tbuckley/cabot-search huggingface dataset:
3,3’-Diindolylmethane cytostatic effects in human prostate cancer cells
Authors: Omar Vivar, Chia-Lei Lin, Gary Firestone, Leonard Bjeldanes
Journal: Cancer Research (2007)

4365   Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer deaths in American males. The rate of incidence of prostate cancer in Asian males is approximately one-tenth that of American males. However, this protection against prostate cancer is lost among Asian men who emigrate to the US, indicating an environmental rather than a genetic component in the prevention of this disease. The consumption of a diet rich in phytochemical-containing vegetables is one possible contributor to the decreased prostate cancer incidence observed in Asian men. 3,3’-Diindolylmethane is a promising anticancer agent derived from Brassica vegetables. In this study we characterized the effect of DIM on cell cycle regulation in both LNCaP and DU145 human prostate cancer cells. DIM has an antiproliferative effect on both LNCaP and DU145 cells, as it significantly inhibits [3H]thymidine incorporation. FACS analysis revealed a DIM mediated G1 cell cycle arrest. DIM strongly inhibited the expression of CDK2 and CDK4 protein and increased p27 protein expression in LNCaP and DU145 cells. DIM increased p27 transcription in both cell lines as shown by quantitative PCR. This DIM-mediated increase in p27 was found to be dependent on the Sp1 transcription factor. Our results indicate a novel cell cycle regulation pathway in which DIM modulates expression of CDK2, CDK4, and p27 leading to the growth arrest of human prostate cancer cells. The results of this study, along with previously published reports of the antiandrogenic activity of DIM, suggest a promising role for this dietary indole in the treatment of prostate cancer.
Abstract 14607: High Level of Plasma Endothelin-1 is a Predictor of 10-Year Mortality in a General Population: The Tanushimaru Study
Authors: Kanako Yokoi, Hisashi Adachi, Yuji Hirai, Mika Enomoto, Ako Fukami, Maki Otsuka, Takanobu Miyamoto, Yasuki Nanjo, Kuniko Yoshikawa, Eishi Esaki, Eita Kumagai, Kinuka Ogata, Akiko Kasahara, Eri Tsukagawa, Kyoko Ohbu, Tsutomu Imaizumi
Journal: Circulation (2011)

OBJECTIVE Endothelin-1 (ET-1) is a potent vasoconstrictor derived from the endothelium. ET-1 is suggested to be associated with high blood pressure, pulmonary hypertension, and renal or heart failu...
Adjuvant chemotherapy alone versus chemoradiation after curative resection for pancreatic cancer : feasibility results of a randomised EORTC/FFCD/GERCOR phase II/III study (40013/22012/0304)
Authors: J. Van Laethem, E. Van Cutsem, P. Hammel, F. Mornex, D. Azria, G. Van Tienhoven, M. Peeters, M. Praet, V. Budach, K. Haustermans
Journal: Journal of Clinical Oncology (2008)

4514 Background: The role of adjuvant therapy in resectable pancreatic cancer is debated. This randomised phase II intergroup study evaluated the feasibility and rate of completion for a modern gemcitabine-based chemoradiotherapy regimen after R0 resection of pancreatic head cancer. Methods: Patients were randomised within 8 weeks after surgery to receive either gemcitabine 1,000 mg/m2 weekly Q3 over 30 min then one week rest (control arm) or gemcitabine 1,000 mg/m2 for two cycles followed by weekly gemcitabine 300 mg/m2 with concurrent radiation of 50.4 Gy given in 28 fractions of 1.8 Gy (experimental arm). The primary endpoints of the phase II study were full completion of treatment and tolerability. Continuation of the trial into phase III with an overall survival primary endpoint was contingent on excluding a treatment completion rate ≤60% AND a rate of grade 4 haematological or GI toxicity ≥40% using a one step Bryant & Day phase II design. Results: Between September 2004 and January 2007, 90 patients were enrolled. Median follow-up was 12.3 months. Treatment arms were balanced in terms of patient and tumour characteristics. Five patients were ineligible in the control arm. The relative median gemcitabine dose intensities were 97.4% in the control arm and 93.4% in the experimental arm, with dose reductions in 38.5% and 22.4% of patients, respectively. In the experimental arm, combined radiation and gemcitabine was delivered to 30 of 45 patients (66.7%) but not given to 11 because of refusal, rapid progression, postop complications, or post- gem toxicity. Radiotherapy treatment details have not been submitted for the other four treated patients. Grade 4 toxicity was low, with 0% and 2.2% in the control and experimental arms, respectively. Treatment was completed per protocol by 86.7 % and 73.3 % (80% CI 63.1–81.9%) of patients in the control and experimental arms, respectively. In the whole series, one year overall survival was 79.4% (95% CI: 66.1–87.9) and median DFS was 10.9 months. Conclusions: Modern gemcitabine-based chemoradiotherapy is feasible and well-tolerated in a multicenter setting. A phase III continuation of the study requiring 400 additional patients is in preparation. No significant financial relationships to disclose.
Predicting non-sentinel lymph node involvement in breast cancer patients
Authors: H. E. Kohrt, R. A. Olshen, W. H. Goodson, R. V. Rouse, L. Bailey, V. Philben, F. M. Dirbas, F. E. Stockdale, R. W. Carlson, S. S. Jeffrey
Journal: Journal of Clinical Oncology (2006)

