tbuckley/cabot-search huggingface dataset:
The impact of lymph node ratio (LNR) on survival in patients with colorectal cancer
Authors: R. W. Gentry, H. Spencer, G. Dykstra-Long, R. Govindarajan
Journal: Journal of Clinical Oncology (2008)

15053 Background: The reason for improved survival in colorectal cancer subjects with increased numbers of lymph nodes (LN) removed is controversial. An inverse relationship has been shown between lymph node ratio (LNR, ratio of positive to total number of LN removed) and survival in subjects with non-metastatic disease when at least 10 lymph nodes are sampled. To assess the effect on those with less than 10 nodes removed, a retrospective study of subjects treated at the Central Arkansas Veterans Healthcare System (CAVHS) was conducted. Methods: Data on subjects with a diagnosis of colorectal cancer attending CAVHS from January 1991 to October 2005 was obtained from the tumor registry. The number of LNs dissected, the number of positive and negative LNs, LNR, treatment and overall survival was analyzed. The number of resected nodes was grouped as follows: none (LNG0, n=150), 1–10 (LNG1, n=320), 11–14 (LNG2, n=35), and >14 (LNG3, n=26). LNR groups were analyzed as follows: LNR <0.05 (n=275), 0.05–0.19 (n=19), 0.2–0.39 (n=24), and 0.4–1.0 (n=67). The Kaplan-Meier method was used to estimate the survival distribution of each group, and log rank tests were used to compare these distributions. Results: A total of 531 subjects met the inclusion criteria, of which 384 had colon and 147 had rectal cancer. Nodal status was documented in 381 subjects. LNR < 0.05 had superior survival compared to those in 0.4–1.0 group (p=0.028). Node negative subjects had better survival compared to those with node positive disease. (p=0.029). There was no survival difference between LNG0, LNG1, LNG2 and LNG3 (p=0.435). Number of lymph nodes removed did not influence survival in those who had node negative disease (p=0.259) and node positive (p=0.754) disease. Treatment did not impact survival in those with no nodes examined (p=0.39). Conclusions: LowerLNR was associated with survival, even in the LNG1. The ratio rather than the number of LN removed appears to have an impact on the survival of non-metastatic colorectal cancer subjects. Impact of Lymph Node Ratio on Survival LNR N Median OS (95% CI) p-value (0 - 0.05) 275 85.8 mos. (61.9, 106.6) 0.028 (0.05 - 0.20) 19 66.8 mos. (29.5,—) (0.2 - 0.40) 24 42.2 mos. (34.5, 87.4) (0.40 - 1.0) 63 32.0 mos. (25.9, 58.5) No significant financial relationships to disclose.
Abstract 185: Tripartite Motif E3 Ubiquitin Ligase Family Proteins Regulate Intracellular Signaling During the Progression of Heart Failure
Authors: Jenna Alloush, Eric X Beck, Sayak Bhattacharya, Zhaobin Xu, Liubov Guschina, Anjella Manoharan, Noah Weisleder
Journal: Circulation Research (2014)

