tbuckley/cabot-search huggingface dataset:
Markers of bone turnover (ICTP, NTX) and serum matrix metalloproteinase 1 (MMP1) as prognostic markers in breast cancer patients (BC) with bone metastases (BM) treated with bisphosphonates (BP)
Authors: L. A. Costa, I. Alho, S. Casimiro, A. G. Oliveira, I. Luís, A. Fernandes, M. Bicho, S. M. Ali, K. Leitzel, L. Demers, A. Lipton
Journal: Journal of Clinical Oncology (2008)

1024 Background: NTX and ICTP have been evaluated as prognostic markers in patients with BM. In contrast to NTX, ICTP is not affected by BP therapy (Costa, et al., JCO 2002) and is derived from MMPs collagenolytic activity. In this prospective study we analyzed whether the baseline level of ICTP, NTX and MMP1 was predictive of skeletal related events (SREs): pathologic fractures (PF), radiation to treat BM (RT) or spinal cord compression (SCC); time to progression (TTP); and overall survival (OS) in BC patients with BM under BP therapy. Methods: We studied 71 BC patients, median age: 64 years. At baseline, serum levels of the MMP1, and ICTP, and urine levels of NTX were measured. The MMP1 active form was determined by EIA-reagents obtained from R&D Systems (limit of detection 0.39 ng/mL); ICTP was determined with RIA reagents from Orion Diagnostica (reference range: 2.5–4.0 μg/L); and NTX was determined by ELISA - Osteomark (reference range: 10 to 60 BCE /mmol creatinine). SREs occurrence was recorded during the study and BM status was evaluated every 4 months. BP therapy: 50 - IV zoledronate, 29 - IV pamidronate, and 5 patients - oral clodronate (13: >1 BP). The proportional hazards model was used to investigate the correlation of log MMP1, log ICTP and log NTX baseline level with time to first SRE (TTSRE), TTP, and OS; and linear regression with the skeletal morbidity rate (SMR). Results: The median follow-up was 21 months with a median TTP of 10 months, median TTSRE of 8 months, and a median OS of 28 months. During the time period on study, 50 patients had ≥ 1 SRE (35-PF; 32-RT; 6-SCC). The median value of the measured biomarkers was: MMP1 - 3.04 (0,2–13.39); ICTP -11.6 (3.2–68); NTX- 122 (29.6–2165). ICTP levels (HR: 1.93, 95% CI 1.28–2.90, p=0.002) and NTX levels (HR: 1.88, CI 1.07–3.31, p=0.026) were associated with increased mortality risk but not with TTP or SMR. ICTP and MMP1, but not NTX, were associated to a shorter TTSRE: ICTP-HR 1.49, 95% CI 1.01–2.21, (p=0.04); MMP1- HR 1.51, 95% CI 1.04–2.20 (p=0.028). Conclusions: This study suggests that serum levels of ICTP and MMP1 might be useful to detect patients with relevant osteoclast-independent mechanism of tumor-induced osteolysis. No significant financial relationships to disclose.
The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in t(4;11)(q21;q23)-containing acute lymphoblastic leukemia
Authors: JR Downing, DR Head, SC Raimondi, AJ Carroll, AM Curcio-Brint, TA Motroni, MG Hulshof, DJ Pullen, PH Domer
Journal: Blood (1994)
Occurrence of Thyroid Cancer in San Francisco
Authors: Merrill J. Alexander
Journal: New England Journal of Medicine (1955)

IN the literature, the occurrence of cancer of the A thyroid gland has been studied at numerous teaching hospitals and large clinics by comparison, over a period, with the type of goiter seen clinically, with the number of thyroid operations, with the number of deaths or with the number of autopsies. Sokal,1 after estimating prevalence and incidence by combining clinical data, mortality statistics and autopsy statistics, presents his conclusions in a more tangible and vivid manner. He states that in a hypothetical city of 1,000,000 there would be 25 patients with thyroid cancer at any given time, that on the . . .
Use of tumor site as a prognosticator: Population-based analysis of rectosigmoid and rectum cancers
Authors: K. P. Raj, A. Ziogas, A. R. Barleben, M. J. Stamos, J. A. Zell
Journal: Journal of Clinical Oncology (2009)

