tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Investigation of a novel small molecule furin inhibitor with regards pseudomonas aeruginosa exotoxin A-induced cytotoxicity in human airways
Authors: James Reihill, Brian Walker, Lorraine Martin
Journal: European Respiratory Journal (2014)

Background: Pseudomonas aeruginosa (PA) is a key pathogenic factor in several pulmonary conditions including COPD, CF and pneumonia. PA secretes a number of virulence factors including exotoxin A (EXA), a highly toxic product activated by the action of the pro-protein convertase furin, which contributes to mortality in patients and animal models. Within our laboratory we have recently developed a novel small molecule-based inhibitor of furin potentially relevant in this context.  Hypothesis: QUB-TL1 prevents EXA-induced airway epithelial cell (AEC) cytotoxicity as a consequence of furin inactivation.  Methods: Recombinant furin activity was performed by monitoring cleavage of a fluorogenic substrate (pERTKR-NHMec). Turnover of the same substrate was monitored upon addition to the apical surface of differentiated AECs to assess surface furin activity in the presence or absence of QUB-TL1. Cytotoxicity was assessed using a commercial LDH assay kit.  Results: QUB-TL1 inhibits recombinant and endogenous furin activity (detected at the apical surface of normal and CF AECs). Moreover EXA-induced epithelial cell cytotoxicity is significantly reduced (>80%) in the presence of QUB-TL1. Further studies demonstrated QUB-TL1 itself was non-toxic and cell impermeable thus affording a sustained duration of action at the airways surface whilst limiting off-target effects.  Conclusions: QUB-TL1 represents a novel cell impermeable inhibitor of furin that abrogates EXA-induced cytotoxicity in AECs thus may be of therapeutic value with regards PA lung infections.
Symptom clustering among patients visiting a supportive oncology clinic.
Authors: Kathryn C. Wrammert, Gwendolynn Harrell, Michael O'Neill, Anjali Grandhige, Danielle Moulia, Aynur Aktas
Journal: Journal of Clinical Oncology (2014)

188 Background: Multiple symptoms are common and often severe in patients with cancer. Identification of symptoms which cluster may serve to elucidate the pathophysiology of the disease and aid in symptom management. Our aim was to define symptom clusters occurring among cancer outpatients receiving chemotherapy. Methods: New and returning patients referred to a supportive oncology clinic (SOC) from our health system’s oncologists from November 2011 through May 2014 completed the Condensed Memorial Symptom Assessment Scale plus a sexual dysfunction structured assessment. Data were collected prospectively from 323 consecutive initial visits. Patients rated from 0-4 how bothersome 15 cancer symptoms were; symptoms were then graded as present (1+) or absent (0). Hierarchical cluster analysis with average linkage was used to identify symptom clusters. The absolute value of the correlation between symptoms was used as the measure of similarity between pairs of symptoms. A correlation of ≥0.6 was used to define the final clusters. A symptom cluster was defined as two or more symptoms that predictably occur together. Results: Three clusters were identified: 1. Psychological (worrying, feeling sad, feeling nervous); 2. Treatment-related (lack of energy, feeling drowsy, difficulty concentrating, dry mouth, constipation); 3. Gastrointestinal (weight loss, lack of appetite, nausea). Pain, difficulty sleeping, shortness of breath, and loss of interest did not cluster with any symptom. Gastrointestinal symptoms are important within the clusters. The prevalence of worrying, feeling sad, and feeling nervous did not cluster with lack of energy or difficulty in sleeping, nor pain with worrying or feeling sad. Conclusions: Three symptom clusters were identified as showing high absolute correlation: a psychological cluster, treatment-related cluster, and gastrointestinal cluster. Identifying symptom clusters may promote our understanding of the pathophysiology of cancer, help prioritize effective pharmacotherapies, and identify drugs likely to help more than one symptom.
Sequential estrogen receptor determinations from primary breast cancer and at relapse: Prognostic and therapeutic relevance
Authors: V. Spataro, K. Price, A. Goldhirsch, F. Cavalli, E. Simoncini, M. Castiglione, C.-M. Rudenstam, J. Collins, J. Lindtner, R.D. Gelber
Journal: Annals of Oncology (1992)
How American oncologists treat breast cancer: an assessment of the influence of clinical trials.
Authors: D Belanger, M Moore, I Tannock
Journal: Journal of Clinical Oncology (1991)