Heart failure is a major complication of cardiovascular disease that frequently involves initial cardiac hypertrophy that provides transient compensation for decreased heart function. Eventually, decompensation leads to compromised cardiac structure and progression into heart failure. Investigation of the downstream effector pathways for these growth factors has identified molecules involved in the progression of cardiac hypertrophy and heart failure, including phosphoinositide 3-kinase (PI3K) and Akt (Protein Kinase B). MG53, a tripartite motif (TRIM) protein family member designated as TRIM72, is highly expressed in skeletal and cardiac muscle and is known to have cardioprotective effects through modulation of PI3K signaling mechanisms. It is essential for the activation of PI3K-mediated intracellular signaling in cardiomyocytes and TRIM72 overexpression is sufficient to induce PI3K signaling. As TRIM72 regulates PI3K signaling it may play a role in regulation of heart failure, which is supported by our findings that TRIM72 levels increase in the failing mouse heart. Our recent studies also show that TRIM72 can form heterodimers with other members of the TRIM family proteins that contains approximately 70 different members in the human genome. Many TRIM family proteins are known to act as E3 ubiquitin ligases that target the ubiquitin proteasome to particular proteins. Through this activity, TRIM72 homodimers and heterodimers can resolve specific substrates that can modulate aspects of the PI3K/Akt signaling cascade. Our recent studies have resolved multiple binding partners for TRIM72 in the TRIM family that are co-regulated during heart failure. Resolving the target substrates of the heterodimers formed by these various family members and determining their role in regulating PI3K/Akt signaling mechanisms during cardiac hypertrophy will be further defined as our studies continue.
Meta-analyses of studies on bone marrow micrometastases: an independent prognostic impact remains to be substantiated.
Authors: I Funke, W Schraut
Journal: Journal of Clinical Oncology (1998)

In 1997, the immunocytologic detection of isolated tumor cells in bone marrow, termed micrometastasis, will be optionally included in the tumor-node-metastasis (TNM) classification indicated M1(i). In the present meta-analyses, 20 studies, which included 2,494 patients, regarding the prognostic influence of a positive bone marrow micrometastases (BMM) status on relapse-free and/or overall survival were analyzed.The literature search included the Medline and Current Contents bibliographic data bases from August 1980 to June 1997. The statistical evaluation considered the prognostic influence of the prevalence of micrometastatic cells in bone marrow on relapse-free and/or overall survival. The comparable effect estimate and its corresponding 95% confidence interval (CI) were calculated with the Mantel-Haenszel method using the originally published data of the retrieved studies.The presence of epithelial cells in bone marrow was detectable in all carcinoma types, with a median prevalence of approximately 35%. Fourteen of 20 studies found a positive correlation between positive BMM status and reduced relapse-free survival by univariate analysis, but only five of 11 studies confirmed positive BMM status as an independent predictor of short disease-free survival. Regarding overall survival, positive BMM status was identified univariately in five of 12 studies, but multivariately in only two studies, as an independent factor of poor survival. Despite the heterogeneity of the studies, calculation of the relative risk (RR) for reduced relapse-free survival was possible for breast cancer, which resulted in a Mantel-Haenszel RR (RR(MH)) of 1.34 (95% CI, 1.27 to 1.42).In conclusion, the results suggest that the prognostic impact of epithelial cells in bone marrow remains to be substantiated by further studies using standardized methodic protocols before its entrance in the TNM classification.
Cystatin C adds prognostic value over conventional predictors of cardiovascular disease outcomes: Results from the long-term intervention with Pravastatin in ischaemic disease (LIPID) trial
Authors: Malcolm West, David R. Sullivan, Jillian Patterson, Anthony C. Keech, Paul Nestel, Paul P. Glasziou, Adrienne Kirby, Tanja Zeller, David Colquhoun, Stefan Blankenberg, John Simes, Andrew Tonkin, Lipid Study Investigators
Journal: Circulation (2011)

Background Blood levels of the polypeptide, cystatin C, have been reported to be associated with increased cardiovascular mortality. However, cystatin C levels reflect renal dysfunction, and whethe...
Beverage purchases from stores in Mexico under the excise tax on sugar sweetened beverages: observational study
Authors: M Arantxa Colchero, Barry M Popkin, Juan A Rivera, Shu Wen Ng
Journal: BMJ (2016)

