tbuckley/cabot-search huggingface dataset:
Phase I study of imetelstat (GRN163L) in combination with paclitaxel (P) and bevacizumab (B) in patients (pts) with locally recurrent or metastatic breast cancer (MBC).
Authors: M. Kozloff, G. W. Sledge, F. M. Benedetti, A. Starr, J. A. Wallace, M. J. Stuart, D. Gruver, K. Miller
Journal: Journal of Clinical Oncology (2010)

2598 Background: Following debulking chemotherapy, tumor regrowth may rely on proliferation of a cellular subcompartment with progenitor cell or “stem cell”-like properties. Self-renewal of this stem cell compartment requires the presence of telomerase, making inhibition of telomerase an appealing therapeutic strategy. Imetelstat, the first targeted telomerase inhibitor in clinical trials, is a 13-mer lipidated oligonucleotide that binds to the template RNA strand of telomerase. Methods: Pts with locally recurrent or MBC were treated with imetelstat in addition to P+B as in the previous E2100 study. Pts with prior adjuvant taxane therapy within 12 months were excluded. In a standard 3+3 dose-escalation design, imetelstat (160-375 mg/m2 2-hr IV infusion) was administered on days 1, 8, and 15 of a 28-day cycle. Study objectives were to define the maximally tolerated dose (MTD) and obtain preliminary safety and efficacy. Dose-limiting toxicities were determined by presence of hematologic toxicities and receipt of therapy during the first cycle. Results: 14 pts were treated; 3 pts with de novo MBC; 6 pts with prior (neo)adjuvant taxane. A median of 4 cycles (range 1-9) of imetelstat and P were initiated; B could be continued as per E2100 and a median of 5 cycles (range 1-11) of B were initiated. No DLTs were observed within the initial 28-day treatment cycle. The most common toxicities were cytopenias. Grade ≥ 2 neutropenia within the first cycle resulted in 5 pts (35.7%) with dose reductions of P. Eleven pts (78.6%) had dose delays/omissions of imetelstat and/or P in later cycles due to neutropenia and/or thrombocytopenia. Other grade ≥2 AEs occurring in > 1 pt include: lymphopenia, fatigue, nausea/vomiting, diarrhea, chest pain, and rash. 13 pts are evaluable for response. To date, 1 CR, 4 PRs (ORR = 38.5%) and 5 SDs have been reported. Two pts remain on study. Conclusions: To date, the MTD has not been defined in this study. Although the majority of patients had dose reductions/delays of imetelstat and/or P, objective responses (38.5%) have been seen. Alternative dosing schedules are currently being tested to allow for full doses of P and longer exposure of imetelstat. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Geron Genentech Geron Genentech
WHO warns European countries to be on alert for Zika
Authors: Anne Gulland
Journal: BMJ (2016)

European countries need to be on the alert for the Zika virus and act to control it now, the World Health Organization has urged.

In a statement released on 3 February Zsuzsanna Jakab, WHO’s regional director for Europe, said that countries should take urgent action to control populations of mosquitoes of the Aedes genus, enhance surveillance and detection, step up research and inform people at risk, particularly pregnant …
Public health—the frontline cuts begin
Authors: Gareth Iacobucci
Journal: BMJ (2016)

<h3>ABSTRACT</h3> Understanding the regulatory mechanisms that control sexually dimorphic gene expression is a key part of understanding the processes that govern the rate of sex chromosome evolution and phenotypic sex differences. Epigenetic modifications play a major role in tissue-specific gene expression regulation and have been hypothesized to dramatically impact the speed of sex chromosome divergence. The guppy sex chromosomes are an emerging model for studying the initial stages of divergence between the X and Y. In this study, we use comparative epigenomics to identify conserved sex-specific DNA methylation patterns in gonad and muscle tissue between the Trinidadian guppy (<i>Poecilia reticulata</i>) and its sister species, Endler’s guppy (<i>Poecilia wingei</i>). We find that the oldest part of the guppy sex chromosome shows a conserved pattern of male hypomethylation, consistent with a key role in testis-specific gene expression. This pattern provides a potential mechanism for theoretical predictions that sex chromosome divergence can occur remarkably quickly in evolutionary time, and without widespread degradation of the Y chromosome gene content. Our cross-species comparative epigenomic analysis also provides a robust comparative framework to understand constraints of epigenetic programming. We observe conserved, testis-specific hypomethylated regions near key autosomal developmental genes and a potentially imprinted locus. These observations are consistent with DNA methylation in testis from other vertebrates, and suggest broad conservation of DNA methylation patterns in these regions. Our comparative framework reveals conserved DNA methylation differences between males and females across two related species, providing novel insights into the relationship between epigenetic and evolutionary processes.
Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors
Authors: N. Shirina, R. E. Coleman, Y. M. Chen
Journal: Journal of Clinical Oncology (2006)

