Preliminary feasibility assessment on the investigation of bronchogenic adenocarcinoma angiogenesis with dynamic multi-slice spiral computed tomography

International Nuclear Information System (INIS)

Li Shenjiang; Xiao Xiangsheng; Li Huimin; Liu Shiyuan; Li Chengzhou; Zhang Chenshi; Tao Zhiwei

2003-01-01

Objective: To evaluate the feasibility on the investigation of bronchogenic adenocarcinoma angiogenesis with dynamic multi-slice spiral computed tomography (MSCT) . Methods: 27 patients with bronchogenic adenocarcinomas (diameter ≤4 cm) underwent multi-location dynamic contrast material-enhanced (90 ml, 4 ml/s) serial CT. These dynamic images were processed with the 'time lapse' software and the 'functional CT' software. Peak heights of bronchogenic adenocarcinoma and the aorta, perfusion and mean transit time (MTT) were measured. Ratio of peak height of the bronchogenic adenocarcinoma to that of the aorta was calculated. Perfusion and mean transit time images were obtained. Results: Peak height of bronchogenic adenocarcinoma was (36.66 ± 13.53) HU. No statistically significant difference in the peak height was found between our results and the results of Ukihide et al (mean peak height 34.1 HU) (t =0.981, P = 0.335). Bronchogenic adenocarcinoma-to-aorta ratio was (15.72±4.66 )%. The difference in bronchogenic adenocarcinoma -to-aorta ratio between our results and the results of Zhang and Kono (mean malignant SPN-to-aorta ratio 14.6%) did not reach statistical significance (t=1.244, P=0.225). The mean perfusion value (3.278 ml·min - · kg -1 ) was in the range of that (1.36-2.98 ml·min -1 ·kg -1 ) measured with a single photon emission CT (SPECT). Mean transit time was (17.60 ± 4.52) s. Conclusion: It is feasible to investigate bronchogenic adenocarcinoma angiogenesis with dynamic MSCT

[Esophageal bronchogenic cyst: an uncommon cause of dysphagia in adults. Case report and literature review].

Science.gov (United States)

Ceniceros-Cabrales, Ana P; Sánchez-Fernández, Patricio

2018-01-01

Bronchogenic cysts result from abnormal budding of the primitive tracheobronchial tube and are rare congenital cystic lesions. The location of the cyst depends on the embryological stage of abnormal budding. Although periesophageal bronchogenic cysts have been frequently reported, a completely intramural cyst is very rare. A 42-year-old female patient, a three-month course with retrosternal pain associated with food intake, accompanied by intermittent dysphagia to solids. Esophagogram, high resolution thoracic tomography and endoscopic ultrasound are performed, concluding a probable esophageal bronchogenic cyst. Resection is performed by video-assisted thoracic surgery, without complications. Patient presents with adequate evolution and complete remission of the symptomatology. Bronchogenic cysts of the esophageal wall are extremely uncommon lesions. Its surgical treatment is indicated to be symptomatic; video-assisted thoracoscopic surgery resection is of choice, with excellent long-term results and minimal morbidity. Copyright: © 2018 Permanyer.

67Ga-emission computed tomography in bronchogenic carcinoma

International Nuclear Information System (INIS)

Ichiya, Yuichi; Oshiumi, Yoshihiko; Kuwabara, Yasuo; Wada, Makoto; Ayabe, Zenji; Matsuura, Keiichi

1982-01-01

Both conventional 67 Ga scintigraphy and 67 Ga emission computed tomography (ECT) were performed in 36 patients with bronchogenic carcinoma to evaluate clinical significance of 67 Ga-ECT as an adjunctive method. Each patient received 111 -- 185 MBq (3 -- 5 mCi) of 67 Ga-citrate intravenously. A rotation #betta# camera (Shimadzu LFOV-E) was used for ECT study, and a #betta# camera (Searle LFOV) was used for conventional scintigraphy. The detectability of 67 Ga scintigraphy with ECT in primary tumors and regional lymph node metastases was compared retrospectively with that of conventional 67 Ga scintigraphy alone. There was little improvement in detection of primary and metastatic lesions by adding 67 Ga-ECT. Only 3 primary tumors were demonstrated more distinctly by 67 Ga-ECT. However, there was no lesion which was detected only by 67 Ga-ECT. Our data indicate that inclusion of 67 Ga-ECT in the routine examination is unnecessary in cases with bronchogenic carcinoma. (author)

Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma

International Nuclear Information System (INIS)

Toyohira, Ken; Yasumoto, Kosei; Manabe, Hideo; Ohta, Mitsuo; Terashima, Hiromi

1979-01-01

Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I and II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size. (author)

Staging of bronchogenic carcinoma by computerized tomography

International Nuclear Information System (INIS)

Sommer, B.; Bauer, W.M.; Rath, M.; Fenzl, G.; Stelter, W.J.; Lissner, J.

1981-01-01

It was possible to check the information obtained by CT scanning in 36 patients out of 49 who had been subjected to computerized tomography, in respect of the extension of the primary tumour (T stage), and in 25 patients in respect of the degree of mediastinal lymphatic node involvement (N stage). In all 49 patients, the presence of bronchogenic carcinoma had been safely established. In 97% of the cases, assessment of the extension of the primary tumour was found to be correct. Assessment of the N stage, however, is more problematic, since detection of mediastinal lymphatic nodes by computerized tomography does not necessarily tell us something about their metastatic involvement. If all recognizable lymphatic nodes are interpreted as potential metastases, we have no false negative but 61% false positive results because of the frequency of postinflammatory or anthracotic lymphatic nodes. In case of exclusive assessment of lymphatic node enlargement above 1 cm diameter, the rate of metastatic nodes increases considerably (83%). Computerized tomography is definitely superior to all roentgenological methods in assessing the stage of a bronchogenic carcinoma; hence, it could occupy a key position in determining the diagnostic and therapeutic approach in patients with this disease. (orig.) [de

Bronchogenic cysts in adults - analysis of 15 cases and review of the literature

International Nuclear Information System (INIS)

Souza, Ricardo Pires de; Setubal, Roger; Florencio, Filipe Toledo; Gomes, Marcio Rogerio Alcala; Mayo, Suzete Varela; Leiro, Luis Carlos Filgueira; Soares, Aldemir Humberto

1997-01-01

Bronchogenic cysts are congenital anomalies resulting from abnormal budding of the tracheobronchial tree. Generally are asymptomatic in adults, unless infected or compressing neighbouring structures, and usually are discovered on routine examinations. Controversially, more recent studies report a high incidence of symptoms in adults, but worthlessed in routine examinations. The authors report 15 patients seen at the Pneumology and Thoracic Surgery and Image Diagnosis Departments of the Heliopolis Hospital, Sao Paulo State, between 1977 and 1996 (20 years), which undergone surgical excision for pulmonary (n=11) and mediastinal (n=4) bronchogenic cysts. There were 11 men and 4 women, with ages between 17 and 74 years. Sixty-six percent were symptomatic at the time of diagnosis. All the patients were investigated with chest radiographs, and 4 of them with computed tomography. All cysts localized in the mediastinum were excised locally, while the intrapulmonary ones needed pulmonectomy in a variable degree. Through a literature and a casuistic analysis the authors discuss the main etiology, clinical, surgical and radiological features of bronchogenic cysts. (author)

Bronchogenic adenocarcinoma presenting as a synchronous solitary lytic skull lesion with ischaemic stroke--case report and literature review.

LENUS (Irish Health Repository)

O'Connell, David

2011-01-01

The authors describe a rare case of metastatic bronchogenic adenocarcinoma in a 55-year-old man presenting with concomittant solitary lytic skull lesion and ischaemic stroke. Metastatic bronchogenic carcinoma is known to present as lytic skull lesions. Primary brain tumours are also known to cause ischaemic brain injury. An underlying stroke risk may be exagerated by cranial tumour surgery. Patients with brain tumours are well known to be predisposed to an increased risk of developing thromboembolic disease. It is unusual to see metastatic bronchogenic adenocarcinoma presenting as ischaemic stroke with a background of concomittant cerebral metastasis. The aetio-pathogenesis of this rare occurrence is discussed with a review of literature.

Bronchogenic Cysts Located in Neck Region: An Uncommon Entity ...

African Journals Online (AJOL)

Herein we present a child with a bronchogenic cyst, which was located at the right side of the cervical oesophagus displacing it to the left. At operation we found that the cyst had a common wall with the oesophagus, which was completely excised. Preoperative diagnosis was esophageal duplication, however, ...

Effect of radiotherapy on the immunocompetence in patients with bronchogenic carcinoma and laryngeal cancer

International Nuclear Information System (INIS)

Oshitani, Takashi

1981-01-01

We evaluated the immunocompetence of 80 patients with bronchogenic carcinoma and 17 patients with laryngeal cancer undergoing radiotherapy, using collectively many types of immunological parameters. In patients with bronchogenic carcinoma, no significant difference was seen with PHA and PPD skin tests, but the reactivity of PHA skin tests gradually decreased in the course of treatment. It was assumed that radiotherapy might not interfere with the recognition of antigen. Lymphocyte blastoid transformations with PHA, Con A and PWM were all inhibited significantly. Since these three mitogens can stimulate the different groups of lymphocyte, the inhibition to the proliferative function of lymphocyte due to radiotherapy would seem to cover a wide area, including T and B lymphocyte. Concerning the comparative radiosensitivity of T and B lymphocyte, no significant result was obtained. However, in the dose of 20Gy the percentage of T lymphocyte decreased, while the percentage of B lymphocyte increased. The percentage of early rosetts, one subset of T cell, decreased more sensitively than that of T cell, but there was no significant difference. Immunocompetence of cases in stage III, which was significantly high before treatment, decreased to the same level as those in stage IV according to the treatment. In patients with laryngeal cancer, lymphocyte counts and reactivity of PHA skin tests were not influenced by radiotherapy, and then reactivity of PPD skin tests and lymphocyte blastoid transformations with PHA and Con A tended to increase instead. (J.P.N.)

CT in the staging of bronchogenic carcinoma

International Nuclear Information System (INIS)

McLoud, T.C.; Kosiuk, J.P.; Templeton, P.A.; Shepard, J.O.; Moore, E.H.; Mathisen, D.J.; Wain, J.C.; Grillo, H.C.

1989-01-01

The authors previously presented a study of the accuracy of CT in the staging of bronchogenic carcinoma by means of correlative lymph node mapping and sampling in 85 patients. This study has now been extended to include 143 patients. Abnormal nodes (greater than or equal to 1 cm) were localized according to the ATS classification of regional lymph node mapping. One hundred thirty-eight patients underwent mediastinoscopy and 116, thoracotomy. In each case, lymph node groups 2R, 4R, 2L, 4L (paratracheal), 7 (subcarinal), and 5 (aorticopulmonary) underwent biopsy on the appropriate sides. Hilar nodes were resected with the surgical specimen. A total of 554 nodes were sampled. Overall sensitivity of CT for all the lymph node groups was similar to the previous study and was 40.5% with a specificity of 84.2%. Sensitivity was highest for group 5 (83%), and lowest for the subcarinal area (25%) (group 7). Specificity ranged from 71% for 10R hilar nodes to 90% for the subcarinal nodes. The positive predictive value was 34% and the negative predictive value was 87%. This study corroborates the authors' previous results and shows that when careful correlation of individual lymph nodes groups identified on CT is done with those sampled at surgery, the accuracy of CT in staging bronchogenic carcinoma is limited

Oblique hilar tomography, computed tomography, and mediastinoscopy for prethoracotomy staging of bronchogenic carcinoma

International Nuclear Information System (INIS)

Khan, A.; Gersten, K.C.; Garvey, J.; Khan, F.A.; Steinberg, H.

1985-01-01

Preoperative oblique hilar tomography was used to evaluate hilar lymph nodes in 150 patients with clinically resectable bronchogenic carcinoma. CT was also used in the evaluation of mediastinal lymph nodes in 50 of these patients. Subsequently, all patients underwent mediastinoscopy and/or thoracotomy. Hilar and mediastinal nodes were evaluated for the presence of metastasis, and these findings were then correlated with the radiographic findings of oblique hilar tomography and CT. CT was found to be a reliable method for prethoracotomy staging of bronchogenic carcinoma and for selecting patients for mediastinoscopy. Thus patients with negative mediastinal CT need not undergo mediastinoscopy prior to thoracotomy, while mediastinoscopy and biopsy should be done in patients with enlarged mediastinal nodes on CT. Oblique hilar tomography is an accurate method for evaluation of hilar adenopathy and for predicting mediastinal involvement by extrapolation

[Benefits of cisplatin-based polychemotherapy in non-small cell bronchogenic carcinoma. Kyushu Lung Cancer Chemotherapy Study Group].

Science.gov (United States)

Ohta, M; Hara, N; Ichikawa, Y; Kanda, T; Shima, K; Tamura, K; Hokama, M

1988-06-01

We studied the efficacy of cisplatin-based polychemotherapy for non-small-cell lung cancer. One hundred nineteen patients with adenocarcinoma or large cell carcinoma were randomized to receive cyclophosphamide, adriamycin, cisplatin and mitomycin C (CAPM) or mitomycin C, cytosine arabinoside and tegafur (MCT), and 48 patients with squamous cell carcinoma were randomized to receive cisplatin, adriamycin and peplomycin (PAP) or mitomycin C, cyclophosphamide, tespamine, toyomycin and tegafur (MCTTT). Radiation was given to the chest in patients with stage I-III disease. The response rates were CAPM, 34.5%; MCT, 13.1% (p less than 0.01) and PAP, 63.3%; MCTTT, 42.3%. A significant difference in response rate between the CAPM and MCT regimens was observed only in stage IV patients and not in stage I-III patients. The median survival was 9.5 months in the CAPM arm vs. 6.5 months in the MCT arm (p less than 0.007), and 8.5 months in the PAP arm vs. 6.5 months in the MCTTT arm. Improved median survival for the CAPM regimen was noted only in stage IV patients and not in stage I-III patients when compared to patients given the MCT regimen, respectively. Nausea and vomiting were significantly increased in patients with cisplatin-based polychemotherapy. Myelosuppression was more severe with the CAPM regimen than with the other chemotherapy regimens. We concluded that cisplatin-based polychemotherapy, CAPM and PAP therapy were of more benefit to patients with disseminated non-small-cell lung cancer than MCT and MCTTT therapy.

Evaluation of hilar 67Ga-citrate uptake in bronchogenic carcinoma

International Nuclear Information System (INIS)

Matsuno, Noriyo; Kuyama, Junpei; Uchida, Yoshitaka; Hatano, Osamu; Imai, Yasunori; Uno, Kimiichi; Minoshima, Satoshi.

1995-01-01

We evaluated hilar uptake on 67 Ga-citrate scintigraphy and correlated with hilar lymph node metastases in one-hundred seventeen cases (two-hundred thirty four hila) of bronchogenic carcinoma. Hilar uptake was classified into three grades independently on anterior and posterior chest views: no uptake (grade 0), uptake equal to that in the thoracic vertebrae (grade 1), and uptake higher than that in the thoracic vertebrae (grade 2). If a summed grade of anterior and posterior view was larger than 3, hilar uptake was considered as positive. In forty-four cases (forty-nine hila) with hilar lymph node metastases, positive hilar uptake was found in ten cases (eleven hila), resulting in sensitivity of 22% based on cases and 23% based on hila. In seventy-three cases (one-hundred forty-six hila) without hilar lymph node metastases, positive hilar uptake was found in six cases (ten hila), resulting in specificity of 91% based on cases and 93% based on hila. In comparison to scintigraphic findings of unilaterally positive hilar uptake, findings of bilaterally positive hilar uptake showed significantly lower accuracy in determining presence of hilar lymph node metastases. No definite correlation between hilar uptake and histopathology or 67 Ga-citrate uptake in a primary tumor was observed. The results indicate that usefulness of 67 Ga-citrate scintigraphy is limited when evaluating hilar lymph node metastases in bronchogenic carcinoma. (author)

Coexistence of bronchial atresia and bronchogenic cyst: diagnostic criteria and embryologic considerations

International Nuclear Information System (INIS)

Kuhn, C.; Kuhn, J.P.

1992-01-01

We report a case in a neonate of concurrent bronchial atresia and bronchogenic cyst. An accurate, noninvasive, preoperative diagnosis of this unusual combination of anomalies was made by ultrafast computed tomography (UFCT). This case supports the hypothesis that bronchial atresia results from an event occurring in the 5th-6th week of embryological development, rather than after the 16th week as previously believed. (orig.)

Radiotherapy of bronchogenic carcinoma

International Nuclear Information System (INIS)

Heilmann, H.P.

1982-01-01

Radiotherapy of branchogenic carcinoma comprises; palliative treatment, postoperative or pre-operative radiotherapy, radiotherapy as part of a combination of chemotherapy and radiotherapy of small cell carcinoma and curative radiotherapy of non-operable non-small cell carcinoma. Atelectasis and obstruction are indications for palliative radiotherapy. Postoperative radiotherapy is given only in cases of incomplete resection or mediastinal metastases. In the treatment of small cell carcinoma by combined irradiation and chemotherapy the mediastinum and primary tumour are irradiated, generally after chemotherapy, and the C.N.S. receives prophylactic radiotherapy. Curative radiotherapy is indicated in cases of non-operable small cell carcinoma. Irradiation with doses of 60-70 Gy produced 5-years-survival rates of 10-14% in cases classified as T 1 -T 2 N 0 M 0 . (orig.) [de

Intraarterial digital subtraction angiography in bronchogenic carcinoma treated with bronchial artery infusion

International Nuclear Information System (INIS)

Gao-Jun Teng; Xi-Lei Chai; Guang-Ru Gao; Cheng-Fong Chu; Xian-Guang Zhou; Zhu-Yi Zhang; Ru-Li Xiang

1991-01-01

Intra-arterial digital subtraction angiography (IADSA) has been used with advantage for control of the results of bronchial artery infusion of drugs for primarily unresectable bronchogenic carcinoma. The IADSA has been performed as road mapping prior to therapy. Drug treatment has been performed with 4 different regimes, depending on tumour type. Debulking and in some cases complete healing are the results, which are superior to other reported treatments. (author). 7 refs.; 4 figs.; 3 tabs

The use of CT scan in the pre-operative staging of bronchogenic carcinoma

International Nuclear Information System (INIS)

Pada, C.C.

1992-01-01

Surgery remains the treatment of choice in patients with localized bronchogenic carcinoma. Pre-operative identification of inoperability spares the patient from unnecessary surgery. This prospective study was carried out to determine the correctness of judgement regarding a patient's operability or inoperability based on the pre-operative staging of CT scan; to find out the sensitivity, specificity and overall accuracy of the CT scan in estimating tumor description, nodal status and metastatic spread to the chest. Staging was done by 3 senior radiologists aware of the diagnosis. Both the surgical and histopathologic findings and staging were gathered and used as measurement of truth in arriving at the CT scan's accuracy. Overall accuracy rate of CT scan in determining operability or inoperability is 80%; tumor description accuracy of assessment is 87% and nodal status estimation has an accuracy of 60%. Sensitivity of CT scan is assessment of metastatic spread to the chest is 93%. There is no statistically significant difference in the judgement of operability or interpretability by CT scan compared to surgical and histopathologic results. The CT scan is recommended as a valuable tool in the pre-operative staging of patients with bronchogenic carcinoma who are candidates for surgery. (auth.). 21 refs.; 8 tabs

Radioisotope scans in the evaluation of metastatic bronchogenic carcinoma

International Nuclear Information System (INIS)

Gutierrez, A.C.; Vincent, R.G.; Bakshi, S.; Takita, H.

1975-01-01

In this study, we evaluated the accuracy of radioisotope scans in detecting metastatic lesions in patients with bronchogenic carcinoma. To be included in the study, the patient had to have undergone liver, brain, and/or bone scanning within 10 weeks of autopsy. Other means of evaluating these organs for metastatic involvement were used as well. The liver was checked by palpation and by determination of enzyme levels. A history, physical examination, and neurologic examination were used to establish the possibility of brain metastases. For studying bones, a history, physical examination, and conventional x-ray films were employed. Results of the scans and other tests were compared with findings at autopsy, and accuracy rates for each method of study were determined

Effects of histamine and 5-hydroxytryptamine on the growth rate of xenografted human bronchogenic carcinomas.

Science.gov (United States)

Sheehan, P F; Baker, T; Tutton, P J; Barkla, D H

1996-01-01

1. The influence of histamine and 5-hydroxytryptamine (5-HT) antagonists and agonists on the volume doubling times (Td) of human bronchogenic carcinomas propagated as s.c. xenografts in immunosuppressed mice was examined. 2. The H2-receptor antagonists, cimetidine and ranitidine, increased Td. 3. Treatment with the H2-receptor agonist, 4-methyl histamine, had no effect on Td. 4. Co-administration of 4-methyl histamine and cimetidine abolished the effects of cimetidine. 5. The 5-HT2-receptor antagonists, cinanserin and ketanserin, both increased Td. 6. Treatment with the 5-HT1/2-receptor agonist quipazine (0.1 mg/kg, reflecting 5-HT2 agonist activity) decreased Td, while a higher dose (10.0 mg/kg) had no effect. 7. The 5-HT1/2-receptor antagonist, methiothepin, decreased Td. 8. The 5-HT uptake inhibitor, fluoxetine, increased Td in one tumour line but not in another, while the 5-HT releaser/depletor, fenfluramine, increased Td. 9. Histamine may stimulate tumour growth through the histamine H2-receptor, while the dominant effect of 5-HT is 5-HT1-receptor inhibition. 10. Tumour growth in some bronchogenic carcinomas may involve 5-HT uptake mechanisms.

Anesthetic management for lobectomy of a 2-month-old infant with bronchogenic cyst: Case report along with review of literature

Directory of Open Access Journals (Sweden)

T Bansal

2017-01-01

Full Text Available Bronchogenic cyst, a benign congenital cystic lesion of the lung, is a rare cause of respiratory distress in children comprising 7.5% of all mediastinal masses. A thorough preoperative evaluation is crucial to plan for definitive intra- and post-operative management. All patients should be thoroughly evaluated for the presence of compression, deviation or distortion of airways and great veins. The easiest means of providing one lung ventilation in pediatrics is to intubate the main stem bronchus of the nonoperated lung. Other options available for pediatric one lung ventilation are single lumen endobronchial tubes, micro cuff tubes, Marraro bilumen tubes, and bronchial blockers. We hereby present a case report of a 2-month-old infant posted for excision of bronchogenic cyst along with a review of literature.

An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

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Yu Yu Thar

2016-01-01

Full Text Available Small cell neuroendocrine carcinoma (SNEC is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

Hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland

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Philip C Johnston

2013-01-01

Full Text Available Tumours metastasizing to the pituitary gland are uncommon. Symptomatic patients with pituitary metastases can present with diabetes insipidus, headache, visual field defects and/or anterior pituitary hormonal dysfunction. Treatment options for pituitary metastases include, surgical resection, cranial or parasellar irradiation and/or chemotherapy, and hormonal replacement if indicated. The overall prognosis of pituitary metastases is poor. We present a case of hypopituitarism as the presenting feature of bronchogenic carcinoma with metastases to the pituitary gland.

Mediastinal Bronchogenic Cyst With Acute Cardiac Dysfunction: Two-Stage Surgical Approach.

Science.gov (United States)

Smail, Hassiba; Baste, Jean Marc; Melki, Jean; Peillon, Christophe

2015-10-01

We describe a two-stage surgical approach in a patient with cardiac dysfunction and hemodynamic compromise resulting from a massive and compressive mediastinal bronchogenic cyst. To drain this cyst, video-assisted mediastinoscopy was performed as an emergency procedure, which immediately improved the patient's cardiac function. Five days later and under video thoracoscopy, resection of the cyst margins was impossible because the cyst was tightly adherent to the left atrium. We performed deroofing of this cyst through a right thoracotomy. The patient had an uncomplicated postoperative recovery, and no recurrence was observed at the long-term follow-up visit. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Upper cervical bronchogenic cyst: A rare condition at a rare location

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Ranjeet Kumar Jha

2018-01-01

Full Text Available Intraspinal bronchogenic cyst (SBC is a rare but important cause of spinal cord compression, commonly seen in the cervicothoracic spine. We report a case of a 43-year-old male, presenting with complaints of neck pain, radiating to right shoulder, with numbness of right hand and fingers. Magnetic resonance imaging of the cervical spine revealed an intradural extramedullary, ventral cystic lesion extending from C2 to C4 vertebral levels. Complete surgical excision was performed, and the patient had a complete relief of symptoms postoperatively. Only 11 cases of SBCs have been reported in literature. We discuss the peculiar location of this lesion, possible embryological reasons and the overall surgical outcome of SBC.

Coexisting bronchogenic carcinoma and pulmonary tuberculosis in the same lobe: radiologic findings and clinical significance

International Nuclear Information System (INIS)

Kim, Young Il; Goo, Jin Mo; Im, Jung Gi; Kim, Hyae Young; Song, Jae Woo

2001-01-01

Bronchogenic carcinoma can mimic or be masked by pulmonary tuberculosis (TB), and the aim of this study was to describe the radiologic findings and clinical significance of bronchogenic carcinoma and pulmonary TB which coexist in the same lobe. The findings of 51 patients (48 males and three females, aged 48-79 years) in whom pulmonary TB and bronchogenic carcinoma coexisted in the same lobe were analyzed. The morphologic characteristics of a tumor, such as its diameter and margin, the presence of calcification or cavitation, and mediastinal lymphadenopathy, as seen at CT, were retrospectively assessed, and the clinical stage of the lung cancer was also determined. Using the serial chest radiographs available for 21 patients, the possible causes of delay in the diagnosis of lung cancer were analyzed. Lung cancers with coexisting pulmonary TB were located predominantly in the upper lobes (82.4%). The mean diameter of the mass was 5.3 cm, and most tumors (n=42, 82.4%) had a lobulated border. Calcification within the tumor was seen in 20 patients (39.2%), and cavitation in five (9.8%). Forty-two (82.4%) had mediastinal lymphadenopathy, and more than half the tumors (60.8%) were at an advanced stage [IIIB (n=11) or IV (n=20)]. The average delay in diagnosing lung cancer was 11.7 (range, 1-24) months, and the causes of this were failure to observe new nodules masked by coexisting stable TB lesions (n=8), misinterpretation of new lesions as aggravation of TB (n=5), misinterpretation of lung cancer as tuberculoma at initial radiography (n=4), masking of the nodule by an active TB lesion (n=3), and subtleness of the lesion (n=1). Most cancers concurrent with TB are large, lobulated masses with mediastinal lymphadenopathy, indicating that the morphologic characteristics of lung cancer with coexisting pulmonary TB are similar to those of lung cancer without TB. The diagnosis of lung cancer is delayed mainly because of masking by a tuberculous lesion, and this suggests that

CT in the staging of bronchogenic carcinoma: Analysis by correlative lymph node mapping and sampling

International Nuclear Information System (INIS)

McLoud, T.C.; Woldenberg, R.; Mathisen, D.J.; Grillo, H.C.; Bourgoulin, P.M.; Shepard, J.O.; Moore, E.H.

1987-01-01

Although previous studies have evaluated the accuracy of CT in staging the mediastinum in bronchogenic carcinoma, none has determined the sensitivity and specificity of CT in the assessment of individual lymph node groups by correlative nodal sampling at surgery. CT scans were performed on 84 patients with bronchogenic carcinoma. Abnormal nodes (≥ 1 cm) were localized according to the ATS classification of regional lymph node mapping. Seventy-nine patients had mediastinoscopy and 64 patients underwent thoracotomy. In each case, biopsies of lymph node groups 2R, 4R, 2L, 4L (paratracheal), 7 (subcarinal), and 5 (aorticopulmonary) were performed on the appropriate side. Hilar nodes (10R and 11R, 10L and 11L) were resected with the surgical specimen. A total of 292 nodes were sampled. Overall sensitivity for all lymph node groups was 40%, and specificity, 81%. Sensitivity was highest for the 4R (paratracheal) group (82%) and lowest for the subcarinal area (20%). Specificity ranged from 71% for 11R nodes (right hilar) to 94% for 10L (left peribronchial). The positive predictive value was 34%, and the negative predictive value, 84%. This study suggests that the more optimistic results previously reported may have resulted from lack of correlation of individual lymph node groups identified on CT with those sampled at surgery

Expression of alveolar type II cell markers in acinar adenocarcinomas and adenoid cystic carcinomas arising from segmental bronchi. A study in a heterotopic bronchogenic carcinoma model in dogs.

Science.gov (United States)

TenHave-Opbroek, A. A.; Hammond, W. G.; Benfield, J. R.; Teplitz, R. L.; Dijkman, J. H.

