tbuckley/cabot-search huggingface dataset:
Hemorrhagic malignant pleural effusion: Diagnosis, survival rate, and response to talc pleurodesis
Authors: Edward Altman, Yousef Abed El Ghani, Elite Sheleg, Maya Kolin, Vadim Sonkin, Hector I. Cohen
Journal: European Respiratory Journal (2014)

Introduction: Hemorrhagic malignant pleural effusion (HMPE) is diagnosed in 47-50% of all malignant pleural effusions (MPE).  Objectives: To evaluate clinical, radiological, and morphological manifestations of HMPE and results of talc pleurodesis treatment.  Material and methods: Retrospective review of the medical charts of 135 MPE patients. HMPE group-42 patients, simple MPE group-63 patients; median age 67.9y, 43 males, 62 females.  Results:  Pronounced dyspnea (HMPE vs. simple MPE; 100% vs. 88.9%, P=0.024), chest pain (59.5% vs. 60.3%, P=1), general deterioration (78.6% vs. 74.6%, P=0.411) combined with large pleural effusion (81% vs. 50.8%, P=0.001) and thickening of parietal pleura (73.8% vs. 68.3%, P=0.349) were more specific for HMPE.  Cytological examination of HMPE showed more malignant pleural fluid cells (81% vs. 63.5%, P=0.043). Histological examination revealed poorly differentiated types of tumors in 69.05% of HMPE (bronchogenic 33.33%, intestinal 16.67%, breast 14.3%) vs. 7.94% of simple MPE. Thoracoscopy in 19 HMPE patients showed bleeding nodules (94.7%) on thickened parietal pleura (84.2%), but none in simple MPE. Pleurodesis with talc by slurry (59%) and poudrage (41%) was less effective in HMPE patients after one month (failed response; 33.3% vs. 21.6, P=0.019), three months (42.9% vs. 25.7%, P=0.017), and six months (42.9% vs. 21.7%, P=0.035). Survival in HMPE was significantly lower (3.06 months vs. 5.37 months, P=0.0005).  Conclusions:  HMPE had more severe clinical-radiological manifestations due to poorly differentiated malignant process. Talc pleurodesis was less effective in HMPE and survival was poor.
Marrow Transplantation in the Busulfan-Treated Rat: Preclinical Model of Aplastic Anemia&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: G W Santos, P J Tutschka
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Marrow Transplantation in the Busulfan-Treated Rat: Preclinical Model of Aplastic Anemia Get access George W. Santos, George W. Santos Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter J. Tutschka Peter J. Tutschka Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 6, December 1974, Pages 1781–1785, https://doi.org/10.1093/jnci/53.6.1781 Published: 01 December 1974 Article history Received: 06 June 1974 Accepted: 23 August 1974 Published: 01 December 1974
포스터 발표 : 한국인에서 원인미상의 간세포암은 증가하는가?
Authors: 박상훈, 오길찬, 장현주, 이자영, 박철희, 한태호, 박현주, 이동근, 김진봉, 김종혁, 장웅기, 김동준, 이명석, 박충기
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 과거 원인미상의 간세포암은 전체 간세포암의 10-30%를 차지하였으나, HCV의 발견으로 최근에는 약 5% 정도로 감소된 것으로 보고 되어 있다. 원인미상의 간세포암의 원인으로 당뇨병이나 비만이 독립적인 위험인자일 것으로 추정되는 연구보고가 있었고, 최근에는 원인미상의 간경변증의 약 30-50%가 비알코올성 지방간염(nonalcoholic steatohepatitis, 이하 NASH로 함) 때문이라는 보고가 있었다. 최근에 NASH가 간경변증을 거쳐 간세포암을 일으킬 수 있으며, 전체 간세포암의 13%를 차지할 정도로 원인미상 간세포암의 원인으로 NASH를 포함한 비알코올성 지방간질환(NAFLD)이 차지하는 비율이 높다는 연구보고가 있었다. NASH가 심한 섬유화나 간경변증을 일으키는 위험인자로는 고령, 당뇨병, 비만 등으로 알려져 있으며, 이러한 위험인자를 가진 NASH 환자는 간세포암으로 발생이 높을 것으로 추정된다. 본 연구의 목적은 최근 서구화된 식생활로 비만 인구가 늘어가는 한국에서 원인미상의 간세포암이 증가되었는지 후향적으로 알아보고, 원인미상 간세포암 환자의 특성이 위험인자를 지닌 NASH 환자와 일치하는지 확인하여, 원인미상 간세포암의 원인으로 NASH가 차지하는 정도를 간접적으로 확인하고자 하였다. 대상과 방법: 의료원에 내원한 환자에서 A군은 1993-1995년, B군은 2000-2002년으로 하여, 그 기간에 간세포암으로 진단받은 1071예를 대상으로 하였다. 간세포암 진단은 조직검사나 영상소견 및 AFP로 하였으며, 비특이적인 영상소견을 보이면서 조직검사를 시행하지 않은 경우는 대상에서 제외하였다. 간세포암의 원인이 명확하지 않으면서 HBc Ab만 양성인 경우는 원인미상 간세포암에서 제외하여 따로 분리하였다. 대상 예는 모두 후향적으로 조사하였으며 원인미상 간세포암이 증가했는지 알아보기 위해 분석하였다. 결과: 원인미상 간세포암에서 BMI가 측정되었던 34예 중 BMI>25 이었던 예는 12예였으며, DM 8/48, HTN 11/48, hyperlipidemia 9/48 예였다. 원인별 분석은 Table 1과 같으며 원인미상의 간세포암은 통계적으로 유의하게 증가되는 소견을 보였다.
Table 1. A(1993-1995년)와 B(2000-2003년) group 사이의 간세포암 원인별 분석	
원인	                     A (%)	    B(%)	
HBV	                130 (51.8%)	    473 (61.4%)	
HCV	                10 (3.9%)	    76 (9.8%)	
Alcohol	                33 (13.1%)	    71 (9.2%)	
HBV+Alcohol	    65 (25.9%)	    79 (10.3%)	
HCV+Alcohol	    5 (2.0%)	    16 (2.1%)	
Cryptogenic	     6 (2.4%)	    42 (5.5%)＊	
Total	                251	                770	
젨젨젨젨젨 ＊p<0.05 
결론: 한국인에서 HCV가 완전히 배제되었다고 생각되는, 2000-2002년의 원인미상 간세포암의 발생율은 1993-1995년에 비해 증가되는 결과를 보였다. 이는 원인미상 간세포암에서 비알코올성 지방간질환에 의한 원인이 증가되었을 것으로 생각되나, 후향적 연구의 한계로 결론을 도출하기에는 부족하였다. 앞으로 전향적 대규모 연구가 이루어져야 한다고 생각된다.
Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma.
Authors: M E King, C E Pfeifle, S B Howell
Journal: Journal of Clinical Oncology (1984)

