tbuckley/cabot-search huggingface dataset:
Results from a phase I study of intraventricular administration of rituximab in patients with recurrent lymphomatous meningitis
Authors: J. L. Rubenstein, A. Shen, L. Abrey, D. Combs, C. Haqq, L. Damon, J. O'Brien, P. O'Connor, M. Prados, M. Shuman
Journal: Journal of Clinical Oncology (2004)

6593 Background: CNS complications of non-Hodgkin's lymphoma (NHL) remain an important cause of morbidity and death in patients with intermediate or high-grade disease. We previously conducted an analysis of the safety and pharmacokinetics of intrathecal Rituximab administration in nonhuman primates (Rubenstein et al; Blood 2003). These results constitute the basis for the current phase I study of intraventricular Rituximab administration. Methods: Six patients with recurrent or refractory CD20 + leptomeningeal NHL were treated at UCSF or at MSKCC. Nine planned injections of Rituximab at 10 mg and at 25 mg dose levels were administered through an Ommaya reservoir over a 5 week period. Matched CSF and serum levels of Rituximab were measured at baseline, 1, 2, 4, 8, 24 and 96 hours. To define early transcriptional events caused by Rituximab, gene expression profile analysis was conducted on B-lymphoma cells purified from CSF at baseline, 1, 2, and 4 hours post-Rituximab administration. Results: Our preliminary results suggest that intraventricular administration of Rituximab was well-tolerated. Toxicities observed include mild leukoencephalopathy and paresthesias, each occurring in one patient. Pharmacokinetic parameters were similar to those defined in nonhuman primates. High peak drug levels were obtained within the ventricles with evidence for rapid craniospinal axis distribution; Rituximab was reproducibly detectable within the lumbar sac at 4 hours. Administration of Rituximab by LP in resulted in a 5-fold increase in intraventricular concentration at 90 minutes. Cytologic responses were immediately detected in 4 patients. One patient had complete resolution of parenchymal as well as leptomeningeal NHL and marked improvement in ocular NHL. Gene expression profile analysis provided evidence for the activation of an apoptotic pathway after Rituximab exposure. Conclusions: Intraventricular Rituximab administration represents a novel means of treatment of CNS involvement of NHL. Efficacy and safety data are promising but additional studies and follow-up are required to evaluate this route of administration. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Genentech Genentech
SYMPTOMATIC AND FULMINANT HEPATITIS B IN INFANCY AFTER UNIVERSAL HEPATITIS B VACCINATION: CLINICAL OUTCOME AND RISK FACTORS
Authors: Yu-Ru Tseng, Huey-Ling Chen, Fu-Chang Hu, Man-Shan Kong, Yao-Jong Yang, Hung-Chang Lee, Jia-Feng Wu, Yen-Hsuan Ni, Hong-Yuan Hsu, Mei-Hwei Chang, Wan-Hsin Wen
Journal: Hepatology (2011)
Risk of vitamin D deficiency rises with breast feeding after age 1, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

The risk of vitamin D deficiency increases progressively in babies who continue to be breast fed beyond the age of 1, even when they also eat solid foods, shows a study published in the American Journal of Public Health , whose authors recommend vitamin D supplements for these children.1

Exclusively breastfed infants are at increased risk of developing rickets because of limited transfer of vitamin D …
Induction of Malignant Bone Tumors in Rats by 1- (2-Hydroxyethyl) -1 -nitrosourea2
Authors: A. Pelfrene, P. Mirvish, B. Gold
Journal: JNCI Journal of the National Cancer Institute (1976)

Forty male MRC-W rats were treated chronically with 1-(2-hydroxyethyl)-1-nitrosourea in drinking water (total dose, 330 mg/rat). Fifteen rats (38%) developed osteogenic osteosarcomas or chondrosarcomas of the lower vertebrae. This was the first time that an orally administered organic compound induced a high incidence of these tumors.
ERCC1, RRM1 and XPD mRNA expression as a predictive marker of outcome in non-small-cell lung cancer (NSCLC) patients after platinum/gemcitabine induction chemotherapy followed by surgery
Authors: E. Felip, R. Rosell, M. Taron, L. Santome, P. Mendez, M. Sanchez, J. J. Sanchez, C. Queralt, J. Baselga, J. Majo
Journal: Journal of Clinical Oncology (2004)

