tbuckley/cabot-search huggingface dataset:
Pathologic stages IA and IIA Hodgkin's disease: results of treatment with radiotherapy alone (1968-1980).
Authors: M A Cornbleet, U Vitolo, J E Ultmann, H M Golomb, D Oleske, M L Griem, D J Ferguson, J B Miller
Journal: Journal of Clinical Oncology (1985)

Between Jan 1, 1968, and Dec 31, 1980, 108 previously untreated patients with Hodgkin's disease pathologic stages (PSs) IA (29 patients) and IIA (79 patients) initially received radiotherapy alone. One postoperative death (due to pulmonary embolus) (0.9%) occurred, with one serious complication (0.9%). Between 1968 and 1973, patients were randomized to receive either involved field radiation treatment (RTIF) or extended field radiation treatment (RTEF). Since 1973 all patients have received RTEF, 4,000 cGy in four to five weeks, with a median follow-up of 7.4 years. Complete remission (CR) was achieved in 102 patients (94.4%), with no significant difference according to treatment or stage. Of the complete responders, 25 patients relapsed: 5/15 RTIF and 20/87 RTEF (P = .6). Twenty-one of 25 relapsing patients achieved a second CR. Disease free survival rates at five and ten years constituted: PS IA, 78.6% for both; PS IIA, 74.8% and 73.1% (P = .6); RTEF, 76.7% for both; RTIF, 73.3% and 66.7% (P = .7). Eighteen patients have died: eight of recurrent lymphoma, two of pulmonary embolus, one each of myocardial infarction, pulmonary fibrosis, and acute nonlymphocytic leukemia (ANLL) (following salvage chemotherapy), and one of diffuse histiocytic lymphoma (DHL). Four patients died in remission of unrelated causes. Actuarial survival rates at five and ten years constituted: PS IA, 95.7% and 72.4%; PS IIA, 89.6% and 81.4% (P = .3); RTIF, 93.7% for both; RTEF, 90.7% and 71.2% (P = .2). Age, sex, number of sites, and mediastinal involvement did not influence the outcome. Acute toxicity was modest and more frequent among those receiving RTEF (P = .08). Chronic toxicity (onset more than 30 days after completion of treatment) was identified in 16 patients: 1/16 RTIF; 15/92 RTEF (P = .5). Three patients developed a second malignancy: one carcinoma of the cervix in situ; one ANLL (following salvage chemotherapy); and one DHL of the stomach. At least 75% of patients with PS IA and IIA Hodgkin's disease were cured by radiation alone, with a risk of secondary malignancy following radiation alone of 0.9%. Since the majority of relapsing patients were successfully salvaged by chemotherapy, radiation alone appears to be the initial treatment of choice in this group of patients.
A phase II, multicenter study of bendamustine HCl plus rituximab in relapsed indolent B-cell and mantle-cell non-Hodgkin’s lymphoma (NHL)
Authors: M. E. Williams, P. Cohen, A. Tulpule, R. H. Van der Jagt, J. A. Herst, A. Bessudo, B. Lemieux, L. S. Schwartzberg, J. W. Oliver, K. S. Robinson
Journal: Journal of Clinical Oncology (2006)

