tbuckley/cabot-search huggingface dataset:
Prostaglandin in Human Breast Cancer: Evidence Suggesting That an Elevated Prostaglandin Production Is a Marker of High Metastatic Potential for Neoplastic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P H Rolland, P M Martin, J Jacquemier, A M Rolland, M Toga
Journal: JNCI Journal of the National Cancer Institute (1980)

Prostaglandin (PG) production by human breast cancers was investigated in 91 lesions selected so that the distribution of histologic type was similar to that of the general population of mammary carcinomas. With regard to the shape characteristics of the tumors, PG production was higher in lesions classified T1 and T2 than in lesions classified T3 and T4 (T-classification is based on extent of tumor as graded by the International Union Against Cancer), higher in tumors exhibiting a high cellularity than in lesions with a low tumor cell density and higher in tumors in which the cells were still adherent to each other. A high PG production was associated with the presence of neoplastic cells in tumor lymphatic and blood vessels and in axillary lymph nodes. PG production by node metastases was always higher than that by the primary tumor sites. The analysis of the stroma reaction and the presence of edema and necrosis suggest that an active PG synthesis occurred in lesions in which the tumor cell-surrounding stroma presented characteristics of low resistance to invasive growth of cancer cells. With regard to histologic differentiation and histoprognostic grade of lesions, PG production was elevated in carcinomas that retained a minute part of the acinoductal differentiation and in tumors with a moderate or high degree of cancer. A lesion containing a steroid receptor (SR) tended to produce less PG than did an SR-negative tumor. PG production increased slightly according to ages and times of menopause of the patients. PG production occurred early in the natural course of breast cancer and was elevated in tumors at a time when active tumor invasion proceeded. By contrast, PG production decreased later in the course of tumor development. These results indicated that elevated PG production can be used as a marker of high metastatic potential for neoplastic cells in breast cancer.
Evaluation of the effect of calpain inhibitor AK295 on paclitaxel-induced neuropathy and antitumor activity in human cancer xenograft models.
Authors: Y. Sun, P. De, N. Alami, S. Asress, N. Dey, J. Heitner, B. Leyland-Jones
Journal: Journal of Clinical Oncology (2010)

e13510 Background: Paclitaxel is a chemotherapeutic agent that induces apoptosis of tumor cells in several cancer types including ovarian and breast cancer. However, the neurotoxic side effects of paclitaxel limit its therapeutic potential. Paclitaxel treatment has been shown to produce changes in the mitochondrial membrane-potential to increase intracellular Ca2+ causing the activation of calpain. AK295 is a calpain inhibitor which prevents the peripheral neuropathy induced by paclitaxel. The objective of this study is to find out whether or not AK295 prevents paclitaxel-induced neuropathy without affecting the antitumor activity of paclitaxel in human xenograft models. Methods: Immunocompromized mice bearing subcutaneous tumors (MDA-MB-231 and Ovcar3) (n=8/group) were treated with paclitaxel (20mg/kg, every 4th day for 3 weeks, i.v.) and AK295 (24mg/kg/day, oral or Alzet pump for 14 days), as single agent and in combination. Results: The data showed (a) AK295 alone had no effect on the growth of the tumors, (b) treatment with AK295 does not interfere with the antitumor effect of paclitaxel, and (c) the combination of paclitaxel and AK295 was surprisingly more effective (tumor growth inhibition: 51.7% on day 14) in the breast cancer model compared to paclitaxel alone (40.9% on day 20). In terms of neuropathy, MS Wang et al (Brain 2004; 127, 671) demonstrated complete protection (paclitaxel + AK295) versus ∼50% (paclitaxel alone) in tail sensory nerve action potential. Similarly, complete protection (paclitaxel + AK295) versus ∼60% (paclitaxel alone) was observed for neuromuscular function when tested on a Rotarod apparatus. Conclusions: These results demonstrate for the first time a significant improvement in the therapeutic index (complete neurotoxicity prevention with enhancement of antitumor potency) of paclitaxel in human xenograft models. No significant financial relationships to disclose.
Doxorubicin-induced skin necrosis in the swine model: protection with a novel radical dimer.
Authors: S D Averbuch, G Gaudiano, T H Koch, N R Bachur
Journal: Journal of Clinical Oncology (1986)