7142 Background: Nucleotide excision repair (NER) is the main DNA repair pathway. ERCC1, RRM1 and XPD are involved in the NER pathway, and tumor upregulation of these genes can lead to chemotherapy failure. Methods: We have analyzed ERCC1, RRM1 and XPD mRNA expression levels using real-time PCR in paraffin-embedded surgical specimens from 67 consecutive stage IIB-III NSCLC patients treated with induction platinum/gemcitabine followed by surgery between September 1998 and December 2002. Results: Radiographic response was observed in 57% of patients. Median survival was 38 months. Fifty-two patients with complete resection attained a 45 month median survival; while ten with incomplete resection had a 6.8 month median survival, and five unresectable patients had a 5.6 month median survival. There were no significant differences in survival according to ERCC1, RRM1 and XPD expression levels. Patients were divided into quartiles according to gene expression levels. For RRM1 levels, patients in the lowest quartile had a decreased risk of death compared to those in the top quartile (RR=0.30; P=0.033). Median survival for the 17 patients in the lowest quartile was 52 months, while for the 15 in the top quartile, it was 26 months (P=0.018). On comparing the characteristics of these 17 patients with the remaining 50, no differences in initial staging were observed. However, the 17 patients in the lowest quartile had more complete resections (94% vs 72%; P=0.03), and pathologic complete responses (29% vs 0%; P=0.00001). No significant differences were observed according to ERCC1 and XPD levels. Conclusions: Platinum-gemcitabine treated patients with low RRM1 levels have better outcomes. Based on these findings we will prospectively analyze the role of RRM1 expression in a neoadjuvant clinical trial. No significant financial relationships to disclose.
Targeting downstream or epigenetic modulation of ErbB1/2 signaling increased radiosensitivity in human cancer cells: Alternative strategies for therapeutic resistance
Authors: In-Ah Kim, Mina No, So Yeon Kim, Jang Mi Lee, Jin Hee Shin, Il Han Kim
Journal: Clinical Cancer Research (2008)

A29   A series of studies have shown solid preclinical and clinical evidences regarding the potential value of targeting ErbB1/B2 signaling to enhance the anti-tumor activity of ionizing radiation. However, therapeutic resistance, resulting from several factors including activation of downstream pathway or alternative survival pathways, as well as molecular resistance mechanisms, has been emerged as an important issue. We tried to identify possible approach to tackle this issue may limit therapeutic benefit of ErbB1/B2 targeted therapy combined with radiation.  We evaluated the inhibitors targeting downstream signaling of ErbB1/B2 and histone deacetylase inhibitor LBH589 (Novartis, USA) would radiosensitize a pannel of human tumor cells having activation of erbB1/B2 signaling. Selective inhibiton of PI3K-Akt-mTOR pathway components using pharmacologic inhibitors significantly attenuated p-Akt (Ser473), p-70S6K (Thr421/Ser424), p-S6 ribosomal protein (Ser235/236) expressions and radiosensitizeda panel of cell lines. Selective inhibition of MEK-ERK pathway components markedly attenuated p-MAPK (Thr202/Tyr204) expression level but radiosensitizing effect was not remarkable. Histone deaceylase inhibitor, LBH589 significantly enhanced the radiosensitivity of the cell lines we tested. Abrogation of radiation induced G2/M arrest, prolonged γH2AX foci, aberrant mitotic features and incresed apoptosis were usual findings. LBH589 increased acetylation of histone H3, tubulin and also increased acetylation of HSP90 which was associated with ubiquitination and downregulation of client oncoproteins ErbB1, ErbB2, c-raf-1 p-Akt and p-MAPK levels. Specific inhibition of HDAC6 isotype by RNAi increased acetylation of HSP90 reduced the chaperone association with client proteins and increased radiosensitivity. Ectopic overexpression of HDAC6 led to partial rescue from LBH589 mediated radiosensitization for erb B1/B2 activated cells  Taken together, these results suggest possible mechanisms to counteract the ErbB1/B2 prosurvival signaling which is implicated in radioresistance, and propose the alternative strategies to overcome therapeutic resistances of available ErbB1 or ErbB2 inhibitors.
High dose chemotherapy (HDC) and autologous peripheral stem cell transplantation (APSCT) in multiple myeloma: Pre-transplant renal dysfunction is a negative predictive factor for survival
Authors: O. Kuzhan Dr., B. Öztürk, A. Özet, F. Arpaci, S. Kömürcü, M. Öztürk, F. Kılıçlı, M. Safalı, S. Ataergin
Journal: Journal of Clinical Oncology (2008)