7528 Background: Bendamustine HCl, a novel alkylating hybrid agent, has single-agent activity in multiple hematologic and solid tumors. In vitro data have demonstrated the multifunctional mechanisms of bendamustine by which cell death occurs via both apoptosis and mitotic catastrophe. Bendamustine has shown activity in NHL cell lines that are refractory to conventional alkylator chemotherapies. The combination of bendamustine and rituximab has shown a synergistic effect on NHL cells. The efficacy and safety of bendamustine in combination with rituximab in patients with relapsed NHL were evaluated. Methods: This phase II, multicenter study enrolled adult patients with relapsed, indolent, rituximab-sensitive B-cell or mantle-cell NHL. Patients received rituximab 375 mg/m 2 IV on day 1 and bendamustine 90 mg/m 2 IV on days 2 and 3 of a 28-day cycle for 4 to 6 cycles. An additional dose of rituximab 375 mg/m 2 IV was given 1 week prior to the first cycle of bendamustine and 4 weeks after the last cycle. Results: The intent-to-treat population included 67 patients (57% males; median age, 60 years) with indolent NHL (81%) or mantle-cell NHL (16%) (data not available [3%]). A total of 81% of patients had stage III/IV disease. Patients had relapsed from a median of 1 prior therapy; 37% had prior treatment with rituximab. In the 57 evaluable patients, the overall objective response rate (ORR) was 87% (complete response [CR], 33%). The ORR for the 9 evaluable mantle-cell NHL patients was 89% (CR, 33%). For all patients, the median duration of response and progression-free survival had not been reached after a median follow-up of 3.7 months (range, 0–14.2 months). This therapy was well tolerated. Most commonly reported nonhematologic toxicities were grade 1/2 gastrointestinal events, with nausea being the greatest (38%). The primary grade 3/4 hematologic toxicity was neutropenia (29%), with 1 event of sepsis. Conclusions: Bendamustine in combination with rituximab was well tolerated and produced high response rates in patients with relapsed indolent and mantle-cell NHL. These results suggest bendamustine in combination with rituximab provides a potential benefit over single-agent rituximab therapy. [Table: see text]
Antibodies to Pharmacologically Active Molecules: Specificities and Some Applications of Antiprostaglandins
Authors: Lawrence Levine
Journal: Pharmacological Reviews (1973)

Because of the low concentrations of these prostaglandin compounds in tissues and fluids and because of the large number of closely related structures, analytical procedures for their quantitative and qualitative estimation are not adequate or are restricted to only a few laboratories. Specific antibodies can now quantitate the following compounds: PGF2α, PGF1α, 15-keto-PGF2α, 13, 14-dihydro-15-keto-PGF2α, and 13,14-dihydro-PGF2α. For some analyses, the samples can be assayed and identified with only one antiserum. For other analyses, a combination of antisera must be used for positive identification. Antisera directed toward PGB, which indirectly measure POE or PGA or both, i.e., POE or PGA can be converted to PGB by treatment with NaOH, are also available; it is hoped that soon antisera that can measure the PGE metabolites will be produced.

Knowledge of the levels of prostaglandins, prostaglandin metabolites, and activities of the prostaglandin synthetic and metabolic enzymes in tissues and biological fluids would help to establish a physiological role(s) for the prostaglandin system.
Everolimus Plus Hormonotherapy (Ht) Induces Survival Gain in Late Metastatic Breast Cancer (Mbc) After Progression: Could this Line Be Better Than a Late New Chemotherapy (Ct) Line?
Authors: M. Pouget, E. Planchat, C. Abrial, I. van Praagh, M. Arbre, F. Kwiatkowski, P. Dubray-Longeras, H. Devaud, Q. Wang-Lopez, H. Mahammedi, X. Durando, P. Chollet, M. Mouret-Reynier
Journal: Annals of Oncology (2014)
The evaluation of BRCA1 and ERCC1 expression as predictors of platinum response in ovarian cancer
Authors: J. I. Weberpals, K. Clark-Knowles, A. O'Brien, O. Antoniouk, K. Garbuio, J. Dimitroulakos
Journal: Journal of Clinical Oncology (2008)