1993-01-01

The type II alveolar epithelial cell is one of two pluripotential stem cell phenotypes in normal mammalian lung morphogenesis; cells manifesting this phenotype have been found to constitute bronchioloalveolar regions of canine adenocarcinomas. We now studied type II cell expression in canine acinar adenocarcinomas and adenoid cystic (bronchial gland) carcinomas, using the same bronchogenic carcinoma model (subcutaneous bronchial autografts treated with 3-methylcholanthrene). Distinctive features of type II cells are the approximately cuboid cell shape, large and roundish nucleus, immunofluorescent staining of the cytoplasm for the surfactant protein SP-A, and presence of multilamellar bodies or their precursory forms. Cells with these type II cell characteristics were found in the basal epithelial layer of all tumor lesions and in upper layers as far as the lumen, singly or in clusters; they were also found in early invasive carcinomatous lesions but not in bronchial glands or bronchial epithelium before carcinogen exposure. Immunoblots of tumor homogenates showed reactive proteins within size classes of SP-A (28 to 36 kd) or its dimeric form (56 to 72 kd). These findings and those previously reported are consistent with the concept that chemical carcinogenesis in the adult bronchial epithelium may lead to type II cell carcinomas of varying glandular (acinar, adenoidcystic or bronchioloalveolar) growth patterns. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 PMID:8386445

Surgical treatment of an esophageal bronchogenic cyst with massive upper digestive tract hematoma without esophagectomy: a case report and the review of the literature

Directory of Open Access Journals (Sweden)

Cheng Y

2018-05-01

Full Text Available Yuanjun Cheng,1,* Donglai Chen,2,* Li Shi,1 Wentao Yang,1 Yonghua Sang,1 Shanzhou Duan,1 Yongbing Chen1 1Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China; 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China *These authors contributed equally to this work Abstract: Esophageal bronchogenic cysts are extremely rare. Here we report a case of massive upper digestive tract hematoma and bronchogenic cyst mimicking aortic dissection that was safely removed without esophagectomy. A 30-year-old man was referred to our hospital for the treatment of a mediastinal cystic tumor located in the submucosa of the distal esophagus. His chief complaints were dysphagia > 1 week and severe persistent upper abdominal pain mimicking aortic dissection with constant vomiting for 1 day after gastroscopy examination. The serum level of carbohydrate antigen (CA199 was > 1,000 U/mL and CA125 was 4,816 U/mL. Hemoglobin levels decreased from 122 g/L to 85 g/L in 5 days. Imaging examinations detected a huge hematoma of the gastric wall. Preoperative diagnosis was difficult. Although the pain indicated a possible aortic dissection, the abnormal levels of tumor biomarkers suggested malignancy. The patient underwent left thoracotomy. The cyst showed an exophytic lesion connected to the esophageal wall at the level of the gastroesophageal junction. Muddy brown contents were obtained by aspiration of the mass intraoperatively. Because enucleation could not be performed, esophageal myotomy in the distal esophagus and partial resection of the cyst were selected. Histopathological examination indicated a bronchogenic cyst of the esophagus. At a follow-up visit 3 months later, the patient had no signs of disease recurrence or any complaints. Postoperative tumor biomarkers returned to normal range. The present report summarizes the clinical details of the case and

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

Science.gov (United States)

Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

2014-04-01

Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

The role of CT in the diagnosis of bronchogenic carcinoma not detected by plain radiograph

International Nuclear Information System (INIS)

Choi, Byoung Wook; Choe, Kyu Ok; Lee, Je Hyuk; Ryu, Seok Jong

2000-01-01

To evaluate the role of CT and CT features in the diagnosis of bronchogenic carcinomas not detected by plain radiography. Eighteen patients [19 primary cancer lesions, M:F=16:2, aged 43-75 (mean, 56.3) years] with lung cancer initially not detected by plain radiography were involved in this study. CT scanning was performed in all cases, and fibrobronchoscopy, and sputum cytology, each in 17. Lesions were divided into two groups: the central type, if on or proximal to the segmental bronchus, and the peripheral type, if distal to this. Plain radiographs were analysed for possible causes of occultness and for clinical characteristics including cell type, location, and size. We focused on the CT findings, comparing cases undetected by CT with those undetected by bronchoscopy. In the central type, the cause of occultness, as seen on plain radiographs, was small size, no secondary findings, or confusing shadow from hilar vessels. In the peripheral type, the cause was overlapping shadow due to normal structures of the chest, or combined diseases. Eight lesions were first detected by sputum cytology, 6 by bronchoscopy, and 5 by CT. Fourteen lesions were the central type (main bronchus 2, lobar bronchus 7, segmental bronchus 5), and five were peripheral. Central-type lesions were either squamous cell carcinoma (n=11), adenocarcinoma (n=1), small cell carcinoma (n=1), or large cell carcinoma (n=1). The peripheral type were either squamous cell carcinoma (n=2), adenocarcinoma (n=2), or large cell carcinoma (n=1). Size ranged from 0.2 to 4(mean, 2; central 1.7, peripheral 2.8) cm. Surgical resection was possible in 15 patients (16 cancers, including 13 at stage I). Only two were at a stage which rendered them unresectable. CT revealed 13 cancers, including all those which were peripheral. The finding were endobronchial nodule (n=4), bronchial wall thickening (n=1), perihilar mass (n=3), parenchymal mass (n=2), and subpleural mass (n=3). In six central-type cases [endobronchial

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

Directory of Open Access Journals (Sweden)

Abdel Kader Y

2013-07-01

in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.Keywords: bevacizumab, non-small cell lung cancer, NSCLC, pemetrexed

Lung cancer - small cell

Science.gov (United States)

Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

Lung cancer: Value of computed tomography in radiotherapy planning and evaluation of tumour remission

International Nuclear Information System (INIS)

Feyerabend, T.; Schmitt, R.; Richter, E.; Bohndorf, W.

1990-01-01

434 CT examinations of 133 patients with histologically proven bronchogenic carcinoma (22 out of 133 with small cell lung cancer) were analysed before and after radiotherapy. The study evaluates the use of CT for determining target volume, tumour volume and remission rate: 1. Concerning determination of target volume conventional roentgendiagnostic simulator methods are much inferior to CT aided planning; as for our patients changes of the target volume were necessary in 50%, in 22% the changes were crucial. This happened more often in non-small cell lung cancer than in small cell carcinomas. 2. The response rate (CR + PR) after radiotherapy (based on the calculated tumour volumes by CT) was 70 to 80%. The rate of CR of the primary was 45% (non-small cell carcinoma) and 67% (small cell carcinoma). 3. The crucial point for the evaluation of tumour remission after radiotherapy is the point of time. One to three months and four to nine months after irradiation we found complete remissions in 19% and 62%, respectively. Hence, the evaluation of treatment results earlier than three months after radiotherapy may be incorrect. We deem it indispensable to use CT for determination of target, calculation of dose distribution and accurate evaluation of tumour remission and side effects during and after irradiation of patients with bronchogenic carcinoma. (orig.) [de

Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

DEFF Research Database (Denmark)

Bork, E; Hansen, M; Urdal, P

1988-01-01

Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

[Optimization of radiotherapy planning for non-small cell lung cancer (NSCLC) using 18FDG-PET].

Science.gov (United States)

Schmidt, S; Nestle, U; Walter, K; Licht, N; Ukena, D; Schnabel, K; Kirsch, C M

2002-10-01

In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most causes (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm2, after redefinition using PET 166 cm2. In 20 patients with disturbed ventilation caused by the tumour (atelectasis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation.

Cardiac dynamic magnetic resonance of a giant lung carcinoma invading the left atrium : do not let the imaging fool you

NARCIS (Netherlands)

Pozzoli, Alberto; Klinkenberg, Theo J.; De Maat, Gijs E.; Mariani, Massimo A.

This study aimed to report on a non-small-cell lung cancer (NSCLC) originating from the right lung lower lobe and circulatory extension into the left atrium. Atrial involvement is an uncommon feature of advanced NSCLC, occurring in up to 10% of patients with bronchogenic carcinoma. In this case, the

Lung cancer - non-small cell

Science.gov (United States)

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 ...

The difference of the regional pulmonary function after treatment between bronchial tuberculosis and bronchogenic carcinoma using positron emission tomography, N-13 gas and Tc-MAA

International Nuclear Information System (INIS)

Suzuki, Tsuneo; Kawada, Hiroshi; Toyoda, Emiko; Kabe, Jyunzaburou

1993-01-01

The authors studied regional pulmonary function after treatment with bronchial plastic surgery for bronchial lesion from bronchial tuberculosis and with irradiation for bronchial lesion from carcinoma using positron emission tomography and Tc-MAA. Six patients with bronchial tuberculosis and 6 with bronchogenic carcinoma were examined. Two of the 6 bronchial tuberculosis patients were examined before and after surgery. In all 6 patients with bronchial tuberculosis, ventilation and alveolar volume were recovered with improvement of bronchial lesion. In 2 patients examined before and after surgery, lung function of the normal disease-free side became worse after surgery. This phenomenon was explained by the fact that the compensated pulmonary function of contra lateral lung due to decreased function of the diseased side returned to normal function with improvement of the diseased lung. On the other hand, the regional pulmonary function did not improve in 2 patients with main bronchial lesion from bronchogenic carcinoma, even if atelectasis of the diseased lung was improved by irradiation. However, the regional pulmonary function was improved with the recovery of bronchial obstruction in lobar atelectasis by carcinoma. The difference of the results depended on whether pulmonary blood flow disturbance existed or not. If pulmonary blood flow disturbance was severe, ventilatory function was not recovered due to the mechanism of maintaining the ventilation-perfusion equilibrium. (author)

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...

Accelerated Fractionation In The Treatment of Brain Metastasis From Non-Small Cell Carcinoma of The Lung

International Nuclear Information System (INIS)

Hong, Seong Eon

1994-01-01

Purpose: Metastatic cancer to the brain is a major problem for the patients with bronchogenic carcinoma, and most of these patients have a limited survival expectancy. To increase tumor control and/or to decrease late morbidity with possible shortening in over-all treatment period, multiple daily fraction technique for brain metastasis was performed. The author represented the results of accelerated fractionation radiotherapy in patients with brain metastases from non-small cell lung cancer. Materials and Methods: Twenty-six patients with brain metastases from non-small cell lung cancer between 1991 and 1993 received brain radiotherapy with a total dose of 48 Gy, at 2 Gy per fraction, twice a day with a interfractional period of 6 hours, and delivered 5 days a week. The whole brain was treated to 40 Gy and boost dose escalated to 8 Gy for single metastatic lesion by reduced field. Twenty-four of the 26 patients completed the radiotherapy. Radiotherapy was interrupted in two patients suggesting progressive intracerebral disease. Results: This radiotherapy regimen appears to be comparable to the conventional schema in relief from symptoms. Three of the 24 patients experienced nausea and or vomiting during the course of treatment because of acute irradiation toxicity. The author observed no excessive toxicity with escalating dose of irradiation. An increment in median survival, although not statistically significant (p>0.05), was noted with escalating doses(48 Gy) of accelerated fractionation (7 months) compared to conventional treatment(4.5 months). Median survival also increased in patients with brain solitary metastasis(9 months) compared to multiple extrathoracic sites(4 months), and in patients with good performance status(9 months versus 3.5 months), they were statistically significant(p<0.01). Conclusion: The increment in survival in patients with good prognostic factors such as controlled primary lesion, metastasis in brain only, and good performance status

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 ...

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....

CEBPG transcription factor correlates with antioxidant and DNA repair genes in normal bronchial epithelial cells but not in individuals with bronchogenic carcinoma

International Nuclear Information System (INIS)

Mullins, D'Anna N; Crawford, Erin L; Khuder, Sadik A; Hernandez, Dawn-Alita; Yoon, Youngsook; Willey, James C

2005-01-01

Cigarette smoking is the primary cause of bronchogenic carcinoma (BC), yet only 10–15% of heavy smokers develop BC and it is likely that this variation in risk is, in part, genetically determined. We previously reported a set of antioxidant genes for which transcript abundance was lower in normal bronchial epithelial cells (NBEC) of BC individuals compared to non-BC individuals. In unpublished studies of the same NBEC samples, transcript abundance values for several DNA repair genes were correlated with these antioxidant genes. From these data, we hypothesized that antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that inter-individual variation in expression and/or function of one or more of these transcription factors is responsible for inter-individual variation in risk for BC. The putative transcription factor recognition sites common to six of the antioxidant genes were identified through in silico DNA sequence analysis. The transcript abundance values of these transcription factors (n = 6) and an expanded group of antioxidant and DNA repair genes (n = 16) were measured simultaneously by quantitative PCR in NBEC of 24 non-BC and 25 BC individuals. CEBPG transcription factor was significantly (p < 0.01) correlated with eight of the antioxidant or DNA repair genes in non-BC individuals but not in BC individuals. In BC individuals the correlation with CEBPG was significantly (p < 0.01) lower than that of non-BC individuals for four of the genes (XRCC1, ERCC5, GSTP1, and SOD1) and the difference was nearly significant for GPX1. The only other transcription factor correlated with any of these five target genes in non-BC individuals was E2F1. E2F1 was correlated with GSTP1 among non-BC individuals, but in contrast to CEBPG, there was no significant difference in this correlation in non-BC individuals compared to BC individuals. We conclude that CEBPG is the transcription factor primarily responsible for regulating

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...

Sequential radiotherapy and adriamycin in the management of bronchogenic carcinoma: the question of additive toxicity

Energy Technology Data Exchange (ETDEWEB)

Ruckdeschel, J.C.; Baxter, D.H.; McKneally, M.F.; Killam, D.A.; Lunia, S.L.; Horton, J.

1979-08-01

Intrapleural immunotherapy, radiotherapy and chemotherapy were employed in that sequence in 22 patients with Stage III non-oat cell bronchogenic carcinoma confined to the thorax. Seven patients received intrapleural BCG in a pilot study and 15 were randomized between intrapleural BCG and intrapleural saline. Isoniazid was begun on day 14 and irradiation (3000 rad in 10 fractions) to the primary lesion, mediastinum and ipsilateral supraclavicular nodes was started on day 21. One to two weeks following irradiation, CAMP chemotherapy was initiated (Cyclophosphamide 300 mg/M/sup 2/ iv, d. 1,8; Adriamycin 20 mg/M/sup 2/ iv, d. 1,8; Methotrexate 15 mg/M/sup 2/ iv, d. 1,8 and Procarbazine 100 mg/M/sup 2/ p.o., d. 1 to 10). Chemotherapy was given for a total of six months. Two patients expired prior to radiotherapy (1 tumor progression, 1 myocardial infarction) and 2 patients were lost to follow-up. Nausea, vomiting, alopecia and fatigue were universal side effects of the chemotherapy. Esophagitis occurred in 9 patients, 7 prior to and 2 after initiation of Adriamycin. In only one case did Adriamycin exacerbate a previous radiation esophagitis. No patient developed clinical radiation pneumonitis, although all had eventual radiation fibrosis. Congestive heart failure occurred in 1 patient with known valvular heart disease and responded to diuretics. Three patients developed localized herpes zoster infections. One patient developed radiation myelitis one year after initiating therapy and six months after completing all chemotherapy. The major side effect was leukopenia with relative platelet sparing. Although significant morbidity was encountered in this primarily older patient population (mean age 64.8 years) recall reactions involving irradiated intrathoracic structures were not a significant clinical problem.

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 ...

Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

NARCIS (Netherlands)

El Sharouni, S.Y.

2009-01-01

This thesis concerns the treatment of stage III non-small cell lung cancer (NSCLC) and limited disease small-cell lung cancer (SCLC). We described a systematic review on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCLC stage III with the aim to define the

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...

Regional immunotherapy has a detrimental effect on the response to combined irradiation and chemotherapy in locally advanced non-small cell bronchognic carcinoma

International Nuclear Information System (INIS)

Ruckdeschel, J.C.; De Vore, C.; Caradonna, R.; Horton, J.; McKneally, M.F.; Kellar, S.; McIlduff, J.B.; Baxter, D.H.; Killam, D.; Sedransk, N.

1981-01-01

Twenty-one patients with stage III M 0 non-oat cell bronchogenic carcinoma confined to the thorax were randomized to receive either intrapleural BCG (10 7 cfu, Tice strain) or intrapleural saline 3 weeks prior to beginning combined irradiation and chemotherapy. Radiation to the primary tumor and regional nodes was given at a dose of 3,000 rad in ten sessions and was followed in 7-14 days by CAMP chemotherapy (cyclophosphamide, adriamycin, methotrexate, and procarbazine) for a planned duration of 6 months. Isoniazid, 300 mg/day, was given to all patients for 3 months starting 1 week after intrapleural therapy. There were no significant differences in pretreatment prognostic factors or in response to radiation therapy. The patients receiving intrapleural BCG in addition to radiation and chemotherapy had a median survival of 18 weeks, significantly shorter than that for the patients receiving intrapleural saline (54 weeks, P=0.017). (orig.)

Morphometric Characterization of Small Cell Lymphocytic Lymphoma

Directory of Open Access Journals (Sweden)

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.

Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

DEFF Research Database (Denmark)

Bork, E; Hansen, M; Urdal, P

1988-01-01

Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...... determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy....

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

Plain radiologic findings of primary lung cancer by histologic types

International Nuclear Information System (INIS)

Lee, Young Seok; Park, Jae Hyung; Choi, Byung In; Yeon, Kyung Mo; Kim, Chu Wan

1983-01-01

Plain chest films are the most useful modality in diagnosis of primary lung cancer, but it is difficult to interpret the radiologic findings by histological types. Authors reviewed chest films of 324 cases of histologically confirmed primary lung cancer from January 1974 to April 1982 at Seoul National University. The results are as follows; 1. Incidence was most common in the 6th decade as 34.4%. Male to female sex radio was 3.8 : 1 and there was no sex difference in Adenocarcinoma. 2. Distribution of histologic types of primary lung cancers as follows; Squamous cell carcinoma 50.6%, Small cell carcinoma 22.5%, Large cell carcinoma 9.3%, Bronchogenic adeno carcinoma 10.5%, Bronchioloalveolar cell carcinoma 1.9%, Adenosquamous carcinoma 0.6%, Carcinoid tumor 0.3%, Adenoid cystic carcinoma 0.3%. 3. Radiologic findings by histologic types are follows; a) Squamous cell carcinoma commonly present as collapse (51.8%), peripheral mass (40.8%), pneumonitis (37.2%), hilar involvement (34.8%), and in single abnormality, peripheral mass (44.4%). b) Small cell carcinoma commonly present as hilar involvement (78.1%), mediastinal widening or mass (53.4%) and in single abnormality, hilar involvement (58.3%). c) Large cell carcinoma commonly present as hilar involvement (50%), pneumonia (46.7%), collapse (40%), peripheral mass (36.7%) and in single abnormality, large peripheral mass (33.3%). d) Bronchogenic adenocarcinoma commonly present as peripheral mass (44.1%), collapse (41.2%), pleural effusion (35.2%) and in single abnormality, peripheral mass (50%). e) Solitary peripheral mass commonly present as lobulation (48%) and spiculated margin (51%), but no specific findings by histologic types. Cavitary formation was most common in Squamous cell carcinoma

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

Science.gov (United States)

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.

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

Radiotherapy of non-parvicellular bronchogenic carcinoma

International Nuclear Information System (INIS)

Sack, H.

1984-01-01

Radiotherapeutic results of non-oat-cell carcinoma of the lung are limited by the fact that 50 to 80% of the patients have occult distant metastases at the time of diagnosis. Surgery is the treatment of choice in early stages. Only when operation is not possible because of general reasons definite radiation therpy is indicated in curative intent. The 5 year survival rates reach 20%. Pre- and postoperative radiotherapy have not ameliorated the results of surgery alone in the majority of patients and are indicated therefore only in special situations described, e. g. pancoast carcinoma. Most patients are inoperable. Among these only those should be irradiated in curative intention in whom the risk of occult distant metastases is small. Then 5 years survival rates about 9% are realistic. For the majority of patients radiotherapy has palliative possibilities, indications are hemoptisis, atelectasis, cough, pain, vena cava superior syndrom, and symptoms by distant metastases. A palliative effect can be reached with low side effects and in short treatment time. (orig.) [de

Cellular radiosensitivity of small-cell lung cancer cell lines

DEFF Research Database (Denmark)

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...

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)

Primary Small Cell Carcinoma of the Upper Urinary Tract

Directory of Open Access Journals (Sweden)

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.

Neuroendocrine small cell carcinoma of the uterine cervix.

Science.gov (United States)

Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

2010-07-01

Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

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,

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.

Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent Stem Cells.

Science.gov (United States)

Mathapati, Santosh; Siller, Richard; Impellizzeri, Agata A R; Lycke, Max; Vegheim, Karianne; Almaas, Runar; Sullivan, Gareth J

2016-08-17

Hepatocyte-like cells (HLCs) generated in vitro from human pluripotent stem cells (hPSCs) provide an invaluable resource for basic research, regenerative medicine, drug screening, toxicology, and modeling of liver disease and development. This unit describes a small-molecule-driven protocol for in vitro differentiation of hPSCs into HLCs without the use of growth factors. hPSCs are coaxed through a developmentally relevant route via the primitive streak to definitive endoderm (DE) using the small molecule CHIR99021 (a Wnt agonist), replacing the conventional growth factors Wnt3A and activin A. The small-molecule-derived DE is then differentiated to hepatoblast-like cells in the presence of dimethyl sulfoxide. The resulting hepatoblasts are then differentiated to HLCs with N-hexanoic-Tyr, Ile-6 aminohexanoic amide (Dihexa, a hepatocyte growth factor agonist) and dexamethasone. The protocol provides an efficient and reproducible procedure for differentiation of hPSCs into HLCs utilizing small molecules. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Small cell extraskeletal osteosarcoma: a rare case report

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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.

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.

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...

Erlotinib in previously treated non-small-cell lung cancer

International Nuclear Information System (INIS)

Smrdel, U.; Kovac, V.

2006-01-01

Background. Erlotinib is a novel biological anti-tumour agent in the treatment of advanced non small cell lung cancer. It represents the molecularly-targeted therapy which has been studied extensively. Case report. We present a case of a patient who suffered from advanced non-small-cell lung cancer. After the progress of disease following a prior chemotherapy he was treated with erlotinib with remarkable effect which was shown at chest x ray and symptoms were quite reduced. Conclusions. In selected patients with advanced non-small-cell lung cancer Erlotinib improves survival and symptom control as it results in presented case. (author)

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

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

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.)

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.

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.

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...

A mass that has no (EBUS echo

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Matthew K. Rosenblum

Full Text Available We report findings for a patient that underwent endobronchial ultrasound (EBUS guided transbronchial needle aspiration (TBNA for diagnostic purposes after an abnormal chest CT. The patient initially presented with cough and shortness of breath. Chest CT revealed a 6 cm soft tissue mass with mildly enlarged right hilar lymph nodes (LNs and a small right sided pleural effusion. Based on these radiologic findings, the patient underwent an EBUS guided FNA of the mass. To our surprise, the mass was hypoechoic by EBUS and on aspiration, the syringe filled with yellow fluid. This finding in combination with a re-review of the CT scans with a special focus on the Hounsfield Units of the lesion confirmed the diagnosis of a mediastinal bronchogenic cyst. This case demonstrates the role of Hounsfield units in analyzing mediastinal masses and highlights the effectiveness of EBUS guided TBNA in diagnosis and treatment of bronchogenic cysts. Keywords: Bronchogenic cysts, Endobronchial ultrasound, Hounsfield units

Small cell cervical cancer: an unusual finding at cholecystectomy.

LENUS (Irish Health Repository)

Boyle, Emily

2012-02-01

BACKGROUND: Small cell carcinoma of the cervix is a rare cancer, comprising less than 3% of all cervical neoplasms. It uniformly has a poor prognosis, and has a high mortality even with early stage disease. It can metastasise rapidly and metastatic sites include lung, liver, brain, bone, pancreas and lymph nodes. CASE: Here, we report the case of a 60-year-old woman with no symptoms of cervical pathology who developed post-renal failure following a laparoscopic cholecystectomy. The cause was bilateral ureteric obstruction from metastatic small cell cervical cancer and metastases were subsequently found on her gallbladder specimen. CONCLUSION: This is an unusual presentation of small cell cervical cancer and demonstrates the aggressive nature of this disease.

Small molecule probes for plant cell wall polysaccharide imaging

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

Science.gov (United States)

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 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

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....

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.

Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report

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Jignasa N. Bhalodia

2011-01-01

Full Text Available Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE.

Small cell lung cancer: chemo- and radiotherapy

International Nuclear Information System (INIS)

Drings, P.

1992-01-01

Small-Cell Lung Cancer - Chemo- and Radiotherapy: Small-cell lung cancer (SCLC) should be regarded as a systematic disease for which systematic therapy, i.e. chemotherapy, is considered as the cornerstone of treatment. Combination chemotherapy consisting of 2 or mostly 3 active drugs, given at an adequate dose, should be used. Thoracic radiation therapy promises both survival and local-regional control benefits to patients though its optimal role remains to be definitively established. The results of treatment have reached a plateau with a remission rate of up to 90% in stage 'limited disease' and 60% in stage 'extensive disease'. But considering long-term results diseasefree survival and cure only seem possible in 5-10% of patients with limited disease. (orig.) [de

A rare bladder cancer - small cell carcinoma: review and update

Directory of Open Access Journals (Sweden)

Ismaili Nabil

2011-11-01

Full Text Available Abstract Small cell carcinoma of the bladder (SCCB is rare, highly aggressive and diagnosed mainly at advanced stages. Hematuria is the main symptom of this malignancy. The origin of the disease is unknown; however the multipotent stem cell theory applies best to this case. Histology and immunohistochemistry shows a tumour which is indistinguishable from small cell lung carcinoma (SCLC. Coexistence of SCCB with other types of carcinoma is common. The staging system used is the TNM-staging of bladder transitional cell carcinoma. The treatment is extrapolated from that of SCLC. However, many patients with SCCB undergo radical resection which is rarely performed in SCLC. Patients with surgically resectable disease ( or = cT4bN+M+ should be managed with palliative chemotherapy based on neuroendocrine type regimens comprising a platinum drug (cisplatin in fit patients. The prognosis of the disease is poor mainly in the case of pure small cell carcinoma. Other research programs are needed to improve the outcome of SCCB.

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

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

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

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...

Local therapy for small cell carcinoma of the cervix

International Nuclear Information System (INIS)

Nakamura, C.; Chen, Y.; DuBeshter, B.; Angel, C.; Dawson, A.; Casey, W.

1996-01-01

Objective: Small cell carcinoma of the uterine cervix is a rare and aggressive tumor. This tumor is similar to small cell carcinoma of the lung with a tendency to metastasize early. While there has been an increasing interest in the use of chemotherapy regimens similar to those used for small cell carcinoma of the lung, the optimum local therapy for small cell carcinoma of the cervix remains unknown. We reviewed the treatment outcome of patients with small cell carcinoma of the cervix diagnosed in our cancer center with an emphasis on the local/regional disease control. Material and Methods: Between 1983 and 1993, medical records of patients diagnosed with carcinoma of the uterine cervix were reviewed. There were 281 patients with carcinoma of the uterine cervix referred to our department for radiation treatment. Seven patients had pathologic diagnosis of either small cell or neuroendocrine histology. Details of the treatments and follow-up information of these patients were reviewed with a medium follow-up period of three years (range - 1 to 4 years). Results: Five patients had pure small cell histology. Two patients had mixed histology: one with mixed small cell anaplastic neuroendocrine cells and a small foci of adenocarcinoma, the other had mixed small cell and squamous cell histology. Four patients had clinical stage IB disease. The others had IIA, IIB, and IIIB disease, respectively. All patients received either irradiation (XRT) alone or as part of the local therapy. Three patients received XRT alone, one received surgery followed by XRT, one received XRT followed by surgery, and the remaining two had triple modality treatment (chemotherapy, surgery, and XRT). Three patients were alive without evidence of disease recurrence at the last follow-up. Two of these received adjuvant chemotherapy in addition to local therapy. The third patient, whose tumor was smaller than one cm at the time of diagnosis, received XRT alone. Four patients died with disease

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

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

A role of computed tomography or magnetic resonance imaging for cystic lung diseases in children

International Nuclear Information System (INIS)

Yanagihara, Jun; Shimotake, Takashi; Deguchi, Eiichi; Tokiwa, Kazuaki; Iwai, Naomi

1995-01-01

Fourteen children with cystic lung diseases were imaged using computed tomography (CT) and/or magnetic resonance imaging (MRI). These patients studied included 7 patients with bronchogenic cyst of lung, 4 with pulmonary sequestration, 1 with congenital cystic adenomatoid malformation, 1 with lung abscess, and 1 with cystic bronchoectasis. MRI identified all lesions seen on the chest radiographs. It was particularly valuable delineating contents of bronchogenic cyst without the need for contrast material enhancement. However, MRI was not quite as sensitive as CT that detected very small abnormalities, because MRI had more artifacts than those of CT. In conclusion, we believe that both CT and MRI are needed for differential diagnosis of lung diseases in children. (author)

A role of computed tomography or magnetic resonance imaging for cystic lung diseases in children

Energy Technology Data Exchange (ETDEWEB)

Yanagihara, Jun; Shimotake, Takashi; Deguchi, Eiichi; Tokiwa, Kazuaki; Iwai, Naomi [Kyoto Prefectural Univ. of Medicine (Japan)

1995-06-01

Fourteen children with cystic lung diseases were imaged using computed tomography (CT) and/or magnetic resonance imaging (MRI). These patients studied included 7 patients with bronchogenic cyst of lung, 4 with pulmonary sequestration, 1 with congenital cystic adenomatoid malformation, 1 with lung abscess, and 1 with cystic bronchoectasis. MRI identified all lesions seen on the chest radiographs. It was particularly valuable delineating contents of bronchogenic cyst without the need for contrast material enhancement. However, MRI was not quite as sensitive as CT that detected very small abnormalities, because MRI had more artifacts than those of CT. In conclusion, we believe that both CT and MRI are needed for differential diagnosis of lung diseases in children. (author).

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

Energy Technology Data Exchange (ETDEWEB)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J. [and others

1995-12-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to {alpha}-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMV{Beta} vector; and (2) the antibiotic hygromycin-resistant transfected cells.

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

International Nuclear Information System (INIS)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J.

1995-01-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to α-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMVΒ vector; and (2) the antibiotic hygromycin-resistant transfected cells

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

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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.

New small molecules targeting apoptosis and cell viability in osteosarcoma.

Directory of Open Access Journals (Sweden)

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.

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)

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

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...

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.

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

Should patients with extrapulmonary small-cell carcinoma receive prophylactic cranial irradiation?

LENUS (Irish Health Repository)

Naidoo, Jarushka

2013-09-01

Extrapulmonary small-cell carcinoma (EPSCC) is a rare disease. Management is based on small-cell lung carcinoma. Prophylactic cranial irradiation (PCI) is not routinely administered in EPSCC. This study investigates the role of PCI in EPSCC, by analyzing the incidence, treatment, and survival of patients with brain metastases in a national cohort. Disease biology and epidemiology are also investigated.

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.

