tbuckley/cabot-search huggingface dataset:
Waterpipe smoking in Lebanese women: A lower prevalence but a higher risk of dependence
Authors: Pascale Salameh, Georges Khayat, Mirna Waked
Journal: European Respiratory Journal (2011)

Introduction: Waterpipe smoking has gained in popularity among Lebanese women. Our objective was to evaluate whether nicotine dependence is higher in smoking women compared with men.

Methods: Data were taken from a cross-sectional study on Lebanese residents aged 40 years and above. After an oral informed consent, subjects answered a questionnaire, including smoking history, cigarette and waterpipe dependence using validated dependence questionnaires (Fagerstrom for cigarettes and LWDS-11 for waterpipe).

Results: 1066 males and 1134 females were interviewed; respectively, 58.7% and 42.9% of them had ever smoked cigarettes, while 6.9% versus 6.7% had ever smoked waterpipe (p<0.001). Similar results were found for actual and previous smokers. However, when looking at dependence, patterns differed between genders: 57.5% vs 49.1% in cigarette smokers (p=0.041), 35.9% vs 51.6% in waterpipe smokers (p=0.076), and 67.9% vs 43.6% in mixed smokers. These results were confirmed by dependence dose-effect relationship (p=0.05 for trend) and multivariate analysis (ORa=2.28). The main components of waterpipe dependence in women were positive and negative reinforcement (p<0.05), but not nicotine dependence or psychological craving. In female waterpipe smokers, a higher prevalence of respiratory disease and symptoms were found.

Discussion and conclusion: Since tobacco dependence seems highly associated with tobacco related diseases, waterpipe smoking women could be at a higher risk of disease; they should be considered as real smokers, and receive particular attention during tobacco related health education and in smoking cessation treatments.
PWE-155 The effect of excluding neoadjuvant chemotherapy on survival from locally advanced oesophageal or oesophagogastric junctional (ogj) cancer
Authors: JR O'Neill, E Kennedy, V Save, B Langdale-Brown, S Paterson-Brown
Journal: Gut (2015)

<h3>Introduction</h3> Patients clinically staged with &gt; T2 or node positive (&gt;cT2/cN+) oesophageal or OGJ cancer are routinely considered for neoadjuvant chemotherapy prior to attempted curative resection (NA). Patients with cardiovascular comorbidity are often precluded from NA and the effect on survival in a contemporary setting is not clear. <h3>Method</h3> Single centre retrospective study of all patients undergoing attempted curative therapy for &gt;cT2/cN+ mid or lower oesophageal or OGJ adenocarcinoma or squamous cell carcinoma diagnosed between 2001 and 2013. Uni and multivariable survival analyses were performed using a prospectively-maintained audit database. <h3>Results</h3> A total of 371 patients were included and 289 (78%) commenced NA comprising predominantly 2 cycles of cisplatin and 5-fluorouracil (n = 264; 91%) with 274 (95%) undergoing subsequent resection. Patients undergoing surgery alone (S) were significantly older (mean = 8 years, p &lt; 0.001) but were well matched with patients undergoing NA for clinical stage, gender and histology. Based on intention to treat, NA was associated with a significantly improved median overall survival compared to S (29 months compared to 21 months; P = 0.008). Recurrence-free survival did not, however, differ between NA and S (p = 0.585). The 90 day in-hospital mortality rate was higher in S compared to NA (10% vs. 3%; P = 0.011), likely reflecting the increased comorbidity of these patients. When patients dying in hospital within 90 post-operative days were excluded, the overall survival benefit of NA over S was reduced to a median of 2.7 months (p = 0.04). Pathological tumour size, differentiation, pT, pN and R stage were associated with survival (all P &lt; 0.01) but did not differ significantly between patients undergoing NA or S suggesting a limited down-staging effect of NA. To assess histological response to chemotherapy, the Mandard tumour regression grade (TRG) was determined, blinded to outcome, in a subset of 111 patients undergoing NA. Only 21 patients (19%) exhibited a histological response to NA (TRG I-III) and TRG was not associated with survival (P = 0.08). <h3>Conclusion</h3> Resection carries a significantly higher perioperative mortality risk in patients with &gt;cT2/cN+ oesophageal or OGJ cancer and comorbidity precluding neoadjuvant therapy. In clinically stage-matched patients, neoadjuvant chemotherapy was associated with a significant survival benefit over surgery alone. A low histological response rate to chemotherapy was noted and in those patients surviving to discharge the overall survival benefit of NA was limited to a median of &lt;3 months. More effective therapies are needed. <h3>Disclosure of interest</h3> None Declared.
GPs in UK follow lung cancer guidelines less closely than in other countries, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