The treatment of doxorubicin (DOX) extravasation tissue injury is poorly defined. A swine model has been developed to study DOX skin toxicity and potential pharmacologic antidotes. Intradermal injections of DOX in miniature female weanling swine produced predictable and dose-dependent ulcerations that closely resemble lesions observed in humans following extravasation of DOX. The ulcers reached maximal size at 3 weeks following DOX administration and were completely healed by 7 weeks. Bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3) is a radical dimer that can react with DOX in vitro to produce deoxydoxorubicin aglycone, an inactive anthracycline metabolite. When DHM3 was administered into the same intradermal injection site 15 minutes after DOX, the maximum ulcer size was reduced 80%, and the healing time was reduced to 5 weeks. The protection from toxicity was highly dependent on the time interval between DOX and DHM3 injections, with no protection noted after a 60-minute interval. Our data verify the swine model as a useful tool to study DOX-induced extravasation injury. Furthermore, DHM3 is an effective antidote for DOX-induced skin necrosis and has potential for clinical use.
비알콜성 지방간에서 간조직 손상과 혈중 렙틴의 연관성
Authors: 김경오 ( Kyoung Oh Kim ), 박상훈 ( Sang Hoon Park ), 박철희 ( Cheol Hee Park ), 한태호 ( Tai Ho Han ), 유교상 ( Kyo Sang Yoo ), 김종혁 ( Jong Hyeok Kim ), 이명석 ( Myung Seok Lee ), 김동준 ( Dong Jun Kim ), 박충기 ( Choong Kee Park ), 조현득 ( Hyun Deuk Cho )
Journal: Clinical and Molecular Hepatology (2005)

목적: NAFLD는 거대공포성 지방증(macrovesicular steatosis)을 특징으로 하며, 조직학적으로 단순지방증과 NASH를 모두 포함하는 질환이다. 단순지방증에서 NASH가 발생하는 정확한 기전은 알려져 있지 않지만, 최근 렙틴이 NASH의 발생 및 간경변증으로의 진행에 관련이 있음을 시사하는 연구들이 있었다. 저자들은 NAFLD 환자에서 혈중 렙틴과 조직 소견을 비교하여 연관성을 알아보고자 하였다. 대상과 방법: 2001년 7월부터 20
Abstract 18016: Maternal Age is a Modifiable Risk Factor for Congenital Heart Disease
Authors: Claire E Schulkey, Suk D Regmi, Rachel A Magnan, Megan T Danzo, Alayna K Hutchinson, Herman Luther, Adam A Panzer, David B Wilson, Patrick Y Jay
Journal: Circulation (2014)