4123 Background: The study examines the prognostic significance of tumor location exclusively in rectosigmoid and rectal cancers. Although tumor location has traditionally been regarded as a prognostic determinant, data in support of this claim are lacking. We set out to determine this using data from a large population-based California Cancer Registry (CCR). Methods: A retrospective analysis of surgically treated cancer cases involving the rectum and rectosigmoid from 1994–2006 with a follow-up until January 2008 in CCR was conducted. Sub-site tumor location of the cancers involving the rectum was either defined as rectosigmoid or mid/distal rectum. Site-specific survival analyses were conducted by Kaplan-Meier method and hazard ratio calculated using Cox proportional hazard ratios (HR). Results: A total of 33,418 rectal cancer cases were identified, including 12,407 (37.1%) rectosigmoid cancers and 21,011 (62.9%) mid/distal rectum cancers. No significant differences by tumor location were noticed for age, gender, stage, histological type, grade or socioeconomic status. Fewer rectosigmoid cancers received radiation (81.9% vs. 62.3% p=&lt;0.0001)) compared to mid/distal rectum cancers. After adjustment for treatment and relevant clinical factors, an improved rate of CRC-specific survival was noticed in non-metastatic rectosigmoid cancers when compared to cancers involving the mid/distal rectum. A significant decrease in mortality was observed in Stage-I [HR- 0.74(0.63–0.86)], Stage-II [HR-0.76(0.69–0.85)] and Stage-III [HR- 0.90 (0.83–0.98)] rectosigmoid cancers when compared to mid/distal rectum cancers. Number of lymph nodes examined (&gt;12 vs. &lt;12) was an independent prognostic factor for survival in Stage-II patients [HR-0.74 (0.63–0.87)]. Conclusions: Among locoregional cases, rectosigmoid cancers were found to have an improved CRC-specific survival compared to mid/distal rectum cancers, which was independent of other relevant clinical factors. [Table: see text] No significant financial relationships to disclose.
Docetaxel, oxaliplatin, and capecitabine (TEX regimen) for patients with metastatic gastric cancer: Interim results from a phase II trial by the German AIO Group
Authors: M. H. Moehler, P. Thuss-Patience, D. Arnold, W. Grothe, A. Stein, T. Seufferlein, L. Mantovani Loeffler, M. Geissler, R. D. Hofheinz, H. Schmoll
Journal: Journal of Clinical Oncology (2009)

4554 Background: Combination regimens of 3 drugs have shown promising activity as treatment for patients (pts) with metastatic gastric cancer (GC). Docetaxel combined with cisplatin and 5-FU (CF) improved overall survival and response rates when compared to standard CF. However, the identification of less toxic and more convenient variants of this regimen is still important. We have previously established a regimen with docetaxel (T) combined with oxaliplatin (E) and capecitabine (X) in a phase I trial [Grothe et al., Proc. ASCO 2006]. Results of a preplanned interim analysis of subsequent multicenter phase II trials of the TEX regimen are presented here. Methods: Pts with metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, and no prior chemotherapy for advanced disease (adjuvant allowed) were enrolled. TEX regimen was administered as defined: T 35 mg/m2 and E 70 mg/m2 on days (d) 1 and 8, with X 800 mg/m2 bid on d1–14 every 22 days Toxicity assessment was done 3-weekly while CT scans were repeated 9-weekly. Results: 35 of 48 pts were enrolled until 06/08: 28 male / 7 female, median age 59 (36–81) years, ECOG PS 0/1/2 69%/31%/0%, gastric / gastroesophageal cancer 60%/40%, distant metastases 96%, tumor in situ 37%. The most common toxicities reported were (CTC grade [gr] 3/4): diarrhea 20%/3%, vomiting 11%/3%, asthenia and neurotoxicity each 9%/0%. Mucositis and hand-foot-syndrome were observed in (grade 1+2 / grade 3) 29%/0% and 26%/3%, respectively. Hematoxicity was mild with grade 3 anemia in 10% and no other grade 3/4 toxicity except one episode of febrile neutropenia . Of 25 pts evaluable so far, first tumor response assessment revealed (RECIST criteria) partial response in 36% and stable disease in 40% of patients. Conclusions: TEX is a safe and tolerable regimen for patients with metastatic gastric cancer. Preliminary efficacy results indicate promising activity. Mature data including progression free survival will be presented at the meeting. [Table: see text]
Abstract P4-09-06: The prognostic role of RANK single nucleotide polymorphisms in breast cancer patients with bone metastases
Authors: S Casimiro, A Ferreira, I Alho, M Melo, R Brás, AL Costa, AR Sousa, A Mansinho, C Abreu, C Pulido, D Macedo, TR Pacheco, L Costa
Journal: Cancer Research (2016)

