tbuckley/cabot-search huggingface dataset:
COX 2 inhibition and bowel strictures.
Authors: Laurence Maiden, Ingvar Bjarnason
Journal: Gut (2004)

The letter by Mir et al ( Gut 2004; 53 :154) caught our attention and seems to have caught the editorial staff dozing.

Mir et al present a patient who had been regularly taking conventional non-steroidal anti-inflammatory drugs (NSAIDs) for 26 years for axial spondylarthropathy and ascribe the presence of distal ileal stricturing and ulceration solely to the use of a cyclooxygenase 2 (COX 2) selective inhibitor …
The ability of SDF-1/CXCR4 axis to proliferation adhesion and invasion of small lung cancer cell
Authors: Jian An Huang, Tao Chen, Chuan Yong Mu, Yuan Zeng Gu
Journal: European Respiratory Journal (2012)

Objective  To investigate the effect on tumor invasion and the role of PI3K signaling pathway after the binding of SDF-1 and CXCR4 receptor.   Methods  Flow cytometry (FCM) and RT-PCR were utilized to detect the expression of CXCR4 in NCI-H446. CCK-8 assay was utilized to detect the proliferation of tumor cells treated by SDF-1,CXCR4 antagonist AMD3100 and the PI3K inhibitor LY294002.Chemotaxis and transwell invasion experiments were made in different groups to observe the changes of adhesion and invasion ability.   Results  NCI-H446 with high expression of CXCR4(91.6±2.1%). Compare with the control group,SDF-1,AMD3100 did not affect the proliferation of NCI-H446. LY294002(20μmol/L) could inhibit the proliferation of NCI-H446. 24h, 48h, 72h inhibition rates were 19.4%, 31.3%, 18.4%. Compared with the normal control group,100ng/ml of SDF-1 increased the adhesion ability of NCI-H446,OD values were 1.253±0.107 VS 0.783±0.071(P    Conclusion  Small cell lung cancer cell line NCI-H446 has a high expression of the chemokine CXCR4, its ligand SDF-1 can promote the adhesion and invasion of the tumor cells. PI3K signaling pathway involved in the proliferation works in the adhesion and invasion of NCI-H446 by CXCR4 activation.
Even low levels of air pollution are linked to more deaths in over 65s, study finds
Authors: I. Torjesen
Journal: BMJ (2015)

Death rates in people aged over 65 are higher in areas where the air contains more fine particulate matter (PM2.5), even when levels are in line with recommended standards, a study published online in Environmental Health Perspectives has shown.1

Although exposure to high levels of fine particulate matter has been shown to increase mortality, the effect of levels within the recommended range has been unclear. In the United States the Environmental Protection Agency (EPA) recommends that PM2.5 exposure should not exceed a 12 microgram/m3 yearly average or a 35 microgram/m3 daily average. The World Health …
Hidden genes in birds
Authors: Tomáš Hron, Petr Pajer, Jan Pačes, Petr Bartůněk, Daniel Elleder
Journal: Genome biology (2015)

Abstract We report that a subset of avian genes is characterized by very high GC content and long G/C stretches. These sequence characteristics correlate with the frequent absence of these genes from genomic databases. We provide several examples where genes in this subset are mistakenly reported as missing in birds. www.dx.doi.org/10.1186/s13059-015-0725-y
Complications and management of implanted venous access catheters.
Authors: J J Lokich, A Bothe, P Benotti, C Moore
Journal: Journal of Clinical Oncology (1985)

A totally implanted subclavian venous access system composed of a reservoir and silastic catheter was employed in 92 patients receiving infusion chemotherapy and/or hyperalimentation. The major catheter complication was subclavian or jugular vein thrombosis observed in 15 patients (16%). Thrombosis was observed in the ipsilateral subclavian or jugular vein surrounding the catheter without restricting function, except in two patients with thrombosis in the vein at the end of the catheter. Prophylaxis with low-dose Coumadin was effective in preventing thrombosis in high-risk patients as defined by a history of prior thrombosis. Streptokinase and/or heparin relieved the signs and symptoms of thrombosis, but clot dissolution or reversal of collateral flow was not observed. Explantation of the catheter was not necessary in all patients in that embolic complications of the thrombosis were not observed, and the system was retained and functioned in five patients in spite of the presence of thrombosis around the catheter. Other complications of the implanted system include "pocket" infection, catheter migration, and occlusion. Most complications may be managed without obligate catheter removal.
Effect of sorafenib in symptomatic metastatic medullary thyroid cancer
Authors: F. Kober, M. Hermann, A. Handler, G. Krotla
Journal: Journal of Clinical Oncology (2007)

