tbuckley/cabot-search huggingface dataset:
A method to identify the best candidates for multiorgan resection among patients with T4 gastric carcinoma
Authors: L. F. Onate-Ocana, V. Aiello-Crocifoglio, D. Gallardo-Rincón, R. Brom-Valladares, M. Becker, R. Herrera-Goepfert, J. F. Carrillo, A. Beltrán-Ortega
Journal: Journal of Clinical Oncology (2007)

15141 Background: Background: Indications for gastrectomy in T4 gastric carcinoma (GC) remain controversial. Our aim was to develop a method for the selection of patients with T4 GC with best chances to receive a benefit from multiorgan resection. Methods: We analyzed a cohort of patients with T4 GC treated from January 1987 to December 2005. Relevant clinical, pathological and therapeutic variables were recorded. Prognostic factors associated with survival were defined by Kaplan-Meier and Cox’s methods. Factors associated to surgical morbidity were selected by Logistic Regression analysis. Results: 718 patients were included (gastrectomy performed in 169). Presence of metastasis (Hazard ratio=1.68 [HR], 95% confidence interval [CI] 1.19–2.36), albumin &lt;3 g/dL plus lymphocytes &lt;1,000 cells/mm3 (HR=2.9, 95% CI 1.8–4.6), presence of ascites (HR=2.1, 95% CI 1.06–4.2), 50 years old or more (HR=1.37, 95% CI 1.02–1.8) and surgical resection not possible (HR=2.6, 95% CI 1.7–4.1) define patients with the worst survival (model p=0.00001). Including only patients who underwent surgical resection, presence of metastases, extent of gastrectomy, serum albumin level and R1-R2 residual were determinants of poor survival (model p=0.00001). Surgical morbidity and mortality were 39% and 10.7%, respectively. The significant factor associated to surgical morbidity were extent of gastrectomy, age, serum albumin and lymphocyte count (model p=0.0001). Conclusion: The decision to perform a curative gastrectomy in patients with T4 GC must be balanced between the chances of long-term survival and the chances to survive a potentially fatal operation. Abscence of lymph node and distant metastases, adequate blood lymphocyte count and normal serum albumin levels could help to select those patients with high probability to receive benefit from multiorgan resection as long as R0 resection is performed. The role of preoperative chemoradiation or perioperative chemotherapy in T4 GC must be defined. No significant financial relationships to disclose.
Is the polymerase chain reaction or cure of Helicobacter pylori infection of help in the differential diagnosis of early gastric mucosa-associated lymphatic tissue lymphoma?
Authors: B Rudolph, E Bayerdörffer, M Ritter, S Müller, C Thiede, B Neubauer, N Lehn, E Seifert, P Otto, R Hatz, M Stolte, A Neubauer
Journal: Journal of Clinical Oncology (1997)

PURPOSE The differential diagnosis of early gastric mucosa-associated lymphatic tissue (MALT) lymphoma based on Helicobacter pylori gastritis may be difficult when lymphoepithelial lesions are not detected. The aim of the present study was to investigate the question whether the polymerase chain reaction (PCR) or cure of H pylori infection may be of help in this respect. PATIENTS AND METHODS Twenty patients with suspected low-grade gastric MALT lymphomas were treated in a double-blinded, randomized, crossover trial with 2,250 mg of either amoxicillin or placebo, both in combination with omeprazole, for 14 days with the aim to cure H pylori infection. PCR was performed using primers specific for the CDR3 region to detect monoclonal B cells. RESULTS In five of 20 patients, MALT lymphomas were finally diagnosed. Three of these five patients went into complete remission, while two were referred to surgery. In the 15 patients with gastritis, complete regression was observed in all cases. With respect to PCR, monoclonal bands were detected in all four of the analyzed lymphoma patients before histology showed lymphoma. In addition, monoclonal bands were found in three patients with gastritis. In the patients with gastritis and monoclonal PCR, complete regression took longer as compared with the remaining 12 patients with polyclonal PCR and gastritis (P = .0209). Successful H pylori eradication was associated with earlier diagnosis of the MALT lymphoma (P = .0237). CONCLUSION CDR3-PCR may be of help in the differential diagnosis of early gastric MALT lymphoma. Furthermore, H pylori eradication may lead to earlier diagnosis.
Oral terbutaline alone and in combination with theophylline: dose, plasma concentration, and effect in long-term treatment of bronchial asthma
Authors: G Stalenheim, B Lindstrom, G Lonnerholm
Journal: European Respiratory Journal (1989)