18025 Background: HDC with APSCT has been used for two decades in the treatment of multiple myeloma with its proven superiority over standard chemotherapy. We report here the outcome of our patients with multiple myeloma who underwent HDC and APSCT in GATA Bone Marrow Transplantation Center. Methods: Between May 1997 and June 2007, totally 48 patients (28 male and 20 female) with median age of 53 years (min-max: 34-72) underwent HDC and APSCT. All patients received high dose melphalan after 3 or 4 cycles of induction chemotherapy (VAD: vincristine, doxorubicin, dexametasone). Results: The rate of transplant related mortality was 2%. One patient died of acute respiratory distress syndrome prior to engraftment. Median follow-up was 26.1 months (min-max: 0.3–122.9). Five year disease free survival and overall survival was %30, and %50, respectively. Patients with pretransplant renal dysfunction (serum creatinine >1.5) lived shorter (%60 vs. %0; p=0,002) (Figure 1). Relapse (88%) was the leading cause of death. One secondary breast cancer and two lung cases were diagnosed. Secondary malignancy was the main cause of nonrelapse related mortality. Two patients received interferon and five thalidomide as posttransplant maintenance therapy. The relapsed patients received thalidomide (n=12), bortezomib (n=3), and interferon (n=2). Conclusions: The outcome of our patients transplanted in GATA BMT Center is similar to other centers worldwide. Pretransplant renal dysfunction is a negative predictive factor for survival. New treatment options should be developed for MM patients with renal dysfunction. No significant financial relationships to disclose.
Non cutaneous AIDS-associated Kaposi’s sarcoma
Authors: J. Stebbing, D. Mazhar, C. Palmieri, C. Thirlwell, T. Powles, M. Nelson, B. Gazzard, M. Bower
Journal: Journal of Clinical Oncology (2006)

9555 Background: Acquired immune deficiency syndrome related Kaposi’s sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe for the first time a proportion of patients with AIDS-KS who presented with no evidence of cutaneous disease. Methods: From our cohort of 5,932 individuals infected with the human immunodeficiency virus (HIV-1) treated in the HAART era, 319 were identified with KS. Of these, 11 patients (5.4%) were diagnosed with KS without the presence of any cutaneous disease. We compared their survival, clinical, immunologic and virologic characteristics to other individuals with KS. Results: There were no statistically significant differences in survival, CD4 count or HIV viral load at KS presentation. We observed that tumour-associated edema (p=0.046) and non-oral gastro-intestinal KS (p=0.042) were significantly more common in patients with non-cutaneous KS. Only 1 case of non-cutaneous KS was observed prior to the era of highly active anti-retroviral therapy (HAART). Conclusions: Non-cutaneous KS is a recognisable condition; patients should be treated with the standard of care as their prognosis is not inferior. This is likely to reflect a strong immune response, in the era of HAART. No significant financial relationships to disclose.
UK nurse who contracted Ebola is readmitted to hospital
Authors: Anne Gulland
Journal: BMJ (2016)

Pauline Cafferkey, the Scottish nurse who contracted Ebola virus disease while working in Sierra Leone, has been readmitted to hospital with symptoms relating to the disease for a second time.

Cafferkey spent almost a month in a special isolation unit at the Royal Free Hospital in London at the beginning of last year after contracting Ebola while working in a Save the Children clinic in Kerry Town, Sierra Leone.