Abstract Background: Receptor activator of NF-kB (RANK) pathway regulates bone remodeling and is involved in breast cancer (BC) progression. RANK over-expression in primary BC associates with poor prognosis and metastasis development. In patients with BC, RANK and RANK-ligand (RANKL) single nucleotide polymorphisms (SNPs) have also been associated with BC risk and bone metastasis (BM)-free survival , respectively. Here we analyze the association of five RANK missense SNPs with prognosis of patients with BM from BC. Methods: Missense RANK SNPs (rs34945627, rs12721431, rs35184120, rs35993683, rs61751992) were genotyped in germline DNA from a retrospective cohort of 76 patients with BM from BC, under bisphosphonates; and a cohort of 80 healthy volunteers (samples from Biobanco-IMM, Lisbon, Portugal). Genotypic allelic frequencies were assessed using TaqMan assays (Applied Biosystems). SNP rs34945627 was analyzed with regard to clinicopathological characteristics, skeletal-related events (SRE), bone progression-free interval (BPFi), and overall survival (OS). Univariate association with clinicopathological characteristics was performed using Fisher's exact test and Wilcoxon rank-sum test; univariate differences between survival rates were tested for significance using the log-rank test, while multivariate analysis for survival was tested using Cox proportional hazards models. Results: SNP rs34945627 had a minor allele frequency of 11.84% (n=9) in BC patients versus 1.25% (n=1) in healthy individuals, whereas the remaining SNPs had a minor allele frequency of 2.60% (n=2) in BC patients. Therefore, for inferential analysis only SNP rs34945627 was considered. No differences between alleles were observed regarding clinicopathological characteristics, including treatment. Homozygous patients (CC) had increased OS when compared to heterozygous patients (CT) controlling for age at diagnosis, visceral involvement, radiographic pattern of BM and baseline urine NTX (adjusted HR 5.76, 95% CI 2.10-15.81; p&amp;lt;0.001). No association could be seen with regard to SREs (adjusted HR 1.43, 95% CI 0.46-4.46; p=0.54) or BPFi (adjusted HR 0.26, 95% CI 0.06-1.17; p=0.08). Conclusions: RANK SNP rs34945627 seems to be a marker of poor prognosis in patients with BC and BM. Further studies are required to characterize the biological and clinical significance of this finding. Citation Format: Casimiro S, Ferreira A, Alho I, Melo M, Brás R, Costa AL, Sousa AR, Mansinho A, Abreu C, Pulido C, Macedo D, Pacheco TR, Costa L. The prognostic role of RANK single nucleotide polymorphisms in breast cancer patients with bone metastases. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-06.
Case 37-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Faysal M. Hasan, Eugene J. Mark
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 28-year-old man was admitted to the hospital because of increasing dyspnea, a dry cough, and fever.The patient was well until four months earlier, when a lymph node, 10 cm, was palpated in his right axilla. Microscopical examination of a biopsy specimen of the node, performed at another hospital, revealed findings believed suggestive of a lymphoma of intermediate grade. Routine laboratory tests and staging studies were reported to be negative, including an x-ray examination of the chest, computed tomographic (CT) scans of the thorax and abdomen, and microscopical examination of a biopsy specimen of the bone . . .
Self‐Assembly Protein Nanogels for Safer Cancer Immunotherapy
Authors: Alberto Purwada, Ye F. Tian, Weishan Huang, Kathleen M. Rohrbach, Simrita Deol, Avery August, Ankur Singh
Journal: Advanced Healthcare Materials (2016)

Soluble antigen-based cancer vaccines have poor retention in tissues along with suboptimal antigen processing by dendritic cells. Multiple booster doses are often needed, leading to dose-limiting systemic toxicity. A versatile, immunomodulatory, self-assembly protein nanogel vaccine is reported that induces robust immune cell response at lower antigen doses than soluble antigens, an important step towards biomaterials-based safer immunotherapy approaches.
Platelet Survival and Morphology in Homocystinuria Due to Cystathionine Synthase Deficiency
Authors: Edward R. Uhlemann, John H. TenPas, Anne W. Lucky, Joseph D. Schulman, S. Harvey Mudd, N. Raphael Shulman
Journal: New England Journal of Medicine (1976)

In homocystinuria due to cystathionine synthase deficiency thromboembolism is a major cause of mortality and morbidity. Recent studies by others identified an abnormally shortened platelet survival and increased platelet vacuolization in patients with homocystinuria. When we studied six additional patients, however, we found the platelet survival to be within normal limits for each. The mean survival (+/-1 S.D.) was 9.75+/-0.94 days (normal, 9.27+/-1.06). In addition, platelets from five patients with homocystinuria and three obligate heterozygotes could not be distinguished from those of seven normal control subjects by electron microscopy. Specifically, no increased vacuolization was observed. Genetic heterogeneity, technical differences of differences in plasma homocystine concentrations could account for these descrepant results. The mechanism of thrombosis in homocystinuria remains an open question.
Case 26-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Sidney S. Braman, Eugene J. Mark
Journal: New England Journal of Medicine (1991)