8529 Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or &gt; 3 lesions. Results: In general, patients with &gt; 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with &gt; 3 lesions. In patients with lung cancer and other solid tumors who had &gt; 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with &gt; 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with &gt; 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid. [Table: see text] [Table: see text]
Management of the Deaf Child
Journal: BMJ (1964)

When confronting deafness in a child management consists in either medical or surgical treatment or an auditory prosthesis. In the case of inflammatory or infectious pathologies of the outer ear and the middle ear medical treatment is indicated. For a seromucous otitis some suggest the combination of an antibiotic with a corticosteroid for two weeks while others opt for mucolytics for one month. For acute otitis media with perforation or otorrhea or chronic otitis treatment is based on ear drops or on antibiotic therapy in order to dry the ear prior to proceeding with surgery or instrument-fitting. In surgery the use of a transtympanic aerator depends on the magnitude of hypoacusis the season and associated factors especially sensorineural deafness. The goal of surgery performed on a case of chronic otitis is to eradicate the cholesteatomatous and progressive lesions to protect the ear from infection by sealing a tympanic perforation and to improve audition. Aplasias of the ear are minor and major aplasias. An auditory prosthesis is indicated in the event of bilateral deafness however in the case of slight deafness the prosthesis may be limited to scholastic activities. A new method for rehabilitating profound bilateral cases of deafness is the cochlear implant intended for children who have not received any benefit from conventional high-powered prostheses. Auditory therapy or speech therapy teaches the child to discriminate sounds and to give them their own meaning and allows training of the voice and articulation in speech. In light of the burden of treatment for the family and society the parents may request genetic counseling to evaluate their risk of having a child suffering from such an auditory handicap preventive measures may be taken to decrease this risk such as vaccination against rubella the mumps and information campaigns for parents and adolescents are also preventive measures.
Association of germline polymorphism in the SPARC gene and tumor recurrence in patients with resected gastric cancer.
Authors: P. M. Wilson, T. Winder, D. G. Power, D. Yang, W. Zhang, Y. Ning, P. O. Bohanes, L. H. Tang, M. A. Shah, H. Lenz
Journal: Journal of Clinical Oncology (2010)

4054 Background: SPARC (Secreted Protein Acidic and Rich in Cysteine) is a glycoprotein involved in cellular adhesion acting as a key regulator of cell-matrix interactions. SPARC protein overexpression is frequently observed in gastric carcinoma and plays an important role in tumor progression, proliferation and metastasis. We tested whether two potentially functional germline variations (rs1059829 and rs3210714) within the SPARC gene are associated with clinical outcome in patients with surgically resected gastric cancer. Methods: Either blood or FFPE tissues specimens of 137 patients (54 females and 83 males; median age = 55 yrs; range = 21-85 yrs) were obtained at University of Southern California (n = 105) and Memorial Sloan-Kettering Cancer Center medical facilities (n = 32). The median follow-up was 3.3 years. Sixty-one of 137 patients (45%) had tumor recurrence, with a probability of 3-year recurrence of 52%. Genomic DNA was isolated from peripheral blood or FFPE tissues and two polymorphisms within the SPARC gene were determined by PCR-RFLP technique. Results: Patients carrying at least one G allele of the SPARC rs1059829 polymorphism (GG; AG) showed a median TTR of 3.7 years compared to 2.1 years TTR for patients with AA (p = 0.033, log-rank test). In multivariate analysis SPARC rs1059829 showed to be an independent prognostic factor for TTR after adjusting for race, N-stage, T-stage and type of chemotherapy in (adjusted p value = 0.037). SPARC rs3210714 showed no significant associations for TTR. Conclusions: Our data suggest that the SPARC rs1059829 polymorphism significantly affects tumor recurrence and may therefore act as independent prognostic marker in patients with surgically resected gastric cancer. However, this data warrants further validation in large, biomarker embedded clinical trials. No significant financial relationships to disclose.
Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms.
Authors: M L Grossbard, J M Lambert, V S Goldmacher, N L Spector, J Kinsella, L Eliseo, F Coral, J A Taylor, W A Blättler, C L Epstein
Journal: Journal of Clinical Oncology (1993)