Carcinoma broncogénico epidermoide en un hombre de 21 años Epidermoid bronchogenic carcinoma in a 21 year old black man

Directory of Open Access Journals (Sweden)

John Jairo Duque Alzate

1999-01-01

Full Text Available Hombre de 21 años de edad de raza negra, natural del Chocó (Colombia, quien ha desempeñado diversos oficios; presentó un síndrome de dificultad respiratoria de dos meses de evolución, dolor pleurítico derecho, insuficiencia cardíaca congestiva y síntomas sistémicos. En la necropsia se encontró una masa tumoral blanco-grisácea de 10 x 8 cm, homogénea, con áreas de necrosis, originada en el bronquio principal de los lóbulos inferior y medio derechos y que invadió por vecindad en forma de coraza todo el pericardio causando una pericarditis constrictiva tumoral. El estudio microscópico correspondió a un carcinoma broncogénico tipo epidermoide bien diferenciado. El carcinoma broncogénico se asocia frecuentemente con el consumo de cigarrillo pero su incidencia ha c.umentado entre las personas no fumadoras, lo que sugiere la posibilidad de otros factores que influyen en su presentación como son los contaminantes atmósféricos, la predisposición genética, la dieta deficiente en vitamina A y carotenos, la presencia de ciertos virus y cambios inmunológicos. Este tumor constituye el 16% de todos los cánceres en el hombre y e113% en las mujeres; aparece con mayor frecuencia entre los 40 y los 70 años y sólo del1 al 5% de los casos se presenta en menores de 40 años. A 21 year cid black man, native from Chocó (Colombia, variously employed, who presented with a respiratory difficulty syndrome of two months of evolution, right pleuritic pain, congestive cardiac failure and systemic symptoms. A homogeneic white .grayish tumor measuring 8 by 10 cm with necrotic areas was found at necropsy. The tumor originated in the main bronchial tube of the lower and middle lobes of the right lung and invaded the entire pericardial vicinity forming a cuirass and causing tumoral constrictive pericarditis. Microscopic studies revealed a well differentiated squamous type bronchogenic carcinoma. Bronchogenic carcinomas are frequently associated with

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...

Iris metastasis in small-cell lung carcinoma

NARCIS (Netherlands)

Roenhorst, Anke W. J.; van den Bergh, Alphons C. M.; van Putten, John W. G.; Smit, Egbert F.

2007-01-01

Small-cell lung cancer (SCLC) is characterized by rapid growth and early metastasis. Despite its sensitivity to cytotoxic treatment, until now treatments have failed to control or cure this disease in most patients. Here, we describe a patient with SCLC in which symptoms caused by iris metastasis

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...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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

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

Directory of Open Access Journals (Sweden)

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.

Small cell carcinoma of the larynx: results of therapy

International Nuclear Information System (INIS)

Sole, J.; Juergens, A.; Musulen, E.; Lacasta, A.; Guedea, F.; Quer, M.; Leon, X.; Lopez Pousa, A.; Lerma, E.

1994-01-01

Small cell carcinoma is a rare malignant tumor of the larynx. Since this lesion was first described, only 58 cases have been reported in the literature. Between December 1985 and March 1992, five patients with small cell carcinoma of the larynx were treated at the Hospital de la Santa Creu i Sant Pau in Barcelona, Spain. One patient was treated with radiation therapy alone, three patients with chemotherapy and radiation therapy, and one patient with surgery, chemotherapy and radiation therapy. Local and distant control was achieved in only one patient who was observed for 12 months after radiation therapy. Four patients died, one of local disease without distant metastasis at 6 months following treatment, one of local and distant disease at 53 months after radiation therapy, and two of distant metastasis without local disease at 22 and 36 months following treatment. In spite of the fact that only one of the five patients presented in this series is alive and free of disease 12 months following treatment, recent published information suggests that chemotherapy and radiotherapy are currently the most effective form of therapy for small cell carcinoma of the larynx. 16 Refs

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 .)....

A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

Science.gov (United States)

Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

1992-12-01

Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

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

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...

Changes in cell-mediated immunity in patients undergoing radiotherapy

International Nuclear Information System (INIS)

Rafla, S.; Yang, S.J.; Meleka, F.

1978-01-01

The cell-mediated immune status of 147 patients who received radiotherapy was evaluated using in vitro tests (PHA, E-rosette, and spontaneous blastogenesis) both before and 6 weeks after the end of radiation. All patients have verified malignancies, involving the bronchus in 29 cases, breast in 28, female genital system in 26, head and neck in 20 and bladder in 15. Patients suffering from bronchogenic carcinomas or malignancies of the head and neck showed a relative high degree of immune suppression. Our findings indicate a trend towards some improvement in PHA reactivity, as well as in the percentage of E-rosette-forming cells after treatment, which is more noticeable in patients with pelvic or breast tumors. A relationship seems to exist between the tumor load and the immune status, which reverts to a normal pattern when the former is extinguished. Moreover, patients with poor clinical response display a profoundly depressed level of immune status without any improvement after treatment

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

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 ...

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.

Small molecules enhance CRISPR genome editing in pluripotent stem cells.

Science.gov (United States)

Yu, Chen; Liu, Yanxia; Ma, Tianhua; Liu, Kai; Xu, Shaohua; Zhang, Yu; Liu, Honglei; La Russa, Marie; Xie, Min; Ding, Sheng; Qi, Lei S

2015-02-05

The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells. Copyright © 2015 Elsevier Inc. 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

Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

Directory of Open Access Journals (Sweden)

Charlotte T A H Wetzels

Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

Actin and microtubule networks contribute differently to cell response for small and large strains

Science.gov (United States)

Kubitschke, H.; Schnauss, J.; Nnetu, K. D.; Warmt, E.; Stange, R.; Kaes, J.

2017-09-01

Cytoskeletal filaments provide cells with mechanical stability and organization. The main key players are actin filaments and microtubules governing a cell’s response to mechanical stimuli. We investigated the specific influences of these crucial components by deforming MCF-7 epithelial cells at small (≤5% deformation) and large strains (>5% deformation). To understand specific contributions of actin filaments and microtubules, we systematically studied cellular responses after treatment with cytoskeleton influencing drugs. Quantification with the microfluidic optical stretcher allowed capturing the relative deformation and relaxation of cells under different conditions. We separated distinctive deformational and relaxational contributions to cell mechanics for actin and microtubule networks for two orders of magnitude of drug dosages. Disrupting actin filaments via latrunculin A, for instance, revealed a strain-independent softening. Stabilizing these filaments by treatment with jasplakinolide yielded cell softening for small strains but showed no significant change at large strains. In contrast, cells treated with nocodazole to disrupt microtubules displayed a softening at large strains but remained unchanged at small strains. Stabilizing microtubules within the cells via paclitaxel revealed no significant changes for deformations at small strains, but concentration-dependent impact at large strains. This suggests that for suspended cells, the actin cortex is probed at small strains, while at larger strains; the whole cell is probed with a significant contribution from the microtubules.

Antiproliferative effects of small fruit juices on several cancer cell lines.

Science.gov (United States)

Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Tanaka, R; Murofushi, N; Nishimura, H

2000-01-01

Juices prepared from small fruits, mainly growing in the northern part of Japan, were studied in an attempt to explore the feasibility of an assay that screens cytotoxic properties. Screening of 43 small fruit juices indicated that Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray and Sorbus sambucifolia Roem, strongly inhibited the proliferation of all cancer cell lines examined and yet these juices were substantially less cytotoxic toward normal human cell lines.

MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

Directory of Open Access Journals (Sweden)

Debin Ma

2015-09-01

Full Text Available MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.

Impact of mobility on call block, call drops and optimal cell size in small cell networks

OpenAIRE

Ramanath , Sreenath; Voleti , Veeraruna Kavitha; Altman , Eitan

2011-01-01

We consider small cell networks and study the impact of user mobility. Assuming Poisson call arrivals at random positions with random velocities, we discuss the characterization of handovers at the boundaries. We derive explicit expressions for call block and call drop probabilities using tools from spatial queuing theory. We also derive expressions for the average virtual server held up time. These expressions are used to derive optimal cell sizes for various profile of velocities in small c...

Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

Science.gov (United States)

2017-04-12

Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Radiosensitization of C225 on human non-small cell lung cancer cell line H-520

International Nuclear Information System (INIS)

Zhang Yingdong; Wang Junjie; Liu Feng; Zhao Yong

2008-01-01

Objective: To investigate the efficacy of C225 (cetuximab), a chimeric human-mouse anti-epithelial growth factor receptor monoclonal antibody, combined with 60 Co gamma irradiation against human non-small cell lung cancer cell line H-520. Methods: H-520 cells were treated either with different dose of 60 Co irradiation (1,2,4,6,8 and 10 Gy)alone or together with C225 (100 nmol/L). Colony forming capacity was determined to create the survival curve 10 days after the treatment. Cells in different groups were harvested 72 hours after irradiation for apoptosis analysis or 48 hours after irradiation for cell cycle analysis by flow cytometry assay. Results: The clone number in combinational treatment group was less than that in irradiation only group, which suggested that the cell survival rate in the combinational treatment group was significantly decreased comparing with irradiation only group (F=6.36, P O + G 1 phases for C225 treatment, in G 2 + M phases for 60 Co irradiation, and in both G 0 + G 1 and G 2 + M phases for C225 in combination with 60 Co irradiation. Conclusions: C225 has radiosensitizing effects on H-520 cells, which may through the enhancement of 60 Co irradiation-induced cell death and cell cycle arrest. This study provides a supportive evidence for clinical treatment in non-small cell lung cancer. (authors)

Distributed Initial Synchronization for 5G small cells

DEFF Research Database (Denmark)

Berardinelli, Gilberto; Tavares, Fernando Menezes Leitão; Tirkkonen, Olav

2014-01-01

Time synchronization in a large network of small cells enables efficient interference management as well as advanced transmission techniques which can boost the network throughput. In this paper, we focus on the distributed initial synchronization problem and propose different solutions aiming at...

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.

Small-size biofuel cell on paper.

Science.gov (United States)

Zhang, Lingling; Zhou, Ming; Wen, Dan; Bai, Lu; Lou, Baohua; Dong, Shaojun

2012-05-15

In this work, we demonstrated a novel paper-based mediator-less and compartment-less biofuel cell (BFC) with small size (1.5 cm × 1.5 cm). Ionic liquid functionalized carbon nanotubes (CNTs-IL) nanocomposite was used as support for both stably confining the anodic biocatalyst (i.e., NAD(+)-dependent glucose dehydrogenase, GDH) for glucose electrooxidation and for facilitating direct electrochemistry of the cathodic biocatalyst (i.e., bilirubin oxidase, BOD) for O(2) electroreduction. Such BFC provided a simple approach to fabricate low-cost and portable power devices on small-size paper, which can harvest energy from a wide range of commercial beverages containing glucose (e.g., Nescafe instant coffee, Maidong vitamin water, Watermelon fresh juice, and Minute Maid grape juice). These made the low-cost paper-based biodevice potential for broad energy applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells

OpenAIRE

Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Kanterewicz, Beatriz; Balius, Trent; Belani, Chandra P.; Hershberger, Pamela A.

2010-01-01

We observed a 53% response rate in non-small cell lung cancer (NSCLC) patients treated with vorinostat plus paclitaxel/carboplatin in a Phase I trial. Studies were undertaken to investigate the mechanism (s) underlying this activity. Growth inhibition was assessed in NSCLC cells by MTT assay after 72 h of continuous drug exposure. Vorinostat (1 µM) inhibited growth by: 17±7% in A549, 28±6% in 128-88T, 39±8% in Calu1, and 41±7% in 201T cells. Vorinostat addition to carboplatin or paclitaxel le...

In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

DEFF Research Database (Denmark)

Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

1998-01-01

receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor.

Science.gov (United States)

Hayes-Jordan, Andrea A; Ma, Xiao; Menegaz, Brian A; Lamhamedi-Cherradi, Salah-Eddine; Kingsley, Charles V; Benson, Jalen A; Camacho, Pamela E; Ludwig, Joseph A; Lockworth, Cynthia R; Garcia, Gloria E; Craig, Suzanne L

2018-05-01

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing's sarcoma gene (EWSR1) and the Wilms' tumor suppressor gene (WT1). Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4) within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT. Copyright © 2018. Published by Elsevier Inc.

Efficacy of ONC201 in Desmoplastic Small Round Cell Tumor

Directory of Open Access Journals (Sweden)

Andrea A. Hayes-Jordan

2018-05-01

Full Text Available Desmoplastic Small Round Cell Tumor (DSRCT is a rare sarcoma tumor of adolescence and young adulthood, which harbors a recurrent chromosomal translocation between the Ewing’s sarcoma gene (EWSR1 and the Wilms’ tumor suppressor gene (WT1. Patients usually develop multiple abdominal tumors with liver and lymph node metastasis developing later. Survival is poor using a multimodal therapy that includes chemotherapy, radiation and surgical resection, new therapies are needed for better management of DSRCT. Triggering cell apoptosis is the scientific rationale of many cancer therapies. Here, we characterized for the first time the expression of pro-apoptotic receptors, tumor necrosis-related apoptosis-inducing ligand receptors (TRAILR1-4 within an established human DSRCT cell line and clinical samples. The molecular induction of TRAIL-mediated apoptosis using agonistic small molecule, ONC201 in vitro cell-based proliferation assay and in vivo novel orthotopic xenograft animal models of DSRCT, was able to inhibit cell proliferation that was associated with caspase activation, and tumor growth, indicating that a cell-based delivery of an apoptosis-inducing factor could be relevant therapeutic agent to control DSRCT.

Fully synthetic phage-like system for screening mixtures of small molecules in live cells.

Science.gov (United States)

Byk, Gerardo; Partouche, Shirly; Weiss, Aryeh; Margel, Shlomo; Khandadash, Raz

2010-05-10

A synthetic "phage-like" system was designed for screening mixtures of small molecules in live cells. The core of the system consists of 2 mum diameter cross-linked monodispersed microspheres bearing a panel of fluorescent tags and peptides or small molecules either directly synthesized or covalently conjugated to the microspheres. The microsphere mixtures were screened for affinity to cell line PC-3 (prostate cancer model) by incubation with live cells, and as was with phage-display peptide methods, unbound microspheres were removed by repeated washings followed by total lysis of cells and analysis of the bound microspheres by flow-cytometry. Similar to phage-display peptide screening, this method can be applied even in the absence of prior information about the cellular targets of the candidate ligands, which makes the system especially interesting for selection of molecules with high affinity for desired cells, tissues, or tumors. The advantage of the proposed system is the possibility of screening synthetic non-natural peptides or small molecules that cannot be expressed and screened using phage display libraries. A library composed of small molecules synthesized by the Ugi reaction was screened, and a small molecule, Rak-2, which strongly binds to PC-3 cells was found. Rak-2 was then individually synthesized and validated in a complementary whole cell-based binding assay, as well as by live cell microscopy. This new system demonstrates that a mixture of molecules bound to subcellular sized microspheres can be screened on plated cells. Together with other methods using subcellular sized particles for cellular multiplexing, this method represents an important milestone toward high throughput screening of mixtures of small molecules in live cells and in vivo with potential applications in the fields of drug delivery and diagnostic imaging.

Small GTP-binding proteins in human endothelial cells

NARCIS (Netherlands)

de Leeuw, H. P.; Koster, P. M.; Calafat, J.; Janssen, H.; van Zonneveld, A. J.; van Mourik, J. A.; Voorberg, J.

1998-01-01

Small GTP-binding proteins of the Ras superfamily control an extensive number of intracellular events by alternating between GDP- and GTP-bound conformation. The presence of members of this protein family was examined in human umbilical vein endothelial cells employing RT-PCR. Sequence analysis of

Retrofit designs for small bench-type blood cell counters.

Science.gov (United States)

Ferris, C D

1991-01-01

This paper describes several retrofit designs to correct operational problems associated with small bench-type blood cell counters. Replacement electronic circuits as well as modifications to the vacuum systems are discussed.

Treatment of Primary Cutaneous CD4 Small/Medium T cell Lymphoproliferative Disorder with Intralesional Triamcinolone Acetonide.

Science.gov (United States)

2018-02-15

12. REPORT TYPE 02/15/2018 Poster 4. TITLE AND SUBTITLE Treatment of Primary Cutaneous CD4+ Small/Medium T- cell Lymphoproliferative Disorder with...cutaneous CD4+ small/medium T- cell lymphoproliferative disorder (LPD) is a generally indolent cutaneous T- cell proliferation. Most cases follow a benign...lmmunohistochemistry showed diffuse CD3+ CD4+ T- cells without CD30, TIA1 or CD10. A subset of medium to large cells expressed BCL-6. Small subsets of B- cells and CDB

Collision tumor of Small Cell Carcinoma and Squamous Cell Carcinoma of maxillary sinus

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Irfan Sugianto

2016-06-01

Full Text Available Two kinds of different malignant tumors occurring within the same organ is defined as collision tumor. Small Cell Carcinoma (SmCC is high-grade derived from neuroendocrine cell tumors, occurance in the head and neck is rare. Squamous Cell Carcinoma (SCC is the most common malignancies encountered in head and neck area, but the occuranceof collision tumor is very rare. This report describe a 82 year-old woman patient with a SmCC and SCC that occurred in the maxillary sinus. CT was performed including with enhancement, MRI examination was T1WI, STIR and contrast enhancement. We also conducted analysis of Dynamic Contrast Enhancement (DCE. Histopathologic examination revealed small cell carcinoma. A distant metastasis was not detected. After patient received chemoradiotherapy (CCRT, most of  tumorwas reduced although a part of the tumor was remained. Pathological examination of surgery tumor specimen revealed that specimen consisted of SCC and SmCC was disappeared, and six months after surgery, the patient suffered tumor recurrence and multiple metastasis to the organs in the abdomen. This time we have to report that the experience one cases that are considered collision cancer of SmCC and SCC that occurred in the maxillary sinus.

Radiation, an ideal cytotoxic for the study of cell biology in the small intestine

International Nuclear Information System (INIS)

Potten, C.

2003-01-01

Epithelial tissues are highly polarised with the proliferative compartment sometimes subdivided into units of proliferation in many instances. My interests have been in trying to understand how many cellular constituents exist, what their function is and intercommunicants are that ensure appropriate steady state cell replacement rates. Radiation has proved to be a valuable tool to induce cell death, reproductive sterilisation, and regenerative proliferation in these systems, the responses to which can provide information on the number of regenerative cells (a function associated with stem cells). Such studies have helped define the epidermal proliferative units and the structurally similar units on the dorsal surface of the tongue. The radiation responses considered in conjunction with a wide range of cell kinetic lineage tracking and somatic mutation studies with complex mathematical modelling, provide insights into the functioning of the poliferative units (crypts) of the small intestine. Comparative studies have then been undertaken with the crypts in the large bowel. In the small intestine, which rarely develops cancer, various protective mechanisms have evolved to ensure the genetic integrity of the stem cell compartment. Stem cells in the small intestinal crypts have an intolerance of genotoxic damage (including that induced by very low doses of radiation), they do not undergo cell cycle arrest and repair but commit an altruistic p53 dependent cell suicide (apoptosis). This process is compromised in the large bowel by bcl-2 expression. Recent studies have suggested a second genome protection mechanism operating in the stem cells of the small intestinal crypts that may also have a p53 dependence. Such studies have allowed the cell lineages and genome protection mechanisms operating in the small intestinal crypts to be defined

The computed tomographic findings of bronchogenic carcinoma presenting as a solitary peripheral pulmonary mass

International Nuclear Information System (INIS)

Kim, Hong; Kim, Ok Bae; Woo, Seong Ku; Suh, Soo Jhi; Kim, Sung Soo

1985-01-01

It is difficult to distinguish benign from malignant, ulmonary nodule by conventional roentgenologic examination. But CT makes it easier to evaluate adjacent parenchymal invasion, pleural or mediastinal extension, or early metastasis to intra- or extrathoracic lymph node as well as distant organs, although only a solitary peripheral pulmonary nodule is seen on plain radiograph. Authors reviewed CT of 22 cases of histopathologically confirmed primary lung cancer seen as a solitary peripheral pulmonary mass from May 1980 to September 1984 at Dongsan Medical Center, Keimyung University. The results are as follows: 1. The incidence was most common in the 6th decade (36%). Male to female ratio was 10 : 1 and 2 females all had bronchioloalveolar cell carcinoma. 2. The distribution of histologic cell type were as follows: squamous cell carcinoma 40%, adenocarcinoma, small cell carcinoma, bronchioloalveolar cell carcinoma and unclassified carcinoma 14% in each cases, and adenoid cystic carcinoma 4%. 3. The computed tomographic findings were as follows: a) Superior and posterior basal segments of both lower lobes were most frequently involved (68%). b) The mean diameter of the mass was 48 mm, and most common in the range of 30-49 mm in the greatest dimension (46%). c) The mean CT attenuation value was 57 H.U., and most common in the group of 41-70 H. U. (64%). d) Lymph node metastasis was found in 13 (59%) of 22 cases, and the involved nodes were as follows: hilar nodes 10 cases, paratracheal nodes 8 cases, subcarinal nodes 7 cases and extrathoracic nodes 3 cases. In 2 of 3 cases with small cell carcinoma, diffuse multiple lymph nodes were involved. e) Distant metastasis was seen relatively early in 3 cases: cerebral metastasis in 1 cases of squamous cell carcinoma, right adrenal metastasis without intrathoracic lymph node metastasis or invasion of adjacent structure in 1 case of bronchioloalveolar cell carcinoma, and liver and bone metastasis in 1 case of unclassified

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

Science.gov (United States)

Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

Science.gov (United States)

Hamilton, Gerhard

2014-01-01

Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS. PMID:24608973

Surgery in limited stage small cell lung cancer

DEFF Research Database (Denmark)

Lassen, U; Hansen, H H

1999-01-01

The role of surgery in small cell lung cancer (SCLC) is controversial. Surgery has several potential advantages because it may reduce the frequency of local relapses, it does not impede the intensity of chemotherapy, it does not affect the bone marrow, and surgical staging may be of prognostic...

Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

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Fei Long

2015-01-01

Full Text Available Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

New data for venous thromboembolism in patients with small cell lung cancer: A review.

Science.gov (United States)

Dimakakos, Evangelos; Livanios, Konstantinos; Gkiozos, Ioannis; Charpidou, Adriani; Ntalakou, Eleutheria; Kainis, Llias; Syrigos, Konstantinos

2017-01-01

Malignancy is an important predisposing factor for thromboembolic disease. Patients with malignancy display 4 to 10 times greater risk than the general population. As for lung cancer, that risk seems to further increase and become up to 20 times higher. The aim of this article is to review the International literature in order to highlight for the first time, the correlation between thromboembolic disease and small cell lung cancer. PubMed, Medline and Embase databases were searched from 1990 up to 2016, for retrospective and prospective studies that investigate the correlation between thromboembolic disease and small cell lung cancer. The incidence rate of thromboembolic disease found in these studies ranged between 6.8% and 11.5%. Thromboembolic disease is associated with a reduced survival in patients with small cell lung cancer and six factors seemed to increase the risk of thromboembolism: chemotherapy, cisplatin treatment, smoking, extensive disease, the infiltration of the superior vena cava and multiple concomitant diseases. Thromboembolic disease shows an increased incidence in patients with small cell lung cancer and more research with well-designed studies is required in order to study in detail the anticoagulation treatment and the survival in small cell lung cancer patients.

Preliminary results in combined therapy (polychemotherapy and radiotherapy) of small cell bronchial cancer

International Nuclear Information System (INIS)

Gaertner, C.; Rjabuchin, J.S.; Michina, Z.P.; Motorina, L.I.

1984-01-01

The effective therapy of small cell lung cancer is the combination of polychemotherapy and radiation treatment. A randomized small cell lung cancer study of 141 patients revealed that with an agressive treatment more than 50 % complete remissions and nearly 90 % complete and partial remissions can be achieved by corresponding selection of patients. (author)

Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

LENUS (Irish Health Repository)

Rahma, M B.

2016-09-01

A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

Cellular radiosensitivity of small-cell lung cancer cell lines

International Nuclear Information System (INIS)

Krarup, Marianne; Poulsen, Hans Skovgaard; Spang-Thomsen, Mogens

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 on the construction of continuous exponential growth curves. Methods and Materials: Fifteen SCLC cell lines were studied, applying a slightly modified clonogenic assay and a growth extrapolation method. A dose-survival curve was obtained for each experiment and used for calculating several survival parameters. The multitarget single hit model was applied to calculate the cellular radiosensitivity (D 0 ), the capacity for sublethal damage repair (D q ), and the extrapolation number (n). Values for α and β were determined from best-fit curves according to the linear-quadratic model and these values were applied to calculate the surviving fraction after 2-Gy irradiation (SF 2 ). Results: In our investigation, the extrapolation method proved to be inappropriate for the study of in vitro cellular radiosensitivity due to lack of reproducibility. The results obtained by the clonogenic assay showed that the cell lines studied were radiobiologically heterogeneous with no discrete features of the examined parameters including the repair capacity. Conclusion: The results indicate that SCLC tumors per se are not generally candidates for hyperfractionated radiotherapy

Small Molecule-Photoactive Yellow Protein Labeling Technology in Live Cell Imaging

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Feng Gao

2016-08-01

Full Text Available Characterization of the chemical environment, movement, trafficking and interactions of proteins in live cells is essential to understanding their functions. Labeling protein with functional molecules is a widely used approach in protein research to elucidate the protein location and functions both in vitro and in live cells or in vivo. A peptide or a protein tag fused to the protein of interest and provides the opportunities for an attachment of small molecule probes or other fluorophore to image the dynamics of protein localization. Here we reviewed the recent development of no-wash small molecular probes for photoactive yellow protein (PYP-tag, by the means of utilizing a quenching mechanism based on the intramolecular interactions, or an environmental-sensitive fluorophore. Several fluorogenic probes have been developed, with fast labeling kinetics and cell permeability. This technology allows quick live-cell imaging of cell-surface and intracellular proteins without a wash-out procedure.

Performance Enhancement of Small Molecular Solar Cells by Bilayer Cathode Buffer.

Science.gov (United States)

Sun, Qinjun; Zhao, Huanbin; Zhou, Miao; Gao, Liyan; Hao, Yuying

2016-04-01

An effective composite bilayer cathode buffer structure is proposed for use in small molecular solar cells. CsF was doped in Alq3 to form the first cathode buffer, leading to small serial resistances. BCP was used as the second cathode buffer to block the holes to the electrode. The optimized bilayer cathode buffer significantly increased the short circuit and fill factor of devices. By integrating this bilayer cathode buffer, the CuPc/C60 small molecular heterojunction cell exhibited a power conversion efficiency of up to 0.8%, which was an improvement of 56% compared to a device with only the Alq3 cathode buffer. Meanwhile, the bilayer cathode buffer still has a good protective effect on the performance of the device.

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

Science.gov (United States)

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.

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.

Clinical applications of the computed tomography of the thorax

Energy Technology Data Exchange (ETDEWEB)

Hong, Seong Eun; Kim, Ho Kyun; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

1980-06-15

The computed tomography of the thorax has had considerably less impact in patient management than that of head and abdomen, because the convention chest radiography is a much more sensitive and accurate examination than the plain film studies of the head and abdomen. It has progressively been identified that the computed tomography of chest is superior to the conventional radiography in detection of small pulmonary nodules including occult metastatic lesions, in evaluation of character of hilar enlargement, and in staging of known bronchogenic caner. And especially in mediastinum, the computed tomography is supported to the any other conventional radiography in outlining lesions and determining character and extent of lesions. At the department of radiology, Kyung Hee University Hospital , 87 cases of computed tomography of chest were performed with EMI-CT 5005 whole-body scanner from October 1977 to August 1979. The results were as following; 1. The fifty eight cases of considered to be pathologic findings were 23 pleural thickening and/or effusion, 14 bronchogenic carcinoma, 8 inflammatory lesions of lung parenchyme, 6 mediastinal lesions, 3 metastinal lesions, 3 COPD, 1 trauma, respectively. 2. No gravity-dependent change was noted in patients with chronic obstructive pulmonary disease (COPD), which was frequently seen in normal subjects. Diminished numbers of pulmonary vessels was noted in COPD. 3. Small nodules in lung, retrosternal, posterior costophrenic and subpleural regions, which were not found on conventional radiography, can be detected by chest CT. 4. Differentiation of dilated central pulmonary artery from pulmonary mass in enlarged hilum and determination of adjacent mediastinal invasion, manifested by obliterated fat plane, was possible. 5. The cases of mediastinal widening such as paraspinal ilpomatosis, pericardial fat pad, teratoma, and bronchogenic cyst were easily determined by means of measuring the attenuation coefficiencies. 6. Small amount

Clinical applications of the computed tomography of the thorax

International Nuclear Information System (INIS)

Hong, Seong Eun; Kim, Ho Kyun; Kim, Soon Yong

1980-01-01

The computed tomography of the thorax has had considerably less impact in patient management than that of head and abdomen, because the convention chest radiography is a much more sensitive and accurate examination than the plain film studies of the head and abdomen. It has progressively been identified that the computed tomography of chest is superior to the conventional radiography in detection of small pulmonary nodules including occult metastatic lesions, in evaluation of character of hilar enlargement, and in staging of known bronchogenic caner. And especially in mediastinum, the computed tomography is supported to the any other conventional radiography in outlining lesions and determining character and extent of lesions. At the department of radiology, Kyung Hee University Hospital , 87 cases of computed tomography of chest were performed with EMI-CT 5005 whole-body scanner from October 1977 to August 1979. The results were as following; 1. The fifty eight cases of considered to be pathologic findings were 23 pleural thickening and/or effusion, 14 bronchogenic carcinoma, 8 inflammatory lesions of lung parenchyme, 6 mediastinal lesions, 3 metastinal lesions, 3 COPD, 1 trauma, respectively. 2. No gravity-dependent change was noted in patients with chronic obstructive pulmonary disease (COPD), which was frequently seen in normal subjects. Diminished numbers of pulmonary vessels was noted in COPD. 3. Small nodules in lung, retrosternal, posterior costophrenic and subpleural regions, which were not found on conventional radiography, can be detected by chest CT. 4. Differentiation of dilated central pulmonary artery from pulmonary mass in enlarged hilum and determination of adjacent mediastinal invasion, manifested by obliterated fat plane, was possible. 5. The cases of mediastinal widening such as paraspinal ilpomatosis, pericardial fat pad, teratoma, and bronchogenic cyst were easily determined by means of measuring the attenuation coefficiencies. 6. Small amount

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

Science.gov (United States)

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.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators.