5587 Background: Platinum resistance is a contributing factor to the poor prognosis in advanced epithelial ovarian cancer (OC). Elevated levels of the DNA repair proteins Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) have been associated with platinum resistance in various malignancies, including lung and breast. A comparative analysis of both BRCA1 and ERCC1 expression as predictors of platinum response in OC has not yet been done. Methods: Clinicopathologic data was collected retrospectively on 41 patients who underwent surgical staging and adjuvant platinum-based chemotherapy at The Ottawa Hospital between 1997 and 2005. RNA was extracted from frozen tissue in the Ottawa Ovarian Tumor Bank and relative BRCA1 and ERCC1 mRNA expression was determined by real-time PCR. Gene expression for 22 patients was compared using the Oligo GEArray DNA Damage Signaling Pathway Microarray. OC cell lines with known BRCA1 and ERCC1 expression were exposed to chemotherapy drugs in combination with molecular inhibitors and cell viability was compared by MTT assay. Results: Response to chemotherapy, time to progression (TTP), and overall survival (OS) were reported using RECIST criteria. Linear regression analyses revealed that in optimally debulked patients, low BRCA1 expression was a stronger predictor of a longer TTP (P=0.017, r2=0.41) and OS (P=0.003, r2=0.56). Patients were classified into two groups according to relative high and low BRCA1 mRNA expression. The median OS by Kaplan-Meier estimates for BRCA1-low was 51 months, and for BRCA1-high was 33 months, illustrating that patients with low tumor expression of BRCA1 have a more favorable survival, P=0.033, HR=2.34, 95%CI[0.21–1.09]. Microarray analysis revealed a similar pattern of select DNA repair gene expression for patients with low BRCA1 expression that corresponded to patients with a more favorable survival. The addition of an HDAC inhibitor to platinum drugs, but not to taxol, induced synergistic cytotoxicity in the A2780s cell line that expressed relatively high levels of BRCA1 and ERCC1. Conclusions: Low BRCA1 and ERCC1 expression correlate with improved survival in patients with advanced OC and BRCA1 may be a more clinically useful predictive marker of response to platinum chemotherapy. No significant financial relationships to disclose.
Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection
Authors: Daniel C. Beachler, Aimée R. Kreimer, Mark Schiffman, Rolando Herrero, Sholom Wacholder, Ana Cecilia Rodriguez, Douglas R. Lowy, Carolina Porras, John T. Schiller, Wim Quint, Silvia Jimenez, Mahboobeh Safaeian, Linda Struijk, John Schussler, Allan Hildesheim, Paula Gonzalez
Journal: JNCI Journal of the National Cancer Institute (2015)

Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known. Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided. The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001). This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.
Management of psychotropic drugs during pregnancy
Authors: Margaret S Chisolm, Jennifer L Payne
Journal: BMJ (2016)

Psychiatric conditions (including substance misuse disorders) are serious, potentially life threatening illnesses that can be successfully treated by psychotropic drugs, even during pregnancy. Because few rigorously designed prospective studies have examined the safety of these drugs during pregnancy, the default clinical recommendation has been to discontinue them, especially during the first trimester. However, in the past decade, as more evidence has accumulated, it seems that most psychotropic drugs are relatively safe to use in pregnancy and that not using them when indicated for serious psychiatric illness poses a greater risk to both mother and child, including tragic outcomes like suicide and infanticide. This review presents an up to date and careful examination of the most rigorous scientific studies on the effects of psychotropic drugs in pregnancy. The lack of evidence in several areas means that definite conclusions cannot be made about the risks and benefits of all psychotropic drug use in pregnancy.
Lack of late toxicity in patients treated with cisplatin-containing combination chemotherapy for metastatic testicular cancer.
Authors: M Boyer, D Raghavan, P J Harris, J Lietch, A Bleasel, J C Walsh, S Anderson, C S Tsang
Journal: Journal of Clinical Oncology (1990)

To date, the prevalence and nature of the late toxicity of cisplatin-based combination chemotherapy for advanced testicular cancer has been poorly documented. Thirty men with a median age of 35 years (range, 23 to 63), who had undergone such treatment were assessed with detailed investigation to determine the type and frequency of chronic toxicity. The median follow-up from the time of commencement of chemotherapy was 75 months (range, 48 to 126). The most common late toxic effects were high tone hearing loss in 23 men (77%) and electrophysiological evidence of peripheral nerve damage in 15 (50%). Both the hearing and nerve abnormalities were predominantly asymptomatic. In addition, elevation of serum cholesterol, noted in 20 patients (67%), was significant (P = .014) when compared with a control population. Hyperuricemia was present in nine patients (30%). Only one patient, with other risk factors (smoking, family history), had evidence of ischaemic heart disease while 20% (all with a smoking history) had a diminished single breath diffusing capacity for carbon monoxide (DLCO). Cisplatin-based chemotherapy is relatively free of major long-term side effects and should not be withheld for fear of late toxicity.
PROPEL: Results of the pivotal, multicenter, phase II study of pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL)
Authors: O. O'Connor, B. Pro, L. Pinter-Brown, L. Popplewell, N. Bartlett, M. Lechowicz, K. Savage, B. Coiffier, M. Saunders, S. Horwitz
Journal: Journal of Clinical Oncology (2009)