She was then readmitted to the Royal Free in October after developing meningitis …
<i>Notes from the Field</i>: Ebola Virus Disease Response Activities During a Mass Displacement Event After Flooding — Freetown, Sierra Leone, September–November, 2015
Authors: Jeffrey Ratto, Wade Ivy, Anne Purfield, James Bangura, Anthony Omoko, Isaac Boateng, Nadia Duffy, George Sims, Bryan Beamer, Teresa Pi-Sunyer, Sarian Kamara, Sulaiman Conteh, John Redd
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Since the start of the Ebola virus disease (Ebola) outbreak in West Africa, Sierra Leone has reported 8,706 confirmed Ebola cases and 3,956 deaths. During September 15-16, 2015, heavy rains flooded the capital, Freetown, resulting in eight deaths, home and property destruction, and thousands of persons in need of assistance. By September 27, approximately 13,000 flood-affected persons registered for flood relief services from the government. On September 17, two stadiums in Freetown were opened to provide shelter and assistance to flood-affected residents; a total of approximately 3,000 persons stayed overnight in both stadiums (Sierra Leone Ministry of Health and Sanitation, personal communication, September 2015). On the same day the stadiums were opened to flood-affected persons, the Ministry of Health and Sanitation (MoHS) and Western Area Ebola Response Center (WAERC) staff members from CDC, the World Health Organization (WHO), and the African Union evaluated the layout, logistics, and services at both stadiums and identified an immediate need to establish Ebola response activities. The patient in the last Ebola case in the Western Area, which includes Freetown, had died 37 days earlier, on August 11; however, transmission elsewhere in Sierra Leone was ongoing, and movement of persons throughout the country was common.
Challenges in the adjuvant chemotherapy of a patient with colorectal cancer with impaired drug metabolism due to multiple single nucleotide polymorphisms (SNPs).
Authors: N. H. Yamaguchi, V. Assaly, F. Moura, M. Arruda, S. Donatangelo, A. Galvao, E. Maranho, N. D. Comforti-Froes
Journal: Journal of Clinical Oncology (2010)

e13658 Background: Adjuvant chemotherapy for stage III colorectal cancer is a standard procedure and utilizes two classical drugs: a fluoropyrimidine derivative and the oxaliplatin, in different regimens: XELOX, mFOLFOX6, and recently, FLOX. Single nucleotide polymorphism have been involved in different patterns of toxicities but these findings have not been addressed in clinical trials. Methods: We studied the SNPs involved in the metabolism of fluoropyrimidines and oxaliplatin of a 52 years old lady with a pT3N2M0 colorectal grade II adenocarcinoma, with unusual toxicity to the chemotherapy regimens After one clinical oncologist had given her XELOX with oxaliplatin IV for one infusion only. The patient got very sick, and despite calcium and magnesium, there were acute and subsequent peripheral neurotoxicities, swallowing difficulties, cold hypersensitivity, diplopia, grade 3 fatigue, and grade 2 diarrhea concomitant to the use of oral antibiotics and grade 3 cough. With three more infusions of mFOLFOX6 even with a 6 hours infusion of oxaliplatin, she had a grade 3 fatigue, grade 2 mucositis and grade 3 neurosensory toxicities. Results: The patient had different impairment in drug metabolism of the SNPs tested. Regarding the fluoropyrimidines' metabolism, the patient was homozygous to methyl tetrahydrofolate reductase (MTHFR), heterozygous to dihydropyrimidine dehydrogenase (DPD). Related to thymidylate synthase (TS), the patient presented a 2R/3R in the promoter region of the TS gene (TSER), and also showed heterozygosis in 3R (3RC). However, she did not carry a polymorphism in the region 3'UTR (TYM) of TS. Regarding platin compounds metabolism, the patient was a noncarrier of any SNPs at the GSTM1 and GSTT1, but was a heterozygous carrier of GSTP1. Conclusions: In conclusion, there was a possibility that part of the toxicities could be due to the impaired metabolism of the drugs and regimens involved. This case illustrates the need to study more accurately what we call personalized medicine, once until nowadays, it is much more present in the theoretical than in the practical setting of the adjuvant treatments in colorectal cancer. No significant financial relationships to disclose.
A randomized, placebo-controlled phase II trial of ZD6474 plus docetaxel, in patients with NSCLC
Authors: J. V. Heymach, B. E. Johnson, J. A. Rowbottom, P. Fidias, C. Lu, D. Prager, J. Roubec, E. Csada, I. Dimery, R. S. Herbst
Journal: Journal of Clinical Oncology (2005)