Science.gov (United States)

Zou, Xiaojing; Qu, Mingyi; Fang, Fang; Fan, Zeng; Chen, Lin; Yue, Wen; Xie, Xiaoyan; Pei, Xuetao

2017-01-01

Platelets (PLTs) are produced by megakaryocytes (MKs) that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI), nicotinamide (NIC), Src inhibitor (SI), and Aurora B inhibitor (ABI)) and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications.

Small Molecule Supplements Improve Cultured Megakaryocyte Polyploidization by Modulating Multiple Cell Cycle Regulators

Directory of Open Access Journals (Sweden)

Xiaojing Zou

2017-01-01

Full Text Available Platelets (PLTs are produced by megakaryocytes (MKs that completed differentiation and endomitosis. Endomitosis is an important process in which the cell replicates its DNA without cytokinesis and develops highly polyploid MK. In this study, to gain a better PLTs production, four small molecules (Rho-Rock inhibitor (RRI, nicotinamide (NIC, Src inhibitor (SI, and Aurora B inhibitor (ABI and their combinations were surveyed as MK culture supplements for promoting polyploidization. Three leukemia cell lines as well as primary mononuclear cells were chosen in the function and mechanism studies of the small molecules. In an optimal culture method, cells were treated with different small molecules and their combinations. The impact of the small molecules on megakaryocytic surface marker expression, polyploidy, proliferation, and apoptosis was examined for the best MK polyploidization supplement. The elaborate analysis confirmed that the combination of SI and RRI together with our MK induction system might result in efficient ploidy promotion. Our experiments demonstrated that, besides direct downregulation on the expression of cytoskeleton protein actin, SI and RRI could significantly enhance the level of cyclins through the suppression of p53 and p21. The verified small molecule combination might be further used in the in vitro PLT manufacture and clinical applications.

The small molecule inhibitor QLT0267 Radiosensitizes squamous cell carcinoma cells of the head and neck.

Directory of Open Access Journals (Sweden)

Iris Eke

Full Text Available BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC. METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl and ILK(-/- mouse fibroblasts were used. Cells grew either two-dimensionally (2D on or three-dimensionally (3D in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose. ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay, cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A

Small molecule alteration of RNA sequence in cells and animals.

Science.gov (United States)

Guan, Lirui; Luo, Yiling; Ja, William W; Disney, Matthew D

2017-10-18

RNA regulation and maintenance are critical for proper cell function. Small molecules that specifically alter RNA sequence would be exceptionally useful as probes of RNA structure and function or as potential therapeutics. Here, we demonstrate a photochemical approach for altering the trinucleotide expanded repeat causative of myotonic muscular dystrophy type 1 (DM1), r(CUG) exp . The small molecule, 2H-4-Ru, binds to r(CUG) exp and converts guanosine residues to 8-oxo-7,8-dihydroguanosine upon photochemical irradiation. We demonstrate targeted modification upon irradiation in cell culture and in Drosophila larvae provided a diet containing 2H-4-Ru. Our results highlight a general chemical biology approach for altering RNA sequence in vivo by using small molecules and photochemistry. Furthermore, these studies show that addition of 8-oxo-G lesions into RNA 3' untranslated regions does not affect its steady state levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interference Mitigation and Sum Rate Optimization for MIMO Downlink Small Cells

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H. H. Kha

2016-12-01

Full Text Available This paper addresses interference issues in multiuser multiple-input multiple-output (MIMO downlink heterogeneous networks in which multiple small cells are deployed in macrocell coverage. With the higher priority to access the frequency bands, the macro base station (MBS will exploit eigenmode transmission along with water-filling based power allocation to maximize its data rate. To avoid harmful interference to macro users, we propose structures of the precoders at the small cell BSs (SBSs as cascades of two precoding matrices. In addition, to mitigate intra-tier inference in small cells, the SBSs exploit the user scheduling schemes for their associated users. We investigate two user scheduling schemes using the minimum interference leakage and maximum signal to noise ratio criteria. The sum rate of the selected users can be further improved by power allocation. We develop an iterative algorithm using difference of convex functions (d.c. programming to tackle the mathematical challenges of the nonconvex power allocation problem, Numerical simulation results show that the proposed strategy outperforms the conventional methods in terms of the achievable sum rate.

Suitability of small diagnostic peripheral-blood samples for cell-therapy studies.

Science.gov (United States)

Stephanou, Coralea; Papasavva, Panayiota; Zachariou, Myria; Patsali, Petros; Epitropou, Marilena; Ladas, Petros; Al-Abdulla, Ruba; Christou, Soteroulla; Antoniou, Michael N; Lederer, Carsten W; Kleanthous, Marina

2017-02-01

Primary hematopoietic stem and progenitor cells (HSPCs) are key components of cell-based therapies for blood disorders and are thus the authentic substrate for related research. We propose that ubiquitous small-volume diagnostic samples represent a readily available and as yet untapped resource of primary patient-derived cells for cell- and gene-therapy studies. In the present study we compare isolation and storage methods for HSPCs from normal and thalassemic small-volume blood samples, considering genotype, density-gradient versus lysis-based cell isolation and cryostorage media with different serum contents. Downstream analyses include viability, recovery, differentiation in semi-solid media and performance in liquid cultures and viral transductions. We demonstrate that HSPCs isolated either by ammonium-chloride potassium (ACK)-based lysis or by gradient isolation are suitable for functional analyses in clonogenic assays, high-level HSPC expansion and efficient lentiviral transduction. For cryostorage of cells, gradient isolation is superior to ACK lysis, and cryostorage in freezing media containing 50% fetal bovine serum demonstrated good results across all tested criteria. For assays on freshly isolated cells, ACK lysis performed similar to, and for thalassemic samples better than, gradient isolation, at a fraction of the cost and hands-on time. All isolation and storage methods show considerable variation within sample groups, but this is particularly acute for density gradient isolation of thalassemic samples. This study demonstrates the suitability of small-volume blood samples for storage and preclinical studies, opening up the research field of HSPC and gene therapy to any blood diagnostic laboratory with corresponding bioethics approval for experimental use of surplus material. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Detection of cytoskeletal proteins in small cell lung carcinoma

Czech Academy of Sciences Publication Activity Database

Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

1999-01-01

Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

Directory of Open Access Journals (Sweden)

Gerhard Hamilton

2014-03-01

Full Text Available Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4 inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose-Polymerase 1 (PARP1 inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS.

Interference-robust Air Interface for 5G Small Cells

DEFF Research Database (Denmark)

Tavares, Fernando Menezes Leitão

the existing wireless network infrastructure to the limit. Mobile network operators must invest in network expansion to deal with this problem, but the predicted network requirements show that a new Radio Access Technology (RAT) standard will be fundamental to reach the future target performance. This new 5th...... to the fundamental role of inter-cell interference in this type of networks, the inter-cell interference problem must be addressed since the beginning of the design of the new standard. This Ph.D. thesis deals with the design of an interference-robust air interface for 5G small cell networks. The interference...

Epigenetic silencing of MicroRNA-503 regulates FANCA expression in non-small cell lung cancer cell.

Science.gov (United States)

Li, Ning; Zhang, Fangfang; Li, Suyun; Zhou, Suzhen

2014-02-21

It is reported that MicroRNA-503 (miR-503) regulates cell apoptosis, and thus modulates the resistance of non-small cell lung cancer cells (NSCLC) to cisplatin. However, the exact role of miR-503 in NSCLC remains unknown. In the present study, the level of miR-503 expression in NSCLC was evaluated using realtime PCR, and the DNA methylation status within miR-503 promoter was analyzed by Combined Bisulfite Restriction Analysis (COBRA) or bisulfite-treated DNA sequencing assays (BSP). We found that the expression of miR-503 was significantly decreased in NSCLC tissues compared to normal tissues. A statistically significant inverse association was found between miR-503 methylation status and expression of the miR-503 in tumor tissues (PFANCA) gene and represses its expression at the transcriptional level. Taken together, our results suggest that miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin at least in part by targeting FANCA. Copyright © 2014 Elsevier Inc. All rights reserved.

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...

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

Directory of Open Access Journals (Sweden)

Minxia Liu

2016-09-01

Full Text Available 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 transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

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

Science.gov (United States)

Liu, Minxia; Zhou, Kecheng; Cao, Yi

2016-09-26

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 transfection were used to investigate interaction between the miRNA and target gene. miR-944 was significantly down-regulated in NSCLC and had many putative targets. Moreover, the forced expression of miR-944 significantly inhibited the proliferation of NSCLC cells in vitro. By integrating mRNA expression data and miR-944-target prediction, we disclosed that EPHA7 was a potential target of miR-944, which was further verified by luciferase reporter assay and microRNA transfection. Our data indicated that miR-944 targets EPHA7 in NSCLC and regulates NSCLC cell proliferation, which may offer a new mechanism underlying the development and progression of NSCLC.

A case of squamous cell lung cancer after treating with radiation for small cell lung cancer

International Nuclear Information System (INIS)

Hayashi, Toshinari; Ide, Hiroshi; Siomi, Katsuhiko; Nakamura, Yukinobu; Tada, Shinya; Kageyama, Hiroshi; Kido, Masamitsu

1999-01-01

A 77-year-old man was admitted due to an abnormal shadow on a chest X-ray film in September 1993. Small cell lung cancer was diagnosed by transbronchial lung biopsy of left S 3 . Because of his pulmonary and renal dysfunction, he received only 40 Gy irradiation alone, and the tumor shadow disappeared. After 38 months' observation, a new nodular shadow was detected in the left upper lung field in March 1997. A tumor was found in left B 3 by bronchoscopy, and biopsy revealed squamous cell carcinoma. Because of his advanced age and hypoxia, he has had no active treatment. This was a rare case of small cell lung cancer with long term survival, treated only by radiation, in which a different histologic type of carcinoma appeared in the same radiation field. (author)

Molecular biologic study about the non-small cell lung carcinoma (2) : p53 gene alteration in non-small cell lung carcinoma

International Nuclear Information System (INIS)

Park, Jong Ho; Zo, Jae Ill; Paik, Hee Jong; Kim, Mi Hee

1996-12-01

The main purpose of this research was to identify of the p53 and 3p gene alteration in non-small cell lung cancer patients residing in Korea. Furthermore, we analyzed the relationship between the p53 and 3p gene alterations and the clinicopathologic results of lung cancer patients. And we have investigated the role of PCR-LOH in analyzing tumor samples for LOH of defined chromosomal loci. We have used the 40 samples obtained from the lung cancer patients who were diagnosed and operated curatively at Korea Cancer Center Hospital. We have isolated the high molecular weight. DNA from the tumors and normal tissues. And we have amplified the DNA with PCR method and used the microsatellite assay method to detect the altered p53 and 3p gene. The conclusions were as follow: 1) The 3p gene alteration was observed in 9/39 (23.1%) and p53 gene alteration was observed in 15/40 (37.5%) of resected non-small cell lung cancer. 2) There was no correlations between the 3p or p53 gene alterations and prognosis of patients, but further study is necessary. 3) PCR-LOH is a very useful tool for analyzing small amount of tumor samples for loss of heterozygosity of defined chromosomal loci. (author). 10 refs

Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

Directory of Open Access Journals (Sweden)

Takahiro Nagatake

Full Text Available Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4, and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119, and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1. A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip, thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg, pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy, cholecystokinin (Cck, secretin (Sct, and tryptophan hydroxylase 1 (Tph1. In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells.

Comparison of the calculated absorbed dose using the Cadplan™ treatment planning software and Tld-100 measurements in an Alderson-Rando phantom for a bronchogenic treatment

Energy Technology Data Exchange (ETDEWEB)

Gutiérrez Castillo, J. G., E-mail: jggc59@hotmail.com [Departamento de Física, Hospital de Oncología, IMSS, CMN Siglo XXI, Cuauhtémoc 330 Col. Doctores (Mexico); Álvarez Romero, J. T., E-mail: trinidad.alvarez@inin.gob.mx, E-mail: fisarmandotorres@gmail.com, E-mail: victor.tovar@inin.gob.mx; Calderón, A. Torres, E-mail: trinidad.alvarez@inin.gob.mx, E-mail: fisarmandotorres@gmail.com, E-mail: victor.tovar@inin.gob.mx; M, V. Tovar, E-mail: trinidad.alvarez@inin.gob.mx, E-mail: fisarmandotorres@gmail.com, E-mail: victor.tovar@inin.gob.mx [SSDL, Departamento de Metrología ININ, Salazar, Estado de México 15245 (Mexico)

2014-11-07

To verify the accuracy of the absorbed doses D calculated by a TPS Cadplan for a bronchogenic treatment (in an Alderson-Rando phantom) are chosen ten points with the following D's and localizations. Point 1, posterior position on the left edge with 136.4 Gy. Points: 2, 3 and 4 in the left lung with 104.9, 104.3 and 105.8 Gy, respectively; points 5 and 6 at the mediastinum with 192.4 and 173.5 Gy; points 7, 8 and 9 in the right lung with 105.8, 104.2 and 104.7 Gy, and 10 at posterior position on right edge with 143.7 Gy. IAEA type capsules with TLD 100 powder are placed, planned and irradiated. The evaluation of the absorbed dose is carried out a curve of calibration for the LiF response (nC) {sup vs} {sup DW}, to several cavity theories. The traceability for the DW is obtained with a secondary standard calibrated at the NRC (Canada). The dosimetric properties for the materials considered are determined from the Hounsfield numbers reported by the TPS. The stopping power ratios are calculated for nominal spectrum to 6 MV photons. The percent variations among the planned and determined D in all the cases they are < ± 3%.

[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.

Expression of cadherin and NCAM in human small cell lung cancer cell lines and xenografts

DEFF Research Database (Denmark)

Rygaard, K; Møller, C; Bock, E

1992-01-01

characterised, the cadherin family and the Ig superfamily member, neural cell adhesion molecule (NCAM). We investigated expression of these two adhesion molecule families in small cell lung cancer (SCLC) cell lines and xenografts by immunoblotting. Nineteen tumours established from 15 patients with SCLC were......Tumour cell adhesion, detachment and aggregation seem to play an important part in tumour invasion and metastasis, and numerous cell adhesion molecules are expressed by tumour cells. Several families of cell-cell adhesion molecules have been described, of which two groups are particularly well...... embryonic development, which may play a role in connection with tumour invasion and metastasis, was found in 14/18 NCAM expressing SCLC tumours. Individual tumours grown as cell lines and as nude mouse xenografts showed no qualitative differences in cadherin or NCAM expression....

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

Science.gov (United States)

Wu, Chia-Yung; Roybal, Kole T.; Puchner, Elias M.; Onuffer, James; Lim, Wendell A.

2016-01-01

There is growing promise in using engineered cells as therapeutic agents. For example, synthetic Chimeric Antigen Receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, excessive activity and poor control over such engineered T cells can cause severe toxicities. We present the design of “ON-switch” CARs that enable small molecule-control over T cell therapeutic functions, while still retaining antigen specificity. In these split receptors, antigen binding and intracellular signaling components only assemble in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate both cell autonomous recognition and user control. PMID:26405231

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....

Impact of Users Identities and Access Conditions on Downlink Performance in Closed Small-Cell Networks

KAUST Repository

Radaydeh, Redha; Gaaloul, Fakhreddine; Alouini, Mohamed-Slim

2015-01-01

This paper investigates the effect of various operation parameters on the downlink user performance in overlaid small-cell networks. The case study considers closed-access small cells (e.g., femtocells), wherein only active authorized user

Metabolomics of Small Numbers of Cells: Metabolomic Profiling of 100, 1000, and 10000 Human Breast Cancer Cells.

Science.gov (United States)

Luo, Xian; Li, Liang

2017-11-07

In cellular metabolomics, it is desirable to carry out metabolomic profiling using a small number of cells in order to save time and cost. In some applications (e.g., working with circulating tumor cells in blood), only a limited number of cells are available for analysis. In this report, we describe a method based on high-performance chemical isotope labeling (CIL) nanoflow liquid chromatography mass spectrometry (nanoLC-MS) for high-coverage metabolomic analysis of small numbers of cells (i.e., ≤10000 cells). As an example, 12 C-/ 13 C-dansyl labeling of the metabolites in lysates of 100, 1000, and 10000 MCF-7 breast cancer cells was carried out using a new labeling protocol tailored to handle small amounts of metabolites. Chemical-vapor-assisted ionization in a captivespray interface was optimized for improving metabolite ionization and increasing robustness of nanoLC-MS. Compared to microflow LC-MS, the nanoflow system provided much improved metabolite detectability with a significantly reduced sample amount required for analysis. Experimental duplicate analyses of biological triplicates resulted in the detection of 1620 ± 148, 2091 ± 89 and 2402 ± 80 (n = 6) peak pairs or metabolites in the amine/phenol submetabolome from the 12 C-/ 13 C-dansyl labeled lysates of 100, 1000, and 10000 cells, respectively. About 63-69% of these peak pairs could be either identified using dansyl labeled standard library or mass-matched to chemical structures in human metabolome databases. We envisage the routine applications of this method for high-coverage quantitative cellular metabolomics using a starting material of 10000 cells. Even for analyzing 100 or 1000 cells, although the metabolomic coverage is reduced from the maximal coverage, this method can still detect thousands of metabolites, allowing the analysis of a large fraction of the metabolome and focused analysis of the detectable metabolites.

KCNQ1 channels sense small changes in cell volume

DEFF Research Database (Denmark)

Grunnet, Morten; Jespersen, Thomas; MacAulay, Nanna

2003-01-01

Many important physiological processes involve changes in cell volume, e.g. the transport of salt and water in epithelial cells and the contraction of cardiomyocytes. In this study, we show that voltage-gated KCNQ1 channels, which are strongly expressed in epithelial cells or cardiomyocytes......, and KCNQ4 channels, expressed in hair cells and the auditory tract, are tightly regulated by small cell volume changes when co-expressed with aquaporin 1 water-channels (AQP1) in Xenopus oocytes. The KCNQ1 and KCNQ4 current amplitudes precisely reflect the volume of the oocytes. By contrast, the related...... KCNQ2 and KCNQ3 channels, which are prominently expressed in neurons, are insensitive to cell volume changes. The sensitivity of the KCNQ1 and KCNQ4 channels to cell volume changes is independent of the presence of the auxiliary KCNE1-3 subunits, although modulated by KCNE1 in the case of KCNQ1...

EGFR T790M mutation after chemotherapy for small cell lung cancer transformation of EGFR-positive non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Tomoaki Sonoda

Full Text Available In non-small cell lung cancer (NSCLC with an epidermal growth factor receptor (EGFR mutation, 50%–65% of cases acquire resistance after treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs because of an EGFR T790M point mutation and 3%–14% of these cases transformed to small cell lung cancer (SCLC. Generally, the EGFR T790M secondary mutation develops with ongoing ATP competitive inhibition. We present a case of a 76-year-old woman with lung adenocarcinoma harboring an EGFR-L858R mutation who received first-line gefitinib and developed SCLC transformation. She was administered several chemotherapy agents, including a platinum doublet. The primary lesion that showed SCLC transformation had reconverted to adenocarcinoma with EGFR L858R and T790M mutations at the time of a second re-biopsy. Therefore, she was administered osimertinib, which resulted in clinical remission. This case suggested that serial biopsies are necessary even after SCLC transformation. Keywords: NSCLC, EGFR mutation, SCLC transformation, T790M, Osimertinib

222Rn alpha dose to organs other than lung

International Nuclear Information System (INIS)

Harley, N.H.; Robbins, E.S.

1991-01-01

The alpha dose to cells in tissues or organs other theft the lung has been calculated using the solubility coefficients for 222 Rn measured in human tissue. The annual alpha dose equivalent f rom 222 Rn and decay products in most tissues is a maximum of 30% of the annual average natural background dose equivalent (1 mSv) for external and internally deposited nuclides. The dose to the small population of lymphocytes located in or under the bronchial epithelium is a special case and their annual dose equivalent is essentially the same as that to basal cells in bronchial epithelium (200 mSv) for continuous exposure to 200 Bq M -3 . The significance of this dose is uncertain because the only excess cancer observed in follow up studies of underground miners with high 222 Rn exposure is bronchogenic carcinoma

Desmoplastic small round cell tumour: Cytological and immunocytochemical features

Directory of Open Access Journals (Sweden)

Filho Adhemar

2005-01-01

Full Text Available Abstract Background Desmoplastic small round cell tumor (DSRCT is a rare and highly aggressive neoplasm. The cytological diagnosis of these tumors can be difficult because they show morphological features quite similar to other small round blue cells tumors. We described four cases of DSRCT with cytological sampling: one obtained by fine needle aspiration biopsy (FNAB and three from serous effusions. The corresponding immunocytochemical panel was also reviewed. Methods Papanicolaou stained samples from FNAB and effusions were morphologically described. Immunoreaction with WT1 antibody was performed in all cytological samples. An immunohistochemical panel including the following antibodies was performed in the corresponding biopsies: 34BE12, AE1/AE3, Chromogranin A, CK20, CK7, CK8, Desmin, EMA, NSE, Vimentin and WT1. Results The smears showed high cellularity with minor size alteration. Nuclei were round to oval, some of them with inconspicuous nucleoli. Tumor cells are clustered, showing rosette-like feature. Tumor cells in effusions and FNA were positive to WT1 in 3 of 4 cytology specimens (2 out 3 effusions and one FNA. Immunohistochemical reactions for vimentin, NSE, AE1/AE3 and WT1 were positive in all cases in tissue sections. Conclusion The use of an adjunct immunocytochemical panel coupled with the cytomorphological characteristics allows the diagnosis of DSRCT in cytological specimens.

Role of free radicals in an adriamycin-resistant human small cell lung cancer cell line

NARCIS (Netherlands)

Meijer, C.; Mulder, N H; Timmer-Bosscha, H; Zijlstra, J G; de Vries, E G

1987-01-01

In two Adriamycin (Adr) resistant sublines (GLC4-Adr1 and GLC4-Adr2) of a human small cell lung carcinoma cell line, GLC4, cross-resistance for radiation was found. GLC4-Adr1 has an acquired Adr resistance factor of 44 after culturing without Adr for 20 days and GLC4-Adr2, the same subline cultured

Spectral and energy efficiency analysis of uplink heterogeneous networks with small-cells on edge

KAUST Repository

Shakir, Muhammad Zeeshan

2014-12-01

This paper presents a tractable mathematical framework to analyze the spectral and energy efficiency of an operator initiated deployment of the small-cells (e.g., femtocells) where the small-cell base stations are deliberately positioned around the edge of the macrocell. The considered deployment facilitates the cell-edge mobile users in terms of their coverage, spectral, and energy efficiency and is referred to as cell-on-edge (COE) configuration. The reduction in energy consumption is achieved by considering fast power control where the mobile users transmit with adaptive power to compensate the path loss, shadowing and fading. In particular, we develop a moment generating function (MGF) based approach to derive analytical bounds on the area spectral efficiency and exact expressions for the energy efficiency of the mobile users in the considered COE configuration over generalized-K fading channels. Besides the COE configuration, the derived bounds are also shown to be useful in evaluating the performance of random small-cell deployments, e.g., uniformly distributed small-cells. Simulation results are presented to demonstrate the improvements in spectral and energy efficiency of the COE configuration with respect to macro-only networks and other unplanned deployment strategies. © 2014 Elsevier B.V. All rights reserved.

Radiation cell survival and growth delay studies in multicellular spheroids of small-cell lung carcinoma

International Nuclear Information System (INIS)

Duchesne, G.M.; Peacock, J.H.

1987-01-01

The radiation sensitivity of two small-cell lung carcinoma cell lines growing as multicellular spheroids in static culture was determined using clonogenic cell survival and growth delay as endpoints. Growth delay determination suggested that clonogenic cell kill was less than was obtained by direct assay of cell survival. Recovery from potentially lethal damage was assayed in one line (HC12) but was not demonstrable, and clonogenic cell survival decreased with time in treated spheroids with diameters greater than 300 μm which contained a hypoxic cell population. Microscopic examination of the treated spheroids showed the emergence of an abnormal giant-cell population, and the progressive clonogenic cell loss that occurred after treatment was thought to be due to oxygen and nutrient deprivation of the remaining viable cells by this doomed cell population. Correction of the growth delay measurements for changes in cell size and clonogenic cell population allowed correlation of the growth delay and cell survival data. (author)

Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers

DEFF Research Database (Denmark)

Rumessen, Jüri Johannes; Thuneberg, Lars

1991-01-01

Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle......Anatomy, interstitial cells of Cajal, small intestine, gut motility, pacemaker cells, smooth muscle...

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...

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.

Science.gov (United States)

Wu, Chia-Yung; Roybal, Kole T; Puchner, Elias M; Onuffer, James; Lim, Wendell A

2015-10-16

There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control. Copyright © 2015, American Association for the Advancement of Science.

Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

Directory of Open Access Journals (Sweden)

Vitor Fiorin de Vasconcellos

2013-10-01

Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

Science.gov (United States)

Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

2012-02-01

Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

Elective brain irradiation in patients with small-cell carcinoma of the lung: preliminary report

International Nuclear Information System (INIS)

Katsenis, A.T.; Karpasitis, N.; Giannakakis, D.; Maragoudakis, N.; Kiparissiadis, P.

1982-01-01

The brain is a common site of metastases in small-cell carcinoma of the lung. Prophylactic brain irradiation with doses of 4000-4500 rads in 3-4 weeks appears to decrease the occurrence of brain metastases although it does not prevent this completely. In a group of patients with small-cell carcinoma of the lung and without evidence of brain metastases, the authors review the site and extent of the primary, the methods of treatment, the techniques of brain irradiation, and the relapses rate in relation to the status of the primary and the rate of brain metastases in another group without prophylactic brain irradiation. They further attempt to investigate combined modalities of treatment which would prolong life and prevent neurological complications in the small number of long survivors with small-cell carcinoma of the lung. (Auth.)

Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

Science.gov (United States)

2016-10-01

reported in other contexts including breast cancer and bladder cancer . While beyond the scope of this grant, and not funded by this mechanism, we...have participated in a recent collaborative analysis of common genomic alterations in small cell bladder cancer vs. small cell lung cancer . A paper...of the project is to study drug resistance mechanisms in vitro and using tumors from lung cancer patients with epidermal growth factor receptor

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

Science.gov (United States)

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.

Differentiation-inducing effects of small fruit juices on HL-60 leukemic cells.

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Yoshizawa, Y; Kawaii, S; Urashima, M; Fukase, T; Sato, T; Murofushi, N; Nishimura, H

2000-08-01

Epidemiological studies indicate that high intakes of fruits and vegetables are associated with a reduced risk of cancer, and several plant-derived drugs have been developed in medical oncology. Since only a small part of the flora has been tested for any kind of bioactivity, we chose small fruits as sources of differentiation-inducing activity against HL-60 leukemic cells. We have prepared juices from various small fruits that grow mainly in the northern part of Japan. Screening of 43 samples indicated that juices of Actinidia polygama Maxim., Rosa rugosa Thunb., Vaccinium smallii A. Gray, and Sorbus sambucifolia Roem. strongly induced differentiation of HL-60 cells to monocyte/macrophage characteristics in a concentration-dependent manner as indicated by histochemical and biochemical examinations.

The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells.

Science.gov (United States)

van Keimpema, Martine; Grüneberg, Leonie J; Schilder-Tol, Esther J M; Oud, Monique E C M; Beuling, Esther A; Hensbergen, Paul J; de Jong, Johann; Pals, Steven T; Spaargaren, Marcel

2017-03-01

The forkhead transcription factor FOXP1 is generally regarded as an oncogene in activated B cell-like diffuse large B-cell lymphoma. Previous studies have suggested that a small isoform of FOXP1 rather than full-length FOXP1, may possess this oncogenic activity. Corroborating those studies, we herein show that activated B cell-like diffuse large B-cell lymphoma cell lines and primary activated B cell-like diffuse large B-cell lymphoma cells predominantly express a small FOXP1 isoform, and that the 5'-end of the Foxp1 gene is a common insertion site in murine lymphomas in leukemia virus- and transposon-mediated insertional mutagenesis screens. By combined mass spectrometry, (quantative) reverse transcription polymerase chain reaction/sequencing, and small interfering ribonucleic acid-mediated gene silencing, we determined that the small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma lacks the N-terminal 100 amino acids of full-length FOXP1. Aberrant overexpression of this FOXP1 isoform (ΔN100) in primary human B cells revealed its oncogenic capacity; it repressed apoptosis and plasma cell differentiation. However, no difference in potency was found between this small FOXP1 isoform and full-length FOXP1. Furthermore, overexpression of full-length FOXP1 or this small FOXP1 isoform in primary B cells and diffuse large B-cell lymphoma cell lines resulted in similar gene regulation. Taken together, our data indicate that this small FOXP1 isoform and full-length FOXP1 have comparable oncogenic and transcriptional activity in human B cells, suggesting that aberrant expression or overexpression of FOXP1, irrespective of the specific isoform, contributes to lymphomagenesis. These novel insights further enhance the value of FOXP1 for the diagnostics, prognostics, and treatment of diffuse large B-cell lymphoma patients. Copyright© Ferrata Storti Foundation.

MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

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Lang, Yaoguo; Xu, Shidong; Ma, Jianqun; Wu, Jun [Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Jin, Shi; Cao, Shoubo [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Yu, Yan, E-mail: yuyan@hrbmu.edu.cn [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China)

2014-07-18

Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

Multidrug resistance and retroviral transduction potential in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Theilade, M D; Gram, G J; Jensen, P B

1999-01-01

Multidrug resistance (MDR) remains a major problem in the successful treatment of small cell lung cancer (SCLC). New treatment strategies are needed, such as gene therapy specifically targeting the MDR cells in the tumor. Retroviral LacZ gene-containing vectors that were either pseudotyped...... for the gibbon ape leukemia virus (GALV-1) receptor or had specificity for the amphotropic murine leukemia virus (MLV-A) receptor were used for transduction of five SCLC cell lines differing by a range of MDR mechanisms. Transduction efficiencies in these cell lines were compared by calculating the percentage...... of blue colonies after X-Gal staining of the cells grown in soft agar. All examined SCLC cell lines were transducible with either vector. Transduction efficiencies varied from 5.7% to 33.5% independent of the presence of MDR. These results indicate that MDR does not severely impair transduction of SCLC...

