Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

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Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

Circulating Zonulin Correlates with Density of Enteroviruses and Tolerogenic Dendritic Cells in the Small Bowel Mucosa of Celiac Disease Patients.

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Vorobjova, Tamara; Raikkerus, Helerin; Kadaja, Lumme; Talja, Ija; Uibo, Oivi; Heilman, Kaire; Uibo, Raivo

2017-02-01

Impaired intestinal integrity, including increased permeability of the small bowel mucosa, has been shown in patients with celiac disease (CD) as well as with type 1 diabetes (T1D). Zonulin (ZO, pre-haptoglobin), a tight junction regulator, plays a particular role in the regulation of intestinal barrier function and in the pathogenesis of the above-mentioned diseases. To investigate whether enteroviruses (EVs) and immunoregulatory cells are associated with intestinal permeability in patients with CD alone and with coexistent T1D. Altogether 80 patients (mean age 10.68 ± 6.69 years) who had undergone small bowel biopsy were studied. Forty patients with functional dyspepsia and normal small bowel mucosa formed the control group. The circulating ZO level in sera was evaluated using ELISA. The densities of EV, FOXP3+ regulatory T cells (Tregs), indoleamine 2,3-dioxygenase (IDO+) dendritic cells (DCs) and glutamic acid dexarboxylase (GAD)65+ cells in small bowel mucosa were investigated by immunohistochemistry. The expression analysis of FOXP3, tight junction protein 1 (TJP1), gap junction (GJA1), IDO and CD103 genes was evaluated by real-time PCR. The ZO level was higher in CD patients compared to subjects with a normal small bowel mucosa, particularly in those with Marsh IIIc atrophy (p = 0.01), and correlated with the density of EV (r = 0.63; p = 0.0003) and IDO+ DCs (r = 0.58; p = 0.01) in the small bowel mucosa. The density of GAD65+ epithelial cells was correlated with the density of EV (r = 0.59; p = 0.03) and IDO+ DCs (r = 0.78; p = 0.004) in CD patients. The relative expression of FOXP3 mRNA in the small bowel mucosa tissue was significantly higher in patients with CD, compared to subjects with a normal mucosa, and correlated with the density of EV (r = 0.62; p = 0.017) as well as with the relative expression of IDO mRNA (r = 0.54; p = 0.019). The CD is associated with elevation of the circulating ZO level, the value of which

Controlling destiny through chemistry: small-molecule regulators of cell fate.

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Firestone, Ari J; Chen, James K

2010-01-15

Controlling cell fate is essential for embryonic development, tissue regeneration, and the prevention of human disease. With each cell in the human body sharing a common genome, achieving the appropriate spectrum of stem cells and their differentiated lineages requires the selective activation of developmental signaling pathways, the expression of specific target genes, and the maintenance of these cellular states through epigenetic mechanisms. Small molecules that target these regulatory processes are therefore valuable tools for probing and manipulating the molecular mechanisms by which stem cells self-renew, differentiate, and arise from somatic cell reprogramming. Pharmacological modulators of cell fate could also help remediate human diseases caused by dysregulated cell proliferation or differentiation, heralding a new era in molecular therapeutics.

Therapeutic approaches to preventing cell death in Huntington disease.

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Kaplan, Anna; Stockwell, Brent R

2012-12-01

Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Current concepts of chemotherapy and radiotherapy for small cell lung cancer

International Nuclear Information System (INIS)

Braun, T.J.; Bunn, P.A. Jr.

1986-01-01

Small cell lung cancer (SCLC) was projected to account for 20%-25% of the greater than 140,000 newly diagnosed lung cancers in 1985. If considered a separate disease entity, it would be the fourth leading cause of death by cancer. Previous studies have demonstrated distinct clinical and biologic features of small cell lung cancer, and early therapeutic trial results have demonstrated a high sensitivity to both chemotherapy and radiotherapy. More recent results demonstrated a marked survival improvement with the use of combination chemotherapy, which potentially cured a small minority of patients. Unfortunately, in most patients, drug resistance usually develops, as do chronic, often debilitating toxicities in the few long-term survivors. Although therapeutic advances have plateaued, new and important insights into the basic biology of the disease made the last several years offer the possibility of exciting new treatment approaches within the next decade. This chapter addresses our current understanding of therapy for small cell lung cancer, the current therapy questions under investigation, and potential future directions in clinical research

Transport of radiolabelled glycoprotein to cell surface and lysosome-like bodies of absorptive cells in cultured small-intestinal tissue from normal subjects and patients with a lysosomal storage disease

International Nuclear Information System (INIS)

Ginsel, L.A.; Onderwater, J.J.M.; Daems, W.T.

1979-01-01

The transport of 3 H-fucose and 3 H-glucosamine-labelled glycoproteins in the absorptive cells of cultured human small-intestinal tissue was investigated with light- and electron-microscopical autoradiography. The findings showed that these glycoproteins were completed in the Golgi apparatus and transported in small vesicular structures to the apical cytoplasm of these cells. Since this material arrived in the cell coat on the microvilli and in the lysosome-like bodies simultaneously, a crinophagic function of these organelles in the regulation of the transport or secretion of cell-coat material was supported. In the absorptive cells of patients with fucosidosis or Hunter's type of lysosomal storage disease, a similar transport of cell-coat material to the lysosome-like bodies and a congenital defect of a lysosomal hydrolase normally involved in the degradation of cell-coat material, can explain the accumulation of this material in the dense bodies. (orig.) [de

Small white matter lesion detection in cerebral small vessel disease

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Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

2015-03-01

Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

High-content screening of small compounds on human embryonic stem cells.

Science.gov (United States)

Barbaric, Ivana; Gokhale, Paul J; Andrews, Peter W

2010-08-01

Human ES (embryonic stem) cells and iPS (induced pluripotent stem) cells have been heralded as a source of differentiated cells that could be used in the treatment of degenerative diseases, such as Parkinson's disease or diabetes. Despite the great potential for their use in regenerative therapy, the challenge remains to understand the basic biology of these remarkable cells, in order to differentiate them into any functional cell type. Given the scale of the task, high-throughput screening of agents and culture conditions offers one way to accelerate these studies. The screening of small-compound libraries is particularly amenable to such high-throughput methods. Coupled with high-content screening technology that enables simultaneous assessment of multiple cellular features in an automated and quantitative way, this approach is proving powerful in identifying both small molecules as tools for manipulating stem cell fates and novel mechanisms of differentiation not previously associated with stem cell biology. Such screens performed on human ES cells also demonstrate the usefulness of human ES/iPS cells as cellular models for pharmacological testing of drug efficacy and toxicity, possibly a more imminent use of these cells than in regenerative medicine.

Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

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S. Suresh Kumar

2014-12-01

Full Text Available Human pluripotent stem cells, including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs, hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4, epidermal growth factor (EGF, fibroblast growth factor (FGF, keratinocyte growth factor (KGF, hepatocyte growth factor (HGF, noggin, transforming growth factor (TGF-α, and WNT3A are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation.

Recent Developments in β-Cell Differentiation of Pluripotent Stem Cells Induced by Small and Large Molecules

Science.gov (United States)

Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Singh, A. J. A. Ranjith; Peng, I-Chia; Priya, Sivan Padma; Hamat, Rukman Awang; Higuchi, Akon

2014-01-01

Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation. PMID:25526563

Lung cancer - non-small cell

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Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Research shows that smoking marijuana may help cancer cells grow. But there is no direct link between ...

Recent advances in the treatment of non-small cell and small cell lung cancer.

Science.gov (United States)

Stinchcombe, Thomas E

2014-01-01

Recent presentations at the American Society of Clinical Oncology (ASCO) meeting from 30 May to 3 June, 2014, will impact routine clinical care and the development of clinical trials in non-small cell lung cancer (NSCLC) and extensive stage small cell lung cancer (ES-SCLC). Patients with activating epidermal growth factor receptor (EGFR) mutations, defined as exon 19 and exon 21 L858R point mutations, experience a high objective response rate and prolonged progression-free survival with EGFR tyrosine kinase inhibitors. However, inevitably, patients experience disease progression and the most common mechanism of acquired resistance is an EGFR exon 20 T790M mutation. Several agents (AZD9291, CO-1686 and HM61713) have demonstrated impressive activity in patients with T790M resistance mutations. Additional data on the efficacy of first-line therapy with afatinib and the combination of erlotinib and bevacizumab for patients with EGFR mutant NSCLC were presented. The results of a phase III trial of crizotinib compared to platinum-pemetrexed in the first-line setting, and a phase I trial and expansion cohort of ceritinib, provided additional efficacy and toxicity data for patients with anaplastic lymphoma kinase rearranged NSCLC. A phase III trial of cisplatin and gemcitabine, with and without necitumumab, revealed an improvement in overall survival with the addition of necitumumab in patients with squamous NSCLC. In the second-line setting, a phase III trial of docetaxel with ramucirumab or placebo revealed an improvement in overall survival with the addition of ramucirumab. In extensive stage small cell lung cancer phase III trials of consolidative thoracic radiation therapy and prophylactic cranial radiation failed to reveal an improvement in overall survival.

Survival outcomes for oligometastasis in resected non-small cell lung cancer.

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Shimada, Yoshihisa; Saji, Hisashi; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2015-10-01

We investigated the factors associated with post-recurrence survival and the treatment for non-small-cell lung cancer patients with postoperative distant recurrence, especially oligometastasis. We reviewed the data of 272 patients with distant recurrence who underwent resection of non-small-cell lung cancer from January 2000 through December 2011. The type of distant recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n = 196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy (surgery 5, radiotherapy 9, sequential local and systemic therapy 28, chemoradiotherapy 5). Multivariate analysis revealed older age, non-adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver metastases, bone metastases, and polymetastasis had significant associations with unfavorable post-recurrence survival. Subgroup analysis of patients with oligometastasis showed histology and disease-free interval had a great impact on survival. Smoking history and histology were associated with survival in patients with lung oligometastasis, whereas systemic treatment and longer disease-free interval were related to increased post-recurrence survival in those with brain oligometastasis. This study showed that an oligometastatic state per se was a significant favorable factor. Optimization of personalized systemic treatment and adding local treatment are important in the management of patients with non-small-cell lung cancer and oligometastasis. © The Author(s) 2015.

Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist.

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Sugawara, Reiko; Lee, Eun-Jung; Jang, Min Seong; Jeun, Eun-Ji; Hong, Chun-Pyo; Kim, Jung-Hwan; Park, Areum; Yun, Chang Ho; Hong, Sung-Wook; Kim, You-Me; Seoh, Ju-Young; Jung, YunJae; Surh, Charles D; Miyasaka, Masayuki; Yang, Bo-Gie; Jang, Myoung Ho

2016-04-04

Eosinophils play proinflammatory roles in helminth infections and allergic diseases. Under steady-state conditions, eosinophils are abundantly found in the small intestinal lamina propria, but their physiological function is largely unexplored. In this study, we found that small intestinal eosinophils down-regulate Th17 cells. Th17 cells in the small intestine were markedly increased in the ΔdblGATA-1 mice lacking eosinophils, and an inverse correlation was observed between the number of eosinophils and that of Th17 cells in the small intestine of wild-type mice. In addition, small intestinal eosinophils suppressed the in vitro differentiation of Th17 cells, as well as IL-17 production by small intestinal CD4(+)T cells. Unlike other small intestinal immune cells or circulating eosinophils, we found that small intestinal eosinophils have a unique ability to constitutively secrete high levels of IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β. Moreover, small intestinal eosinophils isolated from IL-1Ra-deficient mice failed to suppress Th17 cells. Collectively, our results demonstrate that small intestinal eosinophils play a pivotal role in the maintenance of intestinal homeostasis by regulating Th17 cells via production of IL-1Ra. © 2016 Sugawara et al.

A Case of Non-Small Cell Lung Cancer with Possible “Disease Flare” on Nivolumab Treatment

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Shotaro Chubachi

2016-01-01

Full Text Available Background. Recent clinical trials proven the clinically significant efficacy and tolerability of nivolumab, a programmed death 1 (PD-1 inhibitor, in previously treated patients with non-small cell lung cancer (NSCLC. Case Presentation. Here, we describe the case of a patient who experienced possible “disease flare” immediately after initiation of nivolumab treatment. A 54-year-old man was diagnosed with Stage IIB (T2N1M0 lung adenocarcinoma. After 7 years from recurrence, 10th line chemotherapy, nivolumab, was initiated. Six weeks later, after 3 cycles of nivolumab treatment, rapid lung cancer progression was observed with an increase in the size of the primary lesion, multiple novel nodules on both lungs, and multiple novel brain metastases. Conclusion. We believe that physicians should be made aware that, in a subset of NSCLC patients, disease flare might occur on nivolumab treatment.

Specifically targeted gene therapy for small-cell lung cancer

DEFF Research Database (Denmark)

Christensen, C.L.; Zandi, R.; Gjetting, T.

2009-01-01

Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease.

Science.gov (United States)

Lottaz, Daniel; Buri, Caroline; Monteleone, Giovanni; Rösmann, Sandra; Macdonald, Thomas T; Sanderson, Ian R; Sterchi, Erwin E

2007-03-01

Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epithelium.

[Small-cell lung cancer: epidemiology, diagnostics and therapy].

Science.gov (United States)

Pešek, Miloš; Mužík, Jan

Authors present actual overview of information on diagnostic and therapeutic procedures in small-cell lung cancer (SCLC). This highly aggressive type of lung cancer is diagnosed in 14.8 % of Czech lung cancer patients. Vast majority of those patients (87 %) suffer from advanced and metastatic disease in the time of diagnosis. In this issue are presented prognostic factors, staging diagnostic procedures and therapeutic recommendations. The backbone of actual SCLC treatment is combined chemotherapy and radiotherapy and less frequently, carefully in selected cases, surgical procedures. SCLC should be have as chemosensitive, chemoresistent or chemorefractory disease. Actual cytostatic combinations used in 1st line treatment, different schedules of chemoradiotherapy, drugs used in second line treatment and schedules and timing of prophylactic brain irradiation are presented. In near future, perspectively, there are some promissible data on antitumour immunotherapy based on anti CTLA-4 and anti PD-1/PE-L1 antibodies also in SCLC patients.Key words: cancer immunotherapy - concomitant chemoradiotherapy - chemotherapy - chest radiotherapy - lung resections - prophylactic brain irradiation - small cell lung cancer.

Case report 331: Small cell osteosarcoma of the tibia with diffuse metastatic disease

International Nuclear Information System (INIS)

Roessner, A.; Miebs, T.; Grundmann, E.; Immenkamp, M.; Hiddemann, W.; Althoff, J.

1985-01-01

In summary, the case is presented of a 29-year-old woman who developed a sclerosing small-cell osteosarcoma in the upper end of the tibia. The unique features in this case are reflected both in its morphology and protracted clinical course, while its histological pattern resembles in some features a small cell variant of the highly malignant osteosarcoma described by Sim and Martin. In addition to the unusual clinical course, the failure in response to chemotherapy underscores that this tumor differed in its biological behavior from other highly malignant types of osteosarcoma. The importance of DNA analysis is stressed. (orig./WU)

Long-term survival in small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U; Osterlind, K; Hansen, M

1995-01-01

PURPOSE: To describe in patients with small-cell lung cancer (SCLC) the characteristics of those who survive for > or = 5 years, to identify long-term prognostic factors, to analyze survival data of 5-year survivors, and to study 10-year survival in patients entered before 1981. PATIENTS......, especially tobacco-related cancers and other tobacco-related diseases....

Small-Molecule Induction Promotes Corneal Epithelial Cell Differentiation from Human Induced Pluripotent Stem Cells

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Alexandra Mikhailova

2014-02-01

Full Text Available Human induced pluripotent stem cells (hiPSCs offer unique opportunities for developing novel cell-based therapies and disease modeling. In this study, we developed a directed differentiation method for hiPSCs toward corneal epithelial progenitor cells capable of terminal differentiation toward mature corneal epithelial-like cells. In order to improve the efficiency and reproducibility of our method, we replicated signaling cues active during ocular surface ectoderm development with the help of two small-molecule inhibitors in combination with basic fibroblast growth factor (bFGF in serum-free and feeder-free conditions. First, small-molecule induction downregulated the expression of pluripotency markers while upregulating several transcription factors essential for normal eye development. Second, protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63 positive after 5 weeks of differentiation. Third, corneal epithelial-like cells were obtained upon further maturation.

Re-education begins at home: an overview of the discovery of in vivo-active small molecule modulators of endogenous stem cells.

Science.gov (United States)

Um, JungIn; Lee, Ji-Hyung; Jung, Da-Woon; Williams, Darren R

2018-04-01

Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.

Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study

OpenAIRE

Morrow, C. J.; Trapani, F.; Metcalf, R. L.; Bertolini, G.; Hodgkinson, C. L.; Khandelwal, G.; Kelly, P.; Galvin, M.; Carter, L.; Simpson, K. L.; Williamson, S.; Wirth, C.; Simms, N.; Frankliln, L.; Frese, K. K.

2016-01-01

Background Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ?liquid biopsies? such as circulating tumour cells (CTCs) are minimally invasive...

A Case of Primary Gastric Small-Cell Carcinoma in an Elderly Patient

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Fa-Chang Yu

2012-03-01

Full Text Available We report a case of primary small-cell carcinoma of the stomach in a 75-year-old man. The patient was admitted to our hospital with a 1-week history of intermittent tarry stool. An upper gastrointestinal examination revealed a large stage A2 ulcer in the greater curvature of the body of the stomach, and pathological findings from biopsy specimens revealed small-cell carcinoma. The tumor cells were small-sized, composed of hyperchromatic nuclei with scant cytoplasm, and stained positive for cytokeratin, synaptophysin, and chromogranin A. The patient was diagnosed with primary small-cell carcinoma of the stomach. He declined further evaluation and received palliative management. This is a rare carcinoma of the stomach, with aggressive manifestations and a poor prognosis. The mean survival of patients with primary gastric small-cell carcinoma is reported to be 7 months. The choice of treatment for this disease is still controversial. This rare gastric tumor should be listed in the differential diagnosis of gastric carcinoma in the elderly.

Small cell glioblastoma or small cell carcinoma

DEFF Research Database (Denmark)

Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H

2013-01-01

was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

2011-01-01

Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

Radiodiagnosis of diseases of the small intestine

International Nuclear Information System (INIS)

Anon.

1987-01-01

Roentgenological image of diseases, development anomalies, various diseases of the small intestine is presented. Roentgenological semiotics of chronic enterocolotis, absorption failure syndrome, Crohn's disease, tuberculosis, abdominal actinomycosis, carcenoid, benign tumors, small intestine cancer, is given. To state final correct diagnosis a complex investigation, comprising angiography, computer tomography and ultrasound diagnosis, is necessary

Human Induced Pluripotent stem cells and their derivatives for disease modeling and therapeutic applications in Alzheimer's disease

DEFF Research Database (Denmark)

Pires, C.; Hall, V.; Freude, K. K.

2016-01-01

Human induced pluripotent stem cells (hiPSCs) have recently been generated for various inherited diseases. These hiPSC have the capacity to differentiate into any given cell type withthe help of small compounds and growth factors aiding the process. In Alzheimer’s disease (AD) several specific...... neural subpopulations in the brain are more susceptible to degeneration and apoptosis and hiPSCs can be used in order to generate these subpopulations in cell culture dishes via directed differentiation. Subsequently these cells can be used to optimize small compound screens to identify novel drug......, followed by a description of the methods used to generate isogenic controls. We will also discuss the possibilities and limitations of current neural differentiation protocols for AD to obtain relevant neuronal subtypes. In the end we will elaborate on the possibilities and current issues of hiPSC for cell...

Stages of Small Cell Lung Cancer

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... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Nagla Abdel Karim

2015-01-01

Full Text Available Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%–14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%–80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

Multi-User MIMO Across Small Cells

DEFF Research Database (Denmark)

Finn, Danny; Ahmadi, Hamed; Cattoni, Andrea Fabio

2014-01-01

The main contribution of this work is the proposal and assessment of the MU-MIMO across Small Cells concept. MU-MIMO is the spatial multiplexing of multiple users on a single time-frequency resource. In small cell networks, where the number of users per cell is low, finding suitable sets of users...... to be co-scheduled for MU-MIMO is not always possible. In these cases we propose MU-MIMO-based cell reassignments of users into adjacent cells to enable MU-MIMO operation. From system level simulations we found that, when the initial number of users per small cell is four, cell reassignment results in a 21.......7% increase in the spectral efficiency gain attributed to MU-MIMO, and a higher percentage increase when the initial number of users per cell is lower. Going forward, we will extend this work to also consider energy savings through switching off small cells which are emptied by the reassignment process....

Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

Science.gov (United States)

Rooney, Claire; Sethi, Tariq

2015-10-01

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report.

Science.gov (United States)

Ho, Won Jin; Rooper, Lisa; Sagorsky, Sarah; Kang, Hyunseok

2018-05-09

Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months. Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

New small molecules targeting apoptosis and cell viability in osteosarcoma.

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Doris Maugg

Full Text Available Despite the option of multimodal therapy in the treatment strategies of osteosarcoma (OS, the most common primary malignant bone tumor, the standard therapy has not changed over the last decades and still involves multidrug chemotherapy and radical surgery. Although successfully applied in many patients a large number of patients eventually develop recurrent or metastatic disease in which current therapeutic regimens often lack efficacy. Thus, new therapeutic strategies are urgently needed. In this study, we performed a phenotypic high-throughput screening campaign using a 25,000 small-molecule diversity library to identify new small molecules selectively targeting osteosarcoma cells. We could identify two new small molecules that specifically reduced cell viability in OS cell lines U2OS and HOS, but affected neither hepatocellular carcinoma cell line (HepG2 nor primary human osteoblasts (hOB. In addition, the two compounds induced caspase 3 and 7 activity in the U2OS cell line. Compared to conventional drugs generally used in OS treatment such as doxorubicin, we indeed observed a greater sensitivity of OS cell viability to the newly identified compounds compared to doxorubicin and staurosporine. The p53-negative OS cell line Saos-2 almost completely lacked sensitivity to compound treatment that could indicate a role of p53 in the drug response. Taken together, our data show potential implications for designing more efficient therapies in OS.

Small bowel ultrasound in patients with celiac disease

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Bartusek, D. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: dbartusek@fnbrno.cz; Valek, V. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: v.valek@fnbrno.cz; Husty, J. [Department of Radiology, Masaryk University hospital Brno (Czech Republic)], E-mail: jhusty@fnbrno.cz; Uteseny, J. [Department of Pediatric Internal Medicine, Masaryk University hospital Brno (Czech Republic)], E-mail: juteseny@fnbrno.cz

2007-08-15

Objective: Celiac disease (CD) is a common, lifelong disease with small bowel malabsorption based on genetically conditioned gluten intolerance. The clinical manifestation could be very heterogeneous. The proof of celiac disease is now based mainly on clinical and laboratory (antibodies and enterobiopsy) signs, which are in some cases problematic and inconvenient. Materials and methods: In our study we have examined 250 patients with suspection or with proven celiac disease and we evaluated specific ultrasound small bowel changes in this group. In the next step, we chose 59 patients with laboratory proved celiac disease and we statistically compared ultrasound, other laboratory and clinical findings in different forms and stages of the disease. Results: Specific small bowel pathologies in patients with celiac disease (like changes of intestinal villi in different parts of small bowel, abnormal peristalsis and mesenterial lymphadenopathy) can be well visualized by ultrasound and in combination with clinical and laboratory signs ultrasound examination could have an important role in screening, determination of diagnosis and monitoring of patients with different forms of celiac disease.

Small bowel ultrasound in patients with celiac disease

International Nuclear Information System (INIS)

Bartusek, D.; Valek, V.; Husty, J.; Uteseny, J.

2007-01-01

Objective: Celiac disease (CD) is a common, lifelong disease with small bowel malabsorption based on genetically conditioned gluten intolerance. The clinical manifestation could be very heterogeneous. The proof of celiac disease is now based mainly on clinical and laboratory (antibodies and enterobiopsy) signs, which are in some cases problematic and inconvenient. Materials and methods: In our study we have examined 250 patients with suspection or with proven celiac disease and we evaluated specific ultrasound small bowel changes in this group. In the next step, we chose 59 patients with laboratory proved celiac disease and we statistically compared ultrasound, other laboratory and clinical findings in different forms and stages of the disease. Results: Specific small bowel pathologies in patients with celiac disease (like changes of intestinal villi in different parts of small bowel, abnormal peristalsis and mesenterial lymphadenopathy) can be well visualized by ultrasound and in combination with clinical and laboratory signs ultrasound examination could have an important role in screening, determination of diagnosis and monitoring of patients with different forms of celiac disease

Oligometastatic non-small-cell lung cancer: current treatment strategies

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Richard PJ

2016-11-01

Full Text Available Patrick J Richard, Ramesh Rengan Department of Radiation Oncology, University of Washington, Seattle, WA, USA Abstract: The oligometastatic disease theory was initially described in 1995 by Hellman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each. Keywords: oligometastatic, non-small-cell lung cancer, oligoprogressive, treatment

The Inter-Cell Interference Dilemma in Dense Outdoor Small Cell Deployment

DEFF Research Database (Denmark)

Polignano, Michele; Mogensen, Preben; Fotiadis, Panagiotis

2014-01-01

The deployment of low-power small cells is envisaged as the main driver to accommodate the mobile broadband traffic growth in cellular networks. Depending on the spatial distribution of the user traffic, a densification of the small cells may be required in confined areas. However, deploying more...... and more cells in given areas may imply an increase of the inter-cell interference among the small cells. This study aims at investigating if the inter-cell interference among outdoor small cells may represent an impairment to the user experience, and evaluates if and in what conditions the interference...... coordination is worthwhile compared to the universal frequency reuse. Results show that the inter-cell interference depends on the small cell deployment in the urban environment (e.g. streets and squares) and on the network load condition. In case of deployment along urban streets, the inter-cell interference...

State of the art toward defining the role of radiation therapy in the management of small cell bronchogenic carcinoma

International Nuclear Information System (INIS)

Salazar, O.M.; Creech, R.H.

1980-01-01

This review article with 70 references discusses the state of the art in defining the role of radiotherapy in managing small cell bronchogenic carcinoma (SCBC). It reviews the history of therapeutic approaches to SCBC. Several issues of particular interest to limited disease are discussed. They are: local radiation therapy for limited disease, combined radiation therapy and chemotherapy in limited disease, combination chemotherapy alone for limited disease, and an overview of the treatment of limited disease. A section on extensive disease discusses the role of radiation therapy and chemotherapy, chemotherapy only for extensive disease, and an overview of the treatment of extensive disease. An additional section discusses the use of elective brain irradiation in small cell bronchogenic carcinoma

Small Cell Carcinoma of the Ovary of Hypercalcemic Type: A Case Report

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S. Zaied

2012-01-01

Full Text Available Introduction. The small cell carcinoma of hypercalcemic type of ovary is a very aggressive tumor. It is associated with two-thirds of cases with hypercalcemia most often asymptomatic. It occurs mostly for young women. The treatment combines surgery, chemotherapy, and radiotherapy. Case Presentation. We report a case of small cell carcinoma of the ovary hypercalcemic type in a young Tunisian woman aged 25 years after a severe abdominal pain syndrome and a large ovarian mass discovered in scanner; a laparotomy was performed by radical surgery. The pathological examination of the specimen confirmed the diagnosis. The radiological assessment performed after surgery showed a continuing evolution. Palliative chemotherapy was established, and the patient had died two months after diagnosis. Conclusion. The hypercalcemic small cell carcinoma of the ovary is a rare disease of poor prognosis.

Lung carcinoma: Recent progress and current controversies in small cell limited disease

International Nuclear Information System (INIS)

Turrisi, Andrew T.

1996-01-01

or clinical observations of whole organ treatment. Little data exists about partial organ tolerance particularly in diseased lungs in patients that have lung cancers. Strategies to investigate partial intolerance will be discussed. Potential roles of chemotherapy will be discussed. Platinum containing chemotherapeutic regimens dominate at this time. There are new agents with novel mechanisms of action including gernatative, the taxanes, top-I inhibitors and vinorelbul. There are still unfavorable interplays with certain chemotherapeutic agents and their combined modality use is questionable. 'Neo-adjuvant chemotherapy' to radiotherapy in Stage IIIA and IIIB will be discussed, and strategies for weekly and daily concurrent platinum with radiotherapy. Prophylactic cranial irradiation, an extremely contentious issue will be outlined. The roles of continuous hyperfractionated accelerated radiotherapy, dose escalation, volume reduction will be explored. Results of randomized trials in small cell, non-small cell, and PCI will be discussed. The role of surgery in stage IIIA will be reviewed

Challenges for heart disease stem cell therapy

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Hoover-Plow J

2012-02-01

Full Text Available Jane Hoover-Plow, Yanqing GongDepartments of Cardiovascular Medicine and Molecular Cardiology, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, USAAbstract: Cardiovascular diseases (CVDs are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1 improved identification, recruitment, and expansion of autologous stem cells; (2 identification of mobilizing and homing agents that increase recruitment; and (3 development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.Keywords: mobilization, expansion, homing, survival, engraftment

Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

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Song, Gaoguang; Liu, Yujie; Wang, Yanying; Ren, Guanjun; Guo, Shuai; Ren, Junling; Zhang, Li; Li, Zhili

2015-02-02

Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression. Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis. Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks). The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression. Copyright © 2014 Elsevier B.V. All rights reserved.

FDG-PET imaging for the staging and follow-up of small cell lung cancer

International Nuclear Information System (INIS)

Schumacher, T.; Brink, I.; Mix, M.; Reinhardt, M.; Moser, E.; Nitzsche, E.; Herget, G.; Digel, W.; Henke, M.

2001-01-01

The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6 x limited disease, 12 x extensive disease, 5 x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic

Computed tomography of the spleen and liver in sickle cell disease

International Nuclear Information System (INIS)

Magid, D.; Fishman, E.K.; Siegelman, S.S.

1984-01-01

The spleen was assessed in 10 patients with sickle cell disease studied with computed tomography (CT) for abdominal pain and/or unexplained fever. Patients with homozygous sickle cell anemia were found to have small, densely calcified spleens with occasional low-density infarcts. Five of six had hepatomegaly, and there was one case each of hepatic abscess, infarcts, and hemochromatosis. All patients with heterozygous sickle cell disease were found to have splenomegaly, with a variety of findings including acute hemorrhage, acute and chronic infarcts, rupture, and possible sequestration. It was concluded that CT is useful for evaluating the status of the spleen and liver in symptomatic patients with sickle cell disease

Effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer

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Shu-Hui Yao

2016-03-01

Full Text Available Objective: To evaluate the effect of cryoablation sequential chemotherapy on patients with advanced non-small cell lung cancer. Methods: A total of 39 cases with advanced non-small cell lung cancer who received cryoablation sequential chemotherapy and 39 cases with advanced non-small cell lung cancer who received chemotherapy alone were selected and enrolled in sequential group and control group, disease progression and survival of two groups were followed up, and contents of tumor markers and angiogenesis molecules in serum as well as contents of T-lymphocyte subsets in peripheral blood were detected. Results: Progressionfree survival and median overall survival (mOS of sequential group were longer than those of control group, and cumulative cases of tumor progression at various points in time were significantly less than those of control group (P<0.05; 1 month after treatment, serum tumor markers CEA, CYFRA21-1 and NSE contents, serum angiogenesis molecules PCDGF, VEGF and HDGF contents as well as CD3+CD4-CD8+CD28-T cell content in peripheral blood of sequential group were significantly lower than those of control group (P<0.05, and contents of CD3+CD4+CD8-T cell and CD3+CD4-CD8+CD28+T cell in peripheral blood were higher than those of control group (P<0.05. Conclusions: Cryoablation sequential chemotherapy can improve the prognosis of patients with advanced non-small cell lung cancer, delay disease progression, prolong survival time, inhibit angiogenesis and improve immune function.

Management of non-small cell lung cancer with oligometastasis.

Science.gov (United States)

Villaruz, Liza C; Kubicek, Gregory J; Socinski, Mark A

2012-08-01

Patients with oligometastatic Non-Small Cell Lung Cancer (NSCLC) present a potential opportunity for curative therapy; however, the challenge remains the definitive treatment of their localized disease and ablation of their limited overt metastatic sites of disease. In selecting patients with oligometastatic NSCLC for definitive therapy, proper staging through radiographic studies, including PET and brain MRI, and the pathologic staging of the mediastinal lymph nodes and potential sites of metastatic disease, are critical. With that in mind, the available literature suggests that in highly selected patients with solitary metastases to the brain, adrenals and other organs, long term survival may be achieved with combined definitive therapy of both the primary lung tumor and the solitary metastatic site.

Sickle cell disease with orbital infarction and epidural hematoma

International Nuclear Information System (INIS)

Naran, A.D.; Fontana, L.

2001-01-01

Although bone infarction is a common feature in sickle cell disease, the involvement of the orbit is an unusual complication. Intracranial bleeding is another uncommon and serious complication. Few cases of orbital infarction alone have been reported. We report imaging findings (CT, bone scan, MRI) in a 16-year-old boy with sickle cell disease with orbital infarction and epidural hematoma. The precise cause of epidural hematoma is not well known, but it is probably related to vaso-occlusive episodes and the tearing of small vessels. (orig.)

Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns.

Science.gov (United States)

Vanoli, Alessandro; Di Sabatino, Antonio; Martino, Michele; Klersy, Catherine; Grillo, Federica; Mescoli, Claudia; Nesi, Gabriella; Volta, Umberto; Fornino, Daniele; Luinetti, Ombretta; Fociani, Paolo; Villanacci, Vincenzo; D'Armiento, Francesco P; Cannizzaro, Renato; Latella, Giovanni; Ciacci, Carolina; Biancone, Livia; Paulli, Marco; Sessa, Fausto; Rugge, Massimo; Fiocca, Roberto; Corazza, Gino R; Solcia, Enrico

2017-10-01

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and

Radiotherapy alone for non-small cell lung carcinoma. Five-year disease-free survival and patterns of failure

International Nuclear Information System (INIS)

Koukourakis, M.; Skarlatos, J.; Kosma, L.; Yannakakis, D.; Giatromanolaki, A.

1995-01-01

One hundred and fifty-three patients with inoperable non-small cell lung cancer (NSCLC) treated with radiotherapy alone have been retrospectively analysed. Normalized Total Dose (NTD) as defined by Macejewski, TN-stage (AJC-system) and histology have been examined with respect to 5-year disease-free survival (DFS) and the patterns of failure so as to identify subgroups of patients that routinely should be treated with radical intent. The 5-year DFS for T1, 2-N0, 1 and T3-N0, 1 staged patients was 30% (7/23) and 25% (4/16) respectively when the tumor NTD (a/b=10 Gy) was 56-64 Gy vs. 12% (5/41) and 0% (0/10) when the NTD was 48-55 Gy. This difference was statistically significant for the squamous cell histology group. The higher doses significantly altered the patterns of death in N0, 1 staged squamous cell carcinoma and adenocarcinoma patients. Forty-five percent (22/55) and 41% (12/29) of squamous cell adenocarcinoma patients respectively, died from local relapse without evidence of distant metastases when NTD less than 55 Gy were given vs. 21% (9/42) and 13% (2/15) when the NTD delivered was 56-64 Gy (p<0.05). Although for N2, 3 staged patients or patients with direct extension of the tumor into the mediastinum death from local relapse occurred in 38% (10/26) of the high NTD treated patients vs. 51% (19/37) of the low-dose treated ones, the difference was not statistically significant. It is concluded that NSCLC patients should not a priori be considered as non-radiocurable. At least 30% of the patients with early local stages can be long-term disease-free survivors with readiation NTD up to 60 Gy and better results are to be expected with higher doses. Advanced T-stage without mediastinal involvement should be treated with radical intent since a high NTD could give cure rates of over 25%. The disappointing results for patients with mediastinal disease could perhaps be attributed to the low NTD delivered. For patients with good performance status

General Information about Small Cell Lung Cancer

Science.gov (United States)

... Lung Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points Small ...

Differential distribution of inflammatory cells in large and small airways in smokers

NARCIS (Netherlands)

Battaglia, Salvatore; Mauad, Thais; van Schadewijk, Annemarie M.; Vignola, Antonia M.; Rabe, Klaus F.; Bellia, Vincenzo; Sterk, Peter J.; Hiemstra, Pieter S.

2007-01-01

BACKGROUND: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been

Imaging features of renal complications after crizotinib treatment for non–small-cell lung cancer: a case report

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Wan Ying Chan, MBBS

2016-09-01

Full Text Available Crizotinib has been approved for the treatment of advanced ALK-positive non–small cell lung cancer. Its use is associated with the development of complex renal cysts. However, there is limited literature regarding imaging features of renal cystic disease during crizotinib therapy and its complications or progression. Here, we describe a case of a patient with ALK-positive advanced non–small cell lung cancer who developed complex renal cyst during crizotinib treatment. The renal cyst is complicated by infection and abscess formation. Subsequent renal biopsy, antibiotics treatment, and open drainage of loculated renal abscess showed no malignant cells and contributed to the diagnosis. The imaging features should be recognized as renal cystic disease of crizotinib treatment and not to be mistaken as new metastasis and disease progression.

Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.

Science.gov (United States)

Aguisanda, Francis; Yeh, Charles D; Chen, Catherine Z; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

2017-06-28

Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. We have generated induced pluripotent stem cells (iPSCs) from two WD patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of neutral lipid accumulation, severely deficient LAL activity, and increased LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the WD phenotype in these cells. In addition, δ-tocopherol (DT) and hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy. The results demonstrate that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. DT and HPBCD both reduce LysoTracker dye staining in WD cells. The cells may be used to further dissect the pathology of WD, evaluate compound efficacy, and serve as a platform for high-throughput drug screening to identify new compounds for therapeutic development.

Perforated small intestine in a patient with T-cell lymphoma; a rare cause of peritonitis

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Petrişor Banu

2016-04-01

Full Text Available The nontraumatic perforations of the small intestine are pathological entities with particular aspects in respect to diagnosis and treatment. These peculiarities derive from the nonspecific clinical expression of the peritonitis syndrome, and from the multitude of causes that might be the primary sources of the perforation: foreign bodies, inflammatory diseases, tumors, infectious diseases, etc. Accordingly, in most cases intestinal perforation is discovered only by laparotomy and the definitive diagnosis is available only after histopathologic examination. Small bowel malignancies are rare; among them, lymphomas rank third in frequency, being mostly B-cell non Hodgkin lymphomas. Only 10% of non-Hodgkin lymphomas are with T-cell. We report the case of a 57 years’ old woman with intestinal T-cell lymphoma, whose first clinical symptomatology was related to a complication represented by perforation of the small intestine. Laparotomy performed in emergency identified an ulcerative lesion with perforation in the jejunum, which required segmental enterectomy with anastomosis. The nonspecific clinical manifestations of intestinal lymphomas make from diagnosis a difficult procedure. Due to the fact that surgery does not have a definite place in the treatment of the small intestinal lymphomas (for cases complicated with perforation, and beyond the morbidity associated with the surgery performed in emergency conditions, prognosis of these patients is finally given by the possibility to control the systemic disease through adjuvant therapy.

Stem cell therapy: the great promise in lung disease.

Science.gov (United States)

Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

2008-06-01

Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation.

Small cell networks deployment, management, and optimization

CERN Document Server

Claussen, Holger; Ho, Lester; Razavi, Rouzbeh; Kucera, Stepan

2018-01-01

Small Cell Networks: Deployment, Management, and Optimization addresses key problems of the cellular network evolution towards HetNets. It focuses on the latest developments in heterogeneous and small cell networks, as well as their deployment, operation, and maintenance. It also covers the full spectrum of the topic, from academic, research, and business to the practice of HetNets in a coherent manner. Additionally, it provides complete and practical guidelines to vendors and operators interested in deploying small cells. The first comprehensive book written by well-known researchers and engineers from Nokia Bell Labs, Small Cell Networks begins with an introduction to the subject--offering chapters on capacity scaling and key requirements of future networks. It then moves on to sections on coverage and capacity optimization, and interference management. From there, the book covers mobility management, energy efficiency, and small cell deployment, ending with a section devoted to future trends and applicat...

Gastrointestinal and hepatic complications of sickle cell disease.

Science.gov (United States)

Ebert, Ellen C; Nagar, Michael; Hagspiel, Klaus D

2010-06-01

Sickle cell disease (SCD) is an autosomal recessive abnormality of the beta-globin chain of hemoglobin (Hb), resulting in poorly deformable sickled cells that cause microvascular occlusion and hemolytic anemia. The spleen is almost always affected by SCD, with microinfarcts within the first 36 months of life resulting in splenic atrophy. Acute liver disorders causing right-sided abdominal pain include acute vaso-occlusive crisis, liver infarction, and acute hepatic crisis. Chronic liver disease might be due to hemosiderosis and hepatitis and possibly to SCD itself if small, clinically silent microvascular occlusions occur chronically. Black pigment gallstones caused by elevated bilirubin excretion are common. Their small size permits them to travel into the common bile duct but cause only low-grade obstruction, so hyperbilirubinemia rather than bile duct dilatation is typical. Whether cholecystectomy should be done in asymptomatic individuals is controversial. The most common laboratory abnormality is an elevation of unconjugated bilirubin level. Bilirubin and lactate dehydrogenase levels correlate with one another, suggesting that chronic hemolysis and ineffective erythropoiesis, rather than liver disease, are the sources of hyperbilirubinemia. Abdominal pain is very common in SCD and is usually due to sickling, which resolves with supportive care. Computed tomography scans might be ordered for severe or unremitting pain. The liver typically shows sickled erythrocytes and Kupffer cell enlargement acutely and hemosiderosis chronically. The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

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Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

1999-10-01

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Regulatory Role of Small Nucleolar RNAs in Human Diseases

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Grigory A. Stepanov

2015-01-01

Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

Pathophysiology of acute small bowel disease with CT correlation

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Sarwani, N.; Tappouni, R.; Tice, J.

2011-01-01

The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

Morphometric Characterization of Small Cell Lymphocytic Lymphoma

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Chisoi Anca

2014-11-01

Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

Concurrent chemoradiotherapy for limited-disease small cell lung cancer in elderly patients aged 75 years or older

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Shimizu, Toshio; Sekine, Ikuo; Sumi, Minako

2007-01-01

The optimal treatment for limited-disease small cell lung cancer (LD-SCLC) in patients aged 75 years or older remains unknown. Elderly patients with LD-SCLC who were treated with chemoradiotherapy were retrospectively reviewed to evaluate their demographic characteristics and the treatment delivery, drug toxicities and antitumor efficacy. Of the 94 LD-SCLC patients treated with chemotherapy and thoracic radiotherapy at the National Cancer Center Hospital between 1998 and 2003, seven (7.4%) were 75 years of age or older. All of the seven patients were in good general condition, with a performance status of 0 or 1. Five and two patients were treated with early and late concurrent chemoradiotherapy, respectively. While the four cycles of chemotherapy could be completed in only four patients, the full dose of radiotherapy was completed in all of the patients. Grade 4 neutropenia and thrombocytopenia were noted in seven and three patients, respectively. Granulocyte-colony stimulating factor support was used in five patients, red blood cell transfusion was administered in two patients and platelet transfusion was administered in one patient. Grade 3 or more severe esophagitis, pneumonitis and neutropenic fever developed in one, two and three patients, respectively, and one patient died of radiation pneumonitis. Complete response was achieved in six patients and partial response in one patient. The median survival time was 24.7 months, with three disease-free survivors for more than 5 years. Concurrent chemoradiotherapy promises to provide long-term benefit with acceptable toxicity for selected patients of LD-SCLC aged 75 years or older. (author)

Synchronous Oligometastatic Non-Small Cell Lung Cancer and Isolated Renal Cell Carcinoma: A Case Report and Literature Review.

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Nguyen, Timothy K; Louie, Alexander V

2015-10-27

A 58-year-old gentleman presenting with a progressive headache, visual disturbance, decreased appetite, and weight loss was found to have a localized clear cell carcinoma of the kidney and synchronous Stage IV non-small cell lung cancer with a solitary brain metastasis. This case illustrates the challenges in distinguishing between primary and metastatic disease in a patient with both renal cell carcinoma and lung cancer. We highlight the uncertainties in the diagnosis and management of this unique clinical scenario and the potential implications on prognosis.

Progress and potential of non-inhibitory small molecule chaperones for the treatment of Gaucher disease and its implications for Parkinson disease.

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Jung, Olive; Patnaik, Samarjit; Marugan, Juan; Sidransky, Ellen; Westbroek, Wendy

2016-05-01

Gaucher disease, caused by pathological mutations GBA1, encodes the lysosome-resident enzyme glucocerebrosidase, which cleaves glucosylceramide into glucose and ceramide. In Gaucher disease, glucocerebrosidase deficiency leads to lysosomal accumulation of substrate, primarily in cells of the reticulo-endothelial system. Gaucher disease has broad clinical heterogeneity, and mutations in GBA1 are a risk factor for the development of different synucleinopathies. Insights into the cell biology and biochemistry of glucocerebrosidase have led to new therapeutic approaches for Gaucher disease including small chemical chaperones. Such chaperones facilitate proper enzyme folding and translocation to lysosomes, thereby preventing premature breakdown of the enzyme in the proteasome. This review discusses recent progress in developing chemical chaperones as a therapy for Gaucher disease, with implications for the treatment of synucleinopathies. It focuses on the development of non-inhibitory glucocerebrosidase chaperones and their therapeutic advantages over inhibitory chaperones, as well as the challenges involved in identifying and validating chemical chaperones.

Small airways disease: time for a revisit?

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Stockley JA

2017-08-01

Full Text Available James A Stockley,1 Brendan G Cooper,1 Robert A Stockley,2 Elizabeth Sapey3 1Department of Lung Function and Sleep, 2Department of Respiratory Medicine, University Hospital Birmingham, 3Institute of Inflammation and Ageing, Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham, UK Abstract: It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies. This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease. There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care. Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD. However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD. The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies. Furthermore, population studies have not consistently demonstrated their ability to diagnose disease. However, the landscape may be changing. As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance. Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity

Patient-derived stem cells: pathways to drug discovery for brain diseases

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Alan eMackay-Sim

2013-03-01

Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

Personalizing Therapy in Advanced Non–Small Cell Lung Cancer

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Villaruz, Liza C.; Burns, Timothy F.; Ramfidis, Vasilis S.; Socinski, Mark A.

2016-01-01

The recognition that non–small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation–driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes. PMID:24258572

Diaphragm disease of the small intestine: an interesting case report.

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Ullah, Sana; Ajab, Shereen; Rao, Rajashekhar; Raghunathan, Girish; DaCosta, Philip

2015-06-01

Diaphragm disease of small intestine usually presents with nonspecific clinical features. Radiological investigations often fail to differentiate it from small intestinal tumors and inflammatory bowel disease. It is therefore diagnosed on final histology after surgical resection. We hereby report an interesting case of a suspected small bowel tumor later diagnosed as diaphragm disease on histology. © The Author(s) 2014.

Triage of Limited Versus Extensive Disease on 18F-FDG PET/CT Scan in Small Cell lung Cancer

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Saima Riaz

2017-06-01

Full Text Available Objective(s: Small cell lung cancer (SCLC is an aggressive neuroendocrine carcinoma, which accounts for 10-15% of pulmonary cancers and exhibits early metastatic spread. This study aimed to determine the added value of 18F-FDG PET/CT imaging in tumor, node, and metastasis (TNM staging of SCLC, compared to the conventional computed tomography (CT scan and its potential role as a prognosticator.Methods: This retrospective review was conducted on 23 patients, who were histopathologically diagnosed to have SCLC and referred for undergoing 18F-FDG PET/CT scanning during October 2009-December 2015. The rate of agreement between the CT and 18F-FDG PET/CT findings for TNM staging was calculated using the Cohen’s kappa (κ. The median follow-up time was eight months, ranging 27-3 months. The overall and disease-free survival rates were calculated based on the extent of disease.Results: 19 cases were male and four female with the mean age of 58±9 years. The 18F-FDG PET/CT identified limited and extensive diseases in 2 (8.7% and 21 (91.3% patients, respectively. In addition, the results of the Cohen’s kappa demonstrated a strong (κ=0.82, fair (κ=0.24, and poor (κ=0.12 agreement between the PET/CT and CT findings for determining tumor, node, and metastasis stages, respectively. The 18F-FDG PET/CT scans upstaged disease in 47% of the cases with visceral and osseous metastasis. The disease-free survival rates for the limited and extensive diseases were 100% and 23% within the 12-month follow-up. In addition, 8 (35% patients expired during the follow-up period.Conclusion: Improved nodal and metastatic disease identification highlights the role of 18F-FDG PET/CT scanning in initial staging of SCLC with prognostic implications.

Cost and effectiveness studies in non-small cell lung cancer

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Pinar Yalcin-Balcik

2015-02-01

Full Text Available Lung cancer disease diagnosis and treatment is costly. As the numbers of inflicted rise so does the economic burden assumed for this cancer type. When the treatment expenditures are considered for all types of cancer, the lung cancer is thought to occupy a 20% share. The disease examined in two basic groups as small-cell lung cancer and non-small cell lung cancer (NSCLC is the most frequently encountered type of its kind nationally and in the World. This study considers the cost, effectiveness and cost effectiveness of platinum based chemotherapy medications with active ingredients pemetrexed and gemcitabine used for NSCLC. A review of studies relevant to the advanced stage NSCLC where majority of patients are positioned is foreseen to be useful to the decision makers since policy makers, regulating authorities and physicians require more information due to increased overall finance and costs, as well as treatment cost effectiveness. Furthermore, due to the entry attempt of pemetrexed active ingredient to the list of reimbursed medications for the first stage lung cancer treatment, it is assumed that a review of studies containing pemetrexed and gemcitabine will draw the attention of decision makers at the Social Security Instutition. [TAF Prev Med Bull 2015; 14(1.000: 55-64

Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

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Benoit, Danielle S. W.; Schwartz, Michael P.; Durney, Andrew R.; Anseth, Kristi S.

2008-10-01

Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

Risk factors and management of oligometastatic non-small cell lung cancer.

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Patel, Akshar N; Simone, Charles B; Jabbour, Salma K

2016-08-01

Non-small cell lung cancer (NSCLC) is an aggressive malignancy with close to half of all patients presenting with metastatic disease. A proportion of these patients with limited metastatic disease, termed oligometastatic disease, have been shown to benefit from a definitive treatment approach. Synchronous and metachronous presentation of oligometastatic disease have prognostic significance, with current belief that metachronous disease is more favorable. Surgical excision of intracranial and extracranial oligometastatic disease has been shown to improve survival, especially in patients with lymph node-negative disease, adenocarcinoma histology and smaller thoracic tumors. Definitive radiation to sites of oligometastatic disease and initial thoracic disease has also been shown to have a similar impact on survival for both intracranial and extracranial disease. Recent studies have reported on the use of targeted agents combined with ablative doses of radiation in the oligometastatic setting with promising outcomes. In this review, we present the historical and current literature describing surgical and radiation treatment options for patients with oligometastatic NSCLC. © The Author(s), 2016.

Sickle Cell Disease (For Parents)

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... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Parents / Sickle Cell Disease What's ... español Enfermedad de células falciformes What Is Sickle Cell Disease? Sickle cell disease is a condition in ...

Specific and Nonspecific B-Cell Function in the Small Intestines of Patients with Whipple's Disease ▿

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Geelhaar, Anika; Moos, Verena; Schinnerling, Katina; Allers, Kristina; Loddenkemper, Christoph; Fenollar, Florence; LaScola, Bernard; Raoult, Didier; Schneider, Thomas

2010-01-01

Whipple's disease is a chronic multisystemic infection caused by Tropheryma whipplei that is characterized by arthritis, weight loss, and diarrhea. The immunological defects in the duodenal mucosa, the site of major replication of the agent underlying the pathogenesis of Whipple's disease, are poorly understood. Mucosal immunoglobulins are essential for the defense against intestinal pathogens; therefore, we analyzed the B-cell response in duodenal specimens and sera of Whipple's disease patients. Whereas systemic immunoglobulin production was affected only marginally, duodenal biopsy specimens of Whipple's disease patients contained reduced numbers of immunoglobulin-positive plasma cells and secreted less immunoglobulin compared to healthy controls but showed a weak secretory IgA response toward T. whipplei. This T. whipplei-specific intestinal immune response was not observed in controls. Thus, we were able to demonstrate that general mucosal immunoglobulin production in Whipple's disease patients is impaired. However, this deficiency does not completely abolish T. whipplei-specific secretory IgA production that nonetheless does not protect from chronic infection. PMID:20696822

Small cell carcinoma arising in Barrett's esophagus: a case report and review of the literature

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Markogiannakis Haridimos

2008-01-01

Full Text Available Abstract Introduction Gastrointestinal tract small cell carcinoma is an infrequent and aggressive neoplasm that represents 0.1–1% of gastrointestinal malignancies. Very few cases of small cell esophageal carcinoma arising in Barrett's esophagus have been reported in the literature. An extremely rare case of primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus is herein presented. Case presentation A 62-year-old man with gastroesophageal reflux history presented with epigastric pain, epigastric fullness, dysphagia, anorexia, and weight loss. Esophagogastroscopy revealed an ulceroproliferative, intraluminar mass in the distal esophagus obstructing the esophageal lumen. Biopsy showed small cell esophageal carcinoma. Contrast-enhanced chest and abdominal computed tomography demonstrated a large tumor of the distal third of the esophagus without any lymphadenopathy or distant metastasis. Preoperative chemotherapy with cisplatine and etoposide for 3 months resulted in a significant reduction of the tumor. After en block esophagectomy with two field lymph node dissection, proximal gastrectomy, and cervical esophagogastric anastomosis, the patient was discharged on the 14th postoperative day. Histopathology revealed a primary small cell carcinoma of the distal third of the esophagus arising from dysplastic Barrett's esophagus. The patient received another 3 month course of postoperative chemotherapy with the same agents and remained free of disease at 12 month review. Conclusion Although small cell esophageal carcinoma is rare and its association with dysplastic Barrett's esophagus is extremely infrequent, the high carcinogenic risk of Barrett's epithelium should be kept in mind. Prognosis is quite unfavorable; a better prognosis might be possible with early diagnosis and treatment strategies incorporating chemotherapy along with oncological radical surgery and/or radiotherapy as part of a

Concomitant loss of SMARCA2 and SMARCA4 expression in small cell carcinoma of the ovary, hypercalcemic type.

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Jelinic, Petar; Schlappe, Brooke A; Conlon, Niamh; Tseng, Jill; Olvera, Narciso; Dao, Fanny; Mueller, Jennifer J; Hussein, Yaser; Soslow, Robert A; Levine, Douglas A

2016-01-01

Small cell carcinoma of the ovary, hypercalcemic type is an aggressive tumor generally affecting young women with limited treatment options. Mutations in SMARCA4, a catalytic subunit of the SWI/SNF chromatin remodeling complex, have recently been identified in nearly all small cell carcinoma of the ovary, hypercalcemic type cases and represent a signature molecular feature for this disease. Additional biological dependencies associated with small cell carcinoma of the ovary, hypercalcemic type have not been identified. SMARCA2, another catalytic subunit of the SWI/SNF complex mutually exclusive with SMARCA4, is thought to be post-translationally silenced in various cancer types. We analyzed 10 archival small cell carcinoma of the ovary, hypercalcemic type cases for SMARCA2 protein expression by immunohistochemistry and found that SMARCA2 expression was lost in all but one case. None of the 50 other tumors that primarily or secondarily involved the ovary demonstrated concomitant loss of SMARCA2 and SMARCA4. Deep sequencing revealed that this loss of SMARCA2 expression is not the result of mutational inactivation. In addition, we established a small cell carcinoma of the ovary, hypercalcemic type patient-derived xenograft and confirmed the loss of SMARCA2 in this in vitro model. This patient-derived xenograft model, established from a recurrent tumor, also had unexpected mutational features for this disease, including functional mutations in TP53 and POLE. Taken together, our data suggest that concomitant loss of SMARCA2 and SMARCA4 is another hallmark of small cell carcinoma of the ovary, hypercalcemic type-a finding that offers new opportunities for therapeutic interventions.

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

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Meijer, Richard P.; Meinhardt, Wim; Poel, Henk G. van der; Rhijn, Bas W. van; Kerst, J. Martijn; Pos, Floris J.; Horenblas, Simon; Bex, Axel

2013-01-01

The objectives of this study were to assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population. (author)

Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

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Koay, Eugene J. [Baylor College of Medicine, Houston, Texas (United States); MD Anderson Cancer Center, Houston, Texas (United States); Teh, Bin S., E-mail: bteh@tmh.org [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States); Paulino, Arnold C.; Butler, E. Brian [Methodist Hospital, Houston, Texas (United States); Methodist Hospital Research Institute, Houston, Texas (United States)

2012-05-01

Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results-Medicare database (1991-2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.

Treatment Trends and Outcomes of Small-Cell Carcinoma of the Bladder

International Nuclear Information System (INIS)

Koay, Eugene J.; Teh, Bin S.; Paulino, Arnold C.; Butler, E. Brian

2012-01-01

Purpose: Treatment for small-cell carcinoma of the bladder is largely guided by case reports, retrospective reviews, and small prospective trials. This study aimed to study outcomes using a large population-based database. Methods: The Surveillance, Epidemiology, and End Results–Medicare database (1991–2005) was used to analyze how different treatment combinations of specific bladder surgeries, chemotherapy, and radiation affected patient outcomes. Trends in the use of these combinations over time were also analyzed. Results: A total of 533 patients were retrieved from the database. A bladder-sparing approach involving transurethral resection of the bladder tumor (TURBT) combined with chemotherapy and radiation yielded no significant difference in overall survival compared with patients undergoing at least a cystectomy (of whom over 90% received radical cystectomy) with chemotherapy (p > 0.05). The analysis of treatment trends indicated that these two general strategies for cure combined to account for fewer than 20% of patients. A majority of patients (54%) received TURBT as their only surgical treatment, and a subset analysis of these patients indicated that chemotherapy played a role in all stages of disease (p < 0.05) whereas radiation improved overall survival in regional-stage disease (p < 0.05). Conclusion: Relatively few patients with small-cell carcinoma of the bladder receive potentially curative therapies. Chemotherapy should be a major component of treatment. Cystectomy and bladder-sparing approaches represent two viable strategies and deserve further investigation to identify the patients who may benefit from organ preservation or not. In addition, the role of radiation in regional-stage disease should be investigated further, because it positively affects survival after TURBT.

Intraabdominal desmoplastic small round cell tumor: Report of a case and literature review.

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Koniari, Katerina; Mahera, Helen; Nikolaou, Marinos; Chatzis, Odysseas; Glezakou, Ourania; Magiasis, Vasilios; Kiratzis, Georgios

2011-01-01

Desmoplastic small round cell tumor is a rare malignancy with poor prognosis that predominantly affects young males. Its etiopathogenesis is still unknown and diagnosis can be achieved only by immunohistochemistry and cytogenetic studies. Due to our limited knowledge of the pathologic and clinical nature of this disease, there is no clear consensus regarding the optimal therapeutic procedures for treating this neoplasm. A high degree of care and improvements in diagnostic capabilities are required in order to identify this entity and avoid misdiagnosis. We report a new case of a 29-year-old male who proceeded to our Emergency Department complaining about non-specific abdominal pain. Physical examination revealed no abnormalities except for a palpable mass in the lower abdomen and a diffuse abdominal pain. Computed Tomography scan showed enlarged paraortic and mesenteric lymphadenopathy, thickness of the small bowel wall and dispersed masses intraperitoneally. He underwent an exploratory laparotomy and the resultant biopsy revealed desmoplastic small round cell tumor. Diagnosis of desmoplastic small round cell tumor can easily be missed because it presents with few early warning symptoms and signs, while the routine blood tests are within normal limits. A high degree of suspicion, a thorough physical examination, a full imaging check and an aggressive therapeutic approach are required in order to identify this disease and fight for a better quality of life for these patients. In addition we make a review of the literature in an effort to clarify the epidemiological, clinical and pathological aspects of this entity.

Prediction of disease-free survival by the PET/CT radiomic signature in non-small cell lung cancer patients undergoing surgery

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Kirienko, Margarita; Fogliata, Antonella; Sollini, Martina [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Cozzi, Luca [Humanitas Clinical and Research Center, Radiotherapy and Radiosurgery, Rozzano, Milan (Italy); Antunovic, Lidija [Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy); Lozza, Lisa [Orobix Srl, Bergamo (Italy); Voulaz, Emanuele [Humanitas Clinical and Research Center, Thoracic Surgery, Rozzano, Milan (Italy); Rossi, Alexia [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Radiology, Rozzano, Milan (Italy); Chiti, Arturo [Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan (Italy); Humanitas Clinical and Research Center, Nuclear Medicine, Rozzano, Milan (Italy)

2018-02-15

Radiomic features derived from the texture analysis of different imaging modalities e show promise in lesion characterisation, response prediction, and prognostication in lung cancer patients. The present study aimed to identify an images-based radiomic signature capable of predicting disease-free survival (DFS) in non-small cell lung cancer (NSCLC) patients undergoing surgery. A cohort of 295 patients was selected. Clinical parameters (age, sex, histological type, tumour grade, and stage) were recorded for all patients. The endpoint of this study was DFS. Both computed tomography (CT) and fluorodeoxyglucose positron emission tomography (PET) images generated from the PET/CT scanner were analysed. Textural features were calculated using the LifeX package. Statistical analysis was performed using the R platform. The datasets were separated into two cohorts by random selection to perform training and validation of the statistical models. Predictors were fed into a multivariate Cox proportional hazard regression model and the receiver operating characteristic (ROC) curve as well as the corresponding area under the curve (AUC) were computed for each model built. The Cox models that included radiomic features for the CT, the PET, and the PET+CT images resulted in an AUC of 0.75 (95%CI: 0.65-0.85), 0.68 (95%CI: 0.57-0.80), and 0.68 (95%CI: 0.58-0.74), respectively. The addition of clinical predictors to the Cox models resulted in an AUC of 0.61 (95%CI: 0.51-0.69), 0.64 (95%CI: 0.53-0.75), and 0.65 (95%CI: 0.50-0.72) for the CT, the PET, and the PET+CT images, respectively. A radiomic signature, for either CT, PET, or PET/CT images, has been identified and validated for the prediction of disease-free survival in patients with non-small cell lung cancer treated by surgery. (orig.)

Nerve Invasion by Epithelial Cells in Benign Breast Diseases

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Yu-Jan Chan

2009-03-01

Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

Early Prediction of Disease Progression in Small Cell Lung Cancer: Toward Model-Based Personalized Medicine in Oncology.

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Buil-Bruna, Núria; Sahota, Tarjinder; López-Picazo, José-María; Moreno-Jiménez, Marta; Martín-Algarra, Salvador; Ribba, Benjamin; Trocóniz, Iñaki F

2015-06-15

Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification. The biomarker model we developed incorporates an underlying latent variable (disease) representing (unobserved) tumor size dynamics, which is assumed to drive biomarker production and to be influenced by exposure to treatment. Here, we show that by integrating CT scan data, the population model can be expanded to include patient outcome. Moreover, we show that in conjunction with routine medical monitoring data, the population model can support accurate individual predictions of outcome. Our combined model predicts that a change in disease of 29.2% (relative standard error 20%) between two consecutive CT scans (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply this framework to an external dataset containing biomarker data from 22 small cell lung cancer patients (four patients progressing during follow-up). Using only data up until the end of treatment (a total of 137 lactate dehydrogenase and 77 neuron-specific enolase observations), the statistical framework prospectively identified 75% of the individuals as having a predictable outcome in follow-up visits. This included two of the four patients who eventually progressed. In all identified individuals, the model-predicted outcomes matched the observed outcomes. This framework allows at risk patients to be identified early and therapeutic intervention/monitoring to be adjusted individually, which may improve overall patient survival. ©2015 American Association for Cancer Research.

Abnormal diffusion-weighted MRI in medulloblastoma: does it reflect small cell histology?

International Nuclear Information System (INIS)

Kotsenas, A.L.; Roth, T.C.; Manness, W.K.; Faerber, E.N.

1999-01-01

A 12-year-old boy presented with the classic CT and MRI findings of medulloblastoma and the unusual finding of increased signal on diffusion MRI. The small-cell histology of medulloblastoma may account for the increased signal seen on diffusion MRI. Diffusion MRI with echoplanar technique may be useful in evaluation of these tumors and metastatic disease. (orig.)

Radioaerosol lung imaging in small airways disease

Energy Technology Data Exchange (ETDEWEB)

Weiss, T; Dorow, P; Felix, R

1981-06-01

Aerosol inhalation lung imaging was performed in 35 asymptomatic smokers who have been selected on the basis of abnormal findings in small airways pulmonary function tests. Qualitative (image inspection) and quantitative (aerosol distribution index = ADI) analysis of the radioaerosol lung patterns was accomplished. Compared to healthy subjects as well as to patients with chronic obstructive lung disease significant differences of mean aerosol distribution homogeneity were observed. A characteristic type of abnormal aerosol pattern, indicating peripheral airways obstruction, was found in 71% of the patients with small airways disease.

Oligometastatic disease at presentation or recurrence for nonsmall cell lung cancer.

Science.gov (United States)

Gomez, Daniel R; Niibe, Yuzuru; Chang, Joe Y

2012-01-01

Oligometastatic Non-Small Cell Lung Cancer (NSCLC) presents a unique opportunity for potential curative therapy. Improved cancer staging using PET/CT, MRI, and future cellular and molecular staging with circulating tumor cells and/or molecular markers will identify more patients with truly oligometastasis disease that will benefit from definitive local treatment. Recent development of noninvasive local ablative therapy such as stereotactic radiotherapy makes it possible to eradicate multiple local diseases with minimal side effect. Novel systemic therapy may also control systemic spread and therefore make it possible to improve survival by eliminating local diseases. More research, particularly prospective studies, is ideally randomized studies are needed to validate the concept of oligometastasis.

System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells.

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Malina, Halina Z

2011-01-19

in disease development. In the knockout cells, incorrect interactions between proteins were observed without the protein modification by small molecules, indicating the abnormality of the protein network in the transgenic system. The irreversible protein-protein interactions lead to protein aggregation and cell degeneration, which are observed in all aging-associated diseases.

Merkel cell carcinoma metastatic to the small bowel mesentery

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Guang-Yu Yang

2011-03-01

Full Text Available Merkel cell carcinoma (MCC is an uncommon cutaneous malignant tumor that presents as a rapidly growing skin nodule on sun-exposed areas of the body. MCC is aggressive with regional nodal and distant metastases to the skin, lung, and bones. There have been no reports of metastatic MCC to the mesentery and 6 reports describing metastasis to the small intestine. We present a case of metastatic MCC to the mesentery with infiltration to the small bowel, 8 years after original tumor resection. This is the 5th metastasis and it encased the small bowel resulting in a hair-pin loop contributing to the unusual clinical presentation. Although MCC metastatic to the bowel is uncommon, it is not rare. It is important to recognize the unusual manifestations of this disease as they are becoming more common in the future. Routine radiologic surveillance and thorough review of systems are important to patient follow-up.

Energy efficient design of cognitive small cells

NARCIS (Netherlands)

Wildemeersch, Matthias; Wildemeersch, Matthias; Quek, Tony Q.S.; Rabbachin, Alberto; Slump, Cornelis H.; Huang, Aiping; Kim, Dong-In; Mueller, P.

2013-01-01

Heterogeneous networks consisting of a macrocell tier and a small cell tier are considered an attractive solution to cope with the fierce increase of mobile traffic demand. Nevertheless, a massive deployment of small cell access points (SAPs) leads also to a considerable increase in energy

Effects of icotinib on advanced non-small cell lung cancer with different EGFR phenotypes.

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Pan, Huiyun; Liu, Rong; Li, Shengjie; Fang, Hui; Wang, Ziwei; Huang, Sheng; Zhou, Jianying

2014-09-01

Icotinib is the first oral epidermal growth factor receptor (EGFR) tyrosine kinase receptor inhibitor, which has been proven to exert significant inhibitory effects on non-small cell lung cancer in vitro. Clinical evidence has showed that the efficacy of Icotinib on retreating advanced non-small cell lung cancer is comparable to Gefitinib. However, different phenotypes of EGFR can affect the therapeutic outcomes of EGFR tyrosine kinase receptor inhibitor. Therefore, our study focused on efficacy and safety of Icotinib in patients with advanced non-small cell lung cancer of different EGPR phenotypes. Clinical data of patients with advanced non-small cell lung cancer who received Icotinib treatment from August, 2011 to May, 2013 were retrospectively analyzed. Kaplan-Meier analysis was used for survival analysis and comparison. 18 wild-type EGFR and 51 mutant type were found in a total of 69 patients. Objective response rate of patients with mutant type EGFR was 54.9 % and disease control rate was 86.3 %. Objective response rate of wild-type patients was 11.1 % (P = 0.0013 vs mutant type), disease control rate was 50.0 % (P = 0.0017). Median progression-free survival (PFS) of mutant type and wild-type patients were 9.7 and 2.6 months, respectively (P Icotinib included rash, diarrhea, itching skin with occurrence rates of 24.6 % (17/69), 13.0 % (9/69), and 11.6 % (8/69), respectively. Most adverse reactions were grade I-II. Icotinib has great efficacy in EGFR mutated patients, making it an optimal regimen to treat EGFR mutated patients. Furthermore, most of adverse reactions associated with Icotinib treatment were tolerable.

Associations Between Cerebral Small-Vessel Disease and Alzheimer Disease Pathology as Measured by Cerebrospinal Fluid Biomarkers

NARCIS (Netherlands)

Kester, M.I.; Goos, J.D.C.; Teunissen, C.E.; Benedictus, M.R.; Bouwman, F.H.; Wattjes, M.P.; Barkhof, F.; Scheltens, P.; van der Flier, W.M.

2014-01-01

IMPORTANCE: It remains unclear if and how associations between cerebral small-vessel disease and Alzheimer disease (AD) pathology lead to cognitive decline and dementia. OBJECTIVE: To determine associations between small-vessel disease and AD pathology. DESIGN, SETTING, AND PARTICIPANTS:

Intestinal T-cell responses in celiac disease - impact of celiac disease associated bacteria.

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Veronika Sjöberg

Full Text Available A hallmark of active celiac disease (CD, an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the "Swedish CD epidemic" and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8(+ T cells (Tc17 and CD4(+ T cells (Th17, with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.

Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

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Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

2016-09-01

Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

Intra-abdominal desmoplastic small cell tumor in a girl : a case report

International Nuclear Information System (INIS)

Lee, Young Seok

1998-01-01

Desmoplastic small cell tumor is a rare primary intra-abdominal disease with a predilection for the adolescent boy. This aggressive tumor involved multiple intraperitoneal organs, peritoneal, mesentery and omental seedings, and sometimes retroperitoneal extension. The author reports a case of this rare tumor, demonstrated by CT, MRI and US, in a 14-year-old girl. (author). 9 refs., 2 figs

Small Engine, Big Power: MicroRNAs as Regulators of Cardiac Diseases and Regeneration

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Darukeshwara Joladarashi

2014-09-01

Full Text Available Cardiac diseases are the predominant cause of human mortality in the United States and around the world. MicroRNAs (miRNAs are small non-coding RNAs that have been shown to modulate a wide range of biological functions under various pathophysiological conditions. miRNAs alter target expression by post-transcriptional regulation of gene expression. Numerous studies have implicated specific miRNAs in cardiovascular development, pathology, regeneration and repair. These observations suggest that miRNAs are potential therapeutic targets to prevent or treat cardiovascular diseases. This review focuses on the emerging role of miRNAs in cardiac development, pathogenesis of cardiovascular diseases, cardiac regeneration and stem cell-mediated cardiac repair. We also discuss the novel diagnostic and therapeutic potential of these miRNAs and their targets in patients with cardiac diseases.

Radiation therapy alone for early stage non-small cell carcinoma of the lung

International Nuclear Information System (INIS)

Chun, Ha Chung; Lee, Myung Za

2002-01-01

To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy along and define the optimal radiotherapeutic regimen for these patients. A retrospective review was performed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 69 Gy. No patients were lost to follow-up. The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and 21%, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and 25%, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was 43%. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented 78% of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm (0% vs 36%). Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70

Oligometastatic Disease at Presentation or Recurrence for Nonsmall Cell Lung Cancer

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Daniel R. Gomez

2012-01-01

Full Text Available Oligometastatic Non-Small Cell Lung Cancer (NSCLC presents a unique opportunity for potential curative therapy. Improved cancer staging using PET/CT, MRI, and future cellular and molecular staging with circulating tumor cells and/or molecular markers will identify more patients with truly oligometastasis disease that will benefit from definitive local treatment. Recent development of noninvasive local ablative therapy such as stereotactic radiotherapy makes it possible to eradicate multiple local diseases with minimal side effect. Novel systemic therapy may also control systemic spread and therefore make it possible to improve survival by eliminating local diseases. More research, particularly prospective studies, is ideally randomized studies are needed to validate the concept of oligometastasis.

Prophylactic cranial irradiation in small cell lung cancer: a single institution experience.