INTRODUCTION:  Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. We previously reported the same risk for newborn mice that carry a mutation of the cardiac transcription factor NKX2-5. Whether the basis of the risk resides with the mother or oocyte is unknown. We describe here characteristics of the mechanism by which maternal age acts a risk factor for congenital heart disease in  Nkx2-5  +/-  mice.   METHODS and RESULTS:  First, we performed reciprocal ovarian transplants between young and old mothers in a C57BL/6N X FVB/N F1 hybrid background. The incidence of VSD in the  Nkx2-5  +/-  offspring was associated with the age of the mother and not the ovary. This result clearly indicates the existence of an age-related maternal factor that interacts with embryonic cardiac development. Second, a high-fat diet did not increase the maternal age-based risk, so abnormal glucose metabolism and obesity do not simply explain the mechanism. Third, the risk associated with maternal aging is a quantitative genetic trait. It was highest in the inbred C57BL/6N background, intermediate in the C57BL/6N X FVB/N F1 hybrid, and insignficant in the C57BL/6N X A/J F1 hybrid. Maternal genetic polymorphisms must determine the activity of the factor that mediates the age-based risk. Finally and most surprisingly, voluntary exercise by mothers can abrogate the age-based risk. Running wheels in breeding cages reduced the incidence of VSD from 20 to 9% for the offspring of old mothers. The lower incidence is similar to that observed in the offspring of young, sedentary mothers.   CONCLUSION:  A mother’s age, genes, and exercise influence a pathway that interacts with embryonic cardiac development. Interventions aimed at the mother could meaningfully reduce the risk of congenital heart disease in offspring who carry a deleterious mutation.
Systemic Benefit of Gm-Csf-Encoding, Oncolytic Herpes Virus (Talimogene Laherparepvec, T-Vec) in Metastatic Melanoma: Phase Ii Assessment
Authors: N. Senzer, C. Bedell, S. Horvath, J.J. Nemunaitis
Journal: Annals of Oncology (2014)
Concentrations of the DNA methyltransferase inhibitor 5-fluoro-2’-deoxycyticine (FdCyd) &amp; its metabolites 5-fluoro-2’-deoxyuridine (FdUrd), 5-fluorouracil (FU), 5-fluorouridine (FUrd), &amp; 5-fluorocytosine (FC) in plasma of patients treated with FdCyd
Authors: J. H. Beumer, R. A. Parise, E. M. Newman, J. H. Doroshow, T. W. Synold, H. Lenz, M. J. Egorin
Journal: Journal of Clinical Oncology (2006)

2023 Background: The DNA methyltransferase inhibitor, FdCyd, is in phase I clinical trials. It is combined with tetrahydrouridine (THU), a cytidine deaminase inhibitor, to prevent rapid metabolism of FdCyd to the pharmacologically active metabolites FdUrd, FU, FUrd, &amp; FC. We assessed the plasma levels of these active, yet undesired, metabolites in patients receiving FdCyd+THU. Methods: We developed a hydrophilic interaction chromatography LC-MS/MS assay capable of simultaneously quantitating FdCyd &amp; metabolites. Patients were treated with 5 daily, 3-h infusions of FdCyd at doses of 5–80 mg/m 2 . Plasma was obtained before &amp; at the end of infusions (EOI) on days 1 &amp; 5. Results: The lower limits of quantitation for FU, FdUrd, FUrd, FC &amp; FdCyd were 1, 1.5, 10, 3, &amp; 10 ng/ml, respectively, &amp; the assay for each analyte was linear over a 300–1000 fold range of concentrations. Plasma FdCyd increased with dose from 19–96 ng/ml at 5 mg/m 2 to 1600–1728 ng/ml at 80 mg/m 2 , as previously described. FdUrd was not detectable in plasma of patients treated with FdCyd doses &lt;20 mg/m 2 , &amp; then increased from 2.31 ng/ml at 20 mg/m 2 to 3.5–5.7 ng/ml at 80 mg/m 2 . FU was present in plasma of patients treated at all doses studied, &amp; FU concentrations increased with dose. Inter-patient variability in concentrations was 1.5–3 fold (FdUrd) and 2–4 fold (FU). FUrd &amp; FC were only present in the day 1 plasma sample of one patient, who was treated at 40 mg/m 2 , &amp; were not present in the day 5 sample of that patient. No FdCyd or metabolite was detected in day 5 pretreatment plasma of the 2 patients treated with 80 mg/m 2 of FdCyd. Conclusions: FdCyd administered with THU undergoes little catabolism. The EOI FU and FdUrd concentrations in plasma of patients treated with FdC+THU are &lt;10% those observed after therapeutic continuous infusions of FU or FdUrd. Thus, selective inhibition of DNA methylation with FdCyd+THU is feasible. The LC-MS/MS assay developed will be a valuable tool to pharmacologically support continuing clinical development of FdCyd. Support: NO1-CM52202, P30CA47904, U01CA62505, &amp; P30CA33572. No significant financial relationships to disclose.
Molecular phylogenetic evidence that the phylum Haplosporidia has an alveolate ancestry.
Authors: M E Siddall, N A Stokes, E M Burreson
Journal: Molecular Biology and Evolution (1995)