PURPOSE This phase I trial was undertaken to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the B-cell-restricted immunotoxin anti-B4-blocked ricin (anti-B4-bR) when it is administered by 7-day continuous infusion. PATIENTS AND METHODS Thirty-four patients with relapsed and refractory B-cell neoplasms (26 non-Hodgkin's lymphoma [NHL], four chronic lymphocytic leukemia [CLL], four acute lymphoblastic leukemia [ALL]) received 7-day continuous infusion anti-B4-bR. Successive cohorts of at least three patients were treated at doses of 10 to 70 micrograms/kg/d for 7 days with the dose increased by 10 micrograms/kg/d for each cohort. The initial three cohorts of patients (10, 20, and 30 micrograms/kg/d x 7 days) also received a bolus infusion of 20 micrograms/kg before beginning the continuous infusion. RESULTS The MTD was reached at 50 micrograms/kg/d x 7 days. The DLTs were National Cancer Institute Common Toxicity Criteria (NCI CTC) grade IV reversible increases in AST and ALT, and grade IV decreases in platelet counts. Adverse reactions included fevers, nausea, headaches, myalgias, hypoalbuminemia, dyspnea, edema, and capillary leak syndrome. Potentially therapeutic serum levels of anti-B4-bR could be sustained for 4 days in patients treated at the MTD. Two complete responses (CRs), three partial responses (PRs), and 11 transient responses (TRs) were observed. CONCLUSION Anti-B4-bR can be administered safely by 7-day continuous infusion with tolerable, reversible toxicities to patients with relapsed B-cell neoplasms. Although occasional responses were seen, future trials will use anti-B4-bR in patients with lower tumor burdens to circumvent the obstacle of immunotoxin delivery to bulk disease.
Nearly 10% in US have had problem with drug use, survey finds
Authors: M. McCarthy
Journal: BMJ (2015)

Nearly 10% of people in the United States, more than 23.3 million, have or have had a problem with drug use, and the vast majority went untreated, says a study published online by JAMA Psychiatry on 18 November.1

The study’s lead author, Bridget F Grant, of the National Institute on Alcohol Abuse and Alcoholism in Rockville, Maryland, and colleagues analyzed data collected from in-person interviews with 36 309 adults in the 2012-13 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC III), a cross sectional representative survey of the US.

The interviews were designed to measure the prevalence of drug use disorder (DUD), alcohol use …
Patient preferences for interferon alfa in multiple myeloma.
Authors: H Ludwig, E Fritz, J Neuda, B G Durie
Journal: Journal of Clinical Oncology (1997)

PURPOSE Interferon alfa treatment in multiple myeloma marginally improves relapse-free and overall survival. Often it does so at the expense of toxicity and financial cost. If patients are unwilling or unable to participate in the decision of whether to initiate such treatment, known patient preferences can serve as guidelines for the physician. We interviewed myeloma patients in the United States to obtain information that might facilitate medical decision-making. PATIENTS AND METHODS Three hundred fifty-five myeloma patients throughout the United States were interviewed by telephone. Without identifying interferon alfa as the treatment agent, interviewers described potential adverse effects, financial cost, and self-injection procedures. The potential benefits of four treatment choices, derived from a meta-analysis of published data, were presented as gains in remission rate (+10%), remission duration (an additional 4 and 7 months, respectively, for induction and maintenance treatment), and overall survival (an additional 3 and 6 months, respectively, for induction and maintenance treatment). Patients' choices for or against use of the unidentified substance were recorded, and interferon was subsequently disclosed as the treatment. The profiles of patients making different choices were determined using multivariate regression techniques. RESULTS Approximately half of the patients accepted the unidentified treatment if remission and/or survival improved by at least 6 months. Accepters were younger and more likely to have used interferon. Of patients who rejected the unidentified treatment, 25% to 50% would have been willing to accept it if the benefits were &gt; or = 12 months. Test/retest reliability of all choices, determined in 36 cancer patients, was 0.896. CONCLUSION In multiple myeloma, interferon therapy and, by inference, other treatments with comparable features are acceptable to approximately half of the patients if a 6-month gain in relapse-free or overall survival can be expected.
Epithelial Blood Group Antigens in Colon Polyps. I. Morphologic Distribution and Relationship to Differentiation 2
Authors: H. Denk, J. H. Holzner, I. Obiditsch-Mayr
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Epithelial Blood Group Antigens in Colon Polyps. I. Morphologic Distribution and Relationship to Differentiation Get access H. Denk, H. Denk Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Holzner, J. H. Holzner Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Obiditsch-Mayr I. Obiditsch-Mayr Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 6, June 1975, Pages 1313–1317, https://doi.org/10.1093/jnci/54.6.1313 Published: 01 June 1975 Article history Received: 06 January 1975 Accepted: 28 February 1975 Published: 01 June 1975
Cisplatin-fluorouracil exclusive chemotherapy for T1-T3N0 glottic squamous cell carcinoma complete clinical responders: five-year results.
Authors: O Laccourreye, D Brasnu, V Bassot, M Ménard, D Khayat, H Laccourreye
Journal: Journal of Clinical Oncology (1996)