Oral terbutaline, in gradually increasing doses from 2.5 to 10 mg three times daily (t.i.d.) was administered to 12 patients with chronic bronchial asthma. There was a linear relationship between dose and steady-state plasma concentrations in individual patients, but the plasma levels varied fourfold between patients taking similar doses. The need for other medication tended to decrease, and the symptom score, peak expiratory flow rate (PEFR) and forced expiratory volume in one second (FEV1) improved significantly during the treatment, with a roughly linear dose-effect relationship for the doses 2.5, 5 and 7.5 mg t.i.d. An increase in the dose from 7.5 to 10 mg did not improve PEFR and FEV1 any further. Side-effects were generally few and mild. Oral theophylline 200 mg t.i.d. added to terbutaline 10 mg t.i.d. brought about a further improvement in pulmonary function without adding any troublesome side-effects. Our data indicate that there is little to gain by prescribing terbutaline doses higher than 7.5 mg t.i.d. Instead, theophylline might be added, since this combination seems to have a favourable therapeutic index.
Preliminary results of a randomized trial of adjuvant doxorubicin for sarcomas: lack of apparent difference between treatment groups.
Authors: K Antman, H Suit, D Amato, J Corson, W Wood, K Proppe, D Harmon, R Carey, J Greenberger, R Blum
Journal: Journal of Clinical Oncology (1984)

Forty-two patients with localized intermediate and high-grade sarcoma were randomized after optimal primary treatment to receive five cycles of adjuvant doxorubicin 90 mg/m2 every three weeks (20 patients) or observation (22 patients). Patients were stratified for grade, size, extent of surgical margin, and soft tissue versus other sarcomas. Groups appeared balanced for histology and superficial versus deep lesions. Eight patients (19%) have died. Follow-up times range from two to 69 months (median, 16 months). Two patients receiving doxorubicin (10%) developed cardiotoxicity presenting as pulmonary edema. One patient returned to normal activity on digoxin and diuretics; the other (age, 28 years) died of intractable failure and arrhythmias after four weeks. While a nonsignificant difference in local control, metastasis-free survival, disease-free survival, and survival was observed for extremity lesions, the advantage may be outweighed by the risk of cardiotoxicity. Seventy-six percent of the control patients with extremity lesions remain disease free. Because control patients do well, a very large study is required to define the role of adjuvant doxorubicin.
Participation in a randomized phase III study (evaluating the role of adjuvant docetaxel in high-risk breast cancer patients) improves treatment strategies and individual patient care in recruiting centers: The ADEBAR-Trial
Authors: W. Janni, H. Sommer, B. Rack, D. Steinfeld, D. Augustin, M. Heinrigs, K. Gauger, M. Kiechle, N. Harbeck, K. Friese
Journal: Journal of Clinical Oncology (2005)

789 Background: Substantial improvements in the treatment of breast cancer were made possible by a large number of clinical trials. While the scientific impact of clinical trials is undisputable, the individual patient’s benefit of participating in a clinical trial remains controversial. On the basis of a phase III trial, we evaluated its impact on current treatment practice. Methods: ADEBAR is a multicenter phase III trial to evaluate whether breast cancer patients with > 3 axillary lymph node metastases benefit from a sequential anthracycline-docetaxel regimen (E90C-D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21d, followed by 4 cycles docetaxel [D] 100mg/m2 q21d) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m2 d 1+8, 5-FU 500mg/m2 d 1+8 and C 75 mg/m2 d 1–14, q4w). A questionnaire was sent to all participating centers (comprising large hospital departments and community oncology practices) in order to evaluate, in which extent their participation in the ADEBAR-study had changed their treatment strategies and patient care. Results: 49.5% (n=98) of the questionnaires were returned. In the year preceding ADEBAR, 63.2% of the study centers had not entered high-risk breast cancer patients into a clinical trial. Outside of the ADEBAR protocol, 44.2% of high-risk patients would have routinely received less effective chemotherapy, such as CMF or EC/CMF. 41,1% of the study centers reported that participating in the trial had increased their intensity of patient care and 80.0% noted an improvement in their professional knowledge by being part of an investigators’ network. One third of the centers (31.8%) reported substantial improvements in the overall quality of their patient care. Conclusions: Our results indicate that, by participating in clinical trials, treatment strategies and individual patient care may be improved recruiting centers. Moreover, our excellent recruitment demonstrates that modern trials have the potential of motivating additional clinical centers to participate in clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis, Pfizer, sanofi-aventis
Extra hour of sitting each day is linked to 22% higher odds of type 2 diabetes
Authors: Michael McCarthy
Journal: BMJ (2016)