The phylogenetic position of the phylum Haplosporidia among other protists was investigated with the complete 16S-like rRNA gene sequences from two species in the phylum: Haplosporidium nelsoni, a parasite of oysters, and Minchinia teredinis, a parasite of shipworms. Because the lack of obvious morphological homologies with other protists hampered decisions regarding taxonomic composition for sequence alignment and phylogenetic analysis, the complete sequences for these two haplosporidians were directed as search queries to the blast/ncbi.nlm.nih.gov electronic mail server. The results of this heuristic similarity search provided a basis for constructing a preliminary higher-taxonomic-level analysis comparing the haplosporidians with species from the slime molds, fungi, algae, amoebae, ciliates, dinoflagellates, and apicomplexans. Maximum parsimony yielded equivocal results, whereas transversionally weighted parsimony suggested an affinity with the alveolates (i.e., the ciliates, dinoflagellates, and apicomplexans). Multiple alignment of the two haplosporidian sequences against 17 taxa in a secondary analysis focusing on the alveolates and subsequent parsimony analysis placed the phylum Haplosporidia as a monophyletic group within the Alveolata and as a taxon of equal rank with the other three alveolate phyla. The precise placement within the Alveolata was sensitive to weighting.
The efficacy and risk of prophylactic entecavir for hepatitis B virus-related hepatocellular carcinonma receiving transcatheter arterial chemoembolization.
Authors: Xing Li, Xiang Zhong, Zhan-Hong Chen, Yan-Fang Xing, Xiao-kun Ma, Zhi-Huan Lin, Qu Lin, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2015)

388 Background: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log 10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusions: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.
The use of pembrolizumab for the treatment of metastatic uveal melanoma.
Authors: Lisa A. Kottschade, Robert R. McWilliams, Svetomir Markovic, Matthew Stephen Block, Jose Villasboas Bisneto, Anthony QuocAnh Pham, Roxana Stefania Dronca
Journal: Journal of Clinical Oncology (2015)

9010 Background: Uveal melanomas are a rare type of melanoma with only 5-7 cases per 1 million persons diagnosed each year. Patients with metastatic melanoma of uveal origin, tend to have lower response rates on traditional therapies, as well as are usually excluded from clinical trials. Herein we report our experience with 7 patients with metastatic uveal melanoma who received pembrolizumab as part Merck's expanded access program. Methods: Patients were considered eligible for treatment on this protocol, if they were ≥ 12 years old, diagnosed with unresectable metastatic melanoma, had progressed on prior ipilimumab therapy, and if BRAF mutant had progressed on BRAF inhibition therapy. Patients had to have good performance status (ECOG of 0 or 1) and adequate organ and marrow function. Patients could have CNS disease, but needed to be clinically stable, prior to enrollment and could not be receiving other concurrent therapy for their cancer. Patients were treated with 2 mg/kg of pembrolizumab IV over q3 weeks until disease progression, unacceptable toxicity or for up to 2 years. Results: Between 4/15/2014 and 8/6/2014, we enrolled a total of 7 patients with metastatic uveal melanoma onto study MK-3475-030. Median age at enrollment was 64, with 5 patients being female. As of the data cutoff date of 1/27/2014 median progression free survival was 12.2 weeks (range 3.14-41) with 2 patients still currently receiving therapy without progression. There was 1 CR, 1 PR and 1 patient with SD. Three patients had PD and 1 patient was excluded as she discontinued therapy after 1 dose due to grade 4 endocrine toxicity. Other toxicities were as expected and were usually grade 1 or 2 in nature. Conclusions: While this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. Toxicities were acceptable and expected. Patients were all pretreated, most with 2+ regimens. Treatment with pembrolizumab appears to be a viable option for patients with metastatic uveal melanoma. Clinical trial information: NCT02083484.
Spontaneous Regression in Virus-Induced Murine Leukemia. II. Influence of Environmental Factors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Marvin A. Rich, Rodney Clymer, Seung Karl
Journal: JNCI Journal of the National Cancer Institute (1969)