<b>Study question</b>&nbsp;What has been the effect on purchases of beverages from stores in Mexico one year after implementation of the excise tax on sugar sweetened beverages? <b>Methods</b>&nbsp;In this observational study the authors used data on the purchase of beverages in Mexico from January 2012 to December 2014 from an unbalanced panel of 6253 households providing 205 112 observations in 53 cities with more than 50 000 inhabitants. To test whether the post-tax trend in purchases was significantly different from the pretax trend, the authors used a difference in difference fixed effects model, which adjusts for both macroeconomic variables that can affect the purchase of beverages over time, and pre-existing trends. The variables used in the analysis included demographic information on household composition (age and sex of household members) and socioeconomic status (low, middle, and high). The authors compared the predicted volumes (mL/capita/day) of taxed and untaxed beverages purchased in 2014—the observed post-tax period—with the estimated volumes that would have been purchased if the tax had not been implemented (counterfactual) based on pretax trends. <b>Study answer and limitations</b>&nbsp;Relative to the counterfactual in 2014, purchases of taxed beverages decreased by an average of 6% (−12 mL/capita/day), and decreased at an increasing rate up to a 12% decline by December 2014. All three socioeconomic groups reduced purchases of taxed beverages, but reductions were higher among the households of low socioeconomic status, averaging a 9% decline during 2014, and up to a 17% decrease by December 2014 compared with pretax trends. Purchases of untaxed beverages were 4% (36 mL/capita/day) higher than the counterfactual, mainly driven by an increase in purchases of bottled plain water. <b>What this study adds</b>&nbsp;The tax on sugar sweetened beverages was associated with reductions in purchases of taxed beverages and increases in purchases of untaxed beverages. Continued monitoring is needed to understand purchases longer term, potential substitutions, and health implications. <b>Funding, competing interests, data sharing</b>&nbsp;This work was supported by grants from Bloomberg Philanthropies and the Robert Wood Johnson Foundation and by the Instituto Nacional de Salud Pública and the Carolina Population Center. The authors have no competing interests. No additional data are available.
Oral melphalan, prednisone and thalidomide for newly diagnosed myeloma patients
Authors: A. Palumbo, A. Bertola, P. Musto, M. Nunzi, V. De Stefano, L. Catalano, T. Caravita, C. Cangialosi, S. Bringen, M. Boccadoro
Journal: Journal of Clinical Oncology (2004)

6549 Background: Thalidomide (T) alone or in combination has been tested and proved effective in multiple myeloma. No data are available on the association of T with oral Melphalan and Prednisone (MP) in newly diagnosed patients. Here, we evaluated the potential additive and synergistic effect of the combination Melphalan, Prednisone and Thalidomide (MPT) Methods: Between June 2002 and June 2003, 42 patients (median age 72, range 61–80) with newly diagnosed symptomatic multiple myeloma received 6 courses of MP (melphalan 4 mg/sqm and prednisone 40 mg/sqm for 7 days every month) plus T 100 mg/day continuously until any sign of disease progression or relapse. The dose of T was reduced to 50% when grade 2 WHO toxicity occurred, and suspended for any grade 3. All patients have completed the 6 assigned MP courses and were evaluated for both toxicity and response rate. Results: T increased the hematologic toxicity induced by MP: grade 3–4 WHO neutropenia was observed in 14% of patients. Constipation occurred in 28% of patients. Neurological toxicity was recorded in 38% of patients. The major acute adverse events were infections (26%) and deep-vein thrombosis (19%). One patient died for septicemia, and one for pulmonary thromboembolism. T discontinuation was required in 36% of patients (thromboembolic event, infection, costipation, hematologic toxicity). After treatment, partial responses (myeloma protein reduction >50%) were observed in 93% of patients, no responses (myeloma protein reduction <50%) in 7%. Complete remissions (disappearance of monoclonal protein and negative immunofixation) were 26%, near complete remissions (disappearance of monoclonal protein and positive immunofixation) were 19%, responses with myeloma protein reduction 90–99% were 12%. Time required to obtain the maximum response was 4 months in 88% of patients. Conclusions: The incidence of infections and deep-vein thrombosis was high, suggesting the need for antibiotic and anticoagulant prophylaxis. MPT induced a response rate significantly higher in comparison with any other conventional chemotherapy program. The CR rate was similar to those observed after transplant. No significant financial relationships to disclose.
Phase II trial of paclitaxel plus doxorubicin plus carboplatin in patients with intermediate risk, high risk, or recurrent endometrial carcinoma
Authors: T. Shoji, H. Kurachi, T. Tabata, J. Kigawa, S. Nishimura, K. Hosokawa, M. Suzuki, M. Hatae, T. Shiozawa, T. Sugiyama
Journal: Journal of Clinical Oncology (2008)