To evaluate cisplatin-fluorouracil exclusive chemotherapy (EC) for T1-T3N0 glottic squamous cell carcinoma complete clinical responders (CCR) after cisplatin-fluorouracil induction chemotherapy (IC).A retrospective analysis was performed of 58 patients with T1-T3N0 glottic squamous cell carcinoma CCR after IC consecutively managed at our department between 1985 and 1992. Twenty-one CCR were managed with EC. Thirty-seven CCR were managed with IC and a conventional laryngeal-preservation modality. Analyses of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor were performed using the Kaplan-Meier actuarial life-table method. In CCR managed with EC, the independent factors of age, tumor classification, exact tumor location, true vocal cord motion, arytenoid cartilage motion, total dosage of drugs delivered, and number of courses received were tested for potential correlation with survival, local recurrence, nodal recurence, and distant metastasis.The 5-year survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor rates in CCR managed with EC were 95.2%, 70.7%, 0%, 0%, and 14.3%, respectively. The 5-year rates of survival, local control, nodal recurrence, distant metastasis, and metachronous second primary tumor in CCR managed with IC and a conventional laryngeal-preservation modality were 86.1%, 97%, 2.7%, 6%, and 14.5%, respectively. Local recurrence was statistically more likely in CCR managed with EC (P = .002). Local recurrence in CCR managed with EC was always salvaged with partial laryngectomy or radiation therapy, which resulted in an overall 100% local control and laryngeal-preservation rate within this group. In CCR managed with EC, none of the variables analyzed was statistically related to survival, local recurrence, nodal recurrence, or distant metastasis.The present retrospective studies demonstrated that within T1-T3N0 glottic squamous cell carcinoma CCR, there is clearly a significant subset of patients with chemocurable tumors who achieved both perfect preservation of structure-supporting voice and long-term survival after EC. Careful monthly follow-up evaluation allowed for timely successful salvage of local recurrence after EC without the need for total laryngectomy. Such management did not appear to increase the risk for subsequent nodal failure, subsequent distant metastasis, or reduced survival.
PTH-329 Expression of pigment epithelium-derived factor in colorectal cancer
Authors: RL Harries, J Cai, J Li, S Owen, K Harding, J Torkington, W Jiang
Journal: Gut (2015)

<h3>Introduction</h3> Pigment epithelium-derived factor (PEDF) is a 50kDa, secreted glycoprotein that has been identified as a member of the serpin gene family and has been shown to exhibit neurotrophic, neuroprotective, anti-angiogenic and anti-tumourigenic effects. The aims of our study were to determine the expression profile of PEDF in a range of colorectal cell lines and its association with clinical and pathological data. <h3>Method</h3> Six human cell lines (RKO and HT115 are colonic adenocarcinoma, HRT-18 is rectal adenocarcinoma, COLO-201 is metastatic adenocarcinoma (originating from ascites), LS174T is a mucinous adenocarcinoma, and CCD-33C0 is a normal colorectal fibroblast cell line) were analysed using polymerase chain reaction (PCR) and quantitative transcript analysis (qPCR). Primary colorectal cancer tissue was collected at operation and analysed using qPCR. <h3>Results</h3> PEDF transcript was positive in RKO, HRT-18, LS174T and CCD-33C0 cell lines but negative in HT115 and COLO-201. On qPCR, PEDF expression was highly positive in CCD-33C0. PEDF expression was significantly higher in tissue from mucinous tumours compared to adenocarcinoma (p = 0.0421). PEDF expression was lower in colorectal tissue from palliative resections compared to radical resections, with a trend towards significance (p = 0.097). <h3>Conclusion</h3> PEDF expression was higher in the normal colorectal cell line when compared to colorectal cancer cell lines. There was a trend towards decreased expression in colorectal cancer tissue from palliative resections suggesting a possible tumour suppressor role and may indicate a potential role in primary tumour growth. Further work is proposed to investigate the effect of PEDF expression on cell function. <h3>Disclosure of interest</h3> None Declared.
Immunotherapy with INO-3112 (HPV16 and HPV18 plasmids + IL-12 DNA) in human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCCa)
Authors: Z. Yang, C. Aggarwal, R. Cohen, M. Morrow, J. Bauml, G. Weinstein, J. Boyer, J. Lee, D. Weiner, M. Bagarazzi
Journal: Annals of Oncology (2015)
대간간학회지 제6차 춘계학술대회 초록집 : 구연 ; Thioacetamide에 의한 실험적 간경변증에서 Pentoxifylline이 섬유화와세포주기에 미치는 영향
Authors: 장기택 ( Jang Gi Taeg ), 김미란 ( Kim Mi Lan ), 정인평 ( Jeong In Pyeong ), 조은숙 ( Jo Eun Sug ), 이민재 ( Lee Min Jae ), 이미숙 ( Lee Mi Sug ), 장자준 ( Jang Ja Jun )
Journal: Clinical and Molecular Hepatology (2000)