14065 Background: RET receptor tyrosin kinase activity plays a major role in medullary thyroid cancer (MTC) tumor growth. Sorafenib is an oral agent that selectively targets RET tyrosine kinases. Methods: 5 patients (pts) with metastatic MTC with excessive elevation of calcitonin(CTN) serum levels entered this pilotstudy. Hypercalcitonemia-related symptoms were present in all pts (3 severe diarrhea, 2 moderate) and metastasis- related symptoms were present in 4 pts (2 severe pain, 2 moderate). All pts had had prior thyreoidectomy and cervical +- mediastinal lymphnode dissection, 4 pts had prior octreotide therapy, 3 prior chemotherapy. Pts received 800 mg or 400 mg (weight &lt; 50 kg) Sorafenib as a starting dose. According to the protocol, the dose was reduced gradually in 200 mg scale when pts revealed therapy induced side effects to avoid worsening of quality of life. Sorafenib has to be administered at least 3 months, the scheduled duration of therapy was 6 months. Physical examination, calcitonin and CEA levels were monitored every 4 weeks, measurable metastatic lesions were controlled by appropriate means 3 and 6 months after starting therapy. Primary objective was to assess the effect on CTN dependent symptoms, second objectives included assessments of tumor response (RECIST) and biochemical response. Results: After 2–3 months CTN decreased to levels &gt;50% of baseline in all pts, to levels &gt;90% in 2 pts. According to that all pts were free of CTN related symptoms after 4 weeks. In 4 pts CEA levels reacted in a similar way. After 6 months controls of metastatic lesions were classified as CR-1 pt, PR-1 pt, NC-3 pts. 2 pts with severe metastasis-related pain were off analgesics after 3 months of treatment. Due to side effects Sorafenib dosage was reduced to 50% of the initial dose in all patients. Interestingly marked TSH - elevations were observed in 3 pts which indicates a direct influence to the hypothalamic-pituary-axis. Conclusion: Sorafenib has to be considered as an effective teatment of symptomatic, metastatic MTC. No significant financial relationships to disclose.
A Fiber-Modified, Secretory Leukoprotease Inhibitor Promoter-Based Conditionally Replicating Adenovirus for Treatment of Ovarian Cancer
Authors: Daniel T. Rein, Martina Breidenbach, Tyler O. Kirby, Tie Han, Gene P. Siegal, Gerd J. Bauerschmitz, Minghui Wang, Dirk M. Nettelbeck, Yuko Tsuruta, Masato Yamamoto, Peter Dall, Akseli Hemminki, David T. Curiel
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The use of conditionally replicating adenoviruses (CRAD) is dependent on molecular differences between tumor cells and nontumor cells. Transcriptional targeting of CRAD replication via tumor-specific promoters is an effective way to control replication regulation. Genetic fiber pseudotyping is an approach for circumventing low expression of the primary adenovirus serotype 5 (Ad5) receptor by using the distinct adenovirus serotype 3 (Ad3) receptor for entry into and subsequent killing of ovarian cancer cells. Experimental Design: In this study, we constructed a fiber-modified CRAD containing the secretory leukoprotease inhibitor (SLPI) promoter to control viral replication via the E1A gene (Ad5/3SLPI). To evaluate the liver toxicity of chimeric 5/3 fiber-modified CRADs, we compared Ad5/3SLPI with Ad5/3Cox-2L, a CRAD with E1A under control of the Cox-2 promoter, and Ad5/3Δ24, a CRAD that replicates in cancer cells inactive in the retinoblastoma/p16 pathway by use of an in vivo hepatotoxicity model and by a model system that uses slices of human liver. Results: We show efficient viral replication and oncolysis of Ad5/3SLPI in both multiple ovarian cancer cell lines and primary tumor cell spheroids as well as therapeutic efficacy in an orthotopic mouse model of peritoneal carcinomatosis. Ad5/3SLPI showed significantly decreased liver toxicity compared with other 5/3 fiber-modified control vectors examined. Conclusions: In summary, Ad5/3SLPI is a promising vector candidate for treating metastatic ovarian cancer and showed robust virus replication, oncolysis, and in vivo therapeutic efficacy. Ad5/3SLPI showed comparatively low liver toxicity and therefore holds potential for patient use in the clinic.
Biochemotherapy for Advanced Melanoma: Maybe It Is Real
Authors: David Khayat, Chantal Bernard-Marty, Jean-Baptiste Meric, Olivier Rixe
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.10.2411 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12011117 Biochemotherapy for Advanced Melanoma: Maybe It Is Real David KhayatxDavid KhayatSearch for articles by this author , Chantal Bernard-MartyxChantal Bernard-MartySearch for articles by this author , Jean-Baptiste MericxJean-Baptiste MericSearch for articles by this author , Olivier RixexOlivier RixeSearch for articles by this author Show More Salpetrière Hospital, Paris, France https://doi.org/10.1200/JCO.2002.20.10.2411 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Pathology of Soft Tissue Sarcoma
Authors: Brian P. Rubin, John R. Goldblum
Journal: Journal of the National Comprehensive Cancer Network (2007)