16511 Background: We conducted a phase II trial to evaluate the safety and efficacy of the six cycles of paclitaxel/doxorubicin/carboplatin (TAC) chemotherapy in women with intermediate risk, high risk, or recurrent endometrial carcinoma. Methods: Eligible patients had intermediate risk, high risk, or recurrent endometrial carcinoma. The other eligibility criteria included preserved organ function, aged 20-75, and Performance Status 0 to 2. Treatment was conducted with doxorubicin (45 mg/m2 day 1), paclitaxel (150 mg/m2/3 hr day 2) and carboplatin (AUC 5 day 2), every 21 days for a maximum of six cycles. These doses were decided based on our previous phase I trial (2005 ASCO Annual Meeting abstract No: 5084). Primary endpoint was treatment complete rate, and secondary endpoints included toxicity, response rate (RR), and progression-free survival (PFS). Planned sample size was 45 patients (pts). Results: 45 pts were enrolled on this trial from November 2005 to August 2007 and all pts were eligible. As the number of the pts reached our planned sample size, we decided to make an early analysis except PFS. Median age was 57 yrs (range 28–75) with PS 0 in 37 pts, 1 in 7 pts, and 2 in 1 pts. Averaged treatment cycles was 5.2 (range 1–6), and the complete rate of planned six cycles of TAC chemotherapy was 73.3% (33/45 pts). Grade 3/4 adverse effect included leukopenia (82.2%), neutropenia (97.8%), anemia (64.4%) and thrombocytopenia (31.1%), febrile neutropenia (20.0%) and nausea (13.3%). No grade 3/4 cardiac toxicity and neurotoxicity, and no treatment-related death were observed. Averaged administration of filgastrim was 2.9 days/cycle. Eight pts had measurable disease, and RR was 50% (4/8 pts). Conclusions: The chemotherapy of TAC is well tolerated with short term filgastrim support. If an expected PFS can get it in the future analysis, this regimen will be one of the leading candidates for the first-line chemotherapy of endometrial carcinoma. No significant financial relationships to disclose.
Rapid and prolonged palliation of symptoms with improved quality of life (QOL) with endocrine therapy (anastrazole) in metastatic breast cancer (MBC)
Authors: J. Samuel, D. Osafo
Journal: Journal of Clinical Oncology (2006)