Previous pharmacokinetic modeling has suggested that cytosine arabinoside (ara-C) may be an ideal agent for peritoneal administration in the treatment of intraabdominal neoplasms. In vitro drug sensitivity testing with clonogenic assays demonstrated sensitivity to the high concentrations of ara-C potentially achievable by intraperitoneal (IP) administration in five of nine patients with ovarian carcinoma. The kinetics of IP ara-C were then studied in three patients, and a 2 to 3 log concentration gradient was observed between the peritoneal compartment and plasma. Subsequently, the clinical efficacy of IP ara-C given for a five-day course every four weeks was evaluated in 10 patients with ovarian carcinoma who had failed systemic chemotherapy. Chemical peritonitis did not occur and systemic toxicity was minimal. Two patients were rendered free of disease and are alive without disease 14+ and 15+ months since therapy was discontinued. These results demonstrate that there is a very large pharmacologic advantage to the IP route of administration for ara-C, that ara-C is active against advanced ovarian carcinoma, and that the IP route of administration permits the cytokinetically rational use of very long durations of exposure for this cell-cycle phase-specific agent.
How to improve patients and investigators’ information on clinical trials: The example of French registry for clinical trials in oncology
Authors: E. Manach, I. Pauporté, N. Bachouche, S. Détry, J. Barbare
Journal: Journal of Clinical Oncology (2008)