The evaluation and treatment of soft tissue sarcomas has never been more demanding than it is today. The pathologist plays a central role in this process and is an integral member of the multidisciplinary sarcoma treatment team. This article provides a brief summary of the role of the soft tissue pathologist and includes sections on methods of diagnosis, frozen section, classification of sarcomas, expert consultation, molecular pathology, grading, assessment of treatment response, and tumor banking.
Different cutoff values of serum SP-D for German and Japanese to diagnose idiopathic interstitial pneumonias are related to different SFTPD gene polymorphisms
Authors: Yasushi Horimasu, Noboru Hattori, Nobuhisa Ishikawa, Sonosuke Tanaka, Koji Yoshioka, Francesco Bonella, Shinichiro Ohshimo, Josune Guzman, Ulrich Costabel, Nobuoki Kohno
Journal: European Respiratory Journal (2012)

Introduction:  Surfactant protein (SP) -D is a member of the C-type lectin superfamily. Serum SP-D is applied as a diagnostic biomarker for various interstitial lung diseases in Japan, but not in European countries. It is also known that rs721917 single nucleotide polymorphism (SNP) in surfactant protein D (SFTPD) gene might influence serum SP-D levels.   Aims:  This study was aimed to evaluate serum levels and genetic backgrounds of SP-D both in German and Japanese cohorts.   Methods:  Serum levels of SP-D were measured and compared between patients with idiopathic interstitial pneumonias (IIPs) and healthy subjects (HS) both in German and Japanese cohorts. In addition, rs721917 SNP was genotyped by polymerase chain reaction. The power of serum SP-D to discriminate IIPs from HS was examined by receiver operating characteristic analysis based on ethnicity and rs721917 genotype.   Results:  The serum levels of SP-D in IIPs were significantly higher than in HS for both German and Japanese cohort (both p   Conclusions:  Our data suggest the possibility of serum SP-D to be used as diagnostic biomarkers for IIPs in Germans. The cutoff value of serum SP-D is higher in the German than in the Japanese cohort, and this difference might be related to the difference of rs721917 genotype distribution.
YKL-40 induces IL-8 expression from bronchial epithelium via MAPK (JNK, ERK1/2) and NF-κB pathways, causing bronchial smooth muscle proliferation and migration
Authors: Hao Tang, Yu Sun, Bing Li, Qingyu Xiu, Zhaoquan Shi
Journal: European Respiratory Journal (2012)

