tbuckley/cabot-search huggingface dataset:
Immunity to Malaria and Naturally Acquired Antibodies to the Circumsporozoite Protein of<i>Plasmodium falciparum</i>
Authors: Stephen L. Hoffman, Richard Wistar, W. Ripley Ballou, Michael R. Hollingdale, Robert A. Wirtz, Imogene Schneider, Hariyani A. Marwoto, Wayne T. Hockmeyer
Journal: New England Journal of Medicine (1986)

A candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.
CSIG-08NITROSOUREAS IMPROVE SURVIVAL IN THE SECONDARY-LIKE AKT SUBTYPE OF GLIOBLASTOMA
Authors: Anna Joy, Ivan Smirnov, Mark Reiser, Gordon Mills, Seungchan Kim, Burt Feuerstein
Journal: Neuro-Oncology (2015)

The PI3K/AKT pathway regulates response to chemotherapeutics. We hypothesized this pathway varies between Glioblastoma (GB) patients and this effects response to therapeutics. We classified GB based on Akt pathway genes in a test set of tumors, and 5 Akt pathway subtypes resulted. The subtypes fit previous classifications, but further divided classes, yielding new subtypes with differing clinical and molecular features. We expanded this work into data sets within The Cancer Genome Atlas (TCGA), and investigated subtypes response to chemotherapeutics. We find one AKT subtype, called Secondary-Like, has a 4½ year survival advantage with nitrosourea treatment. This remained significant after correcting for age. This subtype has hallmarks of secondary GBM - younger age, longer survival and enrichment in IDH1 mutant and glioma CpG Island Methylator Phenotype (G-CIMP) tumors. We are currently validating these results in a second dataset and analyzing the contribution of the IDH1 and non-IDH1 mutant Secondary-Like tumors.
Mildred Hilario Genesio de Souza
Authors: Krishna Somers
Journal: BMJ (2016)

Born and raised in Uganda, Mildred Hilario Genesio de Souza (“Hilary”) went to school in Goa, followed by university education in Bombay. On returning to Uganda he was appointed general duties medical officer in the district of Masindi, where he was for many years the only medical practitioner …
Older Patients, Cognitive Impairment, and Cancer: An Increasingly Frequent Triad
Authors: Martine Extermann
Journal: Journal of the National Comprehensive Cancer Network (2005)

The incidence of both cancer and cognitive impairments from various origins increases with age. Oncologists are increasingly being confronted with cancers occurring in patients with cognitive impairment, yet very few studies have addressed the problem. Cognitive impairment affects a patients' survival to an extent similar to an average cancer, and this can be an important thing to consider, especially in the adjuvant setting. Cognitive impairment also predisposes patients to delirium in the surgery setting or during hospitalization. Because effective preventive measures exist, careful attention should be paid to identifying patients at risk. Cognitive impairment does not automatically mean inability to consent, but particular precautions should be taken. For outpatient treatments such as chemotherapy, a comprehensive multidisciplinary approach is key for a good outcome. Proper caregiver support should be ensured up-front, and aggressive supportive care should be used. In the setting of an experienced geriatric oncology team, patients with cognitive impairment appear more likely to receive standard oncologic therapies. Cancer patients with cognitive impairment are at high risk of concomitant depression.
Chronomodulated (<i>Chrono</i>) vs constant (<i>Cst</i>) rate infusional 5-fluorouracil (FU) with or without cisplatin (CDDP) in patients with advanced or metastatic pancreatic cancer. A multicenter randomized trial of the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer (EORTC 05962)
Authors: F. A. Levi, N. Tubiana-Mathieu, C. Focan, C. Brézault-Bonnet, B. Coudert, C. Carvalho, D. Genet, S. Giacchetti, M.-A. Lentz, B. Baron
Journal: Journal of Clinical Oncology (2004)