531 Background: Current convention is to perform a completion axillary lymph node dissection (ALND) for invasive breast cancer (BC) patients (pts) with positive sentinel lymph node(s) (+SLN), even though &lt;50% will have non-sentinel lymph node metastasis (+NSLN). Our goal was to develop and compare predictive models of NSLN status among +SLN pts to identify for whom completion ALND may be omitted. Methods: We constructed 3 models by recursive partitioning with receiver-operating-characteristic curves (RP-ROC), boosted classification and regression trees (CART), and a multivariate logistic regression (MLR) informed by CART. Models were developed using a multi-institutional database of 1,040 BC pts who underwent SLN biopsy and completion ALND at academic or community hospitals as part of a prospective, consented study. Accuracies were compared to the Memorial Sloan-Kettering Breast Cancer Nomogram (Nomogram). Results: 976 BC pts had evaluable SLNs and 285 had +SLNs; 101(35.4%) +SLN pts had +NSLNs. Tumor size, lymphovascular invasion (LVI), and SLN metastasis size were the best predictors of risk (multivariate P-values&lt;0.001) of +NSLN. 39 of 156 +SLN pts (25%) with T1 tumors had +NSLNs vs. 62 of 129 (48%) with T2/T3 tumors. 73.7% with LVI vs 19.5% without LVI had +NSLNs. 4.7% of pts with isolated tumor cells, 42% with micrometastasis and 71% with macrometastasis in SLN had +NSLNs. MLR informed by CART identified 2 highly predictive variables, the LVI × size of SLN metastasis [OR 4.73(3.11–7.20, 95%CI), P&lt;0.001] and tumor size × size of SLN metastasis [OR 1.18(1.10–1.26, 95%CI), P&lt;0.001]. While RP-ROC and boosted CART stratified pts into low-risk (4.3%-9.9%), moderate-risk (33.3%-42.9%), and high-risk (62.2%-93%) groups, MLR predicted NSLN status with accuracy superior to RP-ROC, boosted CART, and the Nomogram: 83.3%, 76.7%, 67.7%, and 76.7%, respectively, after 10-fold cross validation. The Nomogram’s sensitivity was significantly inferior to those of RP-ROC, boosted CART, and MLR: 53.8%, 78.8%, 78.2%, and 78.0%, respectively. Conclusions: In pts with +SLNs, interactions between clinicopathologic characteristics are highly informative in predicting risk of +NSLN. However, neither our methods nor the Nomogram achieved sufficient accuracy to recommend a change in current clinical practice. No significant financial relationships to disclose.
A 26-year-old woman with respiratory decompensation in the immediate postpartum period at Mount Sinai Medical Center in New York City
Authors: Daniel R Bunker, Klaus T Meinhof, Robert J Hiensch, Olivia Ghaw, Christian D Becker
Journal: Thorax (2015)

A 26-year-old previously healthy woman developed sudden-onset hypoxaemic respiratory failure 3 days post partum. During pregnancy, the patient had displayed haematuria (26–50 red blood cells/high-power field on urine dipstick) and proteinuria (30 mg/dL on urine dipstick), which at the time was not further investigated. The pregnancy and vaginal delivery were otherwise uncomplicated. On the morning of planned discharge from the maternity ward, the patient developed sudden dyspnoea, tachypnoea, tachycardia and severe hypoxaemia (PaO2 of 48 mm Hg on room air) accompanied by 5 mL of bright red haemoptysis. Chest auscultation was normal. ECG showed sinus tachycardia with an S1Q3T3 pattern and urgent bedside echocardiogram showed evidence of right heart strain.