Each extra hour of sitting or reclining each day was associated with 22% higher odds of having type 2 diabetes, a study published in Diabetologia has found.1

Researchers at Maastricht University in the Netherlands analysed data on 2497 participants from the Maastricht study who had been asked to wear an accelerometer taped to their thigh, 24 hours a day for eight consecutive days. Unlike typical accelerometers the study devices were able to detect …
Evaluation of three stratification systems predicting recurrence and prognosis in patients with brain metastases after tumor removal and whole-brain irradiation.
Authors: V. Lee, K. N. Hung, D. T. Chua, D. L. Kwong, T. W. Leung, G. K. Au
Journal: Journal of Clinical Oncology (2010)

2061 Background: To investigate if recursive partitioning analysis (RPA), score index for radiosurgery (SIR) and basic score for brain metastases (BS-BM) can predict survival of patients with brain metastases after tumour removal and whole-brain irradiation. Methods: 563 patients with brain metastases diagnosed between July 2004 to June 2009 were reviewed. Of these, 62 patients received resection of brain tumours followed by whole-brain irradiation (range 20-30Gy in 4-10 fractions). They were stratified according to RPA, SIR and BS-BM classes. Apart from RPA, SIR and BS-BM, other clinical parameters including age, number of brain metastases, Karnofsky Performance Status, ECOG performance status, time between operation and whole-brain irradiation were also analyzed for any correlation with survival. Results: Mean age of these 62 patients was 57.3 years (25 males and 37 females). The commonest site of the primary was non-small cell lung cancer (33 patients) followed by breast (13 patients) and renal cell carcinoma (7 patients). 21 patients presented with brain metastases at initial diagnosis. 41 patients had solitary metastasis and 12 and 4 patients had two and three brain metastases respectively. 47 patients received resection of all brain tumours and 15 patients received resection of only 1 -2 brain tumours. Median follow up was 12.0 months. Median survival in patients in RPA class I was 15.8 months; RPA class II, 11.0 months. Median survival in patients with BS-BM score 0 is 9.0 months; BS-BM score 1, 11.0 months; BS-BM score 2, 15.1 months; BS-BM score 3, 18.9 months. In univariate analysis, RPA, BS-BM and Score Index for Radiosurgery (SIR) were significant predictors of overall survival (p = 0.016, 0.001 and 0.015, respectively). In multivariate analysis, only BS-SM was the only predictor of overall survival (p = 0.002). Conclusions: Apart adopted for patients with brain metastases who received radiosurgery, RPA, SIR and especially BS-SM are good predictors of overall survival in those who received tumour removal and whole-brain irradiation. It is feasible to employ these scoring systems to identify patients with short survival. No significant financial relationships to disclose.
Methylcholanthrene Carcinogenesis in the North American Opossum (Didelphis virginiana)J
Authors: Edwin J. Andrews
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Methylcholanthrene Carcinogenesis in the North American Opossum (Didelphis virginiana)J Get access Edwin J. Andrews Edwin J. Andrews Department of Comparative Medicine, The Pennsylvania State University, The Milton S. Hershey Medical Center College of Medicine, Hershey, Pa. 17033 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1217–1225, https://doi.org/10.1093/jnci/51.4.1217 Published: 01 October 1973 Article history Received: 28 March 1973 Accepted: 14 May 1973 Published: 01 October 1973
Abstract 069: Mitochondrial Mechanisms Of Reverse Remodeling In Heart Failure
Authors: Preeti Ahuja, William R MacLellan, Yibin Wang
Journal: Circulation Research (2013)