The present study was designed to assess the preferred methods of treatment of breast cancer by American oncologists, and the impact of clinical trials on their practice. We mailed 465 questionnaires to surgical, radiation, or medical oncologists. The questionnaire described five hypothetic patients with breast cancer, and respondents were asked to select their preferred treatment for each patient. For primary breast cancer, most physicians would offer the choice of local excision followed by radiation therapy or modified radical mastectomy. About 80% of physicians would prescribe adjuvant chemotherapy for a premenopausal woman with estrogen receptor-negative, axillary node negative breast cancer, and for a postmenopausal woman with estrogen receptor-negative, node-positive disease. This policy was favored by male and female physicians of each specialty. Almost all respondents would treat a young woman with inflammatory breast cancer with initial chemotherapy followed by radiation and/or surgery, and about 60% would recommend chemotherapy to a postmenopausal patient with estrogen receptor-negative disease and minimally symptomatic bone metastases. Clinical trials have compared treatment strategies that could be applied to patients described in our questionnaire. Preferred treatments for primary breast cancer, and for inflammatory breast cancer are supported by the results of clinical trials. Recommendation of adjuvant chemotherapy for node-negative breast cancer is not based on a consistent demonstration of improvement in survival, although randomized trials with short follow-up have shown delay to recurrence. Recommendation of adjuvant chemotherapy for a postmenopausal woman with node-positive breast cancer is contrary to the results of large randomized controlled trials (and to a meta-analysis), which have shown that this policy does not lead to improved survival. Our report suggests that even large randomized clinical trials may have a minimal impact on practice if their results run counter to belief in the value of the treatment.
Concurrent paclitaxel, carboplatin and radiotherapy (CMT) with subcutaneous amifostine in advanced squamous cell head and neck cancer (SCCHN): Preliminary results of a phase II study
Authors: A. Law, T. Kennedy, P. Pellitteri, D. Christie, E. Swartzentruber, C. Bettleyon, C. Thomas, J. Lewson, M. Halupa, O. Yumen
Journal: Journal of Clinical Oncology (2004)

5564 Background: CRT for stage III/IV SCCHN improves tumor control at the cost of increased toxicity. Radioprotector, amifostine, administered intravenously (iv) significantly reduced the incidence of ≥ grade 2 acute xerostomia. This interim analysis reports efficacy and subcutaneous (sc) amifostine effects on the incidence of acute treatment toxicities. Methods: Eligibility included previously untreated TNM stage III, IV SCCHN, ECOG PS 0–1, adequate organ function, and informed consent. All patients received a percutaneous endoscopic gastrostomy, and vigorous dental and nutritional support during therapy. Paclitaxel (40mg/m2) and Carboplatin (100mg/m2) were administered iv weekly for six weeks. Patients received amifostine as two, 250mg sc injection (2.5ml total) 30 minutes prior to daily radiotherapy (1.8 to 2.0 Gy/day). Radiotherapy was given daily five times a week to a total dose of 70–72 Gy. Diphenhydramine 25mg, dexamethasone 4mg, odanestron 8mg, and acetaminophen 1000mg were given 30mins prior to amifostine. Results: Of eighteen patients entered to date, thirteen have completed treatment and were evaluable. Mean age was 54 years. Primary sites are oropharynx (12), oral cavity (1). Grade 3 hematologic toxicities: neutropenia (0%), thrombocytopenia (8%), anemia (0%). Grade 3 non-hematologic toxicities: nausea (1%), mucositis (10%). The incidence of ≥ grade 2 xerostomia was 53%. Median accumulated radiotherapy dose to onset of xerostomia was 58 Gy. There was no grade 3 amifostine-associated cutaneous toxicity. All patients completed radiotherapy without treatment breaks. Eight patients (62%) had a complete clinical response (CR) and 5 (38%) had a partial response (PR). Total clinical response rate was 100%. Conclusions: Concurrent chemoradiation with daily sc amifostine proves feasible with high response rate. This approach is a well-tolerated outpatient treatment program. Subcutaneous amifostine offers convenience of administration and reduces the severity of acute radiotherapy and chemotherapy associated toxicities. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Medimmune Pharmaceutical Company
Complete 18FDG positron emission tomography (PET) response after induction chemotherapy (IC) is correlated with long survival in patients (pts) with locally advanced non-small cell lung cancer (LA NSCLC)
Authors: D. Schallier, H. Everaert, B. Neyns, N. Baelde, M. Meysman, C. Fontaine, J. De Grève
Journal: Journal of Clinical Oncology (2006)