The spontaneous regression of a virus-induced murine leukemia has been observed to date in 71% of 630 leukemic mice inoculated with the strain of Friend virus that causes a regressing leukemia. The incidence of leukemia induced by this virus strain was constant in mice inoculated at 2 days through 9 weeks of age. Regression was observed only in those mice inoculated at 4 weeks of age or older. The severity of the leukemic response in younger mice was such that significant numbers were dead prior to the period during which regression could occur. The inverse relationship between virus titer and regression that was observed could be similarly explained by an accelerated appearance of irreparable histologic trauma or death. Several lines of evidence suggested at least two determinants for spontaneous regression: infection by the appropriate virus genome and the presence of those environmental factors that permit the mouse to survive long enough for the regression to be expressed. During a 200-day observation period of several groups of mice, 30–50% of mice whose leukemia had regressed eventually redeveloped signs of the disease. In 140 of the 231 mice in which the disease regressed, recurrence has not been observed to date. In those animals in which leukemia did recur, it was identical to the erythrocytic disease that had previously regressed. Recurrence of leukemia invariably occurred between 70 and 130 days post inoculation; at this time infectious virus could again be isolated from leukemic mice but not from those with regression. This virus, as well as that isolated from mice whose primary leukemic response did not regress, induced a leukemia in recipient mice that subsequently regressed.
Applying the Principles of McDonaldization to Medicine—Reply
Authors: E. Ray Dorsey, George Ritzer
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Outcomes of critically ill patients with lung cancer
Authors: M. Soares, M. Darmon, C. G. Ferreira, J. Salluh, S. De Miranda, M. Adda, N. Spector, E. Azoulay
Journal: Journal of Clinical Oncology (2006)

16001 Background: Recent advances in oncology and critical care have resulted in improved survival in critically ill cancer patients. An appraisal of the prognosis of critically ill patients with lung cancer is timely. Methods: The aim of this study was to evaluate the outcomes and prognostic factors of critically ill cancer patients with lung cancer. From 2000 to 2005, patients with either small-cell (SCLC) or non-small-cell lung cancer (NSCLC) admitted at two intensive care units (ICU) in Brazil and France were included. Patients with postoperative care, ICU stay &lt;24 h and readmissions were excluded. Demographics, clinical, cancer related and outcome variables were collected. Hospital mortality was the outcome variable of interest. Variables selected in the univariate analysis (p &lt; 0.25) and those considered clinically relevant were entered in a multivariable logistic regression analysis [results were expressed as odds-ratios (OR), 95% confidence interval (CI)]. Results: A total of 132 patients were studied (INCA = 87, St Louis Hospital = 45). Their mean age was 61 ± 10 years and 73% were males. Twenty-five (19%) had SCLC and 107 (81%), NSCLC. The SAPS II score was 48 ± 21 points. The main reasons for ICU admission were severe sepsis (45%) and acute respiratory failure (33%). During ICU stay, 96 (73%) patients received mechanical ventilation, 76 (58%) vasopressors and 11 (8%) dialysis; 15 (11%) patients were treated with chemotherapy and 6 (5%), radiation therapy. Thirty-eight (29%) patients had end-of-life decisions. ICU and hospital mortality were 43% and 60%, respectively. Multivariable analysis identified three independent determinants of hospital mortality: airway obstruction/infiltration by cancer [OR = 2.87 (1.34–8.13), p &lt; 0.001], number of organ failures [OR = 1.91 (1.01–2.74), p = 0.047] and performance status 3–4 before admission [OR = 2.90 (0.94–8.95), p = 0.065]. Conclusions: Improved survival in overall ICU cancer patients extends to patients with lung cancer, including those needing mechanical ventilation. Interestingly, the characteristics of the cancer are not associated with the outcome and should not be the grounds for the ICU decision making. Mortality is increased with the number of organ dysfunctions, in particular when respiratory failure is due to cancer progression. No significant financial relationships to disclose.