Managing inter-cell interference with advanced receivers and rank adaptation in 5G small cells

DEFF Research Database (Denmark)

Tavares, Fernando Menezes Leitão; Berardinelli, Gilberto; Catania, Davide

2015-01-01

-cell interference management. In this paper, we evaluate whether it is possible to rely on such advanced receivers as the main tool to deal with the inter-cell interference problem. We present a system-level performance evaluation in three different dense indoor small cell scenarios using a receiver model...... that includes both interference rejection combining (IRC) and successive interference cancellation (SIC) principles, as well as different rank adaptation strategies. Our results confirm that interference suppression receivers with a supportive system design can indeed represent a valid alternative to frequency...

Circulating blocking factors of lymphoid-cell cytotoxicity in x-ray-induced rat small-bowel adenocarcinoma

International Nuclear Information System (INIS)

Stevens, R.H.; Brooks, G.P.; Osborne, J.W.

1979-01-01

Circulating blocking factors capable of abrogating cell-mediated immune responses measured by in vitro lymphoid-cell cytotoxicity were identified in the sera of Holtzman outbred rats 6 to 9 months after a single exposure of only the temporarily exteriorized, hypoxic ileum and jejunum to 1700 to 2000 R of X radiation. Such factors were found to exist in the serum of every animal exposed to the ionizing radiation regardless of whether a visibly identifiable small-bowel adenocarcinoma existed or subsequently would develop. Protection of cultured x-ray-induced rat small-bowel cancer cells from destruction by tumor-sensitized lymphoid cells as measured by the release of lactoperoxidase-catalyzed radioiodinated membrane proteins from the tumor target cells was conferred by the action of the blocking factors at both effector and target cell levels. The results of this study demonstrate that exposure of only the rat small intestine to ionizing radiation leads to elaboration of circulating factors identifiable several months postirradiation which will block cell-mediated immune responses directed against cancer cells developing in the exposed tissue

Tuberculous pneumonia and bacteriaI pneumonia in diabetic patients: comparison of CT findings

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Kim, Yoo Kyung; Shim, Sung Shine [College of Medicine, Chungnam Univ., Daejeon (Korea, Republic of); Kim, Jin Hwan [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

2004-07-01

To compare the CT findings of tuberculous pneumonia (TBPN) with those of bacterial pneumonia (BAPN) in diabetic patients and to evaluate the usefulness of CT in the differential diagnosis of these two diseases. The chest CT scans of 23 diabetic patients with TBPN (M:F=21:2; mean age, 59 yrs.) and of 37 diabetic patients with BAPN (M:F=21:16; mean age, 63 yrs.) were evaluated by two radiologists with regard to low attenuation areas in regions of consolidation, cavities, air bronchogram, volume changes, ground-glass attenuation, findings of bronchogenic spread, and other associated findings. The involvement of each segment was recorded in all patients. The frequencies of multiple small low-attenuation areas in regions of consolidation (52%, 0%), multiple cavities (35%, 3%), loss of volume (70%, 30%) and findings of bronchogenic spread (96%, 30%) were significantly higher in TBPN than in BAPN (p< .05). Low-attenuation masses and bizarre-shaped cavities were noted only in TBPN. Large areas of ground-glass attenuation (4%, 38%) and bilateral pleural effusions (0%, 19%) were more common in BAPN, while air-bronchogram was common in both groups (96%, 86%). The involvement of the superior segment was significantly more common in TBPN (p< .05). In the diabetic patients with pulmonary consolidation, CT findings of multiple small low-attenuation areas, multiple cavities, bizarre-shaped cavities, low attenuation masses in cavities, volume loss, and findings of bronchogenic spread are more suggestive of TBPN, while large areas of ground-glass attenuation and bilateral pleural effusions are more suggestive of BAPN. CT may be useful in the differential diagnosis between TBPN and BAPN.

Merkel cell polyomavirus in Merkel cell carcinogenesis: small T antigen-mediates c-Jun phosphorylation.

Science.gov (United States)

Wu, Julie H; Simonette, Rebecca A; Nguyen, Harrison P; Rady, Peter L; Tyring, Stephen K

2016-06-01

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer associated with the Merkel cell polyomavirus (MCPyV). The MCPyV genome, which is clonally integrated in the majority of MCCs, encodes the regulatory small T (sT) antigen. Previously, reports have established MCPyV sT antigen as a potent oncogene capable of inducing cell transformation. In the current study, we demonstrate a distinct role for c-Jun hyperactivation in MCPyV sT antigen pathogenesis. As MCPyV sT antigen's association with aggressive cancer growth has been previously established, this finding may represent a potential therapeutic target for the treatment of MCCs.

PDGFR-Β expression in small cell lung cancer patients

International Nuclear Information System (INIS)

Shinohara, Eric T.; Gonzalez, Adriana; Massion, Pierre P.; Olson, Sandra J.; Albert, Jeffrey M.; Shyr, Yu; Carbone, David P.; Johnson, David H.; Hallahan, Dennis E.; Lu Bo

2007-01-01

Background: Platelet derived growth factor (PDGF) and PDGFR-β are expressed and have been found to have prognostic value in several human cancers. Data in non-small-cell cancer cell lines have suggested that PDGFR is a therapeutic target for drug development. In the current study PDGFR-β expression and prognostic value in small cell lung cancer (SCLC) was investigated. Methods and Materials: Paraffin-embedded tissue blocks from 53 patients with limited and extensive stage SCLC were obtained for immunohistochemical staining. Tumors from each patient were sampled 3 times and stained with PDGFR-β specific antibody. Patients were divided into low and high staining groups based on intensity. Results: There was high intensity PDGFR-β staining in 20 patients with SCLC. Another 29 expressed low intensity PDGFR-β staining, with only 4 patients showing no PDGFR-β staining. There was no statistically significant difference in 5 year overall survival between patients with low levels of PDGFR-β staining vs. those with high level staining SCLC tumors (p = 0.538). Conclusions: The present study found that the majority of SCLC patients express, at least, a low level of PDGF-β. However, the level of PDGFR-β expression was not a statistically significant predictor of 5 year overall survival in SCLC

A High-Throughput Small Molecule Screen for C. elegans Linker Cell Death Inhibitors.

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Andrew R Schwendeman

Full Text Available Programmed cell death is a ubiquitous process in metazoan development. Apoptosis, one cell death form, has been studied extensively. However, mutations inactivating key mammalian apoptosis regulators do not block most developmental cell culling, suggesting that other cell death pathways are likely important. Recent work in the nematode Caenorhabditis elegans identified a non-apoptotic cell death form mediating the demise of the male-specific linker cell. This cell death process (LCD, linker cell-type death is morphologically conserved, and its molecular effectors also mediate axon degeneration in mammals and Drosophila. To develop reagents to manipulate LCD, we established a simple high-throughput screening protocol for interrogating the effects of small molecules on C. elegans linker cell death in vivo. From 23,797 compounds assayed, 11 reproducibly block linker cell death onset. Of these, five induce animal lethality, and six promote a reversible developmental delay. These results provide proof-of principle validation of our screening protocol, demonstrate that developmental progression is required for linker cell death, and suggest that larger scale screens may identify LCD-specific small-molecule regulators that target the LCD execution machinery.

Dclk1+ small intestinal epithelial tuft cells display the hallmarks of quiescence and self-renewal

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Chandrakesan, Parthasarathy; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Taylor, Vivian E.; Li, James D.; Ali, Naushad; Sureban, Sripathi M.; Qante, Michael; Wang, Timothy C.; Bronze, Michael S.; Houchen, Courtney W.

2015-01-01

To date, no discrete genetic signature has been defined for isolated Dclk1+ tuft cells within the small intestine. Furthermore, recent reports on the functional significance of Dclk1+ cells in the small intestine have been inconsistent. These cells have been proposed to be fully differentiated cells, reserve stem cells, and tumor stem cells. In order to elucidate the potential function of Dclk1+ cells, we FACS-sorted Dclk1+ cells from mouse small intestinal epithelium using transgenic mice expressing YFP under the control of the Dclk1 promoter (Dclk1-CreER;Rosa26-YFP). Analysis of sorted YFP+ cells demonstrated marked enrichment (~6000 fold) for Dclk1 mRNA compared with YFP− cells. Dclk1+ population display ~6 fold enrichment for the putative quiescent stem cell marker Bmi1. We observed significantly greater expression of pluripotency genes, pro-survival genes, and quiescence markers in the Dclk1+ population. A significant increase in self-renewal capability (14-fold) was observed in in vitro isolated Dclk1+ cells. The unique genetic report presented in this manuscript suggests that Dclk1+ cells may maintain quiescence, pluripotency, and metabolic activity for survival/longevity. Functionally, these reserve characteristics manifest in vitro, with Dclk1+ cells exhibiting greater ability to self-renew. These findings indicate that quiescent stem-like functionality is a feature of Dclk1-expressing tuft cells. PMID:26362399

A Distributed Taxation Based Rank Adaptation Scheme for 5G Small Cells

DEFF Research Database (Denmark)

Catania, Davide; Cattoni, Andrea Fabio; Mahmood, Nurul Huda

2015-01-01

The further densification of small cells impose high and undesirable levels of inter-cell interference. Multiple Input Multiple Output (MIMO) systems along with advanced receiver techniques provide us with extra degrees of freedom to combat such a problem. With such tools, rank adaptation...

MRI findings of small cell neuroendocrime carcinoma of the uterine cervix: A case report

Energy Technology Data Exchange (ETDEWEB)

Won, You Sun; Yi, Boem Ha; Lee, Hae Kyung; Lee, Min Hee; Choi, Seo Youn; Kwak, Jeong Ja [Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon (Korea, Republic of)

2015-10-15

Small cell neuroendocrine carcinoma of the uterine cervix is a rare primary neoplasm, accounting for less than 5% of all uterine cervical cancers. The tumor is known to have an aggressive behavior and poor prognosis. In this article, we present the MRI findings of 5 cases of pathologically-proven small cell neuroendocrine carcinoma of the uterine cervix, including diffusion-weighted images.

Hanging drop culture enhances differentiation of human adipose-derived stem cells into anterior neuroectodermal cells using small molecules.

Science.gov (United States)

Amirpour, Noushin; Razavi, Shahnaz; Esfandiari, Ebrahim; Hashemibeni, Batoul; Kazemi, Mohammad; Salehi, Hossein

2017-06-01

Inspired by in vivo developmental process, several studies were conducted to design a protocol for differentiating of mesenchymal stem cells into neural cells in vitro. Human adipose-derived stem cells (hADSCs) as mesenchymal stem cells are a promising source for this purpose. At current study, we applied a defined neural induction medium by using small molecules for direct differentiation of hADSCs into anterior neuroectodermal cells. Anterior neuroectodermal differentiation of hADSCs was performed by hanging drop and monolayer protocols. At these methods, three small molecules were used to suppress the BMP, Nodal, and Wnt signaling pathways in order to obtain anterior neuroectodermal (eye field) cells from hADSCs. After two and three weeks of induction, the differentiated cells with neural morphology expressed anterior neuroectodermal markers such as OTX2, SIX3, β-TUB III and PAX6. The protein expression of such markers was confirmed by real time, RT-PCR and immunocytochemistry methods According to our data, it seems that the hanging drop method is a proper approach for neuroectodermal induction of hADSCs. Considering wide availability and immunosuppressive properties of hADSCs, these cells may open a way for autologous cell therapy of neurodegenerative disorders. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Expression of myc family oncoproteins in small-cell lung-cancer cell lines and xenografts

DEFF Research Database (Denmark)

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

1993-01-01

A number of genes have altered activity in small-cell lung cancer (SCLC), but especially genes of the myc family (c-myc, L-myc and N-myc) are expressed at high levels in SCLC. Most studies have explored expression at the mRNA level, whereas studies of myc family oncoprotein expression are sparse....... WE examined the expression of myc proto-oncogenes at the mRNA and protein level in 23 cell lines or xenografts. In the cell lines, the doubling time and the cell-cycle distribution, as determined by flow-cytometric DNA analysis, were examined to establish whether the level of myc......-myc. In general, the level of expression of c-myc and N-myc was similar at the mRNA and the protein level. Expression of c-myc was positively correlated with the proliferative index (sum of S and G2+M phases) of cell lines, but not with the population doubling time. In general, L-myc-expressing cell lines had...

A mass that has no (EBUS) echo.

Science.gov (United States)

Rosenblum, Matthew K; Wang, Sue X; Seeley, Eric J

2018-01-01

We report findings for a patient that underwent endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA) for diagnostic purposes after an abnormal chest CT. The patient initially presented with cough and shortness of breath. Chest CT revealed a 6 cm soft tissue mass with mildly enlarged right hilar lymph nodes (LNs) and a small right sided pleural effusion. Based on these radiologic findings, the patient underwent an EBUS guided FNA of the mass. To our surprise, the mass was hypoechoic by EBUS and on aspiration, the syringe filled with yellow fluid. This finding in combination with a re-review of the CT scans with a special focus on the Hounsfield Units of the lesion confirmed the diagnosis of a mediastinal bronchogenic cyst. This case demonstrates the role of Hounsfield units in analyzing mediastinal masses and highlights the effectiveness of EBUS guided TBNA in diagnosis and treatment of bronchogenic cysts.

Indomethacin induces apoptosis via a MRPI-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRPI

NARCIS (Netherlands)

de Groot, D. J. A.; van der Deen, M.; Le, T. K. P.; Regeling, A.; de Jong, S.; de Vries, E. G. E.

2007-01-01

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRPI) function. The doxorubicin-resistant MRPI-overexpressing human SCLC cell line

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

Crypt base columnar stem cells in small intestines of mice are radioresistant

NARCIS (Netherlands)

Hua, G.; Thin, T.H.; Feldman, R.; Haimovitz-Friedman, A.; Clevers, H.; Fuks, Z.; Kolesnick, R.

2012-01-01

BACKGROUND & AIMS: Adult stem cells have been proposed to be quiescent and radiation resistant, repairing DNA double-strand breaks by nonhomologous end joining. However, the population of putative small intestinal stem cells (ISCs) at position +4 from the crypt base contradicts this model, in that

Advances of Immunotherapy in Small Cell Lung Cancer

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Jingjing LIU

2014-06-01

Full Text Available Small cell lung cancer (SCLC is complex heterogeneous due to unclear biological characteristics in terms of cell origin, pathogenesis and driver genes etc. Diagnosis and treatment of SCLC has been slowly improved and few breakthroughs have been discovered up to now. Therefore new strategies are urgently needed to improve the efficacy of SCLC treatment. Tumor immunotherapy has potential to restore and trigger the immune system to recognize and eliminate tumor cells, notably it has only minimal adverse impact on normal tissue. Cancer vaccine, adoptive immunotherapy, cytokines and checkpoint inhibitors have now been launched for clinical treatment of SCLC. Ipilimumab is the most promising medicine of immunotherapy. Immunotherapy is expected to bring new vision to the treatment of SCLC. And further researches are needed on such problems affecting efficacy of immunotherapy as the heterogeneity of SCLC, the uncertainty of target for immunotherapy, the immune tolerance, etc.

Adaptive repair induced by small doses of γ radiation in repair-defective human cells

International Nuclear Information System (INIS)

Zasukhina, G.D.; L'vova, G.N.; Vasil'eva, I.M.; Sinel'shchikova, T.A.; Semyachkina, A.N.

1993-01-01

Adaptive repair induced by small doses of gamma radiation was studied in repair-defective xeroderma pigmentosum, gout, and homocystinuria cells. The adaptation of cells induced by small doses of radiation was estimated after subsequent exposure to gamma radiation, 4-nitroquinoline-1-oxide, and N-methyl-N-nitro-N-nitrosoguanidine by three methods: (1) by the reduction in DNA breaks; (2) by induction of resistant DNA synthesis; and (3) by increased reactivation of vaccinia virus. The three cell types in response to the three different mutagens revealed differences in the mechanism of cell defense in excision repair, in the adaptive response, and in Weigl reactivation

A-π-D-π-A Electron-Donating Small Molecules for Solution-Processed Organic Solar Cells: A Review.

Science.gov (United States)

Wang, Zhen; Zhu, Lingyun; Shuai, Zhigang; Wei, Zhixiang

2017-11-01

Organic solar cells based on semiconducting polymers and small molecules have attracted considerable attention in the last two decades. Moreover, the power conversion efficiencies for solution-processed solar cells containing A-π-D-π-A-type small molecules and fullerenes have reached 11%. However, the method for designing high-performance, photovoltaic small molecules still remains unclear. In this review, recent studies on A-π-D-π-A electron-donating small molecules for organic solar cells are introduced. Moreover, the relationships between molecular properties and device performances are summarized, from which inspiration for the future design of high performance organic solar cells may be obtained. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differences in practice patterns and costs between small cell and non-small cell lung cancer patients in Japan

International Nuclear Information System (INIS)

Kuwabara, Kazuaki; Matsuda, Shinya; Fushimi, Kiyohide; Anan, Makoto; Ishikawa, Koichi B.; Horiguchi, Hiromasa; Hayashida, Kenshi; Fujimori, Kenji

2009-01-01

Many reports exist regarding the economic evaluation of evolving chemotherapeutic regimens or diagnostic images for lung cancer (LC) patients. However, it is not clear whether clinical information, such as pathological diagnosis or cancer stage, should be considered as a risk adjustment in lung cancer. This study compared the cost and practice patterns between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) patients. 6,060 LC patients treated at 58 academic hospitals and 14,507 at 257 community hospitals were analyzed. Study variables included demographic variables, comorbid status, cancer stage, use of imaging and surgical procedures, type of adjuvant therapy (chemotherapy, radiation or chemoradiation), use of ten chemotherapeutic agents, length of stay (LOS), and total charges (TC; US$1=100 yen) in SCLC and NSCLC patients. The impact of pathological diagnosis on LOS and TC was investigated using multivariate analysis. We identified 3,571 SCLC and 16,996 NSCLC patients. The proportion of demographic and practice-process variables differed significantly between SCLC and NSCLC patients, including diagnostic imaging, adjuvant therapy and surgical procedures. Median LOS and TC were 20 days and US$6,015 for SCLC and 18 days and US$6,993 for NSCLC patients, respectively (p<0.001 for each variable). Regression analysis revealed that pathological diagnosis was not correlated with TC. Physicians should acknowledge that pathological diagnosis dose not accounts for any variation in cost of LC patients but that should remain as an indicator of appropriate care like selection of chemotherapeutic agents. (author)

Comparison of dengue virus type 2-specific small RNAs from RNA interference-competent and -incompetent mosquito cells.

Directory of Open Access Journals (Sweden)

Jaclyn C Scott

2010-10-01

Full Text Available The exogenous RNA interference (RNAi pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (siRNAs are key components of this pathway. Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to control arbovirus transmission. Using deep sequencing technology, we characterized dengue virus type 2 (DENV2-specific small RNAs produced during infection of Aedes aegypti mosquitoes and A. aegypti Aag2 cell cultures and compared them to those produced in the C6/36 Aedes albopictus cell line. We show that the size and mixed polarity of virus-specific small RNAs from DENV-infected A. aegypti cells indicate that they are products of Dicer-2 (Dcr2 cleavage of long dsRNA, whereas C6/36 cells generate DENV2-specific small RNAs that are longer and predominantly positive polarity, suggesting that they originate from a different small RNA pathway. Examination of virus-specific small RNAs after infection of the two mosquito cell lines with the insect-only flavivirus cell fusing agent virus (CFAV corroborated these findings. An in vitro assay also showed that Aag2 A. aegypti cells are capable of siRNA production, while C6/36 A. albopictus cells exhibit inefficient Dcr2 cleavage of long dsRNA. Defective expression or function of Dcr2, the key initiator of the RNAi pathway, might explain the comparatively robust growth of arthropod-borne viruses in the C6/36 cell line, which has been used frequently as a surrogate for studying molecular interactions between arboviruses and cells of their mosquito hosts.

Interplay between efficiency and device architecture for small molecule organic solar cells.

Science.gov (United States)

Williams, Graeme; Sutty, Sibi; Aziz, Hany

2014-06-21

Small molecule organic solar cells (OSCs) have experienced a resurgence of interest over their polymer solar cell counterparts, owing to their improved batch-to-batch (thus, cell-to-cell) reliability. In this systematic study on OSC device architecture, we investigate five different small molecule OSC structures, including the simple planar heterojunction (PHJ) and bulk heterojunction (BHJ), as well as several planar-mixed structures. The different OSC structures are studied over a wide range of donor:acceptor mixing concentrations to gain a comprehensive understanding of their charge transport behavior. Transient photocurrent decay measurements provide crucial information regarding the interplay between charge sweep-out and charge recombination, and ultimately hint toward space charge effects in planar-mixed structures. Results show that the BHJ/acceptor architecture, comprising a BHJ layer with high C60 acceptor content, generates OSCs with the highest performance by balancing charge generation with charge collection. The performance of other device architectures is largely limited by hole transport, with associated hole accumulation and space charge effects.

Interstitial cells of Cajal and Auerbach's plexus. A scanning electron microscopical study of guinea-pig small intestine

DEFF Research Database (Denmark)

Jessen, Harry; Thuneberg, Lars

1991-01-01

Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy......Anatomy, interstitial cells of Cajal, myenteric plexus, small intestine, guinea-pig, scanning electron microscopy...

Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine

International Nuclear Information System (INIS)

Suzuki, Katsumasa; Fukui, Hirokazu; Kayahara, Takahisa; Sawada, Mitsutaka; Seno, Hiroshi; Hiai, Hiroshi; Kageyama, Ryoichiro; Okano, Hideyuki; Chiba, Tsutomu

2005-01-01

We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine

The Physics of Small Molecule Acceptors for Efficient and Stable Bulk Heterojunction Solar Cells

KAUST Repository

Gasparini, Nicola

2018-01-29

Organic bulk heterojunction solar cells based on small molecule acceptors have recently seen a rapid rise in the power conversion efficiency with values exceeding 13%. This impressive achievement has been obtained by simultaneous reduction of voltage and charge recombination losses within this class of materials as compared to fullerene-based solar cells. In this contribution, the authors review the current understanding of the relevant photophysical processes in highly efficient nonfullerene acceptor (NFA) small molecules. Charge generation, recombination, and charge transport is discussed in comparison to fullerene-based composites. Finally, the authors review the superior light and thermal stability of nonfullerene small molecule acceptor based solar cells, and highlight the importance of NFA-based composites that enable devices without early performance loss, thus resembling so-called burn-in free devices.

The Physics of Small Molecule Acceptors for Efficient and Stable Bulk Heterojunction Solar Cells

KAUST Repository

Gasparini, Nicola; Wadsworth, Andrew; Moser, Maximilian; Baran, Derya; McCulloch, Iain; Brabec, Christoph J.

2018-01-01

Organic bulk heterojunction solar cells based on small molecule acceptors have recently seen a rapid rise in the power conversion efficiency with values exceeding 13%. This impressive achievement has been obtained by simultaneous reduction of voltage and charge recombination losses within this class of materials as compared to fullerene-based solar cells. In this contribution, the authors review the current understanding of the relevant photophysical processes in highly efficient nonfullerene acceptor (NFA) small molecules. Charge generation, recombination, and charge transport is discussed in comparison to fullerene-based composites. Finally, the authors review the superior light and thermal stability of nonfullerene small molecule acceptor based solar cells, and highlight the importance of NFA-based composites that enable devices without early performance loss, thus resembling so-called burn-in free devices.

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

Science.gov (United States)

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.

The In Vitro Anti-Tumor Activity of Phycocyanin against Non-Small Cell Lung Cancer Cells

Directory of Open Access Journals (Sweden)

Shuai Hao

2018-05-01

Full Text Available Phycocyanin, a type of functional food colorant, is shown to have a potent anti-cancer property. Non-small cell lung cancer (NSCLC is one of the most aggressive form of cancers with few effective therapeutic options. Previous studies have demonstrated that phycocyanin exerts a growth inhibitory effect on NSCLC A549 cells. However, its biological function and underlying regulatory mechanism on other cells still remain unknown. Here, we investigated the in vitro function of phycocyanin on three typical NSCLC cell lines, NCI-H1299, NCI-H460, and LTEP-A2, for the first time. The results showed that phycocyanin could significantly induce apoptosis, cell cycle arrest, as well as suppress cell migration, proliferation, and the colony formation ability of NSCLC cells through regulating multiple key genes. Strikingly, phycocyanin was discovered to affect the cell phenotype through regulating the NF-κB signaling of NSCLC cells. Our findings demonstrated the anti-neoplastic function of phycocyanin and provided valuable information for the regulation of phycocyanin in NSCLC cells.

Selectins mediate small cell lung cancer systemic metastasis.

Directory of Open Access Journals (Sweden)

Franziska Heidemann

Full Text Available Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181. However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic.

Cells determine cell density using a small protein bound to a unique tissue-specific phospholipid

Directory of Open Access Journals (Sweden)

Christopher J. Petzold

2013-10-01

Full Text Available Cell density is the critical parameter controlling tendon morphogenesis. Knowing its neighbors allows a cell to regulate correctly its proliferation and collagen production. A missing link to understanding this process is a molecular description of the sensing mechanism. Previously, this mechanism was shown in cell culture to rely on a diffusible factor (SNZR [sensor] with an affinity for the cell layer. This led to purifying conditioned medium over 4 columns and analyzing the final column fractions for band intensity on SDS gels versus biological activity – a 16 kD band strongly correlated between assays. N-terminal sequencing – EPLAVVDL – identified a large gene (424 AA, extremely conserved between chicken and human. In this paper we probe whether this is the correct gene. Can the predicted large protein be cleaved to a smaller protein? EPLAVVDL occurs towards the C-terminus and cleavage would create a small 94 AA protein. This protein would run at ∼10 kD, so what modifications or cofactor binding accounts for its running at 16 kD on SDS gels? This protein has no prominent hydrophobic regions, so can it be secreted? To validate its role, the chicken cDNA for this gene was tagged with myc and his and transfected into a human osteosarcoma cell line (U2OS. U2OS cells expressed the gene but not passively: differentiating into structures resembling spongy bone and expressing alkaline phosphatase, an early bone marker. Intracellularly, two bands were observed by Western blotting: the full length protein and a smaller form (26 kD. Outside the cell, a small band (28 kD was detected, although it was 40% larger than expected, as well as multiple larger bands. These larger forms could be converted to the predicted smaller protein (94 AA + tags by changing salt concentrations and ultrafiltering – releasing a cofactor to the filtrate while leaving a protein factor in the retentate. Using specific degradative enzymes and mass spectrometry, the

Distribution of E-cadherin and ß-catenin in relation to cell maturation and cell extrusion in rat and mouse small intestines

DEFF Research Database (Denmark)

Larsson, Lars-Inge

2006-01-01

of programmed cell death (PCD) in mouse small intestinal epithelium. We have studied if this also occurs in the intact rodent small intestine. Our results confirm that extruded cells are negatie for E-cadherin. However, loss of the E-cadherin-interacting protein ß-cetenin preceded both extrusion and loss of E......-cadherin. Thus, all extruded cells as well as all cells in the process of extrusion lacked staining for ß-catenin. Moreover, almost 80% of all cells undergoing programmed cell death, as detected by the TUNEL reaction, lacked ß-catenin whereas over 70% of such cells were positive for E-cadherin. However, most...... ells lacking ß-catenin did not display signs of PCD as detected by the TUNEL method or by staining for active caspase-3. Therefore, these results suggest that loss of ß-catenin precedes the onset of programmed cell death, loss of E-cadherin and extrusion from the villi....

Full Duplex Communications in 5G Small Cells

DEFF Research Database (Denmark)

Mahmood, Nurul Huda; Gatnau, Marta; Berardinelli, Gilberto

2017-01-01

Full duplex communication promises system performance improvement over conventional half duplex communication by allowing simultaneous transmission and reception. However, such concurrent communication results in strong self interference and an increase in the overall network interference, and can...... only be exploited when traffic is available in both directions. The potential throughput gains of full duplex communication over conventional half duplex transmission in a small cell network with asymmetric traffic conditions is investigated in this contribution. The throughput performance gains...... are analysed using tools from stochastic geometry, and further confirmed through extensive system level simulations. Our findings explicitly quantify how the gains from full duplex communication depend on the traffic profile and the inter-cell interference coupling. The demonstrated throughput gains and delay...

[Clinic significance of nm23, collage IV and PCNA expression in non-small cell lung cancer].

Science.gov (United States)

Yu, Q; Ma, L; Jing, S; Xu, Y; Geng, D

2001-12-20

To study the significance of nm23, collagen IV and PCNA expressions in non-small cell lung cancer. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were examined with SP immunohistochemical technique. Of the 84 cases, there were squamous cell carcinoma 42, adenocarcinoma 42, stage I 27, stage II 24, stage III 24, and stage IV 9. Statistical analysis was performed with Chi-Square test. Expressions of the nm23, collagen IV and PCNA in 84 cases of non-small cell lung cancer were 60. 7% ( 51/ 84) , 75. 0% ( 63/ 84) and 53. 6% ( 45/ 84) respectively. There was negative correlation between the lymph node metastasis and the expressions of nm23 and collagen IV in squamous cell carcinoma, and the expressions of collagen IV and PCNA were associated with tumor differentiation. No correlation was found between TNM stage and expressions of nm23, collagen IV and PCNA. The results indicate that nm23, collagen IV and PCNA participate the modulation of metastasis of non-small cell lung cancer and that they may be used to evaluate the potential of metastasis.

Qualification of academic facilities for small-scale automated manufacture of autologous cell-based products.

