogenicity. Two temporally separate peaks of concomitant resistance were detected during tumour development. The first one was exhibited only by small immunogenic tumours; it was tumour specific and mediated by classical immunological T-cell-dependent mechanisms. The second peak was shared by both immunogenic and non-immunogenic large tumours; it was non-specific, thymus independent and correlated with the activity of a serum factor (neither antibody nor complement) that inhibited the in vitro proliferation of tumour cells. This factor was eluted from a Sephadex G-15 column at fractions corresponding to a molecular weight of approximately 1000 Da and it was recovered from a high-performance liquid chromatography column in one peak presenting maximum absorption at 215 and 266 nm. The data presented in this paper suggest for the first time, to our knowledge, that in spite of the differences between immunogenic and non-immunogenic tumours, a common serum-mediated mechanism seems to underlie the concomitant resistance induced by both types of tumours at late stages of tumour development. PMID:8688319

  18. Isolation of rare circulating tumour cells in cancer patients by microchip technology

    PubMed Central

    Nagrath, Sunitha; Sequist, Lecia V.; Maheswaran, Shyamala; Bell, Daphne W.; Irimia, Daniel; Ulkus, Lindsey; Smith, Matthew R.; Kwak, Eunice L.; Digumarthy, Subba; Muzikansky, Alona; Ryan, Paula; Balis, Ulysses J.; Tompkins, Ronald G.; Haber, Daniel A.; Toner, Mehmet

    2011-01-01

    Viable tumour-derived epithelial cells (circulating tumour cells or CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease1–4. Although extremely rare, CTCs represent a potential alternative to invasive biopsies as a source of tumour tissue for the detection, characterization and monitoring of non-haematologic cancers5–8. The ability to identify, isolate, propagate and molecularly characterize CTC subpopulations could further the discovery of cancer stem cell biomarkers and expand the understanding of the biology of metastasis. Current strategies for isolating CTCs are limited to complex analytic approaches that generate very low yield and purity9. Here we describe the development of a unique microfluidic platform (the ‘CTC-chip’) capable of efficient and selective separation of viable CTCs from peripheral whole blood samples, mediated by the interaction of target CTCs with antibody (EpCAM)-coated microposts under precisely controlled laminar flow conditions, and without requisite pre-labelling or processing of samples. The CTC-chip successfully identified CTCs in the peripheral blood of patients with metastatic lung, prostate, pancreatic, breast and colon cancer in 115 of 116 (99%) samples, with a range of 5–1,281 CTCs per ml and approximately 50% purity. In addition, CTCs were isolated in 7/7 patients with early-stage prostate cancer. Given the high sensitivity and specificity of the CTC-chip, we tested its potential utility in monitoring response to anti-cancer therapy. In a small cohort of patients with metastatic cancer undergoing systemic treatment, temporal changes in CTC numbers correlated reasonably well with the clinical course of disease as measured by standard radiographic methods. Thus, the CTC-chip provides a new and effective tool for accurate identification and measurement of CTCs in patients with cancer. It has broad implications in advancing both cancer biology

  19. Therapy-induced tumour secretomes promote resistance and tumour progression

    PubMed Central

    Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan

    2015-01-01

    Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485

  20. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization

    PubMed Central

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2–66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24–3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15–2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  1. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization.

    PubMed

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2-66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24-3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15-2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  2. Hematogenous Splenic Metastases as an Independent Negative Prognosis Factor at the Moment of Primary Cytoreduction in Advanced Stage Epithelial Ovarian Cancer--A Single Center Experience.

    PubMed

    Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona; Brasoveanu, Vladislav; Popescu, Irinel

    2015-10-01

    Ovarian cancer represents an aggressive gynecological malignancy with a high capacity for dissemination. Once the tumor cells go beyond the pelvic area, upper abdominal involvement, including hepatic, diaphragmatic or even splenic, is frequently seen. The aim of the present study was to determine the impact on survival of parenchymatous versus peritoneal splenic metastases versus splenic hilum lymph node involvement at the time of primary cytoreduction for advanced-stage epithelial ovarian cancer. Sixty-six patients with a mean age of 54.12 years (range=25-80 years) were submitted to splenectomy in the context of primary cytoreduction at the Dan Setlacec Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, between January 2002 and May 2014. Although complete macroscopic resection was attempted in all cases, an R0 resection was achieved only in 57 out of the 66 cases. Histopathological studies confirmed the presence of serous subtype in 61 cases, while in the other five cases, the mucinous subtype was found. When studying the specimens of splenectomy, capsular invasion was found in 35 cases (53%), parenchymatous involvement was present in 19 (28.7%), and hilar involvement was present in 12 (18.1%). The overall morbidity rate was 30%, while the 30-day postoperative mortality rate was 7%. The median overall survival for cases with peritoneal seeding was 58.4 months, while that for patients with parenchymatous involvement was 24.5 months (p=0.0126); patients diagnosed with hilar involvement had a median overall survival of 40.6 months (p=0.362). In conclusion, the presence of parenchymatous splenic metastases at primary cytoreduction for advanced-stage ovarian cancer is associated with significantly poorer survival when compared to hilar or peritoneal seeding. PMID:26408738

  3. An ovary transcriptome for all maturational stages of the striped bass (Morone saxatilis), a highly advanced perciform fish

    PubMed Central

    2012-01-01

    Background The striped bass and its relatives (genus Morone) are important fisheries and aquaculture species native to estuaries and rivers of the Atlantic coast and Gulf of Mexico in North America. To open avenues of gene expression research on reproduction and breeding of striped bass, we generated a collection of expressed sequence tags (ESTs) from a complementary DNA (cDNA) library representative of their ovarian transcriptome. Results Sequences of a total of 230,151 ESTs (51,259,448 bp) were acquired by Roche 454 pyrosequencing of cDNA pooled from ovarian tissues obtained at all stages of oocyte growth, at ovulation (eggs), and during preovulatory atresia. Quality filtering of ESTs allowed assembly of 11,208 high-quality contigs ≥ 100 bp, including 2,984 contigs 500 bp or longer (average length 895 bp). Blastx comparisons revealed 5,482 gene orthologues (E-value < 10-3), of which 4,120 (36.7% of total contigs) were annotated with Gene Ontology terms (E-value < 10-6). There were 5,726 remaining unknown unique sequences (51.1% of total contigs). All of the high-quality EST sequences are available in the National Center for Biotechnology Information (NCBI) Short Read Archive (GenBank: SRX007394). Informative contigs were considered to be abundant if they were assembled from groups of ESTs comprising ≥ 0.15% of the total short read sequences (≥ 345 reads/contig). Approximately 52.5% of these abundant contigs were predicted to have predominant ovary expression through digital differential display in silico comparisons to zebrafish (Danio rerio) UniGene orthologues. Over 1,300 Gene Ontology terms from Biological Process classes of Reproduction, Reproductive process, and Developmental process were assigned to this collection of annotated contigs. Conclusions This first large reference sequence database available for the ecologically and economically important temperate basses (genus Morone) provides a foundation for gene expression studies in these species. The

  4. Evaluation of 30-Day Hospital Readmission After Surgery for Advanced-Stage Ovarian Cancer in a Medicare Population

    PubMed Central

    Eskander, Ramez N.; Chang, Jenny; Ziogas, Argyrios; Anton-Culver, Hoda; Bristow, Robert E.

    2014-01-01

    Purpose To analyze rate, risk factors, and costs associated with 30-day readmission after ovarian cancer surgery. Patients and Methods The SEER-Medicare linked database (1992 to 2010) was used to evaluate readmission rates within 30 days of index surgery in patients with stage IIIC/IV ovarian, primary peritoneal, or fallopian tube cancer. Multivariable logistic regression was used to identify factors associated with readmission. Results Of 5,152 eligible patients, 1,003 (19.5%) were readmitted within 30 days of discharge. Mean patient age was 75 years. Diagnoses associated with readmission included infection (34.7%), dehydration (34.3%), ileus/obstruction (26.2%), metabolic/electrolyte derangements (23.1%), and anemia (12.3%). In multivariable analysis, year of discharge was significantly associated with 30-day readmission (1996 to 2000: odds ratio [OR], 1.32; 95% CI, 1.01 to 1.71; 2001 to 2005: OR, 1.58; 95% CI, 1.24 to 2.0; 2006 to 2010: OR, 1.73; 95% CI, 1.35 to 2.21; referent years 1992 to 1995), as were length of index hospital stay more than 8 days (OR, 1.39; 95% CI, 1.18 to 1.64) and discharge to a skilled nursing facility (OR, 1.3; 95% CI, 1.04 to 1.63). Patients readmitted within 30 days had a significantly greater 1-year mortality rate compared with patients not readmitted (41.1% v 25.1%, respectively; P < .001). The median cost of readmission hospital stay was $9,220 in year 2010 dollars, with a total cost of $9.3 million over the study period. Conclusion Early readmission after surgery for ovarian cancer is common. There is a significant association between 30-day readmission and 1-year mortality. These findings may catalyze development of targeted interventions to decrease early readmission, improve patient outcomes, and control health care costs. PMID:25385738

  5. 6p22.3 amplification as a biomarker and potential therapeutic target of advanced stage bladder cancer

    PubMed Central

    Zhang, Jianmin; Underwood, Willie; Yang, Nuo; Frangou, Costa; Eng, Kevin; Head, Karen; Bollag, Roni J.; Kavuri, Sravan K.; Rojiani, Amyn M.; Li, Yingwei; Yan, Li; Hill, Annette; Woloszynska-Read, Anna; Wang, Jianmin; Liu, Song; Trump, Donald L.; Candace, Johnson S.

    2013-01-01

    Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). In a comparative fashion much less is known about copy number alterations in TCC-UB, but it appears that amplification of chromosome 6p22 is one of the most frequent changes. Using fluorescence in situ hybridization (FISH) analyses, we evaluated chromosomal 6p22 amplification in a large cohort of bladder cancer patients with complete surgical staging and outcome data. We have also used shRNA knockdown candidate oncogenes in the cell based study. We found that amplification of chromosome 6p22.3 is significantly associated with the muscle-invasive transitional cell carcinoma of the urinary bladder (TCC-UB) (22%) in contrast to superficial TCC-UB (9%) (p=7.2-04). The rate of 6p22.3 amplification in pN>1 patients (32%) is more than twice that in pN0 (16%) patients (p=0.05). Interestingly, we found that 6p22.3 amplification is as twice as high (p=0.0201) in African American (AA) than European American (EA) TCC-UB patients. Moreover, we showed that the expression of some candidate genes (E2F3, CDKAL1 and Sox4) in the 6p22.3 region is highly correlated with the chromosomal amplification. In particular, knockdown of E2F3 inhibits cell proliferation in a 6p22.3-dependent manner, whereas knockdown of CDKAL1 and Sox4 has no effect on cell proliferation. Using gene expression profiling, we further identified some common as well as distinctive subset targets of the E2F3 family members. In summary, our data indicate that E2F3 is a key regulator of cell proliferation in a subset of bladder cancer and the 6p22.3 amplicon is a biomarker of aggressive phenotype in this tumor type. PMID:24231253

  6. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  7. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  8. R-CHOP with Iodine-131 Tositumomab Consolidation for Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL): SWOG S0433

    PubMed Central

    Friedberg, Jonathan W.; Unger, Joseph M.; Burack, W. Richard; Gopal, Ajay K.; Raju, Robert N.; Nademanee, Auayporn P.; Kaminski, Mark S.; Li, Hongli; Press, Oliver W.; Miller, Thomas P.; Fisher, Richard I.

    2014-01-01

    Radiolabelled antiCD-20 antibodies have demonstrated single agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). The S0433 clinical trial enrolled patients with newly diagnosed, advanced stage or bulky stage II, histologically confirmed DLBCL. Patients received six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles of CHOP, then iodine-131 tositumomab radioimmunotherapy consolidation 30–60 days after completion of chemotherapy. The primary endpoint was two-year progression-free survival (PFS). Eighty-four eligible patients were enrolled, and 56 patients completed the entire course of protocol treatment. Of the 84 patients evaluable for treatment response, 72 (86%, 95% confidence interval [CI]: 76%–92%) achieved a partial response (n=21) or a confirmed (n=41) or unconfirmed (n=10) complete response to therapy. With a median follow-up of 3.9 years, the 2-year PFS estimate is 69% and the 2-year overall survival estimate is 77%. Rituximab levels at time of radioimmunotherapy did not correlate with toxicity or outcome. Twenty percent of patients had double hit features (MYC+; BCL2+) by immunohistochemistry, and had inferior outcome. These current results suggest that the incorporation of novel agents earlier in therapy may ultimately have greater impact in DLBCL, as early progressions, deaths and declining performance status during CHOP chemotherapy limited the number of patients who ultimately could benefit from radioimmunotherapy consolidation. PMID:24749780

  9. Modeling and Test Data Analysis of a Tank Rapid Chill and Fill System for the Advanced Shuttle Upper Stage (ASUS) Concept

    NASA Technical Reports Server (NTRS)

    Flachbart, Robin; Hedayat, Ali; Holt, Kimberly A.; Cruit, Wendy (Technical Monitor)

    2001-01-01

    The Advanced Shuttle Upper Stage (ASUS) concept addresses safety concerns associated .with cryogenic stages by launching empty, and filling on ascent. The ASUS employs a rapid chill and fill concept. A spray bar is used to completely chill the tank before fill, allowing the vent valve to be closed during the fill process. The first tests of this concept, using a flight size (not flight weight) tank. were conducted at Marshall Space Flight Center (MSFC) during the summer of 2000. The objectives of the testing were to: 1) demonstrate that a flight size tank could be filled in roughly 5 minutes to accommodate the shuttle ascent window, and 2) demonstrate a no-vent fill of the tank. A total of 12 tests were conducted. Models of the test facility fill and vent systems, as well as the tank, were constructed. The objective of achieving tank fill in 5 minutes was met during the test series. However, liquid began to accumulate in the tank before it was chilled. Since the tank was not chilled until the end of each test, vent valve closure during fill was not possible. Even though the chill and fill process did not occur as expected, reasonable model correlation with the test data was achieved.