Science.gov (United States)

Naidoo, J; Kehoe, M; Sasiadek, W; Hacking, D; Calvert, P

2014-03-01

Prophylactic cranial irradiation (PCI) is used to prevent the development of brain metastases in small cell lung carcinoma. PCI confers an overall survival (OS) benefit in both limited and extensive stage disease. We analyze the incidence of symptomatic brain metastases, progression-free survival (PFS) and OS in a cohort of patients who received PCI, in a 5-year period. A retrospective review of all patients who had received PCI between 2006 and 2011 at the Whitfield Clinic was completed. Patient- and disease-related characteristics, the number of patients who developed brain metastases, PFS and OS data were collected. 24 patients were identified. 14 (58.3 %) patients were male, 10 (41.7 %) were female, with a mean age of 62.5 years (range 31-78). All patients were smokers. 12 (50 %) patients had limited stage small cell lung cancer (SCLC), 12 (50 %) had extensive stage disease. 2 (8.2 %) patients developed brain metastases post PCI (p = 0.478.) The median PFS for limited stage SCLC was 13 months (range 3-20) and 10 months (range 5-18) for extensive stage SCLC. Median OS was 15 months (range 4-29) in limited stage SCLC, and 11 months (range 5-29) in extensive stage SCLC. Our study demonstrated a low incidence of symptomatic brain metastases and favourable median PFS and OS in the patients that received PCI, when compared to published phase III data.

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

Science.gov (United States)

Dunne, Margaret R; Elliott, Louise; Hussey, Seamus; Mahmud, Nasir; Kelly, Jacinta; Doherty, Derek G; Feighery, Conleth F

2013-01-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets), natural killer cells, CD56(+) T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

Directory of Open Access Journals (Sweden)

Margaret R Dunne

Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

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Zhang, Su-Fang; Chen, Zhe

2017-09-01

Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

Sickle Cell Anemia Disease (For Kids)

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... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Kids / Sickle Cell Disease What's ... to stay in the hospital. What Causes Sickle Cell Disease? Sickle cell disease is an inherited (say: ...

Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

Science.gov (United States)

Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

2014-01-01

Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics

OpenAIRE

Aguisanda, Francis; Yeh, Charles D.; Chen, Catherine Z.; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

2017-01-01

Background Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. Results We have generated induced pluripotent stem cells (iPSCs...

Therapeutic effect analysis of three dimensional conformal radiotherapy non-small cell lung cancer

International Nuclear Information System (INIS)

Yao Zhijun; Cao Yongzhen; Zhang Wenxue; Liang Feng

2012-01-01

Objective: To analyse the treatment effect of non-small cell lung cancer of three dimensional conformal radiotherapy (3D-CRT) and to study the effect of patient survival related factors. Methods: Retrospective analysis was mack for 136 cases of non-small cell lung cancer, all accept 3D-CRT, through the case data collection and long-term follow-up, using the single factor and multiple factor analysis survival time and its influencing factors. Results: The recent curative effects of 136 cases of patients with three dimensional conformal radiotherapy: Complete response (CR) 14.7% (20/136), partial response (PR) 60.3 (82/136), stable disease(SD) 19.9% (27/136), progression disease (PD) 5.1% (7/136), total effective rate is 75% (102/136). One, two, three, five year survival rate is 79.4%, 45.4%, 22.1%, 12.5%. Side effects: Class 1 radiated esophagitis 35 cases, Class 2 radiated esophagitis 16 cases, Class 3 and above radiated esophagitis 0 case. Class I radiated pneumonia 20 cases, Class 2 radiated pneumonia 9 cases, Class 3 radiated pneumonia 0 case. Single factor analysis shows the influence of gender, age, pathology, phase, dose, and first-phase curative effect to the survival time are of a statistical significance, Multiple factor analysis showed KPS score, phase, dose, first-phase curative effect are the survival time independent factors. Conclusion: 3D-CRT for patients with non-small cell lung carcinoma is a safe, effective treatment method, Side effects are relatively low, and the patients survival time is long after radiotherapy. (authors)

Effectiveness of palliative radiotherapy in patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Chmielewska, E.; Jaskiewicz, P.

2001-01-01

Lung cancer is the most frequent malignant neoplasm in Poland. During the last 25 years it has become the first reason of death of men and the second of women in Poland. Patients with non-small cell lung cancer constitute 75% of all lung cancer patients. The therapy of choice for the advanced, non-small cell lung cancer is radiotherapy with palliative assumption. Many papers indicate that this therapy has no influence on long-term survival, hence it is aimed at reducing the symptoms. The therapy brings relief to 70-80% of patients. At present no other method with similar effectiveness is known. The aim of the is study was to assess the effectiveness of palliative radiotherapy as a treatment of the advanced, non-small cell lung cancel, applied as a remedy for the symptoms resulting from the growth of a lung tumour: Improvement of the quality of life and long-term survivals were assessed and prognostic factors were analysed. Between 1990 and 1995, 2330 patients with lung cancer attended the Outpatient Clinic of the Maria Sklodowska-Curie Memorial Cancer Center in Warsaw. There were 1948 patients with the non-small cell lung cancer. From this group 832 patients were qualified to palliative radiotherapy that included the primary tumour. The documentation was found for 803 patients and this group was analysed. The group constituted of 115 women (14.3%) and 688 men (85.7%), aged 28 to 91 (mean 61). In the majority of cases a significant advancement of the disease was found: stage III A in 388 patients (48.3%) and stage III B in 358 patients (44.6%). Retrospective analysis of the results of the treatment was carried out. The material contained information on 803 patients. The basis for the analysis was the survival time. It was measured from the starting date of the irradiation to the date of death or the date of the last available information that the patient lives. The survival probability was calculated with the Kaplan-Meier method. Multidimensional analysis of the

Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease

International Nuclear Information System (INIS)

Kaasa, S.; Mastekaasa, A.; Lund, E.

1989-01-01

In a prospective controlled clinical trial, 102 patients with inoperable non-small lung cancer (NSCLC), limited disease, stage II and III were treated with combination chemotherapy, cisplatin 70 mg/m 2 i.v. on day one and etoposide 100 mg/m 2 i.v. on day one, and etoposide 200 mg/m 2 orally on days 2 and 3, or radiotherapy given in 15 fractions of 2.8 Gy with two anterior/posterior fields during a period of three weeks. The patients completed a validated self-administered questionnaire before the start of treatment that assessed their psychosocial well-being, disease-related symptoms, personal functioning, and every day activity. These subjective varibles were evaluated together with treatment modality, WHO performance status, weight loss, and stage of disease, with regard to their value in predicting survival. Univariate survival analyses were undertaken for each individual factor, median survival was calculated according to life-table analyses. A step-wise multiple regression analysis was used to measure the prognostic value of the various factors. In the univariate analysis, general symptons (p=0.0006) psychosocial well-being (p=0.0002) and stage of disease (p=0.007) were the best predictive factors. In the multiple regression analyses the subjective variables, general symptons (p<0.01) and psychosocial well-being (p<0.05) were shown to have the best predictive value for the patients' survival. (author). 20 refs.; 4 figs.; 3 tabs

HEp-2 cell image classification method based on very deep convolutional networks with small datasets

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Lu, Mengchi; Gao, Long; Guo, Xifeng; Liu, Qiang; Yin, Jianping

2017-07-01

Human Epithelial-2 (HEp-2) cell images staining patterns classification have been widely used to identify autoimmune diseases by the anti-Nuclear antibodies (ANA) test in the Indirect Immunofluorescence (IIF) protocol. Because manual test is time consuming, subjective and labor intensive, image-based Computer Aided Diagnosis (CAD) systems for HEp-2 cell classification are developing. However, methods proposed recently are mostly manual features extraction with low accuracy. Besides, the scale of available benchmark datasets is small, which does not exactly suitable for using deep learning methods. This issue will influence the accuracy of cell classification directly even after data augmentation. To address these issues, this paper presents a high accuracy automatic HEp-2 cell classification method with small datasets, by utilizing very deep convolutional networks (VGGNet). Specifically, the proposed method consists of three main phases, namely image preprocessing, feature extraction and classification. Moreover, an improved VGGNet is presented to address the challenges of small-scale datasets. Experimental results over two benchmark datasets demonstrate that the proposed method achieves superior performance in terms of accuracy compared with existing methods.

Diverticular Disease of the Small Bowel

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Francisco Emilio Ferreira-Aparicio

2012-10-01

Full Text Available A diverticulum is a bulging sack in any portion of the gastrointestinal tract. The most common site for the formation of diverticula is the large intestine. Small intestine diverticular disease is much less common than colonic diverticular disease. The most common symptom is non-specific epigastric pain and a bloating sensation. Major complications include diverticulitis, gastrointestinal bleeding, acute perforation, pancreatic or biliary (in the case of duodenal diverticula disease, intestinal obstruction, intestinal perforation, localized abscess, malabsorption, anemia, volvulus and bacterial overgrowth. We describe the clinical case of a 65-year-old female patient with a diagnosis on hospital admittance of acute appendicitis and a intraoperative finding of diverticular disease of the small intestine, accompanied by complications such as intestinal perforation, bleeding and abdominal sepsis. This was surgically treated with intestinal resection and ileostomy and a subsequent re-intervention comprising perforation of the ileostomy and stomal remodeling. The patient remained hospitalized for approximately 1 month with antibiotics and local surgical wound healing, as well as changes in her diet with food supplements and metabolic control. She showed a favorable clinical evolution and was dismissed from the hospital to her home. We include here a discussion on trends in medical and surgical aspects as well as early handling or appropriate management to reduce the risk of fatal complications.

Diseases of the small bowel in chronic diarrhea: diagnosis and treatment

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M. Simadibrata

2002-09-01

Full Text Available The incidence of chronic diarrhea in Asia is between 0.8-1.0%. The diseases and abnormalities according to the location, which can cause chronic diarrhea, are divided into three locations: the small bowel, the large bowel and extraintestinal. The small bowel diseases include infectious and non-infectious diseases. The infectious diseases are bacterial infections, parasitic infections etc. The non-infectious diseases include of Crohn’s disease, Celiac sprue, NSAID enteropathy, lactose intolerance, benign tumor, carcinoid tumor, carcinoma, post surgery complications, laxative etc. The approaches to diagnosis include good anamnesis, careful physical examination, supporting laboratory tests, more specialized supporting examinations including X-ray of the colon, esophagogastroduodenum follow-through, enteroclysis, ileo-colonoscopy and endoscopy on the upper portion of the digestive tract including the small intestine with biopsy for histopathology examinations. The treatment for chronic diarrhea is divided into supportive and causal therapy. (Med J Indones 2002; 11: 179-89 Keywords: small bowel, chronic diarrhea, approaches to diagnosis, treatment

Metastatic Extrapulmonary Small Cell Carcinoma to the Cerebellopontine Angle: A Case Report and Review of the Literature

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Debebe Theodros

2015-01-01

Full Text Available Extrapulmonary small cell carcinomas (EPSCC are rare malignancies with poor patient prognoses. We present the case of a 63-year-old male who underwent surgical resection of a poorly differentiated small cell carcinoma, likely from a small intestinal primary tumor that metastasized to the cerebellopontine angle (CPA. A 63-year-old male presented with mild left facial paralysis, hearing loss, and balance instability. MRI revealed a 15 mm mass in the left CPA involving the internal auditory canal consistent with a vestibular schwannoma. Preoperative MRI eight weeks later demonstrated marked enlargement to 35 mm. The patient underwent a suboccipital craniectomy and the mass was grossly different visually and in consistency from a standard vestibular schwannoma. The final pathology revealed a poorly differentiated small cell carcinoma. Postoperative PET scan identified avid uptake in the small intestine suggestive of either a small intestinal primary tumor or additional metastatic disease. The patient underwent whole brain radiation therapy and chemotherapy and at last follow-up demonstrated improvement in his symptoms. Surgical resection and radiotherapy are potential treatment options to improve survival in patients diagnosed with NET brain metastases. We present the first documented case of skull base metastasis of a poorly differentiated small cell carcinoma involving the CPA.

[Small vessel cerebrovascular disease].

Science.gov (United States)

Cardona Portela, P; Escrig Avellaneda, A

2018-05-09

Small vessel vascular disease is a spectrum of different conditions that includes lacunar infarction, alteration of deep white matter, or microbleeds. Hypertension is the main risk factor, although the atherothrombotic lesion may be present, particularly in large-sized lacunar infarctions along with other vascular risk factors. MRI findings are characteristic and the lesions authentic biomarkers that allow differentiating the value of risk factors and defining their prognostic value. Copyright © 2018 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Serum Hepatocyte Growth Factor Is Associated with Small Vessel Disease in Alzheimer’s Dementia

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Yanan Zhu

2018-01-01

Full Text Available Background: While hepatocyte growth factor (HGF is known to exert cell growth, migration and morphogenic effects in various organs, recent studies suggest that HGF may also play a role in synaptic maintenance and cerebrovascular integrity. Although increased levels of HGF have been reported in brain and cerebrospinal fluid (CSF samples of patients with Alzheimer’s disease (AD, it is unclear whether peripheral HGF may be associated with cerebrovascular disease (CeVD and dementia. In this study, we examined the association of baseline serum HGF with neuroimaging markers of CeVD in a cohort of pre-dementia (cognitive impaired no dementia, CIND and AD patients.Methods: Serum samples from aged, Non-cognitively impaired (NCI controls, CIND and AD subjects were measured for HGF levels. CeVD (cortical infarcts, microinfarcts, lacunes, white matter hyperintensities (WMH and microbleeds were assessed by magnetic resonance imaging (MRI.Results: After controlling for covariates, higher levels of HGF were associated with both CIND and AD. Among the different CeVD MRI markers in CIND and AD, only small vessel disease, but not large vessel disease markers were associated with higher HGF levels.Conclusion: Serum HGF may be a useful peripheral biomarker for small vessel disease in subjects with cognitive impairment and AD.

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

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Ma, X-H; Tian, T-D; Liu, H-M; Li, Q-J; Gao, Q-L; Li, L; Shi, B

2017-01-01

To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (picotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

Combination chemotherapy concurrent with small dose radiation therapy for small cell carcinoma of the lung

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Tada, Toshihiko; Fujita, Hiroji; Shintomi, Takenori

1987-01-01

Forty consecutive patients with small cell carcinoma of the lung were treated with chemotherapy, radiotherapy or both. Of 34 patients treated with chemotherapy, 24 were treated with combination chemotherapy, containing cyclophosphamide vincristine methotrexate and procarbazine, concurrent with small dose radiation therapy (500 cGy/5 fraction) as a chemosensitizer (COMPrt). The response rate to this regimen was 81 % (29 % complete) and the 2 year survival rate was 28.6 %. These results have been superior to other regimens and the toxicity was not see to be any higher. After completion of COMPrt regimen, 10 patients were treated with intrathoracic radiation therapy (average dose 3000 cGy) and 3 recieved surgical treatment. Radiation therapy improved the 2-year survival rate (42.2 %) when compared with those patients who received no radiation therapy (18.2 %). Three patients received surgical treatment were considered to be disease-free for 23, 17, and 9 months respectively, after induction of chemotherapy. (author)

Cellular radiosensitivity of small-cell lung cancer cell lines

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Krarup, M; Poulsen, H S; Spang-Thomsen, M

1997-01-01

PURPOSE: The objective of this study was to determine the radiobiological characteristics of a panel of small-cell lung cancer (SCLC) cell lines by use of a clonogenic assay. In addition, we tested whether comparable results could be obtained by employing a growth extrapolation method based...

Randomized study: small cell anaplastic lung cancer treated by combination chemotherapy and adjuvant radiotherapy

International Nuclear Information System (INIS)

Fox, R.M.; Woods, R.L.; Brodie, G.N.; Tattersall, M.H.N.

1980-01-01

Chemotherapy and primary site radiation therapy were compared to chemotherapy alone in a randomized study of 125 patients with small cell cancer of the lung. The sites of initial relapse, as well as disease free and overall survival were analyzed. Radiotherapy to the primary site reduced the rate of local relapse, but median survival was not prolonged in patients with either limited or extensive disease, when the radiation therapy-chemotherapy group was compared to the group that received chemotherapy alone

Potential roles of cell-derived microparticles in ischemic brain disease.

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Horstman, Lawrence L; Jy, Wenche; Bidot, Carlos J; Nordberg, Mary L; Minagar, Alireza; Alexander, J Steven; Kelley, Roger E; Ahn, Yeon S

2009-10-01

The objective of this study is to review the role of cell-derived microparticles in ischemic cerebrovascular diseases. An extensive PubMed search of literature pertaining to this study was performed in April 2009 using specific keyword search terms related to cell-derived microparticles and ischemic stroke. Some references are not cited here as it is not possible to be all inclusive or due to space limitation. Cell-derived microparticles are small membranous vesicles released from the plasma membranes of platelets, leukocytes, red cells and endothelial cells in response to diverse biochemical agents or mechanical stresses. They are the main carriers of circulating tissue factor, the principal initiator of intravascular thrombosis, and are implicated in a variety of thrombotic and inflammatory disorders. This review outlines evidence suggesting that cell-derived microparticles are involved predominantly with microvascular, as opposed to macrovascular, thrombosis. More specifically, cell-derived microparticles may substantially contribute to ischemic brain disease in several settings, as well as to neuroinflammatory conditions. If further work confirms this hypothesis, novel therapeutic strategies for minimizing cell-derived microparticles-mediated ischemia are available or can be developed, as discussed.

Regulatory T cells and B cells: implication on autoimmune diseases

OpenAIRE

Wang, Ping; Zheng, Song Guo

2013-01-01

The regulatory T (Treg) cells play an important role in the maintenance of homeostasis and the prevention of autoimmune diseases. Although most studies are focusing on the role of Treg cells in T cells and T cells-mediated diseases, these cells also directly affect B cells and other non-T cells. This manuscript updates the role of Treg cells on the B cells and B cell-mediated diseases. In addition, the mechanisms whereby Treg cells suppress B cell responses have been discussed.

An immunoglobulin G-4 related sclerosing disease of the small bowel: CT and small bowel series findings

International Nuclear Information System (INIS)

Ko, Young Hwan; Hwang, Dae Hyun; Min, Seon Jeong; Woo, Ji Young; Kim, Jeong Won; Hong, Hye Sook; Yang, Ik; Lee, Yul

2013-01-01

Immunoglobulin G4 (IgG4)-related sclerosing disease is rare and is known to involve various organs. We present a case of histologically proven IgG4-related sclerosing disease of the small bowel with imaging findings on computed tomography (CT) and small bowel series. CT showed irregular wall thickening, loss of mural stratification and aneurysmal dilatation of the distal ileum. Small bowel series showed aneurysmal dilatations, interloop adhesion with traction and abrupt angulation.

Selection of radioresistant cells by vitamin A deficiency in a small cell lung cancer cell line

International Nuclear Information System (INIS)

Terasaki, Takeo; Shimosato, Yukio; Wada, Makio; Yokota, Jun; Terada, Masaaki

1990-01-01

Radiation sensitivity of a human small cell lung cancer cell line, Lu-134-B cells, cultured in serum-supplemented medium and of cells transferred to and cultured in delipidized serum-supplemented (vitamin A-deficient) medium was studied. The cells cultured in serum-supplemented medium showed the phenotype of classic small cell lung cancer sensitive to radiation, while cells transferred to delipidized serum-supplemented medium showed partial squamous cell differentiation and became resistant to radiation. These results suggest that some small cell lung cancer cells in vitro change their morphology and radiosensitivity depending on the culture conditions. The change in radiosensitivity was reproducible, and was not reversible by culture of the radioresistant cells in delipidized serum-supplemented medium with addition of retinoic acid (vitamin A-sufficient medium) for two months, although squamous cells disappeared. Acquisition of radioresistancy was considered to occur as the result of clonal selective growth in delipidized medium of a minor cell population in the original cell culture, based on a study of chromosome number. It was also found that there was no association of myc-family oncogenes with the changes of radiosensitivity in this cell line. (author)

Clinical outcome of primary small cell carcinoma of the urinary bladder

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Hou CP

2013-08-01

Full Text Available Chen-Pang Hou,1,2 Yu-Hsiang Lin,1,2 Chien-Lun Chen,1,2 Phei-Lang Chang,1,2 Ke-Hung Tsui1,2 1Department of Urology, Chang Gung Memorial Hospital-Linko, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Taiwan, Republic of China Purpose: Primary small cell carcinoma of the urinary bladder is a rare malignant disease. It accounts for less than 1% of all urinary bladder carcinomas. The purpose of this study is to review the clinical features, the treatment modalities, and the overall survival of these patients. We also compare the clinical outcomes between patients of bladder small cell carcinoma (SCC and bladder urothelial carcinoma (UC. Materials and methods: We reviewed the charts of patients with bladder tumors from January 1995 to December 2012 in the Chang Gung Memorial Hospital. A total of 2421 malignant bladder tumor patients were reviewed and there were 18 patients who were diagnosed with primary bladder SCC. The patients' characteristics, including age, gender, smoking history, presented symptoms, tumor size, locations, clinical stages, treatment modalities, pathology appearance, recurrence conditions, and survival conditions were all recorded. We also compared the clinical outcomes and the overall survival rates between patients with bladder SCC and those with UC. Results: Bladder SCC accounted for about 0.74% of all bladder malignancies in our institution. The mean age at diagnosis was 70.67 years, and the male-to-female ratio was 2.6:1. Thirteen patients had a history of cigarette smoking. All patients presented with symptoms of gross hematuria, and three of them had bladder tamponade requiring blood clot evacuation by cystoscopy. Only one patient had T1 disease, ten patients had stage III disease, and seven patients had lymph node or distant metastasis (stage IV disease. The mean tumor size was 4.29 cm in diameter. For the majority (61.11% of patients, SCC coexisted with UC components. The average survival time

Cerebral Small Vessel Disease: Cognition, Mood, Daily Functioning, and Imaging Findings from a Small Pilot Sample

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John G. Baker

2012-04-01

Full Text Available Cerebral small vessel disease, a leading cause of cognitive decline, is considered a relatively homogeneous disease process, and it can co-occur with Alzheimer’s disease. Clinical reports of magnetic resonance imaging (MRI/computed tomography and single photon emission computed tomography (SPECT imaging and neuropsychology testing for a small pilot sample of 14 patients are presented to illustrate disease characteristics through findings from structural and functional imaging and cognitive assessment. Participants showed some decreases in executive functioning, attention, processing speed, and memory retrieval, consistent with previous literature. An older subgroup showed lower age-corrected scores at a single time point compared to younger participants. Performance on a computer-administered cognitive measure showed a slight overall decline over a period of 8–28 months. For a case study with mild neuropsychology findings, the MRI report was normal while the SPECT report identified perfusion abnormalities. Future research can test whether advances in imaging analysis allow for identification of cerebral small vessel disease before changes are detected in cognition.

Very small embryonic-like stem cells: implications in reproductive biology.

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Bhartiya, Deepa; Unni, Sreepoorna; Parte, Seema; Anand, Sandhya

2013-01-01

The most primitive germ cells in adult mammalian testis are the spermatogonial stem cells (SSCs) whereas primordial follicles (PFs) are considered the fundamental functional unit in ovary. However, this central dogma has recently been modified with the identification of a novel population of very small embryonic-like stem cells (VSELs) in the adult mammalian gonads. These stem cells are more primitive to SSCs and are also implicated during postnatal ovarian neo-oogenesis and primordial follicle assembly. VSELs are pluripotent in nature and characterized by nuclear Oct-4A, cell surface SSEA-4, and other pluripotent markers like Nanog, Sox2, and TERT. VSELs are considered to be the descendants of epiblast stem cells and possibly the primordial germ cells that persist into adulthood and undergo asymmetric cell division to replenish the gonadal germ cells throughout life. Elucidation of their role during infertility, endometrial repair, superovulation, and pathogenesis of various reproductive diseases like PCOS, endometriosis, cancer, and so on needs to be addressed. Hence, a detailed review of current understanding of VSEL biology is pertinent, which will hopefully open up new avenues for research to better understand various reproductive processes and cancers. It will also be relevant for future regenerative medicine, translational research, and clinical applications in human reproduction.

Very Small Embryonic-Like Stem Cells: Implications in Reproductive Biology

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Deepa Bhartiya

2013-01-01

Full Text Available The most primitive germ cells in adult mammalian testis are the spermatogonial stem cells (SSCs whereas primordial follicles (PFs are considered the fundamental functional unit in ovary. However, this central dogma has recently been modified with the identification of a novel population of very small embryonic-like stem cells (VSELs in the adult mammalian gonads. These stem cells are more primitive to SSCs and are also implicated during postnatal ovarian neo-oogenesis and primordial follicle assembly. VSELs are pluripotent in nature and characterized by nuclear Oct-4A, cell surface SSEA-4, and other pluripotent markers like Nanog, Sox2, and TERT. VSELs are considered to be the descendants of epiblast stem cells and possibly the primordial germ cells that persist into adulthood and undergo asymmetric cell division to replenish the gonadal germ cells throughout life. Elucidation of their role during infertility, endometrial repair, superovulation, and pathogenesis of various reproductive diseases like PCOS, endometriosis, cancer, and so on needs to be addressed. Hence, a detailed review of current understanding of VSEL biology is pertinent, which will hopefully open up new avenues for research to better understand various reproductive processes and cancers. It will also be relevant for future regenerative medicine, translational research, and clinical applications in human reproduction.

T cells in vascular inflammatory diseases

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Lucas L Lintermans

2014-10-01

Full Text Available Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4+ T cells termed effector memory T cells. This expanded population of effector memory T cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, NK cells, B cells and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of effector memory T cells in uniquely dependent on the voltage-gated Kv1.3 potassium channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic effector memory T cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation.

Prophylactic cranial irradiation in patients with small cell lung cancer

DEFF Research Database (Denmark)

Ramlov, Anne; Tietze, Anna; Khalil, Azza Ahmed

2012-01-01

BACKGROUND: Prophylactic cerebral irradiation (PCI) is a standard treatment for all small cell lung cancer (SCLC) patients with response to chemotherapy. The aims of this study were: to evaluate patients undergoing PCI with regard to cerebral recurrence rate, site of recurrence, and overall...... retrospectively with regard to disease stage, treatment, date of PCI, steroid dose during PCI, toxicity, time to recurrence, site of recurrence and time of death. The median follow up time was 16.6months (range 3-54months). RESULTS: Of the 118 patients undergoing PCI, 74 had limited disease (LD-SCLC) and 44 had...... extensive disease (ED-SCLC). The median age was 65years (range 46-80years). The median overall survival of all patients from the time of diagnosis was 16.0months (CI 95% 13.0-19.0), in LD-SCLC it was 24.0months (CI 95% 19.6-28.3), and in ED-SCLC it was 12.0months (CI 95% 9.6-14.4). Twenty-one patients (17...

Primary Small Cell Carcinoma of the Upper Urinary Tract

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Victor Ka-Siong Kho

2010-03-01

Full Text Available We report a case of primary extrapulmonary small cell carcinoma of the distal ureter, with a synchronous small cell carcinoma of the ipsilateral renal pelvis. These tumors, rarely reported in the urinary tract, are locally aggressive and have a poor prognosis. A 77-year-old male bedridden patient presented with fever and chills with left side-flank pain for 3 days. Following a diagnosis of ureteral urothelial carcinoma, hand-assisted laparoscopic nephroureterectomy with bladder cuff excision was carried out. Adjuvant chemotherapy was given after pathologic report of primary small cell carcinoma of the distal ureter and a synchronous small cell carcinoma of the ipsilateral renal pelvis. After 3 cycles of combination chemotherapy, the patient died 4 months postoperatively due to sepsis.

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease

International Nuclear Information System (INIS)

Arriagada, R.; Le Chevalier, T.; Baldeyrou, P.

1985-01-01

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85%. Local control at 2 years was 61% in the first study and 82% in the second. Acute and delayed toxicity effects are discussed

Chemotherapy related toxicity in locally advanced non-small cell lung cancer

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Bahl Amit

2006-01-01

Full Text Available Background: For inoperable non-small cell lung cancer combined chemotherapy and radiotherapy plays an important role as a therapeutic modality. The aim of the present study was to analyze neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and IIIB in Indian patients using Cisplatin and Etoposide combination chemotherapy. Material and methods: Forty patients of locally advanced Non small cell lung cancer received three cycles neoadjuvant chemotherapy using Injection Cisplatin and Etoposide. The patients were taken for Radical radiotherapy to a dose of 60 Gray over 30 fractions in conventional fractionation after completing chemotherapy. Chemotherapy associated toxicity was assessed using common toxicity criteria (CTC v2.0 Results: Forty patients were available for final evaluation. Median age of presentation of patients was fifty-six years. Thirteen patients had Non small cell lung cancer stage IIIA while twenty-seven patients had Stage IIIB disease. Anemia was the most common hematological toxicity observed (seen in 81% of patients. Nausea and vomiting were the most common non -hematological toxicity seen. Sensory neuropathy was seen in 38%of patients. 88% patients developed alopecia. Seven patients developed febrile neutropenias. Conclusion: Neo-adjuvant chemotherapy using Cisplatin and Etoposide continues to be a basic regimen in the Indian set up despite availability of higher molecules, since it is cost effective, well tolerated and therapeutically effective. Blood transfusions, growth factors and supportive care can be used effectively to over come toxicity associated with this regimen.

Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

DEFF Research Database (Denmark)

Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl

2008-01-01

INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan...... and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC...... age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes...

Follow-up of cognitive functioning in patients with small cell lung cancer

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Oosterhout, Ansel G.M. van; Boon, Peter J; Houx, Peter J; Velde, Guul P.M. ten; Twijnstra, Albert

1995-02-15

Purpose: Study of the course of possible treatment-related cognitive impairment in patients with small cell lung cancer. Methods and Materials: Thirty-two consecutive patients with small cell lung cancer underwent successive neurologic and neuropsychologic examinations until 5 months after prophylactic cranial irradiation, and in their pretherapeutic condition were compared to matched controls. Patients with brain metastases were excluded from this study. Results: Neurologic examination revealed central nervous system (CNS) abnormalities only in the 14 patients with brain metastases. In the remaining patients, neuropsychologic tests showed clear differences between the pretherapeutic performance of patients and that of matched controls (p < 0.001), but no significant deterioration either during or after therapy (0.1 < p < 0.8). Conclusion: The difference between the pretherapeutic performance of patients and that of matched controls may indicate disease-related cognitive impairment. Within the observation period, no adverse effects of the used therapy were found. Our observations underline the importance of a pretherapeutic assessment in neurotoxicity research.

Follow-up of cognitive functioning in patients with small cell lung cancer

International Nuclear Information System (INIS)

Oosterhout, Ansel G.M. van; Boon, Peter J.; Houx, Peter J.; Velde, Guul P.M. ten; Twijnstra, Albert

1995-01-01

Purpose: Study of the course of possible treatment-related cognitive impairment in patients with small cell lung cancer. Methods and Materials: Thirty-two consecutive patients with small cell lung cancer underwent successive neurologic and neuropsychologic examinations until 5 months after prophylactic cranial irradiation, and in their pretherapeutic condition were compared to matched controls. Patients with brain metastases were excluded from this study. Results: Neurologic examination revealed central nervous system (CNS) abnormalities only in the 14 patients with brain metastases. In the remaining patients, neuropsychologic tests showed clear differences between the pretherapeutic performance of patients and that of matched controls (p < 0.001), but no significant deterioration either during or after therapy (0.1 < p < 0.8). Conclusion: The difference between the pretherapeutic performance of patients and that of matched controls may indicate disease-related cognitive impairment. Within the observation period, no adverse effects of the used therapy were found. Our observations underline the importance of a pretherapeutic assessment in neurotoxicity research

Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer

International Nuclear Information System (INIS)

Gong, Zhiyun; Lu, Renquan; Xie, Suhong; Jiang, Minglei; Liu, Kai; Xiao, Ran; Shen, Jiabin; Wang, Yanchun; Guo, Lin

2016-01-01

Pro-gastrin releasing peptide (ProGRP) plays the role of oncogene in small cell lung cancer (SCLC). In this study, we aim to explore the biological function of ProGRP in SCLC cells and its potential mechanism. Expression of ProGRP in SCLC tissues and cell lines were detected by immunohistochemistry and western blot analysis, respectively. The transduced cell lines with ProGRP down-regulation were established using RNA interference technology. Cell viability, cologenic, apoptosis-associated assay and the biomarker levels determination for cell supernatant were performed in the transduced cells to elucidate the biological functions and mechanisms of ProGRP in SCLC cells. Our data showed that ProGRP protein was demonstrated a higher level in SCLC tissues and cells compared with the control, and its diagnostic efficiency was better than NSE, further, the higher levels of ProGRP were detected in the patients with extensive disease stage (P < 0.05), were also the unfavorable factor to the prognosis of SCLC patients. Additionally, the concentration of serum ProGRP is a useful biomarker in disease-monitoring of the patients with SCLC. Down-regulation of ProGRP significantly reduced SCLC cell growth, repressed colony formation, but increased cancer cell apoptosis. Additionally, repression of ProGRP also induced change in the cell cycle and output of NSE. Our data indicated that ProGRP serve as the useful biomarker in the management of SCLC and might be a potential therapeutic target. - Highlights: • ProGRP is overexpressed in the tissues and sera of the patients with SCLC. • Down-regulation of ProGRP inhibited cell proliferation. • Inhibition of ProGRP altered cell cycle distribution and triggers the apoptosis of lung cancer cells.

On the surveillance for animal diseases in small herds

DEFF Research Database (Denmark)

Greiner, Matthias; Dekker, Aldo

2005-01-01

Small herds may present a problem in surveillance for infectious animal diseases because typical levels of a within-herd design prevalence are not directly applicable. We suggest a definition of small herds as those smaller than 2/(within-herd design prevalence) on the basis that such herds would...... be expected to have less than two (i.e. only one) infected animals. Consequently, the probability of detecting small herds cannot be improved by choosing a larger sample size within the herd. We derive necessary sample sizes of herds and the probability ("confidence") of detecting disease within a stratum...... conservative (lower) estimates of the confidence for a given sample size and should therefore be preferred....

Phase II study of oral platinum drug JM216 as first-line treatment in patients with small-cell long cancer

NARCIS (Netherlands)

Fokkema, E; Groen, HJM; Uges, DRA; Weil, C; Smith, IE

1999-01-01

Purpose: This multicenter phase II trial wets performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC). Patients and Methods: patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease

Glucose metabolism in small subcortical structures in Parkinson's disease

DEFF Research Database (Denmark)

Borghammer, Per; Hansen, Søren B; Eggers, Carsten

2012-01-01

Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PE...

The 'grey area' between small cell and non-small cell lung carcinomas. Light and electron microscopy versus clinical data in 14 cases

NARCIS (Netherlands)

Mooi, W. J.; van Zandwijk, N.; Dingemans, K. P.; Koolen, M. G.; Wagenvoort, C. A.

1986-01-01

We studied 14 lung tumours which on light microscopy had posed difficulties on classification as either small cell or non-small cell carcinomas. The light and electron microscopical features were compared with patient follow-up data. Electron microscopy showed neuroendocrine granules in 12 cases,

Clinical significance of detection of serum expressions of MMP-2 and TIMP-2 in patients with small cell pulmonary carcinoma

International Nuclear Information System (INIS)

Peng Liang

2008-01-01

Objective: To investigate the clinical significance of changes of serum expressions of matrix metallo-proteinase 2 (MMP-2) and tissue inhibitors of metallo-proteinase 2 (TIMP-2) in patients with small cell lung cancer (SCLC). Methods: Serum MMP-2 and TIMP-2 contents were measured with RIA in 80 patients with small cell lung cancer (SCLC) and 35 controls. Results: The serum contents of MMP-2 and TIMP-2 in patients with SCLC were significantly higher than those in the controls (P<0.01). Among the patients, the serum concentration of the two parameters in patients with wide-spread disease were significantly higher than those in patients with localized disease (P<0.05). Conclusion: Serum concentrations of MMP-2 and TIMP-2 were much increased in patients with SCLC, especially in patients with wide-spread disease. (authors)

Epstein-Barr virus associated T-cell lymphoproliferative disease misdiagnosed as ulcerative colitis: a case report.

Science.gov (United States)

Zheng, Xiaodan; Xie, Jianlan; Zhou, Xiaoge

2015-01-01

Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (LPD) is not uncommon in China, but gastrointestinal involvement is very rare. We report on an immunocompetent patient with EBV-associated T-cell LPD of the colon. The 26-year-old man was initially misdiagnosed with ulcerative colitis (UC). A colon biopsy revealed the presence of small to medium-sized lymphoid cells infiltrating the intestinal wall. The neoplastic cells expressed CD3, CD5, and granzyme B, not CD56. EBV-encoded small ribonucleic acid was detected in the tumor cells of the colon as well as the lymph node, and the T-cell receptor gene rearrangement result displayed δ gene monoclonal rearrangement. The patient died 2 moths after the diagnosis. The clinical course of EBV-associated T-cell LPD is aggressive and the prognosis is poor, the wrong diagnosis may delay treatment. Therefore, we should be very careful to prevent misdiagnosis. When patients have multiple intestinal ulcers that are not typical of UC and the clinical course is unusual, although morphology looks like inflammatory change, pathologist should consider the possibility of EBV-associated LPD. The treatment strategy and prognosis of these two diseases are different.