Respiratory insufficiency in the peripartum period has many potential causes, including PE, amniotic fluid embolism, pulmonary oedema due to tocolytic therapy and peripartum cardiomyopathy. Venous thromboembolism (VTE) is approximately 80 times more common in the first week post partum when compared with the general population1 and PE is a leading cause of maternal mortality in the developed world (whereas postpartum haemorrhage is the most common cause of death in the developing world2). Haemoptysis in the setting of PE occurs in about 5% of patients, and represents pulmonary infarction.3 Given the acute onset of symptoms and echocardiographic findings, PE is the initial concern for this patient.

Unfractionated heparin infusion was started. Shortly thereafter, the patient endorsed worsening dyspnoea and coughed up approximately 100 mL of bright red blood. Her heparin infusion was discontinued, and she was emergently intubated for hypoxaemia. Adequate oxygenation on the mechanical ventilator was difficult to maintain despite frequent endotracheal suctioning, use of high positive end-expiratory pressure and fraction of inspired oxygen (FiO2), initiation of neuromuscular blockade and frequent manual recruitment manoeuvres. Chest X-ray (CXR) showed diffuse, predominantly central opacities (figure 1 …
Preliminary results of a phase II study to evaluate gefitinib combined with docetaxel and cisplatin in patients with recurrent and/or metastatic squamous-cell carcinoma of the head and neck
Authors: J. Belón, A. Irigoyen, I. Rodríguez, Y. Escobar, J. L. Alonso, P. Pastor, J. Valdivia, A. Concha, J. Nuevo, H. Bovio
Journal: Journal of Clinical Oncology (2005)

5563 Background: Docetaxel and cisplatin (D/C) [75 mg/m2 each iv] combination therapy for squamous-cell carcinoma of the head and neck (SCCHN) yields response rates (RRs) of 30–40% and is relatively well tolerated. This study has evaluated the combination of gefitinib (IRESSA) and D/C in patients (pts) with SCCHN. Methods: Pts with histologically confirmed recurrent and/or metastatic SCCHN (≥1 unidimensionally measurable lesion by RECIST, WHO performance status (PS) <2, aged <70 years) received gefitinib 250 mg/day and D/C (75 mg/m2 each iv, every 3 weeks; maximum 6 cycles). Pts with clinical benefit continued gefitinib following completion of combination therapy. Neoadjuvant pretreatment with C-based chemotherapy ≥6 months previously or prior radiotherapy was allowed. Adverse events (AEs) were assessed by NCI-CTC (V3). Results: To date, 17/23 enrolled pts are eligible: median age, 55 years (range 31–69); male/female, 15/2; WHO PS 0/1, 11/6; metastatic sites 1/2–3/>3, 9/3/5 (38.8% lesions); median number D/C cycles, 4 (range 1–6); median duration gefitinib treatment, 71 days (range 7–244). 16/17 pts were evaluable for efficacy: 6 (37.5%) complete responses (CR) and 4 (25.0%) partial responses (PR), giving an RR of 62.5% (95% CI 35.4–84.8). Disease control rate (DCR) [CR + PR + stable disease] was 75% (95% CI 47.6–92.7). Median progression-free survival (PFS) was 5.1 months (95% CI 2.0–7.1). All 17 pts were assessed for safety. Grade 3/4 AEs were: neutropenia, 41.2% (including febrile neutropenia, 23.5%); anemia, 17.7% (secondary to D/C; 1 withdrawal); asthenia, 11.8%; diarrhea, vomiting, anorexia, and leukopenia, all 5.9%. Pts with ≥1 dose reduction: 52.9% (D), 58.8% (C). One pt died (septic shock/febrile neutropenia) 1 week after start of therapy. Conclusions: Gefitinib in combination with D/C has demonstrated encouraging RR and DCR in SCCHN. PFS of 5.1 months is interesting given that the overall survival of pts with recurrent and/or metastatic SCCHN is usually 6 months. The triplet combination did not cause more hematologic AEs than would be expected using D/C alone. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Developing a framework for palliative interventions in respiratory services in Ireland: One year into an action research project
Authors: Bettina Korn, Patricia White, Rory O'Donnell, Caitriona Corcoran, Kay Kealy, Marie Lynch, Liam O'Siorain
Journal: European Respiratory Journal (2011)