  10. Tumours of the upper alimentary tract.

    PubMed

    Head, K W

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. PMID:1086147

  11. Circulating tumour cells in patients with urothelial tumours: Enrichment and in vitro culture

    PubMed Central

    Kolostova, Katarina; Cegan, Martin; Bobek, Vladimir

    2014-01-01

    Introduction: Results of clinical trials have demonstrated that circulating tumour cells (CTCs) are frequently detected in patients with urothelial tumours. The monitoring of CTCs has the potential to improve therapeutic management at an early stage and also to identify patients with increased risk of tumour progression or recurrence before the onset of clinically detected metastasis. In this study, we report a new effectively simplified methodology for a separation and in vitro culturing of viable CTCs from peripheral blood. Method: We include patients diagnosed with 3 types of urothelial tumours (prostate cancer, urinary bladder cancer, and kidney cancer). A size-based separation method for viable CTC - enrichment from unclothed peripheral blood has been introduced (MetaCell, Ostrava, Czech Republic). The enriched CTCs fraction was cultured directly on the separation membrane, or transferred from the membrane and cultured on any plastic surface or a microscopic slide. Results: We report a successful application of a CTCs isolation procedure in patients with urothelial cancers. The CTCs captured on the membrane are enriched with a remarkable proliferation potential. This has enabled us to set up in vitro cell cultures from the viable CTCs unaffected by any fixation buffers, antibodies or lysing solutions. Next, the CTCs were cultured in vitro for a minimum of 10 to 14 days to enable further downstream analysis (e.g., immunohistochemistry). Conclusion: We demonstrated an efficient CTCs capture platform, based on a cell size separation principle. Furthermore, we report an ability to culture the enriched cells – a critical requirement for post-isolation cellular analysis. PMID:25408812

  12. EGFR and microvessel density in canine malignant mammary tumours.

    PubMed

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  13. Unusual dumbbell tumours of the mediastinum and thoracic spine.

    PubMed

    Kilic, Dalokay; Erdogan, Bulent; Sener, Levent; Sahin, Ekber; Caner, Hakan; Hatipoglu, Ahmet

    2006-11-01

    Due to a lack of large clinical series in the literature of chondrosarcomas and hydatid disease presenting as mediastinal dumbbell tumours, clinicians have limited experience on this topic. We present three unusual cases of dumbbell tumour involving the spinal canal; two patients had chondrosarcoma originating from Th8-Th9 and Th10-Th12; one patient had a hydatid cyst at Th5-Th6. We performed a single-stage combined thoracic-neurosurgical approach in two patients, and a double-staged approach in one patient. During the intraspinal dissection, an operating microscope was used under electrophysiological monitoring. Spinal canal reconstruction was not required for any of the cases. Preoperative knowledge of neuroforaminal extension and the relations between the tumour and adjacent neural-vascular structures is essential to prevent spinal cord damage and plan the surgical approach. In chondrosarcomas, prognosis depends on patient age, histological grade, extent of surgery and response to radiotherapy and/or chemotherapy. In this article, the diagnostic and surgical difficulties of these unusual tumours and current treatment modalities are discussed with a review of the relevant literature. PMID:16857360

  14. Combined processes of two-stage Fenton-biological anaerobic filter-biological aerated filter for advanced treatment of landfill leachate.

    PubMed

    Wang, Xiaojun; Han, Jijun; Chen, Zhiwei; Jian, Lei; Gu, Xiaoyang; Lin, Che-Jen

    2012-12-01

    There are numerous non-biodegradable organic materials in the mature landfill leachate. To meet the new discharge standard of China, additional advanced treatment is needed for the effluent from the biological treatment processes of leachate. In this study, a combined process including two stages of "Fenton-biological anaerobic filter (BANF)-biological aerated filter (BAF)" was evaluated to address the advanced treatment need. The Fenton oxidation was applied to reduce chemical oxygen demand (COD) and enhance biodegradability of refractory organics, and the BANF-BAF process was then applied to remove the total nitrogen (TN). The treatment achieved effluent concentrations of COD<70 mg/L, TN<40 mg/L and NH(3)-N<10 mg/L. The removal efficiency of COD and TN were 96.1% and 95.9%, respectively. The effluent quality met the new discharge standard for Pollution Control on the Landfill Site of Municipal Solid of PR China (GB16889-2008). The operation cost of these processes was about 36.1CHY/t (5.70USD/t). PMID:22841597

  15. Effect of Advancing Age and Multiple Chronic Conditions on Mortality in Patients with End-Stage Renal Disease after Implantable Cardioverter-Defibrillator Placement

    PubMed Central

    Krishnaswami, Ashok; Kiley, Mary-Lou; Anthony, Faith F; Chen, Yuexin; Chen, Jason; Rajagopal, Sumanth; Liu, Taylor I; Young, Charlie; Paxton, Elizabeth W

    2016-01-01

    Context: There is insufficient information on the effect that advancing age and multiple chronic conditions (MCC) have on mortality after placement of an implantable cardioverter-defibrillator in patients with end-stage renal disease (ESRD) vs non-ESRD. Objective: To assess whether a differential effect of age and MCC exists between ESRD and non-ESRD. Design: Population-based, retrospective cohort study using data from the national Kaiser Permanente Cardiac Device Registry of patients who underwent placement of an implantable cardioverter-defibrillator between January 1, 2007, and December 31, 2013. Main Outcome Measures: All-cause mortality. Results: Of 7825 patients with implantable cardioverter-defibrillator placement, ESRD-affected patients constituted 4.0% of the cohort (n = 311), were similar in age (p = 0.91), and presented with a larger comorbidity burden (3.3 ± 1.3 vs 2.4 ± 1.5, p < 0.001). The effect of advancing age (every 5 years) on mortality in the ESRD cohort (hazard ratio [HR] = 1.11, 95% confidence interval [CI] = 1.03–1.20) was less than in the non-ESRD cohort (HR = 1.28, 95% CI = 1.25–1.32). Similarly, the effect of each additional comorbidity in the ESRD cohort was less (HR = 1.04, 95% CI = 0.91–1.19) than in the non-ESRD group (HR = 1.20, 95% CI = 1.16–1.25). Lastly, ESRD was independently associated with a 3-fold greater hazard of mortality. Conclusions: Advancing age and increasing number of MCC have a differential effect on mortality risk in patients with ESRD compared with their non-ESRD counterparts. Future studies should focus on assessment of nonlinear relationships of age, MCC, and naturally occurring clusters of MCC on mortality. PMID:26562307

  16. Oncoprotein stability after tumour resection.

    PubMed Central

    Ong, G.; Gullick, W.; Sikora, K.

    1990-01-01

    The means by which oncogenes and their products activate malignant transformation are currently under intense investigation. However, published papers on experiments using human tumour material do not always report in detail their methods of collection or storage of the specimens. In order to assess the stability of oncogene encoded proteins following collection or storage of human tumour biopsies, we have examined the rate of decay of the c-myc, neu and EGF-receptor proteins. Solid tumours, containing amplified copies of each oncogene, were established in nude mice and the stability of the oncogene protein in portions of each tumour, left in phosphate buffered saline at room temperature for varying time intervals, was examined by immunoblotting. Intact EGF-receptor and neu oncoproteins were present even after 24 h under these conditions while the c-myc protein was apparently rapidly degraded after 20 min. These data demonstrate that oncogene products decay at different rates after tumour resection and that collection of human biopsies should take this into account in order to provide the basis for consistent measurements of protein expression. Images Figure 1 Figure 2 Figure 3 PMID:2139576

  17. Solitary fibrous tumour of the supraglottic larynx.

    PubMed

    Grammatica, A; Bolzoni Villaret, A; Ravanelli, M; Nicolai, P

    2016-06-01

    Solitary fibrous tumour (SFT) is a rare, benign, mesenchymal neoplasm that usually arises in the pleura, but rarely involves other sites outside the serosal space (mediastinum, lung, liver, thyroid gland); larynx involvement is very rare with only sporadic cases reported in the literature. We report a case of SFT in a 41-year-old woman with supraglottic laryngeal invovlement; symptoms included dysphonia and mild odynophagia lasting 2 years, and fibre-optic laryngeal evaluation showed a sub-mucosal mass involving the left supraglottis and medial wall of the pyriform sinus. MRI represents the gold standard tool for differential diagnosis (with schwannoma, paraganglioma and haemangioma) and correct staging, while immunohistochemical and cytomorphologic analysis (bcl-2 and CD34 positivity in 90% of cases) is needed for definitive diagnosis. Surgery is the main treatment (endoscopic and open conservative technique), and its goal is a balance between safe oncological resection and good preservation of laryngeal functions; in this particular case an open laryngeal approach was scheduled due to the size of the tumour. Prognosis is good and in only a few cases (especially in pleural SFT) does the biological behaviour take a malignant course. PMID:27070539

  18. Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome

    PubMed Central

    Laird, Alexander; O’Mahony, Fiach C.; Nanda, Jyoti; Riddick, Antony C. P.; O’Donnell, Marie; Harrison, David J.; Stewart, Grant D.

    2013-01-01

    Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly

  19. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  20. Tumour-associated eosinophilia: a review.

    PubMed Central

    Lowe, D; Jorizzo, J; Hutt, M S

    1981-01-01

    In a recent study of cervical carcinoma, 13 cases with a marked eosinophil infiltrate around the tumour were found. The histological appearance of the tumours was distinctive and suggested a specific response, similar to the lymphocyte infiltration in medullary carcinoma of the breast and seminoma. A review of published reports shows that tumour-associated tissue eosinophilia (TATE) and tumour-associated blood eosinophilia (TABE) may be seen in tumours of different histological types from different anatomical sites, and may occur together or separately. Tumours with TATE alone appear to have a better prognosis that those without, while TABE is associated with tumor spread and a poor prognosis. Images PMID:7035499

  1. Decreased xanthine oxidoreductase is a predictor of poor prognosis in early‐stage gastric cancer

    PubMed Central

    Linder, N; Haglund, C; Lundin, M; Nordling, S; Ristimäki, A; Kokkola, A; Mrena, J; Wiksten, J‐P; Lundin, J

    2006-01-01

    Background Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA, RNA and high‐energy phosphates. About half of the patients with breast cancer have a decrease in XOR expression. Patients with breast cancer with unfavourable prognosis are independently identified by the loss of XOR. Aim To assess the clinical relevance of XOR expression in gastric cancer. Methods XOR levels were studied by immunohistochemistry in tissue microarray specimens of 337 patients with gastric cancer and the relation between XOR expression and a series of clinicopathological variables, as well as disease‐specific survival, was assessed. Results XOR was moderately decreased in 41% and was undetectable in another 14% of the tumours compared with the corresponding normal tissue. Decreased XOR was associated with advanced stage, deep tumour penetration, diffusely spread tumour location, positive lymph node status, large tumour size, non‐curative disease, cellular aneuploidy, high S‐phase fraction and high cyclooxygenase‐2 expression, but not with p53 expression or Borrmann classification. Down regulation of XOR was associated with unfavourable outcome, and the cumulative 5‐year gastric cancer‐specific survival in patients with strong XOR expression was 47%, compared with 22% in those with moderate to negative expression (p<0.001). This was also true in patients with stage I–II (p = 0.01) and lymph node‐negative (p = 0.02) disease, as well as in patients with smaller (⩽5 cm) tumours (p = 0.02). Conclusion XOR expression in gastric cancer may be a new marker for a more aggressive gastric cancer biology, similar to that previously reported for breast cancer. PMID:16935971

  2. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    PubMed Central

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  3. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan.

    PubMed

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-Ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal-regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  4. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    PubMed

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  5. Role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Staging of Bladder Cancer

    PubMed Central

    Rabie, Elham; Izadpanahi, Mohammad-Hossein; Dayani, Mohammad-Ali

    2016-01-01

    Introduction Dynamic Contrast Enhanced (DCE)-Magnetic Resonance Imaging (MRI) is a useful technique in which rapid enhancement of tumour by uptake of the contrast agent compared to bladder wall. Aim To evaluate the accuracy of dynamic gadolinium-enhanced MRI in staging of bladder cancer through differentiating superficial tumours from invasive tumours and organ-confined tumours from non-organ-confined tumours. In addition, the benefits of DCE-MRI in diagnosis of tumour progression steps were investigated. Materials and Methods This was a quasi-experimental study in which 45 patients (95.55% men and 4.45% women) were enrolled. Patients with confirmed transitional cell carcinoma by histopathology findings were imaged using 1.5 Tesla MRI systems. Pathology results were considered as the standard reference. Tumour stage was determined by imaging findings and compared with pathologic findings after radical cystectomy. Data were analysed by SPSS version 16 and the level of significance in all tests was considered p<0.001. Results The most common stage that was seen in pathology and MRI findings was T3b. Kappa agreement coefficient between MRI and pathology was 0.7 (p<0.001). The accuracy of MRI in differentiating superficial tumours (≤T1) from invasive tumours (≥ T2a), and organ-confined tumours (≤T2b) from non-organ-confined tumours (≥T3b) was 0.97 and 0.84, respectively. The overall accuracy of MRI was 0.77 (p<0.001). Totally, 10 cases of disagreement between MRI and pathological staging were found, eight (80%) of which were overestimated and two cases (20%) underestimated. MRI detection rate was 0% in stage Ta, 100% in stage T1, 66.7% in stage T2, 86.7% in stage T3, and 100% in stage T4. The sensitivity and specificity of MRI in differentiating superficial tumours from invasive tumours were 0.97 and 1, respectively, and in differentiating organ-confined tumours from non-organ-confined tumours were 0.94 and 0.77, respectively. The Spearman’s correlation

  6. Tailored nanoparticles for tumour therapy.

    PubMed

    Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju; Kao, Chao-Hung; Lee, Kun-Feng; Kuo, Chien-Hung; Lin, Xi-Zhang; Lin, Yuh-Jiuan

    2012-06-01

    Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment. PMID:22905580

  7. Brown tumour of the jaw

    PubMed Central

    Nair, Preeti P; Gharote, Harshkant P; Thomas, Shaji; R, Guruprasad; Singh, Neha

    2011-01-01

    Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented. PMID:22669885

  8. A rare urinary bladder tumour

    PubMed Central

    Haddad-Lacle, Judella Edwina Maria; Haddad, Charles Joseph; Villas, Bruce

    2014-01-01

    This case report describes a 54-year-old man who presented to his primary care physician with low back pain. During his workup, an incidental finding of a bladder mass was diagnosed. He underwent transurethral resection of the bladder tumour and the resulting pathology was consistent with extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Presentation of MALT lymphoma in the urinary bladder is rare. This malignancy is more commonly found in the stomach. The prognosis for this rare tumour is excellent. Our patient showed no sign of recurrence with transurethral excision and radiation alone. PMID:24835803