17004 Background: PET and computerized axial tomography scan (CT) are complimentary tools in the diagnosis and treatment of pts with LA NSCLC. Recent data have shown that response to IC as determined with PET has a better prognostic relevance for long term outcome than CT (Hoekstra et al JCO 2005;23:33:8362–70). Methods: PET and chest CT were performed before and after 3 cycles of IC in pts with LA NSCLC (D. Schallier et al, Suppl JCO 2005;23:165:7285, 6915). Response was defined according to WHO and EORTC criteria for CT and PET respectively (complete response: CR; partial response: PR; stable disease: SD; progressive disease: PD). PET images corrected for attenuation were acquired in 3D on a Siemens Accel camera starting 60 minutes after administration of 307–606 MBq 18 FDG. The maximal standardized uptake value (SUV max ) within the tumor was measured and a SUV max value ≥2.5 was used as a cut off. PET responses were classified either as complete (resolution of the enhanced uptake within the tumor) or non-complete. For each subgroup, classified according to CT and PET response, time to progression (TTP) and survival (S) was calculated and analysed statistically according to Kaplan-Meier and log rank test. Results: 21 pts were eligible for the PET and CT confrontation. Characteristics: 14 male, 7 female; median age 70 y (39–78); median KS: 90 (80–100); stage III A: 9; stage III B: 12; T1,2,3,4: 4/3/7/7; N0,1,2,3: 4/1/11/5. Response: CT: 12 PR; 9 SD; PET: 6 CR, 9 PR, 5SD, 1PD. Nine/12 PR on CT were also CR (5) and PR (4) on PET. Median TTP was correlated significantly with PR and CR (versus SD and non-CR) on CT and PET respectively (288 versus 606 days, p = 0.045 for CT and 299 versus median not reached p = 0.024 for PET); with a median follow up of 19+ month, median S was not significantly correlated with PR on CT but was highly significantly correlated with CR on PET (439 days versus median not reached p = 0.005). Conclusions: Assessment of response to IC using CT or PET largely overlaps. PET appears to be a more ‘sensitive‘ tool to measure response. CR on PET provides a better accuracy for determination of long term outcome than CT. The present results corroborate previously published results. No significant financial relationships to disclose.
Porcine and Ovine Lymphosarcoma: A Review 2
Authors: D. E. Bostock, L. N. Owen
Journal: JNCI Journal of the National Cancer Institute (1973)