Enhancement of myocardial mitochondrial (mt) function resulting in efficient energy production by means of Left ventricular assist device (LVAD) has been suggested in heart failure (HF) which could have important clinical implications and may represent a novel therapeutic target. However, the basis for this improvement remains unknown. To characterize mt biogenesis, mt genomic integrity and mitophagy in reversing pathological remodeling, we investigated LV tissue from post-LVAD human hearts and after reversal of transaortic constriction (TAC) in mice. In Post-LVAD human hearts there was increased expression of mt fusion and biogenesis, mtDNA levels were normalized and deletion mutation rates were significantly reduced with reverse remodeling and these changes were associated with enhancement of mt ETC complex I and II activities and improved cardiac-myocyte morphology. To better understand the mechanisms underlying mt repair/remodeling with LVAD support, we developed a model of aortic banding (AB) and debanding (DB) in mice. C57BL/6 mice were subjected to 2 weeks of AB and subsequent DB for period of 1 to 20 days and cardiac function and hypertrophy were evaluated by echocardiography and real-time PCR, respectively. Compared with control animals, mice that had undergone banding had a robust hypertrophic response with decline in cardiac function. These parameters were reversed following removal of pressure overload by DB. Even 1 day of unloading led to significant increase in the expression of mt fusion and biogenesis genes. Hearts from AB (2 weeks) mice showed a 3.7-fold (P&lt;0.05) increase in frequency of mtDNA deletions. However, mtDNA deletions were significantly reduced in frequency with DB when compared with AB hearts alone. Increase in expression of autophagy related genes could also be observed after hemodynamic unloading in mouse failing hearts. Removal of pressure overload by DB led to 2.58-fold (P&lt;0.05) increase in expression of LC3B when compared to sham and AB mice. Thus, our data strongly suggest that protective effect of enhanced mt biogenesis, fusion/mtDNA repair and removal of damaged mitochondria by mitophagy could play an important role in maintaining mt integrity and function in the adult heart with reverse remodeling.
ERBB2 Emerges as a New Target for Colorectal Cancer
Authors: Eirini Pectasides, Adam J. Bass
Journal: Cancer Discovery (2015)

Abstract Summary: ERBB2 mutations and amplifications are present in 7% of colorectal cancers. The presence of these alterations may be a marker of resistance to anti-EGFR therapy and, more importantly, could help identify patients who would benefit from ERBB2-directed therapy. Cancer Discov; 5(8); 799–801. ©2015 AACR. See related article by Kavuri et al., p. 832.
Abstract P124: Provider Recommendations and Patient Intentions and Confidence to Make Lifestyle Changes Following Acute Coronary Syndromes: Preliminary Data from TRACE-CORE
Authors: Molly E Waring, Jane S Saczynski, David C Parish, Catarina I Kiefe
Journal: Circulation (2012)

Background: Lifestyle changes are associated with prognosis following acute coronary syndromes (ACS). Less is known about patients’ intentions or confidence in their ability to make changes. Purpose: To examine patient report of provider lifestyle recommendations post-ACS and their intentions and confidence to make changes. Methods: Adults in central MA or GA were interviewed during hospitalization for ACS and at 1 month (1M) as part of the NHLBI-funded Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE). At 1M (n=253 to date), patients reported recommendations by clinicians during hospitalization or follow-up visit, intentions (no plans, thinking about, or started to make changes), and confidence (not at all/somewhat, moderately, or very/completely confident). X 2 or Fisher’s exact tests provided p-values. Results: Participants were 65% male, 82% non-Hispanic white and 9% African-American, and aged 61.3±11.0 years. Patient report of provider recommendations ranged from 20% to 83% (Figure). Alcohol reduction was recommended to 13% of occasional, 23% of moderate, and 41% of heavier drinkers (p&lt;0.01). Obese patients were more likely to report weight loss advice (58% versus 14% of overweight patients; p&lt;0.01). Stress management advice was more likely among patients with higher perceived stress (18%, 29%, and 59% across tertiles; p&lt;0.01). Dietary and activity recommendations did not differ by baseline behavior (p=0.13 and p=0.56, respectively). Among patients reporting recommendations, most had started to make changes (range: 54% to 96%; Figure) and intentions were positively associated with confidence for some (diet p&lt;0.01; activity p&lt;0.01; stress p=0.01; cardiac rehab p&lt;0.01) but not all lifestyle changes (alcohol p=1.0; smoking p=0.10; weight p=0.11). Conclusions: Our findings may reflect less-than-ideal counseling rates or poor patient recall. Low confidence to make lifestyle changes may be an important target for intervention post-ACS.
Phase I clinical and pharmacokinetic study of high-dose mitoxantrone combined with carboplatin, cyclophosphamide, and autologous bone marrow rescue: high response rate for refractory ovarian carcinoma.
Authors: P J Stiff, R S McKenzie, D S Alberts, J A Sosman, J R Dolan, N Rad, T McCloskey
Journal: Journal of Clinical Oncology (1994)