Radiotherapy of elderly patients with non-small-cell lung cancer

International Nuclear Information System (INIS)

Nakano, Kikuo; Hiramoto, Takehiko; Kumagai, Kazuhiko; Tukamoto, Yuji; Furonaka, Makoto; Hayakawa, Masanobu; Nakamura, Kenji

1996-01-01

Treatment results of patients aged 75 years or older (elderly group) with non-small-cell lung cancer were compared with those of patients aged 74 years or younger (younger group). In patients with stage III disease, radiotherapy alone resulted in a median survival of 11.5 months in the younger group and 5.5 months in the elderly group. There was a significant difference in survival rate between the two groups (P=0.0008). Moreover, the elderly group patients more frequently died of pneumonia and radiation pneumonitis than the younger group patients. However, results of radiotherapy were similar in the two groups of patients with stage I and II disease. Accordingly, these findings suggested that radiotherapy is an appropriate treatment modality for elderly lung cancer patients, but that individualized radiotherapy is needed for those with locally advanced stage. (author)

Immune-based Therapies for Non-small Cell Lung Cancer.

Science.gov (United States)

Rafei, Hind; El-Bahesh, Ehab; Finianos, Antoine; Nassereddine, Samah; Tabbara, Imad

2017-02-01

Lung cancer is the leading cause of cancer-related death worldwide. Treatment of non-small cell lung cancer has evolved tremendously over the past decade. Specifically, immune checkpoint inhibitors have become an increasingly interesting target of pharmacological blockade. These immune inhibitors have shown promising results in front-line therapy and after failure of multiple lines, as well as in monotherapy and combination with other therapies. Vaccination in non-small cell lung cancer is also an emerging field of research that holds promising results for the future of immunotherapy in non-small cell lung cancer. This review presents a concise update on the most recent data regarding the role of checkpoint inhibitors as well as vaccination in non-small cell lung cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

High-content phenotypic screening and triaging strategy to identify small molecules driving oligodendrocyte progenitor cell differentiation.

Science.gov (United States)

Peppard, Jane V; Rugg, Catherine A; Smicker, Matthew A; Powers, Elaine; Harnish, Erica; Prisco, Joy; Cirovic, Dragan; Wright, Paul S; August, Paul R; Chandross, Karen J

2015-03-01

Multiple Sclerosis is a demyelinating disease of the CNS and the primary cause of neurological disability in young adults. Loss of myelinating oligodendrocytes leads to neuronal dysfunction and death and is an important contributing factor to this disease. Endogenous oligodendrocyte precursor cells (OPCs), which on differentiation are responsible for replacing myelin, are present in the adult CNS. As such, therapeutic agents that can stimulate OPCs to differentiate and remyelinate demyelinated axons under pathologic conditions may improve neuronal function and clinical outcome. We describe the details of an automated, cell-based, morphometric-based, high-content screen that is used to identify small molecules eliciting the differentiation of OPCs after 3 days. Primary screening was performed using rat CG-4 cells maintained in culture conditions that normally support a progenitor cell-like state. From a library of 73,000 diverse small molecules within the Sanofi collection, 342 compounds were identified that increased OPC morphological complexity as an indicator of oligodendrocyte maturation. Subsequent to the primary high-content screen, a suite of cellular assays was established that identified 22 nontoxic compounds that selectively stimulated primary rat OPCs but not C2C12 muscle cell differentiation. This rigorous triaging yielded several chemical series for further expansion and bio- or cheminformatics studies, and their compelling biological activity merits further investigation. © 2014 Society for Laboratory Automation and Screening.

Small cell extraskeletal osteosarcoma: a rare case report

Directory of Open Access Journals (Sweden)

Neelam Sood

2014-01-01

Full Text Available Extraskeletal osteosarcoma is a rare malignant mesenchymal neoplasm and its small cell variant is one among the rarest variant. This article describes a 60-year-old woman presenting with a large, lobulated, painful mass in left thigh with associated history of trauma since 18 months. Her magnetic resonance imaging showed a variegated mixed intensity lesion with associated cystic degeneration, necrosis and matrix arborizing nearby muscles. Fine needle aspiration cytology showed a small cell lesion with very scant osteoid. Tumor was excised and histopathological diagnosis was small cell osteosarcoma involving adjacent muscles and fat with sparing of lymph nodes. The aim of this article is to present the clinical, radiological, cyto-histological and immunohistochemical features of this extremely rare lesion.

Cell transplantation for Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Jia Liu; Hongyun Huang

2006-01-01

OBJECTIVE: The motor symptoms of Parkinson's disease (PD) can be improved by cell transplantation,which has caught general attention from the field of the therapy for PD recently. In this paper, we summarize the cell-based therapy for PD.DATA SOURCES: A search for English literature related to the cellular transplantation of PD from January 1979to July 2006 was conducted in Medline with the key words of "Parkinson's disease, cell transplantation,embryonic stem cells, neural stem cells".STUDY SELECTTON: Data were checked in the first trial, and literatures about PD and cell transplantation were selected. Inclusive criteria: ① PD; ② Cell transplantation. Exclusive criteria: repetitive researches.DATA EXTRACTTON: A total of 100 papers related to cellular transplant and PD were collected and 41literatures were in accordance with the inclusive criteria.DATA SYNTHESIS: PD is a neural degeneration disease that threatens the health of the aged people, and most traditional therapeusis cannot delay its pathological proceeding. Cell transplantation is becoming popular as a new therapeutic tool, and the cells used to transplant mainly included dopamine-secreting cells, fetal ventral mesencephalic cells, embryonic stem cells and neural stem cells up to now. Animal experiment and clinical test demonstrate that cell transplantation can relieve the motor symptoms of Parkinson's disease obviously, but there are some problems need to be solved.CONCLUSTON: Cell transplantation has visible therapeutic efficacy on PD. Following the improvement of technique, and we have enough cause to credit that cell therapy may cure PD in the future.

Drug development for breast, colorectal, and non-small cell lung cancers from 1979 to 2014.

Science.gov (United States)

Nixon, Nancy A; Khan, Omar F; Imam, Hasiba; Tang, Patricia A; Monzon, Jose; Li, Haocheng; Sun, Gavin; Ezeife, Doreen; Parimi, Sunil; Dowden, Scot; Tam, Vincent C

2017-12-01

Understanding the drug development pathway is critical for streamlining the development of effective cancer treatments. The objective of the current study was to delineate the drug development timeline and attrition rate of different drug classes for common cancer disease sites. Drugs entering clinical trials for breast, colorectal, and non-small cell lung cancer were identified using a pharmaceutical business intelligence database. Data regarding drug characteristics, clinical trials, and approval dates were obtained from the database, clinical trial registries, PubMed, and regulatory Web sites. A total of 411 drugs met the inclusion criteria for breast cancer, 246 drugs met the inclusion criteria for colorectal cancer, and 315 drugs met the inclusion criteria for non-small cell lung cancer. Attrition rates were 83.9% for breast cancer, 87.0% for colorectal cancer, and 92.0% for non-small cell lung cancer drugs. In the case of non-small cell lung cancer, there was a trend toward higher attrition rates for targeted monoclonal antibodies compared with other agents. No tumor site-specific differences were noted with regard to cytotoxic chemotherapy, immunomodulatory, or small molecule kinase inhibitor drugs. Drugs classified as "others" in breast cancer had lower attrition rates, primarily due to the higher success of hormonal medications. Mean drug development times were 8.9 years for breast cancer, 6.7 years for colorectal cancer, and 6.6 years for non-small cell lung cancer. Overall oncologic drug attrition rates remain high, and drugs are more likely to fail in later-stage clinical trials. The refinement of early-phase trial design may permit the selection of drugs that are more likely to succeed in the phase 3 setting. Cancer 2017;123:4672-4679. © 2017 American Cancer Society. © 2017 American Cancer Society.

Intercalated radio-chemotherapy in small cell lung cancer

International Nuclear Information System (INIS)

Hoskin, P.J.; Parton, D.; Yarnold, J.R.; Cherryman, G.; Smith, I.E.

1991-01-01

36 patients with small cell lung cancer have been treated using chemotherapy comprising carboplatin, ifosphamide and etoposide. A total of 6 cycles of chemotherapy was given. In 15 patients with limited disease intercalated radio-chemotherapy was used in which two 5-day courses of hyperfractionated radiotherapy were given to the thorax after the 1st and 2nd cycles of chemotherapy. Each course of thoracic radiotherapy delivered 15 Gy in 15 fractions over 5 days. Oesophagitis occurred in 7 patients (40 percent), in 5 of whom this was severe (WHO grade 3). Radiological pneumonitis developed in 6 patients (40 percent) with subsequent fibrosis in 2 patients. These effects are greater than would be expected with this dose of radiation alone and reflect marked enhancement of normal tissue toxicity. (author). 11 refs.; 1 fig.; 1 tab

Research progress in animal models and stem cell therapy for Alzheimer’s disease

Directory of Open Access Journals (Sweden)

Han F

2014-12-01

Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

Psychological therapies for sickle cell disease and pain.

Science.gov (United States)

Anie, Kofi A; Green, John

2015-05-08

Sickle cell disease comprises a group of genetic blood disorders. It occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which, if severe, can reduce mobility; a tendency for small blood capillaries to become blocked causing pain in muscle and bone commonly known as 'crises'; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological interventions for individuals with sickle cell disease might complement current medical treatment, and studies of their efficacy have yielded encouraging results. This is an update of a previously published Cochrane Review. To examine the evidence that psychological interventions improve the ability of people with sickle cell disease to cope with their condition. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and the Internet, handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 17 February 2015. All randomised or quasi-randomised controlled trials comparing psychological interventions with no (psychological) intervention in people with sickle cell disease. Both authors independently extracted data and assessed the risk of bias of the included studies. Twelve studies were identified in the searches and seven of these were eligible for inclusion in the review. Five studies, involving 260 participants, provided data for analysis. One study showed that cognitive behaviour therapy significantly reduced the affective component of pain (feelings about pain), mean difference -0.99 (95% confidence interval -1.62 to -0.36), but

Update on small intestinal stem cells

OpenAIRE

Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

2013-01-01

Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to id...

Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations

Directory of Open Access Journals (Sweden)

Bhatia M

2015-07-01

Full Text Available Monica Bhatia,1 Sujit Sheth21Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, 2Division of Pediatric Hematology and Oncology, Weill Cornell Medical College, New York, NY, USAAbstract: Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD. The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to

Sickle Cell Disease

Science.gov (United States)

... days. Your body may have trouble making enough new cells to replace the ones that you lost. Because ... Indian backgrounds. What are the symptoms of sickle cell disease? People with ... the whites of the eyes (icterus) The effects of SCD vary from person ...

Negative EBUS-TBNA Predicts Very Low Prevalence of Mediastinal Disease in Staging of Non-Small Cell Lung Cancer.

Science.gov (United States)

Taverner, John; Cheang, Mun-Yoong; Antippa, Phillip; See, Katharine; Irving, Louis B; Steinfort, Daniel P

2016-04-01

Confirmation of mediastinal disease (N2/3) in non-small cell lung cancer (NSCLC) generally precludes curative surgical management. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has become a routine first test in mediastinal staging of NSCLC; however, it remains unclear whether a negative EBUS-TBNA should be followed by mediastinoscopy before proceeding to surgery. Understanding the prevalence of metastases in lymph nodes with benign findings on EBUS-TBNA will inform decision making following negative EBUS-TBNA. We examined a retrospective cohort of patients who underwent EBUS-TBNA before resection with mediastinal lymph node sampling for NSCLC between December 2009 and June 2014 in 3 hospitals in Melbourne, Australia. All patients had integrated positron emission tomography/computed tomography (PET/CT) before EBUS-TBNA. Eighty-two matched mediastinal lymph node stations were sampled in 57 patients by both EBUS-TBNA and surgical resection, 47 nodes in patients staged cN0/1 by PET/CT and 35 nodes in patients staged cN2/3. All patients had a negative EBUS-TBNA. Four malignant nodes were identified surgically (4.9% of lymph nodes). The mean size of malignant deposits was 5.5 mm. Per-node negative predictive value was 78/82=0.95. All malignant nodes were located in patients with moderate-high risk disease (cN2/3), giving a disease prevalence in cN2/3 patients of 11%, and 0% in cN0/1. In patients staged cN2, per-node NVP was 0.89. The prevalence of mediastinal nodal disease following negative EBUS-TBNA is very low, at 4.9%. The per-node NVP of EBUS-TBNA is 0.95, decreasing to 0.89 in moderate-high risk patients. We suggest that a negative EBUS-TBNA of mediastinal nodes does not need to be confirmed by mediastinoscopy of those nodal stations, regardless of PET/CT findings.

Double-balloon enteroscope for the diagnosis of small intestine diseases in children

International Nuclear Information System (INIS)

Hernandez Garces, Hector Ruben; Ruenes Domech, Caridad; Hano Garcia, Olga Marina

2010-01-01

A retrospective and descriptive study was conducted to assess the accuracy, effectiveness and extent of the double balloon enteroscope screening in the diagnosis of small intestine diseases in children. Eight patients were studied by means of physical examination and negative complementary ones of small intestine disease, seen between November, 2008 and October, 2009. In three patients there was the clinical and radiological suspicion of Crohn's disease; in other three the suspicion of small intestine tumor and remainder were seen due to hidden bleeding of intestinal origin

Cognitive small cell networks: energy efficiency and trade-offs

NARCIS (Netherlands)

Wildemeersch, M.; Wildemeersch, Matthias; Quek, T.Q.S.; Slump, Cornelis H.; Rabbachin, A.

2013-01-01

Heterogeneous networks using a mix of macrocells and small cells are foreseen as one of the solutions to meet the ever increasing mobile traffic demand. Nevertheless, a massive deployment of small cell access points (SAPs) leads also to a considerable increase in energy consumption. Spurred by

Small-cell osteosarcoma

International Nuclear Information System (INIS)

Edeiken, J.; Raymond, A.K.; Ayala, A.G.; Benjamin, R.S.; Murray, J.A.; Carrasco, H.C.

1987-01-01

Small-cell osteosarcoma, a subtype of osteogenic sarcoma, consists of sheets of round cells that produce an osteoid matrix. It may be confused with Ewing sarcoma if the osteoid matrix is not included in the biopsy. The distinctive radiographic features of an osteoblastic tumor and a pattern of permeative destruction will confirm the histologic diagnosis or indicate the true nature if tumor osteoid is not included in the histological sections. We add 13 patients to the 32 previously reported in the literature. Fourteen (31%) of the 45 are living and well, though three have been followed for only 2 months. The treatments have been so varied that a statistically significant evaluation cannot be developed. The radiographic features are not distinctive, but the diagnosis may be suggested when a tumor has osteoblastic features in the metaphysis and extends well down into the shaft with a pattern of permeative destruction. The radiographic features are especially important when limited biopsies reveal only sheets of round cells, thus suggesting Ewing sarcoma. The presence of an osteoid-producing tumor as evident by osteoblastic new bone formation will lead to the correct diagnosis. (orig.)

Adenosquamous cell carcinoma of the cervix — clinical and prognostic characteristics of the disease

Directory of Open Access Journals (Sweden)

E. K. Tanriverdieva

2012-01-01

Full Text Available Adenosquamous cell carcinoma of the cervix is a rare form of cancer of the cervix. Because of the small number of observations adenosquamous cell carcinoma of the cervix remains poorly understood disease, although the first mention of it dates back to 1956, when A. Glucksmann, and C.D. Cherry first described of mixed carcinoma (adenoacanthoma of the uterine cervix.

MicroRNA-106b-5p regulates cisplatin chemosensitivity by targeting polycystic kidney disease-2 in non-small-cell lung cancer.

Science.gov (United States)

Yu, Shaorong; Qin, Xiaobing; Chen, Tingting; Zhou, Leilei; Xu, Xiaoyue; Feng, Jifeng

2017-09-01

Systemic therapy with cytotoxic agents remains one of the main treatment methods for non-small-cell lung cancer (NSCLC). Cisplatin is a commonly used chemotherapeutic agent, that, when combined with other drugs, is an effective treatment for NSCLC. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. Unfortunately, the potential mechanism underlying such resistance remains unclear. In this study, we explored the mechanism of microRNA-106b-5p (miR-106b-5p), which is involved in the resistance to cisplatin in the A549 cell line of NSCLC. Quantitative real-time PCR was used to test the expression of miR-106-5p in the A549 and the A549/DDP cell line of NSCLC. The cell counting kit-8 assay was used to detect cell viability. Flow cytometry was used to measure cell cycle and cell apoptosis. Luciferase reporter assays and western blot were performed to confirm whether polycystic kidney disease-2 (PKD2) is a direct target gene of miR-106b-5p. Immunohistochemistry was performed to examine the distribution of PKD2 expression in patients who are sensitive and resistant to cisplatin. The experiments indicated that the expression of miR-106b-5p was significantly decreased in A549/DDP compared with that in A549. MiR-106b-5p affected the tolerance of cells to cisplatin by negatively regulating PKD2. Upregulation of miR-106b-5p or downregulation of PKD2 expression can cause A549/DDP cells to become considerably more sensitive to cisplatin. The results showed that miR-106b-5p enhanced the sensitivity of A549/DDP cells to cisplatin by targeting the expression of PKD2. These findings suggest that the use of miR-106b-5p may be a promising clinical strategy in the treatment of NSCLC.

Update on small intestinal stem cells.

Science.gov (United States)

Tesori, Valentina; Puglisi, Maria Ausiliatrice; Lattanzi, Wanda; Gasbarrini, Giovanni Battista; Gasbarrini, Antonio

2013-08-07

Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

The effect of small molecules on nuclear-encoded translation diseases.

Science.gov (United States)

Soiferman, Devorah; Ayalon, Oshrat; Weissman, Sarah; Saada, Ann

2014-05-01

The five complexes of the mitochondrial respiratory chain (MRC) supply most organs and tissues with ATP produced by oxidative phosphorylation (OXPHOS). Inherited mitochondrial diseases affecting OXPHOS dysfunction are heterogeneous; symptoms may present at any age and may affect a wide range of tissues, with many diseases giving rise to devastating multisystemic disorders resulting in neonatal death. Combined respiratory chain deficiency with normal complex II accounts for a third of all respiratory deficiencies; mutations in nuclear-encoded components of the mitochondrial translation machinery account for many cases. Although mutations have been identified in over 20 such genes and our understanding of the mitochondrial translation apparatus is increasing, to date no definitive cure for these disorders exists. We evaluated the effect of seven small molecules with reported therapeutic potential in fibroblasts of four patients with combined respiratory complex disorders, each harboring a known mutation in a different nuclear-encoded component of the mitochondrial translation machinery: EFTs, GFM1, MRPS22 and TRMU. Six mitochondrial parameters were screened as follows; growth in glucose-free medium, reactive oxygen species (ROS) production, ATP content, mitochondrial content, mitochondrial membrane potential and complex IV activity. It was clearly evident that each patient displayed an individual response and there was no universally beneficial compound. AICAR increased complex IV activity in GFM1 cells and increased ATP content in MRPS22 fibroblasts but was detrimental to TRMU, who benefitted from bezafibrate. Two antioxidants, ascorbate and N-acetylcysteine (NAC), significantly improved cell growth, ATP content and mitochondrial membrane potential and decreased levels of intracellular reactive oxygen species (ROS) in EFTs fibroblasts. This study presents an expanded repertoire of assays that can be performed using the microtiter screening system with a small number

Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

Science.gov (United States)

Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

2017-01-01

Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

Science.gov (United States)

Cong, Yu; Lentz, Margaret R; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent; Holbrook, Michael R

2017-04-01

Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

Characterization of the effects of cyclooxygenase-2 inhibition in the regulation of apoptosis in human small and non-small cell lung cancer cell lines.

LENUS (Irish Health Repository)

Alam, Mahmood

2012-02-03

BACKGROUND: Cyclooxygenase-2 enzyme (COX-2) is overexpressed in human non-small cell lung cancer (NSCLC) but is not expressed in small cell lung cancer. Selective COX-2 inhibitors have been shown to induce apoptosis in NSCLC cells, an effect which is associated with the regulation of intracellular MAP kinase (MAPK) signal pathways. Our aims were to characterize the effects of COX-2 inhibition by rofecoxib on apoptosis in human NSCLC and small cell lung cancer cell lines. METHODS: The human NSCLC cell line NCI-H2126 and small cell lung cancer cell line DMS-79 were used. Constitutive COX-2 protein levels were first determined by Western blot test. Levels of apoptosis were evaluated by using propidium iodide staining on FACScan analysis after incubation of NCI-H2126 and DMS-79 with p38 MAPK inhibitor SB202190 (25 ?microM), NF-kappaB inhibitor SN50 (75 microg\\/mL), and rofecoxib at 100 and 250 microM. All statistical analysis was performed by analysis of variance. RESULTS: Western blot test confirmed the presence of COX-2 enzyme in NCI-H2126 and absence in DMS-79. Interestingly, rofecoxib treatment demonstrated a dose-dependent increase in apoptosis in both cell lines. Given this finding, the effect of rofecoxib on NF-kappaB and p38 MAPK pathways was also examined. Apoptosis in both cell lines was unaltered by SN50, either alone or in combination with rofecoxib. A similar phenomenon was observed in NCI-H2126 cells treated with SB202190, either alone or in combination with rofecoxib. In contrast, p38 MAPK inhibition greatly upregulated DMS-79 apoptosis in a manner that was unaltered by the addition of rofecoxib. CONCLUSIONS: Rofecoxib led to a dose-dependent increase in apoptosis in both tumor cell lines. This effect occurred independently of COX-2, NF-kappaB, and p38 MAPK pathways in DMS-79 cells. As such, rofecoxib must act on alternative pathways to regulate apoptosis in human small cell lung cancer cells.

Progress ill Small-Bowel Physiology and Disease

African Journals Online (AJOL)

1971-10-23

Oct 23, 1971 ... The epithelial cell of the small-bowel mucosa is second ... an important part in the entrapment of fat micelles before absorption at the .... died with a gastric carcinoma. ... termed 'Mediterranean' because of its frequency in.

Association of radiotherapy and chemotherapy in limited small cell lung cancers: interest of alternating protocols

International Nuclear Information System (INIS)

Le Chevalier, T.; Arriagada, R.; Ruffie, P.; Cremoux, H. de; Douillard, J.Y.; Tuchais, C.; Chomy, P.; Riviere, A.; Tarayre, M.

1992-01-01

From 1980, alternating protocols of chemotherapy and thorax radiotherapy in limited small cell lung cancers have been elaborated in order to control locally the disease, to improve the total survival and to reduce the toxicity that are bound the simultaneous treatments of chemotherapy and radiotherapy. Thanks to these protocols, the two-year survival rate is 27% and the five-year survival rate, 16%

The prognostic effect of subpleural lesions in early stage non-small cell lung cancer: preliminary report

International Nuclear Information System (INIS)

Lee, Ho Jun; Lee, Hyung Sik; Hur, Won Joo; Lee, Ki Nam; Choi, Pill Jo

1998-01-01

We retrospectively analyzed the impact of subpleural lesions of early stage non-small cell lung cancer on the patterns of failure to support selection of postoperative adjuvant therapy. The study included 91 patients who underwent surgery for early stage non-small cell lung cancer at Donga University hospital from Dec 1990 to Sep 1996. Twenty five patients were excluded due to postoperative mortality (four patients, 4.4%) and stage III (21 patients). Of 66 patients, 22 patients were subpleural lesions (15 patients in stage I, and seven patients in stage II). Postoperative adjuvant radiation therapy was given to seven patients with T2N1 disease. The median follow-up duration was 29.5 months (range; 8-84 months). The overall survival rate was 69.5% at 3 years. For all patients who presented with (22 patients) and without (44 patients) subpleural lesions, 3-year overall survival rates were 35.5% and 84.6%, respectively (p=0.0017). For stage I patients who presented with (15 patients) and without (29 patients) subpleural lesions, 3-year overall survival rates were 33.1% and 92.3%, respectively (p=0.001). For stage II patients who presented with (7 patients) and without (15 patients) subpleural lesions, 3-year overall survival rates were 53.3% and 45.7%, respectively (p=0.911). For patients with T2NO disease (34 patients) who presented with (11 patients) and without (23 patients) subpleural lesions, 3-year overall survival rates were 27.3% and 90.3%,respectively (p=0.009).These observations suggest that the subpleural lesion play an important role as a prognostic factor for early stage non-small cell lung cancer. Especially for T2NO disease, patients with subpleural lesions showed significantly lower survival rate than those without that

Full-Duplex MIMO Small-Cell Networks: Performance Analysis

OpenAIRE

Atzeni, Italo; Kountouris, Marios

2015-01-01

Full-duplex small-cell relays with multiple antennas constitute a core element of the envisioned 5G network architecture. In this paper, we use stochastic geometry to analyze the performance of wireless networks with full-duplex multiple-antenna small cells, with particular emphasis on the probability of successful transmission. To achieve this goal, we additionally characterize the distribution of the self-interference power of the full-duplex nodes. The proposed framework reveals useful ins...

New Serum Markers for Small-Cell Lung Cancer. II. The Neural Cell Adhesion Molecule, NCAM

DEFF Research Database (Denmark)

Vangsted, A.; Drivsholm, L.; Andersen, E.

1994-01-01

The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker...... for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis......, before the patients received chemotherapy. The polyclonal antibody used in the assay recognized all three isoforms of NCAM. The concentration of NCAM was related to clinical parameters of the patients such as age, sex, blood group status, stage of disease, organ site involvement of metastases, survival...

An analysis of the NIH-supported sickle cell disease research portfolio.

Science.gov (United States)

Gavini, Nara; Hoots, W Keith; Mensah, George A; Hanspal, Manjit

2015-02-01

Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease. Published by Elsevier Inc.

Radiological aspects of Crohn's disease in small intestine: iconographic assay

International Nuclear Information System (INIS)

Barros, Nestor de; Juliano, Adriana G.; Polizini, Jose M.R.; Rejtman, Debora; Cerri, Giovanni Guido; Rocha, Manoel de Souza

1999-01-01

The authors present the radiological features of Crohn's disease in small intestine as ways of differential diagnosis of others diseases of duodenum and adjacent organs. In this differentiation or confirmation of Crohn's disease the US and TC have proven to be clinically efficacious in the identification of lesions

Metastatic Small Cell Carcinoma of the Breast from Cancer of the Uterine Cervix: A Case Report

Directory of Open Access Journals (Sweden)

Beom Seok Kwak

2018-01-01

Full Text Available We report here on a case of 51-year-old woman with metastatic small cell carcinoma of the breast that came from her cancer of the uterine cervix. She underwent radical hysterectomy with bilateral salpingo-oophorectomy due to small cell carcinoma of the uterine cervix, and adjuvant radiotherapy was administered to the pelvis. Breast metastasis with a palpable mass then occurred 3 months after the primary surgery. Simple mastectomy and adjuvant chemotherapy were performed. She initially showed a good response to the therapy, yet she ultimately died of multiple metastases with a fulminating disease course. This is an extremely rare case, and only 1 similar case has been reported earlier, so we report on this case along with a review of the relevant literature.

Effective plasmid DNA and small interfering RNA delivery to diseased human brain microvascular endothelial cells.

Science.gov (United States)

Slanina, H; Schmutzler, M; Christodoulides, M; Kim, K S; Schubert-Unkmeir, A

2012-01-01

Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis. Copyright © 2012 S. Karger AG, Basel.

Outcome following radiotherapy for loco-regionally recurrent non-small cell lung cancer

International Nuclear Information System (INIS)

Foo, K.; Yeghiaian-Alvandi, R.; Foroudi, F.

2005-01-01

Local and regional recurrence of non-small cell lung cancer is reported to occur in 13-20% of treatment failures after resection. Reported post-recurrent median survival following radiotherapy ranges from 9 to 14 months. This study examines survival following radiotherapy alone for patients with loco-regionally recurring non-small cell lung cancer after initial surgery. Fifty-five patients, receiving radiotherapy at Westmead Hospital between 1979 and 1997, were eligible for study. Data were collected retrospectively by reviewing patient records. The end-point was overall survival. Symptom control was also recorded. Prognostic factors for analysis included age, sex, original presenting stage, disease-free interval (DFI), performance status, site of recurrence, treatment intent and dose. The median overall survival was 11.5 months (95% confidence interval: 8.1-13.0). Survival following treatment with radical intent was 26 months compared to 10.5 months for patients treated with palliative intent (P = 0.025). There was no significant difference in survival for short (<2 years) or long DFI, performance status, radiation dose, age, sex, site of recurrence or stage. Most patients (55%) had partial or complete resolution of symptoms. Radiotherapy results in overall post-recurrence median survival of nearly 1 year, consistent with previous published data. Radical treatment intent predicts better prognosis as a result of patient selection and higher dose. Radiotherapy is effective at palliating symptoms of this disease Copyright (2005) Blackwell Publishing Asia Pty Ltd

Cell therapeutics to treat diseases of the retina

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Natarajan S

2008-11-01

Full Text Available Background: The adult Bone Marrow Stem Cells (BMSCs have distinct advantages over the other types of stem cells. They are multipotent, can be stored for upto 10 years and considered to be one of the best sources of hematopoietic and mesenchymal stem cells in an adult body. Genetically inherited diseases such as Retinitis Pigmentosa and Degenerative diseases such as Age Related Macular Degeneration remain unsolved as no definitive treatment is available to repair the damages caused to the RPE and Photoreceptors as of now. In this scenario, the technique of Bone Marrow aspiration & isolation of Mono Nucleated Cells (MNCs & intra-vitreal injection of a very small volume of MNCs in human retinal disorders has been standardized and is safe and feasible for human studies (Mohanty et al and autotransplantation of RPEs from periphery to affected area are underpractice(Coffey et al. In this study we report our research work on different approaches to the above diseases using cell therapeuticsStudy 1 Materials & methods: Ciliary Pigment Epithelium was harvested from donor eyes from Aditya Jyot Eye Hospital, Mumbai and was taken to and grown at NCRM lab. The cells were grown in the earlier reported methodology of Brenda et al (Science 2004. Results: The CPE derived Retinal stem cells grew well in the lab. However, the practical difficulties of harvesting the same in patients limited our further steps in this study. Study II:? Materials & methods: Cadaver eye RPE cells were harvested and grown using polymer scaffolds after transporting them over 6 to 12 Hrs. The RPEs were grown on conventional methods and in polymer scaffolds and were subjected to RT-PCR. Results: Human RPEs were able to grow without amniotic membrane and the same was proven by RT-PCR. This would make it possible for the peripheral RPEs taken from patients to be stored and later expanded and used for replacing the diseased cells of the central portion of the retina in future, without having

Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer

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Qiang GL

2015-12-01

Full Text Available Guangliang Qiang, Chaoyang Liang, Fei Xiao, Qiduo Yu, Huanshun Wen, Zhiyi Song, Yanchu Tian, Bin Shi, Yongqing Guo, Deruo Liu Department of Thoracic Surgery, China–Japan Friendship Hospital, Beijing, People’s Republic of China Purpose: This study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD affects recurrence-free survival in non-small-cell lung cancer (NSCLC patients after surgical resection.Patients and methods: A retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD. Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed.Results: A total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3. The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001. Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001. By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival.Conclusion: NSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. Keywords: lung neoplasms, surgery, pulmonary function test, prognosis

Small bowel angiodysplasia and novel disease associations: a cohort study.

LENUS (Irish Health Repository)

Holleran, Grainne

2013-04-01

Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies.

JAK/STAT inhibitors and other small molecule cytokine antagonists for the treatment of allergic disease.

Science.gov (United States)

Howell, Michael D; Fitzsimons, Carolyn; Smith, Paul A

2018-04-01

To provide an overview of janus kinase (JAK), chemoattractant receptor homologous molecule expressed on T H 2 cells (CRTH2), and phosphodiesterase 4 (PDE4) inhibitors in allergic disorders. PubMed literature review. Articles included in this review discuss the emerging mechanism of action of small molecule inhibitors and their use in the treatment of atopic dermatitis (AD), asthma, and allergic rhinitis (AR). Allergic diseases represent a spectrum of diseases, including AD, asthma, and AR. For decades, these diseases have been primarily characterized by increased T H 2 signaling and downstream inflammation. In recent years, additional research has identified disease phenotypes and subsets of patients with non-Th2 mediated inflammation. The increasing heterogeneity of disease has prompted investigators to move away from wide-ranging treatment approaches with immunosuppressive agents, such as corticosteroids, to consider more targeted immunomodulatory approaches focused on specific pathways. In the past decade, inhibitors that target JAK signaling, PDE4, and CRTH2 have been explored for their potential activity in models of allergic disease and therapeutic benefit in clinical trials. Interestingly, although JAK inhibitors provide an opportunity to interfere with cytokine signaling and could be beneficial in a broad range of allergic diseases, current clinical trials are focused on the treatment of AD. Conversely, both PDE4 and CRTH2 inhibitors have been evaluated in a spectrum of allergic diseases. This review summarizes the varying degrees of success that these small molecules have demonstrated across allergic diseases. Emerging therapies currently in development may provide more consistent benefit to patients with allergic diseases by specifically targeting inflammatory pathways important for disease pathogenesis. Copyright © 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Perivascular Spaces, Glymphatic Dysfunction, and Small Vessel Disease

OpenAIRE

Mestre, Humberto; Kostrikov, Serhii; Mehta, Rupal I.; Nedergaard, Maiken

2017-01-01

Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanis...

PRIMA-1Met/APR-246 induces apoptosis and tumor growth delay in small cell lung cancer expressing mutant p53

DEFF Research Database (Denmark)

Zandi, Roza; Selivanova, Galina; Christensen, Camilla Laulund

2011-01-01

Small cell lung cancer (SCLC) is a highly malignant disease with poor prognosis, necessitating the need to develop new and efficient treatment modalities. PRIMA-1(Met) (p53-dependent reactivation of massive apoptosis), also known as APR-246, is a small molecule, which restores tumor suppressor...... function to mutant p53 and induces cancer cell death in various cancer types. Since p53 is mutated in more than 90% of SCLC, we investigated the ability of PRIMA-1(Met) to induce apoptosis and inhibit tumor growth in SCLC with different p53 mutations....

Current Treatments for Surgically Resectable, Limited-Stage, and Extensive-Stage Small Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

2017-12-01

The prevalence of small cell lung cancer (SCLC) has declined in the U.S. as the prevalence of tobacco use has declined. However, a significant number of people in the U.S. are current or former smokers and are at risk of developing SCLC. Routine histological or cytological evaluation can reliably make the diagnosis of SCLC, and immunohistochemistry stains (thyroid transcription factor-1, chromogranin, synaptophysin, and CD56) can be used if there is uncertainty about the diagnosis. Rarely do patients present with SCLC amendable to surgical resection, and evaluation requires a meticulous workup for extra-thoracic metastases and invasive staging of the mediastinum. Resected patients require adjuvant chemotherapy and/or thoracic radiation therapy (TRT), and prophylactic cranial radiation (PCI) should be considered depending on the stage. For limited-stage disease, concurrent platinum-etoposide and TRT followed by PCI is the standard. Thoracic radiation therapy should be started early in treatment, and can be given twice daily to 45 Gy or once daily to 60-70 Gy. For extensive-stage disease, platinum-etoposide remains the standard first-line therapy, and the standard second-line therapy is topotecan. Preliminary studies have demonstrated the activity of immunotherapy, and the response rate is approximately 10-30% with some durable responses observed. Rovalpituzumab tesirine, an antibody drug conjugate, has shown promising activity in patients with high delta-like protein 3 tumor expression (approximately 70% of patients with SCLC). The emergence of these and other promising agents has rekindled interest in drug development in SCLC. Several ongoing trials are investigating novel agents in the first-line, maintenance, and second-line settings. This review will provide an update on the standard therapies for surgically resected limited-stage small cell lung cancer and extensive-stage small cell lung cancer that have been investigated in recent clinical trials. © Alpha

A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection.

Science.gov (United States)

Niu, Xin; Brahmbhatt, Hetal; Mergenthaler, Philipp; Zhang, Zhi; Sang, Jing; Daude, Michael; Ehlert, Fabian G R; Diederich, Wibke E; Wong, Eve; Zhu, Weijia; Pogmore, Justin; Nandy, Jyoti P; Satyanarayana, Maragani; Jimmidi, Ravi K; Arya, Prabhat; Leber, Brian; Lin, Jialing; Culmsee, Carsten; Yi, Jing; Andrews, David W

2017-04-20

Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM. Small-molecule inhibition of Bax/Bak oligomerization allowed cells to evade apoptotic stimuli and rescued neurons from death after excitotoxicity, demonstrating that oligomerization of Bax is essential for MOMP. Our discovery of small-molecule Bax/Bak inhibitors provides novel tools for the investigation of the mechanisms leading to MOMP and will ultimately facilitate development of compounds inhibiting Bax/Bak in acute and chronic degenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

Science.gov (United States)

Cooper, Maryann R; Alrajhi, Abdullah M; Durand, Cheryl R

Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

Preoperative radiation therapy in regionally localized stage III non-small-cell lung carcinoma

International Nuclear Information System (INIS)

Reddy, S.; Faber, L.P.; Baumann, L.M.; Lee, M.S.; Jensik, R.J.; Kittle, C.F.; Bonomi, P.; Taylor, S.; Hendrickson, F.R.