Our previous study, consistent with others, has shown that the serum YKL-40 levels in asthmatics were significantly elevated and were associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. In this study, we investigated the mechanisms involved in YKL-40-mediated IL-8 production from human bronchial epithelial cells (BEAS-2B) and analyzed the soluble factors (including IL-8) secreted by BEAS-2B exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). We found BEAS-2B treated with YKL-40 resulted in a significant increase of IL-8 expression and release. Moreover, YKL-40 mediated phosphorylation of JNK, ERK, but not p38 in BEAS-2B. Transfection using a NF-κB-luciferase reporter also showed YKL-40 induced IL-8 at the transcriptional level. Furthermore, BEAS-2B pretreated with inhibitors of JNK, ERK or NF-κB decreased IL-8 release upon YKL-40 treatment. In addition, we treated BEAS-2B with YKL-40 and added the conditioned culture media (YKL-40-BEAS-2B-CM) to BSMCs, which led to increased proliferation and migration of BSMCs. By comparison, IL-8-depleted YKL-40-BEAS-2B-CM failed to induce the proliferation and migration of BSMCs. In summary, our data provided the first evidence of YKL-40-induced IL-8 expression in BEAS-2B via MAPK (JNK, ERK) and NF-κB pathways, and the induced IL-8 was found to further stimulate the proliferation and migration of BSMCs. Our results raise the possibility that YKL-40 may play a role in asthma by inducing IL-8 production.
Epidemiology of Human Leukemia: Recent Observations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joseph F. Fraumeni, Robert W. Miller
Journal: JNCI Journal of the National Cancer Institute (1967)

Review of recent epidemiologic studies into the origin of human leukemia revealed the following: 1) Mortality statistics have for the first time shown a downturn in leukemia rates for all ages from 1 through 74 years among the U.S. white population, but not among the U.S. nonwhite population or in England. The possibility that this decline resulted from decreasing exposure to X rays in medical practice was not supported by an analysis of the limited mortality data available on cytologic types which should be unequally affected by radiation. 2) Recent leukemia mortality rates for Japanese and U.S. nonwhite children suggest the emergence of an age peak at 3–4 years similar to that previously found among the U.S. white population and in England. 3) Little evidence was found to support the hypothesis that aggregates of childhood leukemia or patient-pet clusters represent foci of infection. Despite recent searches for other infectious patterns in the distribution of human leukemia, the observation most suggestive of a viral influence is the geographic distribution reported for Burkitt's lymphoma in Africa. 4) Recent observations have extended knowledge of groups who are born with or who acquire, from ionizing radiation or chemicals, a high risk of leukemia. Compilation of case reports of certain genetic diseases suggested that the heritable disorders associated with cytogenetic defects predispose to leukemia, whereas disorders with immunologic deficiencies are related to the lymphomas. There was a consistency among these observations which supports the notion that the pre-existing abnormalities have pathogenic significance, rather than being concomitants of the neoplastic process. Further study of high-risk groups should significantly enhance opportunities for recognition of etiologic agents and mechanisms in leukemogenesis.
The role of pneumonectomy in non-tuberculous mycobacterial infections
Authors: G Price
Journal: Thorax (2004)

▴ Shiraishi Y, Nakajima Y, Katsuragi N, et al . Pneumonectomy for nontuberculous mycobacterial infections. Ann Thorac Surg2004;78:399–403

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Surgery has a role in the treatment of patients with atypical mycobacteria who fail medical treatment or have extensive disease localised to one lung. This case series reports over 15 years of experience from the Fukujuji Hospital, Tokyo, reviewing 53 patients who required pulmonary resection for resistant non-tuberculous mycobacterial infections. Of these, 11 underwent …

 [1]: {openurl}?query=rft.jtitle%253DThe%2BAnnals%2Bof%2BThoracic%2BSurgery%26rft.stitle%253DAnn.%2BThorac.%2BSurg.%26rft.issn%253D0003-4975%26rft.aulast%253DShiraishi%26rft.auinit1%253DY.%26rft.volume%253D78%26rft.issue%253D2%26rft.spage%253D399%26rft.epage%253D403%26rft.atitle%253DPneumonectomy%2Bfor%2Bnontuberculous%2Bmycobacterial%2Binfections%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.athoracsur.2004.02.103%26rft_id%253Dinfo%253Apmid%252F15276484%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx
 [2]: /lookup/external-ref?access_num=10.1016/j.athoracsur.2004.02.103&link_type=DOI
 [3]: /lookup/external-ref?access_num=15276484&link_type=MED&atom=%2Fthoraxjnl%2F59%2F11%2F954.atom
 [4]: /lookup/external-ref?access_num=000222999300002&link_type=ISI
The role of pre-receptor glucocorticoid metabolism in regulating the severity and persistence of murine lung injury
Authors: Sian Lax, Michael Wilson, Masao Takata, Paul Stewart, David Thickett
Journal: European Respiratory Journal (2013)