  9. Use of field and airborne advanced remote sensing data for the characterisation of surface erosional stages in agricultural semi-arid soils (central Spain) at various scales

    NASA Astrophysics Data System (ADS)

    Milewski, Robert; Chabrillat, Sabine; Schmid, Thomas; Rodriguez, Manuel; Schuett, Brigitta

    2014-05-01

    The interest in the use of non-invasive remote sensing methods such as visible-near infrared reflectance spectroscopy for the remote determination of mineralogical composition in soils and planetary surfaces has been demonstrated since the 1970s with the development of databases in the laboratory of minerals spectra. Nowadays, quantitative soil spectroscopy has been shown to be a powerful tool for the identification and prediction of soil properties, and has been used in many soil science applications. With the upcoming launch of the next generation of hyperspectral satellite systems such as the German EnMAP (Environmental Mapping) satellite in 2017, new potential toward the quantitative analyses of chemical and physical soil attributes of the Earth's soil surface composition based on reflectance spectroscopy will be opened. In particular, in arid and semi-arid agricultural regions sensitive to soil erosion processes, the analyses of the spatial distribution of combined varying surface soil properties based on advanced hyperspectral methodology could be used to infer erosion and deposition stages in selected areas, although it was never thoroughly demonstrated. To fully utilize the potential of this technology for the assessment of surface soil erosional stages, new adapted approaches have to be developed, providing the context for this study. This research focuses on a semi-arid, agricultural area in Central Spain near Toledo and Madrid, in which airborne hyperspectral and LiDAR data have been obtained. The study area is under the influence of a Mediterranean climate with extended agricultural rainfed uses on mostly evolved soils. There, soil erosion features can be observed that are representative for areas throughout Southern Europe. Such erosion features are associated with different soil horizons and rock outcrops with contrasted physical and chemical characteristic. They are exposed at the surface as a consequence of human induced soil erosion which is

  10. Alpha-fetoprotein production by a malignant mixed müllerian tumour of the uterus.

    PubMed Central

    Phillips, K A; Scurry, J P; Toner, G

    1996-01-01

    A case of alpha-fetoprotein production by a uterine malignant mixed müllerian tumour is described. The patient was a 68 year old woman who developed intraabdominal recurrence of a stage 1 uterine tumour which had been treated surgically seven years previously. Her serum alpha-fetoprotein was raised at 21,000 micrograms/l (normal < 10 micrograms/l) and staining with immunoperoxidase confirmed that the tumour was the site of alpha-fetoprotein production. The patient was treated with combination chemotherapy but died two weeks after the first course. This is believed to be only the second such case reported. Images PMID:8655717

  11. Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma

    PubMed Central

    Baldan, V; Griffiths, R; Hawkins, R E; Gilham, D E

    2015-01-01

    Background: Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. Methods: Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. Results: Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. Conclusion: TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population. PMID:25867267

  12. Inflammation and cancer: advances and new agents.

    PubMed

    Crusz, Shanthini M; Balkwill, Frances R

    2015-10-01

    Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response. PMID:26122183

  13. [A woman with a tumour on the sole of her foot].

    PubMed

    Roest, Yvonne; Kuijpers, Astrid

    2014-01-01

    A 53-year-old woman came to de department of Dermatology with a tumour on the sole of her foot that appeared 5 years ago. A histology test revealed a desmoplastic melanoma. This is a rare type of melanoma that is, in an early stage, frequently mistaken for a benign tumour. Desmoplastic melanoma has a high rate of local recurrence and a low incidence of distant metastases, unlike other melanomas. PMID:25336314

  14. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    PubMed Central

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  15. Prospective assessment of the prognostic value of circulating tumor cells and their clusters in patients with advanced-stage breast cancer.

    PubMed

    Mu, Zhaomei; Wang, Chun; Ye, Zhong; Austin, Laura; Civan, Jesse; Hyslop, Terry; Palazzo, Juan P; Jaslow, Rebecca; Li, Bingshan; Myers, Ronald E; Jiang, Juntao; Xing, Jinliang; Yang, Hushan; Cristofanilli, Massimo

    2015-12-01

    The enumeration of circulating tumor cells (CTCs) provides important prognostic values in patients with metastatic breast cancer. Recent studies indicate that individual CTCs form clusters and these CTC-clusters play an important role in tumor metastasis. We aimed to assess whether quantification of CTC-clusters provides additional prognostic value over quantification of individual CTCs alone. In 115 prospectively enrolled advanced-stage (III and IV) breast cancer patients, CTCs and CTC-clusters were counted in 7.5 ml whole blood using the CellSearch system at baseline before first-line therapy. The individual and joint effects of CTC and CTC cluster counts on patients' progression-free survival (PFS) were analyzed using Cox proportional hazards modeling. Of the 115 patients, 36 (31.3 %) had elevated baseline CTCs (≥5 CTCs/7.5 ml) and 20 (17.4 %) had CTC-clusters (≥2 CTCs/7.5 ml). Patients with elevated CTCs and CTC-clusters both had worse PFS with a hazard ratio (HR) of 2.76 [95 % confidence interval (CI) 1.57-4.86, P log-rank = 0.0005] and 2.83 (1.48-5.39, P log-rank = 0.001), respectively. In joint analysis, compared with patients with <5 CTCs and without CTC-clusters, patients with elevated CTCs but without clusters, and patients with elevated CTCs and with clusters, had an increasing trend of progression risk, with an HR of 2.21 (1.02-4.78) and 3.32 (1.68-6.55), respectively (P log-rank = 0.0006, P trend = 0.0002). The additional prognostic value of CTC-clusters appeared to be more pronounced in patients with inflammatory breast cancer (IBC), the most aggressive form of breast cancer with the poorest survival. Baseline counts of both individual CTCs and CTC-clusters were associated with PFS in advanced-stage breast cancer patients. CTC-clusters might provide additional prognostic value compared with CTC enumeration alone, in patients with elevated CTCs. PMID:26573830

  16. A randomized prospective study of comparison of reservoir ports versus conventional vascular access in advanced-stage ovarian carcinoma cases treated with chemotherapy.

    PubMed

    Sehirali, S; Inal, M M; Ozsezgin, S; Sanci, M; Atli, O; Nayki, C; Yildirim, Y; Tinar, S

    2005-01-01

    Vascular access ports were developed to overcome many of the problems associated with limited peripheral access, combined with the need for frequent venipuncture, in oncology patients receiving long-term intensive therapy. In this study, we compared the effectivity and acceptability of vascular access port with conventional needle application together with complication rates in ovarian cancer patients. Advanced-stage ovarian carcinoma cases under chemotherapy treatment were equally randomized into two groups, implantable vascular access ports applied to one group (22 cases) and conventional vascular access applied to the other (38 cases) as a control group. Anteroposterior thoracic X-rays of implantable port-applied cases were taken before and after the application. Vortex reservoir ports (Horizon Medical Products, Inc., Manchester, GA) were used in the application to the subclavian vein. Classic peripheral venipuncture method (Medikit), Mediflon(trade mark) IV cannula with PTFE radiopaque catheter and injection valve, Eastern Medikit Ltd, Gurgaon, Haryana, India) was used in the control group. Vascular accesses of all cases were controlled just after the application, 12 h after the application, and during each drug or intravenous fluid application. Mean port insertion time was 26.3 min. Total port occlusion was observed in two of the port-applied cases (11.7%) and partial port occlusion was observed in five of the port-applied cases (29%). Heparin and saline combination was used in order to open the port tip, in five cases, two with total occlusion and three with partial occlusion. Infection was observed in only one case (5%) to whom appropriate therapy was given, and the port was taken out. Ports of two cases were also taken out because of skin dehiscence. No change in port tip position was observed in any of the cases. Total occlusion was observed in 16 of the 38 cases (42.1%) with conventional vascular access. In 12 cases (31.5%), a need arose to change the

  17. Impact of Pretreatment Combined {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging on Radiation Therapy Treatment Decisions in Locally Advanced Breast Cancer

    SciTech Connect

    Ng, Sweet Ping; David, Steven; Alamgeer, Muhammad; Ganju, Vinod

    2015-09-01

    Purpose: To assess the diagnostic performance of pretreatment {sup 18}F-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) and its impact on radiation therapy treatment decisions in patients with locally advanced breast cancer (LABC). Methods and Materials: Patients with LABC with Eastern Cooperative Oncology Group performance status <2 and no contraindication to neoadjuvant chemotherapy, surgery, and adjuvant radiation therapy were enrolled on a prospective trial. All patients had pretreatment conventional imaging (CI) performed, including bilateral breast mammography and ultrasound, bone scan, and CT chest, abdomen, and pelvis scans performed. Informed consent was obtained before enrolment. Pretreatment whole-body {sup 18}F-FDG PET/CT scans were performed on all patients, and results were compared with CI findings. Results: A total of 154 patients with LABC with no clinical or radiologic evidence of distant metastases on CI were enrolled. Median age was 49 years (range, 26-70 years). Imaging with PET/CT detected distant metastatic disease and/or locoregional disease not visualized on CI in 32 patients (20.8%). Distant metastatic disease was detected in 17 patients (11.0%): 6 had bony metastases, 5 had intrathoracic metastases (pulmonary/mediastinal), 2 had distant nodal metastases, 2 had liver metastases, 1 had pulmonary and bony metastases, and 1 had mediastinal and distant nodal metastases. Of the remaining 139 patients, nodal disease outside conventional radiation therapy fields was detected on PET/CT in 15 patients (10.8%), with involvement of ipsilateral internal mammary nodes in 13 and ipsilateral level 5 cervical nodes in 2. Conclusions: Imaging with PET/CT provides superior diagnostic and staging information in patients with LABC compared with CI, which has significant therapeutic implications with respect to radiation therapy management. Imaging with PET/CT should be considered in all patients undergoing primary

  18. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of the chromosomal error: A population-based study

    SciTech Connect

    Yoon, P.W.; Khoury, M.J.; Freeman, S.B.

    1996-03-01

    The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women {>=}40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women {>=}40 years old were 4.2/1,000 births for MMI errors and 1.9/1,000 births for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal age-related mechanism acting around the time of conception. 16 refs., 1 fig., 2 tabs.

  19. Consolidation chwemotherapy after concurrent chemoradiotherapy vs. chemoradiotherapy alone for locally advanced unresectable stage III non-small-cell lung cancer: A meta-analysis

    PubMed Central

    Chang, Xiu-Jun; Wang, Zi-Tong; Yang, Lei

    2016-01-01

    Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced unresectable stage III non-small-cell lung cancer (LA-NSCLC). Whether consolidation chemotherapy (CCT) following CCRT is able to further improve the clinical outcome remains unclear. We therefore undertook a meta-analysis to compare the two regimens for LA-NSCLC. A literature search was performed through PubMed, Embase, Cochrane Library and Chinese Biology Medicine, from their inception to November, 2015. Irrelevant studies were excluded using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. Our primary endpoint was overall survival (OS), which was defined as the time from randomisation until death from any cause; the secondary endpoint was progression-free survival (PFS). All analyses were by intention-to-treat. Five phase III randomized controlled trials with 958 patients were included in the present meta-analysis. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Compared with CCRT, CCT after CCRT was not associated with statistically significant differences in OS (OR=1.24; 95% CI: 0.89–1.72; P=0.21) or PFS (OR=1.16; 95% CI: 0.74–1.83; P=0.53), but increased the risk of toxicity, including infection (P=0.02), pneumonitis (P=0.003) and treatment-related death (P=0.04). There were no significant differences in terms of benefit according to particular patient characteristics, such as age, gender, performance status, tumor histology or clinical stage. Thus, the present study failed to support the use of CCT after CCRT over CCRT alone, as there was no significant OS and PFS benefit for LA-NSCLC patients, but the use of CCT after CCRT resulted in increased toxicity. PMID:27446563

  20. Tumours of the soft (mesenchymal) tissues.

    PubMed

    Weiss, E

    1974-01-01

    This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs. PMID:4371740

  1. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

    PubMed Central

    2012-01-01

    Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found

  2. Diagnostic Utility of PET CT in Thymic Tumours with Emphasis on 68Ga-DOTATATE PET CT in Thymic Neuroendocrine Tumour - Experience at a Tertiary Level Hospital in India

    PubMed Central

    Shanthly, Nylla; Oommen, Regi

    2014-01-01

    Introduction:18 Fluorine-fluoro-2-deoxyglucose positron emis–sion tomography/computed tomography (18F- FDG-PET/CT) is of importance in assessing high-risk thymoma and thymic carcinomas. Detection of advanced thymoma versus thymic carcinoma by routine cross sectional anatomical imaging such as computed tomography (CT), magnetic resonance imaging (MRI) often poses a diagnostic dilemma. In this case series we observed the utility of FDG uptake to predict advanced thymoma and distinguish thymoma from thymic cancer. Materials and Methods: We reviewed 18F- FDG-PET/CT scans of 12 patients (8 males, 4 females); age 24-60yrs with thymic epithelial malignancy from January 2011 to May 2013. FDG activity in lesions was quantified using maximum standardised uptake value (SUVmax) and correlated with Masaoka staging and WHO classification. All patients fasted 4 hr prior to 18F-FDG PET/CT. Images from vertex to mid-thigh were acquired 60min post injection of 3.7 -4.7 MBq/kg (Mega Becquerel)/kilogram of18F-FDG and SUV max of each tumour was measured. One patient underwent DOTATATE scan, received 138MBq of 68Gallium (68Ga)-DOTATATE injection IV and imaging was done after 60 min. Results: Higher FDG uptake of SUVmax 7.35 was seen in type B3 thymoma. FDG uptake was higher in thymic carcinoma (20.45 in primary and 17.46 in the node) or neuroendocrine differentiation (NED) than in patients with thymomas (ranged 7.35 - 3.02). No significant association was observed between higher focal FDG uptake and advanced-stage disease in thymoma. In NED 68Ga - DOTATATE imaging identified more lesions than in FDG. Conclusion: PET CT is a valuable diagnostic tool in evaluation of thymic tumours, to assess in initial workup, for treatment response and for prognostication. 68Ga-DOTATATE PET/CT is beneficial in assessing neuroendocrine thymic tumours. Focal FDG uptake cannot predict advanced thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the more aggressive thymoma B3. PMID

  3. Validation of a Computational Model for the SLS Core Stage Oxygen Tank Diffuser Concept and the Low Profile Diffuser - An Advanced Development Design for the SLS

    NASA Technical Reports Server (NTRS)

    Brodnick, Jacob; Richardson, Brian; Ramachandran, Narayanan

    2015-01-01

    The Low Profile Diffuser (LPD) project originated as an award from the Marshall Space Flight Center (MSFC) Advanced Development (ADO) office to the Main Propulsion Systems Branch (ER22). The task was created to develop and test an LPD concept that could produce comparable performance to a larger, traditionally designed, ullage gas diffuser while occupying a smaller volume envelope. Historically, ullage gas diffusers have been large, bulky devices that occupy a significant portion of the propellant tank, decreasing the tank volume available for propellant. Ullage pressurization of spacecraft propellant tanks is required to prevent boil-off of cryogenic propellants and to provide a positive pressure for propellant extraction. To achieve this, ullage gas diffusers must slow hot, high-pressure gas entering a propellant tank from supersonic speeds to only a few meters per second. Decreasing the incoming gas velocity is typically accomplished through expansion to larger areas within the diffuser which has traditionally led to large diffuser lengths. The Fluid Dynamics Branch (ER42) developed and applied advanced Computational Fluid Dynamics (CFD) analysis methods in order to mature the LPD design from and initial concept to an optimized test prototype and to provide extremely accurate pre-test predictions of diffuser performance. Additionally, the diffuser concept for the Core Stage of the Space Launch System (SLS) was analyzed in a short amount of time to guide test data collection efforts of the qualification of the device. CFD analysis of the SLS diffuser design provided new insights into the functioning of the device and was qualitatively validated against hot wire anemometry of the exterior flow field. Rigorous data analysis of the measurements was performed on static and dynamic pressure data, data from two microphones, accelerometers and hot wire anemometry with automated traverse. Feasibility of the LPD concept and validation of the computational model were

  4. Clinical results of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in children with advanced stage rhabdomyosarcoma.