GPs in the United Kingdom adhere less closely to lung cancer guidelines than those working in other countries but show similar or better adherence to guidelines on colorectal cancer, a study of six similar countries has found.1

Many countries have cancer guidelines to support GPs in deciding when to refer patients or investigate symptoms further, recognising their central role in achieving earlier diagnosis as part of improving outcomes with most cancers. The study set out to explore what actions GPs in different countries took to possible cancer symptoms and …
Prevalence and characterization of the insomnia syndrome in an outpatient oncology clinic
Authors: E. E. Prommer
Journal: Journal of Clinical Oncology (2006)

18612 Background: Insomnia is an often overlooked symptom. One potential reason for this neglect is that insomnia is viewed as a normal and temporary reaction to the cancer diagnosis or treatment. Patients themselves may fail to report their sleep difficulties to their physicians for similar reasons. Previous work in understanding insomnia has been limited by the lack of an operational definition of the insomnia syndrome, small sample size and varied instruments for symptom detection. Hence, the proportion of cancer patients meeting diagnostic criteria for the insomnia syndrome is not well known. Recently the diagnosis of the insomnia syndrome has been redefined using a combination of criteria derived from the International Classification of Sleep Disorders and the DSM-IV. The criteria includes)difficulty in initiating and/or maintaining sleep, whereby sleep-onset latency and/or wake after sleep onset is greater than 30 minutes; sleep efficiency (ratio of total sleep time to total time spent in bed) lower than 85%; difficulties occurring at least 3 nights per week; difficulties occurring for at least 6 months; and difficulties causing marked distress or significant impairment in daytime functioning (eg, fatigue, disturbed mood, performance deficits). Methods: 100 consecutive oncology patients were surveyed using the above criteria for the insomnia syndrome. Symptom assessment was also included. Results: The incidence of the insomnia syndrome seems to correspond to previously reported incidences.Patient have more problems staying asleep than going to sleep. Patients may have dramatic inversions of their sleep/wake cycle yet feel that they do not have insomnia. Pain is the most commonly associated symptom associated with insomnia. Conclusions: There is a great need for better tools to asssess the symptom of insomnia. Focusing on specific characteristics of insomnia and distinguishing the insomnia syndrome versus the symptom of insomnia is an effective way establish if there is a need for specific therapy. The addition of symptom assessment further improves the characterisation insomnia. Characteristics of insomnia experienced by the patient may help direct specific treatment modalities. Pain is a frequently associated symptom with insomnia. No significant financial relationships to disclose.
Chronious: A new wearable monitoring system for COPD patients
Authors: Leonardo Govoni, Fabio Ciancitto, Teresa Renda, Francesca Peroli, Monica Picariello, Antonio Corrado, Raffaele L. Dellaca
Journal: European Respiratory Journal (2011)