Introduction

Acute lung injury (ALI) is a major cause of respiratory failure in the critically ill patient. Our current research suggests that local steroid metabolism by alveolar macrophages is defective in ALI patients. As the predominant function of these cells is phagocytosis of apoptotic neutrophils during resolution of inflammation, we sort to investigate the effect of pre-receptor glucocorticoid metabolism in a murine model of ALI.

Methods

Using intra-tracheal instillations of LPS (50µg), we analysed the inflammatory response in the lungs of wild type (WT) mice compared to those deficient in 11β-hydroxysteroid dehydrogenase 1 (HSD1 KO). These mice specifically lack the enzyme which converts inactive cortisone to active cortisol.

Results

Intra-tracheal LPS challenge in WT mice induced significant lung permeability (p=0.002) and neutrophilia (p=0.002) which was associated with hypoxia (p<0.0001), compared to PBS-treated controls. In addition, CD11c+CD11b+ monocytes were recruited (p=0.0003), which differentiate into macrophages within the first 24h post IT-LPS. However in HSD1 KO mice differentiation is delayed (p=0.012) resulting in augmented lung permeability (p=0.022) and prolonged inflammation, as assessed by elevated expression of RAGE (p=0.015), CXCL1/KC (p=0.011) and IL-1β (p=0.041) and increased neutrophilia (p=0.040), compared to WT controls 48hrs post IT-LPS.

Conclusion

Our data indicate that insufficient alveolar glucocorticoid metabolism augments the duration and severity of lung injury. Therefore, therapies targeting defective macrophage HSD1 expression may have value in promoting the resolution of ALI.
Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities.
Authors: J D Hainsworth, J R Gray, S L Stroup, L A Kalman, J E Patten, L G Hopkins, M Thomas, F A Greco
Journal: Journal of Clinical Oncology (1997)

PURPOSE In two sequential phase II studies, we evaluate the feasibility and efficacy of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of small-cell lung cancer. PATIENTS AND METHODS One hundred seventeen patients with small-cell lung cancer were treated between June 1993 and July 1996. The first 38 patients received a lower-dose regimen: paclitaxel 135 mg/m2 by 1-hour infusion, carboplatin at an area under the concentration-time curve (AUC) of 5.0, and etoposide 50 mg alternating with 100 mg orally on days 1 to 10. When only mild myelosuppression was observed, doses of paclitaxel and carboplatin were increased in the subsequent 79 patients (paclitaxel 200 mg/m2 by 1-hour infusion and carboplatin at an AUC of 6.0). All patients received four courses of treatment, administered at 21-day intervals. Patients with limited-stage small-cell lung cancer also received thoracic radiation therapy (1.8 Gy/d; total dose, 45 Gy) administered concurrently with courses 3 and 4 of chemotherapy. RESULTS Seventy-two of 79 patients (91%) who receive the higher-dose regimen had major responses. Thirty-two of 38 (84%) with extensive-stage disease responded (21% complete response rate); median survival was 10 months for this group. With limited-stage disease, the overall response rate was 98%, with 71% complete responses; the median survival time has not been reached at 16 months. Median survival in extensive-stage patients was longer in patients who received the higher-dose regimen (10 months) than in the previous group treated with lower doses (7 months; P = .008). The higher-dose regimen was well tolerated, with myelosuppression being the major toxicity. Compared with the lower-dose regimen, grade 3/4 neutropenia increased from 8% to 38% of courses, but the incidence of hospitalization for neutropenia and fever did not increase. Other nonhematologic toxicities were uncommon, and did not increase substantially with the higher-dose regimen. CONCLUSION Paclitaxel can be added at full dose (200 mg/m2) to a carboplatin/etoposide combination while maintaining a tolerable toxicity profile. Median survival times in both extensive- and limited-stage patients compare favorably with other reported regimens. This regimen merits further investigation, and a randomized trial to compare this regimen with a standard carboplatin/etoposide combination is underway.