Science.gov (United States)

Hourd, Paul; Chandra, Amit; Alvey, David; Ginty, Patrick; McCall, Mark; Ratcliffe, Elizabeth; Rayment, Erin; Williams, David J

2014-01-01

Academic centers, hospitals and small companies, as typical development settings for UK regenerative medicine assets, are significant contributors to the development of autologous cell-based therapies. Often lacking the appropriate funding, quality assurance heritage or specialist regulatory expertise, qualifying aseptic cell processing facilities for GMP compliance is a significant challenge. The qualification of a new Cell Therapy Manufacturing Facility with automated processing capability, the first of its kind in a UK academic setting, provides a unique demonstrator for the qualification of small-scale, automated facilities for GMP-compliant manufacture of autologous cell-based products in these settings. This paper shares our experiences in qualifying the Cell Therapy Manufacturing Facility, focusing on our approach to streamlining the qualification effort, the challenges, project delays and inefficiencies we encountered, and the subsequent lessons learned.

Value of brain computed tomography in small cell lung cancers

International Nuclear Information System (INIS)

Fernet, M.; Breau, J.L.; Goldlust, D.; Israel, L.

1988-01-01

88 patients with small cell lung cancer were studied. Brain scans were performed first at initial staging and repeated at regular intervals during the survey. The results confirm the limited value of brain scans in the detection of metastases in neurologically asymptomatic patients [fr

Argyrophilic nucleolar organizer region in MIB-1 positive cells in non-small cell lung cancer: clinicopathological significance and survival

International Nuclear Information System (INIS)

Kobyakov, Dmitriy Sergeevich; Avdalyan, Ashot Merudzhanovich; Lazarev, Aleksandr Fedorovich; Lushnikova, Elena Leonidovna; Nepomnyashchikh, Lev Moiseevich

2014-01-01

To evaluate the relation between argyrophilic nucleolar organizer region (AgNOR)-associated proteins and clinicopathological parameters and survival in non-small-cell lung cancer (NSCLC). A total of 207 surgical specimens diagnosed as NSCLC were included in this study. Double-staining procedures were performed using antigen Ki-67 (clone MIB-1) and silver nitrate by immunohistochemical and AgNOR-staining methods. The AgNOR area in MIB-1-positive cells of NSCLC is related to clinicopathological parameters under the TNM (tumor, node, and metastasis) system. The survival of patients with small AgNOR area in MIB-1-positive cells is better than that of patients with large AgNOR area. Molecular, biological (AgNOR area in MIB-1-positive cells), and clinicopathological (greatest tumor dimension, metastases to regional lymph nodes, histology, and differentiation) parameters are independent prognostic factors of NSCLC. The AgNOR area in MIB-1-positive cells is related to clinicopathological parameters and survival in NSCLC

Lung bud anomalies: Radiologic findings in 30 patients

International Nuclear Information System (INIS)

Son, Kyung Myung; Yang, Hae Ryoun; Jeon, Jeong Su; Kim, Ok Hwa; Kim, Choon Yul; Bahk, Yong Whee

1990-01-01

Bronchogenic cyst, pulmonary sequestration, congenital cystic adenomatoid malformation and congenital lobar emphysema are four major congenital cystic pulmonary diseases that represent a spectrum of closely related anomalies arising at early stage of embryonic lung bud maturation. Most of them present with recurrent pulmonary infections or chest pain since childhood and usually the diagnosis is made at this age. Sometimes the lesions are silent and found at adult age. We retrospectively analyzed the pain chest radiograms of 30 patients with a lung bud anomaly. The diagnosis was established by surgery and biopsy, but bronchography, computed tomography and ultrasonography aided in the diagnosis, seventeen bronchogenic cysts, 8 pulmonary sequestrations, 2 congenital cystic adenomatoid malformations, 2 congenital lobar emphysema and 1 congenital bronchial stenosis are included in this study. Nine out of 13 intrapulmonary bronchogenic cysts involved the lower lobes: thin-walled cysts with or without air-fluid level were the characteristic chest roentgenographic finding. However, mediastinal bronchogenic cysts showed well-marginated mass. The pulmonary sequestration showed similar cysts mass with or without air-fluid levels in five out of eight patients, but the cyst wall was not so sharply defined as in the bronchogenic cyst. In two patients of congenital cystic adenomatoid malformation, a large thin-walled cyst with air fluid level was noted and differentiation from intrapulmonary bronchogenic cyst was difficult both by chest roentgenogram and computed tomography. Two patients of congenital lobar emphysema and one patient of bronchial stenosis showed unilateral hyperlucent lung without discrete cystic mass formation

Immune checkpoint inhibitors: the new frontier in non–small cell lung cancer treatment

Directory of Open Access Journals (Sweden)

El-Osta HE

2016-08-01

Full Text Available Hazem El-Osta, Kamran Shahid, Glenn M Mills, Prakash Peddi Department of Medicine, Division of Hematology-Oncology, Louisiana State University Health Sciences Center, Shreveport, LA, USA Abstract: Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field. Keywords: checkpoint inhibitors, immunotherapy, nivolumab, non-small-cell lung cancer, pembrolizumab, programmed death-1, programmed death ligand-1

Lipopolysaccharide-binding protein: localization in secretory granules of Paneth cells in the mouse small intestine

DEFF Research Database (Denmark)

Hansen, Gert H; Rasmussen, Karina; Niels-Christiansen, Lise-Lotte

2009-01-01

Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase protein involved in the host's response to endotoxin and mainly synthesized and secreted to the blood by the liver. But in addition, LBP is also made by extrahepatic cells, including the enterocyte-like cell line Caco-2. To study...... in closer detail the synthesis and storage of LBP in the intestinal mucosal epithelium, we performed an immunolocalization of LBP in mouse small intestine. By immunofluorescence microscopy, an antibody recognizing the 58-60 kDa protein of LBP distinctly labeled a small population of cells located deep...... into the crypts. This cell population was also positive for lysozyme and alpha-defensin 4, identifying Paneth cells as the main intestinal LBP-producing cells. By immunogold electron microscopy, intense labeling was observed in the secretory granules of these cells. We conclude that Paneth cells express LBP...

The contribution of computed tomography to the differentiation between inflammatory and neoplastic pulmonary disease

International Nuclear Information System (INIS)

Steinbaecher, M.; Koenig, R.; Kaick, G. van; Schaaf, J.

1984-01-01

Fourty patients suspected of having a bronchogenic carcinoma but who, in fact, had inflammatory pulmonary lesions were examined by computed tomography. The findings were compared with the CT appearances of 40 patients with bronchogenic carcinomas (20 of these underwent surgery). In 28 patients (70%) suspected of having a bronchogenic carcinoma, the CT findings indicated an inflammatory lesion. As might have been expected, there was no single CT criterion which is found only in inflammatory lesions. Chronic inflammatory processes and inflammatory pseudo-tumours (chronic pneumonias and tuberculosis) cannot be distinguished from malignant tumours by CT (12 out of 40 patients, 30%). (orig.) [de

SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer

International Nuclear Information System (INIS)

Cao, Rubo; Ding, Qian; Li, Pindong; Xue, Jun; Zou, Zhenwei; Huang, Jing; Peng, Gang

2013-01-01

Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1). A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression. Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression. SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance

Green heterogeneous small-cell networks: Toward reducing the CO2 emissions of mobile communications industry using uplink power adaptation

KAUST Repository

Shakir, Muhammad Zeeshan; Qaraqe, Khalid A.; Tabassum, Hina; Alouini, Mohamed-Slim; Serpedin, Erchin; Imran, Muhammad Ali

2013-01-01

Heterogeneous small cell networks, or Het- SNets, are considered as a standard part of future mobile networks in which multiple lowpower low-cost user deployed base stations complement the existing macrocell infrastructure. This article proposes an energy-efficient deployment of the cells where the small cell base stations are arranged around the edge of the reference macrocell, and the deployment is referred to as cell-on-edge (COE) deployment. The proposed deployment ensures an increase in the network spectral and energy efficiency by facilitating cell edge mobile users with small cells. Moreover, COE deployment guarantees reduction of the carbon footprint of mobile operations by employing adaptive uplink power control. In order to calibrate the reduction in CO2 emissions, this article quantifies the ecological and associated economical impacts of energy savings in the proposed deployment. Simulation results quantify the improvements in CO2 emissions and spectral and energy gains of the proposed COE deployment compared to macro-only networks and typical small cell deployment strategies where small cells are randomly deployed within a given macrocell. © 2013 IEEE.

Green heterogeneous small-cell networks: Toward reducing the CO2 emissions of mobile communications industry using uplink power adaptation

KAUST Repository

Shakir, Muhammad Zeeshan

2013-06-01

Heterogeneous small cell networks, or Het- SNets, are considered as a standard part of future mobile networks in which multiple lowpower low-cost user deployed base stations complement the existing macrocell infrastructure. This article proposes an energy-efficient deployment of the cells where the small cell base stations are arranged around the edge of the reference macrocell, and the deployment is referred to as cell-on-edge (COE) deployment. The proposed deployment ensures an increase in the network spectral and energy efficiency by facilitating cell edge mobile users with small cells. Moreover, COE deployment guarantees reduction of the carbon footprint of mobile operations by employing adaptive uplink power control. In order to calibrate the reduction in CO2 emissions, this article quantifies the ecological and associated economical impacts of energy savings in the proposed deployment. Simulation results quantify the improvements in CO2 emissions and spectral and energy gains of the proposed COE deployment compared to macro-only networks and typical small cell deployment strategies where small cells are randomly deployed within a given macrocell. © 2013 IEEE.

Development of the novel control algorithm for the small proton exchange membrane fuel cell stack without external humidification

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae-Hoon; Kim, Sang-Hyun; Kim, Wook; Lee, Jong-Hak; Cho, Kwan-Seok; Choi, Woojin [Department of Electrical Engineering, Soongsil University, 1-1 Sangdo-dong, Dongjak-gu, Seoul 156-743 (Korea); Park, Kyung-Won [Department of Chemical/Environmental Engineering, Soongsil University, 1-1 Sangdo-dong, Dongjak-gu, Seoul 156-743 (Korea)

2010-09-15

Small PEM (proton exchange membrane) fuel cell systems do not require humidification and have great commercialization possibilities. However, methods for controlling small PEM fuel cell stacks have not been clearly established. In this paper, a control method for small PEM fuel cell systems using a dual closed loop with a static feed-forward structure is defined and realized using a microcontroller. The fundamental elements that need to be controlled in fuel cell systems include the supply of air and hydrogen, water management inside the stack, and heat management of the stack. For small PEM fuel cell stacks operated without a separate humidifier, fans are essential for air supply, heat management, and water management of the stack. A purge valve discharges surplus water from the stack. The proposed method controls the fan using a dual closed loop with a static feed-forward structure, thereby improving system efficiency and operation stability. The validity of the proposed method is confirmed by experiments using a 150-W PEM fuel cell stack. We expect the proposed algorithm to be widely used for controlling small PEM fuel cell stacks. (author)

Solution processable organic polymers and small molecules for bulk-heterojunction solar cells: A review

International Nuclear Information System (INIS)

Sharma, G. D.

2011-01-01

Solution processed bulk heterojunction (BHJ) organic solar cells (OSCs) have gained wide interest in past few years and are established as one of the leading next generation photovoltaic technologies for low cost power production. Power conversion efficiencies up to 6% and 6.5% have been reported in the literature for single layer and tandem solar cells, respectively using conjugated polymers. A recent record efficiency about 8.13% with active area of 1.13 cm 2 has been reported. However Solution processable small molecules have been widely applied for photovoltaic (PV) devices in recent years because they show strong absorption properties, and they can be easily purified and deposited onto flexible substrates at low cost. Introducing different donor and acceptor groups to construct donor--acceptor (D--A) structure small molecules has proved to be an efficient way to improve the properties of organic solar cells (OSCs). The power conversion efficiency about 4.4 % has been reported for OSCs based on the small molecules. This review deals with the recent progress of solution processable D--A structure small molecules and discusses the key factors affecting the properties of OSCs based on D--A structure small molecules: sunlight absorption, charge transport and the energy level of the molecules.

Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Hougaard, S; Nørgaard, P; Abrahamsen, N

1999-01-01

Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

International Nuclear Information System (INIS)

Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

2016-01-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

Energy Technology Data Exchange (ETDEWEB)

Mi, Shanwei; Xiang, Gang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Yuwen, Daolu [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Su, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

2016-11-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Small-cell comb does not control Varroa mites in colonies of honeybees of European origin

OpenAIRE

Seeley , Thomas; Griffin , Sean

2011-01-01

International audience; We tested the idea that Varroa destructor can be controlled in colonies of the European subspecies of Apis mellifera by providing them with combs built of small cells, in which immature mites might have difficulty developing for lack of space. We established seven pairs of equal-size colonies that started out equally infested with mites. In each pair, one hive contained only standard-cell (5.4 mm) comb, and the other contained only small-cell (4.8 mm) comb. We measured...

Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer

NARCIS (Netherlands)

Schaake-Koning, C.; van den Bogaert, W.; Dalesio, O.; Festen, J.; Hoogenhout, J.; van Houtte, P.; Kirkpatrick, A.; Koolen, M.; Maat, B.; Nijs, A.

1992-01-01

BACKGROUND AND METHODS: Cisplatin (cis-diamminedichloroplatinum) has been reported to enhance the cell-killing effect of radiation, an effect whose intensity varies with the schedule of administration. We randomly assigned 331 patients with nonmetastatic inoperable non-small-cell lung cancer to one

Tamoxifen enhances erlotinib-induced cytotoxicity through down-regulating AKT-mediated thymidine phosphorylase expression in human non-small-cell lung cancer cells.

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Ko, Jen-Chung; Chiu, Hsien-Chun; Syu, Jhan-Jhang; Jian, Yi-Jun; Chen, Chien-Yu; Jian, Yun-Ting; Huang, Yi-Jhen; Wo, Ting-Yu; Lin, Yun-Wei

2014-03-01

Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. Copyright © 2014 Elsevier Inc. All rights reserved.

Primary Small-Cell Carcinoma of the Palate with Cushing’s Syndrome: A Case Report

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Yingqiu Song

2012-01-01

Full Text Available We report a 24-year-old woman presenting with a relapsed soy-bean-size tender mass at the junction of the soft and hard palate and a history of palatine tumor of small cell carcinoma. Reexcision surgery was performed and histopathological features were consistent. The patient was treated with six cycles of chemotherapy consisting of etoposide and cisplatin. After one year, the patient developed bone metastases and Cushing's syndrome, and successfully recovered with subsequent chemotherapy with irinotecan and cisplatin plus radiotherapy. There was no evidence of recurrence or metastasis for more than three years. Small cell carcinoma originating in the head and neck region has been reported to be highly aggressive and has a poor prognosis. This is the first case report of a patient with relapsed primary small cell carcinoma of the palate and successfully treated with second-line chemotherapy and local radiotherapy.

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.

Radiotherapy for stage I-II non-small cell lung cancer

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Okamoto, Yoshiaki; Murakami, Masao; Mizowaki, Takashi; Nakajima, Toshifumi; Kuroda, Yasumasa

1999-01-01

Surgery has been regarded as the standard treatment for patients with non-small cell lung cancer in the early stage, while radiotherapy has become an effective alternative for medically inoperable patients and those who refuse surgery. We reviewed the records of 31 patients with stage I-II non-small cell lung cancer treated by radiotherapy between 1980 and 1997. There were 15 patients in stage I and 16 in stage II. The variables analyzed for influence on cause-specific survival and loco-regional control were: age, performance status, clinical stage, tumor size, tumor site, radiation field, radiation dose, and combination with chemotherapy. The overall and cause-specific 1-, 2-, 3-, and 5-years survival rates were 71% and 77%; 63% and 73%; 34% and 48%; and 17% and 32%, respectively. Five-year survival rate for patients with peripheral tumor in the lung was 72%, with 70% loco-regional control, while the 5-year survival rate of patients whose tumor originated in the central region was 20%, with 25% loco-regional control. These differences had marginal significance on univariate analysis (P=0.07), but only tumor site (central vs peripheral) showed marginal significant influence on cause-specific survival (P=0.08) and loco-regional control (P=0.07) on multivariate analysis. There were no fatal complications, including radiation-induced myelopathy. The present series showed satisfactory results with definitive radiotherapy for patients with medically inoperable stage I-II non-small cell lung cancer, with results similar to those in recent reports of radiotherapy. The only significant variable was that patients with peripheral tumors had a better prognosis than patients with central tumors. (author)

Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine

DEFF Research Database (Denmark)

Rumessen, J J; Mikkelsen, H B; Thuneberg, L

1992-01-01

Evidence showing that interstitial cells of Cajal have important regulatory functions in the gut musculature is accumulating. In the current study, the ultrastructure of the deep muscular plexus and associated interstial cells of Cajal in human small intestine were studied to provide a reference...... a continuous basal lamina, caveolae, intermediate filaments, dense bodies, dense bands, and a well-developed subsurface smooth endoplasmic reticulum), but the arrangement of organelles was clearly different, and cisternae of granular endoplasmic reticulum were abundant. Interstitial cells of Cajal were......, and only few gap junctions with other interstitial cells of Cajal or with the musculature were observed. Compared with interstitial cells of Cajal from other mammals, those associated with the deep muscular plexus in the human small intestine more closely resemble smooth muscle cells...

Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation

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Lakkaraju, Asvin K. K.; Thankappan, Ratheeshkumar; Mary, Camille; Garrison, Jennifer L.; Taunton, Jack; Strub, Katharina

2012-01-01

Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway. PMID:22648169

Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

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Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

2018-03-27

Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

The effect of adenovirus-mediated gene expression of FHIT in small cell lung cancer cells

DEFF Research Database (Denmark)

Zandi, Roza; Xu, Kai; Poulsen, Hans S

2011-01-01

The candidate tumor suppressor fragile histidine traid (FHIT) is frequently inactivated in small cell lung cancer (SCLC). Mutations in the p53 gene also occur in the majority of SCLC leading to the accumulation of the mutant protein. Here we evaluated the effect of FHIT gene therapy alone...

Bystander effects in radiotherapy of non-small cell lung cancer

International Nuclear Information System (INIS)

McKenzie, D.R.

2011-01-01

Full text: School of Physics, The University of Sydney, Australia Objectives The bystander effect causes a response in unirradiated cells that are in communication with cells that receive a radiation dose. In recent work we have shown that there are 3 types bystander effect and that the expression of these effects follows a Ii course. The aim of this work is to identify the conditions for the three types of bystander effects in radiotherapy of non-small cell II cancer. A human non small cell lung cancer cell line (NCI-H460) was irradiated with a 6 MV photon beam produced from a Varian I i near accelerator to doses of 2, 4, 6 and 8 Gy. These cells v termed donor cells. At selected time intervals after exposure (5,15 and 60 min), the medium was transferred to receiver cells of the cell line in separate flasks. The clonogenic survival fraction of the receiver cells was determined following 5 days of incubation comparing cells receiving transfer of medium from exposed cells to cell receiving transfer from sham exposed cells. The experimental design controlled for the density of cells in the donor flask, the e of irradiation on the medium alone and on the donor cell metabolites. The results show a strong time course for the bystander signal expression, which is dependent on the density of cells in the donor receiver flasks. Sub lethal doses of radiation resulted in a proliferative response at short time intervals after exposure [15 min] but a toxic response when medium transfer was carried out after 60 min. A higher cell density in the donor flasks produces an increased response in the receiver flasks for the same volume of medium transferred. The latter response corresponds to Bystander Effect type 1 in which a reduced survival is observed in cells receiving medium from cells that receive a high but not lethal dose. The proliferative response, corresponding to Bystander Effect type 3 is more general and is not strongly dependent on dose. Following a lethal dose of

Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

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Dilip K Das

2011-01-01

Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

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Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

2000-06-01

Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

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.

Percutaneous and laparoscopic assisted cryoablation of small renal cell carcinomas

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Borre, Michael

Aim: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation. Materials and methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made...... Medical® was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI. Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous...

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

Science.gov (United States)

Malina, Halina Z

2011-01-19

The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules

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

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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.

[Small cell neuroendocrine tumour of the bladder: with reference to a case and bibliographical revision].

Science.gov (United States)

Lahoz Tornos, A; Marrón Penón, Maria C; Pardo López, Maria L; Nogueras Gimeno, M A; Pujol Obis, E; Del Villar Sordo, V

2006-09-01

The small cell neuroendocrine tumour is an infrecuent neoplasia, with inmunohistochemistry being the key to diagnosis. We present a new case making reference to treatment and its evolution there after. The clinic, diagnosis and treatment of this tumour is described. Bibliographical revision follours. The neuroendocrine tumour of small cell is an infrecuent neoplasia, in which the inmunohistochemistry study is key in the diagnosis. The differential diagnosis includes the high degree diferentiation transitionals cells carcinoma and primary and secondary linfoma. The standard treatment is based on chemotherapy plus surgery.

A temperature-sensitive dcw1 mutant of Saccharomyces cerevisiae is cell cycle arrested with small buds which have aberrant cell walls.

Science.gov (United States)

Kitagaki, Hiroshi; Ito, Kiyoshi; Shimoi, Hitoshi

2004-10-01

Dcw1p and Dfg5p in Saccharomyces cerevisiae are homologous proteins that were previously shown to be involved in cell wall biogenesis and to be essential for growth. Dcw1p was found to be a glycosylphosphatidylinositol-anchored membrane protein. To investigate the roles of these proteins in cell wall biogenesis and cell growth, we constructed mutant alleles of DCW1 by random mutagenesis, introduced them into a Deltadcw1 Deltadfg5 background, and isolated a temperature-sensitive mutant, DC61 (dcw1-3 Deltadfg5). When DC61 cells were incubated at 37 degrees C, most cells had small buds, with areas less than 20% of those of the mother cells. This result indicates that DC61 cells arrest growth with small buds at 37 degrees C. At 37 degrees C, fewer DC61 cells had 1N DNA content and most of them still had a single nucleus located apart from the bud neck. In addition, in DC61 cells incubated at 37 degrees C, bipolar spindles were not formed. These results indicate that DC61 cells, when incubated at 37 degrees C, are cell cycle arrested after DNA replication and prior to the separation of spindle pole bodies. The small buds of DC61 accumulated chitin in the bud cortex, and some of them were lysed, which indicates that they had aberrant cell walls. A temperature-sensitive dfg5 mutant, DF66 (Deltadcw1 dfg5-29), showed similar phenotypes. DCW1 and DFG5 mRNA levels peaked in the G1 and S phases, respectively. These results indicate that Dcw1p and Dfg5p are involved in bud formation through their involvement in biogenesis of the bud cell wall.

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

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.

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)

Non-Small Cell Lung Cancer Cells Expressing CD44 Are Enriched for Stem Cell-Like Properties

Science.gov (United States)

Leung, Elaine Lai-Han; Fiscus, Ronald R.; Tung, James W.; Tin, Vicky Pui-Chi; Cheng, Lik Cheung; Sihoe, Alan Dart-Loon; Fink, Louis M.; Ma, Yupo; Wong, Maria Pik

2010-01-01

Background The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44− cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44− cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44− cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify

Primary Cutaneous CD4-Positive Small/Medium Pleomorphic T-cell Lymphoma – A Case Report

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Micković Milena

2016-12-01

Full Text Available Primary cutaneous CD4-positive small- to medium-sized pleomorphic T-cell lymphoma is a provisional entity in the 2005 WHO-EORTC classification for cutaneous lymphomas. It is a rare condition and, in most cases, it has a favorable clinical course and prognosis. Primary cutaneous CD4-positive small/medium pleomorphic T-cell lymphoma (PCSM-TCL is defined as a cutaneous T-cell lymphoma with predominantly small- to medium-sized CD4-positive pleomorphic T-cells without a history of patches and plaques typical of mycosis fungoides. PCSM-TCL usually presents as a solitary plaque or tumor on the head, neck, trunk or upper extremities and it is considered to have indolent clinical behavior. Histologically, it is characterized by a dense infiltration of small/medium-sized pleomorphic T-cells that involves the entire dermal thickness, often with nodular extension into the hypodermis. Using immunohistochemical staining, the majority of the reported cases proved to be CD3, CD4 positive and CD8, CD30 negative. However, due to the rarity and heterogeneity of the PCSM-TCL, precise clinicopathologic characteristics of PCSM-TCL have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatments.

Transportable, small high-pressure preservation vessel for cells

International Nuclear Information System (INIS)

Kamimura, N; Sotome, S; Shimizu, A; Nakajima, K; Yoshimura, Y

2010-01-01

We have previously reported that the survival rate of astrocytes increases under high-pressure conditions at 4 0 C. However, pressure vessels generally have numerous problems for use in cell preservation and transportation: (1) they cannot be readily separated from the pressurizing pump in the pressurized state; (2) they are typically heavy and expensive due the use of materials such as stainless steel; and (3) it is difficult to regulate pressurization rate with hand pumps. Therefore, we developed a transportable high-pressure system suitable for cell preservation under high-pressure conditions. This high-pressure vessel has the following characteristics: (1) it can be easily separated from the pressurizing pump due to the use of a cock-type stop valve; (2) it is small and compact, is made of PEEK and weighs less than 200 g; and (3) pressurization rate is regulated by an electric pump instead of a hand pump. Using this transportable high-pressure vessel for cell preservation, we found that astrocytes can survive for 4 days at 1.6 MPa and 4 0 C.

TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/?-catenin signaling

OpenAIRE

Peng, Yun; Cao, Jun; Yao, Xiao-Yi; Wang, Jian-Xin; Zhong, Mei-Zuo; Gan, Ping-Ping; Li, Jian-Huang

2017-01-01

We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transf...

In vitro evaluation of a new nitrosourea, TCNU, against human small cell lung cancer cell lines

DEFF Research Database (Denmark)

Roed, H; Vindeløv, L L; Spang-Thomsen, M

1987-01-01

The cytotoxic activity of a new nitrosourea, TCNU, was compared with that of BCNU in five human small cell lung cancer cell lines in vitro. TCNU was found to be equivalent or inferior to BCNU when compared on a microgram to microgram basis. If the potential of in vitro phase II trials for selection...... of new drugs can be validated, it can be concluded that TCNU is not superior to other nitrosoureas for the treatment of SCCL....

A new class of pluripotent stem cell cytotoxic small molecules.

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Mark Richards

Full Text Available A major concern in Pluripotent Stem Cell (PSC-derived cell replacement therapy is the risk of teratoma formation from contaminating undifferentiated cells. Removal of undifferentiated cells from differentiated cultures is an essential step before PSC-based cell therapies can be safely deployed in a clinical setting. We report a group of novel small molecules that are cytotoxic to PSCs. Our data indicates that these molecules are specific and potent in their activity allowing rapid eradication of undifferentiated cells. Experiments utilizing mixed PSC and primary human neuronal and cardiomyocyte cultures demonstrate that up to a 6-fold enrichment for specialized cells can be obtained without adversely affecting cell viability and function. Several structural variants were synthesized to identify key functional groups and to improve specificity and efficacy. Comparative microarray analysis and ensuing RNA knockdown studies revealed involvement of the PERK/ATF4/DDIT3 ER stress pathway. Surprisingly, cell death following ER stress induction was associated with a concomitant decrease in endogenous ROS levels in PSCs. Undifferentiated cells treated with these molecules preceding transplantation fail to form teratomas in SCID mice. Furthermore, these molecules remain non-toxic and non-teratogenic to zebrafish embryos suggesting that they may be safely used in vivo.

Intrapancreatic Parenchymal Injection of Cells as a Useful Tool for Allowing a Small Number of Proliferative Cells to Grow In Vivo

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Masahiro Sato

2017-08-01

Full Text Available In vivo inoculation of cells such as tumor cells and induced pluripotent stem (iPS/embryonic stem (ES cells into immunocompromised mice has been considered as a powerful technique to evaluate their potential to proliferate or differentiate into various cell types originating from three germ cell layers. Subcutaneous grafting and grafting under the kidney capsule have been widely used for this purpose, but there are some demerits such as the requirement of a large number of tumor cells for inoculation and frequent failure of tumorigenesis. Therefore, grafting into other sites has been explored, including intratesticular or intramuscular grafting as well as grafting into the cochleae, liver, or salivary glands. In this study, we found that intrapancreatic parenchymal injection of cells is useful for allowing a small number of cells (~15 × 103 cells or ~30 cell clumps μL−1·site−1 to proliferate and sometimes differentiate into various types of cells. It requires only surgical exposure of the pancreas over the dorsal skin and subsequent injection of cells towards the pancreatic parenchyma under dissecting microscope-based observation using a mouthpiece-controlled glass micropipette. We now name this technology “intrapancreatic parenchymal cell transplantation (IPPCT”, which will be useful, especially when only a small number of cells or colonies are available.

Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells

International Nuclear Information System (INIS)

Xue Yan; Bi Feng; Zhang Xueyong; Pan Yanglin; Liu Na; Zheng Yi; Fan Daiming

2004-01-01

Hypoxia-induced angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Rho family small GTPases are involved in this process, and Rac1, a prominent member of the Rho family, may be critical in regulating hypoxia-induced gene activation of several angiogenesis factors and tumor suppressors. To further define Rac1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock down gene expression of Rac1 in gastric cancer cell line AGS that expresses a high level of Rac1. Both the mRNA and protein levels of Rac1 in the AGS cells were decreased dramatically after transfection with a Rac1-specific siRNA vector. When the conditioned medium derived from the Rac1 downregulated AGS cells was applied to the human endothelial cells, it could significantly inhibit the cell proliferation. Further study proved that, VEGF and HIF-1α, two angiogenesis promoting factors, were found to be downregulated whereas p53 and VHL, which are tumor suppressors and angiogenesis inhibitors, were upregulated in the Rac1 siRNA transfected cells. Our results suggest that Rac1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting the Rac1 GTPase

Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease

KAUST Repository

Kim, YongHwan

2018-05-22

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.

Spotlight on necitumumab in the treatment of non-small-cell lung carcinoma

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Thakur MK

2017-02-01

Full Text Available Manish K Thakur, Antoinette J Wozniak, Department of Oncology, Karmanos Cancer Center, Detroit, MI, USA Abstract: The treatment options for metastatic non-small-cell lung cancer (NSCLC have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR, when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations. Monoclonal antibodies have also been developed that block the EGFR at the cell surface and work in conjunction with chemotherapy. Necitumumab is a second-generation fully human IgG1 monoclonal antibody that has shown promise in metastatic NSCLC. The benefit has mostly been restricted to squamous cell lung cancer in the frontline setting. Considering that the survival advantage for these patients was modest, there is a need to discover biomarkers that will predict which patients will likely have the best outcomes. This review focuses on the development and clinical trial experience with necitumumab in NSCLC. Keywords: lung cancer, squamous cell, necitumumab, EGFR

A rank-based algorithm of differential expression analysis for small cell line data with statistical control.