1988-01-01

Seventy-four patients seen from January 1975 through December 1982 with clinical stage III M0 non-small-cell carcinoma of the lung were treated with a course of preoperative radiation therapy to be followed by surgical resection. Surgical resection was attempted 4 weeks later. All the patients except two were followed up for a minimum of 5 years or until death. Sixty-four patients (86%) had T3 tumors, while mediastinal nodal involvement was found in 41 (55%). The actuarial 5-year survival and disease-free survival rates for the entire group were 20% and 26%, respectively. Patients with a pathologically complete response had an actuarial disease-free survival rate of 50% at 5 years, compared with only 17% for those with gross residual disease at surgery. One-half of the patients with clinically uninvolved nodes were living disease free at 5 years, compared with only 20% of the patients with N2 disease. The patterns of failure are presented according to the histologic type and stage of the disease

Small molecule probes for plant cell wall polysaccharide imaging

Directory of Open Access Journals (Sweden)

Ian eWallace

2012-05-01

Full Text Available Plant cell walls are composed of interlinked polymer networks consisting of cellulose, hemicelluloses, pectins, proteins, and lignin. The ordered deposition of these components is a dynamic process that critically affects the development and differentiation of plant cells. However, our understanding of cell wall synthesis and remodeling, as well as the diverse cell wall architectures that result from these processes, has been limited by a lack of suitable chemical probes that are compatible with live-cell imaging. In this review, we summarize the currently available molecular toolbox of probes for cell wall polysaccharide imaging in plants, with particular emphasis on recent advances in small molecule-based fluorescent probes. We also discuss the potential for further development of small molecule probes for the analysis of cell wall architecture and dynamics.

Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions.

Science.gov (United States)

Atienza-Amores, Maria; Guerini-Rocco, Elena; Soslow, Robert A; Park, Kay J; Weigelt, Britta

2014-08-01

Small cell carcinoma (SmCC) of the female genital tract constitutes a diagnostic and clinical challenge given its rarity and the lack of standardized therapeutic approaches. Here we review the morphological, clinical and molecular features of gynecologic SmCCs and discuss potential areas for future research. Data for this review article were identified by searches of PubMed, EMBASE and the Internet using the search terms "small cell carcinoma" or "neuroendocrine carcinoma" and "gynecologic", "uterine cervix", "cervix", "uterus", "endometrium", "ovary", "vagina", "fallopian tube" or "vulva", and research articles published in English between 1972 and February 2014 were included. SmCCs arising from different organs within the gynecologic tract share the same histopathologic characteristics, which closely resemble those of small cell lung carcinoma. The expression of at least one immunohistochemical neuroendocrine marker is a common finding. The uterine cervix is the most frequent site of SmCC in the female genital tract. HPV infection seems to play a role in the development of cervical SmCC but not in cancers of other gynecologic sites. FIGO stage is an established prognostic factor, in particular in SCCs of the cervix. Irrespective of the site, SmCCs of the gynecologic tract display an aggressive clinical behavior with few reported long-term survivors. The therapeutic management includes surgery, radiotherapy and chemotherapy. Despite the potential differences in etiology and risk factors, SmCCs from different sites of the gynecologic tract have similar morphologic appearances and clinical behavior. Recent genomic analyses of small cell carcinoma of the lung have revealed potential driver genomic alterations. We posit that the comprehensive genomic characterization of gynecologic SmCCs may lead to the identification of markers that result in an improvement of diagnostic reproducibility of SmCCs of the gynecologic tract, and of molecular aberrations that may be

Limited stage small cell carcinoma of the gastrointestinal tract: a clinicopathologic and prognostic analysis of 27 cases

Directory of Open Access Journals (Sweden)

Chunyan Peng

2013-05-01

Full Text Available Small cell carcinoma of the gastrointestinal tract is a rare and aggressive neuroendocrine tumor. This study aims to analyze the clinical characteristics and potential prognostic factors for patients with limited stage small cell carcinoma of the gastrointestinal tract. The records of 27 patients with limited stage small cell carcinoma of the gastrointestinal tract, who all received surgery with lymphadenectomy, were retrieved and analyzed retrospectively. The median age of patients was 60 years old (range 38-79. The primary locations of tumor were the esophagus (74.1% and stomach (14.8%. The rate of preoperative accurate diagnosis (16.7% was low for small cell carcinoma of the esophagus and stomach. 40.7% of all the patients had regional lymph node metastases. Five patients underwent surgery alone, and the other 22 were treated with surgery + postoperative chemotherapy. All patients had disease progression or recurrence. The overall median survival time was 10 months and the 1-year survival rate was 37.0%. Patients who received postoperative chemotherapy had a median survival time of 12 months, which was superior to the 5-month survival of for those who only had surgery (P<0.0001. TNM stage (P=0.02 and postoperative chemotherapy (P<0.0001 were considered as two prognostic factors in univariate analysis. Postoperative chemotherapy was a significant independent prognostic factor in multivariate analysis (P=0.01. The prognosis for patients with limited stage small cell carcinoma of the gastrointestinal tract remains dismal, however, postoperative chemotherapy may have the potential to improve the outcome for these patients.

Stricturoplasty—a bowel-sparing option for long segment small bowel Crohn's disease

OpenAIRE

Limmer, Alexandra M.; Koh, Hoey C.; Gilmore, Andrew

2017-01-01

Abstract Stricturoplasty is a surgical option for management of severe stricturing Crohn's disease of the small bowel. It avoids the need for small bowel resection and the associated metabolic complications. This report contrasts the indications and technical aspects of two different stricturoplasty techniques. Case 1 describes an extensive Michelassi (side-to-side isoperistaltic) stricturoplasty performed for a 100 cm segment of diseased small bowel in a 45-year-old patient. Case 2 describes...

NKT cells in cardiovascular diseases.

Science.gov (United States)

van Puijvelde, Gijs H M; Kuiper, Johan

2017-12-05

Despite life-style advice and the prescription of cholesterol-lowering and anti-thrombotic drugs, cardiovascular diseases are still the leading cause of death worldwide. Therefore, there is an urgent need for new therapeutic strategies focussing on atherosclerosis, the major underlying pathology of cardiovascular diseases characterized by an accumulation of lipids in an inflamed arterial/vessel wall. CD1d-restricted lipid-sensing natural killer T (NKT) cells, bridging the innate and adaptive immunity, and CD1d-expressing antigen-presenting cells are detected in atherosclerotic lesions of mice and humans. In this review we will summarize studies that point to a critical role for NKT cells in the pathogenesis of atherosclerosis and other cardiovascular diseases by the secretion of pro-atherogenic cytokines and cytotoxins. These pro-atherogenic NKT cells are potential targets for new therapeutic strategies in the prevention and treatment of cardiovascular diseases. Additionally, proteins transferring lipids during atherosclerosis, which are also important in the loading of lipids onto CD1d and possible endogenous ligands responsible for the activation of NKT cells during atherosclerosis will be discussed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Routine clinical use of circulating tumor cells for diagnosis of mutations and chromosomal rearrangements in non-small cell lung cancer-ready for prime-time?

Science.gov (United States)

Pailler, Emma; Faugeroux, Vincent; Oulhen, Marianne; Catelain, Cyril; Farace, Françoise

2017-08-01

In non-small cell lung cancer (NSCLC), diagnosis of predictive biomarkers for targeted therapies is currently done in small tumor biopsies. However, tumor biopsies can be invasive, in some cases associated with risk, and tissue adequacy, both in terms of quantity and quality is often insufficient. The development of efficient and non-invasive methods to identify genetic alterations is a key challenge which circulating tumor cells (CTCs) have the potential to be exploited for. CTCs are extremely rare and phenotypically diverse, two characteristics that impose technical challenges and impact the success of robust molecular analysis. Here we introduce the clinical needs in this disease that mainly consist of the diagnosis of epidermal growth factor receptor ( EGFR ) activating alterations and anaplastic lymphoma kinase ( ALK ) rearrangement. We present the proof-of-concept studies that explore the detection of these genetic alterations in CTCs from NSCLC patients. Finally, we discuss steps that are still required before CTCs are routinely used for diagnosis of EGFR -mutations and ALK -rearrangements in this disease.

PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

International Nuclear Information System (INIS)

Makinoshima, Hideki; Ishii, Genichiro; Kojima, Motohiro; Fujii, Satoshi; Higuchi, Youichi; Kuwata, Takeshi; Ochiai, Atsushi

2012-01-01

Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease. We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines. Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model. PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs

Perceptions of young adults with sickle cell disease concerning their disease experience.

Science.gov (United States)

Matthie, Nadine; Hamilton, Jill; Wells, Diana; Jenerette, Coretta

2016-06-01

To describe the perceptions of young adults with sickle cell disease concerning their disease experience. Sickle cell disease is a lifelong, genetic condition with both acute and chronic painful exacerbations. Little is known of the experiences of young adults with sickle cell disease. This study used a qualitative, descriptive design with semi-structured, life review interviews. Between August 2010-September 2012, purposive sampling was used to recruit participants with a known sickle cell disease diagnosis who were ages 18-35 years, were being seen in an outpatient sickle cell clinic and were English speaking. Participants provided demographic information and responded to two interviews. A content analysis was then used to interpret participants' narratives of their experiences of living with sickle cell disease. A sample of 29 young adults with sickle cell disease consisted of 79·3% females, 35·6% employed full-time or part-time, 71·6% single/never married and 57·8% with sickle cell anaemia. Their mean age was 25·8 with 13·2 years of education. Four major interview themes were identified: (1) struggles to maintain or achieve good quality of life or life satisfactions; (2) strategies to maintain self-care; (3) interruptions to family, work and social roles; and (4) difficulties accessing needed health care. Young adults face many challenges while living with sickle cell disease. With a better understanding of their disease experience and how it influences their quality of life, researchers can begin tailoring appropriate interventions to improve health outcomes in this vulnerable, minority population. © 2015 John Wiley & Sons Ltd.

Maternal periodontal disease in early pregnancy and risk for a small-for-gestational-age infant.

Science.gov (United States)

Boggess, Kim A; Beck, James D; Murtha, Amy P; Moss, Kevin; Offenbacher, Steven

2006-05-01

The objective of the study was to determine whether periodontal disease is associated with delivery of a small-for-gestational-age infant. In a prospective study of oral health, periodontal disease was categorized as health, mild, or moderate/severe on the basis of clinical criteria. Small for gestational age was defined as birth weight less than the 10th percentile for gestational age. A risk ratio (95th percentile confidence interval) for a small-for-gestational-age infant among women with moderate or severe periodontal disease was calculated. Sixty-seven of 1017 women (6.6%) delivered a small-for-gestational-age infant, and 143 (14.3%) had moderate or severe periodontal disease. The small-for-gestational-age rate was higher among women with moderate or severe periodontal disease, compared with those with health or mild disease (13.8% versus 3.2% versus 6.5%, P periodontal disease was associated with a small-for-gestational-age infant, a risk ratio of 2.3 (1.1 to 4.7), adjusted for age, smoking, drugs, marital and insurance status, and pre-eclampsia. Moderate or severe periodontal disease early in pregnancy is associated with delivery of a small-for-gestational-age infant. Understanding the mechanism of periodontal disease-associated adverse pregnancy outcomes could lead to interventions to improve fetal growth.

Present trends in the treatment of advanced non-small-cell lung cancer

International Nuclear Information System (INIS)

Parvez, T.; Iskandrani, A.

2003-01-01

Lung cancer is the leading cause of cancer deaths all over the world. As most patients present with advanced disease, major efforts have been made in the treatment of such disease with systemic chemotherapy. Several new agents and new combinations of chemotherapy have been developed recently. This article reviews the randomized clinical trials investigating chemotherapy for advanced non-small cell lung cancer (NSCLC) in relapse or progressive disease while being treated and in elderly patients. Therapies that incorporate new biological agents to target specific defects in lung cancer are also discussed. Several clinical trials have demonstrated improvement in overall survival as well as quality of life with presently available chemotherapy treatment of advanced NSCLC. Better options are available for the elderly as well as those having relapse after first line chemotherapy. Despite all this progress the 5-year survival rate still remains at a dismal 14%. New therapies with good results are still desired. (author)

Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

Science.gov (United States)

Brown, Melissa A; Weinberg, Rebecca B

2018-01-01

Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

International Nuclear Information System (INIS)

Yan, Jun-Hai; Zhao, Chun-Liu; Ding, Lan-Bao; Zhou, Xi

2015-01-01

The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer

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Yan, Jun-Hai; Zhao, Chun-Liu [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China); Ding, Lan-Bao [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Zhou, Xi, E-mail: modelmap@139.com [Department of Respiratory Medicine, Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 20020 (China)

2015-10-09

The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers. However, the expression pattern and role of FOXD3 in non-small cell lung cancer (NSCLC) have not been well characterized. We report that FOXD3 is significantly downregulated in NSCLC cell lines and clinical tissues. FOXD3 overexpression significantly inhibits cell growth and results in G1 cell cycle arrest in NSCLC A549 and H1299 cells. In a xenograft tumor model, FOXD3 overexpression inhibits tumor growth and angiogenesis. Remarkably, expression of vascular endothelial growth factor (VEGF) was reduced in FOXD3 overexpression models both in vitro and in vivo. These findings suggest that FOXD3 plays a potential tumor suppressor role in NSCLC progression and represents a promising clinical prognostic marker and therapeutic target for this disease. - Highlights: • FOXD3 is downregulated in NSCLC cell lines and tissues. • FOXD3 overexpression inhibited cell proliferation in NSCLC cells. • FOXD3 overexpression led to decreased angiogenesis in NSCLC cells in vitro and in vivo.

F-18 fluorodeoxyglucose positron emission tomography in the mediastinal nodal staging of non-small cell lung carcinoma

International Nuclear Information System (INIS)

Berlangieri, S.U.; Scott, A.M.; Knight, S.; Fitt, G.J.; Hess, E.M.; Pathmaraj, K.; Hennessy, O.F.; Tochon-Danguy, H.J.; Chan, J.G.; Egan, G.F.; Sinclair, R.A.; Clarke, C.P.; McKay, W.J.; St Vincents Hospital, Fitzroy, VIC

1998-01-01

Full text: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG), as a metabolic tumour marker, has been proposed for staging of oncological disease. To determine its role in the mediastinal staging of lung cancer, a prospective comparison of FDG PET with surgery was performed in patients with suspected non-small cell lung carcinoma. The analysis group consists of 70 patients, 49 men and 21 women, mean age 64 yrs (range 41-83 yrs). The PET study was acquired on a Siemens 951/31R scanner over 3 bed positions, 45 minutes following 400MBq FDG. The emission scan was attenuation corrected using measured transmission data. The FDG PET were interpreted by a nuclear physician blinded to the clinical data and the results of the patients' CT scan. On PET, nodes were graded qualitatively on a 5 point scale with scores 4 or greater, positive for tumour involvement. Surgical specimens were obtained in all patients by thoracotomy or mediastinoscopy. The PET metabolic studies and pathology were mapped according to the American Thoracic Society nodal classification resulting in a total of 277 nodal stations evaluated. The PET studies analysed N2 or N3 tumour involvement by nodal station in comparison to histology of pathological specimens or direct visual assessment of the nodal stations at surgery. All patients had proven non-small cell lung carcinoma, except two, in whom, a tissue confirmation of the suspected diagnosis was not attained. PET excluded tumour in 237 of 246 nodal stations (specificity 96%). PET correctly identified 23 of 31 nodal stations with disease (sensitivity 74%). PET correctly staged 260 of 277 nodal stations (accuracy 94%) for disease. FDG PET is an accurate non-invasive functional imaging modality for the mediastinal staging of non-small cell lung cancer and has an important clinical role in the preoperative staging of lung cancer patients

Vocal fold immobility from a primary minor salivary gland small-cell carcinoma: case report.

Science.gov (United States)

Witt, Robert L; Wilson, Patrick A

2009-02-01

Small-cell carcinoma of a minor salivary gland is a rare and to the best of our knowledge previously unreported cause of vocal fold immobility. We describe the case of a 68-year-old woman who presented with hoarseness, dysphagia, and weight loss. Examination revealed left vocal fold immobility. She had no other obvious abnormality of the upper airway, neck, or skin. Computed tomography and magnetic resonance imaging demonstrated a 4-cm submucosal oropharyngeal mass with extension to the parapharyngeal space and involvement of the carotid sheath and the foramen ovale at the skull base; imaging also revealed cervical adenopathy. Fine-needle aspiration biopsy identified the mass as a small-cell carcinoma, a finding that was confirmed by immunohistochemistry. Extensive tumor invasion and multiple comorbidities precluded an aggressive management strategy, and the patient was treated palliatively. She died of her disease shortly after her diagnosis. Vocal fold immobility of unknown etiology mandates imaging from the skull base to the upper mediastinum.

Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease

DEFF Research Database (Denmark)

Almen, Sven; Granerus, Göran; Ström, Magnus

2007-01-01

Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. Methods......: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy; 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans...... was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and...

A small-molecule/cytokine combination enhances hematopoietic stem cell proliferation via inhibition of cell differentiation.

Science.gov (United States)

Wang, Lan; Guan, Xin; Wang, Huihui; Shen, Bin; Zhang, Yu; Ren, Zhihua; Ma, Yupo; Ding, Xinxin; Jiang, Yongping

2017-07-18

Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34 + cell expansion ex vivo. The extent of cell expansion and the immunophenotype of expanded cells were assessed through flow cytometry. The functional preservation of HSC stemness was confirmed by additional cell and molecular assays in vitro. Subsequently, the expanded cells were transplanted into sublethally irradiated NOD/SCID mice for the assessment of human cell viability and engraftment potential in vivo. Furthermore, the expression of several genes in the cell proliferation and differentiation pathways was analyzed through quantitative polymerase chain reaction (qPCR) during the process of CD34 + cell expansion. The SC cocktail supported the retention of the immunophenotype of hematopoietic stem/progenitor cells remarkably well, by yielding purities of 86.6 ± 11.2% for CD34 + cells and 76.2 ± 10.5% for CD34 + CD38 - cells, respectively, for a 7-day culture. On day 7, the enhancement of expansion of CD34 + cells and CD34 + CD38 - cells reached a maxima of 28.0 ± 5.5-fold and 27.9 ± 4.3-fold, respectively. The SC cocktail-expanded CD34 + cells preserved the characteristics of HSCs by effectively inhibiting their differentiation in vitro and retained the multilineage differentiation potential in primary and secondary in vivo murine xenotransplantation trials. Further gene expression analysis suggested that the small-molecule combination strengthened the ability of the cytokines to enhance the Notch

Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor.

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Emma E Vincent

Full Text Available Phase III trials of the anti-insulin-like growth factor-1 receptor (IGF1R antibody figitumumab in non-small cell lung cancer (NSCLC patients have been discontinued owing to lack of survival benefit. We investigated whether inhibition of the highly homologous insulin receptor (IR in addition to the IGF1R would be more effective than inhibition of the IGF1R alone at preventing the proliferation of NSCLC cells. Signalling through IGF1R and IR in the NSCLC cell lines A549 and Hcc193 was stimulated by a combination of IGF1, IGF2 and insulin. It was inhibited by antibodies that block ligand binding, αIR3 (IGF1R and IR47-9 (IR, and by the ATP-competitive small molecule tyrosine kinase inhibitors AZ12253801 and NVPAWD742 which inhibit both IGF1R and IR tyrosine kinases. The effect of inhibitors was determined by an anchorage-independent proliferation assay and by analysis of Akt phosphorylation. In Hcc193 cells the reduction in cell proliferation and Akt phosphorylation due to anti-IGF1R antibody was enhanced by antibody-mediated inhibition of the IR whereas in A549 cells, with a relatively low IR:IGF1R expression ratio, it was not. In each cell line proliferation and Akt phosphorylation were more effectively inhibited by AZ12253801 and NVPAWD742 than by combined αIR3 and IR47-9. When the IGF1R alone is inhibited, unencumbered signalling through the IR can contribute to continued NSCLC cell proliferation. We conclude that small molecule inhibitors targeting both the IR and IGF1R more effectively reduce NSCLC cell proliferation in a manner independent of the IR:IGF1R expression ratio, providing a therapeutic rationale for the treatment of this disease.

Incentives for Starting Small Companies Focused on Rare and Neglected Diseases.

Science.gov (United States)

Ekins, Sean; Wood, Jill

2016-04-01

Starting biotech or pharmaceutical companies is traditionally thought to be based around a scientist, their technology platform or a clinical candidate spun out from another company. Between us we have taken a different approach and formed two small early stage companies after initially leveraging the perspective of a parent with a child with a life-threatening rare disease. Phoenix Nest ( http://www.phoenixnestbiotech.com/ ) was co-founded to work on treatments for Sanfilippo syndrome a devastating neurodegenerative lysosomal storage disorder. In the space of just over 3 years we have built up collaborations with leading scientists in academia and industry and been awarded multiple NIH small business grants. The second company, Collaborations Pharmaceuticals Inc. ( http://www.collaborationspharma.com/ ) was founded to address some of the other 7000 or so rare diseases as well as neglected infectious diseases. The Rare Pediatric Disease Priority Review Voucher is likely the most important incentive for companies working on rare diseases with very small populations. This may also be partially responsible for the recent acquisitions of rare disease companies with late stage candidates. Lessons learned in the process of starting our companies are that rare disease parents or patients can readily partner with a scientist and fund research through NIH grants rather than venture capital or angel investors initially. This process may be slow so patience and perseverance is key. We would encourage other pharmaceutical scientists to meet rare disease parents, patients or advocates and work with them to further the science on their diseases and create a source of future drugs.

Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base

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A. Murinello

2010-07-01

Full Text Available Based on a case of gastric antral vascular ectasia (watermelon stomach that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma. Resumo: Baseados num caso de gastropatia antral com ectasia vascular (estômago em melancia associado a pericardite hemorrágica e a um carcinoma de pequenas células do pulmão com metástases ganglionares ao longo do mediastino e a um carcinoma pavimentocelular síncrono da base da língua, os autores fazem uma revisão dos aspectos clínicos, endoscópicos e histopatológicos deste tipo de gastropatia, da sua associação a outras doenças e das possibilidades terapêuticas actuais por via endoscópica. Referem-se igualmente as causas mais frequentes de pericardite hemorrágica, salientando-se a necessidade de esclarecer se o derrame é ou não de origem neoplásica. Não está referida na literatura a associação deste tipo de gastropatia ao carcinoma de pequenas células do pulmão nem ao carcinoma pavimento-celular da base da língua. A invasão extensa dos gânglios mediastínicos pelo carcinoma de pequenas células do pulmão é ocorrência frequente. Key-words: Gastric antral vascular ectasia, watermelon stomach, small cell lung carcinoma, oat cell lung carcinoma, squamous cell carcinoma of the base

Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

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Yu Cong

2017-04-01

Full Text Available Nipah virus (NiV is a paramyxovirus (genus Henipavirus that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM model following intratracheal (IT and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT and magnetic resonance imaging (MRI to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human

Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

DEFF Research Database (Denmark)

Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

1997-01-01

Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

A small nonhuman primate model for filovirus-induced disease.

Science.gov (United States)

Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L

2011-11-25

Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Copyright © 2011 Elsevier Inc. All rights reserved.

Kaempferol modulates the metastasis of human non-small cell lung cancer cells by inhibiting epithelial-mesenchymal transition

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Meng Hang

2015-06-01

Full Text Available The present study was done to determine whether kaempferol, a natural polyphenol of the flavonoid family, affects Epithelial-Mesenchymal Transition (EMT in non-small cell lung cancer cells. Kaempferol not only inhibited cancer cell proliferation and migration in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indispensible to cellular motility, invasiveness and metastasis. These results indicate that kaempferol suppresses non-small cell lung cancer migration by modulating the expression of EMT proteins. Therefore, kaempferol may be useful as a potential anticancer agent for non-small cell lung cancer.

Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

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Sonia Gon

2013-01-01

Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

DEFF Research Database (Denmark)

Hall, Vanessa Jane

2016-01-01

Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

The Role of Innate and Adaptive Immune Cells in the Immunopathogenesis of Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Nurwidya, Fariz; Damayanti, Triya; Yunus, Faisal

2016-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive inflammatory disease of the airways and lungs that results in limitations of continuous airflow and is caused by exposure to noxious gasses and particles. A major cause of morbidity and mortality in adults, COPD is a complex disease pathologically mediated by many inflammatory pathways. Macrophages, neutrophils, dendritic cells, and CD8+ T-lymphocytes are the key inflammatory cells involved in COPD. Recently, the non-coding small RNA, micro-RNA, have also been intensively investigated and evidence suggest that it plays a role in the pathogenesis of COPD. Here, we discuss the accumulated evidence that has since revealed the role of each inflammatory cell and their involvement in the immunopathogenesis of COPD. Mechanisms of steroid resistance in COPD will also be briefly discussed.

Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

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Ganapati V Hegde

Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

Clinical evaluation of radio and chemotherapy for small cell carcinoma of the lung

International Nuclear Information System (INIS)

Hirota, Saeko; Imajo, Yoshinari; Gose, Kyuhei

1985-01-01

Sixty-nine patients with small cell carcinoma of the lung were treated at Kobe University Hospital from January 1972 to August 1982. The results of treatment were as follows. i) Five year survival rate was greater for stage III cases than for stage IV cases (p < 0.05). ii) Differences of therapeutic effects between two periods, before and after 1977, were evaluated. Cases with stage III small cell carcinoma showed a tendency forwards improved survival rate after 1977, however, no significant difference was seen with stage IV cases before and after 1977. iii) In terms of what therapy improved the survival rate, among stage III patients, 7 were treated with combination chemotherapy and radiotherapy (group A), 14 were treated with single agent chemotherapy and radiotherapy (group B) and 4 with only radiotherapy. Among stage IV cases, 9 belonged to group A and 20 to group B. Better survival rate was seen in group A compared with group B with regard to stage III, although it did not quite reach statistical significance (0.05 < p < 0.1), whereas no significant survival difference was seen with stage IV disease. iv) Significant differences of survival rate were seen between CR (complete remission) and PR (partial remission) patients (p < 0.05) and between CR and PD (progressive disease) patients (p < 0.01), as classified by preliminary therapeutic effects. v) No significant difference in survival rate was noted among the histologic subtypes. (author)

Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

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Mickaël J Ploquin

2016-08-01

Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

Cell Therapy in Cardiovascular Disease

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Hoda Madani

2014-05-01

Full Text Available   Recently, cell therapy has sparked a revolution in ischemic heart disease that will in the future help clinicians to cure patients. Earlier investigations in animal models and clinical trials have suggested that positive paracrine effects such as neoangiogenesis and anti-apoptotic can improve myocardial function. In this regard the Royan cell therapy center designed a few trials in collaboration with multi hospitals such as Baqiyatallah, Shahid Lavasani, Tehran Heart Center, Shahid rajaee, Masih daneshvari, Imam Reza, Razavi and Sasan from 2006. Their results were interesting. However, cardiac stem cell therapy still faces great challenges in optimizing the treatment of patients. Keyword: Cardiovascular disease, Cell therapy.  

The composition of T cell subtypes in duodenal biopsies are altered in coeliac disease patients

DEFF Research Database (Denmark)

Vagner Steenholt, Janni; Nielsen, Christian; Baudewijn, Leen

2017-01-01

One of the hallmarks of Celiac disease (CD) is intraepithelial lymphocytosis in the small intestine. Until now, investigations to characterize the T cell subpopulations within the epithelial layer have not discriminated between the heterodimeric co-receptor molecule, CD8αβ, and the possibly...

Usefulness of MR imaging for diseases of the small intestine: comparison with CT

Energy Technology Data Exchange (ETDEWEB)

Kim, Ji Hoon; Ha, Hyun Kwon; Sohn, Min Jae; Shin, Byung Suck; Lee, Young Suk; Chung, Soo Yoon; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Ulsan University College of Medicine, Seoul (Korea, Republic of)

2000-03-01

To evaluate the usefulness of MR imaging for diseases of the small intestine, emphasizing a comparison with CT. Thirty-four patients who underwent both CT and MR imaging using FLASH 2D and HASTE sequences were analyzed. All patients had various small bowel diseases with variable association of peritoneal lesions. We compared the detectabilities of CT and MR imaging using different MR pulse sequences. The capability for analyzing the characteristics of small intestinal disease was also compared. MR imaging was nearly equal to CT for detecting intraluminal or peritoneal masses, lesions in the bowel and mesentery, and small bowel obstruction, but was definitely inferior for detecting omental lesions. The most successful MR imaging sequence was HASTE for demonstrating bowel wall thickening, coronal FLASH 2D for mesenteric lesions, and axial FLASH 2D for omental lesions. MR imaging yielded greater information than CT in six of 12 inflammatory bowel diseases, while it was equal to CT in six of seven neoplasms and inferior in five of seven mesenteric ischemia. In determining the primary causes of 15 intestinal obstructions, MR imaging was correct in 11 (73%) and CT in nine (60%) patients. MR imaging can serve as an alternative diagnostic tool for patients with suspected inflammatory bowel disease, small intestinal neoplasm or obstruction.

Asthma in Sickle Cell Disease: Implications for Treatment

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Kathryn Blake

2011-01-01

Full Text Available Objective. To review issues related to asthma in sickle cell disease and management strategies. Data Source. A systematic review of pertinent original research publications, reviews, and editorials was undertaken using MEDLlNE, the Cochrane Library databases, and CINAHL from 1947 to November 2010. Search terms were [asthma] and [sickle cell disease]. Additional publications considered relevant to the sickle cell disease population of patients were identified; search terms included [sickle cell disease] combined with [acetaminophen], [pain medications], [vitamin D], [beta agonists], [exhaled nitric oxide], and [corticosteroids]. Results. The reported prevalence of asthma in children with sickle cell disease varies from 2% to approximately 50%. Having asthma increases the risk for developing acute chest syndrome , death, or painful episodes compared to having sickle cell disease without asthma. Asthma and sickle cell may be linked by impaired nitric oxide regulation, excessive production of leukotrienes, insufficient levels of Vitamin D, and exposure to acetaminophen in early life. Treatment of sickle cell patients includes using commonly prescribed asthma medications; specific considerations are suggested to ensure safety in the sickle cell population. Conclusion. Prospective controlled trials of drug treatment for asthma in patients who have both sickle cell disease and asthma are urgently needed.

Adhesive small bowel obstruction due to pelvic inflammatory disease: A case report

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Razan A Al-Ghassab

2018-01-01

Full Text Available We report a rare case of a 32-year-old woman with adhesive small bowel obstruction due to pelvic inflammatory disease. She had no history of abdominal surgery, gynecological complaints or constitutional symptoms of chronic illness. The diagnosis was based on the laparoscopic findings of small bowel adhesions, free peritoneal fluid, “violin string” adhesions of Fitz-Hugh–Curtis syndrome and left hydrosalpinx. Laparoscopic adhesiolysis was performed successfully, and the patient had an uneventful postoperative course. The authors conclude that pelvic inflammatory disease should be included as a cause of adhesive small bowel obstruction in sexually active young women with no history of abdominal surgery or constitutional symptoms of chronic disease. When performed by experienced surgeons, laparoscopy in such patients is feasible and safe.

Factors associated with disease-specific survival of patients with non-small cell lung cancer.

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Souza, Mirian Carvalho de; Cruz, Oswaldo Gonçalves; Vasconcelos, Ana Glória Godoi

2016-01-01

Lung cancer is a global public health problem and is associated with high mortality. Lung cancer could be largely avoided by reducing the prevalence of smoking. The objective of this study was to analyze the effects of social, behavioral, and clinical factors on the survival time of patients with non-small cell lung cancer treated at Cancer Hospital I of the José Alencar Gomes da Silva National Cancer Institute, located in the city of Rio de Janeiro, Brazil, between 2000 and 2003. This was a retrospective hospital cohort study involving 1,194 patients. The 60-month disease-specific survival probabilities were calculated with the Kaplan-Meier method for three stage groups. The importance of the studied factors was assessed with a hierarchical theoretical model after adjustment by Cox multiple regression. The estimated 60-month specific-disease lethality rate was 86.0%. The 60-month disease-specific survival probability ranged from 25.0% (stages I/II) to 2.5% (stage IV). The performance status, the intention to treat, and the initial treatment modality were the major prognostic factors identified in the study population. In this cohort of patients, the disease-specific survival probabilities were extremely low. We identified no factors that could be modified after the diagnosis in order to improve survival. Primary prevention, such as reducing the prevalence of smoking, is still the best method to reduce the number of people who will suffer the consequences of lung cancer. O câncer de pulmão é um problema de saúde pública global e é associado a elevada mortalidade. Ele poderia ser evitado em grande parte com a redução da prevalência do tabagismo. O objetivo deste estudo foi analisar os efeitos de fatores sociais, comportamentais e clínicos sobre o tempo de sobrevida de pacientes com câncer de pulmão de células não pequenas atendidos, entre 2000 e 2003, no Hospital do Câncer I do Instituto Nacional de Câncer José Alencar Gomes da Silva, localizado na

Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach.

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Brenner, Baruch; Tang, Laura H; Shia, Jinruh; Klimstra, David S; Kelsen, David P

2007-02-01

Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach.

CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

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Diana Rosa Fernández Ruiz

2017-02-01

Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

Stricturoplasty-a bowel-sparing option for long segment small bowel Crohn's disease.

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Limmer, Alexandra M; Koh, Hoey C; Gilmore, Andrew

2017-08-01

Stricturoplasty is a surgical option for management of severe stricturing Crohn's disease of the small bowel. It avoids the need for small bowel resection and the associated metabolic complications. This report contrasts the indications and technical aspects of two different stricturoplasty techniques. Case 1 describes an extensive Michelassi (side-to-side isoperistaltic) stricturoplasty performed for a 100 cm segment of diseased small bowel in a 45-year-old patient. Case 2 describes the performance of 12 Heineke-Mikulicz stricturoplasties in a 23-year-old patient with multiple short fibrotic strictures.

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

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Shu Yong-Qian

2010-09-01

Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

Stem cell therapy for ischemic heart diseases.

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Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

2017-01-01

Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Treatment of initially metastatic small-cell lung cancer

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Kohutek, F.; Bystricky, B.; Tamasova, M.

2013-01-01

Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

Prognosis method to predict small-sized breast cancer affected by fibrocystic disease

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S. A. Velichko

2017-01-01

Full Text Available The purpose of the study is to develop an effective radiological symptom-complex of small-sized breast cancer affected by fibrocystic breast disease by using multivariate statistical methods.Materials and methods. Radiological findings of small-sized breast cancer affected by fibrocystic mastopathy were analyzed in 100 patients with histologically verified diagnosis.Results. It was revealed that the conventional approach to the analysis of mammograms based on the detection of the primary, secondary and indirect mammographic signs of small-sized breast cancer is not effective enough - the sensitivity of mammography is only 62%. Fibrocystic disease and moderate-to-severe sclerosing adenosis make small-sized breast cancer hard to visualize by mammography. The detailed analysis of mammograms allowed us to identify the additional manifestations of small-sized breast cancer affected by mastopathy. The computer program allowing us to evaluate the risk of small-size breast cancer and the diagnostic algorithm for detecting small size breast cancer with sensitivity of 92% were developed. 

Isolation and characterization of NIH 3T3 cells expressing polyomavirus small T antigen

International Nuclear Information System (INIS)

Noda, T.; Satake, M.; Robins, T.; Ito, Y.