Background: Traditionally, palliative care services have centred on the needs of patients with malignant disease and there is little evidence of the integration of palliative care into disease-specific services in Ireland. The purpose of this research is to devise, implement and evaluate palliative care responses for people with advanced respiratory disease.

Methods: An action research methodology has been adopted for this multi-site research. This approach provides the opportunity for collaboration, reflection and exploring ways of improving service delivery. It incorporates both qualitative and quantitative methodologies and includes an expert focus group, survey of palliative care education needs, interviews with patients and families and retrospective chart reviews.

Results: To date, the initial planning and action cycles have started. The project outcomes and potential barriers have been identified through an expert focus group. Ongoing retrospective chart reviews highlight the low level of referrals to specialist palliative care. Results from the quantitative survey showed a lack of understanding of what palliative care entails, with 93% of respiratory hospital staff interested in attending palliative care education. Other actions include the establishment of multi-disciplinary, multi-site team meetings to improve patient care.

Conclusions: The reactive and reflective nature of action research has been advantageous in bringing about change in a demanding health care system. This project is developing and evaluating a palliative care model of support, intervention and referral pathways for people with advanced respiratory disease.
Factors affecting survival in pancreatic carcinoma: Analysis from a oncology unit of a general hospital in Peru
Authors: P. Pimentel, B. E. Beltran, L. Riva, R. Reategui, K. Portugal, R. Del Castillo
Journal: Journal of Clinical Oncology (2007)

15184 Background: Pancreatic carcinoma (PC) is one of the most devasting neoplasm , usually diagnosed in advanced stage with a poor outcome . We present the experience in a Medical Oncology Unit in a National General Hospital, analysing the risk factors for survival in PC. Methods: This is a retrospective study with data collected on 224 patients with PC in all stages between 1999 and 2004. Only 82 patients were included because the rest had clinical and radiological diagnosis without histological studies. Survival was calculated using the Kaplan-Meier method. Clinical, surgical and histopathological records were examined by univariate and multivariate analysis to identify the independent prognostic predictors of survival. Results: All of patients had a confirmed hystopathologic diagnosis of PC. Median age was 69 years ( 33–87), 38/82 (46%) were women; 65/82 (79%) had tumor localized in pancreas head and 22/82 (26%) were stage I /II . 60/80 ( 73%) had advanced stages III/IV. Only 19/82 ( 23%) had Whipple surgery with curative intent. On diagnosis Performance status(PS). 2- 4 was present in 56% (46) .For different reasons only 16/82 received treatment based in gemcitabine. Median overall survival for all patients was 5.4 months, with 1 year survival of 32% .On univariate analysis, P.S. ( p=0.077), Whipple surgery with curative intent (p=0.026), Gemcitabine treatment (p=0.002) and CEA ( p=0.002) significantly influence survival. On multivariate analysis, only P.S (p&lt; 0.05), Gemcitabine based treatment ( p=0.005) and CEA ( p= 0.045) independently influence survival. Conclusions: In this retrospective analysis we identified performance status, CEA and Gemcitabine based treatments as independent prognostic factors that influence survival in PC, adressing the role of standar gemcitabine regimens in the treatment of advanced PC and the need of continue research for improve the outcome of this challenging disease. No significant financial relationships to disclose.
First results of a phase III multicenter randomized controlled trial of intensity modulated (IMRT) versus conventional radiotherapy (RT) in head and neck cancer (PARSPORT: ISRCTN48243537)
Authors: C. Nutting, R. A'Hern, M. S. Rogers, M. A. Sydenham, F. Adab, K. Harrington, S. Jefferies, C. Scrase, B. K. Yap, E. Hall
Journal: Journal of Clinical Oncology (2009)