Presentation of CaseAn 81-year-old man was admitted to the hospital because of an intrathoracic mass and weight loss.The patient was well until two years earlier, when fatigue and anorexia developed, with a gradual loss of 18.2 kg in weight by the time of admission to the hospital. Several months before admission the fatigue worsened, and a nonproductive cough developed. Seven weeks before entry an x-ray film of the chest, obtained elsewhere, showed a right pleural effusion, with a shift of the mediastinum to the right side. Eighteen days before admission the patient was seen at a second health . . .
Pulmonary alveolar proteinosis.
Authors: Francesco Bonella, Ilaria Campo
Journal: BMJ (1972)

The term pulmonary alveolar proteinosis (PAP) comprises a heterogeneous group of rare disorders characterized by abundant deposition of surfactant- and lipoproteins in the alveoli. The autoimmune form accounts for 90% of cases and is characterized by the presence of GM-CSF autoantibodies. Secondary PAP is associated with several underlying conditions, mainly hematologic malignancies, infections and inhalation exposure, and is GM-CSF antibody negative. Several conditions can mimic PAP, in particular the radiological findings: the crazy paving pattern on high resolution computed tomography (HRCT) is common also to infections, neoplasms, and other interstitial lung diseases. Bronchoalveolar lavage (BAL) typical findings and the detection of serum GM-CSF antibodies are usually sufficient for the diagnosis of PAP. Whole lung lavage (WLL) is still the gold standard for treatment of PAP and is followed by complete remission in about 50% of cases. Inhalative treatment with GM-CSF alone or in combination with WLL could represent the future approach for patients with autoimmune PAP refractory to WLL alone. The anti CD-20 antibody rituximab represents a further promising approach for autoimmune PAP. The treatment of secondary PAP should be focused on the underlying disease.
A Comparison of Etanercept and Methotrexate in Patients with Early Rheumatoid Arthritis
Authors: Joan M. Bathon, Richard W. Martin, Roy M. Fleischmann, John R. Tesser, Michael H. Schiff, Edward C. Keystone, Mark C. Genovese, Mary Chester Wasko, Larry W. Moreland, Arthur L. Weaver, Joseph Markenson, Barbara K. Finck
Journal: New England Journal of Medicine (2000)

Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown.
Antibiotics: Too Many Names
Authors: Erasto Cortes, Jesus Diaz, Abraham Verghese
Journal: New England Journal of Medicine (1993)

To the Editor: The staggering number of antibiotics to choose from strains the memory. Physicians often latch onto a memorable trade name in preference to a generic name. Residents and medical students seem most likely to correlate a trade name with a generic name when the generic name is reflected in the first or second syllable of the trade name (e.g., Amikin, Amoxil, Alpen, Amcill, and Azlin). Often, another aspect of the name helps one recall the appropriate use of the drug. Unfortunately, these associations may be of no help when one is trying to remember the generic name on . . .
Plasma High-Density Lipoprotein Concentrations in Chronic-Hemodialysis and Renal-Transplant Patients
Authors: John D. Bagdade, John J. Albers
Journal: New England Journal of Medicine (1977)

Since epidemiologic studies show that the risk of clinically evident atherosclerosis correlates negatively with concentrations of high-density lipoprotein, we sought to determine whether patients on chronic hemodialysis or recipients of renal transplants had alterations in this lipoprotein similar to those described in other disorders associated with accelerated forms of atherosclerosis. High-density-lipoprotein cholesterol concentrations in both groups of renal patients were significantly lower than control values (P<0.01), and their ratios of low-density-lipoprotein to high-density-lipoprotein cholesterol were significantly higher (P<0.01) than those observed in both randomly selected controls and in controls matched for plasma lipid levels (control, 2.4±1.2, dialysis, 3.7±2.1, and transplant, 5.4±2.3 mg per 100 ml [mean ±S.D.]). If, as experimental evidence suggests, high-density lipoprotein retards the development of atherosclerosis, and low-density lipoprotein has opposite effects, the higher ratio of low-density-lipoprotein to high-density-lipoprotein cholesterol found in chronic-dialysis and renal-transplant patients may be related to their premature morbidity and mortality from cardiovascular causes. (N Engl J Med 296:1436–1439, 1977)
Abstract 17895: Complementary Prognostic Value of Cardiac Metaiodobenzylguanidine Imaging and Diastolic Wall Strain in Patients With Preserved Left Ventricular Ejection Fraction Admitted for Acute Decompensated Heart Failure
Authors: Shunsuke Tamaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Circulation (2015)