1986-01-01

The polyomavirus small T-antigen gene, together with the polyomavirus promoter, was inserted into retrovirus vector pGV16 which contains the Moloney sarcoma virus long terminal repeat and neomycin resistance gene driven by the simian virus 40 promoter. This expression vector, pGVST, was packaged into retrovirus particles by transfection of PSI2 cells which harbor packaging-defective murine retrovirus genome. NIH 3T3 cells were infected by this replication-defective retrovirus containing pGVST. Of the 15 G418-resistant cell clones, 8 express small T antigen at various levels as revealed by immunoprecipitation. A cellular protein with an apparent molecular weight of about 32,000 coprecipitates with small T antigen. Immunofluorescent staining shows that small T antigen is mainly present in the nuclei. Morphologically, cells expressing small T antigen are indistinguishable from parental NIH 3T3 cells and have a microfilament pattern similar to that in parental NIH 3T3 cells. Cells expressing small T antigen form a flat monolayer but continue to grow beyond the saturation density observed for parental NIH 3T3 cells and eventually come off the culture plate as a result of overconfluency. There is some correlation between the level of expression of small T antigen and the growth rate of the cells. Small T-antigen-expressing cells form small colonies in soft agar. However, the proportion of cells which form these small colonies is rather small. A clone of these cells tested did not form tumors in nude mice within 3 months after inoculation of 10 6 cells per animal. Thus, present studies establish that the small T antigen of polyomavirus is a second nucleus-localized transforming gene product of the virus (the first one being large T antigen) and by itself has a function which is to stimulate the growth of NIH 3T3 cells beyond their saturation density in monolayer culture

Feasibility of omitting clinical target volume for limited-disease small cell lung cancer treated with chemotherapy and intensity-modulated radiotherapy

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Cai, Shuhua; Shi, Anhui; Yu, Rong; Zhu, Guangying

2014-01-01

To analyze the feasibility of omitting clinical target volume (CTV) for limited small cell lung cancer treated with chemotherapy and intensity modulated radiotherapy. 89 patients were treated from January 1, 2008 to August 31, 2011, 54 cases were irradiated with target volume without CTV, and 35 cases were irradiated with CTV. Both arms were irradiated post chemotherapy tumor extent and omitted elective nodal irradiation; dose prescription was 95% PTV56-63 Gy/28-35 F/5.6-7 weeks. In the arm without CTV and arm with CTV, the local relapse rates were 16.7% and 17.1% (p = 0.586) respectively. In the arm without CTV, of the 9 patients with local relapse, 6 recurred in-field, 2 recurred in margin, 1 recurred out of field. In the arm with CTV, of the 6 patients with local relapse, 4 recurred in-field, 1 recurred in margin, 1 recurred out of field. The distant metastases rates were 42.6% and 51.4% (p = 0.274) respectively. Grade 3-4 hematological toxicity and radiation esophagitis had no statistically significant, but grade 3-4 radiation pneumonia was observed in only 7.4% in the arm without CTV, compared 22.9% in the arm with CTV (p = 0.040). The median survival in the arm without CTV had not reached, compared with 38 months in the with CTV arm. The l- years, 2- years, 3- years survival rates of the arm without CTV and the arm with CTV were 81.0%, 66.2%, 61.5% and 88.6%, 61.7%, 56.6% (p = 0.517). The multivariate analysis indicated that the distant metastases (p = 0.000) and PCI factor (p = 0.004) were significantly related to overall survival. Target delineation omitting CTV for limited-disease small cell lung cancer received IMRT was feasible. The distant metastases and PCI factor were significantly related to overall survival

Identification of a distinct small cell population from human bone marrow reveals its multipotency in vivo and in vitro.

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James Wang

Full Text Available Small stem cells, such as spore-like cells, blastomere-like stem cells (BLSCs, and very-small embryonic-like stem cells (VSELs have been described in recent studies, although their multipotency in human tissues has not yet been confirmed. Here, we report the discovery of adult multipotent stem cells derived from human bone marrow, which we call StemBios (SB cells. These isolated SB cells are smaller than 6 ìm and are DAPI+ and Lgr5+ (Leucine-Rich Repeat Containing G Protein-Coupled Receptor 5. Because Lgr5 has been characterized as a stem cell marker in the intestine, we hypothesized that SB cells may have a similar function. In vivo cell tracking assays confirmed that SB cells give rise to three types of cells, and in vitro studies demonstrated that SB cells cultured in proprietary media are able to grow to 6-25 ìm in size. Once the SB cells have attached to the wells, they differentiate into different cell lineages upon exposure to specific differentiation media. We are the first to demonstrate that stem cells smaller than 6 ìm can differentiate both in vivo and in vitro. In the future, we hope that SB cells will be used therapeutically to cure degenerative diseases.

Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

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Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

2015-10-01

The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

PKC 412 sensitizes U1810 non-small cell lung cancer cells to DNA damage

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Hemstroem, Therese H.; Joseph, Bertrand; Schulte, Gunnar; Lewensohn, Rolf; Zhivotovsky, Boris

2005-01-01

Non-small cell lung carcinoma (NSCLC) is characterized by resistance to drug-induced apoptosis, which might explain the survival of lung cancer cells following treatment. Recently we have shown that the broad-range kinase inhibitor staurosporine (STS) reactivates the apoptotic machinery in U1810 NSCLC cells [Joseph et al., Oncogene 21 (2002) 65]. Lately, several STS analogs that are more specific in kinase inhibition have been suggested for tumor treatment. In this study the apoptosis-inducing ability of the STS analogs PKC 412 and Ro 31-8220 used alone or in combination with DNA-damaging agents in U1810 cells was investigated. In these cells Ro 31-8220 neither induced apoptosis when used alone, nor sensitized cells to etoposide treatment. PKC 412 as a single agent induced death of a small number of U1810 cells, whereas it efficiently triggered a dose- and time-dependent apoptosis in U1285 small cell lung carcinoma cells. In both cell types PKC 412 triggered release of mitochondrial proteins followed by caspase activation. However, concomitant activation of a caspase-independent pathway was essential to kill NSCLC cells. Importantly, PKC 412 was able to sensitize etoposide- and radiation-induced death of U1810 cells. The best sensitization was achieved when PKC 412 was administered 24 h after treatments. In U1810 cells, Ro 31-8220 decreased PMA-induced ERK phosphorylation as efficiently as PKC 412, indicating that the failure of Ro 31-8220 to induce apoptosis was not due to weaker inhibition of conventional and novel PKC isoforms. However, Ro 31-8220 increased the basal level of ERK and Akt phosphorylation in both cell lines, whereas Akt phosphorylation was suppressed in the U1810 cells, which might influence apoptosis. These results suggest that PKC 412 could be a useful tool in increasing the efficiency of therapy of NSCLC

Toward precision medicine with next-generation EGFR inhibitors in non-small-cell lung cancer

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Yap TA

2014-09-01

Full Text Available Timothy A Yap,1,2 Sanjay Popat1,3 1Lung Cancer Unit, Department of Medicine, The Royal Marsden National Health Service Foundation Trust, London, United Kingdom; 2The Institute of Cancer Research, London, United Kingdom; 3National Heart and Lung Institute, London, United Kingdom Abstract: The use of genomics to discover novel targets and biomarkers has placed the field of oncology at the forefront of precision medicine. First-generation epidermal growth factor receptor (EGFR inhibitors have transformed the therapeutic landscape of EGFR mutant non-small-cell lung carcinoma through the genetic stratification of tumors from patients with this disease. Somatic EGFR mutations in lung adenocarcinoma are now well established as predictive biomarkers of response and resistance to small-molecule EGFR inhibitors. Despite early patient benefit, primary resistance and subsequent tumor progression to first-generation EGFR inhibitors are seen in 10%–30% of patients with EGFR mutant non-small-cell lung carcinoma. Acquired drug resistance is also inevitable, with patients developing disease progression after only 10–13 months of antitumor therapy. This review details strategies pursued in circumventing T790M-mediated drug resistance to EGFR inhibitors, which is the most common mechanism of acquired resistance, and focuses on the clinical development of second-generation EGFR inhibitors, exemplified by afatinib (BIBW2992. We discuss the rationale, mechanism of action, clinical efficacy, and toxicity profile of afatinib, including the LUX-Lung studies. We also discuss the emergence of third-generation irreversible mutant-selective inhibitors of EGFR and envision the future management of EGFR mutant lung adenocarcinoma. Keywords: afatinib, EGFR, erlotinib, gefitinib, LUX-Lung, NSCLC 

A Case Report of NK-Cell Lymphoproliferative Disease With a Wide Involvement of Digestive Tract Develop Into Epstein-Barr Virus Associated NK/T Cell Lymphoma in an Immunocompetent Patient.

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Chen, Haotian; Zhang, Yu; Jiang, Zhinong; Zhou, Wei; Cao, Qian

2016-03-01

Epstein-Barr virus (EBV) plays an important role in various diseases. EBV-associated lymphoproliferative disease (LPD) is a rare disease with a canceration tendency. It is difficult to differentiate LPD with involvement of digestive tract from Crohn disease due to similar clinical and endoscopic manifestations. We present a case report of multiple ulcers with esophagus, small bowel and the entire colon involved, proved to be NK-Cell LPD, developed into EBV-associated NK/T Cell lymphoma, in an immunocompetent man who was initially misdiagnosed as Crohn disease.This report underscores that intestinal ulcers should be cautiously diagnosed, for it sometimes could be a precancerous lesion.

Relation between small airways disease and parenchymal destruction in surgical lung specimens.

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Willems, L N; Kramps, J A; Stijnen, T; Sterk, P J; Weening, J J; Dijkman, J H

1990-01-01

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema. PMID:2315880

Evaluation of EML4-ALK Fusion Proteins in Non–Small Cell Lung Cancer Using Small Molecule Inhibitors

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Yongjun Li

2011-01-01

Full Text Available The echinoderm microtubule–associated protein-like 4–anaplastic lymphoma kinase (EML4-ALK fusion gene resulting from an inversion within chromosome 2p occurs in approximately 5% of non–small cell lung cancer and is mu-tually exclusive with Ras and EGFR mutations. In this study, we have used a potent and selective ALK small molecule inhibitor, NPV-TAE684, to assess the oncogenic role of EML4-ALK in non–small cell lung cancer (NSCLC. We show here that TAE684 inhibits proliferation and induces cell cycle arrest, apoptosis, and tumor regression in two NSCLC models that harbor EML4-ALK fusions. TAE684 inhibits EML4-ALK activation and its downstream signaling including ERK, AKT, and STAT3. We used microarray analysis to carry out targeted pathway studies of gene expression changes in H2228 NSCLC xenograft model after TAE684 treatment and identified a gene signature of EML4-ALK inhibition. The gene signature represents 1210 known human genes, and the top biologic processes represented by these genes are cell cycle, DNA synthesis, cell proliferation, and cell death. We also compared the effect of TAE684 with PF2341066, a c-Met and ALK small molecule inhibitor currently in clinical trial in cancers harboring ALK fusions, and demonstrated that TAE684 is a much more potent inhibitor of EML4-ALK. Our data demonstrate that EML4-ALK plays an important role in the pathogenesis of a subset of NSCLC and provides insight into the mech-anism of EML4-ALK inhibition by a small molecule inhibitor.

Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance.

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Lobb, Richard J; van Amerongen, Rosa; Wiegmans, Adrian; Ham, Sunyoung; Larsen, Jill E; Möller, Andreas

2017-08-01

Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited treatment options and poor patient survival. NSCLCs are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known. We hypothesised that small extracellular vesicles, exosomes, secreted by mesenchymal NSCLC cells could potentially transfer the chemoresistance phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we used a unique human bronchial epithelial cell (HBEC) model in which the parental cells were transformed from an epithelial to mesenchymal phenotype by introducing oncogenic alterations common in NSCLC. We found that exosomes derived from the oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription factor, in the recipient cells. Additionally, we demonstrate that exosomes from mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a potential mechanism for the induction of a mesenchymal phenotype in recipient cells. Together, this work demonstrates for the first time that exosomes derived from mesenchymal, oncogenically transformed lung cells can transfer chemoresistance and mesenchymal phenotypes to recipient cells, likely via the transfer of ZEB1 mRNA in exosomes. © 2017 UICC.

The emerging role of mast cells in liver disease.

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Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

Retrospctive studies of small ruminant diseases diagnosed at the ...

African Journals Online (AJOL)

Retrospctive studies of small ruminant diseases diagnosed at the Veterinary Teaching Hospital, University of Agriculture, Makurdi, Nigeria. J.W. Jatfa, A.Y. Adenkola, I Victor, A Kisani, S.S. Adamu, P.A. Onyeyili ...

Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

International Nuclear Information System (INIS)

Muggia, F.M.; Blum, R.H.; Foreman, J.D.

1984-01-01

Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages

Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies

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Muggia, F.M. (NYU Medical Center, New York); Blum, R.H.; Foreman, J.D.

1984-01-01

Lung cancer treatment has been considered to have made little progress except for advances in small cell carcinoma. For other histologies an attitude of nihilism has prevailed principally because of lack of effective systemic therapy and of no persuasive evidence that results could be improved by combined modality treatment. On the other hand, favorable results from surgery are confined to a small percent of all patients with this disease. This review emphasizes possibilities for progress in evolving new therapeutic strategies. Although improvement over other systemic therapies is modest, cisplatin-containing regimens yield more consistent response rates and apparent survival advantage relative to single agents. Immediate progression occurs in the minority of patients. In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications. These features encourage the evolution of strategies which begin with chemotherapy and then use consolidation with radiation therapy. Clinical trials using these and newer strategies must be instituted if progress is to occur in the treatment of non-small cell histologies at all stages.

Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Kim, Myung Soo; Lee, Ji Hae; Ha, Bo Ram; Lee, Re Na

2011-01-01

Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ≥2 radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ≥2 radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), V20, V30, V40, MLDipsi, V20ipsi, V30ipsi, and V40ipsi were associated with grade ≥2 radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ≥2 radiation pneumonitis. Concurrent

Postoperative Radiation Therapy for Non-Small Cell Lung Cancer and Thymic Malignancies

International Nuclear Information System (INIS)

Gomez, Daniel R.; Komaki, Ritsuko

2012-01-01

For many thoracic malignancies, surgery, when feasible, is the preferred upfront modality for local control. However, adjuvant radiation plays an important role in minimizing the risk of locoregional recurrence. Tumors in the thoracic category include certain subgroups of non-small cell lung cancer (NSCLC) as well as thymic malignancies. The indications, radiation doses, and treatment fields vary amongst subtypes of thoracic tumors, as does the level of data supporting the use of radiation. For example, in the setting of NSCLC, postoperative radiation is typically reserved for close/positive margins or N2/N3 disease, although such diseases as superior sulcus tumors present unique cases in which the role of neoadjuvant vs. adjuvant treatment is still being elucidated. In contrast, for thymic malignancies, postoperative radiation therapy is often used for initially resected Masaoka stage III or higher disease, with its use for stage II disease remaining controversial. This review provides an overview of postoperative radiation therapy for thoracic tumors, with a separate focus on superior sulcus tumors and thymoma, including a discussion of acceptable radiation approaches and an assessment of the current controversies involved in its use

Small cell carcinoma of the urinary bladder without gross hematuria: a case report.

Science.gov (United States)

Huang, Wanqiu; Luan, Yang; Jin, Lu; Wang, Tao; Chen, Ruibao; Liu, Zheng; Chen, Zhiqiang; Lan, Ruzhu

2015-09-01

Small cell carcinoma of the urinary bladder (SCCB) is a rare and aggressive form of bladder cancer with poor prognosis. Hematuria is the main symptom of this malignancy, and most patients have a history of smoking. The disease incidence of malignant bladder tumors in China is approximately 0.74%. Early and accurate diagnosis of SCCB can ensure timely and appropriate treatment of this malignant disease. Oncologic surgery is the standard treatment; however, it may not be a curative approach. Chemotherapy and/or radiotherapy should be performed following surgical removal. This case report describes a patient with a single neoplasm diagnosed as SCCB that arose because of recurrence of bladder cancer after bladder tumor resection. In contrast to previously reported cases, this patient had no gross hematuria and no history of smoking.

The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

International Nuclear Information System (INIS)

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.

2012-01-01

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

[Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

Science.gov (United States)

Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

2013-05-01

Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

MicroRNA-944 Affects Cell Growth by Targeting EPHA7 in Non-Small Cell Lung Cancer

OpenAIRE

Minxia Liu; Kecheng Zhou; Yi Cao

2016-01-01

MicroRNAs (miRNAs) have critical roles in lung tumorigenesis and development. To determine aberrantly expressed miRNAs involved in non-small cell lung cancer (NSCLC) and investigate pathophysiological functions and mechanisms, we firstly carried out small RNA deep sequencing in NSCLC cell lines (EPLC-32M1, A549 and 801D) and a human immortalized cell line 16HBE, we then studied miRNA function by cell proliferation and apoptosis. cDNA microarray, luciferase reporter assay and miRNA transfectio...

Investigation of stroke in sickle cell disease by 1H nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Wang, Z.; Bogdan, A.R.; Zimmermann, R.A.; Gusnard, D.A.; Leigh, J.S.; Ohene-Frempong, K.

1992-01-01

Localized proton nuclear magnetic resonance spectroscopy (MRS), obtained with stimulated echo and spin echo sequences, MR imaging (MRI) and MR angiography (MRA) were used to study the brain in 13 children and adolescents with sickle cell disease. Regions of interest (ROI) studied by MRS included regions appearing normal on MRI as well as regions showing complications of sickle cell disease, including focal deep white matter areas of high signal intensity (deep white matter ischemia, DWMI) seen on long TR images, focal atropic brain areas, and infarcts. The findings in these studies are summarized as follows: Normal-appearing regions on MRI have normal MRS. In ROI including small areas of DWMI, lactate elevation was not detected, but the levels of N-acetyl-aspartate (NAA) appeared slightly elevated. In areas of DWMI 1-2 cm in size, reduced blood flow could be seen on MRA and lactate elevation could be detected with MRS. When blood flow to a DWMI region was normal, NAA was reduced and there was little lactate elevation, as cell death had already occurred. ROI consisting of atrophic tissue had reduced NAA levels but total creatine levels were not changed. Sometimes lipids, presumably from broken cell membrane, could be detected. In regions of past massive stroke, all metabolites were absent except for small amounts of lactate or lipids. (orig.)

Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy

International Nuclear Information System (INIS)

Roengvoraphoj, Olarn; Eze, Chukwuka; Niyazi, Maximilian; Li, Minglun; Belka, Claus; Manapov, Farkhad; Hildebrandt, Guido; Fietkau, Rainer

2017-01-01

Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear. Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed. Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10-22) and 14 (95% CI 10-18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08-1.92). In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure. (orig.) [de

Definitive Radiotherapy of Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lee, Jong Young; Park, Kyung Ran

1995-01-01

Purpose : The effect of dose escalation of up to 6500 cGy on local control and survival was investigated in locally advanced non-small cell lung cancer. Materials and Methods : Ninety eight patients with biopsy-proven unresectable non-small cell lung cancer without distant metastases or medically inoperable patients with lower-stage were treated with definitive radiotherapy alone. Group A were treated by thoracic irradiation, 6000 cGy or less in total tumor dose with daily fractions of 180 to 200 cGy: and group B was treated with 6500 cGy of same daily fractions. Results : The actuarial overall survival rate for the entire group was 54% at 1 year, 26.6% at 2 years and 16.4% at 3 years with a median survival time of 13 months. Statistically significant prognostic factors that affect survival rate were stage and N-stage. However, no improvement in local control and survival has been seen with higher dose radiotherapy(group B). Conclusion : Dose escalation of up to 6500 cGy was no effect on local control and survival rate. To increase the survival rate of non-small cell lung cancer hyperfractionated radiotherapy or concurrent chemoradiotherapy should be considered

The Prognosis of Small Cell Lung Cancer in Patients with Pulmonary Fibrosis.

Science.gov (United States)

Matsumoto, Yoko; Ohara, Sayaka; Furukawa, Ryutaro; Usui, Kazuhiro

2017-10-01

The purpose of this study was to assess the prognosis of small cell lung cancer (SCLC) based on the underlying pulmonary disease. A total of 204 patients with SCLC were reviewed and categorized into three groups: normal, emphysema and fibrosis. The median overall survival duration (OS) in patients with normal lungs (n=57), with emphysema (n=105) and fibrosis (n=42) was 21.3, 16.4 and 10.8 months (p=0.063). In limited-stage disease (LD), the median OS in patients with fibrosis (7.4 months) was shorter than normal (52.7 months) or emphysema patients (26.4 months) (p=0.034). In extensive-stage disease (ED), the median OS in patients with fibrosis (12.7 months) was not significantly different from normal (11.4 months) or emphysema patients (13.5 months) (p=0.600). Patients with fibrosis had a poorer prognosis than normal or emphysema patients in LD-SCLC, but the coexistence of pulmonary fibrosis did not affect the prognostic outcomes in ED-SCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

DEFF Research Database (Denmark)

Christensen, Camilla L; Kwiatkowski, Nicholas; Abraham, Brian J

2014-01-01

Small cell lung cancer (SCLC) is an aggressive disease with high mortality, and the identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library, we observe that SCLC is sensitive...... to transcription-targeting drugs, in particular to THZ1, a recently identified covalent inhibitor of cyclin-dependent kinase 7. We find that expression of super-enhancer-associated transcription factor genes, including MYC family proto-oncogenes and neuroendocrine lineage-specific factors, is highly vulnerability...

Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement.

Science.gov (United States)

Di Foggia, Valentina; Makwana, Priyanka; Ali, Robin R; Sowden, Jane C

2016-06-01

Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patient-specific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

NARCIS (Netherlands)

De Guio, F. (François); Jouvent, E. (Eric); G.J. Biessels (Geert Jan); S.E. Black (Sandra); C. Brayne (Carol); C. Chen (Christopher); C. Cordonnier (Charlotte); H.F. de Leeuw (Frank); C. Kubisch (Christian); Doubal, F. (Fergus); Duering, M. (Marco); C. Dufouil (Carole); Duzel, E. (Emrah); F. Fazekas (Franz); V. Hachinski (Vladimir); M.K. Ikram (Kamran); J. Linn (Jennifer); P.M. Matthews (P.); B. Mazoyer (Bernard); Mok, V. (Vincent); B. Norrving (Bo); O'Brien, J.T. (John T.); Pantoni, L. (Leonardo); S. Ropele (Stefan); P.S. Sachdev (Perminder); R. Schmidt (Reinhold); S. Seshadri (Sudha); E.E. Smith (Eric); L.A. Sposato (Luciano A); B.C.M. Stephan; Swartz, R.H. (Richard H.); C. Tzourio (Christophe); M.A. van Buchem (Mark); A. van der Lugt (Aad); R.J. van Oostenbrugge (Robert); M.W. Vernooij (Meike); Viswanathan, A. (Anand); D.J. Werring (David); Wollenweber, F. (Frank); J.M. Wardlaw (J.); Chabriat, H. (Hugues)

2016-01-01

textabstractBrain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility

Similar Responses of Intestinal T Cells From Untreated Children and Adults With Celiac Disease to Deamidated Gluten Epitopes.

Science.gov (United States)

Ráki, Melinda; Dahal-Koirala, Shiva; Yu, Hao; Korponay-Szabó, Ilma R; Gyimesi, Judit; Castillejo, Gemma; Jahnsen, Jørgen; Qiao, Shuo-Wang; Sollid, Ludvig M

2017-09-01

Celiac disease is a chronic small intestinal inflammatory disorder mediated by an immune response to gluten peptides in genetically susceptible individuals. Celiac disease is often diagnosed in early childhood, but some patients receive a diagnosis late in life. It is uncertain whether pediatric celiac disease is distinct from adult celiac disease. It has been proposed that gluten-reactive T cells in children recognize deamidated and native gluten epitopes, whereas T cells from adults only recognize deamidated gluten peptides. We studied the repertoire of gluten epitopes recognized by T cells from children and adults. We examined T-cell responses against gluten by generating T-cell lines and T-cell clones from intestinal biopsies of adults and children and tested proliferative response to various gluten peptides. We analyzed T cells from 14 children (2-5 years old) at high risk for celiac disease who were followed for celiac disease development. We also analyzed T cells from 6 adults (26-55 years old) with untreated celiac disease. All children and adults were positive for HLA-DQ2.5. Biopsies were incubated with gluten digested with chymotrypsin (modified or unmodified by the enzyme transglutaminase 2) or the peptic-tryptic digest of gliadin (in native and deamidated forms) before T-cell collection. Levels of T-cell responses were higher to deamidated gluten than to native gluten in children and adults. T cells from children and adults each reacted to multiple gluten epitopes. Several T-cell clones were cross-reactive, especially clones that recognized epitopes from γ-and ω-gliadin. About half of the generated T-cell clones from children and adults reacted to unknown epitopes. T-cell responses to different gluten peptides appear to be similar between adults and children at the time of diagnosis of celiac disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Parikh, Ravi B.; Cronin, Angel M.; Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M.; Lo, Peter C.; Baldini, Elizabeth H.; Johnson, Bruce E.; Chen, Aileen B.

2014-01-01

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients

Definitive Primary Therapy in Patients Presenting With Oligometastatic Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Parikh, Ravi B. [Harvard Medical School, Boston, Massachusetts (United States); Cronin, Angel M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Kozono, David E.; Oxnard, Geoffrey R.; Mak, Raymond H.; Jackman, David M. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Lo, Peter C. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Baldini, Elizabeth H.; Johnson, Bruce E. [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Aileen B., E-mail: achen@lroc.harvard.edu [Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2014-07-15

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, “oligometastatic” disease, may benefit from more aggressive local therapy. Methods and Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival. Using propensity score methods, we investigated the effect of definitive local therapy to the primary tumor on overall survival. Results: Median age at diagnosis was 61 years of age; 51% of patients were female; 12% had squamous histology; and 33% had N0-1 disease. On multivariable analysis, Eastern Cooperate Oncology Group performance status ≥2 (hazard ratio [HR], 2.43), nodal status, N2-3 (HR, 2.16), squamous pathology, and metastases to multiple organs (HR, 2.11) were associated with a greater hazard of death (all P<.01). The number of metastatic lesions and radiologic size of the primary tumor were not significantly associated with overall survival. Definitive local therapy to the primary tumor was associated with prolonged survival (HR, 0.65, P=.043). Conclusions: Definitive local therapy to the primary tumor appears to be associated with improved survival in patients with oligometastatic NSCLC. Select patient and tumor characteristics, including good performance status, nonsquamous histology, and limited nodal disease, may predict for improved survival in these patients.

Reproducibility and variability of quantitative magnetic resonance imaging markers in cerebral small vessel disease

NARCIS (Netherlands)

Guio, F. De; Jouvent, E.; Biessels, G.J.; Black, S.E.; Brayne, C.; Chen, C.; Cordonnier, C.; Leeuw, F.E. de; Dichgans, M.; Doubal, F.; Duering, M.; Dufouil, C.; Duzel, E.; Fazekas, F.; Hachinski, V.; Ikram, M.A.; Linn, J.; Matthews, P.M.; Mazoyer, B.; Mok, V.; Norrving, B.; O'Brien, J.T.; Pantoni, L.; Ropele, S.; Sachdev, P.; Schmidt, R.; Seshadri, S.; Smith, E.E.; Sposato, L.A.; Stephan, B.; Swartz, R.H.; Tzourio, C.; Buchem, M. van; Lugt, A. van der; Oostenbrugge, R.; Vernooij, M.W.; Viswanathan, A.; Werring, D.; Wollenweber, F.; Wardlaw, J.M.; Chabriat, H.

2016-01-01

Brain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these

Sirolimus and Gold Sodium Thiomalate in Treating Patients With Advanced Squamous Non-Small Cell Lung Cancer

Science.gov (United States)

2012-12-13

Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Postoperative Radiation Therapy in Resected N2 Stage Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Lee, Chang Geol

1993-01-01

A total of forty patients with resected N2 stage non-small cell lung cancer treated with postoperative adjuvant radiation therapy between Jan. 1975 and Dec. 1990 at the Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei Cancer Center were retrospectively analysed to evaluate whether postoperative radiation therapy improves survival. Patterns of failure and prognostic factors affecting survival were also analysed. The 5 year overall and disease free survival rate were 26.3%, 27.3% and median survival 23.5 months. The 5 year survival rates by T-stage were T1 66.7%, T2 25.6% and T3 12.5%. Loco-regional failure rate was 14.3% and distant metastasis rate was 42.9% and both 2.9%. Statistically significant factor affecting distant failure rate was number of positive lymph nodes(>= 4). This retrospective study suggests that postoperative radiation therapy in resected N2 stage non-small cell lung cancer can reduce loco-regional recurrence and may improve survival rate as compared with other studies which were treated by surgery alone. Further study of systemic control is also needed due to high rate of distant metastasis

Assesment of prognostic factors in radical radiotherapy for patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Chmielewska, E.

2000-01-01

Lung cancer is still the most severe problem of oncology throughout the word. In Poland there are some 20 000 new cases per annum, among them non-small cell lung cancer accounts for about 16 000 cases. The basic method of therapy of non-small cell lung cancers is surgery; however, in Polish conditions only about 15% of patients qualify for it. Therefore, there remains a large group of patients who are potential candidates for radiotherapy. Evaluation of a group of patients qualified for radical radiotherapy according to uniform rules, treated with the same protocol and assesed by the same group of physicians. The obtained results of therapy allow to evaluate the usefulness of radical radiotherapy in patients with non-operable non-small cell lung cancer and serve as a basis of search for more effective radiotherapy protocols. The aim of the study is to attempt to define the prognostic, therapeutical, clinical-and population-related factors for survival and local control in patients with non-operable, non-small cell lung cancer. Between January 1, 1990, and December 31, 1995, there were 2330 patients with non-small cell lung in the Ambulatory of the Cancer Centre in Warsaw. Basing on the results of clinical examination and additional examination, 260 patients qualified for radical radiotherapy. In this group there were 31 women (12%) and 229 men (88%). In a majority of cases the stage of the disease was advanced: stage IIIA was found in 114 patients (44%), and stage IIIB in 73 patients (28%). Retrospective analysis of the results of treatment was carried out. The material covered 260 patients. The survival time and the time to local progression were the basis for the analysis. The survival probability was calculated whit the Kaplan-Meier method. Multidimensional analysis of the prognostic factors (age, clinical advancement of the disease, performance status, loss of weight, LDH and haemoglobin level, tumour size, pulmonary function, prior exploratory thoracotomy

Serum peptide expression and treatment responses in patients with advanced non-small-cell lung cancer

Science.gov (United States)

An, Juan; Tang, Chuan-Hao; Wang, Na; Liu, Yi; Lv, Jin; Xu, Bin; Li, Xiao-Yan; Guo, Wan-Feng; Gao, Hong-Jun; He, Kun; Liu, Xiao-Qing

2018-01-01

Epidermal growth factor receptor (EGFR) mutation is an important predictor for response to personalized treatments of patients with advanced non-small-cell lung cancer (NSCLC). However its usage is limited due to the difficult of obtaining tissue specimens. A novel prediction system using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been reported to be a perspective tool in European countries to identify patients who are likely to benefit from EGFR tyrosine kinase inhibitor (TKI) treatment. In the present study, MALDI-TOF MS was used on pretreatment serum samples of patients with advanced non-small-cell lung cancer to discriminate the spectra between disease control and disease progression groups in one cohort of Chinese patients. The candidate features for classification were subsequently validated in a blinded fashion in another set of patients. The correlation between plasma EGFR mutation status and the intensities of representative spectra for classification was evaluated. A total of 103 patients that were treated with EGFR-TKIs were included. It was determined that 8 polypeptides peaks were significant different between the disease control and disease progression group. A total of 6 polypeptides were established in the classification algorithm. The sensitivity of the algorithm to predict treatment responses was 76.2% (16/21) and the specificity was 81.8% (18/22). The accuracy rate of the algorithm was 79.1% (34/43). A total of 3 polypeptides were significantly correlated with EGFR mutations (P=0.04, P=0.03 and P=0.04, respectively). The present study confirmed that MALDI-TOF MS analysis can be used to predict responses to EGFR-TKI treatment of the Asian population where the EGFR mutation status differs from the European population. Furthermore, the expression intensities of the three polypeptides in the classification model were associated with EGFR mutation. PMID:29844828

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

Directory of Open Access Journals (Sweden)

Bakonyi Neto Alexandre

2003-01-01

Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

NK cell autoreactivity and autoimmune diseases

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Alessandro ePoggi

2014-02-01

Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.

Stem cell models of polyglutamine diseases and their use in cell-based therapies

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Evangelia eSiska

2015-07-01

Full Text Available Polyglutamine diseases are fatal neurological disorders that affect the central nervous system. They are caused by mutations in disease genes that contain CAG trinucleotide expansions in their coding regions. These mutations are translated into expanded glutamine chains in pathological proteins. Mutant proteins induce cytotoxicity, form intranuclear aggregates and cause neuronal cell death in specific brain regions. At the moment there is no cure for these diseases and only symptomatic treatments are available. Here, we discuss novel therapeutic approaches that aim in neuronal cell replacement using induced pluripotent or adult stem cells. Additionally, we present the beneficial effect of genetically engineered mesenchymal stem cells and their use as disease models or RNAi/gene delivery vehicles. In combination with their paracrine and cell-trophic properties, such cells may prove useful for the development of novel therapies against polyglutamine diseases.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

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Gu, Aiqin; Shi, Chunlei; Xiong, Liwen; Chu, Tianqing; Pei, Jun; Han, Baohui

2013-02-01

To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (Picotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

FDG PET/CT imaging of desmoplastic small round cell tumor: findings at staging, during treatment and at follow-up

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Ostermeier, Austin; Snyder, Scott E.; Shulkin, Barry L. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, MS 220, Memphis, TN (United States); McCarville, M.B. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, MS 220, Memphis, TN (United States); College of Medicine, University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Navid, Fariba [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Pediatrics, College of Medicine, Memphis, TN (United States)

2015-08-15

Desmoplastic small round cell tumor (DSRCT) is a very uncommon soft-tissue tumor of children and young adults. It has an aggressive course with generally poor survival. In general the assessment of tumor burden and response has relied upon CT or MRI. However these tumors are often metabolically active and can be evaluated using FDG PET/CT imaging. The purpose of this study was to determine the metabolic activity of desmoplastic small round cell tumors using FDG PET/CT imaging and the potential utility of FDG PET/CT in this disease. Eight patients (seven male, one female; ages 2-20 years, median 11 years) with confirmed DSRCT underwent 82 positron emission tomography/computed tomography (PET/CT) scans. PET/CT was used for initial staging (seven patients, eight scans), monitoring response to therapy (eight patients, 37 scans) and for surveillance of DSRCT recurrence (six patients, 37 scans). Each scan performed at diagnosis showed abnormally elevated uptake in the primary tumor. Five patients had abdominal pelvic involvement, and two of those also had thoracic disease. Six patients whose scans showed no abnormal sites of uptake at the end of therapy have had progression-free survivals of 2-10 years. One patient whose scan continued to show uptake during treatment died of disease 1.3 years from diagnosis. Another patient with persistent uptake remained in treatment 3 years after initial diagnosis. One surveillance scan identified recurrent disease. FDG PET/CT identified elevated metabolic activity in each patient studied. Despite our small sample size, FDG PET/CT scans appear useful for the management of patients with DSCRT. Patients whose studies become negative during or following treatment may have a prolonged remission. (orig.)

Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

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Harry V. Vinters

2010-11-01

Full Text Available Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA. We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase; ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system; Notch-3 (a marker of progenitor cells; IBA-1 (a marker of microglial cells; glial fibrillary acidic protein, GFAP (a marker of astrocytes; and inducible nitric oxide synthase, iNOS (a marker of inflammation. The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.

Alterations of the cerebral cortex in sporadic small vessel disease: A systematic review of in vivo MRI data.

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Peres, Roxane; De Guio, François; Chabriat, Hugues; Jouvent, Eric

2016-04-01

Cerebral small vessel diseases of the brain are a major determinant of cognitive impairment in the elderly. In small vessel diseases, the most easily identifiable lesions, both at post-mortem evaluation and magnetic resonance imaging, lie in subcortical areas. However, recent results obtained post-mortem, particularly in severe cases, have highlighted the burden of cortex lesions such as microinfarcts and diffuse neuronal loss. The recent development of image post-processing methods allows now assessing in vivo multiple aspects of the cerebral cortex. This systematic review aimed to analyze in vivo magnetic resonance imaging studies evaluating cortex alterations at different stages of small vessel diseases. Studies assessing the relationships between small vessel disease magnetic resonance imaging markers obtained at the subcortical level and cortex estimates were reviewed both in community-dwelling elderly and in patients with symptomatic small vessel diseases. Thereafter, studies analyzing cortex estimates in small vessel disease patients compared with healthy subjects were evaluated. The results support that important cortex alterations develop along the course of small vessel diseases independently of concomitant neurodegenerative processes. Easy detection and quantification of cortex changes in small vessel diseases as well as understanding their underlying mechanisms are challenging tasks for better understanding cognitive decline in small vessel diseases. © The Author(s) 2016.

Proton Beam Therapy of Stage II and III Non–Small-Cell Lung Cancer

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Nakayama, Hidetsugu; Satoh, Hiroaki; Sugahara, Shinji; Kurishima, Koichi; Tsuboi, Koji; Sakurai, Hideyuki; Ishikawa, Shigemi; Tokuuye, Koichi

2011-01-01

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non–small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4–85.4). The median proton dose given was 78.3 Gy (range, 67.1–91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non–small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non–small-cell lung cancer who are unsuitable for surgery or chemotherapy.