Science.gov (United States)

Li, Xiangyu; Cai, Hao; Wang, Xianlong; Ao, Lu; Guo, You; He, Jun; Gu, Yunyan; Qi, Lishuang; Guan, Qingzhou; Lin, Xu; Guo, Zheng

2017-10-13

To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data. © The Author 2017. Published by Oxford University Press.

Experimental Evaluation of Interference Rejection Combining for 5G small cells,

DEFF Research Database (Denmark)

Assefa, Dereje; Berardinelli, Gilberto; Tavares, Fernando Menezes Leitão

2015-01-01

The Interference Rejection Combining (IRC) receiver can significantly boost the network throughput in scenarios characterized by dense uncoordinated deployment of small cells, as targeted by future 5th generation (5G) radio access technology. This paper presents an experimental study...

Small cell foams and blends and a process for their preparation

Science.gov (United States)

Hedstrand, D.M.; Tomalia, D.A.

1995-02-07

Dense star polymers or dendrimers, modified by capping with a hydrophobic group capable of providing a hydrophobic outer shell, act as molecular nucleating agents. These modified dense star polymers or dendrimers are particularly effective for the production of small cell foams.

The miR-599 promotes non-small cell lung cancer cell invasion via SATB2

International Nuclear Information System (INIS)

Tian, Wenjun; Wang, Guanghai; Liu, Yiqing; Huang, Zhenglan; Zhang, Caiqing; Ning, Kang; Yu, Cuixiang; Shen, Yajuan; Wang, Minghui; Li, Yuantang; Wang, Yong; Zhang, Bingchang; Zhao, Yaoran

2017-01-01

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-599 is up-regulated in non-small cell lung cancer (NSCLC) patients. It promoted NSCLC cell proliferation by negatively regulating SATB2. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-599 mimics. Transwell assay showed that miR-599 mimics promoted the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-599 directly binds to the 3'untranslated region of SATB2, and western blotting showed that miR-599 suppresses the expression of SATB2 at the protein level. This study indicates that miR-599 promotes proliferation and invasion of NSCLC cell lines via SATB2. The miR-599 may represent a potential therapeutic target for NSCLC treatment. - Highlights: • miR-599 is up-regulated in NSCLC. • miR-599 promotes the proliferation and invasion of NSCLC cells. • miR-599 inhibitors inhibits the proliferation and invasion of NSCLC cells. • miR-599 targets 3′ UTR of SATB2 in NSCLC cells. • miR-599 inhibits SATB2 in NSCLC cells.

Non-small-cell lung cancer cells combat epidermal growth factor receptor tyrosine kinase inhibition through immediate adhesion-related responses

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Wang HY

2016-05-01

Full Text Available Hsian-Yu Wang,1,2 Min-Kung Hsu,3,4 Kai-Hsuan Wang,1 Ching-Ping Tseng,2,4 Feng-Chi Chen,3,4 John T-A Hsu1,4 1Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 2Institute of Molecular Medicine and Bioengineering, National Chiao Tung University (NCTU, Hsinchu, 3Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes (NHRI, Zhunan, Miaoli County, 4Department of Biological Science and Technology, National Chiao Tung University (NCTU, Hsinchu, Taiwan, Republic of China Background: Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs, such as gefitinib, erlotinib, and afatinib, have greatly improved treatment efficacy in non-small cell lung cancer (NSCLC patients with drug-sensitive EGFR mutations. However, in some TKI responders, the benefits of such targeted therapies are limited by the rapid development of resistance, and strategies to overcome this resistance are urgently needed. Studies of drug resistance in cancer cells typically involve long term in vitro induction to obtain stably acquired drug-resistant cells followed by elucidation of resistance mechanisms, but the immediate responses of cancer cells upon drug treatment have been ignored. The aim of this study was to investigate the immediate responses of NSCLC cells upon treatment with EGFR TKIs.Results: Both NSCLC cells, ie, PC9 and H1975, showed immediate enhanced adhesion-related responses as an apoptosis-countering mechanism upon first-time TKI treatment. By gene expression and pathway analysis, adhesion-related pathways were enriched in gefitinib-treated PC9 cells. Pathway inhibition by small-hairpin RNAs or small-molecule drugs revealed that within hours of EGFR TKI treatment, NSCLC cells used adhesion-related responses to combat the drugs. Importantly, we show here that the Src family inhibitor, dasatinib, dramatically inhibits

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.

Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

International Nuclear Information System (INIS)

Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

2005-01-01

This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

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

Science.gov (United States)

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.

MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma.

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Lu-Kai Wang

Full Text Available Non-small cell lung cancers (NSCLCs cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R, TGF-beta receptor type-1 (TGFBR1, and epidermal growth factor receptor (EGFR, are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.

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

Psychogenic fever in a patient with small cell lung cancer: a case report

International Nuclear Information System (INIS)

Xu, Mengdan; Zhang, Xiaoye; Xu, Zhaoguo; Cui, Guoyuan; Yu, Li; Qi, Xiaoying; Lin, Jia; Liu, Yan

2015-01-01

Fever is common in malignant tumors. We report an exceptional case of psychogenic fever in a patient with small cell lung cancer. This is the first case report of psychogenic fever in a patient with small cell lung cancer. A 61-year-old Chinese man diagnosed with small cell carcinoma on June 30, 2012, came to our department with a complaint of fever lasting more than 1 month. He had undergone chemoradiotherapy for lung cancer 6 months previously. After admission, his body temperature fluctuated in the range of 37 °C to 39 °C. Somatic symptoms associated with anxiety were obvious. A 24-item Hamilton Anxiety Scale was used to assess the patient’s condition. A score of 32 confirmed a diagnosis of severe anxiety. After a week of antianxiety treatment, the patient’s temperature returned to normal. Psychogenic fever is common in cancer patients and deserves more attention. Patients with psychogenic fever must be distinguished from patients with infectious fever (including neutropenic fever), and tumor fever. Additionally, antianxiety or antidepression treatment should be provided. A concern is that continual anxiety may adversely affect anticancer therapy

Illness perceptions and quality of life in Japanese and Dutch patients with non-small-cell lung cancer

NARCIS (Netherlands)

Kaptein, Ad A.; Yamaoka, Kazue; Snoei, Lucia; Kobayashi, Kunihiko; Uchida, Yuka; van der Kloot, Willem A.; Tabei, Toshio; Kleijn, Wim Chr; Koster, Mariska; Wijnands, Giel; Kaajan, Hans; Tran, Tommy; Inoue, Kenichi; van Klink, Rik; van Dooren-Coppens, Eva; Dik, Hans; Hayashi, Fumi; Willems, Luuk; Annema-Schmidt, Dunja; Annema, Jouke; van der Maat, Bas; van Kralingen, Klaas; Meirink, Corrie; Ogoshi, Kyoji; Aaronson, Neil; Nortier, Hans; Rabe, Klaus

2011-01-01

This study examined quality of life (QOL) and illness perceptions in Dutch and Japanese patients with non-small-cell lung cancer, thereby extending the body of knowledge on cultural differences and psychosocial aspects of this illness. 24 Dutch and 22 Japanese patients with non-small-cell lung

SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

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Deyan N. Davidov

2013-04-01

Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

Overexpression of SAMD9 suppresses tumorigenesis and progression during non small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Ma, Qing; Yu, Tao; Ren, Yao-Yao; Gong, Ting; Zhong, Dian-Sheng, E-mail: zhongdsyx@126.com

2014-11-07

Highlights: • SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). • Knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro. • Overexpression of SAMD9 suppressed proliferation and invasion in A549 cells in vitro. • Depletion of SAMD9 increases tumor formation in vivo. - Abstract: The Sterile Alpha Motif Domain-containing 9 (SAMD9) gene has been recently emphasized during the discovery that it is expressed at a lower level in aggressive fibromatosis and some cases of breast and colon cancer, however, the underlying mechanisms are poorly understood. Here, we found that SAMD9 is down-regulated in human non-small cell lung cancer (NSCLC). Furthermore, knockdown of SAMD9 expression is increased the invasion, migration and proliferation in H1299 cells in vitro and overexpression of SAMD9 suppressed proliferation and invasion in A549 cells. Finally, depletion of SAMD9 increases tumor formation in vivo. Our results may provide a strategy for blocking NSCLC tumorigenesis and progression.

Potential role of immunotherapy in advanced non-small-cell lung cancer

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de Mello RA

2016-12-01

Full Text Available Ramon Andrade de Mello,1–3 Ana Flávia Veloso,4 Paulo Esrom Catarina,4 Sara Nadine,5 Georgios Antoniou6 1Department of Biomedical Sciences and Medicine, University of Algarve, Faro, 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Research Center, Cearense School of Oncology, Instituto do Câncer do Ceará, 4Oncology & Hematology League, School of Medicine, State University of Ceará (UECE, Fortaleza, Brazil; 5Instituto de Ciências Biomédicas Abel Salazar (ICBAS, University of Porto, Porto, Portugal; 6Department of Medical Oncology, The Royal Marsden NHS Foundation Trust, London, UK Abstract: Immuno checkpoint inhibitors have ushered in a new era with respect to the treatment of advanced non-small-cell lung cancer. Many patients are not suitable for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (eg, gefitinib, erlotinib, and afatinib or with anaplastic lymphoma kinase inhibitors (eg, crizotinib and ceritinib. As a result, anti-PD-1/PD-L1 and CTLA-4 inhibitors may play a novel role in the improvement of outcomes in a metastatic setting. The regulation of immune surveillance, immunoediting, and immunoescape mechanisms may play an interesting role in this regard either alone or in combination with current drugs. Here, we discuss advances in immunotherapy for the treatment of metastatic non-small-cell lung cancer as well as future perspectives within this framework. Keywords: immunotherapy, non-small-cell lung cancer, nivolumab, pembrolizumab, ipilimumab, clinical trials, PD1, PDL1, CTLA4

Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation

DEFF Research Database (Denmark)

Biskup, Edyta; Naym, David Gram; Gniadecki, Robert

2016-01-01

inhibited by small molecule antagonists VE-821, VE-822 or Chir-124, or by small interfering RNAs (siRNAs). Cell cycle and viability were assessed by flow cytometry. RESULTS: Small molecule inhibitors of ATR and Chk1 potently sensitized all cell lines to PUVA and, importantly, also to UVA, which by itself...... did not cause apoptotic response. VE-821/2 blocked ATR pathway activation and released the cells from the G2/M block caused by UVA and PUVA, but did not affect apoptosis caused by other chemotherapeutics (etoposide, gemcitabine, doxorubicine) or by hydrogen peroxide. Knockdown of ATR and Chk1 with si......RNA also blocked the ATR pathway and released the cells from G2/M block but did not sensitize the cells to UVA as observed with the small molecule inhibitors. The latter suggested that the synergism between VE-821/2 or Chir-124 and UVA was not solely caused by specific blocking of ATR kinase but also ATR...

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference...

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference......, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through...

Small-scale fuel cell cogen: application potentials and market strategies

International Nuclear Information System (INIS)

Vogel, Bernd

2000-01-01

Small (less than 5 kW) fuel-cell cogeneration systems are now being developed for use in residential buildings. The devices are expected to be on the market in five years. The article discusses the potential for their large-scale introduction, the impact of this new technology on the natural gas business, potential applications and marketing strategies

A Biphasic Pleural Tumor with Features of an Epithelioid and Small Cell Mesothelioma: Morphologic and Molecular Findings

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Sarah Hackman

2016-01-01

Full Text Available Malignant mesotheliomas are generally classified into epithelioid, sarcomatoid, desmoplastic, and biphasic types with rare reports of a small cell form. These small cell variants display some morphologic overlap with desmoplastic small round cell tumors (DSRCTs which generally occur within the abdominal cavity of young males and are defined by a characteristic t(11;22(p13;q12 translocation. However, there are rare reports of DSRCTs lacking this translocation. We present a 78-year-old man with a pleura-based biphasic neoplasm with features of both epithelioid mesothelioma and a small cell blastema-like neoplasm. The epithelioid portion showed IHC reactivity for pan cytokeratin, CK5/6, D2-40, and calretinin and the small cell portion marked with CD99, pan cytokeratin, WT1, FLI1, S100, CD200, MyoD1, and CD15. Fluorescence in situ hybridization testing for the t(11;22(p13;q12 translocation disclosed loss of the EWSR1 gene in 94% of tumor cell nuclei, but there was no evidence of the classic translocation. Array based-comparative genomic hybridization (a-CGH confirmed the tumor had numerous chromosome copy number losses, including 11p15.5-p11.12 and 22q12.1-q13.33, with loss of the EWSR1 and WT1 gene regions. Herein, we report novel complex CGH findings in a biphasic tumor and review the molecular genetic alterations in both mesothelioma and DSRCTs.

Outcome of combination chemotherapy in extensive stage small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U N; Hirsch, F R; Osterlind, K

1998-01-01

During the past two decades many different treatment regimens of combination chemotherapy have been applied in extensive stage small-cell lung cancer (SCLC). This study was carried out to identify whether these modifications have resulted in an improved overall survival for extensive stage during...

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

Science.gov (United States)

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.

Palliative Care Intervention in Improving Symptom Control and Quality of Life in Patients With Stage II-IV Non-small Cell Lung Cancer and Their Family Caregivers

Science.gov (United States)

2017-10-16

Caregiver; Psychological Impact of Cancer and Its Treatment; Recurrent Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer.

Science.gov (United States)

Xiao, Lu; Lan, Xiaoying; Shi, Xianping; Zhao, Kai; Wang, Dongrui; Wang, Xuejun; Li, Faqian; Huang, Hongbiao; Liu, Jinbao

2017-05-18

Cytotoxic chemotherapy agents (e.g., cisplatin) are the first-line drugs to treat non-small cell lung cancer (NSCLC) but NSCLC develops resistance to the agent, limiting therapeutic efficacy. Despite many approaches to identifying the underlying mechanism for cisplatin resistance, there remains a lack of effective targets in the population that resist cisplatin treatment. In this study, we sought to investigate the role of cytoplasmic RAP1, a previously identified positive regulator of NF-κB signaling, in the development of cisplatin resistance in NSCLC cells. We found that the expression of cytoplasmic RAP1 was significantly higher in high-grade NSCLC tissues than in low-grade NSCLC; compared with a normal pulmonary epithelial cell line, the A549 NSCLC cells exhibited more cytoplasmic RAP1 expression as well as increased NF-κB activity; cisplatin treatment resulted in a further increase of cytoplasmic RAP1 in A549 cells; overexpression of RAP1 desensitized the A549 cells to cisplatin, and conversely, RAP1 depletion in the NSCLC cells reduced their proliferation and increased their sensitivity to cisplatin, indicating that RAP1 is required for cell growth and has a key mediating role in the development of cisplatin resistance in NSCLC cells. The RAP1-mediated cisplatin resistance was associated with the activation of NF-κB signaling and the upregulation of the antiapoptosis factor BCL-2. Intriguingly, in the small portion of RAP1-depleted cells that survived cisplatin treatment, no induction of NF-κB activity and BCL-2 expression was observed. Furthermore, in established cisplatin-resistant A549 cells, RAP1 depletion caused BCL2 depletion, caspase activation and dramatic lethality to the cells. Hence, our results demonstrate that the cytoplasmic RAP1-NF-κB-BCL2 axis represents a key pathway to cisplatin resistance in NSCLC cells, identifying RAP1 as a marker and a potential therapeutic target for cisplatin resistance of NSCLC.

Epigenetic Modulation with HDAC Inhibitor CG200745 Induces Anti-Proliferation in Non-Small Cell Lung Cancer Cells

OpenAIRE

Chun, Sung-Min; Lee, Ji-Young; Choi, Jene; Lee, Je-Hwan; Hwang, Jung Jin; Kim, Chung-Soo; Suh, Young-Ah; Jang, Se Jin

2015-01-01

Histone modification plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes. Hence, chemical approaches targeting histone-modifying enzymes have emerged onto the main stage of anticancer drug discovery. Here, we investigated the therapeutic potentials and mechanistic roles of the recently developed histone deacetylase inhibitor, CG200745, in non-small cell lung cancer cells. Treatment with CG200745 increased the global level of his...

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

MET and Small-Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Francesco Gelsomino

2014-10-01

Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

Directory of Open Access Journals (Sweden)

Mengli Zheng

2016-09-01

Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

Analysis of the EGFR gene mutation in patients with non- small cell ...

African Journals Online (AJOL)

Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1637-1641 ... Keywords: Non-small cell lung cancer, Epidermal growth factor receptor (EGFR), Targeted therapy, ... inhibitors can be identified by molecular analysis of lung ...

HYPERTHERMIC POTENTIATION OF CISPLATIN TOXICITY IN A HUMAN SMALL-CELL LUNG-CARCINOMA CELL-LINE AND A CISPLATIN-RESISTANT SUBLINE

NARCIS (Netherlands)

HETTINGA, JVE; LEMSTRA, W; MEIJER, C; MULDER, NH; KONINGS, AWT; DEVRIES, EGE; KAMPINGA, HH

1994-01-01

A human small cell lung carcinoma cell line (GLC4) and its subline with in vitro acquired cisplatin (cDDP) resistance (GLC4-cDDP) were used to study the applicability of hyperthermia to interfere with acquired cDDP resistance. GLC4 and GLC4-cDDP did not differ in heat sensitivity (clonogenic

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

Science.gov (United States)

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.

Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

Science.gov (United States)

Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

2016-11-07

Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

DEFF Research Database (Denmark)

Sandfeld-Paulsen, B; Aggerholm-Pedersen, N; Bæk, R

2016-01-01

BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...... Bonferroni correction. Results were adjusted for clinico-pathological characteristics, stage, histology, age, sex and performance status. CONCLUSION: We illustrate the promising aspects associated with the use of exosomal membrane-bound proteins as a biomarker and demonstrate that they are a strong...

Clinical potential of necitumumab in non-small cell lung carcinoma

Directory of Open Access Journals (Sweden)

Genova C

2016-08-01

Full Text Available Carlo Genova,1–3 Fred R Hirsch1 1Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO, USA; 2Lung Cancer Unit, IRCCS AOU San Martino IST, 3Department of Internal Medicine, School of Medicine, University of Genoa, Genoa, Italy Abstract: Despite significant progress, new therapeutic approaches for advanced non-small cell lung cancer (NSCLC are highly needed, particularly for the treatment of patients with squamous cell carcinoma. The epidermal growth factor receptor (EGFR is often overexpressed in NSCLC and represents a relevant target for specific treatments. Although EGFR mutations are more frequent in non-squamous histology, the receptor itself is more often overexpressed in squamous NSCLC. Necitumumab is a human monoclonal antibody that is able to inhibit the EGFR pathway and cause antibody-dependent cell cytotoxicity. This drug has been studied in combination with first-line chemotherapy for advanced NSCLC in two Phase III trials, and a significant survival benefit was reported in squamous NSCLC (SQUIRE trial; by contrast, necitumumab did not prove itself beneficial in non-squamous histotype (INSPIRE trial. On the basis of the SQUIRE results, necitumumab was approved in combination with cisplatin and gemcitabine as a first-line treatment for advanced squamous NSCLC, both in the US and Europe, where its availability is limited to patients with EGFR-expressing tumors. The aim of this review is to describe the tolerability and the efficacy of necitumumab by searching the available published data and define its potential role in the current landscape of NSCLC treatment. Keywords: necitumumab, EGFR, non-small cell lung cancer, monoclonal antibody, H-score

Dithiolethione modified valproate and diclofenac increase E-cadherin expression and decrease proliferation of non-small cell lung cancer cells

OpenAIRE

Moody, Terry W.; Switzer, Christopher; Santana-Flores, Wilmarie; Ridnour, Lisa A.; Berna, Marc; Thill, Michelle; Jensen, Robert T.; Sparatore, Anna; Del Soldato, Piero; Yeh, Grace C; Roberts, David D.; Giaccone, Giuseppe; Wink, David A.

2009-01-01

The effects of dithiolethione-modified valproate, diclofenac and sulindac on non-small cell lung cancer (NSCLC) cells were investigated. Sulfur(S)-valproate and S-diclofenac at 1 μg/ml concentrations significantly reduced prostaglandin (PG)E2 levels in NSCLC cell lines A549 and NCI-H1299 as did the COX-2 inhibitor DuP-697. In vitro, S-valproate, S-diclofenac and S-sulindac half-maximally inhibited the clonal growth of NCI-H1299 cells at 6, 6 and 15 μg/ml, respectively. Using the MTT assay, 10...

Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy.

Science.gov (United States)

Shah, Pratikkumar; Zhu, Xuena; Zhang, Xueji; He, Jin; Li, Chen-zhong

2016-03-09

The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population.

Effects of c-myc oncogene modulation on differentiation of human small cell lung carcinoma cell lines

NARCIS (Netherlands)

Van Waardenburg, RCAM; Meijer, C; Pinto-Sietsma, SJ; De Vries, EGE; Timens, W; Mulder, NM

1998-01-01

Amplification and over-expression of oncogenes of the myc family are related to the prognosis of certain solid tumors such as small cell lung cancer (SCLC). For SCLC, c-myc is the oncogene most consistently found to correlate with the end stage behaviour of the tumour, in particular with survival

Approach for oligometastasis in non-small cell lung cancer.

Science.gov (United States)

Suzuki, Hidemi; Yoshino, Ichiro

2016-04-01

Non-small cell lung cancer (NSCLC) harboring a limited number of distant metastases, referred to as the oligometastatic state, has been indicated for surgery for the past several decades. However, whether the strategy of surgical treatment results in a survival benefit for such patients remains controversial. Experientially, however, thoracic surgeons often encounter long-term survivors among surgically resected oligometastatic NSCLC patients. In this article, the current situation of surgical approach and potential future perspective for oligometastatic NSCLC are reviewed.

Molecular imaging of hypoxia in non-small-cell lung cancer

International Nuclear Information System (INIS)

Yip, Connie; Blower, Philip J.; Goh, Vicky; Landau, David B.; Cook, Gary J.R.

2015-01-01

Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

Molecular imaging of hypoxia in non-small-cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

2015-05-01

Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

D2D-Enabled Small Cell Network Control Scheme Based on the Dynamic Stackelberg Game

Directory of Open Access Journals (Sweden)

Sungwook Kim

2017-01-01

Full Text Available For current and future cellular networks, small cell structure with licensed and unlicensed bandwidth, caching content provisioning, and device-to-device (D2D communications is seen as a necessary architecture. Recently, a series of control methods have been developed to address a myriad of challenges in next-generation small cell networks. In this study, we focus on the design of novel D2D-enabled small cell network control scheme by allowing caching and unlicensed D2D communications. Motivated by game theory and learning algorithm, the proposed scheme adaptively selects caching contents and splits the available bandwidth for licensed and unlicensed communications. Under dynamically changing network environments, we capture the dynamics of the network system and design a new dynamic Stackelberg game model. Based on a hierarchical and feedback based control manner, small base stations and users can be leaders or followers dynamically while improving 5G network performance. Simulations and performance analysis verify the efficiency of the proposed scheme, showing that our approach can outperform existing schemes by about 5%~15% in terms of bandwidth utilization, cache hit ratio, and system throughput.

An air-breathing single cell small proton exchange membrane fuel cell system with AB5-type metal hydride and an ultra-low voltage input boost converter

Energy Technology Data Exchange (ETDEWEB)

Akiyama, Kazuya; Matsumoto, Satoshi; Miyasaka, Akihiro; Shodai, Takahisa [NTT Energy and Environment System Laboratories, 3-1 Morinosato-Wakamiya Atsugi-shi, Kanagawa (Japan)

2009-01-01

A new strategy for increasing the power density of an air-breathing small proton exchange membrane fuel cell (PEMFC) system for the main energy source of portable consumer electronics is presented. The small PEMFC system is composed of a single cell. Utilizing the output voltage of the single cell, we introduce a newly designed ultra-low voltage input boost converter. The boost converter can generate 4.1 V output from input sources with low voltage ranges, such as under 1.0 V. The cathode plate is made from a thin SUS 316L stainless steel plate and has ribs that prevent the cathode from bending. The hydrogen is supplied by a metal hydride (MH) tank cartridge. The MH tank contains highly packed AB5-type MH. The MH tank cartridge has a volume of 13.2 cm{sup 3} and can absorb 6.7 L of hydrogen. The maximum power of the small PEMFC is 4.42 W at room temperature. Using 6.7 L of hydrogen, the small PEMFC can generate 11 Wh of electricity. The power density of the small PEMFC reaches 0.51 Wh cm{sup -3}. And the power density of the whole small PEMFC system, which contains the boost converter, a small Li-ion battery for a load absorber, and a case for the system, reaches 0.14 Wh cm{sup -3}. This value matches that of external Li-ion battery chargers for cell phones. We installed the small PEMFC system in a cell phone and confirmed the operations of calling, receiving, videophone, connecting to the Internet, and watching digital TV. And also confirmed that the small PEMFC system provides approximately 8.25 h of talk time, which is about three times as long as that for the original Li-ion battery. (author)

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

Science.gov (United States)

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.

Photophysical properties of novel small acceptor molecules and their application in hybrid small-molecular/polymeric organic solar cells

Energy Technology Data Exchange (ETDEWEB)

Inal, Sahika; Castellani, Mauro; Neher, Dieter [Universitaet Potsdam, Institut fuer Physik und Astronomie, Potsdam-Golm (Germany); Sellinger, Alan [Institute of Materials Research and Engineering, Singapore (Singapore)

2009-07-01

Recent experimental investigations revealed that the photovoltaic properties of our devices are related to the balance between recombination and field-induced dissociation of interfacial excited states such as exciplexes or geminate polaron pairs. This balance was shown to be affected by the nanomorphology at the heterojunction. We have analyzed the photophysical properties of a new materials couple comprising an electron-donating PPV copolymer and a vinazene-based small molecule acceptor. Steady state and time-resolved photoluminescence (PL) spectroscopy in solution and in the solid state showed the formation of excimers within the acceptor. The associated long-range diffusion promise efficient energy harvesting at the heterojunction. On the other hand, blends of the PPV-derivative and the small molecule revealed strong exciplex formation. Therefore, bilayered hybrid small-molecular/polymeric solar cells have been fabricated by consequently spin-coating the macromolecular donor and the small molecule acceptor from two different solvents. The bilayer architecture limits recombination processes enabling high FFs of around 44% and a technologically important open circuit voltage of 1Volt.

Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer

DEFF Research Database (Denmark)

Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

2014-01-01

BACKGROUND: Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors, and small biopsies may thus...

[Efficacy of MVP chemotherapy combined with concurrent radiotherapy for advanced non-small cell lung cancer].

Science.gov (United States)

Qiao, Tiankui; Zhou, Daoan; Chen, Wei; Wang, Xianglian

2004-12-20

To observe the effects of MVP chemotherapy combined with concurrent radiotherapy for stage IIIB-IV non-small cell lung cancer. Sixty-two patients with stage IIIB-IV non-small cell lung cancer were randomized into two groups, concurrent radiochemotherapy group and MVP che-motherapy group. All patients in two groups were treated with MVP regimen (mitomycin C 6 mg/m² on day 1, vindesine 2 mg/m² on days 1, 8, and cisplatin 80-100 mg/m²). Patients in concurrent radiochemotherapy group received concurrent radiotherapy (46-56 Gy in 5-6 weeks). All patients received 2-4 cycles of MVP chemotherapy. The response rate was 48.4% and 19.4% in concurrent radiochemotherapy group and MVP group respectively (P MVP group.. The results show that efficacy of MVP chemotherapy combined with concurrent radiotherapy is significantly higher than that of MVP chemotherapy alone for advanced non-small cell lung cancer.

Performance Evaluation of Moving Small-Cell Network with Proactive Cache

Directory of Open Access Journals (Sweden)

Young Min Kwon

2016-01-01

Full Text Available Due to rapid growth in mobile traffic, mobile network operators (MNOs are considering the deployment of moving small-cells (mSCs. mSC is a user-centric network which provides voice and data services during mobility. mSC can receive and forward data traffic via wireless backhaul and sidehaul links. In addition, due to the predictive nature of users demand, mSCs can proactively cache the predicted contents in off-peak-traffic periods. Due to these characteristics, MNOs consider mSCs as a cost-efficient solution to not only enhance the system capacity but also provide guaranteed quality of service (QoS requirements to moving user equipment (UE in peak-traffic periods. In this paper, we conduct extensive system level simulations to analyze the performance of mSCs with varying cache size and content popularity and their effect on wireless backhaul load. The performance evaluation confirms that the QoS of moving small-cell UE (mSUE notably improves by using mSCs together with proactive caching. We also show that the effective use of proactive cache significantly reduces the wireless backhaul load and increases the overall network capacity.

A Novel View of the Adult Stem Cell Compartment From the Perspective of a Quiescent Population of Very Small Embryonic-Like Stem Cells.

Science.gov (United States)

Ratajczak, Mariusz Z; Ratajczak, Janina; Suszynska, Malwina; Miller, Donald M; Kucia, Magda; Shin, Dong-Myung

2017-01-06

Evidence has accumulated that adult hematopoietic tissues and other organs contain a population of dormant stem cells (SCs) that are more primitive than other, already restricted, monopotent tissue-committed SCs (TCSCs). These observations raise several questions, such as the developmental origin of these cells, their true pluripotent or multipotent nature, which surface markers they express, how they can be efficiently isolated from adult tissues, and what role they play in the adult organism. The phenotype of these cells and expression of some genes characteristic of embryonic SCs, epiblast SCs, and primordial germ cells suggests their early-embryonic deposition in developing tissues as precursors of adult SCs. In this review, we will critically discuss all these questions and the concept that small dormant SCs related to migratory primordial germ cells, described as very small embryonic-like SCs, are deposited during embryogenesis in bone marrow and other organs as a backup population for adult tissue-committed SCs and are involved in several processes related to tissue or organ rejuvenation, aging, and cancerogenesis. The most recent results on successful ex vivo expansion of human very small embryonic-like SC in chemically defined media free from feeder-layer cells open up new and exciting possibilities for their application in regenerative medicine. © 2017 American Heart Association, Inc.