    PubMed

    Kim, Nam Kyun; Kim, Hyo Sun; Suh, Chang-Ok; Kim, Hyun Ok; Lyu, Chuhl Joo

    2012-09-01

    Regardless of improvement in cure of Rhabdomyosarcoma (RMS), the results in treatment of advanced stage of RMS in children are still dismal. Recently, high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/APBSCT) has been tried to manage the advanced high-risk RMS patients. We investigated the effectiveness of HDC/APBSCT by reviewing the clinical records of high-risk pediatric RMS patients in single institute database. Over twenty years, 37 patients were diagnosed as RMS with high-risk at the time of first diagnosis. These patients were classified as two groups according to treatment method. The first group was HDC/APBSCT and the other was conventional multi-agent chemotherapy group. Differences of clinical results between the two groups were analyzed. The median age of patients was 5 yr, ranging from 6 months to 15 yr. The 5-yr event free survival rate (EFS) of all patients was 24.8% ± 4.8%. HDC/APBSCT group and conventional multi-agent chemotherapy group were 41.3% ± 17.8% and 16.7% ± 7.6% for 5-yr EFS, respectively (P = 0.023). There was a significant difference in the result of HDC/APBSCT between complete remission or very good partial response group and poor response group (50% ± 20.4% vs 37.5% ± 28.6%, P = 0.018). HDC/APBSCT can be a promising treatment modality in high-risk RMS patients. PMID:22969254

  5. Initial Evaluation of Treatment-Related Pneumonitis in Advanced-Stage Non-Small-Cell Lung Cancer Patients Treated With Concurrent Chemotherapy and Intensity-Modulated Radiotherapy

    SciTech Connect

    Yom, Sue S.; Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu, H. Helen; Tucker, Susan L.; Hu, C.-S.; Wei Xiong; Wang Xuanming; Wang Shulian; Mohan, Radhe; Cox, James D.; Komaki, Ritsuko

    2007-05-01

    Purpose: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade {>=}3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. Results: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade {>=}3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). Conclusions: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade {>=}3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.

  6. Brain tumour mortality in immigrants.

    PubMed

    Neutel, C I; Quinn, A; Brancker, A

    1989-03-01

    All Canadian deaths due to malignant brain tumour for the years 1970-73 were identified and analysed for country of birth. The years 1970-73 were chosen since in later years country of birth was no longer available for each death. The brain tumour population consisted of 1551 male and 1058 female deaths and matched controls were chosen from deaths due to other causes. Americans who died of brain tumour in Canada had a standardized mortality ratio (SMR) of 1.0 compared to their fellow Americans in the USA. Italian, German, Dutch and British immigrants had SMR between 1.5 and 2.6 compared to rates in their home countries and between 1.24 and 2.09 when compared to Canadian rates. A series of graphs shows the increased risk for male immigrants quite dramatically, and indicates that for females the increases were less pronounced. Further analysis showed that the excess risk is confined to those who were born in Western Europe while their Canadian-born children experienced the same rates as all Canadians. Based on the limited information available, occupation could not be shown to play a role in establishing risk. An attempt was made to pinpoint the years of immigration which showed the greatest risk. It is concluded that the determination of risk of brain tumour has a strong environmental component. The possibilities for identification of this component are discussed. PMID:2722385

  7. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  8. Tumour vasculature--a potential therapeutic target.

    PubMed Central

    Baillie, C. T.; Winslet, M. C.; Bradley, N. J.

    1995-01-01

    The tumour vasculature is vital for the establishment, growth and metastasis of solid tumours. Its physiological properties limit the effectiveness of conventional anti-cancer strategies. Therapeutic approaches directed at the tumour vasculature are reviewed, suggesting the potential of anti-angiogenesis and the targeting of vascular proliferation antigens as cancer treatments. PMID:7543770

  9. Activity of muscarinic, galanin and cannabinoid receptors in the prodromal and advanced stages in the triple transgenic mice model of Alzheimer's disease.

    PubMed

    Manuel, Iván; Lombardero, Laura; LaFerla, Frank M; Giménez-Llort, Lydia; Rodríguez-Puertas, Rafael

    2016-08-01

    Neurochemical alterations in Alzheimer's disease (AD) include cholinergic neuronal loss in the nucleus basalis of Meynert (nbM) and a decrease in densities of the M2 muscarinic receptor subtype in areas related to learning and memory. Neuromodulators present in the cholinergic pathways, such as neuropeptides and neurolipids, control these cognitive processes and have become targets of research in order to understand and treat the pathophysiological and clinical stages of the disease. This is the case of the endocannabinoid and galaninergic systems, which have been found to be up-regulated in AD, and could therefore have a neuroprotective role. In the present study, the functional coupling of Gi/o protein-coupled receptors to GalR1, and the CB1 receptor subtype for endocannabinoids were analyzed in the 3xTg-AD mice model of AD. In addition, the activity mediated by Gi/o protein-coupled M2/4 muscarinic receptor subtypes was also analyzed in brain areas involved in anxiety and cognition. Thus, male mice were studied at 4 and 15months of age (prodromal and advanced stages, respectively) and compared to age-matched non-transgenic (NTg) mice (adult and old, respectively). In 4-month-old 3xTg-AD mice, the [(35)S]GTPγS binding stimulated by galanin was significantly increased in the hypothalamus, but a decrease of functional M2/4 receptors was observed in the posterior amygdala. The CB1 cannabinoid receptor activity was up-regulated in the anterior thalamus at that age. In 15-month-old 3xTg-AD mice, muscarinic receptor activity was found to be increased in motor cortex, while CB1 activity was decreased in nbM. No changes were found in GalR1-mediated activity at this age. Our results provide further evidence of the relevance of limbic areas in the prodromal stage of AD, the profile of which is characterized by anxiety. The up-regulation of galaninergic and endocannabinoid systems support the hypothesis of their neuroprotective roles, and these are established prior to the

  10. Transient terahertz photoconductivity measurements of minority-carrier lifetime in tin sulfide thin films: Advanced metrology for an early stage photovoltaic material

    NASA Astrophysics Data System (ADS)

    Jaramillo, R.; Sher, Meng-Ju; Ofori-Okai, Benjamin K.; Steinmann, V.; Yang, Chuanxi; Hartman, Katy; Nelson, Keith A.; Lindenberg, Aaron M.; Gordon, Roy G.; Buonassisi, T.

    2016-01-01

    Materials research with a focus on enhancing the minority-carrier lifetime of the light-absorbing semiconductor is key to advancing solar energy technology for both early stage and mature material platforms alike. Tin sulfide (SnS) is an absorber material with several clear advantages for manufacturing and deployment, but the record power conversion efficiency remains below 5%. We report measurements of bulk and interface minority-carrier recombination rates in SnS thin films using optical-pump, terahertz-probe transient photoconductivity (TPC) measurements. Post-growth thermal annealing in H2S gas increases the minority-carrier lifetime, and oxidation of the surface reduces the surface recombination velocity. However, the minority-carrier lifetime remains below 100 ps for all tested combinations of growth technique and post-growth processing. Significant improvement in SnS solar cell performance will hinge on finding and mitigating as-yet-unknown recombination-active defects. We describe in detail our methodology for TPC experiments, and we share our data analysis routines in the form freely available software.

  11. The interweaving of pharmaceutical and medical expectations as dynamics of micro-pharmaceuticalisation: advanced-stage cancer patients' hope in medicines alongside trust in professionals.

    PubMed

    Brown, Patrick; de Graaf, Sabine; Hillen, Marij; Smets, Ellen; van Laarhoven, Hanneke

    2015-04-01

    Existing pharmaceuticalisation research denotes the salience of expectations in novel medicines and in the medical contexts through which these may be accessed. Specific processes of expectation such as hope and trust, alongside their shaping of patients' lifeworlds around pharmaceutical use, remain neglected however. Considering data from in-depth interviews and observations involving thirteen patients with advanced-stage cancer diagnoses who were or had recently been involved in clinical trials, we develop an interpretative phenomenological analysis of the influence of hope and trust upon the accessing of novel medicines through trials, illuminating the depth and texture of pharmaceuticalisation at the micro-level. Trust in clinicians and hope in trial medicines, for self and future patients, were important in the reconfiguring of patients' horizon of possibilities when accessing new medicines. Interwoven processes of trust and hope, embedded within heightened vulnerability, sustained the bracketing out of doubts regarding medicines, trials and professionals. The need to maintain hopes, and trusting relations with professionals who facilitated these hopes, generated meaning and momentum of medicines use which inhibited disengagement from trials. Findings indicate the taken-for-granted, as well as more reflexive, pursuit of solutions through medicines, which in this case-study enabled the generation of evidence through trial involvement. Analyses of micro-level dynamics within both downstream-consumption and upstream-substantiation of pharmaceutical solutions assist more nuanced accounts of interests, agency and expectations within pharmaceuticalisation. PMID:25465500

  12. A voice that wraps around the body--communication problems in the advanced stages of non-small cell lung cancer.

    PubMed Central

    Moore, R. J.; Chamberlain, R. M.; Khuri, F. R.

    2001-01-01

    INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage caused by living with this disease. METHODS: Exploratory, two-part qualitative design. RESULTS: Survivors of non-small cell lung cancer live with multiple fears and losses. These include a diminished sense of self, the loss of health, fears of pain in a future tainted by the threat of death, and increased feelings of alienation due to the loss of previous sources of meaning in life. These experiences significantly affect cancer survivors abilities to communicate with clinicians and significant others. CONCLUSIONS: Survivors of non-small cell lung cancer often have difficulty sharing their experiences with others not suffering a similar affliction. Through their narratives with other survivors, however, patients are better able to initiate a biopsychosocial mechanism which enables them to create a cognitive map. This cognitive map helps survivors share their experiences with others, thereby repairing some of the damage caused by this disease, including the harm done to their communication with other people. PMID:11922184

  13. Detection of comorbidities and synchronous primary tumours via thoracic radiography and abdominal ultrasonography and their influence on treatment outcome in dogs with soft tissue sarcomas, primary brain tumours and intranasal tumours.

    PubMed

    Bigio Marcello, A; Gieger, T L; Jiménez, D A; Granger, L Abbigail

    2015-12-01

    Canine soft tissue sarcomas (STS), primary brain tumours and intranasal tumours are commonly treated with radiotherapy (RT). Given the low metastatic potential of these tumours, recommendations regarding imaging tests as staging are variable among institutions. The purpose of our study was to describe thoracic radiographic and abdominal ultrasonographic findings in dogs with these neoplasms and to investigate association of abnormal findings with alterations in recommended treatment. Medical records from 101 dogs, each having thoracic radiographs and abdominal ultrasound performed as part of their staging, were reviewed. In 98 of 101 (97%), imaging abnormalities were detected, 27% of which were further investigated with fine needle aspiration cytology or biopsy. Nine percent of the detected abnormalities were considered serious comorbidities that altered treatment recommendations, including 3 (3%) which were confirmed as synchronous primary neoplasms. These findings may influence recommendations regarding the decision to perform thoracic radiographs and abdominal ultrasound prior to initiation of RT. PMID:23968175

  14. The peritoneal tumour microenvironment of high-grade serous ovarian cancer.

    PubMed

    Leinster, D Andrew; Kulbe, Hagen; Everitt, Gemma; Thompson, Richard; Perretti, Mauro; Gavins, Felicity N E; Cooper, Dianne; Gould, David; Ennis, Darren P; Lockley, Michelle; McNeish, Iain A; Nourshargh, Sussan; Balkwill, Frances R

    2012-06-01

    High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (α-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with α-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated

  15. Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up

    PubMed Central

    Esser, Stefan; Eisele, Lewin; Schwarz, Birte; Schulze, Christina; Holzendorf, Volker; Brockmeyer, Nobert H; Hower, Martin; Kwirant, Friedhelm; Rudolph, Roland; Neumann, Till; Reinsch, Nico

    2014-01-01

    Introduction Cardiovascular diseases are increasing in aging HIV-positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV-specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts. Methods The HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non-invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke. Results 1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow-up of HIVH. Mean duration of the HIV-infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV-infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV-infection (per y: Hazard ratio (HR): 0.91 [0.88–0.94]) and ART (per y: HR: 0.81 [0.79–0.84]) adjusted for age. The proportion of deceased HIV+ with HIV-RNA ≥50 copies/mL and lower CD4-cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV-RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4-cells: 286.5 cells/µL (IQR: 168.8–482.8) versus 574 cells/µL (IQR: 406–786). 96.1% of the living HIV+ with CVE had HIV-RNA<50 copies

  16. Cervical Cancer Histology, Staging and Survival before and after Implementation of Organised Cervical Screening Programme in Poland