3023 Background: ZD6474 selectively targets two key pathways in tumor growth by inhibiting VEGFR-dependent tumor angiogenesis and EGFR-dependent tumor cell proliferation and survival. The optimal dose of ZD6474 for use in combination with docetaxel (Doc) is being assessed in a two-part randomized, double-blind, placebo-controlled trial of ZD6474/Doc vs Doc alone. Methods: Patients (pts) with locally advanced or metastatic NSCLC after failure of 1st-line platinum-based chemotherapy were recruited to an open-label safety run-in phase, which has now been completed. In the subsequent randomized phase, adult pts received once-daily oral treatment with ZD6474 (100 mg or 300 mg) or placebo, in combination with Doc (75 mg/m2 by i.v. infusion every 21 days). The primary objective is to compare progression-free survival (PFS), and will require a minimum of 40 evaluable pts per treatment arm. PFS will be determined from objective tumor assessments (revised RECIST). Secondary objectives include tolerability, objective response rate and survival. Results: The completed run-in phase comprised 15 pts treated with ZD6474 100 or 300 mg (n = 4 and 11, respectively) plus Doc. The combined use of ZD6474 and Doc did not significantly increase toxicity, or change the exposure to either agent. Doc-related myelosuppression (grade 3 or 4) was experienced by eight pts. Four serious adverse events (AEs) were possibly related to study therapy (toxic-induced encephalopathy, nail infection, non-Q-wave myocardial infarction and bacteremia). Two partial responses were seen in the ZD6474 300 mg cohort, and seven pts exhibited stable disease for ≥12 weeks. Overall median time to disease progression was 15.1 weeks and 19.8 weeks in the ZD6474 100 and 300 mg cohorts, respectively. A total of 127 pts (73 male/54 female; median age 59 years, range 29–82), recruited between May 2003 and July 2004, have received treatment in the randomized phase. Conclusions: The run-in phase demonstrated that combined use of ZD6474 and Doc was generally well tolerated and that AEs were manageable. The randomized phase has completed accrual. When ≥90 progression events have occurred (anticipated by the end of 2004), the randomized phase will be unblinded and the data presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca, Genentech, Ligand AstraZeneca Amgen, AstraZeneca, Genentech Amgen, AstraZeneca, Eli Lilly, Genentech, Genta
P0938 : Olive oil comsumption ameliorates non-alcoholic steatohepatitis induced by hypercaloric and hyperlipidic western diets
Authors: F. Martín, E. Jurado, R. Gallego-Durán, G. Berná, A. Robles-Frías, M.J. Pareja, J.A. del Campo, M. Romero-Gómez
Journal: Journal of Hepatology (2015)
On-line hemodiafiltration with endogenous reinfusion (HFR) versus conventional on-line hemodiafiltration (HDF): Efficiency data
Authors: Sunny Eloot, Natalie Meert, I Becaus, J Billiouw, J De Meester, Raymond Vanholder, Pascal Verdonck, B Van Vlem
Journal: Journal of the American Society of Nephrology (2006)
Carcinogen-Induced Cutaneous Neoplasms in Nonhuman Primates 23
Authors: J. L. Palotay, K. Adachi, R. L. Dobson, J. S. Pinto
Journal: JNCI Journal of the National Cancer Institute (1976)

Dimethylbenzanthracene (DMBA) combined with UV light, dodecylbenzene (DDB), or both was oncogenic when applied to the skin of nonhuman primates. Ten years after the cutaneous application of DMBA and a cocarcinogen, 2 groups of rhesus monkeys (Macaca mulatta) displayed dermal melanosis, papillomas, basal cell tumors, and mesodermal sarcomas (accompanied in one case by hepatic metastasis). One group had been painted for 15 months; the other, for 6 1/2 years. Eight years after the initiation of a 4-year regimen of biweekly applications of DMBA plus a cocarcinogen, papillomas, basal cell tumors, and basosquamous cell epidermal tumors with satellite lipomas were observed in galagos (Galago crossicaudatus). The same carcinogen applied to the skin of pottos (Perodicticus potto) caused death in 6 of the 7 animals within 9 weeks. Neoplasms occurred in 17 of the 19 primates that lived longer than 9 weeks after the cutaneous application of DMBA combined with either UV light or DDB.
Abstract 741: Cardiac I-123 Metaiodobenzylguanidine Imaging Lacks the Power to Predict the Risk of Sudden Death in Chronic Heart Failure Patients With Diabetes Mellitus
Authors: Taku Yasui, Takahisa Yamada, Yuji Okuyama, Takashi Morita, Yoshio Furukawa, Koji Tanaka, Yusuke Iwasaki, Hiromichi Ueda, Takeshi Okada, Masato Kawasaki, Yuki Kuramoto, Masakake Fukunami
Journal: Circulation (2009)