4117 Background: Tolerability and activity of 5-day (d) infusional FU-oxaliplatin were improved with Chrono as compared with Cst in colorectal cancer pts(Lévi et al, Lancet 1997). CDDP addition to FU tended to prolong Progression-Free Survival (PFS) in pancreatic cancer pts(Ducreux et al, Ann Oncol 2002). Methods: A factorial design tested the relative effects of CDDP addition (100 mg/m2/course, c) to FU (c1/c2/c3 : 5/6/6.5 g/m2) and Cst vs Chrono (FU : 10 pm-10 am, peak at 4 am; CDDP : 10 am-10 pm, peak at 4 pm) 5 d q21d. Pts with advanced (25) or M (82) histologically-proven pancreatic cancer were registered in 15 centers. CTC toxicity was assessed q10 d and response q 3c. Survival was the main endpoint. Results: Characteristics : CDDP no/yes, 55/52 pts; Chrono no/yes, 54/53 pts; median age, 63 y; WHO PS 0/1/2, 35/52/20 pts; M sites 0/1/2+, 16/51/36 pts. CDDP increased median PFS from 2.1 months (mo.) [95% CL, 1.9–2.3] to 3.2 mo. [2.5–5.0] and median survival from 5.4 mo. [3.9–8.4] to 8.3 mo. [5.7–11.9]. Median survival (mo.) was 6.1 on Cstand 6.7 on Chrono(NS). CDDP addition reduced the risk of P by 44% (Log rank, p = 0.005) and that of death by 20% (p = 0.26). CDDP significantly increased grade 3–4 toxicity per patient : neutropenia (58 vs 6%), thrombopenia (38 vs 2%), anemia (25 vs 12%). The dose intensities of FU and CDDP were higher with Chrono (p = 0.03). Despite this, Chrono decreased the incidence of grade 3–4 mucositis (8 vs 27%, p = 0.01), anorexia (10 vs 23%) and diarrhea (2 vs 10%). Conclusions: CDDP addition to FU near maximum tolerated doses prolonged PFS in pancreatic cancer pts, with a trend toward improved survival. Chronoameliorated non haematological tolerability and allowed to administer higher DIs. Chrono FU should be combined with a less toxic Pt complex to concurrently improve antitumor efficacy and tolerability in M pancreatic cancer. Support: NCI, ARC (grant 9033), ARTBC, hôp. P Brousse, Villejuif (F). No significant financial relationships to disclose.
Prognostic value of MGMT gene promoter methylation evaluated on ten CpG sites in patients with glioblastoma multiforme: a single-institution experience
Authors: E. De Carlo, L. Gerratana, L. Gurrieri, G. De Maglio, S. Rizzato, A. Follador, S. Pizzolitto, V. Buoro, M. Skrap, F. Pisa, F. Puglisi, G. Fasola
Journal: Annals of Oncology (2015)
Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer
Authors: Martin G. Dalin, Alexis Desrichard, Nora Katabi, Vladimir Makarov, Logan A. Walsh, Ken-Wing Lee, Qingguo Wang, Joshua Armenia, Lyndsay West, Snjezana Dogan, Lu Wang, Deepa Ramaswami, Alan L. Ho, Ian Ganly, David B. Solit, Michael F. Berger, Nikolaus D. Schultz, Jorge S. Reis-Filho, Timothy A. Chan, Luc G.T. Morris
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy, which is resistant to chemotherapy and has high mortality rates. We investigated the molecular landscape of SDC, focusing on genetic alterations and gene expression profiles. Experimental Design: We performed whole-exome sequencing, RNA sequencing, and immunohistochemical analyses in 16 SDC tumors and examined selected alterations via targeted sequencing of 410 genes in a second cohort of 15 SDCs. Results: SDCs harbored a higher mutational burden than many other salivary carcinomas (1.7 mutations/Mb). The most frequent genetic alterations were mutations in TP53 (55%), HRAS (23%), PIK3CA (23%), and amplification of ERBB2 (35%). Most (74%) tumors had alterations in either MAPK (BRAF/HRAS/NF1) genes or ERBB2. Potentially targetable alterations based on supportive clinical evidence were present in 61% of tumors. Androgen receptor (AR) was overexpressed in 75%; several potential resistance mechanisms to androgen deprivation therapy (ADT) were identified, including the AR-V7 splice variant (present in 50%, often at low ratios compared with full-length AR) and FOXA1 mutations (10%). Consensus clustering and pathway analyses in transcriptome data revealed striking similarities between SDC and molecular apocrine breast cancer. Conclusions: This study illuminates the landscape of genetic alterations and gene expression programs in SDC, identifying numerous molecular targets and potential determinants of response to AR antagonism. This has relevance for emerging clinical studies of ADT and other targeted therapies in SDC. The similarities between SDC and apocrine breast cancer indicate that clinical data in breast cancer may generate useful hypotheses for SDC. Clin Cancer Res; 22(18); 4623–33. ©2016 AACR.
Ciliary Streaming in the Bronchial Tree and the Time Element in Carcinogenesis
Authors: A. C. Hilding
Journal: New England Journal of Medicine (1957)

MUCH has been said in the past about the relation of chronic irritation to the development of cancer. Recent concepts are more specific and put carcinogenesis on a physicochemical basis in which the time element plays a large part.1 2 3 4 5 6 Carcinoma in the tracheobronchial tree tends to occur in relation to smoking habits7 8 9 10 and in certain areas of the lungs. The studies described in this report indicate that the ciliary mechanism may be related to the pattern of distribution and may be an agent that furnishes the necessary time factor for carcinogenesis.Present StudyThe present study describes the physiology of . . .
Antigenic Specificity of γ&lt;sub&gt;2&lt;/sub&gt;-Myeloma Globulins&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Leonhard Korngold
Journal: JNCI Journal of the National Cancer Institute (1963)