Proton Beam Therapy of Stage II and III Non-Small-Cell Lung Cancer

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Nakayama, Hidetsugu, E-mail: hnakayam@tokyo-med.ac.jp [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Satoh, Hiroaki [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Sugahara, Shinji [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan); Kurishima, Koichi [Department of Respiratory Medicine, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tsuboi, Koji; Sakurai, Hideyuki [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Ishikawa, Shigemi [Department of Thoracic Surgery, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Tokuuye, Koichi [Proton Medical Research Center, University of Tsukuba Graduate School of Comprehensive Human Sciences, Tsukuba, Ibaraki (Japan); Department of Radiation Oncology, Tokyo Medical University, Shinjuku, Tokyo (Japan)

2011-11-15

Purpose: The present retrospective study assessed the role of proton beam therapy (PBT) in the treatment of patients with Stage II or III non-small-cell lung cancer who were inoperable or ineligible for chemotherapy because of co-existing disease or refusal. Patients and Methods: Between November 2001 and July 2008, PBT was given to 35 patients (5 patients with Stage II, 12 with Stage IIIA, and 18 with Stage IIIB) whose median age was 70.3 years (range, 47.4-85.4). The median proton dose given was 78.3 Gy (range, 67.1-91.3) (relative biologic effectiveness). Results: Local progression-free survival for Stage II-III patients was 93.3% at 1 year and 65.9% at 2 years during a median observation period of 16.9 months. Four patients (11.4%) developed local recurrence, 13 (37.1%) developed regional recurrence, and 7 (20.0%) developed distant metastases. The progression-free survival rate for Stage II-III patients was 59.6% at 1 year and 29.2% at 2 years. The overall survival rate of Stage II-III patients was 81.8% at 1 year and 58.9% at 2 years. Grade 3 or greater toxicity was not observed. A total of 15 patients (42.9%) developed Grade 1 and 6 (17.1%) Grade 2 toxicity. Conclusion: PBT for Stage II-III non-small-cell lung cancer without chemotherapy resulted in good local control and low toxicity. PBT has a definite role in the treatment of patients with Stage II-III non-small-cell lung cancer who are unsuitable for surgery or chemotherapy.

White matters - The influence of cerebral small-vessel disease on depression, cognition and functioning

NARCIS (Netherlands)

Grool, A.M.

2012-01-01

Depression and cognitive impairment are highly prevalent in later life, and frequently co-occur. One of the possible mechanisms that may underlie both conditions is the presence of cerebral small-vessel disease. The presence of cerebral small-vessel disease is strongly associated with common

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis

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Donaldson, David S.; Else, Kathryn J.

2015-01-01

ABSTRACT Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. IMPORTANCE Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the

The Gut-Associated Lymphoid Tissues in the Small Intestine, Not the Large Intestine, Play a Major Role in Oral Prion Disease Pathogenesis.

Science.gov (United States)

Donaldson, David S; Else, Kathryn J; Mabbott, Neil A

2015-09-01

Prion diseases are infectious neurodegenerative disorders characterized by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally, and following exposure, the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsy specimens has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue, we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk of infection and the preclinical diagnosis of disease. Many natural prion diseases are acquired orally. After exposure, the accumulation of some prion diseases in the gut-associated lymphoid tissues (GALT) is important for efficient spread of disease to the brain. However, the relative contributions of GALT in the small and large intestines to oral prion pathogenesis were unknown. We show that the small intestinal

Stem cell treatment of degenerative eye disease

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Ben Mead

2015-05-01

Full Text Available Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs has so far been reliant on mesenchymal stem cells (MSC. Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs, MSC derived from bone marrow (BMSC, adipose tissues (ADSC and dental pulp (DPSC, together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment.

Stem cell treatment of degenerative eye disease.

Science.gov (United States)

Mead, Ben; Berry, Martin; Logan, Ann; Scott, Robert A H; Leadbeater, Wendy; Scheven, Ben A

2015-05-01

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment. Copyright © 2015. Published by Elsevier B.V.

The role of prophylactic cranial irradiation in regionally advanced non-small cell lung cancer. A Southwest Oncology Group Study

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Rusch, V.W.; Griffin, B.R.; Livingston, R.B. (Univ. of Washington, Seattle (USA))

1989-10-01

Lung cancer is the most common malignant disease in the United States. Only the few tumors detected very early are curable, but there has been some progress in the management of more advanced non-small cell lung cancer, particularly in regionally inoperable disease. Prevention of central nervous system relapse is an important issue in this group of patients because brain metastases ultimately develop in 20% to 25% of them. Seventy-three patients with regionally advanced non-small cell lung cancer were entered into a Phase II trial of neutron chest radiotherapy sandwiched between four cycles of chemotherapy including cisplatin, vinblastine, and mitomycin C. Prophylactic cranial irradiation was administered concurrently with chest radiotherapy (3000 cGy in 10 fractions in 15 patients; 3600 cGy in 18 fractions in the remaining 50 patients). Patients underwent computed tomographic scan of the brain before treatment and every 3 months after treatment. The initial overall response rate was 79%, but 65 of the 73 patients have subsequently died of recurrent disease. Median follow-up is 9 months for all 73 patients and 26 months for eight long-term survivors. No patient who completed the prophylactic cranial irradiation program had clinical or radiologic brain metastases. Toxic reactions to prophylactic cranial irradiation included reversible alopecia in all patients, progressive dementia in one patient, and possible optic neuritis in one patient. Both of these patients received 300 cGy per fraction of irradiation. The use of prophylactic cranial irradiation has been controversial, but its safety and efficacy in this trial supports its application in a group of patients at high risk for central nervous system relapse. Further evaluation of prophylactic cranial irradiation in clinical trials for regionally advanced non-small cell lung cancer is warranted.

Plasmablasts During Acute Dengue Infection Represent a Small Subset of a Broader Virus-specific Memory B Cell Pool

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Ramapraba Appanna

2016-10-01

Full Text Available Dengue is endemic in tropical countries worldwide and the four dengue virus serotypes often co-circulate. Infection with one serotype results in high titers of cross-reactive antibodies produced by plasmablasts, protecting temporarily against all serotypes, but impairing protective immunity in subsequent infections. To understand the development of these plasmablasts, we analyzed virus-specific B cell properties in patients during acute disease and at convalescence. Plasmablasts were unrelated to classical memory cells expanding in the blood during early recovery. We propose that only a small subset of memory B cells is activated as plasmablasts during repeat infection and that plasmablast responses are not representative of the memory B cell repertoire after dengue infection.

Optimization of Intracellular Transportation of Gene Therapeutic DNA in Small Cell Lung Cancer (Ph.d.)

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Cramer, Frederik

2013-01-01

Small cell lung cancer (SCLC) is a highly malignant disease characterized as being very aggressive and metastasizing at a rapid pace. The malevolent pace of SCLC cell migration results in almost three out of four SCLC patients having disseminated SCLC at the time of diagnosis. Unfortunately...... has to be able to repeated systemic delivery of gene therapy to cancer cells in a both safe and efficient way. Non-viral delivery vectors fulfill many of these requirements except the latter. It is currently very difficult to systemically transport sufficient amounts of therapeutic DNA, by a non......-viral delivery system, to the nuclei of the SCLC cells. As a result, the gene therapy expression obtained is too low to have any clinical relevance. We have at the Department of Radiation Biology developed a transcriptionally targeting suicide gene therapy system which is built on a double stranded DNA plasmid...

Stem cell therapy for cardiovascular disease : answering basic questions regarding cell behavior

NARCIS (Netherlands)

Bogt, Koen Elzert Adriaan van der

2010-01-01

Stem cell therapy has raised enthusiasm as a potential treatment for cardiovascular diseases. However, questions remain about the in vivo behavior of the cells after transplantation and the mechanism of action with which the cells could potentially alleviate disease symptoms. The objective of the

Primary small cell carcinoma of the esophagus: clinicopathological study of 44 cases

International Nuclear Information System (INIS)

Chen, Wei-Wei; Wu, Wen-Jing; Li, Yu-Hong; Xu, Rui-Hua; Wang, Feng; Zhang, Dong-Sheng; Luo, Hui-Yan; Wang, Zhi-Qiang; Wang, Feng-Hua; Qiu, Miao-Zhen; Ren, Chao; Wei, Xiao-Li

2014-01-01

Primary small cell carcinoma of the esophagus (SCCE) is a highly aggressive disease characterized by early dissemination and poor prognosis. Because of the rarity of this disease, few previous studies have investigated the biomarkers associated with its prognosis. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is a stem cell marker and a member of the canonical Wnt-signaling cascade. However, the clinical role of Lgr5 in SCCE remains unknown. Tissue sections were obtained from 44 patients diagnosed with SCCE and expression of Lgr5 was examined by immunohistochemistry. The correlations between Lgr5 expression, and clinical parameters and prognostic significance were evaluated. Lgr5 was expressed in SCCE cancer tissues. High Lgr5 expression was significantly correlated with lymph node metastasis (p = 0.003), late stage (p = 0.003) and unfavorable response to chemotherapy (p = 0.013) according to RECIST 1.0 criteria. Patients with higher Lgr5 expression levels had shorter overall survival times than those with lower expression levels. These results demonstrated that overexpression of Lgr5 was significantly correlated with lymph node metastasis, tumor stage, and response to chemotherapy. Furthermore, high levels of Lgr5 expression appeared to be associated with poorer survival in patients with SCCE

Accelerating stem cell trials for Alzheimer's disease.

Science.gov (United States)

Hunsberger, Joshua G; Rao, Mahendra; Kurtzberg, Joanne; Bulte, Jeff W M; Atala, Anthony; LaFerla, Frank M; Greely, Henry T; Sawa, Akira; Gandy, Sam; Schneider, Lon S; Doraiswamy, P Murali

2016-02-01

At present, no effective cure or prophylaxis exists for Alzheimer's disease. Symptomatic treatments are modestly effective and offer only temporary benefit. Advances in induced pluripotent stem cell (iPSC) technology have the potential to enable development of so-called disease-in-a-dish personalised models to study disease mechanisms and reveal new therapeutic approaches, and large panels of iPSCs enable rapid screening of potential drug candidates. Different cell types can also be produced for therapeutic use. In 2015, the US Food and Drug Administration granted investigational new drug approval for the first phase 2A clinical trial of ischaemia-tolerant mesenchymal stem cells to treat Alzheimer's disease in the USA. Similar trials are either underway or being planned in Europe and Asia. Although safety and ethical concerns remain, we call for the acceleration of human stem cell-based translational research into the causes and potential treatments of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combined modality therapy for locally advanced non-small cell lung carcinoma

International Nuclear Information System (INIS)

Recine, D.; Rowland, K.; Reddy, S.; Lee, M.S.; Bonomi, P.; Taylor, S.; Faber, L.P.; Warren, W.; Kittle, C.F.; Hendrickson, F.R.

1990-01-01

Multi-modality treatment consisting of cisplatin, VP-16, and 5-fluorouracil chemotherapy given concomitantly with external beam radiation was used to treat 64 patients with locally advanced Stage III non-small cell lung carcinoma. This regimen was used in a preoperative fashion for four cycles in patients considered surgically resectable and with curative intent for six cycles in the remainder of patients. The clinical response rate for the entire group was 84% and the overall local control rate was 74%. The median survival was 13 months with a median follow-up for live patients of 19 months. The actuarial 3-year survival and disease-free survival rates were 30% and 23%, respectively. Histologic complete response was 39% and appeared to predict for survival. The 3-year actuarial survival and disease-free survival rates for 23 resected patients were 69% and 45%, respectively, with the complete histologic responders having a disease-free survival of 78%. The pattern of first recurrence did not appear to differ by histology or presence of lymph nodes in this subset of patients. The actuarial 3-year survival and disease-free survival rates for inoperable patients receiving six cycles of treatment were 18% and 23%, respectively. The local control was 67% with the majority of these patients having Stage IIIB disease. The Mountain International staging system appeared to predict for operability, local recurrence, and survival. This concomitant treatment regimen is feasible, with the major toxicities being leukopenia, nausea, and vomiting

Randomized combined modality trial in small cell carcinoma of the lung

International Nuclear Information System (INIS)

Maurer, L.H.; Tulloh, M.; Weiss, R.B.; Blom, J.; Leone, L.; Glidewell, O.; Pajak, T.F.

1980-01-01

A randomized trial of combined modality therapy employing combination chemotherapy (cyclophosphamide (CTX) and methotrexate (MTX), CTX, MTX and Vincristine (VCR) and CTX, VCR, and high-dose MTX with citrovorum rescue), and radiation therapy was compared to cyclophosphamide and radiation therapy in 258 patients with pulmonary small cell carcinoma. Patients were also randomized: (1) to determine the effects of prophylactic whole brain irradiation; (2) to establish the effects of maintenance chemotherapy. Survival, frequency of response, and site of relapse were different in patients with limited disease (LD) (disease confined to lung, mediastinum, and supraclavicular lymph nodes) when compared with disease spread beyond these sites (extensive disease) (ED). No survival advantage was seen in LD when combination chemotherapy was employed, although the frequency of complete remission was greater with three drugs than with one or two drugs (48% vs 32%). In ED frequency of response was greater for three drugs than for one and two drugs (60% vs 40%), but there was no survival advantage. The median survival time for complete responders was similar for limited or extensive disease (12.1 months), but 23.8% were alive at 24 months with LD compared to none with ED. Maintenance chemotherapy significantly prolonged survival by 16.8 months with 33% alive at 24 months compared to 9% who were unmaintained. Prophylactic whole brain irradiation prevented brain metastases with only 4% developing this complication as compared to 18% of control subjects, but did not influence survival

Subcarinal Lymph Nodes Should be Dissected in All Lobectomies for Non-Small Cell Lung Cancer

DEFF Research Database (Denmark)

Eckardt, Jens; Jakobsen, Erik; Licht, Peter B

2017-01-01

BACKGROUND: Mediastinal staging is of paramount importance for planning of treatment in non-small cell lung cancer (NSCLC). Single institution reports recently claimed that subcarinal lymph node dissection during resection of upper lobe NSCLC could be spared. We used a complete national lung cancer...... registry to investigate patterns of unsuspected mediastinal lymph node involvement after lobectomy. METHODS: During an 11-year period (2004 to 2014) 5,577 consecutive patients who underwent operations for NSCLC were investigated for unsuspected mediastinal lymph node involvement (N2 disease) discovered......: Mediastinal lymph node dissection was performed in 5,577 patients during the operation, and unsuspected N2 disease was discovered in 612 (11.0%), and 193 (3.5%) had subcarinal metastasis. Subcarinal N2 disease was significantly more common in patients with lower-lobe or middle-lobe cancers compared with upper...

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

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Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

Type two innate lymphoid cells; the Janus cells in health and disease

Science.gov (United States)

Maazi, Hadi; Akbari, Omid

2017-01-01

Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

Type two innate lymphoid cells: the Janus cells in health and disease.

Science.gov (United States)

Maazi, Hadi; Akbari, Omid

2017-07-01

Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Survival benefit of radiotherapy to patients with small cell esophagus carcinoma: an analysis of Surveillance Epidemiology and End Results (SEER) data.

Science.gov (United States)

Song, Yaqi; Wang, Wanwei; Tao, Guangzhou; Zhu, Weiguo; Zhou, Xilei; Pan, Peng

2016-03-29

Small cell esophageal carcinoma (SCEC) is a rare malignant tumor. So far, few studies are found to research the effect of radiotherapy (RT) to it. This study is designed to explore the prognostic factors, and analyze survival benefit of RT to patients with SCEC. Patients with SCEC were more likely to be in female, older, higher disease stage than those with non-small cell esophageal carcinoma. RT was used in more than 50% SCEC patients. RT tended be reduced as the disease stage raise in SCEC. Univariate and multivariate analysis showed that age, year, disease stage, and RT were the prognostic factors of survival (P 0.05) and nearly 30% risks of death in distant stage (P > 0.05). SCEC patients between 1973 and 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, year, sex, race, stage, surgery, and RT were summarized. Univariate and multivariate analysis were performed to explore the independent prognostic factors of SCEC. Cox regression survival analysis was performed to evaluate the effect of RT to SCEC based on different stages. Stage, age, year, and RT are independent prognostic factors of SCEC. Survival benefit of RT exists in any disease stage, but is only statistically significant in localized stage of SCEC.

Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

Energy Technology Data Exchange (ETDEWEB)

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Aftab, Blake T. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rudin, Charles M. [Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Medical Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hales, Russell K., E-mail: rhales1@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2013-05-01

Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.

Ultrastructure and pathology of desmoplastic small round cell tumor

International Nuclear Information System (INIS)

Xu Bin; Wang Bo; Gu Junlian; Li Xin; Li Yang

2010-01-01

Objective: To observe the change of ultrastructure and pathology of desmoplastic small round cell tumor (DSRCT) and recognize the characteristics of DSRCT and improve the standard of diagnosis. Methods: One case of primary DSRCT in right leg was observed by light microscope, immunohistochemical method and electron microscope and analyzed with review of the literatures. Results: The size of tumor was 3.2 cm x 2.4 cm x 1.3 cm with gray-yellow on cross-section. Foci of hemorrhage and necrosis were noted. Under light microscope, the tumor was composed of sharply demarcated nests of small rounded or oval cells. The cellular aggregates were surrounded and separated by abundant fibrous connective tissue. The tumor cells were uniform in size and shape, and showed small to moderate amounts of pale cytoplasm with indistinct cell borders. The nuclei were round to oval, with clumped chromatin and marked hyperchromasia. Some cells had one or two indistinct nucleoli. Numerous mitotic figures and areas of necrosis were dentified. The immunohistochemical results showed that the tumor cells were strongly positive for CK, EMA and NSE. There was focal positive staining for desmin with a perinuclear dot-like pattern. However, the tumor cells were negative for CgA, Myogenin, Syn, LCA, SMA, S-100, NF, GFAP, HMB45, HHF-35, CD3, CD10, Actin, CD99, and CD20. Under electron microscope, the tumor cells showed paranuclear cytoplasmic intermediate filaments arranging in globular or whorl array. Conclusion: DSRCT occurs both in the abdomen and at other sites. The patients with DSRCT range widely in age. DSRCT has distinctive histopathologic and ultrastructural features. This tumor shows immunohistochemical feature of epithelial, mesenchymal as well as neural multidirectional differentiation. RT-PCR may be served as an important diagnostic adjunct for DSRAT. The prognosis of the patients with DSRCT is very poor. (authors)

Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis

Science.gov (United States)

Singh, Lavleen; Bhardwaj, Swati; Sinha, Aditi; Bagga, Arvind; Dinda, Amit

2016-01-01

Dense deposit disease is caused by fluid-phase dysregulation of the alternative complement pathway and frequently deviates from the classic membranoproliferative pattern of injury on light microscopy. Other patterns of injury described for dense deposit disease include mesangioproliferative, acute proliferative/exudative, and crescentic GN. Regardless of the histologic pattern, C3 glomerulopathy, which includes dense deposit disease and C3 GN, is defined by immunofluorescence intensity of C3c two or more orders of magnitude greater than any other immune reactant (on a 0–3 scale). Ultrastructural appearances distinguish dense deposit disease and C3 GN. Focal and segmental necrotizing glomerular lesions with crescents, mimicking a small vessel vasculitis such as ANCA-associated GN, are a very rare manifestation of dense deposit disease. We describe our experience with this unusual histologic presentation and distinct clinical course of dense deposit disease, discuss the pitfalls in diagnosis, examine differential diagnoses, and review the relevant literature. PMID:26361799

NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

Science.gov (United States)

Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

2017-07-01

CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

Massive MIMO meets small cell backhaul and cooperation

CERN Document Server

Yang, Howard H

2017-01-01

This brief explores the utilization of large antenna arrays in massive multiple-input-multiple-output (MIMO) for both interference suppression, where it can improve cell-edge user rates, and for wireless backhaul in small cell networks, where macro base stations can forward data to small access points in an energy efficient way. Massive MIMO is deemed as a critical technology for next generation wireless technology. By deploying an antenna array that has active elements in excess of the number of users, massive MIMO not only provides tremendous diversity gain but also powers new aspects for network design to improve performance. This brief investigates a better utilization of the excessive spatial dimensions to improve network performance. It combines random matrix theory and stochastic geometry to develop an analytical framework that accounts for all the key features of a network, including number of antenna array, base station density, inter-cell interference, random base station deployment, and network tra...

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients

Directory of Open Access Journals (Sweden)

Hatim I. Alghamdi

2018-03-01

Full Text Available Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs and non-small cell lung cancers (NSCLCs in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs and Non-small cell lung cancers (NSCLCs registered in the Saudi Cancer Registry (SCR for the period 2009–2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC were included in the analysis, all Saudi nationals. A total of 213 (52.75% deaths occurred among lung cancer patients, 108 (54.82% among SCLCs and 105 (50.72% among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p = 0.04; but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p = 0.025 and a significant difference in stage of tumor (p = 0.006 and (p = 0.035 for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR = 5.87, 95% CI: 2.01 – 17.19 in SCLC and by 3-fold (OR = 3.29, 95% CI: 1.22 – 8.85 in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR = 0.36, 95% CI: 0.14 – 0.93. Age, sex, topography

An overview of mortality & predictors of small-cell and non-small cell lung cancer among Saudi patients.

Science.gov (United States)

Alghamdi, Hatim I; Alshehri, Ali F; Farhat, Ghada N

2018-03-01

Lung cancer ranks as the top cancer worldwide in terms of incidence and constitutes a major health problem. About 90% of lung cancer cases are diagnosed at advance stage where treatment is not available. Despite evidence that lung cancer screening improves survival, guidelines for lung cancer screening are still a subject for debate. In Saudi Arabia, only 14% of lung cancers are diagnosed at early stage and researches on survival and its predictors are lacking. This overview analysis was conducted on predictors of lung cancer mortality according to the two major cancer types, small-cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs) in Saudi Arabia. A secondary data analysis was performed on small-cell lung cancers (SCLCs) and Non-small cell lung cancers (NSCLCs) registered in the Saudi Cancer Registry (SCR) for the period 2009-2013 to estimate predictors of mortality for both lung cancer types. A total of 404 cases (197 SCLC and 207 NSCLC) were included in the analysis, all Saudi nationals. A total of 213 (52.75%) deaths occurred among lung cancer patients, 108 (54.82%) among SCLCs and 105 (50.72%) among NCSLCs. Three quarter of patients are diagnosis with advance stage for both SCLC & NSCLC. Univariate analysis revealed higher mean age at diagnosis in dead patients compared to alive patients for SCLCs (p=0.04); but not NSCLCs, a lower mortality for NSCLCs diagnosed in 2013 (p=0.025) and a significant difference in stage of tumor (p=0.006) and (p=0.035) for both SCLC and NSCLC respectively. In multiple logistic regression, stage of tumor was a strong predictor of mortality, where distant metastasis increased morality by 6-fold (OR=5.87, 95% CI: 2.01 - 17.19) in SCLC and by 3-fold (OR=3.29, 95% CI: 1.22 - 8.85) in NSCLC, compared to localized tumors. Those with NSCLC who were diagnosed in 2013 were less likely to die by 64% compared to NSCLC diagnosed in 2009 (OR=0.36, 95% CI: 0.14 - 0.93). Age, sex, topography and laterality were not associated with

Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Higgins, Kristin [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Chino, Junzo P [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States); Marks, Lawrence B [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States); Ready, Neal [Department of Medicine, Division of Medical Oncology, Duke University of Medical Center, Durham, NC (United States); D' Amico, Thomas A [Department of Surgery, Division of Cardiovascular and Thoracic Surgery, Duke University of Medical Center, Durham, NC (United States); Clough, Robert W; Kelsey, Chris R [Department of Radiation Oncology, Duke University of Medical Center, Durham, NC (United States)

2009-12-01

Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

Preoperative Chemotherapy Versus Preoperative Chemoradiotherapy for Stage III (N2) Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Higgins, Kristin; Chino, Junzo P.; Marks, Lawrence B.; Ready, Neal; D'Amico, Thomas A.; Clough, Robert W.; Kelsey, Chris R.

2009-01-01

Purpose: To compare preoperative chemotherapy (ChT) and preoperative chemoradiotherapy (ChT-RT) in operable Stage III non-small-cell lung cancer. Methods and Materials: This retrospective study analyzed all patients with pathologically confirmed Stage III (N2) non-small-cell lung cancer who initiated preoperative ChT or ChT-RT at Duke University between 1995 and 2006. Mediastinal pathologic complete response (pCR) rates were compared using a chi-square test. The actuarial overall survival, disease-free survival, and local control were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox regression analysis was also performed. Results: A total of 101 patients who initiated preoperative therapy with planned resection were identified. The median follow-up was 20 months for all patients and 38 months for survivors. The mediastinal lymph nodes were reassessed after preoperative therapy in 88 patients (87%). Within this group, a mediastinal pCR was achieved in 35% after preoperative ChT vs. 65% after preoperative ChT-RT (p = 0.01). Resection was performed in 69% after ChT and 84% after ChT-RT (p = 0.1). For all patients, the overall survival, disease-free survival, and local control rate at 3 years was 40%, 27%, and 66%, respectively. No statistically significant differences were found in the clinical endpoints between the ChT and ChT-RT subgroups. On multivariate analysis, a mediastinal pCR was associated with improved disease-free survival (p = 0.03) and local control (p = 0.03), but not overall survival (p = 0.86). Conclusion: Preoperative ChT-RT was associated with higher mediastinal pCR rates but not improved survival.

Expression of the epidermal growth factor receptor in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Damstrup, L; Rygaard, K; Spang-Thomsen, M

1992-01-01

of EGF receptor mRNA in all 10 cell lines that were found to be EGF receptor-positive and in one cell line that was found to be EGF receptor-negative in the radioreceptor assay and affinity labeling. Our results provide, for the first time, evidence that a large proportion of a broad panel of small cell......Epidermal growth factor (EGF) receptor expression was evaluated in a panel of 21 small cell lung cancer cell lines with radioreceptor assay, affinity labeling, and Northern blotting. We found high-affinity receptors to be expressed in 10 cell lines. Scatchard analysis of the binding data...... demonstrated that the cells bound between 3 and 52 fmol/mg protein with a KD ranging from 0.5 x 10(-10) to 2.7 x 10(-10) M. EGF binding to the receptor was confirmed by affinity-labeling EGF to the EGF receptor. The cross-linked complex had a M(r) of 170,000-180,000. Northern blotting showed the expression...

Paget Disease of the Breast

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... under a microscope; they may be found as single cells or as small groups of cells within the epidermis. Who gets Paget disease of the breast? Paget disease of the breast occurs in both women and men, but most cases occur in women. ...

Comparative analysis of the role of small G proteins in cell migration and cell death: Cytoprotective and promigratory effects of RalA

International Nuclear Information System (INIS)

Jeon, Hyejin; Zheng, Long Tai; Lee, Shinrye; Lee, Won-Ha; Park, Nammi; Park, Jae-Yong; Heo, Won Do; Lee, Myung-Shik; Suk, Kyoungho

2011-01-01

Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with inflammation, tumorigenesis, and metastasis. Our results show that small G proteins of the six families differentially regulate cell death and cell cycle distribution. In particular, our results indicate that Rho family of small G proteins is antiapoptotic. Ras, Rho, and Ran families promoted cell migration. There was no significant correlation between the cell death- and cell migration-regulating activities of the small G proteins. Nevertheless, RalA was not only cytoprotective against multiple chemotherapeutic drugs, but also promigratory inducing stress fiber formation, which was accompanied by the activation of Akt and Erk pathways. Our study provides a framework for further systematic investigation of small G proteins in the perspectives of cell death/survival and motility in inflammation and cancer.

Sickle Cell Disease

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... message, please visit this page: About CDC.gov . Learn Tips for Receiving Better Care in the Emergency Department in Our Fact ... related care in the United States. Read Supplement » VIDEO Sickle Cell Disease: When to Transfuse Learn about indications for blood transfusion in patients with ...

On the problem of roentgenological semiotics of small cell lung cancer

International Nuclear Information System (INIS)

Makarycheva, R.I.; Shchukina, O.P.; Gertner, K.; Vetrova, N.A.

1985-01-01

The study was concerned with description of roentgenologic semiotics of central and peripheral small cell lung cancer in 141 patients receiving chemoradiation therapy. The frequency of carcinoma metastatic spreading into intrathoracic lymph nodes was high. Small cell lung cancer showed a good response to conservative treatment, which, in particular, manifested itself in regression of metastases into intrathoracic lymph nodes

Small molecule probes for cellular death machines.

Science.gov (United States)

Li, Ying; Qian, Lihui; Yuan, Junying

2017-08-01

The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need. Here, we provide an overview of small molecule modulators for necroptosis and ferroptosis, two non-apoptotic cell death mechanisms, and discuss the molecular pathways and relevant pathophysiological mechanisms revealed by the judicial applications of such small molecule probes. We suggest that the development and applications of small molecule probes for non-apoptotic cell death mechanisms provide an outstanding example showcasing the power of chemical biology in exploring novel biological mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Inoue, Ryuji; Takada, Yoshiki; Obayashi, Kayoko; Kado, Tetsuji; Yamamoto, Hiroyuki; Hirota, Saeko; Soejima, Toshinori; Suzuki, Yasushi; Mimura, Fumitoshi [Hyogo Medical Center for Adult Disease, Akashi (Japan)

1994-12-01

In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m{sup 2}) on day 1 and vindesine (3mg/m{sup 2}) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author).

Concurrent chemo-radiotherapy for stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Inoue, Ryuji; Takada, Yoshiki; Obayashi, Kayoko; Kado, Tetsuji; Yamamoto, Hiroyuki; Hirota, Saeko; Soejima, Toshinori; Suzuki, Yasushi; Mimura, Fumitoshi

1994-01-01

In patients with unresectable stage III non-small cell lung cancer, we performed chemotherapy and concurrent thoracic radiotherapy. Thirty-five registered patients were intravenously treated with cisplatin (80mg/m 2 ) on day 1 and vindesine (3mg/m 2 ) on days 1, 3 and were irradiated from days 1 to 10 with single doses of 2.5 Gy up to a total dosage of 20 Gy. Each course lasted 28 days. Patients received 3 courses, and a total dosage of 60 Gy was delivered. Response to this treatment was evaluable in terms of results in 35 patients. Twenty-two patients showed partial response (response rate 62.9%), 10 had no change, and 3 cases had progressive disease. In 7.5 to 37.8 months observation, three PR patients are alive for more than 24 months without recurrence, but eight PR patients died of local relapse, and the median survival time was 15.7 months. Throughout this treatment course, grade 4 leukopenia was noted in 66% and grade 3 thrombocytopenia was observed in 3%. However all were reversible condition and no treatment-related death was observed. However, two cases died due to complications of pulmonary abscess, which occurred in the area of radiation pulmonary fibrosis about one year later after treatment. Although this concurrent chemo-radiotherapy is a tolerable treatment for non-small cell lung cancer and obtained a good response rate, it did not improve the survival rate. (author)

Isolated pancreatic metastases from a bronchogenic small cell carcinoma.

LENUS (Irish Health Repository)

Walshe, T

2012-01-31

We describe the case of a 60 year old female smoker who presented with a three month history of weight loss (14 Kg), generalized abdominal discomfort and malaise. Chest radiography demonstrated a mass projected inferior to the hilum of the right lung. Computed Tomography of thorax confirmed a lobulated lesion in the right infrahilar region and subsequent staging abdominal CT demonstrated a low density lesion in the neck of the pancreas. Percutaneous Ultrasound guided pancreatic biopsy was performed, histology of which demonstrated pancreatic tissue containing a highly necrotic small cell undifferentiated carcinoma consistent with metastatic small cell carcinoma of the bronchus.

Modeling Kidney Disease with iPS Cells

Science.gov (United States)

Freedman, Benjamin S.

2015-01-01

Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and ‘disease in a dish’ laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field. PMID:26740740

Tumor cell heterogeneity in Small Cell Lung Cancer (SCLC: phenotypical and functional differences associated with Epithelial-Mesenchymal Transition (EMT and DNA methylation changes.

Directory of Open Access Journals (Sweden)

Alexander Krohn

Full Text Available Small Cell Lung Cancer (SCLC is a specific subtype of lung cancer presenting as highly metastatic disease with extremely poor prognosis. Despite responding initially well to chemo- or radiotherapy, SCLC almost invariably relapses and develops resistance to chemotherapy. This is suspected to be related to tumor cell subpopulations with different characteristics resembling stem cells. Epithelial-Mesenchymal Transition (EMT is known to play a key role in metastatic processes and in developing drug resistance. This is also true for NSCLC, but there is very little information on EMT processes in SCLC so far. SCLC, in contrast to NSCLC cell lines, grow mainly in floating cell clusters and a minor part as adherent cells. We compared these morphologically different subpopulations of SCLC cell lines for EMT and epigenetic features, detecting significant differences in the adherent subpopulations with high levels of mesenchymal markers such as Vimentin and Fibronectin and very low levels of epithelial markers like E-cadherin and Zona Occludens 1. In addition, expression of EMT-related transcription factors such as Snail/Snai1, Slug/Snai2, and Zeb1, DNA methylation patterns of the EMT hallmark genes, functional responses like migration, invasion, matrix metalloproteases secretion, and resistance to chemotherapeutic drug treatment all differed significantly between the sublines. This phenotypic variability might reflect tumor cell heterogeneity and EMT during metastasis in vivo, accompanied by the development of refractory disease in relapse. We propose that epigenetic regulation plays a key role during phenotypical and functional changes in tumor cells and might therefore provide new treatment options for SCLC patients.

Light incoupling in small molecule organic solar cells

Energy Technology Data Exchange (ETDEWEB)

Allinger, Nikola; Meiss, Jan; Riede, Moritz; Leo, Karl [Institut fuer Angewandte Photophysik, Technische Universitaet Dresden, 01069 Dresden (Germany); Gnehr, Wolf-Michael [Heliatek GmbH, Liebigstrasse 26, 01187 Dresden (Germany)

2008-07-01

Light incoupling is an essential topic for optimization of organic solar cells. In our group, we examine light incoupling of different kinds of transparent contacting materials as well as external dielectric coatings, using optical simulation of thin film systems and experimental methods. Thin films of small molecules are prepared by thermal evaporation in a multi-chamber UHV system. Complex refraction indices of various materials are calculated from reflection and transmission measurements of monolayers. For modelling of optical properties of thin film systems, we developed a numerical simulation program based on the transfer matrix method. The cell structures investigated consist of nanolayers of small molecules, using ZnPc/C60 as an acceptor-donor heterojunction. As contact materials, we compare the expensive standard material indium tin oxide (ITO) with more cost-efficient alternatives like thin Ag layers or spin-coated layers of the polymer PEDOT:PSS, and discuss the resulting cell properties. Additional dielectric layers of varying materials, like tris(8-hydroxy-quinolinate)-aluminum (Alq3) or N,N'-tetrakis(4-methoxyphenyl)-benzidine (MeO-TPD), are deposited on top of the stack and their influence on cell efficiencies is investigated.

A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Seonmi Park

2017-04-01

Full Text Available Summary: Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes, and fetal hemoglobin (HbF levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS mutation. : In this resource article, Mostoslavsky, Murphy, and colleagues of the NextGen consortium describe a diverse, comprehensive, and characterized library of sickle cell disease-specific induced pluripotent stem cells (iPSCs from patients of different ethnicities, β-globin gene (HBB haplotypes and fetal hemoglobin (HbF levels. This bank is readily available and accessible to all investigators. Keywords: induced pluripotent stem cells, iPSCs, sickle cell disease, disease modeling, directed differentiation, gene correction

Possible neuroimmunomodulation therapy in T-cell-mediated oral diseases

Directory of Open Access Journals (Sweden)

Tsuyoshi Sato

2015-01-01

Full Text Available Introduction: Recurrent aphthous stomatitis and oral lichen planus are local chronic inflammatory diseases which are implicated in T cell-mediated immunity. According to the systematic review, there is insufficient evidence to support any specific treatment for T-cell mediated oral diseases. The hypothesis: In this paper, we propose a hypothesis that recurrent aphthous stomatitis and oral lichen planus can be treated with selective α7 subunit of nicotinic acetylcholine receptor (α7 -nAChR agonists. Our hypothesis is supported by the following two facts. First, the pathophysiological conditions, T h 1/T h 17 cell activation and autonomic nervous system dysfunction, are observed in T-cell mediated oral diseases as well as in T-cell mediated systemic diseases such as rheumatoid arthritis. Second, the cholinergic anti-inflammatory pathway is inhibited in systemic T-cell mediated chronic inflammatory diseases. On the other hand, treatment with α7 -nAChR agonists which activate the cholinergic anti-inflammatory pathway suppresses neuroinflammation via inhibition of T h 1/T h 17 responses in animal model of systemic T-cell mediated chronic inflammatory diseases. We thus expect that selective α7 -nAChR agonists will be effective for the treatment of T-cell mediated oral diseases. Evaluation of the hypothesis: To test our hypothesis, we need to develop in vivo mouse model of T-cell mediated oral diseases. To evaluate the therapeutic effect of a selective α7 -nAChR agonist, we choose ABT-107 because of its safety and tolerability. We believe that the selective α7 -nAChR agonist, especially ABT-107, may be a therapeutic drug to treat T-cell mediated oral diseases.