PURPOSE To develop an active high-dose chemotherapy regimen for the treatment of ovarian carcinoma. Due to the rapid development a drug resistance, conventional chemotherapy cures only 20% of patients with advanced disease. However, in vitro data demonstrate a steep dose-response curve to a variety of agents, most notably mitoxantrone. PATIENTS AND METHODS A phase I study of escalated bolus mitoxantrone (10 to 25 mg/m2 x 3) and cyclophosphamide (30 to 50 mg/kg x 3) with a 5-day infusion of carboplatin (1,500 mg/m2) and an autologous bone marrow transplant (ABMT) was performed. Mitoxantrone pharmacokinetics were performed to document levels required to kill platinum-resistant ovarian carcinoma in vitro. RESULTS We treated 25 patients; the maximum-tolerated total doses (MTD) were 75 mg/m2 for mitoxantrone, 120 mg/kg for cyclophosphamide, and 1,500 mg/m2 for carboplatin. The dose-limiting toxicity was gastrointestinal, with severe diarrhea, ileus, and resulting sepsis. Transient partial deafness was seen in four patients, and acute renal failure (ARF) occurred in one patient at the first dose level, but was eliminated in subsequent patients with aggressive hydration. There were four early deaths due to ARF (n = 1), Legionella pneumonia (n = 1), and sepsis (n = 2). Peak mitoxantrone levels at the MTD were 623 to 2,810 ng/mL, and the area under the curve (AUC) values of the concentration versus time measurements were 560 to 1,700 ng/mL/h. Of 20 assessable patients, 65% responded, with a 45% complete remission (CR) rate. All six of the assessable patients with ovarian cancer responded: CR in five (83%) and partial remission (PR) in one (17%); the CRs have lasted 7 to 30+ months. Responses were also seen in testicular and breast carcinoma. CONCLUSION This regimen was well tolerated at the MTD and appears promising for relapsed/refractory ovarian carcinoma, with mitoxantrone levels achieved that are active in vitro against platinum-resistant ovarian carcinoma cells.
Sorafenib plus daily low dose temozolomide for relapsed glioblastoma: A phase II study.
Authors: F. Zustovich, L. Landi, G. Lombardi, L. Galli, C. Porta, D. Amoroso, A. Fontana, M. Andreuccetti, C. Galli, A. Falcone, V. Zagonel
Journal: Journal of Clinical Oncology (2011)

2080 Background: There are no phase III trials supporting the role of some treatment for relapsed glioblastomas (GBMs). GBMs are very vascularized neoplasms thus antiangiogenic therapies might obtain some antitumoral effects. Recently, an antiangiogenic such as bevacizumab has given prior encouraging results in phase II studies and is under phase III investigation. From phase II studies also low dose protracted temozolomide (LDPT) seems to have some activity at relapse. Basing on these evidences we planned a phase II trial evaluating the activity of a full oral regimen with sorafenib (S), a tyrosine kinase inhibitor with antiangiogenic activity, associated to LDPT in patients (PTS) with relapsed GBMs. Methods: Recruit able PTS (not previously treated with antiangiogenics) were enrolled in the study and received S 400mg bid plus temozolomide (T) 40mg/m2 a day continuously till unmanageable toxicity or disease progression. Disease evaluation were performed every 2 months with gadolinium enhanced MRI using RECIST criteria. Results: From July 2008 to October 2010, 36 patients were enrolled, 18 male, median age was 59.4 (range =36.5-75.6), ECOG PS was 0 in 2 PTS, 1 in 20 PTS and 2 in 14 PTS. All PTS had histological proven GBMs relapsed after surgery, radiotherapy and temozolomide for at least six months. Five PTS had a prior second line chemotherapy and 5 two prior lines of therapy. No PTS received prior antiangiogenic treatment. Toxicity was manageable; grade 1-2 was (Type/PTS): Hand and foot syndrome (HFS)/7, Hypertension/7, Diarrhoea/6, Anorexia/3, fatigue/9, Nausea/4, stomatitis/1, thrombocytopenia/2, anaemia/2 and toxic hepatitis/3; grade 3-4 was HFS/5, hypertension/1, thrombocytopenia/2 and fatigue/2. All PTS were valuable for response: 3 PTS (8.3%) had PR, 16 (44.4%) had SD and 16 had progression. Median TTP was 2.7 months (CI 95% 1.2-4.2) and Median OS was 7.4 months (CI 95% 5.6-9.1). Conclusions: Based on our experience the combination of S ant LDPT is feasible and safe and has some activity against relapsed GBMs. The TTP of present study is comparable to the one obtained treating a similar subset of patients with bevacizumab (Zustovich et al. Anticancer Res. 2010; 12: 5213-6).