Rabbits were inoculated with 8 purified γ2 multiple myeloma globulins. The antisera were tested for specificity by the Ouchterlony gel diffusion technique. The formation of a spur between the lines of the homologous myeloma globulin and normal γ2-globulin was an indication that the antiserum contained antibody against antigenic determinants lacking from normal γ2-globulin. These antisera were subsequently absorbed with normal γ2-globulins (either fraction II, γ2-globulin, or mixtures of γ2- and γ1-globulin) and retested for their ability to react with the homologous antigen and normal γ2-globulin. Retesting was done by the Ouchterlony method and by immuno-electrophoresis. Absorption with γ2-globulin or fraction II in the range of 2 to 10 mg per ml removed all reactivity with normal γ2-globulin up to 100 mg per ml, but zones of precipitate were still formed with as little as 0.1 mg per ml of the homologous antigen, even after absorption with fraction II at 100 mg per ml. Although these findings do not prove that myeloma globulins are lacking from normal serum, they suggest that their concentration is too low to be detected by the methods used, and that as much as 150 mg per ml of γ2-and γ1-globulins will not remove the antibody against the homologous myeloma globulin.
Pathological Manifestations in an Infant after Maternal Rubella in the Sixteenth Week of Gestation
Authors: C. G. Tedeschi, M. M. Helpern, T. H. Ingalls
Journal: New England Journal of Medicine (1953)

GREGG'S1 observation that rubella in the mother during early pregnancy frequently leads to congenital cataract of the unborn child has been confirmed by numerous investigators.2–4 The effects of the maternal infection on the conceptus vary within a broad range of possibilities: the fetus may escape injury, die or have various combinations of defects as late manifestations — arrested or distorted development of the eyes with anomalies of the teeth, middle ear and heart.2 Rubella is most likely to cause cataract (usually nuclear) when the infection occurs at the fourth to the sixth week of gestation.2, 5 The observation is consistent with . . .
Comparison of Medical and Surgical Therapy for Complicated Gastroesophageal Reflux Disease in Veterans
Authors: Stuart Jon Spechler
Journal: New England Journal of Medicine (1992)

Conventional medical treatment for gastroesophageal reflux disease involves lifestyle modifications and combination drug therapy, but few studies have included these features in their protocols. Antireflux surgery has seldom been studied prospectively, and there have been no trials comparing modern medical and surgical treatments for reflux disease.
Abstract P190: Associations of 24-h Urinary Sodium/potassium (Na/K) Ratio with Recommended Intakes of Na and K: The INTERMAP Study
Authors: Toshiyuki Iwahori, Katsuyuki Miura, Hirotsugu Ueshima, Queenie Chan, Nagako Okuda, Katsushi Yoshita, Alan R Dyer, Paul Elliott, Jeremiah Stamler
Journal: Circulation (2016)

Background: High dietary sodium (Na), low dietary potassium (K) and high dietary sodium/potassium (Na/K) ratio are associated with adverse blood pressure levels and excess risks of cardiovascular diseases. 24-h urine collection is the gold standard for measuring dietary Na, K and Na/K ratio. Recommended levels of Na and K intakes are suggested in WHO guidelines; less than 85 mmol/day for Na; at least 90 mmol/day for K; there is no definitive guideline for Na/K ratio. Objective: Our primary aim was to compare the level of urinary Na/K ratio with the current recommended levels of Na and K intakes suggested in WHO guidelines. Methods: INTERMAP is an international study on associations of multiple dietary variables with blood pressure (BP), based on two timed 24-hr urine collections and dietary data from 4 in-depth 24-h dietary recalls in 4,680 men and women ages 40-59 years in China, Japan, United Kingdom and United States (US). Na/K ratio of 24-hr urine stratified in 1 unit intervals was compared with the current recommended levels of Na and K intakes suggested in WHO guidelines. Na intake was evaluated by urinary Na excretion; K intake by dietary K intake. Results: Thirty-one of the 4,680 INTERMAP participants (0.7%) had urinary Na/K ratio less than 1. The proportions of participants with Na excretion less than 2 g/day (85 mmol/day) among all 4,680 individuals were 77% (n=24), 19% (n=117), and 0.2% (n=11) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples (n=2,195) the proportions were 88% (n=15), 19% (n=70), and 0.3% (n=6), respectively. The proportions of participants with dietary K intake more than 3.51 g/day (90 mmol/day) among all 4,680 individuals were 71% (n=22), 38% (n=233), and 2.4% (n=111) in those with urinary Na/K ratio less than 1, 1 to 2, and more than 4, respectively. In US samples the proportions were 59% (n=10), 38% (n=138), and 2.1% (n=47), respectively. Conclusions: WHO recommends Na intake less than 85 mmol/day, and K intake more than 90 mmol/day. Urinary Na/K ratio less than 1 is needed to ensure reasonable compliance with these recommendations. Currently, very few people satisfy urinary Na/K ratio less than 1, so population-wide efforts are needed to reduce salt (sodium chloride) and increase K intake.
Activity of sorafenib against desmoid tumor/deep fibromatosis (DT/DF).
Authors: M. M. Gounder, C. Antonescu, M. R. Hameed, D. R. D'Adamo, M. Keohan, S. Singer, M. F. Brennan, L. S. Ahn, R. G. Maki
Journal: Journal of Clinical Oncology (2010)