CHRONIOUS is a FP7 European Community project which also includes a new wearable platform for home monitoring of people suffering from chronic diseases.  The wearable system is composed of a shirt made of washable stretch-material into which are sewn 4 ECG electrodes, two bands for respiratory inductive plethismography (RIP) and a reflectance pulseoximeter. The data coming from the sensors are collected and transmitted via wireless connection by the Data Handler, a microcontroller-based acquisition system. To evaluate accuracy and usability of this device, we studied 9 COPD patients (70.8±6.6 years, FEV1 45.1±9%pred) during 1 hour in the seated and 1hour in the supine positions. Patients were breathing spontaneously and data were collected continuously. At the beginning and at the end of each hour flow at the mouth was also measured by a spirometer (Sibelmed, Barcelona, Spain), heart rate (HR) and oxygen saturation (SpO2) by a finger clip pulseoximeter (NONIN, Plymouth, Minnesota, USA) for 10 minutes, to get reference values for comparison. The first measurement for each subject with the spirometer was used to calibrate the RIP using Sackner algorithm, J.Appl.Physiol 1989; 66(1): 410-420.  The evaluation of accuracy was focused on the following parameters: HR, SpO2 and tidal volume (VT). Linear regression analysis on the data acquired resulted as follows: HR r 2 =0.99, m=1.00, q=-0.31, SpO2 r 2 =0.92, m=1.29, q=-27.54, VT r 2 =0.89, m=1.15, q=-0.072. From the signals of the ECG electrodes it was possible to identify PQRST waves within the 3 derivations.  The new wearable monitoring system provided reliable measurements of HR, SpO2, VT and ECG in both supine and seated posture. RIP calibration was still consistent after 1 hour of use.
Genetic variation in CYP19A1 and interleukin-6 and aromatase inhibitor-associated arthralgia in breast cancer survivors.
Authors: J. Mao, I. Su, R. Feng, K. Desai, M. Horn, D. Chan, A. DeMichele
Journal: Journal of Clinical Oncology (2010)

526 Background: Aromatase inhibitor-associated arthralgia (AIAA) is a major symptom in breast cancer survivors (BCS) but its underlying mechanism remains unclear. Because estrogen metabolism and inflammation play important roles in arthritis and are modulated by AIs, we hypothesized that functional genetic polymorphisms in CYP19A1 (aromatase) and Interleukin-6 (IL-6) might be associated with patient-reported AAIA and severity of arthralgia. Methods: We performed a cross-sectional study of postmenopausal stage 0-III BCS receiving adjuvant AI therapy. Patient-reported arthralgia attributed to AI (AIAA) was the primary outcome; severity and interference of arthralgia was measured by Modified Brief Pain Inventory. Genotyping for IL-6 -174G>C (rs1800795), -572G > C (rs1800796) and -597G > A (rs1800797) was done using SNPlex; IL-6 - 373AnTn and CYP19A1 (TTTA)n (rs60271534) repeats were directly sequenced from blood samples. Logistic regression was performed to examine associations between outcomes, genetic variants and possible confounders. Results: Among 390 Caucasian participants with a mean age of 62 (SD 10), 50.8% reported AI as a source of their current arthralgia. Women carrying at least one CYP19A1 7-repeat allele had greater odds of AIAA (adjusted odds ratio [AOR], 1.70, 95% confidence interval [CI], 1.03-1.76, p = 0.03), while women carrying at least one 8-repeat allele had lower odds of AIAA (AOR, 0.40, 95% CI, 0.20-0.79, p = 0.008) after adjusting for time since last menstrual period, type of menopause, education, prior chemotherapy and BMI. The presence of at least one copy of the IL-6 haplotype (-597A, -572C, -373[8A/12T], -174C) was associated with increased pain severity (beta = 2.8, 95% CI, 0.99-4.61, p=0.003 while the presence of the haplotype [-597A, -572G, -373[8A/12T], -174C was associated with decreased pain interference (beta = -0.309, 95% CI. -0.59 to -0.02, p = 0.03, in a model including the same covariates. Conclusions: Genetic variants in CYP19A1 and IL-6 are associated with patient reported-attribution of AIAA, arthralgia severity and interference. These data provide support for a role for host estrogen metabolism and inflammation in the etiology of AAIA. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth
Phase II trial of paclitaxel and topotecan with granulocyte colony-stimulating factor support in stage IV breast cancer.
Authors: G F Fleming, J W Kugler, P C Hoffman, R Ansari, J D Bitran, A Klepsch, D Malone, A A Fasanmade, M J Ratain, E E Vokes
Journal: Journal of Clinical Oncology (1998)