17555 Background: Cancer patients’ willingness to be informed about clinical trials (CT) and their investigation sites is rapidly increasing. In parallel, health professionals are interested on being informed on clinical research in order to provide their patients the best access to innovative treatments. The French cancer plan (2003–2007) launched the creation of a national registry for clinical trials in oncology (RECF). The primary objective was to guarantee patients and investigators comprehensive, high quality and updated information about ongoing CT in France, accessed at INCa's web site (www.e-cancer.fr). A second objective was to establish a single channel for registration of French CT in conformity with the requirements of the International Committee of Medical Journal Editors (ICMJE). Methods: A standard form was sent to all French sponsors in November 2005 asking for data on cancer CT opened for recruitment. From October 2005 to May 2007 the database and web interface were established. A unique web access for patients and investigators was created. Information important for patients, pathology and investigation sites, are presented in the first pages; scientific information, according to the requirements of ICMJE, being accessible under further clicks. A web information page about clinical research, intended for patients and their relatives, was also prepared in collaboration with patients’ advocacy and healthcare professionals. Results: Thanks to the active collaboration of the academic sponsors, about hundred CT were registered as of end of July 2006, date when the RECF was opened to professionals for testing. Since 16 April 2007, the RECF has been available online and continues to be updated; over 300 CT were registered as of end of December 2007 and will be 500 by the end of June 2008. All French academic sponsors have registered their CT. Conclusions: Achieving comprehensiveness is one of the founding principles of the RECF; the publication of the industrial trials will begin in 2008. The basis of a single channel for international registration is established through a close collaboration with the NCI-USA, PDQ and needs to be developed. Specific analysis on patients’ frequentation rate will also be investigated. No significant financial relationships to disclose.
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Authors: Vinay Varadan, Hannah Gilmore, Kristy L.S. Miskimen, David Tuck, Shikha Parsai, Amad Awadallah, Ian E. Krop, Eric P. Winer, Veerle Bossuyt, George Somlo, Maysa M. Abu-Khalaf, Mary Anne Fenton, William Sikov, Lyndsay N. Harris
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer. Experimental Design: In patients enrolled on two multicenter trials (03-311 and 211B), tumor core biopsies were obtained at baseline and after brief exposure to single-agent trastuzumab or nab-paclitaxel. Gene expression profiles were assessed to assign PAM50 subtypes, measure immune cell activation, and were correlated with response. Results: The pCR rate was significantly higher in HER2-enriched tumors in the Discovery, 03-311 (36%, P = 0.043) dataset, as compared with other subtypes, which validated in 211B (50%, P = 0.048). Significant increases in a signature of immune cell admixture (Immune Index) were observed only following brief exposure to trastuzumab in HER2-enriched tumors (Discovery/03-311, P = 0.05; Validation/211B, P = 0.02). Increased Immune Index was predictive of response after brief exposure (03-311, P = 0.03; 211B, P = 0.04), but not at baseline, in addition to increased expression of a CD4+ follicular helper T-cell signature (03-311, P = 0.05; 211B, P = 0.04). Brief exposure to trastuzumab significantly increased gene expression of the T-cell marker PD-1 in HER2-enriched tumors (Discovery/03-311, P = 0.045) and PD-1 positivity by IHC (Validation/211B, P = 0.035). Conclusions: Correlations between pCR rates, increases in Immune Index and markers of T-cell activity following brief exposure to trastuzumab in HER2-enriched tumors provide novel insights into the interaction between tumor biology, antitumor immunity, and response to treatment, and suggest potential clinically useful biomarkers in HER2+ breast cancers. Clin Cancer Res; 22(13); 3249–59. ©2016 AACR.
Insulin-like growth factors are essential to prevent anoikis in oestrogen-responsive breast cancer cells: importance of the type I IGF receptor and PI3-kinase/Akt pathway
Authors: Brendan C. Luey, Felicity E. B. May
Journal: Molecular Cancer (2016)