The incidence of lymphosarcoma at abattoirs in the United States and certain countries in Western Europe ranged from 3–25 per million swine and from <1–160 per million sheep. The figures from France for both species were variable. Incidence of lymphosarcoma, expressed as a percent of all condemnations for neoplasms in abattoirs in the United States and Great Britain was 23–66% for swine, and 21–41% for sheep. In swine the disease was seen mainly in young animals before maturity, but most lymphosarcomas in sheep occurred in adult or aged animals. The pathology was similar to that in the cow, dog, and other species. A herd of swine in Scotland showing evidence of a genetic factor in the trcnsmlsslen of spontaneous lymphosarcoma in young animals, and a flock of sheep with a high incidence of lymphosarcoma reported from Germany are discussed.
Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial
Authors: A. D. Ormerod, K. S. Thomas, F. E. Craig, E. Mitchell, N. Greenlaw, J. Norrie, J. M. Mason, S. Walton, G. A. Johnston, H. C. Williams
Journal: BMJ (2015)

<b>Objective</b> To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. <b>Design </b>Multicentre, parallel group, observer blind, randomised controlled trial. <b>Setting</b> 39 UK hospitals, recruiting from June 2009 to November 2012. <b>Participants</b> 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). <b>Intervention</b> Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. <b>Main outcome measures</b> The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). <b>Results</b> Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was −0.21 (1.00) cm<sup>2</sup>/day in the ciclosporin group compared with −0.14 (0.42) cm<sup>2</sup>/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm<sup>2</sup>/day, 95% confidence interval −0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. <b>Conclusion</b> Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. <b>Trial registration</b> Current Controlled Trials ISRCTN35898459.
Permanent mesh has “limited utility” for vaginal prolapse repair, review finds
Authors: Jacqui Wise
Journal: BMJ (2016)

A Cochrane systematic review has concluded that artificial mesh has some advantages over native tissue for the surgical treatment of vaginal prolapse but is associated with increased morbidity.1

Research published in the Cochrane Library showed that, while transvaginal permanent mesh probably reduces the risk that women will be aware of a prolapse when compared with tissue repair, the overall benefit was small. Permanent mesh was also associated with higher rates of reoperation for prolapse, stress urinary incontinence, and bladder injury during surgery.

A vaginal prolapse occurs when the walls of the vagina become weak and collapse inwards. It is common, affecting as many as half of women who have had children. Symptoms include pelvic heaviness, backache, and bladder, bowel, or sexual dysfunction.

The traditional method of repairing vaginal prolapse using native tissue is associated with …
Complete regression of eyeball metastasis secondary to non-small-cell lung cancer with intravitreal cisplatin and vinorelbin therapy
Authors: Magdalena Kostrzewska, Halina Batura-Gabryel, Michalina Nowak-Gabryel
Journal: European Respiratory Journal (2011)

Purpose: To report a case of a complete regression of intraocular metastasis secondary to non-small-cell lung cancer (NSCLC).

Methods: Retrospective case review of a 61-year-old female patient treated with intravitreal cisplatin and vinorelbin therapy for posterior segment of eyeballs metastases secondary to NSCLS. Best corrected visual acuity, fluorescein angiography and computed tomography with contrast intensification were compared during the 3-month treatment period.

Results: After the 4-rd cycle of chemiotherapy (intravitreal cisplatin and vinorelbin) the best corrected visual acuity had improved to 20/40 from 20/100 and 2 elevated choroidal masses in the superotemporal and inferotemporal quadrants of the right eyeball and 1 mass in the lower-inside quadrant of the left eyeball had completely disappeared.The retina and a retinal pigment epithelial layer were flattened.

Conclusion: Combining intravitreal cisplatin and vinorelbin could be the optimal treatment form for patients with intraocular metastasis of NSCLC.
Clinical and pharmacologic study of ADI-PEG20 in hepatocellular carcinoma
Authors: L. G. Feun, N. Savaraj, C. Wu, M. You, M. Wangpaichitr, A. Marini, D. Levi, J. Bomalaski, M. T. Kuo
Journal: Journal of Clinical Oncology (2008)