    PubMed Central

    Nowakowski, Andrzej; Cybulski, Marek; Buda, Irmina; Janosz, Iwona; Olszak-Wąsik, Katarzyna; Bodzek, Piotr; Śliwczyński, Andrzej; Teter, Zbigniew; Olejek, Anita; Baranowski, Włodzimierz

    2016-01-01

    A population-based organised cervical cancer screening programme (OCCSP) was introduced in Poland in 2006. In this study we have aimed to analyse whether selected parameters related to invasive cervical cancer (ICC) of patients diagnosed in two distant gynaecological oncology centres changed after the first screening round of the programme run between 2006–2008. We have run a retrospective cross-sectional analysis of 189 women diagnosed with ICC between 2002–2005 (directly before introduction of the programme) and 165 patients diagnosed between 2009–2012 (just after the first screening round of the programme) and compared their age at diagnosis, histology, stage of tumours and overall survival (OS). Mean age of patients diagnosed in years 2002–2005 and 2009–2012 was 52.1 and 52.6 years respectively. Squamous cell carcinomas constituted 90.5% and 86.1% of tumours diagnosed in years 2002–2005 and 2009–2012 respectively and the rest of tumours had glandular and other histologies. 74.5% and 61.0% of women diagnosed in years 2002–2005 and 2009–2012 respectively had early ICC (FIGO—International Federation of Gynaecology and Obstetrics stages I-IIA) and the rest had advanced disease (FIGO IIB-IV). We have noticed no significant differences in mean age of patients, histology of tumours and OS of patients with ICC diagnosed before and after the first screening round of OCSSP in Poland. Advanced stages of ICC were more commonly diagnosed after the introduction of OCSSP. Changes only in some clinical parameters of patients with ICC were noticed before and after the first screening round of OCSSP in Poland but OS of patients remained the same. PMID:27196050

  17. Hypothesis: solid tumours behave as systemic metabolic dictators.

    PubMed

    Lee, Yang-Ming; Chang, Wei-Chun; Ma, Wen-Lung

    2016-06-01

    Current knowledge regarding mechanisms of carcinogenesis in human beings centres around the accumulation of genetic instability, amplified cellular signalling, disturbed cellular energy metabolism and microenvironmental regulation governed by complicated cell-cell interactions. In this article, we provide an alternative view of cancer biology. We propose that cancer behaves as a systemic dictator that interacts with tissues throughout the body to control their metabolism and eventually homeostasis. The mechanism of development of this endocrine organ-like tumour (EOLT) tissue might be the driving force for cancer progression. Here, we review the literature that led to the development of this hypothesis. The EOLT phenotype can be defined as a tumour that alters systemic homeostasis. The literature indicates that the EOLT phenotype is present throughout cancer progression. The feedback mechanism that governs the interaction between tumours and various organs is unknown. We believe that investigating the mechanism of EOLT development may advance the current knowledge of regulation within the tumour macroenvironment and consequently lead to new diagnostic methods and therapy. PMID:26843513

  18. Messenger RNA (mRNA) Nanoparticle Tumour Vaccination

    PubMed Central

    Phua, Kyle K.L.; Nair, Smita K.; Leong, Kam W.

    2014-01-01

    Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a more robust immune response. Advances in the past decade have deepened our understanding of gene delivery barriers, mRNA’s biological stability and immunological properties, and support the notion for engineering innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery system. In this review we will first examine the suitability of mRNA for engineering manipulations, followed by discussion of a model framework that highlights the barriers to a robust anti-tumour immunity mediated by mRNA encapsulated in nanoparticles. Finally, by consolidating existing literature on mRNA nanoparticle tumour vaccination within the context of this framework, we aim to identify bottlenecks that can be addressed by future nanoengineering research. PMID:24904987

  19. Medical treatment for gastro-entero-pancreatic neuroendocrine tumours

    PubMed Central

    Berardi, Rossana; Morgese, Francesca; Torniai, Mariangela; Savini, Agnese; Partelli, Stefano; Rinaldi, Silvia; Caramanti, Miriam; Ferrini, Consuelo; Falconi, Massimo; Cascinu, Stefano

    2016-01-01

    Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -β), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing. PMID:27096034

  20. ‘Saddle nose’ deformity caused by advanced squamous cell carcinoma of the nasal septum

    PubMed Central

    Graham, Hamish Edward; Connolly, Cara; Pahal, Gurjinderpal S; Stafford, Francis W

    2014-01-01

    Hidden behind their common garden symptoms, malignant tumours of the nasal cavity are typically advanced when detected. Squamous cell carcinoma (SCC) is the most common histological type of these rare tumours which may simply present with epistaxis or a blocked nose. A 79-year-old woman attended our clinic with a 2-year history of progressive nasal collapse resulting in a ‘saddle nose deformity’. Imaging showed a soft tissue mass with absolute destruction of the nasal septum and bones with hard palate and maxillary involvement. Histology confirmed a poorly differentiated SCC. Following discussion at the local head and neck multidisciplinary team meeting, the patient was offered radiotherapy alone due to her advanced presentation. She has had a good response to treatment with no further disease progression. Nasal septal SCC is far more successfully treated in the early stages. A suspicious clinician is the patients best ally. PMID:25096649

  1. Giant solitary fibrous tumour of the pleura. Case report and review of the literature

    PubMed Central

    Crnjac, Anton; Veingerl, Bojan; Vidovic, Damjan; Kavalar, Rajko; Hojski, Aljaz

    2015-01-01

    Background Solitary fibrous tumours of the pleura (SFTP) are rare tumours. They are mostly benign. Only around 12% of them are malign ant. In the initial stage they are mostly asymptomatic and by growing they cause chest pain, irritating cough and dyspnoea on account of the pressure created on the surrounding structures. Rare giant tumours have compression symptoms on the mediastinal structures. The condition requires tiered diagnostic radiology. Preoperative biopsy is not successful in most cases. The therapy of choice is radical surgical tumour removal. Malignant or non-radically removed benign solitary fibrous tumours of the pleura additionally require neoadjuvant therapy. Case report A 68-year old patient was hospitalized for giant solitary fibrous tumour of the pleura in the right pleural cavity. With its expansive growth the tumour caused the shift of the mediastinum by compressing the lower vena cava, right cardiac auricle as well as the intermediate and lower lobe bronchus. Due to cardiac inflow obstruction and right lung collapse, the patient’s life was endangered with signs of cardio-respiratory failure. After preoperative diagnostic radiology, the tumour was surgically removed. Postoperatively, the patient’s condition improved. No disease recurrence was diagnosed after a year. Conclusions Giant solitary fibrous tumour of the pleura may cause serious and life-threatening conditions by causing compression of the pleural cavity with its expansive growth. Early diagnosis of the condition enables less aggressive as well as video-assisted thoracic surgery in patients with significantly better state of health. Large tumour surgeries in cardio-respiratory affected patients are highly risk-associated procedures. PMID:26834527

  2. The Unique Dorsal Brood Pouch of Thermosbaenacea (Crustacea, Malacostraca) and Description of an Advanced Developmental Stage of Tulumella unidens from the Yucatan Peninsula (Mexico), with a Discussion of Mouth Part Homologies to Other Malacostraca.

    PubMed

    Olesen, Jørgen; Boesgaard, Tom; Iliffe, Thomas M

    2015-01-01

    The Thermosbaenacea, a small taxon of crustaceans inhabiting subterranean waters, are unique among malacostracans as they brood their offspring dorsally under the carapace. This habit is of evolutionary interest but the last detailed report on thermosbaenacean development is more than 40 years old. Here we provide new observations on an ovigerous female of Tulumella unidens with advanced developmental stages in its brood chamber collected from an anchialine cave at the Yucatan Peninsula, which is only the third report on developmental stages of Thermosbaenacea and the first for the genus Tulumella. Significant in a wider crustacean context, we report and discuss hitherto unexplored lobate structures inside the brood chamber of the female originating at the first (maxilliped) and second thoracic segments, which are most likely modified epipods, perhaps serving as gills. At the posterior margin of carapace of the female are rows of large spines preventing the developing stages from falling out. The external morphology of the advanced developmental stages is described in much detail, providing information on e.g., carapace formation and early limb morphology. Among the hitherto unknown structures in the advanced developmental stages provided by this study are the presence of an embryonic dorsal organ and rudimentary 'naupliar processes' of the second antennae. Since most hypotheses on crustacean (and malacostracan and peracaridan) relationship rest on external limb morphology, we use early limb bud morphology of Tulumella to better establish thermosbaenacean limb homologies to those of other crustaceans, which is a necessary basis for future morphology based phylogenetic considerations. PMID:25901753

  3. The Unique Dorsal Brood Pouch of Thermosbaenacea (Crustacea, Malacostraca) and Description of an Advanced Developmental Stage of Tulumella unidens from the Yucatan Peninsula (Mexico), with a Discussion of Mouth Part Homologies to Other Malacostraca

    PubMed Central

    Olesen, Jørgen; Boesgaard, Tom; Iliffe, Thomas M.

    2015-01-01

    The Thermosbaenacea, a small taxon of crustaceans inhabiting subterranean waters, are unique among malacostracans as they brood their offspring dorsally under the carapace. This habit is of evolutionary interest but the last detailed report on thermosbaenacean development is more than 40 years old. Here we provide new observations on an ovigerous female of Tulumella unidens with advanced developmental stages in its brood chamber collected from an anchialine cave at the Yucatan Peninsula, which is only the third report on developmental stages of Thermosbaenacea and the first for the genus Tulumella. Significant in a wider crustacean context, we report and discuss hitherto unexplored lobate structures inside the brood chamber of the female originating at the first (maxilliped) and second thoracic segments, which are most likely modified epipods, perhaps serving as gills. At the posterior margin of carapace of the female are rows of large spines preventing the developing stages from falling out. The external morphology of the advanced developmental stages is described in much detail, providing information on e.g., carapace formation and early limb morphology. Among the hitherto unknown structures in the advanced developmental stages provided by this study are the presence of an embryonic dorsal organ and rudimentary ‘naupliar processes’ of the second antennae. Since most hypotheses on crustacean (and malacostracan and peracaridan) relationship rest on external limb morphology, we use early limb bud morphology of Tulumella to better establish thermosbaenacean limb homologies to those of other crustaceans, which is a necessary basis for future morphology based phylogenetic considerations. PMID:25901753

  4. Animal models of tumour-associated epilepsy.

    PubMed

    Kirschstein, Timo; Köhling, Rüdiger

    2016-02-15

    Brain tumours cause a sizeable proportion of epilepsies in adulthood, and actually can be etiologically responsible also for childhood epilepsies. Conversely, seizures are often first clinical signs of a brain tumour. Nevertheless, several issues of brain-tumour associated seizures and epilepsies are far from understood, or clarified regarding clinical consensus. These include both the specific mechanisms of epileptogenesis related to different tumour types, the possible relationship between malignancy and seizure emergence, the interaction between tumour mass and surrounding neuronal networks, and - not least - the best treatment options depending on different tumour types. To investigate these issues, experimental models of tumour-induced epilepsies are necessary. This review concentrates on the description of currently used models, focusing on methodological aspects. It highlights advantages and shortcomings of these models, and identifies future experimental challenges. PMID:26092434

  5. Evidence for a delay in diagnosis of Wilms’ tumour in the UK compared with Germany: implications for primary care for children

    PubMed Central

    Pritchard-Jones, Kathy; Graf, Norbert; van Tinteren, Harm; Craft, Alan

    2016-01-01

    The UK has a longstanding system of general practice which provides the vast majority of primary care, including that for children. It acts as a 'gatekeeper' to more specialist care. Parents may also use accident and emergency departments as their first point of medical contact for their children. Outcomes in the UK for many conditions in children appear to be worse than in comparable European countries where there is direct access to care by paediatricians. We have therefore looked at pathways to diagnosis and compared outcomes in the childhood kidney cancer, Wilms' tumour, which has been treated in the UK and Germany within the same clinical trial for over a decade. We find that Wilms' tumours are significantly larger in volume and have a more advanced tumour stage at diagnosis in the UK compared to Germany. There is a small (∼3%) difference in event free and overall survival between the two countries. Our data suggest that the system of primary care for children in the UK is less likely to result in the incidental finding of an abdominal mass in a child with no or vague symptoms. This may be a reason for the poorer outcome. PMID:26948824

  6. Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

    PubMed

    Cai, Longmei; Ye, Yanfen; Jiang, Qiang; Chen, Yuxiang; Lyu, Xiaoming; Li, Jinbang; Wang, Shuang; Liu, Tengfei; Cai, Hongbing; Yao, Kaitai; Li, Ji-Liang; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC. PMID:26135619

  7. Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

    ClinicalTrials.gov

    2013-03-29

    Recurrent Melanoma; Stage IIB Melanoma (Locally Advanced); Stage IIC Melanoma (Locally Advanced); Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma (Limited, Resectable)

  8. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    SciTech Connect

    Higginson, Daniel S.; Chen, Ronald C.; Tracton, Gregg; Morris, David E.; Halle, Jan; Rosenman, Julian G.; Stefanescu, Mihaela; Pham, Erica; Socinski, Mark A.; Marks, Lawrence B.