8561 Background: Pralatrexate is a novel targeted antifolate designed to accumulate preferentially in cancer cells. PROPEL, a pivotal phase 2, non-randomized, open-label, international study, is the largest prospective study in patients (pts) with relapsed or refractory PTCL. Methods: Pts received 30 mg/m 2 of pralatrexate intravenously weekly for 6 of 7 weeks, supplemented with B 12 and folic acid. Primary endpoint = objective response rate (ORR); secondary endpoints = response duration, progression-free survival, and overall survival. Eligibility criteria: histologically confirmed PTCL, disease progression after ≥ 1 prior treatment, and ECOG performance status ≤ 2. Pathology was confirmed by independent central review, response to therapy was assessed by independent central review using International Workshop Criteria (IWC). Results: 115 pts were enrolled, 109 were evaluable for efficacy. 111 treated pts included 76 males (68%) and 35 females (32%). Pts had failed a median of 3 prior regimens and thus were heavily pre-treated. 78 pts (70%) failed CHOP, 18 (16%) had previous autologous stem cell transplant. 25% of pts never responded to any prior therapy; 53% did not respond to last prior therapy. The majority (59 pts, 53%) had PTCL not-otherwise specified. The ORR by central review was 27% (n = 29). 11 pts (10% overall, 38% of responders) had a complete response (CR), 18 pts (17%) had a partial response (PR), and 23 (21%) had stable disease. ORR by investigators assessment was 39% (n = 42). The median duration of response cannot be accurately estimated at this time, though responses of &gt; 1 year have been observed. 69% of responses were after just 1 cycle. 5 responding pts went on to transplant. The most frequent Grade (Gr) 3–4 adverse events were mucosal inflammation (Gr 3 = 17%, Gr 4 = 4%) and thrombocytopenia (Gr 3 = 14%, Gr 4 = 19%). Conclusions: The results of PROPEL show that pralatrexate exhibits substantial activity in pts with relapsed or refractory PTCL, as assessed by a rigorous central review, with durable CRs /PRs, irrespective of the amount of prior therapy. [Table: see text]
CCL18 as marker of disease progression in systemic sclerosis
Authors: Jonas Schupp, Gabriela Riemekasten, Corina Kollert, Benedikt Jäger, Joachim Müller-Quernheim, Antje Prasse
Journal: European Respiratory Journal (2012)

Background:   Lung fibrosis is the most common cause of death in systemic sclerosis. CCL18 is associated with poor prognosis and disease deterioration in fibrotic lung diseases. The prognostic relevance in patients with interstitial lung disease in systemic sclerosis was shown by Tiev et al. (Tiev KP, Eur Respir J 2011 38:1355-1360).    Objectives:   To evaluate the role of CCL18 in patients with or without interstitial lung disease in systemic sclerosis.    Methods:   We measured the chemokine CCL18 in sera of 126 patients with progressive systemic sclerosis by ELISA, as well as lung function testing at baseline and every 6 months during follow-up. Pulmonary fibrosis was detected by HR-CT. We computed ROC- and Kaplan-Meier-curves and Cox proportional hazards models to analyze the influence of CCL18 on time to disease progression, defined as decline of the predicted FVC -10 % or death.    Results:   Patients with serum CCL18 concentrations above 140 ng/ml suffered from a significantly higher chance of disease progression (p    Conclusion:   CCL18 predicts disease progression of the lung involvement in patients with systemic sclerosis, independent of age, gender or baseline FVC, especially in patients without any evidence of lung fibrosis. CCL18 in sera might therefore be a tool to identify patients who will suffer from lung function deteroriation in the future and to guide therapeutical interventions in these patients.
Anticoagulant Effects of Synthetic Retinoids Mediated Via Different Receptors on Human Leukemia and Umbilical Vein Endothelial Cells
Authors: Misako Shibakura, Takatoshi Koyama, Takako Saito, Koichi Shudo, Nobuyuki Miyasaka, Ryuichi Kamiyama, Shinsaku Hirosawa
Journal: Blood (1997)
Smoking prevalence and its effect on lung function and soluble adhesion molecules levels in medical students
Authors: Ekaterina Makarova, Nikolay Menkov, Natalia Lubavina, Monica Shonia, Galina Varvarina, Victor Novikov
Journal: European Respiratory Journal (2011)