PURPOSE This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topotecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and topotecan were obtained during cycle 1 to correlate pharmacokinetic parameters with toxicity. PATIENTS AND METHODS Paclitaxel was administered intravenously (i.v.) at 230 mg/m2 over 3 hours on day 1 followed by topotecan 1.0 mg/m2 i.v. over 30 minutes on days 1 to 5. Patients received an abbreviated premedication regimen that consisted of ranitidine 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethasone, all administered i.v. 30 minutes before paclitaxel. Granulocyte colony-stimulating factor (GCSF) was administered at 5 micrograms/kg/d subcutaneously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/microL. Plasma paclitaxel and topotecan concentrations were assessed during the first cycle using limited-sampling strategies. RESULTS Seventeen patients were treated. The majority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) was observed. Nadir AGC correlated strongly with both duration of paclitaxel levels greater than 0.05 mumol/L and maximum concentration (Cmax) of paclitaxel. CONCLUSION This regimen does not produce a response rate superior to that expected with single-agent paclitaxel at doses that do not require growth factor support.
Hypofractionation, not rapid-fractionation.
Authors: C R Thomas, S Milito, A T Turrisi
Journal: Journal of Clinical Oncology (1997)

AbstractOctober 01, 1997 Share on Hypofractionation, not rapid-fractionation.Authors: C R Thomas Jr, S Milito, and A T Turrisi 3rdAuthors Info & AffiliationsPublication: Journal of Clinical OncologyVolume 15, Number 10https://doi.org/10.1200/JCO.1997.15.10.3291 Get Access
Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation.
Authors: J D Rowley
Journal: Journal of Clinical Oncology (1988)

The 14;18 translocation [t(14;18)] is the most common chromosome abnormality noted in the non-Hodgkin's lymphomas (NHL). Although the translocation is seen in various histologic subtypes, it is most commonly associated with the follicular lymphomas, especially the small-cleaved cell (FSC) and mixed-cell (FM) subtypes. The translocation breakpoint has been cloned and DNA probes from the junction on chromosome 18 can now be used to detect the genetic consequences of the translocation in tumors with few dividing cells. This will allow a more precise classification of this subset of lymphomas and should lead to better understanding of the biology of this category of lymphomas. Finally, these insights will help in the development of more effective and possibly less toxic therapy.
Abstract 117: RhoC Regulates VEGF-induced Signaling in Endothelial Cells
Authors: Luke Hoeppner, Sutapa Sinha, Ying Wang, Resham Bhattacharya, Shamit Dutta, Xun Gong, Victoria Bedell, Sandip Suresh, Chang zoon Chun, Ramani Ramchandran, Stephen Ekker, Debabrata Mukhopadhyay
Journal: Circulation Research (2014)