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods and Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard ratio, 1

  9. Haemangioleiomyomatous tumour of the lung.

    PubMed Central

    Soorae, A S; Bharucha, H

    1980-01-01

    A case of haemangioleiomyomatous tumour of the lung, occurring as a peripheral, solitary nodule in an asymptomatic 54-year-old man is presented. The tumour was well-demarcated and microscopically it was characterised by the presence of vascular spaces with endothelial, pericytic, and, predominantly, smooth muscle proliferation. Islands of cartilage and slit-like spaces lined by bronchial epithelium make this a hamartomatous lesion of a quite distinctive and unusual variety, which does not fit any of the well-recognised patterns of hamartomas previously described. The long-term prognosis after limited excision is considered to be favourable. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7358861

  10. Factors associated with initiation of antiretroviral therapy in the advanced stages of HIV infection in six Ethiopian HIV clinics, 2012 to 2013

    PubMed Central

    Nash, Denis; Tymejczyk, Olga; Gadisa, Tsigereda; Kulkarni, Sarah Gorrell; Hoffman, Susie; Yigzaw, Muluneh; Elul, Batya; Remien, Robert H; Lahuerta, Maria; Daba, Shalo; El Sadr, Wafaa; Melaku, Zenebe

    2016-01-01

    Introduction Most HIV-positive persons in sub-Saharan Africa initiate antiretroviral therapy (ART) with advanced infection (late ART initiation). Intervening on the drivers of late ART initiation is a critical step towards achieving the full potential of HIV treatment scale-up. This study aimed to identify modifiable factors associated with late ART initiation in Ethiopia. Methods From 2012 to 2013, Ethiopian adults (n=1180) were interviewed within two weeks of ART initiation. Interview data were merged with HIV care histories to assess correlates of late ART initiation (CD4+ count <150 cells/µL or World Health Organization Stage IV). Results The median CD4 count at enrolment in HIV care was 263 cells/µL (interquartile range (IQR): 140 to 390) and 212 cells/µL (IQR: 119 to 288) at ART initiation. Overall, 31.2% of participants initiated ART late, of whom 85.1% already had advanced HIV disease at enrolment. Factors associated with higher odds of late ART initiation included male sex (vs. non-pregnant females; adjusted odds ratio (aOR): 2.02; 95% CI: 1.50 to 2.73), high levels of psychological distress (vs. low/none, aOR: 1.96; 95% CI: 1.34 to 2.87), perceived communication barriers with providers (aOR: 2.42, 95% CI: 1.24 to 4.75), diagnosis via provider initiated testing (vs. voluntary counselling and testing, aOR: 1.47, 95% CI: 1.07 to 2.04), tuberculosis (TB) treatment prior to ART initiation (aOR: 2.16, 95% CI: 1.43 to 3.25) and a gap in care of six months or more prior to ART initiation (aOR: 2.02, 95% CI: 1.10 to 3.72). Testing because of partner illness/death (aOR: 0.64, 95% CI: 0.42 to 0.95) was associated with lower odds of late ART initiation. Conclusions Programmatic initiatives promoting earlier diagnosis, engagement in pre-ART care, and integration of TB and HIV treatments may facilitate earlier ART initiation. Men and those experiencing psychological distress may also benefit from targeted support prior to ART initiation. PMID:27113335

  11. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  12. The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation

    PubMed Central

    Han, Zhi-Yan; Richer, Wilfrid; Fréneaux, Paul; Chauvin, Céline; Lucchesi, Carlo; Guillemot, Delphine; Grison, Camille; Lequin, Delphine; Pierron, Gaelle; Masliah-Planchon, Julien; Nicolas, André; Ranchère-Vince, Dominique; Varlet, Pascale; Puget, Stéphanie; Janoueix-Lerosey, Isabelle; Ayrault, Olivier; Surdez, Didier; Delattre, Olivier; Bourdeaut, Franck

    2016-01-01

    Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1flox/flox;Rosa26-CreERT2 mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin. PMID:26818002

  13. Intra-tumour signalling entropy determines clinical outcome in breast and lung cancer.

    PubMed

    Banerji, Christopher R S; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E

    2015-03-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample's genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  14. Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

    PubMed Central

    Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

    2015-01-01

    The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

  15. Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis.

    PubMed

    Wang, Zhe; Xiong, Shanshan; Mao, Yubin; Chen, Mimi; Ma, Xiaohong; Zhou, Xueliang; Ma, Zhenling; Liu, Fan; Huang, Zhengjie; Luo, Qi; Ouyang, Gaoliang

    2016-08-01

    Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:27193093

  16. Is quantification of lymphovascular space invasion useful in stage 1B2 cervical carcinomas?

    PubMed

    Scurry, J; Hacker, N F; Barlow, E; Friedlander, M; Jackson, M

    2015-05-01

    The objective was to determine whether quantification of lymphovascular space invasion (LVSI) by simple techniques adds prognostic information above its mere identification in stage 1B2 cervical cancer. The method was to quantify LVSI by extent, density and distance from the advancing front in 88 consecutive stage 1B2 cervical cancers treated by radical hysterectomy and pelvic lymphadenectomy and to compare them with pelvic lymph node status and local and distant recurrence. The results were that LVSI involved more tumour blocks, was denser and extended a further distance in those with positive nodes. However, effective adjuvant therapy confounded the association between quantification of LVSI and local recurrence. Furthermore, pelvic lymph node status was a stronger predictor of distant recurrence than any degree of LVSI. In conclusion, quantifying LVSI in stage 1B2 cervical cancer is a good predictor of lymph node metastasis, but is not useful where the lymph node status is known. PMID:25347062

  17. Hypoxia-mediated tumour targeting.

    PubMed

    Binley, K; Askham, Z; Martin, L; Spearman, H; Day, D; Kingsman, S; Naylor, S

    2003-04-01

    Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy. PMID:12646859

  18. CoMPASs: IOn programme (Care Of Memory Problems in Advanced Stages of dementia: Improving Our Knowledge): protocol for a mixed methods study

    PubMed Central

    Jones, Louise; Harrington, Jane; Scott, Sharon; Davis, Sarah; Lord, Kathryn; Vickerstaff, Victoria; Round, Jeff; Candy, Bridget; Sampson, Elizabeth L

    2012-01-01

    Introduction Approximately 700 000 people in the UK have dementia, rising to 1.2 million by 2050; one-third of people aged over 65 will die with dementia. Good end-of-life care is often neglected, and detailed UK-based research on symptom burden and needs is lacking. Our project examines these issues from multiple perspectives using a rigorous and innovative design, collecting data which will inform the development of pragmatic interventions to improve care. Methods and analysis To define in detail symptom burden, service provision and factors affecting care pathways we shall use mixed methods: prospective cohort studies of people with advanced dementia and their carers; workshops and interactive interviews with health professionals and carers, and a workshop with people with early stage dementia. Interim analyses of cohort data will inform new scenarios for workshops and interviews. Final analysis will include cohort demographics, the symptom burden and health service use over the follow-up period. We shall explore the level and nature of unmet needs, describing how comfort and quality of life change over time and differences between those living in care homes and those remaining in their own homes. Data from workshops and interviews will be analysed for thematic content assisted by textual grouping software. Findings will inform the development of a complex intervention in the next phase of the research programme. Ethics and dissemination Ethical approval was granted by National Health Service ethical committees for studies involving people with dementia and carers (REC refs. 12/EE/0003; 12/LO/0346), and by university ethics committee for work with healthcare professionals (REC ref. 3578/001). We shall present our findings at conferences, and in peer-reviewed journals, prepare detailed reports for organisations involved with end-of-life care and dementia, publicising results on the Marie Curie website. A summary of the research will be provided to participants

  19. Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation

    SciTech Connect

    Portaluri, Maurizio . E-mail: portaluri@hotmail.com; Fucilli, Fulvio I.M.; Castagna, Roberta; Bambace, Santa; Pili, Giorgio; Tramacere, Francesco; Russo, Donatella; Francavilla, Maria Carmen

    2006-11-15

    Purpose: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. Methods and Materials: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). Results: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 {+-} 4.82 Gy (51.53 {+-} 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Conclusion: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.

  20. Electrochemotherapy in combination with chemoradiotherapy in the treatment of oral carcinomas in advanced stages of disease: efficacy, safety, and clinical outcomes in a small number of selected cases

    PubMed Central

    Domanico, Rossana; Trapasso, Serena; Santoro, Mariaquila; Pingitore, Domenico; Allegra, Eugenia

    2015-01-01

    Introduction Electrochemotherapy (ECT) is a new therapeutic method that is used in oncology as palliative treatment in patients with recurrent head and neck tumors and who are not candidates for standard therapeutic options. The aim of our study was to evaluate the cytoreductive effect of ECT in patients subjected to chemoradiotherapy for squamous cell carcinoma of the oral cavity. The primary endpoint of the study was to verify tumor debulking after ECT treatment as neoadjuvant, before conventional chemoradiotherapy. The secondary endpoint was to assess the safety and tolerability of ECT treatment. Materials and methods This experimental study was conducted at the Division of Otolaryngology, University of Catanzaro, Italy. From February 2013 to February 2014, four patients were enrolled, two males and two females, with a mean age of 56 years (range: 47–65 years), and with squamous cell carcinoma of the oral cavity in advanced stages of disease (T3–T4). All patients, with their informed consent, received ECT treatment in accordance with the Standard Operating Procedures defined in the European Standard Operating Procedures on Electrochemotherapy (ESOPE) study, followed by conventional chemoradiotherapy. Their response to ECT treatment was assessed after 30 days. For each patient, the following parameters were evaluated with the appropriate forms: local tumor control, control of pain (analgesia postsurgery scale [APS]), and quality of life (Short Form [36] Health Survey [SF-36]; v1). Results Three of four patients (75%) showed a partial response, whereas in one patient (25%), the disease remained stable. The treatment was well-tolerated by all patients, according to the APS and SF-36 results. Conclusion Although the study was conducted on a small number of cases, data from this study show that ECT represents a safe and effective treatment in terms of tumor cytoreduction and locoregional control of the disease. It also allows good control of postoperative pain

  1. Somatic DNA Hypomethylation in H. pylori-Associated High-Risk Gastritis and Gastric Cancer: Enhanced Somatic Hypomethylation Associates with Advanced Stage Cancer

    PubMed Central

    Leodolter, Andreas; Alonso, Sergio; González, Beatriz; Ebert, Matthias P; Vieth, Michael; Röcken, Christoph; Wex, Thomas; Peitz, Ullrich; Malfertheiner, Peter; Perucho, Manuel

    2015-01-01

    Objectives: Helicobacter pylori-related high-risk gastritis (HRG) is a severe risk factor for gastric cancer (GC). The link between HRG and long-term risk for GC may involve genetic and epigenetic alterations underlying a field defect, i.e. a region of the mucosa prone to cancer development. Global DNA hypomethylation is a pervasive alteration in GC that associates with chromosomal instability and poor prognosis. The aim of this study was to determine the chronology of this alteration along the progression of HRG to GC, to test the hypothesis that it occurs early in the chronology of this pathway and plays a mechanistic role in the long-term cancer risk. Methods: We comparatively measured the genomic methylation level in gastric biopsies from 94 GC patients and 16 of their cancer-free relatives, 38 HRG patients, and 17 GERD patients, using a quantitative enzymatic method. Results: GC biopsies were hypomethylated compared to their matching non-tumor mucosa (P=9.4 × 10−12), irrespective of the tumor location or patients' country of origin. Genome-wide hypomethylation was also found in gastric mucosa of GC (P=1.5 × 10−5) and HRG (P=0.004) patients compared with healthy donors and GC relatives, regardless of the biopsy location within the stomach or previous H. pylori eradication therapy. An enhanced hypomethylation, distinguished by a bi-slope distribution of the differences in methylation between tumor and normal tissues, associated with a more invasive (P=0.005) and advanced stage (P=0.017) type of GC. Conclusions: Universal DNA demethylation in normal gastric mucosa in GC patients appears sporadic rather than familial. Genomic hypomethylation in HRG possibly contributes to a field defect for cancerization that is not reversed by bacterial eradication. Enhanced somatic hypomethylation may stratify GC for prognostic purposes. PMID:25928808

  2. Matrix metalloproteinase-1 is induced by epidermal growth factor in human bladder tumour cell lines and is detectable in urine of patients with bladder tumours.

    PubMed Central

    Nutt, J. E.; Mellon, J. K.; Qureshi, K.; Lunec, J.

    1998-01-01

    The matrix metalloproteinases are a family of enzymes that degrade the extracellular matrix and are considered to be important in tumour invasion and metastasis. The effect of epidermal growth factor (EGF) on matrix metalloproteinase-1 (MMP1) production in two human bladder tumour cell lines, RT112 and RT4, has been investigated. In the RT112 cell line, an increase in MMP1 mRNA levels was found after a 6-h incubation with EGF, and this further increased to 20-fold that of control levels at 24- and 48-h treatment with 50 ng ml(-1) of EGF. MMP2 mRNA levels remained constant over this time period, whereas in the RT4 cells no MMP2 transcripts were detectable, but MMP1 transcripts again increased with 24- and 48-h treatment with 50 ng ml(-1) of EGF. MMP1 protein concentration in the conditioned medium from both cell lines increased with 24- and 48-h treatment of the cells and the total MMP1 was higher in the medium than the cells, demonstrating that the bladder tumour cell lines synthesize and secrete MMP1 protein after continuous stimulation with EGF. MMP1 protein was detected in urine from patients with bladder tumours, with a significant increase in concentration with increased stage and grade of tumour. MMP1 urine concentrations may therefore be a useful prognostic indicator for bladder tumour progression. Images Figure 1 Figure 2 PMID:9683296

  3. Primary Ovarian Malignant Mixed Mullerian Tumour: A Case Report and Brief Review of Literature

    PubMed Central

    Çakir, Tansel; Ilhan, Tolgay Tuyan; Karabagli, Pinar; Çelik, Çetin

    2016-01-01

    Malignant Mixed Mullerian Tumour of the Ovary (OMMMT), also referred to as carcinosarcoma is a very rare tumour accounting for less than 1% of all ovarian cancers. Due to the rarity of OMMMT, little is known about the disease course and outcome of women with these tumours. It is important to evaluate because of its aggressive behaviour with extremely unfavourable prognosis. These tumours are composed of both malignant epithelial and mesenchymal elements. Current data in the literature is still limited to small case series and case reports, therefore, its optimal treatment is somewhat controversial. In the current report, we introduce a case of OMMMT which was successfully treated with Platinum-based combination chemotherapy after optimal cytoreductive surgery. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. Although the most effective treatment is currently unknown, optimal cytoreductive surgery and platinum-based chemotherapy appears to improve the outcomes. Despite the aggressive nature of this tumour and its poor response to the treatment, management works best when cancer is found early. The stage of the disease is the most important prognostic factor. Therefore, the crucial question is how to diagnose the cancer at earlier stages rather than seeking the optimal treatment. PMID:27134951

  4. Simultaneous removal of a tumour of the right atrium and inferior vena cava and coronary bypass-grafting in a patient with recurrent clear renal cell carcinoma

    PubMed Central

    Pietrzyk, Edward; Głuszek, Stanisław; Michta, Kamil; Kot, Marta; Wożakowska-Kapłon, Beata

    2015-01-01

    Metastatic cardiac tumours are the most common malignant cardiac tumours. In the early stages they are usually asymptomatic, but their consequences can be very serious, and the prognosis is poor. We present a patient with recurrent renal cell carcinoma as a tumour of the right atrium and the vena cava inferior in whom cancerous masses were removed with simultaneously coronary artery bypass-grafting. PMID:26855653

  5. Tumour hypoxia promotes melanoma growth and metastasis via High Mobility Group Box-1 and M2-like macrophages

    PubMed Central

    Huber, Roman; Meier, Barbara; Otsuka, Atsushi; Fenini, Gabriele; Satoh, Takashi; Gehrke, Samuel; Widmer, Daniel; Levesque, Mitchell P.; Mangana, Joanna; Kerl, Katrin; Gebhardt, Christoffer; Fujii, Hiroko; Nakashima, Chisa; Nonomura, Yumi; Kabashima, Kenji; Dummer, Reinhard; Contassot, Emmanuel; French, Lars E.