Detachment of epithelial cells from the extracellular matrix initiates programmed cell death by a process termed anoikis. Malignant cells must acquire anoikis resistance to leave the primary tumour and metastasise. Multiple signal transduction pathways can activate anoikis and confer anoikis resistance, but these are not understood in breast cancer.Models for anoikis of oestrogen-responsive breast cancer cells were established and the protective effects of IGF-1 tested. Cleaved PARP was measured by western transfer and cleaved caspase 3 by flow cytometry. Pathways involved in anoikis and in anoikis resistance were investigated with PI3-kinase, Akt, and MEK1 and MEK2 inhibitors. The importance of the type I IGF receptor was investigated by IGF-concentration dependence, siRNA knockdown and pharmacological inhibition. Association between IGF-1R expression and relapse with distant metastasis was analysed in 1609 patients by log rank test.Unattached breast cancer cells required culture in serum-free medium to induce anoikis. Rapid loss of FAK, Akt and Bad phosphorylation was concurrent with anoiks induction, but ERK1 and ERK2 phosphorylation increased which suggested that anoikis resistance is mediated by the PI3-kinase/Akt rather than the Grb2/Ras/MAP-kinase pathway. IGF-1 conferred anoikis resistance in serum-free medium. IGF-1 activated the PI3-kinase/Akt and Grb2/Ras/MAP-kinase pathways but experiments with PI3-kinase, Akt and MEK1 and MEK2 inhibitors showed that IGF protection is via the PI3-kinase/Akt pathway. The concentration dependence of IGF protection, knockdown experiments with siRNA and pharmacological inhibition with figitumumab, showed that IGF-1 signals through the type I IGF receptor. The crucial role of the type I IGF receptor was demonstrated by induction of anoikis in full serum by figitumumab. High IGF-1R expression was associated with reduced time to relapse with distant metastases in oestrogen receptor-positive patients, especially those with aggressive disease which confirms its relevance in vivo.Anoikis resistance of oestrogen-responsive breast cancer cells depends upon IGF activation of the type I IGF receptor and PI3-kinase/Akt pathway. Because IGF-dependent evasion of anoikis will facilitate metastasis by malignant breast cancer cells, effective inhibition of IGF signal transduction should be included in combinations of targeted drugs designed to treat metastatic oestrogen receptor-positive breast cancers.
Effect of initial resection of small-cell carcinoma of the lung: a review of Southwest Oncology Group Study 7628.
Authors: G G Friess, J D McCracken, M L Troxell, R Pazdur, C A Coltman, H J Eyre
Journal: Journal of Clinical Oncology (1985)

The role of surgery in small-cell carcinoma of the lung (SCCL) has been recently re-evaluated. We reviewed the records of 262 patients with limited SCCL on Southwest Oncology Group (SWOG) protocol 7628. Fifteen patients were identified who presented after surgical resection (12 lobectomy, three pneumonectomy). All patients were subsequently treated with chemotherapy, radiotherapy +/- immunotherapy (BCG). Median survival time was 10.5 months. Median survival time of patients with initial surgical resection was 25 months (P = .004). Forty-five percent of the surgical patients were alive at two years v 13.7% of the nonsurgical patients (P less than .05). A second subgroup of 33 patients was identified with small primary tumors who did not undergo surgical resection. Median survival time in this group was ten months (P = .03). Site of initial relapse was clearly documented in 142 patients. Fifty-six percent of patients not receiving surgery had initial relapse within the chest compared to 13% of patients undergoing surgery (P = .002). Whether the survival benefit identified was caused by or was incidental to surgical resection of the primary lesion remains to be determined in randomized prospective trials of operable candidates.
포스터발표 : 그랜드볼룸 ; 주종양의 크기가 5cm 이하인 다발성 간세포암종 환자에서 수술적 치료와 간동맥색전술 후 장기 성적 (초)
Authors: 김승업, 황호경, 주동진, 김도영, 안상훈, 최진섭, 한광협, 이형순, 박준용, 최기홍
Journal: Clinical and Molecular Hepatology (2010)
Growth inhibition and cell death by natural plant products in glioblastoma and medulloblastoma cells.
Authors: Aik Kia Khaw, Wei Yan Yong Jacklyn, M. Pradeepa Hande, M. Prakash Hande
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C16 