10013 Background: DT/DFs are clonal connective tissue malignancies that do not metastasize, but have a significant risk of local recurrence, and are often associated with morbidity and occasionally mortality. Antiestrogens and cytotoxic agents have activity against desmoids, but many patients (pts) fail to respond to such therapy. Imatinib has activity against DT/DF, but response rates are also low. A response of a patient to sorafenib on an expanded access program led us to review our experience with sorafenib for pts with DT/DF. Methods: After IRB approval, we collected and reviewed files for 13 patients with DT/DF treated with sorafenib. Results: We identified 13 pts who received sorafenib for DT/DF. Patient characteristics included: M/F: 6/7; extremity primary site in 4 (31%), abdomen/pelvis in 6 (46%), other in 3 (23%); recurrent disease in 8 (61%); 2 with FAP (15%); 3 with post-surgical DT/DF (23%); multifocal in 6 (46%). Pts had received a median of 2 lines of systemic therapy (range 0-5). Sorafenib was administered at 400 mg oral daily and adjusted for toxicity. Sorafenib was first-line therapy in 4/13 pts. Prior to initiation of sorafenib, 10/13 pts had evidence of progressive disease by imaging, 2/13 pts had worsening symptoms (pain) with stable scans and 1/13 patient had received maximum benefit with chemotherapy. Best response included 6/13 (46%) pts with RECIST 1.1 partial response (PR), 6/13 (46%) with stable disease, and 1 with progression and death. 8/13 (61%) pts met "Choi" criteria for a response: 7 pts had response by size (>10% decrease) and 5 pts had decreased vascularity/increased fibrosis by contrast enhanced MRI/CT. Conclusions: Sorafenib is active against DT/DF. A randomized clinical trial of sorafenib or other tyrosine kinase inhibitors vs other active agents is warranted, given the lack of such comparative data. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer
Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A
Authors: Arthur S Tischler, Ashraf Khan, Ronald A DeLellis
Journal: New England Journal of Medicine (2005)

University of Michigan Ann Arbor, MI 48109 arul@umich.edu Drs. Wang and Chinnaiyan report being listed as inventors on a patent on the findings of this study filed by the University of Michigan. Koziol JA, Zhang JY, Casiano CA, et al. Recursive partitioning as an approach to selection of immune markers for tumor diagnosis. Clin Cancer Res 2003;9:5120-6. McIntosh MW, Pepe MS. Combining several screening tests: optimality of the risk score. Biometrics 2002;58:657-64. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level ≤4.0 ng per milliliter. N Engl J Med 2004;350:2239-46. [Erratum, N Engl J Med 2004;351:1470.] Brass N, Heckel D, Sahin U, Pfreundschuh M, Sybrecht GW, Meese E. Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma. Hum Mol Genet 1997;6:33-9. 1.
Case 2-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Ira S. Nash, John T. Fallon
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 31-year-old man was admitted to the hospital because of severe mitral regurgitation with congestive failure.He was well until the age of 16 years, when dyspnea and a cough developed, with a bout of syncope. A diagnosis of constrictive pericarditis was made, and a pericardiectomy was performed; a tuberculin skin test was reported to be negative. Thereafter the patient felt well until three years before entry, when he began to experience brief bouts of atrial fibrillation and was told that he had a murmur. Two years before admission a prolonged episode of atrial fibrillation was accompanied . . .
Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis
Authors: Li Li, Lori J. Silveira, Nabeel Hamzeh, May Gillespie, Peggy M. Mroz, Annyce S. Mayer, Tasha E. Fingerlin, Lisa A. Maier
Journal: European Respiratory Journal (2016)

A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD. We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO 4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus. We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)–STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine–cytokine receptor interactions, and Toll-like receptor, chemokine and JAK–STAT signalling pathways. We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.