    2016-01-01

    Hypoxia is a hallmark of cancer that is strongly associated with invasion, metastasis, resistance to therapy and poor clinical outcome. Tumour hypoxia affects immune responses and promotes the accumulation of macrophages in the tumour microenvironment. However, the signals linking tumour hypoxia to tumour-associated macrophage recruitment and tumour promotion are incompletely understood. Here we show that the damage-associated molecular pattern High-Mobility Group Box 1 protein (HMGB1) is released by melanoma tumour cells as a consequence of hypoxia and promotes M2-like tumour-associated macrophage accumulation and an IL-10 rich milieu within the tumour. Furthermore, we demonstrate that HMGB1 drives IL-10 production in M2-like macrophages by selectively signalling through the Receptor for Advanced Glycation End products (RAGE). Finally, we show that HMGB1 has an important role in murine B16 melanoma growth and metastasis, whereas in humans its serum concentration is significantly increased in metastatic melanoma. Collectively, our findings identify a mechanism by which hypoxia affects tumour growth and metastasis in melanoma and depict HMGB1 as a potential therapeutic target. PMID:27426915

  6. Cerebral ganglioglio-neuroblastoma: an unusual brain tumour of the neuron series.

    PubMed Central

    Dastur, D K

    1982-01-01

    The pathology of an unusual intracranial neuroectodermal tumour of the neuron series in described and its possible histogenesis discussed. The tumour, in a child aged 5 years with an enlarged head since infancy, presented as a large solid intra-cerebral mass. Histological examination showed four types of cells; (i) the stroma, forming the bulk of the tumour, was astrocytomatous; (ii) lobules of ill defined cells bearing small circular nuclei, representing immature neuroblasts: (iii) the same of other lobules containing neurons in various stages of development; and (iv) dense clusters of cells with hyperchromatic nuclei attempting rosettes, representing an overtly malignant neuroblastoma. This tumour was designated "ganglioglio-neuroblastoma" and probably originated from a slow growing ganglioglioma. Images PMID:7069425

  7. Surgical decision criteria: Bednar tumour of the foot in a child.

    PubMed

    Kubiak, Rainer; Weidner, Katrin; Bruder, Elisabeth; Kalbermatten, Daniel F; Haug, Martin

    2011-12-01

    An 8-year-old boy was admitted for excision of a putative 'blue nevus' on the left foot. Histological examination and immunohistochemistry revealed a Bednar tumour, the pigmented variant of dermatofibrosarcoma protuberans. Surgical options considered by a multidisciplinary team included wide local excision, Mohs micrographic surgery or a staged excision with examination of several histological sections. The third alternative procedure was chosen after consideration of tumour and patient factors to achieve the best possible clinical, cosmetic and functional outcome. After the final surgical procedure with resection of the third metatarsal bone, all peripheral margins were free of tumour, and the interdigital space was reconstructed with a pedicled pulpa flap. Three years after surgery, there was no tumour recurrence, and further long-term follow-up for this patient will be provided. PMID:21719366

  8. The translational potential of circulating tumour DNA in oncology.

    PubMed

    Patel, K M; Tsui, D W Y

    2015-10-01

    The recent understanding of tumour heterogeneity and cancer evolution in response to therapy has raised questions about the value of historical or single site biopsies for guiding treatment decisions. The ability of ctDNA analysis to reveal de novo mutations (i.e., without prior knowledge), allows monitoring of clonal heterogeneity without the need for multiple tumour biopsies. Additionally, ctDNA monitoring of such heterogeneity and novel mutation detection will allow clinicians to detect resistant mechanisms early and tailor treatment therapies accordingly. If ctDNA can be used to detect low volume cancerous states, it will have important applications in treatment stratification post-surgery/radical radiotherapy and may have a role in patient screening. Mutant cfDNA can also be detected in other bodily fluids that are easily accessible and may aid detection of rare mutant alleles in certain cancer types. This article outlines recent advances in these areas. PMID:25889059

  9. The role of surgery in advanced epithelial ovarian cancer

    PubMed Central

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  10. The role of surgery in advanced epithelial ovarian cancer.

    PubMed

    Martín-Cameán, María; Delgado-Sánchez, Elsa; Piñera, Antonio; Diestro, Maria Dolores; De Santiago, Javier; Zapardiel, Ignacio

    2016-01-01

    Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3-17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer. PMID:27594911

  11. Survival in rectal cancer is predicted by T cell infiltration of tumour-associated lymphoid nodules

    PubMed Central

    McMullen, T P W; Lai, R; Dabbagh, L; Wallace, T M; de Gara, C J

    2010-01-01

    Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quantified T cell (CD3, CD25) and dendritic cell (CD1a, CD83) levels at the tumour margin as well as within tumour-associated lymphoid nodules. In normal tissue CD3+, but not CD25+, T cells are concentrated at high levels within lymphoid nodules, with significantly fewer cells found in surrounding normal mucosa (P = 0·001). Mature (CD83), but not immature (CD1a), dendritic cells in normal tissue are also found clustered almost exclusively within lymphoid nodules (P = < 0·0001). In rectal tumours, both CD3+ T cells (P = 0·004) and CD83+ dendritic cells (P = 0·0001) are also localized preferentially within tumour-associated lymphoid nodules. However, when comparing tumour specimens to normal rectal tissue, the average density of CD3+ T cells (P = 0·0005) and CD83+ dendritic cells (P = 0·0006) in tumour-associated lymphoid nodules was significantly less than that seen in lymphoid nodules in normal mucosa. Interestingly, regardless of where quantified, T cell and dendritic cell levels did not depend upon the stage of disease. Increased CD3+ T cell infiltration of tumour-associated lymphoid nodules predicted improved survival, independent of stage (P = 0·05). Other T cell (CD25) markers and different levels of CD1a+ or CD83+ dendritic cells did not predict survival. Tumour-associated lymphoid nodules, enriched in dendritic cells and T cells, may be an important site for antigen presentation and increased T cell infiltration may be a marker for improved survival. PMID:20408858

  12. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

    PubMed Central

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

    2015-01-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

  13. An analysis of T lymphocyte subsets in tumour-transplanted mice on the basis of Lyt antigenic markers and functions

    PubMed Central

    Lala, P. K.; McKenzie, I. F. C.

    1982-01-01

    Small lymphocyte subsets were characterized radioautographically on the basis of several surface markers, viz. surface Ig (S-Ig), Thy-1 and Lyt (Ly-1, Ly-2 and 3) antigens in host lymphoid organs (thymus, spleen and blood) as well as at the tumour site at various stages of subcutaneous growth of two different syngeneic tumours—MPC-11 plasmacytoma and WEHI-164 fibrosarcoma in BALB/c mice. In both tumour-host combinations there was a rise in the levels of null (S-Ig-, Thy-1-) small lymphocytes as well as the Ly-23+ subset of T small lymphocytes at all the sites examined. The absolute number of these two subsets also increased excepting the case of null cell rise in the thymus which was relative. The functional potentials of Lyt subsets were explored by employing in vitro and in vivo assays. While no appreciable levels of anti-tumour cytotoxic T cells (Tc) were detectable by a 51Cr release assay in the host spleen or the tumour-draining lymph nodes at any stage of growth of MPC-11 tumour, such Tc was generated in vitro by a co-cultivation of unprimed spleen cells with irradiated MPC-11 cells. These Tc were Thy-1+ and Ly-12+, as noted from antibody+C′ mediated abrogation of cytotoxicity. These results suggested that the generation of anti-tumour Tc in vivo was suppressed in tumour-bearing hosts. The possibility of a cell-mediated suppression was tested by an adoptive transfer of thymocytes or splenocytes from tumour-bearing mice into naive or pre-immunized recipients which then received fresh tumour transplants. This procedure caused a specific enhancement of tumour growth in three tumour-host combinations: MPC-11 or WEHI-164 tumour in BALB/c mice and W-1 fibrosarcoma in CBA mice. The suppressor lineage lymphocytes appearing in vivo were found to be Thy-1+ and Ly-1-, 2+, as noted from antibody +C′ mediated abrogation of their tumour-growth promoting ability. They appeared earlier (7 days) in the thymus and later (>2 weeks) in the spleen and then persisted during

  14. Malignant Leydig cell tumour of the testis.

    PubMed

    Powari, Manish; Kakkar, Nandita; Singh, S K; Rai, R S; Jogai, Sanjay

    2002-01-01

    A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed. PMID:11803271

  15. Tumours of the liver and biliary system

    PubMed Central

    Ponomarkov, V.; Mackey, L. J.

    1976-01-01

    In this histological classification of liver and gall bladder tumours the tumour types largely correspond to those found in man. The most common tumours in this group are liver cell adenoma, hepatocellular carcinoma, and cholangiocarcinoma. ImagesFig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086149

  16. Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

    NASA Astrophysics Data System (ADS)

    Sykes, Edward Alexander

    Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano

  17. Versatile and enhanced tumour modelling in mice via somatic cell transduction

    PubMed Central

    Rodriguez, Esther; Mannion, Liz; D'Santos, Paula; Griffiths, Meryl; Arends, Mark J; Brindle, Kevin M; Lyons, Scott K

    2014-01-01

    Genetically engineered mouse (GEM) models of cancer currently comprise the most accurate way to experimentally recapitulate the human disease in the laboratory. Given recent advances in genomics and genetic screens, however, as well as an increasing urgency for the translation of effective preclinical treatments into the clinic, there is a pressing need to make these models easier and more efficient to work with. Accordingly, we have developed a versatile lentivirus-based approach to induce tumours from somatic cells of GEMs, add or subtract gene expression and render the tumours imageable from a simple breeding stock. The vectors deliver a tamoxifen-inducible and self-inactivating Cre recombinase, conditional bioluminescent and fluorescent proteins and an shRNA component. Following the transduction of somatic cells, tumours are initiated by Cre-mediated recombination of the inherited floxed alleles. Self-inactivation of Cre expression switches on the expression of luciferase, thereby rendering the recombined cells and resulting tumours bioluminescent. We demonstrate proof of concept of this approach by inducing bioluminescent lung tumours in conditional Kras and p53 mice. We also show that a variant vector expressing shRNA alters tumour growth dynamics and the histological grade associated with the inherited genotype. This approach comprises a versatile means to induce imageable and spontaneous tumour burden in mice. The vectors can be readily customized at the bench to modify reporter readout or tumour phenotype without additional transgenic strain development or breeding. They should also be useful for inducing imageable tumours in organs other than the lung, provided that the inherited conditional genotype is sufficiently penetrant. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:24307564

  18. Craniocaudal tumour extension in uterine cervical cancer on MRI compared to histopathology

    PubMed Central

    de Boer, Peter; Bleeker, Maaike C.G.; Spijkerboer, Anje M.; van de Schoot, Agustinus J.A.J.; Bipat, Shandra; Buist, Marrije R.; Rasch, Coen R.N.; Stoker, Jaap; Stalpers, Lukas J.A.

    2015-01-01

    Purpose To assess the reliability of magnetic resonance imaging (MRI) for evaluation of craniocaudal tumour extension by comparing the craniocaudal tumour extension on the pre-operative MRI and post-operative hysterectomy specimen in patients with early stage uterine cervical cancer. Materials and methods After approval of the institutional review board was acquired, pre-operative MRI and hysterectomy specimen of 21 women with early stage cervical cancer were re-evaluated. The craniocaudal extension on MRI was measured separately by two experienced radiologists and compared with corresponding measurements from the hysterectomy specimen, which were re-evaluated by an experienced pathologist. Results Median craniocaudal extension of uterine cervical cancer on MRI was slightly smaller compared to histopathology (2.1 cm vs. 2.5 cm). The median underestimation was 0.4 cm (range −0.6 cm to 2.2 cm, mean 0.4 cm, standard deviation (SD) ±0.7 cm); Pearson’s correlation was 0.83 (p < 0.001). In two patients (9%) MRI underestimated tumour craniocaudal extension by more than 1.8 cm. Conclusion MRI represents the histopathological craniocaudal tumour extension in the majority of patients with early stage uterine cervical cancer, but with a systematic small underestimation of the real craniocaudal tumour extension. PMID:26937443

  19. Tumours of the upper alimentary tract

    PubMed Central

    Head, K. W.

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147

  20. Tumour angiogenesis-Origin of blood vessels.

    PubMed

    Krishna Priya, S; Nagare, R P; Sneha, V S; Sidhanth, C; Bindhya, S; Manasa, P; Ganesan, T S

    2016-08-15

    The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy. PMID:26934471

  1. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver. PMID:26059599

  2. Surgical treatment of benign parapharyngeal space tumours. Presentation of two clinical cases and revision of the literature.