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

Directory of Open Access Journals (Sweden)

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

Early death during chemotherapy in patients with small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U N; Osterlind, K; Hirsch, F R

1999-01-01

Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were s...

Full Duplex Communication Under Traffic Constraints for 5G Small Cells

DEFF Research Database (Denmark)

Gatnau, Marta; Catania, Davide; Berardinelli, Gilberto

2015-01-01

the framework of 5th generation (5G) small cell systems in order to address its effective gain in such specific scenarios. The factors that affect FD performance are analysed, and its performance is evaluated against a traditional HD communication. System level simulations show that the gain of FD over HD...

Interference-Robust Air Interface for 5G Ultra-dense Small Cells

DEFF Research Database (Denmark)

Tavares, Fernando Menezes Leitão; Berardinelli, Gilberto; Mahmood, Nurul Huda

2016-01-01

An ultra-dense deployment of small cells is foreseen as the solution to cope with the exponential increase of the data rate demand targeted by the 5th Generation (5G) radio access technology. In this article, we propose an interference-robust air interface built upon the usage of advanced receivers...

Small molecule solution-processed bulk heterojunction solar cells with inverted structure using porphyrin donor

Science.gov (United States)

Yamamoto, Takaki; Hatano, Junichi; Nakagawa, Takafumi; Yamaguchi, Shigeru; Matsuo, Yutaka

2013-01-01

Utilizing tetraethynyl porphyrin derivative (TE-Por) as a small molecule donor material, we fabricated a small molecule solution-processed bulk heterojunction (BHJ) solar cell with inverted structure, which exhibited 1.6% power conversion efficiency (JSC (short-circuit current) = 4.6 mA/cm2, VOC (open-circuit voltage) = 0.90 V, and FF (fill factor) = 0.39) in the device configuration indium tin oxide/TiOx (titanium sub-oxide)/[6,6]-phenyl-C61-butyric acid methyl ester:TE-Por (5:1)/MoOx (molybdenum sub-oxide)/Au under AM1.5 G illumination at 100 mW/cm2. Without encapsulation, the small molecule solution-processed inverted BHJ solar cell also showed remarkable durability to air, where it kept over 73% of its initial power conversion efficiency after storage for 28 days under ambient atmosphere in the dark.

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer

DEFF Research Database (Denmark)

Popat, Sanjay; Mellemgaard, Anders; Fahrbach, Kyle

2015-01-01

BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel...... with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient...

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

Single agent- and combination treatment with two targeted suicide gene therapy systems is effective in chemoresistant small cell lung cancer cells

DEFF Research Database (Denmark)

Michaelsen, Signe R; Christensen, Camilla L; Sehested, Maxwell

2012-01-01

Transcriptional targeted suicide gene (SG) therapy driven by the insulinoma-associated 1 (INSM1) promoter makes it possible to target suicide toxin production and cytotoxicity exclusively to small cell lung cancer (SCLC) cells and tumors. It remains to be determined whether acquired chemoresistance......, as observed in the majority of SCLC patients, desensitizes SCLC cells to INSM1 promoter-driven SG therapy....

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

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Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.

Science.gov (United States)

Jiang, Y Q; Xu, X P; Guo, Q M; Xu, X C; Liu, Q Y; An, S H; Xu, J L; Su, F; Tai, J B

2016-09-02

Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P var. and cisplatin was also significantly inhibited (P var. (P var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.

Cisplatin-mediated radiosensitization of non-small cell lung cancer cells is stimulated by ATM inhibition

International Nuclear Information System (INIS)

Toulany, Mahmoud; Mihatsch, Julia; Holler, Marina; Chaachouay, Hassan; Rodemann, H. Peter

2014-01-01

Background and purpose: Cisplatin activates ataxia-telangiectasia-mutated (ATM), a protein with roles in DNA repair, cell cycle progression and autophagy. We investigated the radiosensitizing effect of cisplatin with respect to its effect on ATM pathway activation. Material and methods: Non-small cell lung cancer cells (NSCLC) cell lines (A549, H460) and human fibroblast (ATM-deficient AT5, ATM-proficient 1BR3) cells were used. The effects of cisplatin combined with irradiation on ATM pathway activity, clonogenicity, DNA double-strand break (DNA-DSB) repair and cell cycle progression were analyzed with Western blotting, colony formation and γ-H2AX foci assays as well as FACS analysis, respectively. Results: Cisplatin radiosensitized H460 cells, but not A549 cells. Radiosensitization of H460 cells was not due to impaired DNA-DSB repair, increased apoptosis or cell cycle dysregulation. The lack of radiosensitization demonstrated for A549 cells was associated with cisplatin-mediated stimulation of ATM (S1981) and AMPKα (T172) phosphorylation and autophagy. However, in both cell lines inhibition of ATM and autophagy by KU-55933 and chloroquine diphosphate (CQ) respectively resulted in a significant radiosensitization. Combined treatment with the AMPK inhibitor compound-C led to radiosensitization of A549 but not of H460 cells. As compared to the treatment with KU-55933 alone, radiosensitivity of A549 cells was markedly stimulated by the combination of KU-55933 and cisplatin. However, the combination of CQ and cisplatin did not modulate the pattern of radiation sensitivity of A549 or H460 cells. In accordance with the results that cisplatin via stimulation of ATM activity can abrogate its radiosensitizing effect, ATM deficient cells were significantly sensitized to ionizing radiation by cisplatin. Conclusion: The results obtained indicate that ATM targeting can potentiate cisplatin-induced radiosensitization

PET/CT imaging in response evaluation of patients with small cell lung cancer

DEFF Research Database (Denmark)

Fischer, Barbara M; Mortensen, Jann; Langer, Seppo W

2006-01-01

UNLABELLED: There is an increasing amount of evidence on the usability of PET in response evaluation of non-small cell lung cancer. However, data on SCLC is scarce and mainly retrospective. This prospective study assesses the use of PET (positron emission tomography) and PET/CT in response...... evaluation of patients with small cell lung cancer (SCLC). METHODS: Assignment of early and final response was compared between PET, PET/CT, and CT in 20 patients with SCLC. Final response as assigned by CT (RECIST) served as reference. RESULTS: At response evaluation after one cycle of chemotherapy major...... by PET/CT is feasible, but it is uncertain whether it adds further information to evaluation by RECIST, thus further studies and standardization of methods are needed....

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

Science.gov (United States)

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.

Non-small cell lung cancer in never smokers: a clinical entity to be identified.

Science.gov (United States)

Santoro, Ilka Lopes; Ramos, Roberta Pulcheri; Franceschini, Juliana; Jamnik, Sergio; Fernandes, Ana Luisa Godoy

2011-01-01

It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among never-smokers with non-small cell lung cancer. All consecutive non-small cell lung cancer patients diagnosed (n = 285) between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current) were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable), gender (female vs. male), smoking status (never- vs. ever-smoker), the Karnofsky Performance Status Scale (continuous variable), histological type (adenocarcinoma vs. non-adenocarcinoma), AJCC staging (early vs. advanced staging), and treatment (chemotherapy and/or radiotherapy vs. the best treatment support). Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32%) and have adenocarcinoma (70% vs. 51%). Overall median survival was 15.7 months (95% CI: 13.2 to 18.2). The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors

DEFF Research Database (Denmark)

Kvistborg, P; Bechmann, C M; Pedersen, A W

2009-01-01

Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells. Due to their role as potent inducers of immune responses, these cells are widely used as adjuvant in experimental clinical settings for cancer immune therapy. We have developed a DC-based vaccine using autologous......-small-cell-lung-cancer (NSCLC). In the present paper we retrospectively compare the maturation profile based on surface marker expression on DCs generated from the three patient cohorts and between cancer patient cohorts and a cohort of healthy donors. Vaccines were generated under cGMP conditions and phenotypic profiles of DC...

Green tea extract induces protective autophagy in A549 non-small lung cancer cell line.

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Izdebska, Magdalena; Klimaszewska-Wiśniewska, Anna; Hałas, Marta; Gagat, Maciej; Grzanka, Alina

2015-12-31

For many decades, polyphenols, including green tea extract catechins, have been reported to exert multiple anti-tumor activities. However, to date the mechanisms of their action have not been completely elucidated. Thus, the aim of this study was to assess the effect of green tea extract on non-small lung cancer A549 cells. A549 cells following treatment with GTE were analyzed using the inverted light and fluorescence microscope. In order to evaluate cell sensitivity and cell death, the MTT assay and Tali image-based cytometer were used, respectively. Ultrastructural alterations were assessed using a transmission electron microscope. The obtained data suggested that GTE, even at the highest dose employed (150 μM), was not toxic to A549 cells. Likewise, the treatment with GTE resulted in only a very small dose-dependent increase in the population of apoptotic cells. However, enhanced accumulation of vacuole-like structures in response to GTE was seen at the light and electron microscopic level. Furthermore, an increase in the acidic vesicular organelles and LC3-II puncta formation was observed under the fluorescence microscope, following GTE treatment. The analysis of the functional status of autophagy revealed that GTE-induced autophagy may provide self-protection against its own cytotoxicity, since we observed that the blockage of autophagy by bafilomycin A1 decreased the viability of A549 cells and potentiated necrotic cell death induction in response to GTE treatment. Collectively, our results revealed that A549 cells are insensitive to both low and high concentrations of the green tea extract, probably due to the induction of cytoprotective autophagy. These data suggest that a potential utility of GTE in lung cancer therapy may lie in its synergistic combinations with drugs or small molecules that target autophagy, rather than in monotherapy.

Green tea extract induces protective autophagy in A549 non-small lung cancer cell line

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Magdalena Izdebska

2015-12-01

Full Text Available Background and objectives: For many decades, polyphenols, including green tea extract catechins, have been reported to exert multiple anti-tumor activities. However, to date the mechanisms of their action have not been completely elucidated. Thus, the aim of this study was to assess the effect of green tea extract on non-small lung cancer A549 cells. Material and methods: A549 cells following treatment with GTE were analyzed using the inverted light and fluorescence microscope. In order to evaluate cell sensitivity and cell death, the MTT assay and Tali image-based cytometer were used, respectively. Ultrastructural alterations were assessed using a transmission electron microscope.Results: The obtained data suggested that GTE, even at the highest dose employed (150 μM, was not toxic to A549 cells. Likewise, the treatment with GTE resulted in only a very small dose-dependent increase in the population of apoptotic cells. However, enhanced accumulation of vacuole-like structures in response to GTE was seen at the light and electron microscopic level. Furthermore, an increase in the acidic vesicular organelles and LC3-II puncta formation was observed under the fluorescence microscope, following GTE treatment. The analysis of the functional status of autophagy revealed that GTE-induced autophagy may provide self-protection against its own cytotoxicity, since we observed that the blockage of autophagy by bafilomycin A1 decreased the viability of A549 cells and potentiated necrotic cell death induction in response to GTE treatment.Conclusion: Collectively, our results revealed that A549 cells are insensitive to both low and high concentrations of the green tea extract, probably due to the induction of cytoprotective autophagy. These data suggest that a potential utility of GTE in lung cancer therapy may lie in its synergistic combinations with drugs or small molecules that target autophagy, rather than in monotherapy.

Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

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Reenu Punia

Full Text Available Anthracyclines are efficient and potent agents to treat broad range of cancers but cytotoxicity induced by them limits their use in therapeutics. Use of plant-derived agents help to prevent or delay the process of cancer progression and their combination increases the anti-cancer potential of mainstream compound. However, multidrug resistance is major cause of treatment failure in cancer patients.In this study, combination treatments of fisetin or acacetin with doxorubicin were explored for their potential synergistic effect on non-small-cell lung carcinoma (NSCLC cells.During this study, NSCLC model cell lines A549 and H1299 were used to determine the combinatorial effect of phytochemicals namly acacetin and fisetin with doxorubicin.The effects of individual compounds and their combination on cell viability, clonogenic potential and cell cycle progression were studied. Efflux of doxorubicin was measured by spectrofluorophotometer, whereas accumulation inside the cells was analyzed by flow cytometry and confocal microscopy. Expression of MDR1 was checked by semi-quantitative PCR.The results showed that the cell viability of A549 and H1299 cells were significantly decreased in time- and dose-dependent manner, although A549 cells showed more sensitivity toward doxorubicin than H1299 cells. Mostly, combination of doxorubicin showed good synergy with acacetin in both the cell lines whereas, fisetin exerted synergistic effect only at 72 h of treatment in H1299 cells. Acacetin with doxorubicin caused G2/M arrest by downregulating CDK-cyclin complex in A549 cells. Acacetin-doxorubicin combination decreased the clonogenic potential of A549 and H1299 cells upto 82% and 59%, respectively, as compared to control. Acacetin also decreased efflux of doxorubicin by 59% after 30 mins of exposure to A549 cells and further increased accumulation of doxorubicin inside the cells upto 55% in 2 h. The modulatory effect of acacetin-doxorubicin combination on

Networks of neuroblastoma cells on porous silicon substrates reveal a small world topology

KAUST Repository

Marinaro, Giovanni; La Rocca, Rosanna; Toma, Andrea; Barberio, Marianna; Cancedda, Laura; Di Fabrizio, Enzo M.; Decuzzi, Paolo C W; Gentile, Francesco T.

2015-01-01

The human brain is a tightly interweaving network of neural cells where the complexity of the network is given by the large number of its constituents and its architecture. The topological structure of neurons in the brain translates into its increased computational capabilities, low energy consumption, and nondeterministic functions, which differentiate human behavior from artificial computational schemes. In this manuscript, we fabricated porous silicon chips with a small pore size ranging from 8 to 75 nm and large fractal dimensions up to Df ∼ 2.8. In culturing neuroblastoma N2A cells on the described substrates, we found that those cells adhere more firmly to and proliferate on the porous surfaces compared to the conventional nominally flat silicon substrates, which were used as controls. More importantly, we observed that N2A cells on the porous substrates create highly clustered, small world topology patterns. We conjecture that neurons with a similar architecture may elaborate information more efficiently than in random or regular grids. Moreover, we hypothesize that systems of neurons on nano-scale geometry evolve in time to form networks in which the propagation of information is maximized. This journal is

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

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

Effects of Monoclonal Antibody Cetuximab on Proliferation of Non-small Cell Lung Cancer Cell lines

Directory of Open Access Journals (Sweden)

Zhen CHEN

2010-08-01

Full Text Available Background and objective The epidermal growth factor receptor (EGFR monoclonal antibody cetuximab has been used widely in non-small cell lung cancer patients. The aim of this study is to explore the effect of lung cancer cells (A549, H460, H1299, SPC-A-1 which were treated by cetuximab in vitro. Methods We studied the effects of increasing concentrations of cetuximab (1 nmol/L-625 nmol/L in four human lung cancer cell lines (A549, SPC-A-1, H460, H1229. CCK8 measured the inhibition of cell proliferation in each group. A549, SPC-A-1 were marked by PI and the statuses of apoptosis were observed. Western blot were used to detect the proliferation-related signaling protein and apoptosis-related protein in A549. Results The treatment with cetuximab resulted in the effect on cell proliferation and apoptosis in a time- and dosedependent manner. The expression of activated key enzymes (p-AKT, p-EGFR, p-MAPK in EGFR signaling transduction pathway were down-regulated more obviously. Conclusion Cetuximab is an effective targeted drug in the treatment of lung cancer cell lines, tissues, most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

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.

Targeted therapy for localized non-small-cell lung cancer: a review

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Paleiron N

2016-07-01

Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

Science.gov (United States)

Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

2015-01-01

In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.

Science.gov (United States)

Klimaszewska-Wisniewska, Anna; Halas-Wisniewska, Marta; Tadrowski, Tadeusz; Gagat, Maciej; Grzanka, Dariusz; Grzanka, Alina

2016-01-01

The use of the dietary polyphenols as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention of scientists and clinicians as a plausible approach for overcoming the limitations of chemotherapy (e.g. drug resistance and cytotoxicity). The aim of this study was to investigate whether a naturally occurring diet-based flavonoid, fisetin, at physiologically attainable concentrations, could act synergistically with clinically achievable doses of paclitaxel to produce growth inhibitory and/or pro-death effects on A549 non-small cell lung cancer cells, and if it does, what mechanisms might be involved. The drug-drug interactions were analyzed based on the combination index method of Chou and Talalay and the data from MTT assays. To provide some insights into the mechanism underlying the synergistic action of fisetin and paclitaxel, selected morphological, biochemical and molecular parameters were examined, including the morphology of cell nuclei and mitotic spindles, the pattern of LC3-II immunostaining, the formation of autophagic vacuoles at the electron and fluorescence microscopic level, the disruption of cell membrane asymmetry/integrity, cell cycle progression and the expression level of LC3-II, Bax, Bcl-2 and caspase-3 mRNA. Here, we reported the first experimental evidence for the existence of synergism between fisetin and paclitaxel in the in vitro model of non-small cell lung cancer. This synergism was, at least partially, ascribed to the induction of mitotic catastrophe. The switch from the cytoprotective autophagy to the autophagic cell death was also implicated in the mechanism of the synergistic action of fisetin and paclitaxel in the A549 cells. In addition, we revealed that the synergism between fisetin and paclitaxel was cell line-specific as well as that fisetin synergizes with arsenic trioxide, but not with mitoxantrone and methotrexate in the A549 cells. Our results provide rationale for

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

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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.

Pulmonary tuberculosis

International Nuclear Information System (INIS)

Juhl, J.H.

1987-01-01

Dissemination of the tubercle bacillus is of three types: bronchogenic, hematogenous, and lymphangitic. Bronchogenic dissemination occurs when exudate from a cavity or small area of caseation drains into a bronchus and is aspirated into previously uninfected areas either on the same or on the opposite side. This type of spreading occurs frequently after bleeding and when there is a cavity emptying into a bronchus. Hematogenous dissemination leads to miliary tuberculosis and to extrapulmonary lesions throughout the body. Acute massive hematogenous spread causes miliary tuberculosis, while chronic spread in smaller amounts usually results in the chronic extrapulmonary foci. Lymphangitic dissemination is common in primary infection. It is responsible for involvement with subsequent enlargement of hilar and mediastinal nodes that is often seen in children and in young black adults. The reaction to M. tuberculosis depends on the presence or absence of immunity to tuberculoprotein. In individuals having no tissue hypersensitivity or immunity, primary tuberculosis results. In those with immunity produced by previous infection or BCG vaccination, the reactivation (reinfection) disease may develop

Measurement and apportionment of radon source terms for modeling indoor environments

International Nuclear Information System (INIS)

Harley, N.H.

1990-01-01

This research has two main goals; (1) to quantify mechanisms for radon entry into homes of different types and to determine the fraction of indoor radon attributable to each source and (2) to model and calculate the dose (and therefore alpha particle fluence) to cells in the human and animal tracheobronchial tree that is pertinent to induction of bronchogenic carcinoma from inhaled radon daughters

Interstitial cells of Cajal in human small intestine. Ultrastructural identification and organization between the main smooth muscle layers

DEFF Research Database (Denmark)

Rumessen, J J; Thuneberg, L

1991-01-01

with elastin fibers. The organization shown in this study strongly supports the concept of interstitial cells of Cajal as important regulatory cells also in the human small intestine. The characteristic cytology and organization of interstitial cells of Cajal may provide a basis for future morphological......Previous morphological and electrophysiological studies have supported the hypothesis that interstitial cells of Cajal have important regulatory (pacemaker) functions in the gut. In the current study, interstitial cells of Cajal associated with Auerbach's plexus in human small intestine were...... studied. Freshly resected intestine was examined by light and electron microscopy. The interstitial cells of Cajal resembled modified smooth muscle cells. They had caveolae and dense bodies, an incomplete basal lamina, a very well-developed smooth endoplasmic reticulum, and abundant intermediate (10 nm...

Should patients with laryngeal small cell neuroendocrine carcinoma receive prophylactic cranial irradiation?

NARCIS (Netherlands)

Coca-Pelaz, Andres; Devaney, Kenneth O.; Rodrigo, Juan P.; Halmos, Gyorgy B.; Strojan, Primoz; Mendenhall, William M.; Eisbruch, Avraham; Smee, Robert; Kusafuka, Kimihide; Rinaldo, Alessandra; Ferlito, Alfio

2016-01-01

While small cell neuroendocrine carcinomas (SCNCs) most often arise in the lung, extrapulmonary SCNCs arise in a variety of locations-including the head and neck region. In particular, laryngeal SCNCs-while rare tumors-are nevertheless recognized as distinct lesions. The rarity of laryngeal SCNC

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

Non-small cell lung cancer in never smokers: a clinical entity to be identified

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Ilka Lopes Santoro

2011-01-01

Full Text Available OBJECTIVES: It has been recognized that patients with non-small cell lung cancer who are lifelong never-smokers constitute a distinct clinical entity. The aim of this study was to assess clinical risk factors for survival among neversmokers with non-small cell lung cancer. METHODS: All consecutive non-small cell lung cancer patients diagnosed (n = 285 between May 2005 and May 2009 were included. The clinical characteristics of never-smokers and ever-smokers (former and current were compared using chi-squared or Student's t tests. Survival curves were calculated using the Kaplan-Meier method, and log-rank tests were used for survival comparisons. A Cox proportional hazards regression analysis was evaluated by adjusting for age (continuous variable, gender (female vs. male, smoking status (never- vs. ever-smoker, the Karnofsky Performance Status Scale (continuous variable, histological type (adenocarcinoma vs. non-adenocarcinoma, AJCC staging (early vs. advanced staging, and treatment (chemotherapy and/or radiotherapy vs. the best treatment support. RESULTS: Of the 285 non-small cell lung cancer patients, 56 patients were never-smokers. Univariate analyses indicated that the never-smoker patients were more likely to be female (68% vs. 32% and have adenocarcinoma (70% vs. 51%. Overall median survival was 15.7 months (95% CI: 13.2 to 18.2. The never-smoker patients had a better survival rate than their counterpart, the ever-smokers. Never-smoker status, higher Karnofsky Performance Status, early staging, and treatment were independent and favorable prognostic factors for survival after adjusting for age, gender, and adenocarcinoma in multivariate analysis. CONCLUSIONS: Epidemiological differences exist between never- and ever-smokers with lung cancer. Overall survival among never-smokers was found to be higher and independent of gender and histological type.

Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

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Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

2016-03-01

Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

Reduced expression of bax in small cell lung cancer cells is not sufficient to induce cisplatin-resistance

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Biagosch J

2010-10-01

Full Text Available Abstract Resistance to cisplatin in the course of chemotherapy contributes to the poor prognosis of small cell lung cancer (SCLC. B cell lymphoma-2 is the founding member of a large family of proteins that either promote or inhibit apoptosis. We aimed at investigating if the pro-apoptotic members Bad, Bax, Bim and Bid are involved in cisplatin-resistance. Cisplatin-resistance in the SCLC cell line H1339 was induced by repetitive exposure to cisplatin. Protein expression was quantified by Western Blot and immuno-fluorescence analysis. Protein expression was altered using siRNA interference. Four "cycles" of 0.5 μg/ml cisplatin led to partial cisplatin-resistance in H1339 cells. The expression of Bad, Bim and Bid was comparable in naïve and resistant cells while the expression of Bax was reduced in the resistant clone. But, reducing Bax expression in naïve cells did not lead to altered cisplatin sensitivity neither in H1339 nor in H187 SCLC cells. We conclude that the reduced Bax expression after exposure to cisplatin is not sufficient to induce cis-platin-resistance in SCLC cells.

Results of surgical treatment of T4 non-small cell lung cancer

NARCIS (Netherlands)

Pitz, CCM; de la Riviere, AB; van Swieten, HA; Westermann, CJJ; Lammers, JWJ; van den Bosch, JMM

2003-01-01

Objective: Because of location and invasion of surrounding structures, the role of surgical treatment for T4 tumors remains unclear. Extended resections carry a high mortality and should be restricted for selected patients. This study clarifies the selection process in non-small cell T4 tumors with

Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population.

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Lixia Fan

Full Text Available Non-small cell lung cancer is one of the most common cancers and the leading cause of cancer death worldwide. Genetic variants in regulatory regions of some miRNAs might be involved in non-small cell lung cancer susceptibility and survival. rs12220909 (G/C genetic polymorphism in miR-4293 has been shown to be associated with decreased risk of esophageal squamous cell carcinoma. However, the influence of rs12220909 genetic variation on non-small cell lung cancer susceptibility has not been reported. In order to evaluate the potential association between miR-4293 rs12220909 and non-small cell lung cancer risk in a Chinese population, we performed a case-control study among 998 non-small cell lung cancer cases and 1471 controls. The data shows that miR-4293 rs12220909 was significantly associated with decreased susceptibility to non-small cell lung cancer (GC vs.GG: OR = 0.681, 95%CI = 0.555-0.835, P = 2.19E-4; GG vs. GC+CC: OR = 0.687, 95%CI = 0.564-0.837, P = 1.95E-4, which indicates that rs12220909 in miR-4293 may play a significant role in the development of non-small cell lung cancer.

Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

Science.gov (United States)

Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

2016-06-15

Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues.

Science.gov (United States)

Thomas, Mini; Kularatne, Sumith A; Qi, Longwu; Kleindl, Paul; Leamon, Christopher P; Hansen, Michael J; Low, Philip S

2009-09-01

Potential clinical applications of small interfering RNA (siRNA) are hampered primarily by delivery issues. We have successfully addressed the delivery problems associated with off-site targeting of highly toxic chemotherapeutic agents by attaching the drugs to tumor-specific ligands that will carry the attached cargo into the desired cancer cell. Indeed, several such tumor-targeted drugs are currently undergoing human clinical trials. We now show that efficient targeting of siRNA to malignant cells and tissues can be achieved by covalent conjugation of small-molecular-weight, high-affinity ligands, such as folic acid and DUPA (2-[3-(1, 3-dicarboxy propyl)-ureido] pentanedioic acid), to siRNA. The former ligand binds a folate receptor that is overexpressed on a variety of cancers, whereas the latter ligand binds to prostate-specific membrane antigen that is overexpressed specifically on prostate cancers and the neovasculature of all solid tumors. Using these ligands, we show remarkable receptor-mediated targeting of siRNA to cancer tissues in vitro and in vivo.

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

Energy Technology Data Exchange (ETDEWEB)

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

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

Energy Technology Data Exchange (ETDEWEB)

Wu, Qipeng; Yao, Bei; Li, Ning; Ma, Lei; Deng, Yanchao; Yang, Yang; Zeng, Cheng; Yang, Zhicheng [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Liu, Bing, E-mail: liubing520@gdpu.edu.cn [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006 (China)

2017-03-15

The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H{sub 2}O{sub 2} enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H{sub 2}O{sub 2} level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC. - Highlights: • NOX4-derived H{sub 2}O{sub 2} upregulates Nrf2 expression and activity in NSCLC. • Nrf2 confers apoptosis resistance in NOX4-overexpressed NSCLC cells. • Inhibition of Nrf2 reverses the enhancement effect of NOX4 on cell growth.

Molecular Modeling, Docking, Dynamics and simulation of Gefitinib and its derivatives with EGFR in Non-Small Cell Lung Cancer.

Science.gov (United States)

Reddy, Pulakuntla Swetha; Lokhande, Kiran Bharat; Nagar, Shuchi; Reddy, Vaddi Damodara; Murthy, P Sushma; Swamy, K Venkateswara

2018-02-27

Gefitinib (lressa) is the most prescribed drug, highly effective to treat of non-small cell lung cancer; primarily it was considered targeted therapy is a kinase inhibitor. The non-small cell lung cancer caused by the mutation in the Epithelial Growth Factor Receptor (EGFR) gene, Iressa works by blocking the EGFR protein that helps the cancer cell growth. EGFR protein has lead to the development of anticancer therapeutics directed against EGFR inhibitor including Gefitinib for non-small cell lung cancer. To explore research on Gefitinib and its derivatives interaction with crystal structure EGFR to understand the better molecular insights interaction strategies. Molecular modeling of ligands (Gefitinib and its derivatives) was carried out by Avogadro software till atomic angle stable confirmation obtained. The partial charges for the ligands were assigned as per standard protocol for molecular docking. All docking simulations were performed with AutoDockVina. Virtual screening carried out based on binding energy and hydrogen bonding affinity. Molecular dynamics (MD) and Simulation EGFR was done using GROMACS 5.1.1 software to explore the interaction stability in a cell. The stable conformation for EGFR protein trajectories were captured at various time intervals 0-20ns. Few compounds screen based on high affinity as the inhibitor for EGFR may inhibit the cell cycle signalling in non-small cell lung cancer. These result suggested that a computer aided screening approach of a Gefitinib derivatives compounds with regard to their binding to EGFR for identifying novel drugs for the treatment of non-small cell lung cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A new in vitro screening system for anticancer drugs for the treatment of non-small cell lung cancer

International Nuclear Information System (INIS)

Hanauske, U.; Hanauske, A.R.; Clark, G.M.; Tsen, D.; Buchok, J.; Hoff, D.D. von

1989-01-01

We have evaluated a semiautomated radiometric assay (BACTEC 460 system) for screening of activity of anticancer drugs against human non-small cell lung cancer cell lines. Cells from seven cell lines were exposed to standard antineoplastic agents at four different concentrations using a 1-h incubation. Alpha 2-interferon was tested using a continuous incubation. In vitro drug activity was analyzed as a function of the clinically achievable serum concentration. Our results indicate that two cell lines (CALU-3, SK-MES-1) exhibit in vitro drug sensitivity patterns closest to those observed in clinical studies. These two cell lines might therefore be most useful for screening new anticancer compounds for activity against non-small cell lung cancer. The radiometric assay is a semiautomated system which has advantages over other, more time-consuming screening systems

Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients.

Science.gov (United States)

Rijavec, Matija; Silar, Mira; Triller, Nadja; Kern, Izidor; Cegovnik, Urška; Košnik, Mitja; Korošec, Peter

2011-09-01

The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-naïve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemo-naïve metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.