10767 Background: Efficacy of anastrazole in receptor positive post-menopausal MBC; rapid palliation of symptoms with improved QOL. Methods: Case Report: A 62 year old woman diagnosed with right breast cancer in 1995, stage IIB, underwent surgery, adjuvant chemotherapy, and tamoxifen for 5 years. In February 2004, a left supraclavicular lymph node (1 cm) was felt. Chest x-ray (CXR) showed blunting of right cardiophrenic angle. CT scan of the neck showed multiple left cervical lymph nodes. In April 2004, her condition deteriorated rapidly needing hospitalization. She developed 15 pound weight loss, anemia, anorexia, shortness of breath, dyspnea on exertion, dry cough, and chest pain. CXR showed large right pleural effusion needing multiple thoracentesis. Hemorrhagic exudative effusion was seen with negative cytology and cultures. She also developed multiple palpable left cervical and left axillary lymphadenopathy. Breast exam was normal. Mammogram was not diagnostic but ultrasound of breast showed a 2.5cm left breast mass, axillary lymphadenopathy and additional lesions in the breast. Left cervical lymph node biopsy showed metastatic adenocarcinoma favoring primary breast cancer. A diagnosis of 2 nd primary breast cancer with metastasis was made. Within 1 week of palliative capecitabine, she was readmitted with significant mucositis, diarrhea, dehydration, dysphagia, electrolyte imbalance, and reaccumulation of right pleural effusion. She lost 35 lbs. in 4 months. She was aggressively resuscitated and also needed thoracocentesis. Markers from prior biopsy showed Estrogen receptor 20%, Progesterone receptor &lt;5%, and HER 2 (Herceptest) 3+. Palliative hormonal therapy with anastrazole was started in July 2004. Results: Within 4 weeks, she improved significantly with disappearance of lymphadenopathy and resolution of effusion. Performance status improved to ECOG 0. She is continuing anastrazole, 17 months since the diagnosis of debilitating metastatic breast cancer. Conclusions: Anastrazole is approved for the treatment of hormone receptor positive post-menopausal MBC. We describe the efficacy of endocrine therapy (anastrazole) leading to rapid and meaningful palliation of symptoms with improved QOL. No significant financial relationships to disclose.
IMRT and cetuximab in stage 3 non-small cell lung cancer: The NEAR trial (NCT00115518)
Authors: A. D. Jensen, M. W. Münter, H. G. Bischoff, E. Herpel, R. Haselmann, C. Timke, U. Haberkorn, P. E. Huber, M. Thomas, J. Debus, K. K. Herfarth
Journal: Journal of Clinical Oncology (2007)

18168 Background: For stage 3 non-small cell lung cancer (NSCLC), RCHT is the treatment of choice with sometimes marked side- effect. Hence, patients with co-morbidities may not be eligible for combined treatment. Based on the results at other tumor sites, a combined- modality treatment with the EGFR antibody cetuximab and IMRT should be evaluated in a prospective phase II trial. Methods: Pts with inoperable stage 3 NSCLC ineligible for RCHT are included in the trial. Treatment consists of cetuximab weekly and concurrent IMRT with 50 Gy to CTV and subsequent boost to GTV to 66 Gy. Staging and f/u include CT, FDG-PET, and lung function prior to/after completion of treatment (response assessment) plus CT scans in 3 mo intervals. Overall treatment time is 4 months. Side-effects and efficacy were assessed. Results: So far, 17 of 30 pts (median 70 yrs; 57–82 yrs) have been enrolled. The median f/u from treatment start was 6 months (1–17). 3 pts are still being treated, 13 pts have completed, and one pt died prior to completion of treatment. Where available, EGFR staining yielded a median receptor score of 2 (0–3) in 12 pts. 3/12 pts showed strong (3+), 2/12 showed no EGFR expression. The treatment was well tolerated with only 1 treatment-related °3 morbidity (esophagitis). All pts showed acneiforme skin rash (°I), but no significant reduction of lung function. 2 pts with underlying heart disease developed thrombembolic complications (arterial &amp; pulmonary embolisms). We observed PR in 10/13 and SD in 3/13 pts (RECIST). All pts showed a marked reduction of SUV in PET even if CT did not show PR. Conclusion: Preliminary results of IMRT combined with cetuximab suggest a reasonably safe treatment with only mild side-effects and encouraging local response. Addition of cetuximab does not seem to increase toxicity of RT. [Table: see text]
Development of self-micellizing solid dispersion system employing amphipathic copolymer for the improvement of dissolution and oral bioavailability of cyclosporine A
Authors: Hiroki Suzuki, Hideyuki Sato, Yoshiki Kojo, Takahiro Mizumoto, Kayo Yuminoki, Naohumi Hashimoto, Yoshiki Seto, Satomi Onoue
Journal: Asian Journal of Pharmaceutical Sciences (2015)
Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte.
Authors: C Haioun, E Lepage, C Gisselbrecht, B Coiffier, A Bosly, H Tilly, P Morel, C Nouvel, R Herbrecht, M F D'Agay
Journal: Journal of Clinical Oncology (1994)

PURPOSE Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.