Introduction: Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging has been reported to provide prognostic information in patients with heart failure with preserved ejection fraction (HFpEF). On the other hand, diastolic wall strain (DWS) has been recently introduced as a simple and feasible echocardiographic index in assessing left ventricular (LV) diastolic stiffness, and has been shown to be associated with poor outcome in patients with HFpEF. Hypothesis: We assessed the hypothesis that cardiac MIBG imaging and DWS might have a complementary prognostic value in HFpEF patients admitted for acute decompensated heart failure (ADHF). Methods: We studied 70 consecutive patients admitted for ADHF and discharged with survival whose LV ejection fraction measured by echocardiography was ≧40% (age: 77±12 years, male: 49%, NYHA class at discharge: 2.2±0.8). Cardiac MIBG imaging and echocardiography were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate were calculated from the chest anterior view images obtained at 20 and 200min after isotope injection. DWS was determined in the LV M-mode echocardiogram using a validated formula. The endpoints were unplanned hospitalization for worsening heart failure (WHF) and pump failure death (PFD). Results: During a follow-up period of 2.0±0.8 years, 20 patients had WHF and 7 patients had PFD. At multivariate Cox analysis, out of the variables including clinical, hemodynamic, biochemical, MIBG and echocardiographic parameters, H/M on delayed image (late H/M) and DWS were significantly independently associated with WHF (p=0.0058) and PFD (p=0.0160), respectively. Kaplan-Meier analysis showed that the patients with late H/M &lt;1.73 (mean value) and those with DWS &lt;0.292 (mean value) had a significantly higher risk of WHF and PFD, respectively (Figure). Conclusions: Cardiac MIBG imaging and DWS had a complementary prognostic value in HFpEF patients admitted for ADHF.
Updated 12-year results of a randomized clinical trial comparing standard-dose to high-dose myeloablative chemotherapy in the adjuvant treatment of breast cancer with more than three positive nodes (LN+)
Authors: A. M. Gianni, G. Bonadonna, G. Michelangelo
Journal: Journal of Clinical Oncology (2007)

549 Aims: We conducted a multicenter randomized trial comparing sequential adjuvant standard-dose with high-dose chemotherapy in breast cancer patients younger than 60 years, with 4 or more positive nodes. Patients: Following surgery, patients were stratified by number of positive nodes (4–9 or 9), and randomly assigned to either conventional Epi–CMF (3 courses of epirubicin 120 mg/m 2 , followed by 6 courses of CMF), or high-dose chemotherapy (HDS) with stem cells support (one course of cyclophosphamide 7 g/m 2 , followed by one course of methotrexate 8 g/m 2 with leukovorin rescue, by two courses of epirubicin 120 mg/m 2 , and by one course of thiotepa 600 mg/m 2 plus melphalan 160–180 mg/m 2 with stem cell autografting). Tamoxifen (20 mg/d × 5 yr) was also planned regardless of menopausal and receptor status. The study was designed with a power of 80% to detect a 15% increase in progression-free survival at 5 years in the HDS arm. Results: Of the initially enrolled 398 patients, 16 were ineligible, and the remaining 382 patients (Epi–CMF: 197 patients, HDS: 185 patients) were analyzed according to intent-to- treat. One patient treated with HDS (0.5%) died of interstitial pneumonia. With a median follow-up of 136 months, the 12-year progression-free survival rates were 44% and 52% for the Epi–CMF and the HDS groups, respectively, and the overall survival rates were 51% and 60%, respectively. However, among the 68 patients younger than 36 years, and the 189 patients with 4–9 LN+, those in the HDS group showed a trend for a progression-free survival advantage (HR 0.76 and 0.74, respectively). Conclusions: In the intent-to-treat analysis the 9% overall survival advantage associated with the HDS regimen failed to reach statistical significance in a study powered to detect a 15% difference. To reliably define the role of high-dose therapy, meta-analysis of patient data from all relevant randomized trials (such as that planned by the Early Breast Cancer Trialists’ Collaborative Group) is needed. Supported in part by AIRC and Pharmacia &amp; Upjohn, Milano, Italy. No significant financial relationships to disclose.