The purpose  of the study was to investigate the prevalence of tobacco smoking in students of Nizhny Novgorod Medical State Academy (Russia) and its effects on lung function and serum levels of soluble intercellular adhesion molecules (sICAM) sCD50 (sICAM-3) and sCD54 (sICAM-3).   Materials and methods:  Data were collected between 2009-2010 using a structured questionnaire on 149 medical students (42 males and 107 females), aged 20±1 years. The questionnaire included questions regarding personal characteristics, dependence and quitting smoking, consequences on health. Lung function tests were performed in 31 students (16 smokers and 15 non-smokers). The serum concentrations of sICAM-1 and -3 were determined using ELISA-method.   Results:  There were 18,8% of current smokers (from which 46% females); an index of duration of smoking was 3,0±1,9 pack/years. The early age of the beginning of smoking (of 9-14 years) has been registered. Means of FVC and PEF in smoking students were significantly lower than in non-smoking (81,1±5,9 vs 87,5±9,1% and 75±9,7 vs 84,9+7,6%, respectively). The serum levels of sCD50 and sCD54 in smoker (140,4±57,7 U/l and 78,9±29,7U/l, respectively) were significantly reduced compared with non-smoker (242,4+54,4 U/l and 172,7+51,5 U/l, respectively).   Conclusion:  These results indicate high level of tobacco use among medical students in this Russian city, especially among females. The reduced levels of FVC and PEF, as well as of sICAM-1 and -3 in smoker compared with non-smoker were revealed. Decrease in levels of sCD50 and sCD54 in smokers might be due to inhibitory effect of smoking on intercellular adhesion.
Effectiveness and Safety of Tegafur-Gimeracil-Oteracil Potassium(Ts-1) for Metastatic Breast Cancer
Authors: Kazuo Ishizuna, Makoto Kojima, Jun Ninomiya, Miho Kawashima, Miwako Nozaki, Retsu Shimada, Haruhiko Aikawa, Hidetsugu Yamagishi, Toshihisa Ogawa, Masatoshi Oya
Journal: Annals of Oncology (2014)
Reduction in Corticosteroid Use Among Patients Receiving Omalizumab in Real World Settings: A Systematic Literature Review of Non-Randomized Studies
Authors: Reynold A. Panettieri, Jonathan Corren, Susan Gabriel, Kimberly M. Ruiz, Bethany Sawchyn, Jennifer A. Colby, Meryl Mendelson
Journal: Journal of Allergy and Clinical Immunology (2016)
Clinical results of shaped beam radiosurgery and X-ray assisted patient positioning for prostate cancer
Authors: G. Soete, D. Verellen, D. Michielsen, F. Keuppens, G. Storme
Journal: Journal of Clinical Oncology (2005)

4702 Background: Cure rates of localized prostate cancer after radical prostatectomy, brachytherapy or external beam radiotherapy are comparable. Therefore the choice between these treatments largely depends upon their potential toxicity. We analyzed side effects and biochemical control of patients with localized prostate cancer treated with shaped beam radiosurgery (SBRS). The Novalis Body (BrainLAB AG., Heimstetten, Germany) system was used for patient positioning. Methods: Between May 2000 and October 2002, 100 patients (90% stage T1-T2) were treated. Median follow-up is 12m (range 3–29m). Depending upon the risk group the patient belonged to, the isocenter dose was either 70 Gy or 78 Gy in 2 Gy/fraction. Positioning prior to each treatment was performed using Novalis Body. The system is based on automated image fusion between digitally reconstructed radiographs from the planning CT and orthogonal X-ray images and was shown to be superior to conventional positioning. Treatment was done by SBRS using the m3 mMLC micromultileaf collimator. Toxicity was scored using RTOG criteria and biochemical failure was defined according to the ASTRO consensus panel definition. Results: Acute grade 0/1/2 gastro-intestinal (GI) toxicity was seen in 88/12/0 patients. Acute grade 0/1/2 genito-urinary toxicity was seen in 46/39/15 patients. No late GI side effects have occurred thus far. One patient experienced late radiation cystitis with hematuria, which was controlled by coagulation. Two-year biochemical control after SBRS was 96%. Conclusions: Prostate cancer patients treated by SBRS therapy and using X-ray assisted positioning show a low rate of early side effects. Further follow-up is needed to confirm the low rate of late side effects and the favorable biochemical control. No significant financial relationships to disclose.