Primary Hepatic Small Cell Carcinoma: Two Case Reports, Molecular Characterization and Pooled Analysis of Known Clinical Data.

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Shastri, Aditi; Msaouel, Pavlos; Montagna, Cristina; White, Sherry; Delio, Maria; Patel, Kunjan; Alexis, Karenza; Strakhan, Marianna; Elrafei, Tarek N; Reed, Louis Juden

2016-01-01

Primary hepatic small cell carcinoma (HSCC) is a rare malignancy that has previously been described in only few case reports. The clinicopathological course, natural history, molecular markers and ideal treatment strategy for this tumor have not been fully elucidated. Herein, we report on two cases of spontaneously arising, metastatic primary HSCC that were treated at our Institution. Both patients succumbed to their disease within two months of initial presentation. Both cases underwent postmortem examination and no evidence of a pulmonary or other non-hepatic small cell primary was found. Unlike pulmonary small cell tumors, these two hepatic primaries showed only locoregional spread and very few distant metastases. Formalin-fixed samples were obtained at autopsy and sequenced using single-nucleotide polymorphism arrays and whole-genome sequencing. Four mutations in the epidermal growth factor receptor (EGFR) gene known to be associated with response to tyrosine kinase inhibitors (TKIs) were detected in one of the two HSCC samples. A systematic review and pooled analysis of all previously reported cases of primary HSCCs was conducted. The median overall survival was estimated at 4 months. Surgical resection was significantly associated with longer overall survival (hazard ratio =0.13, 95% confidence interval=0.03-0.69). Although several case reports of primary HSCC have been reported prior to this publication, to our knowledge this is the first time that molecular and systematic analysis has been conducted in order to more fully characterize this rare disease. Our results indicate that surgical resection, when feasible, may be a valid option in primary HSCC, and that some tumors may respond to TKIs against EGFR. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Agressive small cell carcinoma of the ovary, hypercalcemic type, surgery and oncological treatment: case report].

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Kapoun, M; Bouda, J; Presl, J; Vlasák, P; Slunečko, R

2015-06-01

Small cell carcinoma of the ovary (SCCOHT) is a rare tumor typically affecting young women. It is a highly malignant tumor accompanied with poor prognosis, early relapse and low survival rates. The most significant prognostic factor is stage of the disease. Due to above mentioned factors there are no guidelines for therapy of this rare tumor. We present a case of 22-years-old patient initially treated with antibiotics under diagnosis of pelvic inflammatory disease. Due to persistent mass at left adnexa, she was indicated for diagnostic laparoscopy, converted to laparotomy and left adnexectomy with frozen section revealing unspecified malignant tumor of left ovary. A conservative operation was performed and, after diagnosis of SCCOHT was established, the patient was indicated for adjuvant chemotherapy.

Current therapy of small cell lung cancer

DEFF Research Database (Denmark)

Sorensen, M; Lassen, U; Hansen, H H

1998-01-01

This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated...

Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment.

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Liu, Yang; Dong, Yan-Hong; Lyu, Pei-Yuan; Chen, Wei-Hong; Li, Rui

2018-03-05

Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of "hypertension", "cerebral small vessel disease", "white matter lesions", "enlarged perivascular spaces", "lacunar infarcts", "cerebral microbleeds", and "cognitive impairment" in the database of PubMed. Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. In recent years, studies have demonstrated that hypertension-related changes (e.g., small vascular lesions, inflammatory reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy) can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure (BP) control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the numbers, volumes, and anatomical locations of CSVD and cognitive impairment.

Coeliac disease

African Journals Online (AJOL)

2013-03-08

Mar 8, 2013 ... Two factors are involved in the development of coeliac disease, namely the ... degradation by gastric, pancreatic and intestinal brush ... epithelial layer with chronic inflammatory cells in patients ... Coeliac disease increases the risk of malignancies, such as small bowel adenocarcinoma and enteropathy-.

The role of mismatch repair in small-cell lung cancer cells

DEFF Research Database (Denmark)

Hansen, L T; Thykjaer, T; Ørntoft, T F

2003-01-01

The role of mismatch repair (MMR) in small-cell lung cancer (SCLC) is controversial, as the phenotype of a MMR-deficiency, microsatellite instability (MSI), has been reported to range from 0 to 76%. We studied the MMR pathway in a panel of 21 SCLC cell lines and observed a highly heterogeneous...... pattern of MMR gene expression. A significant correlation between the mRNA and protein levels was found. We demonstrate that low hMLH1 gene expression was not linked to promoter CpG methylation. One cell line (86MI) was found to be deficient in MMR and exhibited resistance to the alkylating agent MNNG...

Cetuximab and biomarkers in non-small-cell lung carcinoma

Directory of Open Access Journals (Sweden)

Patil N

2012-07-01

Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

Performance of a Fuel-Cell-Powered, Small Electric Airplane Assessed

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Berton, Jeffrey J.

2004-01-01

Rapidly emerging fuel-cell-power technologies may be used to launch a new revolution of electric propulsion systems for light aircraft. Future small electric airplanes using fuel cell technologies hold the promise of high reliability, low maintenance, low noise, and - with the exception of water vapor - zero emissions. An analytical feasibility and performance assessment was conducted by NASA Glenn Research Center's Airbreathing Systems Analysis Office of a fuel-cell-powered, propeller-driven, small electric airplane based on a model of the MCR-01 two-place kitplane (Dyn'Aero, Darois, France). This assessment was conducted in parallel with an ongoing effort by the Advanced Technology Products Corporation and the Foundation for Advancing Science and Technology Education. Their project - partially funded by a NASA grant - is to design, build, and fly the first manned, continuously propelled, nongliding electric airplane. In our study, an analytical performance model of a proton exchange membrane (PEM) fuel cell propulsion system was developed and applied to a notional, two-place light airplane modeled after the MCR-01 kitplane. The PEM fuel cell stack was fed pure hydrogen fuel and humidified ambient air via a small automotive centrifugal supercharger. The fuel cell performance models were based on chemical reaction analyses calibrated with published data from the fledgling U.S. automotive fuel cell industry. Electric propeller motors, rated at two shaft power levels in separate assessments, were used to directly drive a two-bladed, variable-pitch propeller. Fuel sources considered were compressed hydrogen gas and cryogenic liquid hydrogen. Both of these fuel sources provided pure, contaminant-free hydrogen for the PEM cells.

Stem cell treatment for chronic lung diseases.

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Tzouvelekis, Argyris; Ntolios, Paschalis; Bouros, Demosthenes

2013-01-01

Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. In view of the current disappointing status of available pharmaceutical agents, there is an urgent need for alternative more effective therapeutic approaches that will not only help to relieve patient symptoms but will also affect the natural course of the respective disease. Regenerative medicine represents a promising option with several fruitful therapeutic applications in patients suffering from chronic lung diseases. Nevertheless, despite relative enthusiasm arising from experimental data, application of stem cell therapy in the clinical setting has been severely hampered by several safety concerns arising from the major lack of knowledge on the fate of exogenously administered stem cells within chronically injured lung as well as the mechanisms regulating the activation of resident progenitor cells. On the other hand, salient data arising from few 'brave' pilot investigations of the safety of stem cell treatment in chronic lung diseases seem promising. The main scope of this review article is to summarize the current state of knowledge regarding the application status of stem cell treatment in chronic lung diseases, address important safety and efficacy issues and present future challenges and perspectives. In this review, we argue in favor of large multicenter clinical trials setting realistic goals to assess treatment efficacy. We propose the use of biomarkers that reflect clinically inconspicuous alterations of the disease molecular phenotype before rigid conclusions can be safely drawn. Copyright © 2013 S. Karger AG, Basel.

The Resource Mapping Algorithm of Wireless Virtualized Networks for Saving Energy in Ultradense Small Cells

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Sai Zou

2015-01-01

Full Text Available As the current network is designed for peak loads, it results in insufficient resource utilization and energy waste. Virtualized technology makes it possible that intelligent energy perception network could be deployed and resource sharing could become an effective energy saving technology. How to make more small cells into sleeping state for energy saving in ultradense small cell system has become a research hot spot. Based on the mapping feature of virtualized network, a new wireless resource mapping algorithm for saving energy in ultradense small cells has been put forward when wireless resource amount is satisfied in every small cell. First of all, the method divides the virtual cells. Again through the alternate updating between small cell mapping and wireless resource allocation, least amount of small cells is used and other small cells turn into sleeping state on the premise of guaranteeing users’ QoS. Next, the energy consumption of the wireless access system, wireless resource utilization, and the convergence of the proposed algorithm are analyzed in theory. Finally, the simulation results demonstrate that the algorithm can effectively reduce the system energy consumption and required wireless resource amount under the condition of satisfying users’ QoS.

small cell lung cancer in a Chinese population

African Journals Online (AJOL)

clinical significance in patients with non-small cell lung cancer (NSCLC) in Hubei province ... diagnosis, tumor stage, treatment, progression .... Table 4: Association between EGFR mutation, gender and histologic type in 138 NSCLC patients.

Twenty-seven years of phase III trials for patients with extensive disease small-cell lung cancer: disappointing results.

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Isao Oze

Full Text Available BACKGROUND: Few studies have formally assessed whether treatment outcomes have improved substantially over the years for patients with extensive disease small-cell lung cancer (ED-SCLC enrolled in phase III trials. The objective of the current investigation was to determine the time trends in outcomes for the patients in those trials. METHODS AND FINDINGS: We searched for trials that were reported between January 1981 and August 2008. Phase III randomized controlled trials were eligible if they compared first-line, systemic chemotherapy for ED-SCLC. Data were evaluated by using a linear regression analysis. RESULTS: In total, 52 trials were identified that had been initiated between 1980 and 2006; these studies involved 10,262 patients with 110 chemotherapy arms. The number of randomized patients and the proportion of patients with good performance status (PS increased over time. Cisplatin-based regimens, especially cisplatin and etoposide (PE regimen, have increasingly been studied, whereas cyclophosphamide, doxorubicin, and vincristine-based regimens have been less investigated. Multiple regression analysis showed no significant improvement in survival over the years. Additionally, the use of a PE regimen did not affect survival, whereas the proportion of patients with good PS and the trial design of assigning prophylactic cranial irradiation were significantly associated with favorable outcome. CONCLUSIONS AND SIGNIFICANCE: The survival of patients with ED-SCLC enrolled in phase III trials did not improve significantly over the years, suggesting the need for further development of novel targets, newer agents, and comprehensive patient care.

KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer

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Jun Ma

2015-08-01

Full Text Available Background/Aims: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers. Methods: Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research. Results: We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27, inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells. Conclusions: These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

The impact of microscopic disease on the tumor control probability in non-small-cell lung cancer

International Nuclear Information System (INIS)

Siedschlag, Christian; Boersma, Liesbeth; Loon, Judith van; Rossi, Maddalena; Baardwijk, Angela van; Gilhuijs, Kenneth; Stroom, Joep

2011-01-01

Purpose: To indicate which clinical target volume (CTV) margin (if any) is needed for an adequate treatment of non-small-cell lung cancer (NSCLC) using either 3D conformal or stereotactic radiotherapy, taking the distribution of the microscopic disease extension (MDE) into account. Methods and materials: On the basis of the linear-quadratic biological model, a Monte-Carlo simulation was used to study the impact of MDE and setup deviations on the tumor control probability (TCP) after typical 3D conformal and stereotactic irradiation techniques. Setup deviations were properly accounted for in the planning target volume (PTV) margin. Previously measured distributions of MDE outside the macroscopic tumor in NSCLC patients were used. The dependence of the TCP on the CTV margins was quantified. Results: The presence of MDE had a demonstratable influence on the TCP in both the 3D conformal and the stereotactic technique when no CTV margins were employed. The impact of MDE on the TCP values was greater in the 3D conformal scenario (67% TCP with MDE; 84% TCP without MDE) than for stereotactic radiotherapy (91% TCP with MDE; 100% TCP without MDE). Accordingly, an increase of the CTV margin had the greatest impact for the 3D conformal technique. Larger setup errors, with appropriate PTV margins, lead to an increase in TCP for both techniques, showing the interdependence of CTV and PTV margins. Conclusions: MDE may not always be eradicated by the beam penumbra or existing PTV margins using either 3D conformal or stereotactic radiotherapy. Nonetheless, TCP modeling indicates an overall local control rate above 90% for the stereotactic technique, while a non-zero CTV margin is recommended for better local control of MDE when using the 3D conformal technique.

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

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Al-Habib, Mey; Yu, Zongdong

2013-01-01

One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

Advanced sickle cell associated interstitial lung disease presenting ...

African Journals Online (AJOL)

Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by ...

Progenitor cell-based treatment of glial disease

DEFF Research Database (Denmark)

Goldman, Steven A

2017-01-01

-based neurodegenerative conditions may now be compelling targets for cell-based therapy. As such, glial cell-based therapies may offer potential benefit to a broader range of diseases than ever before contemplated, including disorders such as Huntington's disease and the motor neuron degeneration of amyotrophic lateral...

Predicting carotid artery disease and plaque instability from cell-derived microparticles.

Science.gov (United States)

Wekesa, A L; Cross, K S; O'Donovan, O; Dowdall, J F; O'Brien, O; Doyle, M; Byrne, L; Phelan, J P; Ross, M D; Landers, R; Harrison, M

2014-11-01

Cell-derived microparticles (MPs) are small plasma membrane-derived vesicles shed from circulating blood cells and may act as novel biomarkers of vascular disease. We investigated the potential of circulating MPs to predict (a) carotid plaque instability and (b) the presence of advanced carotid disease. This pilot study recruited carotid disease patients (aged 69.3 ± 1.2 years [mean ± SD], 69% male, 90% symptomatic) undergoing endarterectomy (n = 42) and age- and sex-matched controls (n = 73). Plaques were classified as stable (n = 25) or unstable (n = 16) post surgery using immunohistochemistry. Blood samples were analysed for MP subsets and molecular biomarkers. Odds ratios (OR) are expressed per standard deviation biomarker increase. Endothelial MP (EMP) subsets, but not any vascular, inflammatory, or proteolytic molecular biomarker, were higher (p < .05) in the unstable than the stable plaque patients. The area under the receiver operator characteristic curve for CD31(+)41(-) EMP in discriminating an unstable plaque was 0.73 (0.56-0.90, p < .05). CD31(+)41(-) EMP predicted plaque instability (OR = 2.19, 1.08-4.46, p < .05) and remained significant in a multivariable model that included transient ischaemic attack symptom status. Annexin V(+) MP, platelet MP (PMP) subsets, and C-reactive protein were higher (p < .05) in cases than controls. Annexin V(+) MP (OR = 3.15, 1.49-6.68), soluble vascular cell adhesion molecule-1 (OR = 1.64, 1.03-2.59), and previous smoking history (OR = 3.82, 1.38-10.60) independently (p < .05) predicted the presence of carotid disease in a multivariable model. EMP may have utility in predicting plaque instability in carotid patients and annexin V(+) MPs may predict the presence of advanced carotid disease in aging populations, independent of established biomarkers. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Primary Small Cell Carcinoma of the Stomach Successfully Treated With Cisplatin and Etoposide

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Shu-Chen Kuo

2009-11-01

Full Text Available We report a 44-year-old man with primary gastric small cell carcinoma who showed a remarkable response to chemotherapy specific for pulmonary small cell carcinoma. The patient had been admitted to another local hospital because of intermittent epigastralgia. An upper gastrointestinal examination there revealed an ulcerative tumor, 5 cm in diameter, on the lesser curvature side of the cardia, and endoscopic biopsy reported adenocarcinoma. Computed tomography revealed a mass over the lesser curvature of the stomach and some enlarged regional lymph nodes. Radical total gastrectomy, lymph node dissection, Roux-en-Y esophagojejunostomy and splenectomy were performed at our hospital. Pathology revealed gastric mucosa infiltrated by small-sized tumor cells with scanty cytoplasm and hyperchromatic nuclei. Immunohisto- chemically, the tumor cells were positive for synaptophysin, chromogranin A, and CD56. Primary gastric small cell carcinoma was diagnosed. The postoperative course, complicated by shock due to bleeding, wound infection and intra-abdominal abscess, took more than 2 months to resolve. Follow-up computed tomography showed tumor recurrence with multiple enlarged lymph nodes in the aortocaval region and hepatic hilum. The patient received palliative chemotherapy consisting of cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1–3 every 28 days, and had partial response to the chemotherapy, with a progression-free survival of 10 months. Chemotherapy with cisplatin and etoposide used for small cell carcinoma of the lung is a good treatment for gastric small cell carcinoma.

Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.

Directory of Open Access Journals (Sweden)

Gergely Tóth

Full Text Available The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson's and Alzheimer's diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228, that targets α-synuclein, a key protein in Parkinson's disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.

Borrelia burgdorferi in small mammal reservoirs in Kentucky, a traditionally non-endemic state for Lyme disease.

Science.gov (United States)

Buchholz, Matthew J; Davis, Cheryl; Rowland, Naomi S; Dick, Carl W

2018-04-01

The incidence of tick-borne zoonoses such as Lyme disease has steadily increased in the southeastern United States. Southeastern states accounted for 1500 of over 28,000 confirmed cases of Lyme disease reported in the United States during 2015. Borrelia burgdorferi, the etiologic agent of Lyme disease, is maintained in small mammal reservoirs and vectored to new hosts by ixodid ticks. This study examined ecological relationships of the B. burgdorferi/vector/reservoir system in order to understand the dynamics of Lyme disease risk in Kentucky. Small mammals were captured using live traps from November 2014 to October 2015. Ticks were removed and blood and tissue collected from small mammals were screened for B. burgdorferi DNA by PCR with primers specific to the OspA gene. Prevalence of B. burgdorferi (21.8%) in Kentucky small mammals was comparable to the lowest recorded prevalence in regions where Lyme disease is endemic. Moreover, infestation of small mammals by Ixodes scapularis, the primary vector of B. burgdorferi, was rare, while Dermacentor variabilis comprised the majority of ticks collected. These findings provide ecological insight into the relative paucity of Lyme disease in Kentucky.

Sport participation in adolescents with sickle cell disease.

Science.gov (United States)

Al-Rimawi, Hala; Jallad, Samer

2008-10-01

Adolescents with blood diseases should be encouraged to participate in exercise. Physical activity helps to build stronger muscles, to give better support to the joints, and to improve the patient's overall health and fitness. It also improves emotional well being by improving self-esteem and providing social interaction. Sports and exercise in sickle cell anemia and sickle cell trait need special consideration. Young athletes with sickle cell disease are at high risk of dehydration, heat-related injury, exhaustion, painful episodes, and hip joint problems. Gradual acclimatization to heat, humidity and high altitude, slow conditioning over weeks and avoidance of dehydration are recommended for all adolescents with sickle cell disease to make their sport activity safe. Effort should be made to educate those with sickle cell disease that their condition is not a handicap and that they are fit to lead a normal life.

Tracking the Evolution of Non-Small-Cell Lung Cancer

DEFF Research Database (Denmark)

Jamal-Hanjani, Mariam; Wilson, Gareth A.; McGranahan, Nicholas

2017-01-01

Background Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine...... as a prognostic predictor. (Funded by Cancer Research UK and others; TRACERx ClinicalTrials.gov number, NCT01888601 .)....

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology.

Science.gov (United States)

Jadczyk, T; Faulkner, A; Madeddu, P

2013-05-01

Regenerative medicine holds great promise as a way of addressing the limitations of current treatments of ischaemic disease. In preclinical models, transplantation of different types of stem cells or progenitor cells results in improved recovery from ischaemia. Furthermore, experimental studies indicate that cell therapy influences a spectrum of processes, including neovascularization and cardiomyogenesis as well as inflammation, apoptosis and interstitial fibrosis. Thus, distinct strategies might be required for specific regenerative needs. Nonetheless, clinical studies have so far investigated a relatively small number of options, focusing mainly on the use of bone marrow-derived cells. Rapid clinical translation resulted in a number of small clinical trials that do not have sufficient power to address the therapeutic potential of the new approach. Moreover, full exploitation has been hindered so far by the absence of a solid theoretical framework and inadequate development plans. This article reviews the current knowledge on cell therapy and proposes a model theory for interpretation of experimental and clinical outcomes from a pharmacological perspective. Eventually, with an increased association between cell therapy and traditional pharmacotherapy, we will soon need to adopt a unified theory for understanding how the two practices additively interact for a patient's benefit. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

ORAL-THERAPY FOR SMALL-CELL LUNG-CANCER

NARCIS (Netherlands)

POSTMUS, PE; SMIT, EF

After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to

Prognostic stratification of patients with T3N1M0 non-small cell lung cancer: which phase should it be?

Science.gov (United States)

Kilicgun, Ali; Tanriverdi, Ozgur; Turna, Akif; Metin, Muzaffer; Sayar, Adnan; Solak, Okan; Urer, Nur; Gurses, Atilla

2012-06-01

In the 1997 revision of the TNM staging system for lung cancer, patients with T3N0M0 disease were moved from stage IIIA to stage IIB since these patients have a better prognosis. Despite this modification, the local lymph node metastasis remained the most important prognostic factor in patients with lung cancer. The present study aimed to evaluate the prognosis of patients with T3N1 disease as compared with that of patients with stages IIIA and IIB disease. During 7-year period, 313 patients with non-small cell lung cancer (297 men, 16 women) who had resection were enrolled. The patients were staged according the 2007 revision of Lung Cancer Staging by American Joint Committee on Cancer. The Kaplan-Meier statistics was used for survival analysis, and comparisons were made using Cox proportional hazard method. The 5-year survival of patients with stage IIIA disease excluding T3N1 patients was 40%, whereas the survival of the patients with stage IIB disease was 66% at 5 years. The 5-year survival rates of stage III T3N1 patients (single-station N1) was found to be higher than those of patients with stage IIIA disease (excluding pT3N1 patients, P = 0.04), while those were found to be similar with those of patients with stage IIB disease (P = 0.4). Survival of the present cohort of patients with T3N1M0 disease represented the survival of IIB disease rather than IIIA non-small cell lung cancer. Further studies are needed to suggest further revisions in the recent staging system regarding T3N1MO disease.

Mantle-cell lymphoma.

Science.gov (United States)

Barista, I; Romaguera, J E; Cabanillas, F

2001-03-01

During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

UP-scaling of inverted small molecule based organic solar cells

DEFF Research Database (Denmark)

Patil, Bhushan Ramesh; Madsen, Morten

Organic solar cells (OSC), in spite of being a promising technology, still face challenges regarding large-scale fabrication. Although efficiencies of up to 12 % has been reached for small molecule OSC, their performance, both in terms of device efficiency and stability, is significantly reduced...... during up-scaling processes. The work presented here is focused on an approach towards up-scaling of small molecule based OSC with inverted device configuration. Bilayer OSC from Tetraphenyldibenzoperiflanthene (DBP) and Fullerenes (C70), as electron donor and acceptor respectively, with cell area...

CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain

Directory of Open Access Journals (Sweden)

Sebastiano Cavallaro

2013-01-01

Full Text Available Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC and the pharmacological tools that may be used to interfere with this signaling axis.

Analysis of prognostic factors in patients with non-small cell lung cancer treated conventional radical teleradiotherapy

International Nuclear Information System (INIS)

Pluta, E.

2007-01-01

Radical surgery is the treatment of choice in non-small cell lung cancer, however, only about 20-30% of patients with early stage of disease (stage I, II and possibly IIIA) qualify for it. For the remaining patients, unable to tolerate surgery because of underlying medial disease, advanced age, respiratory insufficiency, or those who refused to undergo operation, radiation therapy is a clinically accepted alternative. Five - year survival for patients receiving radical radiation treatment alone ranges from 12-32%. We reviewed the records of 227 patients with inoperable non-small cell lung cancer, treated in our Institute between 1970-1990. In our group: 40% patients have unresectable tumor, 21% had bad pulmonary function tests results, 15% had cardiac risk, 6% were over 76 years of age, and 18% refused to agree to surgery. Treatment was delivered using megavoltage irradiation in doses ranging from 60 to 72 Gy. The survival probability was calculated by the Kaplan-Meier method. Overall survival (OS) probability at two years was 34% and at five years - 10%. Two - years local control was observed in 54% and five-year in 41%. The disease - specific survival (DSS) rates at 2 and 5 years were 30% and 8% respectively. The significant favorable prognostic factor for DSS and OS were tumor size (T1,T2, N0) and early stage (I), no weight loss, and complete radiological regression of the tumor 8 weeks after irradiation. The significant favorable prognostic factors for local control were good performance status (over 80 points acc. to Karnofsky scale), no weight loss, early stage (I), and complete radiological regression of the tumor 8 weeks after irradiation. 1. New therapeutic strategies involving chemotherapy should be considered for larger tumors (T2, T3, N1, N2). 2. Patients with a good performance status and small tumor (T1N0, T2N0) would benefit most from treatment with radiation alone. (author)

Non small-cell lung cancer and treatment options after tyrosine kinase inhibitors failure in the first line

International Nuclear Information System (INIS)

Chowaniecova, G.

2014-01-01

Introduction: Advanced non-small cell lung cancer with present epidermal growth factor receptor (EGFR) sensitising mutation is standardly treated with tyrosine kinase inhibitors (TKI). During treatment a resistance to TKI develops, disease progresses. We differ primary and secondary resistance. The most effective treatment after TKI failure is not definitively proven. Standard chemotherapy is usually introduced, eventually it is possible to use other TKI in the next lines. Case: The author presents a case of 60-year old patient with lung adenocarcinoma with EGFR sensitising mutation, where primary resistance to TKI was observed. Chemotherapy after progression was introduced. Planned therapy with afatnib was not carried out due to deterioration of patient´s condition. Conclusion: Presented case of EGFR mutation-positive patient represents an example of not very frequent primary resistance to TKI. Mechanisms of primary resistance are not well understood. Treatment after first line TKI failure in non-small cell lung cancer with EGFR mutation represents a challenge for medical research. (author)

Treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer

International Nuclear Information System (INIS)

Zhang Li; Wang Lvhua; Zhang Hongxing; Chen Dongfu; Xiao Zefen; Wang Mei; Feng Qinfu; Liang Jun; Zhou Zongmei; Ou Guangfei; Lv Jima; Yin Weibo

2008-01-01

Objective: To retrospectively analyze treatment results of radiotherapy for medically inoperable stage I/II non-small cell lung cancer. Methods: Between Jan. 2000 and Dec. 2005, fifty-eight such patients were enrolled into the database analysis, including 37 with clinical stage I and 21 with stage II disease. Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy. Forty- three patients were treated with 3-D conformal radiotherapy (3D-CRT) and 15 with conventional radiotherapy. Results: The 1-, 2- and 3-year overall survival rates were 85%, 54% and 30%, and the median survival time was 26.2 months for the whole group. The corresponding figures were 88%, 60%, 36% and 30.8 months for cancer-specific survival; 84%, 64%, 31% and 30.8 months for Stage I disease; 81%, 47%, 28% and 18.8 months for Stage II disease; 95%, 57%, 33% and 30.8 months for 3D-CRT group and 53%, 44%, 24% and 15.3 months for conventional radiotherapy group. By logrank test, tumor volume, pneumonitis of Grade II or higher and weight loss more than 5% showed statistically significant impact on overall survival. Tumor volume was the only independent prognostic factor in Cox multivariable regression. Pneumonitis and esophagitis of Grade II or higher were 16% and 2%, respectively. Age and lung function before treatment had a significant relationship with pneumonitis. Failure included the local recurrence (33%) and distant metastasis (21%). There was no difference between the treatment modalities and failure sites. Conclusions: For medically inoperable early stage non-small cell lung cancer patients, tumor volume is the most important prognostic factor for overall survival. The conformal radiotherapy marginally improves the survival. The age and pulmonary function are related to the incidence of treatment induced pneumonitis. (authors)

Cell ageing: a flourishing field for neurodegenerative diseases

Directory of Open Access Journals (Sweden)

Dora Brites

2015-06-01

Full Text Available Cellular senescence is viewed as an irreversible cell-cycle arrest mechanism involving a complexity of biological progressive processes and the acquisition of diverse cellular phenotypes. Several cell-intrinsic and extrinsic causes (stresses may lead to diverse cellular signaling cascades that include oxidative stress, mitochondrial dysfunction, DNA damage, excessive accumulation of misfolded proteins, impaired microRNA processing and inflammation. Here we review recent advances in the causes and consequences of brain cell ageing, including the senescence of endothelial cells at the central nervous system barriers, as well as of neurons and glial cells. We address what makes ageing an important risk factor for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and cerebrovascular disease. In particular, we highlight the importance of defects in mitochondrial dynamics, in the cathepsin activity imbalance, in cell-cell communication, in the accumulation of misfolded and unfolded proteins and in the microRNA profiling as having potential impact on cellular ageing processes. Another important aspect is that the absence of specific senescence biomarkers has hampered the characterization of senescent cells in ageing and age-associated diseases. In accordance, the senescence-associated secretory phenotype (SASP or secretome was shown to vary in distinct cell types and upon different stressors, and SASP heterogeneity is believed to create subsets of senenescent cells. In addition to secreted proteins, we then place extracellular vesicles (exosomes and ectosomes as important mediators of intercellular communication with pathophysiological roles in disease spreading, and as emerging targets for therapeutic intervention. We also discuss the application of engineered extracellular vesicles as vehicles for drug delivery. Finally, we summarize current knowledge on methods to rejuvenate senescent cells

NASA Alternative Orion Small Cell Battery Design Support

Science.gov (United States)

Haynes, Chuck

2016-01-01

The NASA Orion Crew Module Reference Design was produced to address large scale thermal runaway (TR) hazard with specific safety controls for the Orion Spacecraft. The design presented provides the description of a full scale battery design reference for implementation as a drop in replacement to meet all spacecraft energy requirements with compatible 120 Vdc electrical and mechanical interface using small cell technology (18650) packaging. The 32V SuperBrick incorporates unique support features and an electrical bus bar arrangement that allows cells negative can insertion into heat sink that is compressively coupled to the battery enclosure to promote good thermal management. The housing design also provides an internal flame suppression "filter tray" and positive venting path internal to the enclosure to allow hot effluent ejecta to escape in the event of single cell TR. Virtual cells (14P Banks) that are supported to provide cell spacing with interstitial materials to prevent side can failures that can produce cell to cell TR propagation. These features were successfully test in four separate TR run with the full scale DTA1 test article in February 2016. Successfully Completed Test Objectives - Four separate TR test runs with Full-Scale DTA1 housing with Two SuperBricks, Two SuperBrick Emulators All Tests resulted in "clean" gas with less than 6 C rise at Battery vent All Tests resulted in less than 2 C temperature rise on cold-plate outlet All Tests resulted in less than 6 psi pressure rise in the battery housing Test Run 1 -One neighbor cell TR, highest remaining neighbor 139 C. Ejecta shorted to bus caused prolonged additional heating, One shorted cell did experience TR after 12 minutes, remaining cells had adequate thermal margin Test Run 2 - No cell to cell propagation, highest neighbor cell 112 C; Test Run 3 - No cell to cell propagation, highest neighbor cell 96 C; Test Run 4 - No cell to cell propagation, highest neighbor cell 101 C; Primary TR testing

Are mast cells instrumental for fibrotic diseases?

Directory of Open Access Journals (Sweden)

Catherine eOvered-Sayer

2014-01-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a fatal lung disorder of unknown etiology characterised by accumulation of lung fibroblasts and extracellular matrix deposition, ultimately leading to compromised tissue architecture and lung function capacity. IPF has a heterogeneous clinical course; however the median survival after diagnosis is only 3-5 years. The pharmaceutical and biotechnology industry has made many attempts to find effective treatments for IPF, but the disease has so far defied all attempts at therapeutic intervention. Clinical trial failures may arise for many reasons, including disease heterogeneity, lack of readily measurable clinical end points other than overall survival, and, perhaps most of all, a lack of understanding of the underlying molecular mechanisms of the progression of IPF.The precise link between inflammation and fibrosis remains unclear, but it appears that immune cells can promote fibrosis by releasing fibrogenic factors. So far, however, therapeutic approaches targeting macrophages, neutrophils, or lymphocytes have failed to alter disease pathogenesis. A new cell to garner research interest in fibrosis is the mast cell. Increased numbers of mast cells have long been known to be present in pulmonary fibrosis and clinically correlations between mast cells and fibrosis have been reported. More recent data suggests that mast cells may contribute to the fibrotic process by stimulating fibroblasts resident in the lung, thus driving the pathogenesis of the disease. In this review, we will discuss the mast cell and its physiological role in tissue repair and remodelling, as well as its pathological role in fibrotic diseases such as IPF, where the process of tissue repair and remodelling is thought to be dysregulated.

Breviscapine suppresses the growth of non-small cell lung cancer

Indian Academy of Sciences (India)

Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells.However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimedto study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 and A549 cells ...

Radiopharmaceutical Stem Cell Tracking for Neurological Diseases

Directory of Open Access Journals (Sweden)

Paulo Henrique Rosado-de-Castro

2014-01-01

Full Text Available Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasive in vivo imaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases.

Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.

Science.gov (United States)

Catelain, Cyril; Pailler, Emma; Oulhen, Marianne; Faugeroux, Vincent; Pommier, Anne-Laure; Farace, Françoise

2017-01-01

Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.

Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

DEFF Research Database (Denmark)

Fox, Ira J; Daley, George Q; Goldman, Steven A

2014-01-01

Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

CT-guided intratumoral gene therapy in non-small-cell lung cancer

International Nuclear Information System (INIS)

Kauczor, H.U.; Heussel, C.P.; Thelen, M.; Schuler, M.; Huber, C.; Weymarn, A. von; Bongartz, G.; Rochlitz, C.

1999-01-01

The objective of this study was to prove the principle of CT-guided gene therapy by intratumoral injection of a tumor suppressor gene as an alternative treatment approach of incurable non-small-cell lung cancer. In a prospective clinical phase I trial six patients with non-small-cell lung cancer and a mutation of the tumor suppressor gene p53 were treated by CT-guided intratumoral gene therapy. Ten milliliters of a vector solution (replication-defective adenovirus with complete wild-type p53 cDNA) were injected under CT guidance. In four cases the vector solution was completely applied to the tumor center, whereas in two cases 2 ml aliquots were injected into different tumor areas. For the procedure the scan room had been approved as a biosafety cabinet. Gene transfer was assessed by reverse transcription and polymerase chain reaction in biopsy specimens obtained under CT guidance 24-48 h after therapy. Potential therapeutic efficacy was evaluated on day 28 after treatment using spiral CT. The CT-guided gene therapy was easily performed in all six patients without intervention-related complications. Besides flu-like symptoms, no significant adverse effects of gene therapy were noted. Three of the four patients with central injection exhibited gene transfer in the posttreatment biopsy. Gene transfer could not be proven in the two patients with multiple 2 ml injections. After 28 days, four of the six patients showed stable disease at the treated tumor site, whereas other tumor manifestations progressed. Computed tomography-guided injections are an adequate and easy-to-perform procedure for intratumoral gene therapy. (orig.)

Phase I Study of Concurrent Whole Brain Radiotherapy and Erlotinib for Multiple Brain Metastases From Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Lind, Joline S.W.; Lagerwaard, Frank J.; Smit, Egbert F.; Senan, Suresh

2009-01-01

Purpose: Erlotinib has shown activity in patients with brain metastases from non-small-cell lung cancer. The present dose-escalation Phase I trial evaluated the toxicity of whole brain radiotherapy (WBRT) with concurrent and maintenance erlotinib in this patient group. Methods and Materials: Erlotinib (Cohort 1, 100 mg/d; Cohort 2, 150 mg/d) was started 1 week before, and continued during, WBRT (30 Gy in 10 fractions). Maintenance erlotinib (150 mg/d) was continued until unacceptable toxicity or disease progression. Results: A total of 11 patients completed WBRT, 4 in Cohort 1 and 7 in Cohort 2. The median duration of erlotinib treatment was 83 days. No treatment-related neurotoxicity was observed. No treatment-related Grade 3 or greater toxicity occurred in Cohort 1. In Cohort 2, 1 patient developed a Grade 3 acneiform rash and 1 patient had Grade 3 fatigue. Two patients in Cohort 2 developed erlotinib-related interstitial lung disease, contributing to death during maintenance therapy. The median overall survival and interval to progression was 133 and 141 days, respectively. Six patients developed extracranial progression; only 1 patient had intracranial progression. In 7 patients with follow-up neuroimaging at 3 months, 5 had a partial response and 2 had stable disease. Conclusion: WBRT with concurrent erlotinib is well tolerated in patients with brain metastases from non-small-cell lung cancer. The suggestion of a high intracranial disease control rate warrants additional study.