Vascular permeability factor/vascular endothelial growth factor A (VEGF) is a central regulator of angiogenesis and potently promotes vascular permeability. VEGF plays a key role in the pathologies of heart disease, stroke, and cancer. Therefore, understanding the molecular regulation of VEGF signaling is an important pursuit. Rho GTPase proteins play various roles in vasculogenesis and angiogenesis. While the functions of RhoA and RhoB in these processes have been well defined, little is known about the role of RhoC in VEGF-mediated signaling in endothelial cells and vascular development. Here, we describe how RhoC modulates VEGF signaling to regulate endothelial cell proliferation, migration and permeability. We found VEGF stimulation activates RhoC in human umbilical vein endothelial cells (HUVECs), which was completely blocked after VEGF receptor 2 (VEGFR-2) knockdown indicating that VEGF activates RhoC through VEGFR-2 signaling. Interestingly, RhoC knockdown delayed the degradation of VEGFR-2 compared to control siRNA treated HUVECs, thus implicating RhoC in VEGFR-2 trafficking. In light of our results suggesting VEGF activates RhoC through VEGFR-2, we sought to determine whether RhoC regulates vascular permeability through the VEGFR-2/phospholipase Cγ (PLCγ) /Ca 2+ /eNOS cascade. We found RhoC knockdown in VEGF-stimulated HUVECs significantly increased PLC-γ1 phosphorylation at tyrosine 783, promoted basal and VEGF-stimulated eNOS phophorylation at serine 1177, and increased calcium flux compared with control siRNA transfected HUVECs. Taken together, our findings suggest RhoC negatively regulates VEGF-induced vascular permeability. We confirmed this finding through a VEGF-inducible zebrafish model of vascular permeability by observing significantly greater vascular permeability in RhoC morpholino (MO)-injected zebrafish than control MO-injected zebrafish. Furthermore, we showed that RhoC promotes endothelial cell proliferation and negatively regulates endothelial cell migration. Our data suggests a scenario in which RhoC promotes proliferation by upregulating -catenin in a Wnt signaling-independent manner, which in turn, promotes Cyclin D1 expression and subsequently drives cell cycle progression.
Phase I and Pharmacokinetic Study of Farnesyl Protein Transferase Inhibitor R115777 in Advanced Cancer
Authors: J. Zujewski, I.D. Horak, C.J. Bol, R. Woestenborghs, C. Bowden, D.W. End, V.K. Piotrovsky, J. Chiao, R.T. Belly, A. Todd, W.C. Kopp, D.R. Kohler, C. Chow, M. Noone, F.T. Hakim, G. Larkin, R.E. Gress, R.B. Nussenblatt, A.B. Kremer, K.H. Cowan
Journal: Journal of Clinical Oncology (2000)

To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks.Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1.Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months.R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1, 000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing.
Radiotherapy dose and fractionation in Kaposi's sarcoma
Authors: Z. Ozgen, H. Ozyurt, S. Ozden, S. Bilge, N. Ozseker, A. Marti, A. Mayadagli
Journal: Journal of Clinical Oncology (2008)

21523 Background: We aimed to investigate the clinical responses of local classical Kaposi's sarkoma (CKS) treated with different radiotherapy regimes. Methods: Fifteen patients with the diagnosis of CKS treated with radiotherapy were analyzed retrospectively. Total 19 lesions were irradiated. 13 (%68) were localized in lower extremity and 6 (%32) were in the other parts of the body. Depending on the tumor size, location and the depth, three different radiotherapy regimes were implemented. The total dose of 8 Gy was delivered to 14 (%71) of lesions either with 6–9 MeV electron or photon (Co60) beams in one fraction. 3 (%16) of the lesions were treated with 12Gy (6 Gy/day, in two days), and 2 (%11) of them treated with 20 Gy in 5 fractions. Boluses were adopted to improve the radiation distribution over the skin of lower extremities during treatment with Co60. All lesions were treated locally with a 2–3-cm safety margins. Results: The median of age was 70 (range: 41–80). The male: female ratio was 11/4. Median follow-up was 27 months. The lesions irradiated with 8 Gy were responded completely in a rate of %77. The complete response rates (CRR) with 12 Gy and 20 Gy were found to be %66 and %100, respectively. There was no CRR difference between the photon and electron beam treatment. CRR and overall survival rates were not statically different for the all three radiotherapy regimes. The tolerance to the treatment was high and the side effects were similar in all groups. Conclusions: Although the response rates seem to be high, the consideration of treatment results in a wide perspective is not satisfactory. Therefore plannig the new treatment regimes helps to increase the response rates of current treatment modalities. No significant financial relationships to disclose.