tbuckley/cabot-search huggingface dataset:
Phase II study of docetaxel with or without plinabulin (NPI-2358) in patients with non-small cell lung cancer (NSCLC).
Authors: A. C. Mita, R. S. Heist, O. Aren, P. N. Mainwaring, L. Bazhenova, S. M. Gadgeel, R. H. Blum, J. Polikoff, J. Biswas, M. A. Spear
Journal: Journal of Clinical Oncology (2010)

7592 Background: Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) that acts on the cytoskeleton to destabilize tumor vascular endothelial cell cohesion with additional cytotoxic activity, leading to selective tumor vascular disruption and necrosis. As VDAs target tumor vasculature through different mechanisms than anti-VEGF pathway agents, the activity and safety profiles are different. VDAs have demonstrated intriguing activity in oncology, particularly in NSCLC where there is potential differentiation from other agents in patient subsets such as those with squamous cell carcinoma or at risk for bleeding events. Positive outcomes were seen in preclinical and early clinical studies in NSCLC with plinabulin and docetaxel, resulting in the initiation of this trial (the ADVANCE study). Methods: The trial will enroll a total of 167 patients with advanced NSCLC who have received prior chemotherapy. Patients were randomized to receive docetaxel alone or docetaxel with plinabulin. Docetaxel (75 mg/m2) was given on Day 1 and in those in the combination arm, plinabulin was added on Days 1 and 8 in 21-day cycles. Two different doses of plinabulin were tested sequentially (30 mg/m2, 20 mg/m2). Primary endpoint is overall survival; secondary endpoints include progression-free survival, response and safety. Results: Enrollment of the 110 patients in the 30 mg/m2 plinabulin dose group is complete, and continues in the 20 mg/m2 plinabulin dose group. Neutropenia was seen as expected with docetaxel. Nausea, vomiting, fatigue, fever, tumor pain, and diarrhea as consistent with plinabulin effects were seen. Of interest, the incidence of neutropenia appeared lower in the combination arm (4% vs. 27%) (consistent with preclinical studies) and the incidence of ileus appeared higher in the combination arm. Out of 64 currently evaluable patients, 6/27 (22%) in the combination arm group had a PR while 2/37 (5%) in the docetaxel arm group had PR (p = 0.04). The results indicate the safety and antitumor activity of the combination. Conclusions: The results demonstrate marked antitumor activity of the combination compared to the control arm, with an acceptable safety profile. Efficacy and safety continue to be compared in a 20 mg/m2 plinabulin dose group to determine the optimal dose to bring into phase III testing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nereus Pharmaceuticals Nereus Pharmaceuticals
Scurvy Following Bilateral Adrenalectomy
Authors: D. Chamberlain, N. V. Addison
Journal: BMJ (1958)

In differential diagnosis, too, the transaminase levels may be of help.On several occasions we found it useful in assessing-whether severe cardiac pain was due to prolonged angina pectoris or actual infarction, the transaminase results correlating in each case correctly with electrocardiographic findings and subsequent clinical progress.No diagnostic rise in transaminase levels was detected in two cases of pulmonary infarction, two cases of gall-bladder dysfunction, two cerebral catastrophes, and six cases of pneumonia.It is of interest that one case of active rheumatic pericarditis (not included in this series) revealed a transiently raised serum transaminase level.This suggests concurrent myocardial damage of a temporary nature, and it will be of interest in the future to ascertain whether serum trans- aminase levels will help in assessing activity in cases of rheumatic carditis where this is in doubt.In carrying out these estimations of serum transaminase levels the method of Frankel and Reitman (1957) was found to have several inherent disadvantages regarding cost and technique.These seem to be overcome in the method described by King (1958), and the simpler technique and its cheapness should place it well within the scope of all routine laboratories.Summary Serum transaminase estimations in a small number of cases of myocardial infarction are related to clinical, electrocardiographic, and necropsy findings.The test's possible value and advantages in early differential diag- nosis and prognosis are discussed.This series reveals close correlation between peak transaminase levels, size of infarct, and immediate outcome.Evidence is presented which shows that cases in which transaminase values rise above 250 SGO-T units do not usually recover.We thank Dr. R. Mowbray and Dr. T. A. Grimson for permission to publish this report
Ultrastructural, Immunocytochemical, and Cytogenetic Characterization of a Human Epithelioid Sarcoma Cell Line (RM-HS1)
Authors: Brian R. Reeves, Cyril Fisher, Sandra Smith, V. Doreen Courtenay, David Robertson
Journal: JNCI Journal of the National Cancer Institute (1987)