    PubMed

    Fernández Ferro, Martin; Fernández Sanromán, Jacinto; Costas López, Alberto; Sandoval Gutiérrez, Jesús; López de Sánchez, Annahys

    2008-01-01

    Parapharyngeal space (PPS) tumours, most of them benign, account for some 0.5% of tumours of the head and neck. The importance of these tumours lies mainly in two aspects: on the one hand, the difficulty of early diagnosis, due to the lack of symptoms in the initial stages and, on the other, the extreme complications of performing surgery in the parapharyngeal region. This article discusses two clinical cases of parapharyngeal space tumours: a 45 year old man and a 60 year old woman. We revise the scientific literature and analyse the diagnostic and therapeutic procedures used, placing special emphasis on describing the different surgical approaches to the parapharyngeal space: transcervical, transcervical-transparotid, transpalatal or transoral, transmandibular and orbitozygomatic, all of which, used alone or combined with others, allow for complete resection of these tumours with minimum morbidity. PMID:18167484

  3. FRA-1 as a driver of tumour heterogeneity: a nexus between oncogenes and embryonic signalling pathways in cancer.

    PubMed

    Dhillon, A S; Tulchinsky, E

    2015-08-20

    Tumour heterogeneity is a major factor undermining the success of therapies targeting metastatic cancer. Two major theories are thought to explain the phenomenon of heterogeneity in cancer--clonal evolution and cell plasticity. In this review, we examine a growing body of work implicating the transcription factor FOS-related antigen 1 (FRA-1) as a central node in tumour cell plasticity networks, and discuss mechanisms regulating its activity in cancer cells. We also discuss evidence from the FRA-1 perspective supporting the notion that clonal selection and cell plasticity represent two sides of the same coin. We propose that FRA-1-overexpressing clones featuring high plasticity undergo positive selection during consecutive stages of multistep tumour progression. This model underscores a potential mechanism through which tumour cells retaining elevated levels of plasticity acquire a selective advantage over other clonal populations within a tumour. PMID:25381818

  4. Analysis of HLA class I-II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer.

    PubMed

    Gamzatova, Z; Villabona, L; van der Zanden, H; Haasnoot, G W; Andersson, E; Kiessling, R; Seliger, B; Kanter, L; Dalianis, T; Bergfeldt, K; Masucci, G V

    2007-09-01

    In solid tumors, human leucocyte antigen (HLA)-A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA-A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA-A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III-IV was found. Thirty-two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 loci by the polymerase chain reaction/sequence-specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA-A1 and HLA-A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA-A3 was decreased. HLA-A2 homozygotes were twofold higher in patients. The A2-B8 haplotype was significantly increased (corrected P value). A2-B5, A2-B15, A2-DRB1*03, A2-DRB1*04, A2-B15-Cw3, and A2-B8-DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non-corrected analysis. HLA-B15 and HLA-Cw3 were only present in HLA-A2-positive patients showing that the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations. PMID:17661908

  5. [Pancreatic tumour in a child].

    PubMed

    Schouenborg Schultz, Thea; Thyssen Vestergaard, Esben

    2014-07-28

    Abdominal pain is a common symptom in children and recurrent abdominal pain (RAP) has a prevalence of 8.4% in childhood. In 90-95% of RAPs no organic disease is identified. Thus, it is important that the few of somatic origin are diagnosed. We describe a case concerning a 12-year-old girl, diagnosed with a solid pseudopapillary tumour of the pancreas. The symptoms were RAP and postprandial vomiting. The purpose of this article is to increase the knowledge of "alarm findings" indicating an organic disease in children with RAP. PMID:25292323

  6. Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

    PubMed Central

    Leek, R. D.; Landers, R.; Fox, S. B.; Ng, F.; Harris, A. L.; Lewis, C. E.

    1998-01-01

    Angiogenesis is an essential requirement for tumour growth and metastasis and is regulated by a complex network of factors produced by both stromal cells and neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to promote tumour angiogenesis. We have demonstrated recently that high numbers of tumour-associated macrophages (TAMs) are significantly associated with increased tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We have also shown that TAMs are a major source of TNF-alpha in invasive breast carcinomas, and that macrophage-like stromal cells as well as tumour cells synthesize TP in such tumours. However, little is known of the factors that regulate the production or activity of these factors in the tumour microenvironment. As TNF-alpha has been shown to up-regulate TP expression in tumour cells in vitro we performed an immunohistochemical study to investigate the possibility that TNF-alpha may be involved in the regulation of TP expression by malignant breast epithelial cells in vivo. To do this, we used a cocktail of non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha-expressing macrophages and TNF-alpha bound to its receptors on tumour cells and endothelial cells in a series of 93 invasive carcinomas of the breast. A semiquantitative grading system was then used to compare these staining patterns with that for TP in the same biopsies. TNF-alpha immunoreactivity was also compared with various important tumour variables known to relate to outcome in this disease (microvessel density, node status, grade, stage, receptor status and macrophage infiltration), as well as relapse-free and overall survival data for these patients. Our data show significant positive correlations between TNF-alpha bound to its receptors on tumour cells and: (1) TP protein production by tumour cells, and (2) axillary lymph

  7. Expression of blood group antigens in urinary tract tumours: prospective fluorescence study using cryostat sections of fresh frozen tissues.

    PubMed Central

    Thorpe, S J; Abel, P; Henderson, D; Jones, N; Feizi, T

    1986-01-01

    Cryostat sections of fresh frozen tissues were used in a prospective study of blood group H and A antigen fluorescence in 73 transitional cell carcinomas of the bladder. The aim was to evaluate antigen expression without subjecting the tumour tissues to organic solvents that extract blood group active glycolipids. Deletion of the genetically predicted antigen was twice as common in tumours of pT1 or greater stage than those of pTa stage and also twice as common in poorly differentiated than in moderately well differentiated tumours. The considerable heterogeneity and overlap, however, in patterns of reactivity in tumours of various histopathological stages and grades and the effect of secretor status on antigenicity meant that there was no obvious antigenic feature that correlated precisely with invasive stage or differentiation grade. It remains to be determined whether the antigen positive and antigen negative tumours represent different disease entities with differing clinical courses. Our results indicate, however, that studies of the blood group antigens in urinary tract tumours are more likely to be of value in research into biochemical disorders in the neoplastic process than in routine clinical assessment as a guide to treatment. Images Fig 1 Fig 2 Fig 3 PMID:3540013

  8. Electrochemotherapy on liver tumours in rabbits.

    PubMed Central

    Ramirez, L. H.; Orlowski, S.; An, D.; Bindoula, G.; Dzodic, R.; Ardouin, P.; Bognel, C.; Belehradek, J.; Munck, J. N.; Mir, L. M.

    1998-01-01

    Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies. Images Figure 1 Figure 2 PMID:9649121

  9. Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

    PubMed Central

    Loncaster, J A; Cooper, R A; Logue, J P; Davidson, S E; Hunter, R D; West, C M L

    2000-01-01

    The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaign PMID:10944602

  10. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth

    PubMed Central

    Grivennikov, Sergei I.; Wang, Kepeng; Mucida, Daniel; Stewart, C. Andrew; Schnabl, Bernd; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Osterreicher, Christoph H.; Hung, Kenneth E.; Datz, Christian; Feng, Ying; Fearon, Eric R.; Oukka, Mohamed; Tessarollo, Lino; Coppola, Vincenzo; Yarovinsky, Felix; Cheroutre, Hilde; Eckmann, Lars; Trinchieri, Giorgio; Karin, Michael

    2013-01-01

    Approximately 2% of colorectal cancer is linked to pre-existing inflammation known as colitis-associated cancer, but most develops in patients without underlying inflammatory bowel disease. Colorectal cancer often follows a genetic pathway whereby loss of the adenomatous polyposis coli (APC) tumour suppressor and activation of β-catenin are followed by mutations in K-Ras, PIK3CA and TP53, as the tumour emerges and progresses1,2. Curiously, however, ‘inflammatory signature’ genes characteristic of colitis-associated cancer are also upregulated in colorectal cancer3,4. Further, like most solid tumours, colorectal cancer exhibits immune/inflammatory infiltrates5, referred to as ‘tumour elicited inflammation’6. Although infiltrating CD4+ TH1 cells and CD8+ cytotoxic T cells constitute a positive prognostic sign in colorectal cancer7,8, myeloid cells and T-helper interleukin (IL)-17-producing (TH17) cells promote tumorigenesis5,6, and a ‘TH17 expression signature’ in stage I/II colorectal cancer is associated with a drastic decrease in disease-free survival9. Despite its pathogenic importance, the mechanisms responsible for the appearance of tumour-elicited inflammation are poorly understood. Many epithelial cancers develop proximally to microbial communities, which are physically separated from immune cells by an epithelial barrier10. We investigated mechanisms responsible for tumour-elicited inflammation in a mouse model of colorectal tumorigenesis, which, like human colorectal cancer, exhibits upregulation of IL-23 and IL-17. Here we show that IL-23 signalling promotes tumour growth and progression, and development of a tumoural IL-17 response. IL-23 is mainly produced by tumour-associated myeloid cells that are likely to be activated by microbial products, which penetrate the tumours but not adjacent tissue. Both early and late colorectal neoplasms exhibit defective expression of several barrier proteins. We propose that barrier deterioration induced by

  11. Transillumination imaging of intraocular tumours.

    PubMed

    Kjersem, Bård; Krohn, Jørgen

    2013-06-01

    The purpose of this paper is to discuss a recently described modification of a standard photo slit lamp system for ocular transillumination, with special emphasis on the light transmission through the eye wall and the photographic technique. Transillumination photography was carried out with the Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG, Koeniz, Switzerland). After having released the background lighting optic fibre cable from its holder, the patient was positioned at the slit lamp, and the fibre tip was gently pressed against the sclera or the cornea of the patient's eye. During about 1/1000 of a second, the eye was illuminated by the flash and the scleral shadow of the tumour was exposed to the camera sensor. The images were of good diagnostic quality, making it easy to outline the tumours and to evaluate the involvement of intraocular structures. None of the examined patients experienced discomfort or negative side effects. The method is recommended in cases where photographic transillumination documentation of intraocular pathologies is considered important. PMID:23641762

  12. Frequent intragenic rearrangements of DPYD in colorectal tumours.

    PubMed

    van Kuilenburg, A B P; Etienne-Grimaldi, M-C; Mahamat, A; Meijer, J; Laurent-Puig, P; Olschwang, S; Gaub, M-P; Hennekam, R C M; Benchimol, D; Houry, S; Letoublon, C; Gilly, F-N; Pezet, D; Andre, T; Faucheron, J-L; Abderrahim-Ferkoune, A; Vijzelaar, R; Pradere, B; Milano, G

    2015-06-01

    Dihydropyrimidine dehydrogenase is a crucial enzyme for the degradation of 5-fluorouracil (5FU). DPYD, which encodes dihydropyrimidine dehydrogenase, is prone to acquire genomic rearrangements because of the presence of an intragenic fragile site FRA1E. We evaluated DPYD copy number variations (CNVs) in a prospective series of 242 stage I-III colorectal tumours (including 87 patients receiving 5FU-based treatment). CNVs in one or more exons of DPYD were detected in 27% of tumours (deletions or amplifications of one or more DPYD exons observed in 17% and 10% of cases, respectively). A significant relationship was observed between the DPYD intragenic rearrangement status and dihydropyrimidine dehydrogenase (DPD) mRNA levels (both at the tumour level). The presence of somatic DPYD aberrations was not associated with known prognostic or predictive biomarkers, except for LOH of chromosome 8p. No association was observed between DPYD aberrations and patient survival, suggesting that assessment of somatic DPYD intragenic rearrangement status is not a powerful biomarker to predict the outcome of 5FU-based chemotherapy in patients with colorectal cancer. PMID:25348620

  13. Nuclear Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

    2012-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

  14. Cerebrospinal fluid rhinorrhoea in pituitary tumours1

    PubMed Central

    Cole, I E; Keene, Malcolm

    1980-01-01

    Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123

  15. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  16. Classification of odontogenic tumours. A historical review.

    PubMed

    Philipsen, Hans Peter; Reichart, Peter A

    2006-10-01

    Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon. PMID:16968232

  17. The early days of spinal tumour surgery.

    PubMed

    Ellis, Harold

    2011-12-01

    In numerous examples in this series of essays on 'The Early Days of ...' there is argument and debate about who should be given the credit for introducing a particular major advance in treatment. However, in the story of the management of tumours involving the spinal cord, there is no doubt at all about priority; the surgeon was Victor Horsley and the date was June 1887! The patient was a Captain Gilbey, a business man and a retired Army officer. In 1884, shortly after his wife's death following a road traffic accident, he developed severe upper thoracic back pain. He was seen over succeeding months and years by numbers of specialists, whose diagnoses ranged from an aneurysm to neurasthenia, and whose treatments included advice to take a long sea voyage, to have Turkish baths and to take the cure at the medicinal baths at Aix-la-Chapelle. His various medical advisors thought his condition to be functional, even though he was gradually losing sensation and movement in his legs and trunk, was having considerable difficulty in passing his urine and was now requiring morphia for the pain. PMID:22263323

  18. Quantity and accessibility for specific targeting of receptors in tumours

    NASA Astrophysics Data System (ADS)

    Hussain, Sajid; Rodriguez-Fernandez, Maria; Braun, Gary B.; Doyle, Francis J.; Ruoslahti, Erkki

    2014-06-01

    Synaphic (ligand-directed) targeting of drugs is an important potential new approach to drug delivery, particularly in oncology. Considerable success with this approach has been achieved in the treatment of blood-borne cancers, but the advances with solid tumours have been modest. Here, we have studied the number and availability for ligand binding of the receptors for two targeting ligands. The results show that both paucity of total receptors and their poor availability are major bottlenecks in drug targeting. A tumour-penetrating peptide greatly increases the availability of receptors by promoting transport of the drug to the extravascular tumour tissue, but the number of available receptors still remains low, severely limiting the utility of the approach. Our results emphasize the importance of using drugs with high specific activity to avoid exceeding receptor capacity because any excess drug conjugate would lose the targeting advantage. The mathematical models we describe make it possible to focus on those aspects of the targeting mechanism that are most likely to have a substantial effect on the overall efficacy of the targeting.

  19. Emergent properties of a computational model of tumour growth

    PubMed Central

    2016-01-01

    While there have been enormous advances in our understanding of the genetic drivers and molecular pathways involved in cancer in recent decades, there also remain key areas of dispute with respect to fundamental theories of cancer. The accumulation of vast new datasets from genomics and other fields, in addition to detailed descriptions of molecular pathways, cloud the issues and lead to ever greater complexity. One strategy in dealing with such complexity is to develop models to replicate salient features of the system and therefore to generate hypotheses which reflect on the real system. A simple tumour growth model is outlined which displays emergent behaviours that correspond to a number of clinically relevant phenomena including tumour growth, intra-tumour heterogeneity, growth arrest and accelerated repopulation following cytotoxic insult. Analysis of model data suggests that the processes of cell competition and apoptosis are key drivers of these emergent behaviours. Questions are raised as to the role of cell competition and cell death in physical cancer growth and the relevance that these have to cancer research in general is discussed. PMID:27413638

  20. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

    PubMed Central

    Ince, Tan A.; Sousa, Aurea D.; Jones, Michelle A.; Harrell, J. Chuck; Agoston, Elin S.; Krohn, Marit; Selfors, Laura M.; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S.; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T.; Merritt, Melissa A.; Foster, Rosemary; Rueda, Bo R.; Crum, Christopher P.; Brugge, Joan S.; Mills, Gordon B.

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861