Based on the recent studies using in vitro and in vivo models, it is suggested that natural plant products could be used as anti-cancer agents in chemotherapy. However, detailed molecular mechanism(s) of action of these drugs remain to be elucidated. In the present study, we have investigated the anti-proliferative activity, cytotoxic effect and telomere-telomerase regulation of two potential anti-cancer drugs, genistein and curcumin, on human glioblastoma and medulloblastoma cells. Using appropriate assays, we have determined the effect of curcumin and genistein on cell viability, cell cycle arrest, DNA damage, telomere length, and telomerase expression following treatment. Using superarray, we have analysed gene expression patterns of selected signal transduction pathways in human tumour cells following drug treatment. There was a dose-dependent effect on the cell viability following drug treatments. Increased levels of DNA damage was detected in cells treated with curcumin which might have resulted in G2/M arrest and apoptosis. On the contrary, Genistein induced G2/M arrest without apparent increase in cell death or DNA damage. Both the drugs seem to have telomerase inhibitory function in the cancer cell lines studied which was accompanied by telomere shortening. Our data suggests that curcumin exhibits higher growth inhibitory effect in the cancer cells with long telomeres. Gene expression studies have revealed the down-regulation of cell cycle regulated genes and genes that involve in signalling pathways such as NFKB, MAP kinase, AKT, and TNF receptor superfamily in drug treated cells. Genes that regulate metastasis such as MMP1, 2 and NME1, 4 were also found to be suppressed after drug treatments. As telomerase is expressed in more than 90% of human tumours, telomerase inhibition is projected as an attractive target for anti-cancer therapy. We propose that curcumin and genistein may elicit their anti-cancer properties on the telomere-telomerase pathway thereby inducing DNA damage, cell cycle arrest and apoptosis. These results may have implications in cancer therapy by preventing recurrence of tumours.    *This research is supported by Academic Research Fund, Ministry of Education, Singapore.
Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial
Authors: F. B. Stehman, S. Ali, D. G. Gallup, H. Key
Journal: Journal of Clinical Oncology (2006)

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M 2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p &lt; 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p &lt; 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.
Semiquantitative histomorphometric analysis of myocardium following partial left ventriculectomy: 1‐year follow‐up
Authors: Jovan D. Vasiljević, Petar Otašević, Zoran B. Popović, Aleksandar N. Nešković, Radoslav Vidaković, Zoran V. Popović, Branislav Radovančević, O. Howard Frazier, Siniša Gradinac
Journal: European Journal of Heart Failure (2005)
Increased proximal tubular cell catalytic iron content
Authors: R A Zager, B A Schimpf, C R Bredl, C A Foerder
Journal: Journal of the American Society of Nephrology (1992)

Journal of the American Society of Nephrology : JASN 3(1):p 116-118, July 1992. | DOI: 10.1681/ASN.V31116
Abstract MP087: Relation of Risk Factor Profile at Baseline and 39-Year Follow-up to Peripheral Arterial Disease - - The Chicago Healthy Aging Study (CHAS)
Authors: Thanh Huyen T Vu, Kiang Liu, Mary M McDermott, Jeremiah Stamler, Donald M Lloyd-Jones, Daniel B Garside, Martha L Daviglus
Journal: Circulation (2012)

Background: Low burden of CVD risk factors (RF) at younger ages is associated with substantially reduced risk for future clinical CVD events. There is no information available regarding associations of long-term patterns in RF profile, from young adulthood to older age, with prevalence at older age of low ankle brachial index (ABI), a marker for peripheral arterial disease (PAD). Methods: Using data from the Chicago Healthy Aging Study (CHAS), we assessed associations of patterns in RF profile -- from baseline (1967-73) to follow-up (2007-10) -- with prevalence of PAD at follow-up (see Table for definitions of RFs and RF groups). ABI was calculated as the ratio of Doppler recorded systolic pressures in the lower and upper extremities, and categorized as follows: low ABI/PAD (ABI&lt;1.00) vs. normal (1.00 ≤ABI ≤1.40). Participants with an ABI &gt;1.40 (n=24) were excluded from the analysis. Results: The study sample consisted of 1,340 participants (27.8% women, 9.2% African Americans) ages 24-45 years, free of major ECG abnormalities and MI at baseline. After 39 years of follow-up, 15.5 percent of persons with no adverse baseline RF levels remained RF-free at follow-up (Group A). The prevalence of PAD was lowest in this Group A (3.7%) and highest (19.9% -- 5 times higher) in Group E, with ≥2 RFs at both baseline and follow-up (p-value &lt; .001). Likewise, with adjustment for baseline age, sex, ethnicity, education, and minor ECG abnormalities, the odds for PAD in Group A was lowest compared with other groups. Further, decrease in number of RFs from baseline to follow-up (Group C) was associated with lower likelihood for PAD compared to increase in number of RFs over time (Groups B and D) and to presence of ≥2 RFs at both baseline and follow-up (Group E). Conclusion: Long-term absence of risk factors is associated with lowest prevalence of PAD at 39 year follow-up. Greater risk factor burden in young adulthood and development of risk factors over decades were both associated with greater likelihood of PAD later in life.