A cell line (RM-HS1) derived from a human epithelioid sarcoma was established in tissue culture. Ultrastructurally, the cells show features of those found within the primary tumor. A mixed mesenchymal-epithelial phenotype, defined by reactivity with antibodies to epithelial membrane antigen and to vimentin and keratin intermediate filaments, was found in the tumor, and a similar phenotype persisted in the cultured cells. Cytogenetic analysis revealed a mode of 66 chromosomes. With the use of a variety of banding techniques together with in situ hybridization of a 3H-labeled molecular probe for 18s and 28s ribosomal RNA genes (pX1r101), the karyotypes were shown to contain extensive numerical and structural rearrangements, with up to 24 marker chromosomes.
The evolution of cancer care for children and adults.
Authors: J V Simone, J Lyons
Journal: Journal of Clinical Oncology (1998)

AbstractSeptember 01, 1998 Share on The evolution of cancer care for children and adults.Authors: J V Simone and J LyonsAuthors Info & AffiliationsPublication: Journal of Clinical OncologyVolume 16, Number 9https://doi.org/10.1200/JCO.1998.16.9.2904 Get Access
Cyclin D1 polymorphism, biochemoprevention and risk of upper aero-digestive tract cancer development
Authors: J. G. Izzo, W. N. Hittelman, D. D. Liu, J. J. Lee, X. Wu, W. K. Hong, V. A. Papadimitrakopoulou
Journal: Journal of Clinical Oncology (2004)

1006 Background: We previously showed that the presence of the cyclin D1 (CD1) A870G polymorphism, in advanced pre-invasive lesions (APL) of the upper aero-digestive tract (UADT), was associated with persistent CD1 overexpression during retinoid treatment and risk of cancer development. To validate our findings, we examined the correlation between CD1 A870G polymorphism, protein expression and clinical outcome in individuals with laryngeal APL enrolled in a chemoprevention trial. Methods: 37 subjects with APL of the larynx, persisting after anti-reflux intervention, were enrolled in a prospective phase II chemoprevention study. The subjects received 12-month biochemopreventive therapy with high-dose 13-cis-retinoic acid, a-interferon and a-tocopherol, unless the lesions progressed. Following induction therapy, progression-free subjects were randomized into a 4-HPR/placebo-maintenance therapy. Tissue biopsies were obtained before and 12, 36 month after therapy. CD1 polymorphism was assessed by RLFP analysis, CD1 protein expression by immunohistochemistry. Association of CD1 genotype and protein expression with response and time to progression were investigated. Results: Allele and genotype frequencies were similar to those previously described. CD1 genotype was not associated with sex, age, race, degree of dysplasia, smoking status.The CD1 genotype A groups (AA or AG) developed cancer more rapidly that the GG group (Cancer-Free survival AA/AG: 1-yr 71.4% [95%CI: 51.3%, 99.5%]; 2-yr: 39.7% [95%CI:20.3%,77.7%] vs GG: 1.45-yr: 83.3% [95%CI:58.3%,100%], p=0.05). A similar trend was found for progression-free survival. Conclusions: These results confirm our findings that the CD1 A870G polymorphism is associated with decreased likelihood of response to retinoid-based biochemoprevention, and a shorter cancer-free survival. Subject carrying the CD1 A allele might require alternative chemopreventive interventions. Investigations are ongoing to characterize the biological consequences of the CD1 A870G polymorphism in this patients population. (UO1 CA79437, RO1 DE13157, EDRN 86390). No significant financial relationships to disclose.
Predicting gene promoter methylation in lung tumors through examination of sputum and serum
Authors: S. A. Belinsky, M. Grimes, D. Johnson, D. Levy, J. Schiller
Journal: Journal of Clinical Oncology (2006)