15584 Background: It has been reported that hepatocellular carcinoma (HCC) possess low levels of argininosuccinate synthetase (ASS), a key enzyme needed to synthesize arginine (Arg) from citrulline. Thus, Arg depletion using pegylated arginine deiminase (ADI-PEG20 from Polaris Inc.) results in tumor cell death. Clinical trials using ADI-PEG20 have shown antitumor activity in HCC (J.Gastro.Hep. 207:86- 91,2007). However, not all HCC lack ASS expression. In addition to a clinical trial of ADI-PEG20 in HCC, we have studied ASS expression in tumor samples. Methods: Eligibility criteria include: advanced, unresectable HCC with KPS>70. Treatment: Patients (pts) were treated with ADI-PEG20 at 160 IU/m2 i.m. weekly. CT/MRI scans were done every 2 months. ASS expression was performed by immunohistochemical staining as well as by real time RT-PCR(RPCR). RRT-PCR was performed using a set of ASS primer and GADPH primer which have similar efficiency of amplification. The ratio of GADPH and ASS was calculated. Normal human fibroblast (BJ-1) which express ASS and is resistant to ADI-PEG20 was used as positive control, and melanoma cell line which lack ASS expression was used as negative control. Results: 9 pts were treated. Median age was 72. 6 pts had prior chemo, 1 pt had RFA.Toxicity included mild fatigue and discomfort at injection site. No grade 3 or 4 toxicities occurred. 3 pts (33%) had prolonged time to tumor progression of 4 (+),17, and 28(+) months. One patient remains on treatment after 28 months. Five tumor samples were obtained for ASS study. The GADPH/ASS ratio ranged from 0.31 to 31, while BJ-1 which is resistant to ADI-PEG20 has a ratio of 6. ADI-PEG20 also induced autophagy in cell lines which possess low levels of ASS expression. Conclusions: Major clinical benefit with prolonged time to tumor progression and minor toxicity can be obtained in HCC pts with ADI-PEG20 therapy. The benefit is most likely related to autophagy in tumors which lack ASS expression. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Polaris Inc. Polaris Inc. Polaris Inc.
Detection of Tumor Antibodies in Patients With Gastrointestinal Carcinomas by a Solid-Phase Radioimmunoassay2
Authors: I. Berczi, L. S. McMorris, T. K. Thorlakson, R. H. Thorlakson, J. A. Kellen, A. H. Sehon
Journal: JNCI Journal of the National Cancer Institute (1979)

Metastatic tumors from livers of 5 patients with gastrointestinal carcinomas and from the liver of 1 patient with malignant breast carcinoma were extracted with 3 M KCl; similar extracts were prepared from normal human colon and liver and from human fetal gut. The extracts were depleted of serum globulins by passage through reverse immunoadsorbent columns consisting of rabbit antibodies to the F(ab)2 fragment of human IgG and were then coupled to CNBr-activated paper disks. These "antigen" disks were used in a radioimmunoassay, with the aid of 125I-labeled rabbit antihuman F(ab')2 antibodies for the assay of circulating tumor antibodies produced by cancer patients. Statistical evaluation of the results with plasma samples from 47 patients with colorectal carcinomas and from 7 patients with other gastrointestinal disorders (polyps, villous papilloma, diverticulitis, and Crohn's disease) indicated that a significant number of patients had antibodies to cross-reactive tumor antigen(s). The cross-reactive tumor antigen(s) involved in the reaction was not detected in extracts of the gastrointestinal tract from 12-week human fetuses and did not cross-react with carcinoembryonic antigen.
Simple and versatile synthetic polydopamine-based surface supports reprogramming of human somatic cells and long-term self-renewal of human pluripotent stem cells under defined conditions
Authors: Ping Zhou, Fujian Wu, Tiancheng Zhou, Xiujuan Cai, Siqi Zhang, Xiaohong Zhang, Qiuhong Li, Yongliang Li, Yunfei Zheng, Mengke Wang, Feng Lan, Guangjin Pan, Duanqing Pei, Shicheng Wei
Journal: Biomaterials (2016)