LBA6006 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]
Preliminary results of an escalating dose phase I clinical trial of the anti-EGFR monoclonal antibody nimotuzumab in combination with external radiotherapy in patients diagnosed with stage IIb, III or IV non-small cell lung cancer unsuitable for radical therapy
Authors: D. G. Bebb, A. M. Brade, C. Smith, S. Rorke, I. Sherman
Journal: Journal of Clinical Oncology (2008)

3037 Background: EGFR is associated with poorer outcome in non-small cell lung cancer (NSCLC). Nimotuzumab, a humanized monoclonal antibody directed against the extracellular domain of human EGFR1, does not exhibit the typical skin and GI toxicity seen with this class of agents. Here we outline the preliminary results of a phase I trial of this agent given with palliative radiation in patients with NSCLC. Methods: Eligible patients (age >18 years; stage IIB, III, or IV NSCLC; unsuitable for radical radiation or chemo-radiation; measurable disease within the radiation field) received an escalating dose of nimotuzumab (100, 200, 400mg) as a weekly 30 min IV infusion weeks 1–8, 2 to 6 hrs after radiation (30 Gy 10 fractions, Mon-Fri). If response or disease stability was observed, nimotuzumab was continued every other week from week 10 until progression or toxicity. Results: Arm 1 (100mg): 6 patients (age 60–81; median 76) stage IIIA - 2; IIIB - 3; IV - 1 were enrolled. 4 PR and two SD were observed. Median survival is 43.5 weeks. All progressed, five died. One patient is still alive at 84 weeks. Two SAEs reported, neither attributable to Nimotuzumab. Arm 2 (200mg): 7 patients (age 59–86; median 66) stages IIIB - 2; IV - 5 have been enrolled: 3 PR and 4 SD were observed. Five progressed, three died of disease. One SAE was not attributable to Nimotuzumab. Arm 3 (400mg): 5 patients (age 46–75; median 65) stages IIIB-2; IV-3 have been enrolled: 2 PR have been observed to date. Conclusions: Nimotuzumab administered concurrently with radiation is well tolerated at all three doses in NSCLC patients and is feasible in NSCLC patients unsuitable for radical treatment. Substantial radiological responses and 100% disease control rate have been seen. The absence of side effects and rash makes it therapeutically attractive. Updated results will be presented at the congress. Treatment Arm Nimotuzumab dose Number of Patients Stage IIIA/IIIB/IV Response PR/SD/PD Grade III/IV Rash Median Overall Survival (weeks) Arm 1 100 mg 6 2 / 3 / 1 4 / 2 / 0 0 43.5 Arm 2 200 mg 7 0 / 2 / 5 3 / 4 / 0 0 NR Arm 3 300 mg 5 0 / 2 / 3 2 / 3 / 0 0 NR NR: Not Reached No significant financial relationships to disclose.
The art and science of predicting postrevascularization improvement in left ventricular (LV) function in patients with severely depressed LV function**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Marcelo F Di Carli, Rory Hachamovitch, Daniel S Berman
Journal: Journal of the American College of Cardiology (2002)
Selective inhibition of MMP-14 inhibits tumor growth, invasion and angiogenesis
Authors: L. Devy, S. Nicholson, A. Muruganandam, L. Naa, N. Yanamandra, C. Pazmany, D. Rank, C. Tenhoor, P. Henderikx, D. Dransfield
Journal: Journal of Clinical Oncology (2008)

14022 Background: Improved selectivity towards specific MMPs is an attractive non-cytotoxic approach to cancer therapy. Very few selective MMP inhibitors have been developed that allow a pharmacological assessment of targeting specific MMPs. MMP-14 is a membrane-bound zinc-endopeptidase that drives the pericellular proteolysis that leads to tumor cell invasion. It does this directly by degrading extracellular matrix components and activating zymogens such as proMMP-2. Methods: To examine the contribution of this protease to tumor growth, we used DX-2400, a selective human MMP-14 antibody obtained by phage display. Results: This antibody displays potent anti-invasive and anti-angiogenic activity in vitro and inhibits the proliferation and angiogenesis of human tumors in preclinical models, decreasing their metastatic spread. Conclusions: Our studies have pharmacologically validated the role of MMP-14 in tumor growth and demonstrate the potential of a selective MMP-14 inhibitor for the treatment of solid tumors. No significant financial relationships to disclose.