7208 Background: Personalized medicine may be a key approach in improving survival for advanced lung cancer. Success for this approach is seen with the response of cancer patients with an activating mutation within the epidermal growth factor receptor to the growth fact inhibitor, gefitinib. Genes involved in all types of normal cell function are targeted for inactivation by promoter hypermethylation during lung cancer development. This makes gene-specific promoter hypermethylation an attractive target for novel treatment strategies. One obstacle to targeted therapy is accessibility of tissue from peripheral tumors for methylation analysis. The purpose of this study was to determine the predictive power of sputum and serum to detect NSCLC through analysis for methylation of genes in these fluids. Methods: Tissue, serum, and sputum were obtained from 72 stage III NSCLC patients participating in a Phase III trial of Carboplatin, Paclitaxel and Radiotherapy, With or Without Thalidomide (ECOG 3598). Methylation specific PCR assessed methylation of the p16, MGMT, DAPK, RASSF1A, PAX5-α, PAX5-β, H-cadherin, and GATA5 genes. Results: At least one gene was methylated in 89% of tumors. Prevalence for methylation ranged from 15–47% and did not differ between gender. Methylation of ≥ 3 genes was seen in ∼50% of tumors. The agreement between sputum or serum in classifying methylation status of any gene in the tumor ranged from 54– 69%. The reduced sensitivity was presumably due in part to absence of tumor DNA in the biological fluids of methylation positive tumors. Logistic regression models revealed 3.1 (CI, 1.2, 8.2) and 4.2 (1.1, 16.1) increased odds for methylation of the p16 and MGMT gene, respectively in tumors if the serum or sputum was positive for methylation. The effect of tumor histology for predicting methylation using sputum and serum is being examined. Conclusion: These studies demonstrate for genes such as p16 and MGMT the possibility of interrogating biological fluids to predict for methylation in the primary tumor. (Supported by CA-89551). No significant financial relationships to disclose.
Treg phenotype in T-cell lymphomas
Authors: D. Morales, B. E. Beltran, C. Castañeda, A. Carrasco, P. Quiñones, A. Yabar
Journal: Journal of Clinical Oncology (2007)

18513 Background: Foxp3 is a key regulatory gene required for the development and function of: regulatory CD4 + CD25 high T cells (T reg ) specialized in maintaining the balance between immunity and tolerance and activated conventional CD4 + CD25 low T cells without suppressive activity. Previous studies had reported the origin of Adult T-cell Leukemia/Lymphoma cells (ATLL) in Foxp3 T cells and in other lymphomas types the FOXP3 expression was only detected in the reactive T-cell background. Our objetive was to determine the presence of T reg phenotype cells by the FOXP3 expression in T-cell lymphomas. Methods: A retrospective study was performed on 48 samples collected from diverse T-cell lymphomas in our institution. A highly sensitive immunohistochemical method was used to demonstrate T reg phenotype by FOXP3 protein expression with a mouse monoclonal antibody (clone 236A/E7ABCAM) in most formalin-fixed paraffin-embedded tissue sections from lymph nodes, skin, bone marrow and extranodal sites samples as cavum and stomach. We did not co-stained with CD25 and considered a FOXP3+ tissue when positivity was &gt; 20% of tumor cells. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Among the 48 evaluable T-cell lymphomas collected, 33 were ATLL, 8 unspecified peripheral T-cell lymphomas (U-PTCL), 6 mycosis fungoides (MF) and 1 cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma. Among the 33 ATLL: lymphomatous=17, acute=11, smoldering=1, chronic=1, cutaneous=1 and undefined=2. FOXP3 expression in tumour cells was detected in 24% (8/33) of ATLL cases and in 37% (3/8) of U-PTCL. It was negative in MF tumour cells and aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma Among the ATLL cases FOXP3 positivity were obtained in 35% (6/17) of lymphomatous type; 18% (2/11) of acute ones and none in others ATLL types studied. Interestingly 3 U-PTCL had Treg phenotype and were related to EBV (LMP1 positive); two had extranodal primary ( parotide and cavum) and one was nodal. We failed to demonstrate any correlation between FOXP3 status and survival. Conclusions: Some ATLL and U-PTCL had T reg phenotype. In our work Foxp3 expression was not found to be a prognostic factor. No significant financial relationships to disclose.
Depression-Related Increases and Decreases in Appetite: Dissociable Patterns of Aberrant Activity in Reward and Interoceptive Neurocircuitry
Authors: W. Kyle Simmons, Kaiping Burrows, Jason A. Avery, Kara L. Kerr, Jerzy Bodurka, Cary R. Savage, Wayne C. Drevets
Journal: American Journal of Psychiatry (2016)

Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites.Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings.Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings.Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes.
New Insights Into the Negative Regulation of Hematopoiesis by Chemokine Platelet Factor 4 and Related Peptides
Authors: Laurence Lecomte-Raclet, Mònica Alemany, Anabelle Sequeira-Le Grand, Jean Amiral, Gérard Quentin, Anne Marie Vissac, Jacques P. Caen, Zhong Chao Han
Journal: Blood (1998)
Polyoncogenicity and Insulinoma-Inducing Ability of BK Virus, a Human Papovavirus, in Syrian Golden Hamsters&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: S Uchida, S Watanabe, T Aizawa, A Furuno, T Muto
Journal: JNCI Journal of the National Cancer Institute (1979)

Newborn hamsters were inoculated intracerebrally with a series of purified and concentrated BK virus samples originating from a single stock of Gardner's original strain. Most (60-100%) of the hamsters developed various tumors 3-9 months later. The frequent types of tumors were ventricular tumors (choroid plexus papillomas and ependymomas: 7-53%), malignant insulinomas (0-92%), and osteosarcomas (0-50%). The T-antigen was positive in 59 of 60 tumors tested, but the virus was rescued by the cell fusion method from only 1 of 11 cell lines derived from these tumors. The incidence of insulinomas varied greatly with the virus sample; the two samples that showed the highest incidence (47 and 92%) originated from one parental virus stock, and all the other samples with the lower incidences (0-9%) originated from another ancestral stock. These results suggest the presence of a BK virus mutant(s) differing in capacity to induce insulinoma. A functional insulinoma cell line was thus established.
Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction.
Authors: J A Ajani, J A Roth, M B Ryan, J B Putnam, R Pazdur, B Levin, J U Gutterman, M McMurtrey
Journal: Journal of Clinical Oncology (1993)

PURPOSE The curative resection rate in patients with potentially resectable carcinoma of the esophagus is approximately 55% and their median survival time is 11 months. Preoperative chemotherapy with high doses of chemotherapeutic agents was used to evaluate clinical and pathologic responses, curative resection rate, toxicity, and survival. Colony-stimulating factor (CSF) was added to reduce the severity of myelosuppression. PATIENTS AND METHODS Twenty-six consecutive assessable patients with potentially resectable adenocarcinoma of the esophagus or gastroesophageal junction were treated with two preoperative courses of intensive chemotherapy (etoposide, doxorubicin, and cisplatin [EAP]) with granulocyte-macrophage CSF (GM-CSF). Additional three conventional-dose postoperative chemotherapy courses without GM-CSF were given to patients who responded to preoperative chemotherapy. RESULTS A median of three courses (range, one to six), were administered. Of 27 patients, 26 were assessable for response to preoperative EAP; 13 (50%) achieved a major response. Among 23 patients who underwent surgery, 15 (65%) had a curative resection (58% of 26 assessable patients); none of the patients had a pathologic complete response, but two patients had only microscopic carcinoma in the resected specimen. Six patients had carcinoma present at the resection margins and received postoperative radiotherapy. Two patients were found to have liver metastases at exploration. At a median follow-up of 22 months, the median survival of 26 patients was 12.5 months (range, 2 to 32 +). Fourteen patients died of their carcinoma; two patients died of treatment-related causes; one died of an unrelated CNS arterial malformation; and the causes of death in two patients remain unknown. Seven patients are alive with no evidence of relapse. Major toxicities of this regimen included severe myelosuppression, nausea and vomiting, infections, and severe constitutional symptoms related to GM-CSF. However, subcutaneous injection of GM-CSF was well tolerated. CONCLUSION High-dose EAP is active against locoregional adenocarcinoma of the esophagus and gastroesophageal junction but can be associated with significant toxicity. Although this strategy remains attractive and needs to be developed further, less toxic and more effective regimens need to be identified.
Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial
Authors: D. Lorusso, G. Scambia, S. Pignata, R. Sorio, G. Amadio, S. Lepori, A. Mosconi, C. Pisano, G. Mangili, G. Maltese, R. Sabbatini, G. Artioli, T. Gamucci, M. Di Napoli, E. Capoluongo, V. Ludovini, F. Raspagliesi, G. Ferrandina
Journal: Annals of Oncology (2015)
Dietary glycemic index and glycemic load, and breast cancer risk: A case-control study
Authors: L.S.A. Augustin, L. Dal Maso, C. La Vecchia, M. Parpinel, E. Negri, S. Vaccarella, C.W.C. Kendall, D.J.A. Jenkins, S. Franceschi
Journal: Annals of Oncology (2001)
춘계학술대회 : 포스터발표 ; 간경변증 : 활동성 위정맥류 출혈 환자에서 응급 balloon occluded retrograde transvenous obliteraion의 치료 효과
Authors: 홍윤석, 이현웅, 이정민, 이승현, 이석근, 장병국, 정우진, 박경식, 조광범, 황재석, 안성훈, 김영환, 최진수, 권중혁
Journal: Clinical and Molecular Hepatology (2007)
Comment on Weber et al. Type 1 Diabetes Is Associated With an Increased Risk of Fracture Across the Life Span: A Population-Based Cohort Study Using The Health Improvement Network (THIN). Diabetes Care 2015;38:1913–1920
Authors: Viral N. Shah
Journal: Diabetes Care (2015)

Weber et al. (1) analyzed population-based data from The Health Improvement Network (THIN) in the U.K., and they showed increased risk for incident fracture across the life span in type 1 diabetes. Most of the previous studies and meta-analyses, including ours (2), showed a higher risk for fractures in people with type 1 diabetes. However, Weber et al. showed, for the first time, higher fracture incidence even in children and adolescents …
Breakthrough zygomycoses in patients receiving antifungal therapy with voriconazole
Authors: L. Balasubramanian, S. M. Trifilio, M. Tallman, J. Mehta, C. Bennett
Journal: Journal of Clinical Oncology (2005)

6664 Background: Invasive fungal infections are an important cause of mortality and morbidity in immunocompromized hosts. Zygomycetes are increasing concomitant to widespread use of antifungal therapy with voriconazole since its release in May 2002. Methods: We retrospectively analyzed the clinical records of 109 patients at Robert H Luire Comprehensive Cancer Center who were on Voriconazole for prophylaxis, empiric or pathology proven therapy during a period of May 2003 till December 2004. Voriconazole levels were checked on all patients on the drug. Invasive Zygomycete infection was considered a breakthrough if infection was detected by clinical, radiologic, culture or biopsy proven while patient was on voriconazole. Case series analysis with similar criteria was also performed on three other published data from Seattle, Iowa and Boston. Results: 4 of 109 patients had proven infection with invasive zygomycosis with 1 Rhizomucor and 1 Mucor from lung and 2 Rhizopus species from sinuses. Average age was 37, 2/4 were status post matched unrelated hematopoietic transplant and 2/4 were undergoing cytotoxic chemotherapy for hematologic malignancies. 2/4 isolates in culture had MIC performed to voriconazole with value >4. Voriconazole levels in 2/3 were <1μg/ml, 1/3 was 4 and fourth is pending. Of interest 3/4 patients are still alive with two patients 10 months or more since infection. Case series analysis reveals 18/417 patients on voriconazole at four institutions developing invasive zygomycosis with involvement of the lung in 14, gastrointestinal tract in 3, sinus in 3. Mean duration of exposure to the drug prior to breakthrough infection is 63 days. More data and collaboration from several transplant centers is expected with the RADAR group in the next months. Conclusion: A novel way of performing a retrospective analysis includes data collection from all patients on voriconazole who had levels and fungal cultures performed at the same lab. Invasive Zygomycosis appears to be on the increase with more prevalent use of voriconazole with postulated selective pressure or increased survival of profoundly immounocompromised hosts. Early detection and prompt institution of appropriate therapy results in improved survival. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer