tbuckley/cabot-search huggingface dataset:
Pioglitazone may reduce cardiovascular events in high risk patients with prediabetes
Authors: Susan Mayor
Journal: BMJ (2016)

Pioglitazone, an insulin sensitising agent, may reduce the risk of myocardial infarction (MI) and stroke after a recent transient ischaemic attack (TIA) or stroke in patients without diabetes who are insulin resistant, a randomised trial has shown.1

The study investigated whether treating insulin resistance, which previous research has shown to affect more than half of people without diabetes who have an ischaemic stroke or TIA, could offer a new approach to reducing the subsequent risk of stroke …
Kinetics Of Cell Replication Of The Uterine Cervix. V. Behavior of DNA-Replicating Tumor Cells in Invasive Squamous Carcinomas in Mice2, 3
Authors: C. A. Rubio, Y. Kock
Journal: JNCI Journal of the National Cancer Institute (1981)

Journal Article Kinetics Of Cell Replication Of The Uterine Cervix. V. Behavior of DNA-Replicating Tumor Cells in Invasive Squamous Carcinomas in Mice, Get access C. A. Rubio, C. A. Rubio Search for other works by this author on: Oxford Academic PubMed Google Scholar Y. Kock Y. Kock Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 6, June 1981, Pages 1137–1141, https://doi.org/10.1093/jnci/66.6.1137 Published: 01 June 1981 Article history Received: 04 June 1980 Accepted: 28 November 1980 Published: 01 June 1981
Site-selective cAMP analogs at micromolar concentrations induce growth arrest and differentiation of acute promyelocytic, chronic myelocytic, and acute lymphocytic human leukemia cell lines
Authors: G Tortora, P Tagliaferri, T Clair, O Colamonici, LM Neckers, RK Robins, YS Cho- Chung
Journal: Blood (1988)
The impact of the inclusion of clinical data review on overall radiographic response and progression in oncology clinical trials as assessed by blinded independent central review
Authors: N. Wangler, K. Borradaile, R. Ford
Journal: Journal of Clinical Oncology (2009)

6511 Background: The United States Food and Drug Administration (USFDA) advocates blinded independent central review (BICR) of radiographic exams for oncology registration studies when the primary study endpoint is based on tumor measurements, such as progression-free survival, time to progression or objective response rate. However, a proportion of subjects progress clinically prior to radiographic evidence of disease progression and in certain indications, measurement of cutaneous lesions may be incorporated into response criteria calculations. Methods: BICR data from 4,183 subjects in the following indications: lymphoma, melanoma, breast cancer, and colorectal cancer, was blinded, pooled, and reviewed to determine the impact of clinical review on best response and date of progression following BICR of radiographic images. Results: Inclusion of clinical data and/or clinical photography impacted 27% (47/171) of lymphoma subjects, affecting the assessment of the best response (13%), best response date (16%) and/or the date of progression (19%); 12% (13/107) of melanoma subjects, affecting the assessment of the best response (6%), best response date (5%), and/or the date of progression (8%); 10% (308/2,947) of breast cancer subjects, affecting the assessment of the best response (4%), best response date (4%), and/or the date of progression (9%); 3% (32/958) of colorectal cancer subjects, affecting the assessment of the best response (2%), best response date (2%), and/or the date of progression (2%). Conclusions: When using BICR to determine endpoints in oncology clinical trials, inclusion of a clinical review may be relevant in 27% of subjects for lymphoma, 12% for melanoma, 10% for breast cancer, and 3% for colorectal cancer. [Table: see text]
A phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advanced stage ovarian, primary peritoneal, and fallopian tube cancer
Authors: C. Aghajanian, P. Sabbatini, F. Derosa, S. Gerst, D. R. Spriggs, J. Dupont, M. L. Hensley, S. Pezzulli, J. Konner, R. J. Schilder
Journal: Journal of Clinical Oncology (2005)

5047 Background: Elevated expression of EGFR in ovarian cancer is associated with poor prognosis. This study is being conducted to assess the feasibility of adding the anti-EGFR antibody cetuximab (C225) to standard upfront chemotherapy for ovarian cancer. Methods: Previously untreated patients (pts) with stage III or IV epithelial ovarian carcinoma, primary peritoneal carcinoma, or fallopian tube carcinoma are eligible for this study. KPS must be ≥70% and tumors must be EGFR positive. Pts receive an initial dose of C225 of 400 mg/m2 on Day 1 of Cycle 1, followed by 250 mg/m2 weekly. Paclitaxel (P, 175 mg/m2) and carboplatin (C, AUC=6mg/ml.min) are given on D1 of each 3-wk cycle. Pts may receive a max. of 6 cycles during initial treatment. Pts with complete clinical response (cCR) receive 6 months consolidation with weekly C225. The primary objective is progression-free survival (PFS); response rate and toxicity are also assessed. A total of 39 eligible pts are planned for accrual; 31 pts have been accrued to date. Results: The first 17 pts completing 6 cycles of initial treatment are reported. Median age 54 yrs. (range 37–75). 10 pts (IIIA-1, IIIB-1, IIIC-8) were opt debulked, 4 pts (IIIC-4) subopt debulked and 3 pts were Stage IV. 71% ovarian, 23% primary peritoneal, 6% fallopian tube carcinoma. Histology: 100% serous adenocarcinoma. 15 of 17 pts were evaluable for response; 2 pts with wrong diagnosis were unevaluable. 13 pts (87%) had unconfirmed cCR. 10 (100%) of opt debulked pts and 3 (75%) of subopt debulked pts had cCR. 15 pts (88%) received the planned dose of C225; 16 pts (94%) and 17 pts (100%) received planned doses of P and C, respectively. Median no. (range): C225 doses, 18 (1–18); C225 doses/cycle, 3 (1–3); and cycles of C225/P/C completed, 6 (1–6). Gr 3 toxicities: febrile neutropenia (12%), diarrhea (6%), and hypersensitivity (6%). No Gr 4 toxicities were noted. Fifteen pts (88%) had acneform rash (Gr 1/2 53%/35%). Conclusions: Preliminary data for this ongoing study indicate the combination of C225 with P and C is well tolerated in this patient population. Data on tolerability of prolonged maintenance cetuximab will be available for presentation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Confirmed pulmonary tuberculosis leading to late diagnosis of lung cancer - Study case
Authors: Mimi Floarea Nitu, Mihai Olteanu, Raluca Marinas, Madalina Olteanu, Cristina Calarasu, Alina Miulescu
Journal: European Respiratory Journal (2013)

We report the case of a 56 years old man, unemployed, smoker, that was admitted for fever, chills, productive cough and progressive dyspnea symptoms that were present for the last two months and were not influenced by an antibiotic treatment for 10 days. Physical exam: pale sweated skin, fever, onychomycosis, diminished breath sounds and rough sounds in middle areas of the lungs, SaO2 – 96%. Chest x-ray revealed nodular opacities of different sizes and small associated cavitations in both upper areas of the lungs. Sputum smears and culture were positive for mycobacterium tuberculosis. So the diagnosis for him was pulmonary tuberculosis and he was treated with specific antituberculosis treatment.  After 90 days his condition got worse and the thorax and abdominal computed tomography evidenced a tumor like mass of 8/7 cm in the right upper lobe with central necrosis and multiple thoracic lymph nodes (some organized in lymphatic masses), also many round shaped tumor like masses inside the liver. Final diagnosis: Right lung cancer T2N2M1 (stage IV), Confirmed pulmonary tuberculosis situated on both upper lobes.  Conclusion: Confirmed simultaneous pulmonary tuberculosis delayed thorax computed tomography and the diagnosis of the lung cancer in upper right lobe. Patients that are diagnosed with tuberculosis, smoker or ex- smokers, should be investigated more carefully taking in consideration the possible association with cancer, and other investigations for diagnosing neoplastic diseases should be done in the same time with the ones for TB.
A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603
Authors: E. M. O’Reilly, D. Niedzwiecki, D. R. Hollis, T. S. Bekaii-Saab, T. Pluard, A. Duffy, F. Overcash, S. P. Ivy, R. M. Goldberg
Journal: Journal of Clinical Oncology (2008)

4515 Background: S is an oral broad-spectrum tyrosine kinase (TK) inhibitor with potential utility in PAC given the perturbation of multiple signaling pathways and stromal alterations noted in PAC. CALGB conducted an NCI-sponsored phase II study of S in patients (pts) with previously-treated PAC. Methods: Eligibility included: PAC previously treated with front-line gemcitabine (gem) therapy, or progression of disease (PD) during or within 3-months of completion of adjuvant therapy, or newly metastatic disease following therapy for locally advanced PAC; performance status 0–2; measurable disease by RECIST; no prior anti-VEGF therapy; no evidence of duodenal invasion on CT. S was dosed at 50 mg daily for 28 days followed by 14 days of rest (1 cycle). Re-staging was performed after each of the first 4 cycles of therapy. Study design: Single-arm, multi-center cooperative group, 3-stage design, with response criteria of at least stable disease (SD) in 1/19, 2/39, for expansion. Planned accrual was 64. Primary endpoint: Response rate (RECIST). Secondary endpoints: Duration of response, toxicity, PFS, and survival. Results: From 11/06 to 11/07, 77 pts were accrued with the criteria met for full accrual (1 withdrew consent). Pt characteristics were: male 54%, female 46%, age: median 65 yrs, range 42- 87, and PS 0/1/2 45%/48%/7%. Prior therapy included: gem 61%, gem-based combination 37%, TK inhibitor 14%, radiation therapy 14%. Sites of disease were: liver 84%, lung 30%, other 19%. As of 12/07, 52 pts are evaluable for response. Response criteria for continuation were met at the two interim analyses. SD occurred in 7 pts [13%, 95% CI (3.6%, 22%)] and PD in 29 (56%). Number of cycles received was: 1- 86%; 2- 12%, 3- 2%. Dose modification was needed in 21%. Median PFS was 41 days (CI 37–57d), and median OS 97 days (CI 79–127d). Grade 3–5 toxicities included: hematologic 13% (G3), fatigue 12%, bleeding 6% (G3), nausea 4% (G3), Thrombosis/embolism 2% (G3), TTP/renal failure 2%, GI perforation 2% (G5). Conclusions: Preliminary analysis of a large cooperative group phase II study of S in previously-treated PAC suggests modest single agent activity and no new safety signals in this patient population. Final results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer
The surgeon’s impact on ER status.
Authors: Kristin A. Skinner, Rachel Leah Farkas, Krisitn Mccarthy, Ping Tang, Leanne Hellman, Jeanette Fronk, Carl H. Andrus, James L. Peacock, David G. Hicks
Journal: Journal of Clinical Oncology (2012)

153 Background: Long ischemic times prior to tissue fixation can lower the accuracy of immunohistochemical staining (IHC). The purpose of this study was to identify factors that impact the time to fixation (TTF), and to determine if TTF impacts prognostic factor (PF) patterns and if TTF can be changed with simple interventions. Methods: Surgeries performed between 2008 and June 2011 for which TTF was noted and PF testing was done were reviewed. TTF, patient age and race, surgeon, date and type of surgery, tumor size, nodal status, grade, and status of ER/PR and HER2 by IHC were noted. TTF was dichotomized into &gt; or &lt;60 minutes. In-Services (IS) for pathology and surgical staff were completed. TTF before and after the IS were compared. Associations between TTF and other factors were assessed using standard methods for contingency tables. Predictors of ER status were evaluated by multivariate analysis. Results: Mean TTF was 72 minutes (range 12-445) TTF was significantly associated with surgeon, type of specimen, and ER status (Table). TTF was an independent predictor of ER status by multivariate analysis. TTF was shorter and less variable after IS. Conclusions: TTF varied significantly between surgeons. IS training of the surgeons and OR and pathology staff can decrease TTF. Longer TTF was associated with increased ER negativity, suggesting that longer ischemic time interferes with IHC for ER. If prolonged TTF leads to false negative ER staining, patients may not receive optimal therapies. To minimize this risk, the breast surgeon should take an active role in minimizing the TTF. [Table: see text]
Phase 1 study of weekly anti-vascular endothelial growth factor receptor-1 (VEGFR-1) monoclonal antibody IMC-18F1 in patients with advanced solid malignancies
Authors: S. S. Krishnamurthi, P. M. LoRusso, P. H. Goncalves, F. Fox, E. K. Rowinsky, J. Schwartz, H. Youssoufian
Journal: Journal of Clinical Oncology (2008)

14630 Background: VEGFR-1 is expressed on both tumor vasculature and a wide range of human tumors. IMC-18F1 is a recombinant human monoclonal IgG1 antibody that directly targets VEGFR-1 so as to block ligand binding and, in turn, downstream VEGFR-1 signaling. VEGFR-1 activation is also critical for epithelial-mesenchymal transformation and is a mediator of circulating hematopoietic progenitor cells that condition the microenvironment enabling the growth of tumor metastases. Methods: This Phase 1 study of IMC- 18F1 was designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity of IMC-18F1 administered weekly at doses of 2, 3, 6, and 12 mg/kg IV (Cohorts 1–4). If safety, PK, and pharmacodynamic data supported less frequent dosing, then schedules of 15 mg/kg every 2 weeks and 20 mg/kg every 3 weeks (Cohorts 5 and 6) were to be evaluated. Results: A total of 14 patients have received treatment as part of Cohorts 1–4. To date, there have not been IMC-18F1-related, grade > 2 adverse events (AE) nor dose- limiting toxicities observed. The most common AEs considered at least possibly-related to study drug include fatigue (n = 5), nausea (n = 3), and anemia (n = 2). Following the final infusion in Cycle 1; the mean half-life of IMC-18F1 increased with increasing dose (85.9 - 205.4 hrs); the mean clearance decreased with increasing dose (0.208–0.067 mL/hr/kg), suggesting that saturation of elimination was being approached. Cmax and AUCinf increased in a greater-than-dose-proportional manner, indicating that the PK of IMC-18F1 was nonlinear. Conclusions: Enrollment on this study continues, with an evaluation of 15 mg/kg every-2-week and 20 mg/kg every-3- week schedules based on supportive PK and toxicity profiles. The preliminary safety, PK, and biological activity data support further disease- directed development of IMC-18F1. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration ImClone Systems Incorporated ImClone Systems Incorporated
Neoadjuvant chemotherapy does not effect presence of micrometastases in bone marrow of breast cancer patients
Authors: G. Gebauer, T. Fehm, K. Klich, M. Anna-Maria, P. Baier, H. Maul, M. Eichbaum, N. Fersis, C. Sohn
Journal: Journal of Clinical Oncology (2005)

867 Background: The idea of adjuvant systemic therapy in breast cancer patients is to eliminate occult tumor cells which may already disseminate at a very early stage. The presence of occult tumor cells in bone marrow of breast cancer patients without evidence for clinically relevant metastatic disease is associated with worse overall and disease-free survival. However, it is unclear whether cytostatics may eliminate those occult tumor cells. Methods: Bone marrow aspirates obtained during surgery in breast cancer patients with locally resticed disease without evidence of a metastatic tumor cell spread were immunohistochemically stained with anti-cytokeratin antibodies in order to detect disseminated tumor cells. In a matched pair analysis bone marrow results of patients receiving neoadjuvant chemotherapy were matched with patients undergoing surgery first followed by adjuvant therapy. Results: Thirtyfour patients receiving neoadjuvant CTx were included into the analysis and matched for clinical stage and age with 34 breast cancer patients undergoing primary surgery. Detection rate of micrometastases was 23 out of 34 in the neoadjuvant group compared to 13 out of 34 in patients receiving surgery first followd by adjuvant therapy. Both groups did not significantly differ in clincal stage, age or bone marrow status. Interestingly, in 2 patients receiving trastuzumab in a neoadjuvant setting, no disseminated tumor cells were detected after systemic therapy. Conclusions: Our results suggest, that bone marrow status - which is highly correlated to survival - is not affected by cytostatic therapy. Therefore, adjuvant therapies in patients with micrometastases in bone marrow may include additional strategies in order to specifically target cells of a minimal residual disease. No significant financial relationships to disclose.
A phase I trial of AVN944 in patients with advanced hematologic malignancies
Authors: R. B. Klisovic, G. Tricot, S. Coutre, T. Kovacsovics, F. Giles, T. Genna, D. K. Bol, J. W. Strovel, J. M. Hamilton, B. Mitchell
Journal: Journal of Clinical Oncology (2007)

14026 Background: AVN-944 is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that catalyzes the rate- limiting step in guanine nucleotide synthesis, and induces apoptosis in malignant hematopoietic cell lines in vitro. Methods: This phase I study employed open-label dose escalations in patients (pts) with relapsed, refractory hematologic cancers with safety, pharmacokinetic (PK), pharmacodynamic, &amp; efficacy endpoints. Between 12/05 and 1/07 a total of 70 cycles of AVN944 at 25 (7pts), 50 (6pts), 75 (7pts), 100 (7pts) or 125 mg (3pts) b.i.d. orally X 21d every 28d were administered to 30 pts with AML (12), ALL (2), CLL (3), and multiple myeloma (13). Peripheral blood mononuclear cell (PBMC) or leukemic blast samples were obtained from all pts pre and post-receiving AVN944 to determine effects on GTP pools, IMPDH activity, and to correlate these changes to response in a 32-gene set that relates directly to cellular pathways dependent upon guanine nucleotide biosynthesis. Results: Pharmacokinetics were dose proportional with mean T max =1 hour, T 1/2 =1.5 hours, Cmax=2800 ng/ml and AUC=7228 hr.ng/ml at the 100 mg b.i.d. dose. Toxicities were generally mild-moderate and/or not attributed to AVN944. Twelve serious adverse events (SAEs) occurred in 8 pts; 7 of 8 had AML. No SAEs was attributed to AVN944. DLT was not seen. No protocol defined responses were seen. Twelve of 24 assessable pts had stable disease of 2 to 10 months duration. Changes in the gene expression set correlated with disease stability. Conclusions: AVN944 is well tolerated with oral b.i.d. dosing. Stabilization of disease was observed in half of the pts. Gene expression correlated with stable versus progressive disease. [Table: see text]
Viral Interference of Types 1 and 2 Plaque-Producing Agents Derived From Cal-1 Strain of Marek's Disease Herpesvirus and Turkey Herpesvirus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E. F. Kaleta, R. A. Bankowski
Journal: JNCI Journal of the National Cancer Institute (1972)

Chicken kidney cell (CKC) cultures, inoculated with types 1 and 2 plaque-producing agents (PPA) of the Cal-1 strain of Marek's disease herpesvirus (MDHV) or with turkey herpesvirus (HVT), were refractory to superinfection with the Cal-11914 strain of Newcastle disease virus (NDV) 3–4 days after inoculation of the herpesvirus. The state of refractoriness to superinfection with NDV (intrinsic interference) appeared before development of cytopathic changes induced by type-1 PPA and was maintained up to 25 days post inoculation. Thereafter, CKC cultures infected with type-1 PPA were susceptible to superinfection with NDV. CKC cultures inoculated with type-2 PPA or HVT remained refractory to NDV challenge up to 20 days after inoculation with either herpesvirus. Homologous interference between the virulent type-1 PPA and the avirulent strains (type-2 PPA and HVT) was not detectable when type 2 and HVT were simultaneously inoculated with type 1 into CKC cultures. Similar results were obtained when type-1 PPA was inoculated 24 hours before superinoculation with type 2 or HVT. However, homologous interference was detected when type-2 PPA or HVT was inoculated 24 hours before inoculation of type 1. Repression of the growth of type-1 PPA foci in CKC cultures depended on the number of foci of type 2 or of HVT in the culture plates. Decreasing numbers of type-1 foci in CKC cultures preinfected with either type 2 or HVT caused lower titers of interferon.
Antiviral effect of ribavirin plus interferon in chronic hepatitis C.
Authors: P Ciccorossi, A Ricchiuti, S Petruccelli, F Costa, M Bellini, P Arpe, Pd Carrara, F Maggi, L Vatteroni, M Pistello, M Bendinelli, G Maltinti, S Marchi
Journal: Hepatology (1998)
From the Centers for Disease Control and Prevention. Contraceptive practices before and after an intervention promoting condom use to prevent HIV infection and other sexually transmitted diseases among women--selected US sites, 1993-1995
Journal: JAMA (1997)

A Centers for Disease Control analysis of longitudinal data on condom use promotion for control of HIV/sexually transmitted diseases (STDs) refuted concerns that such promotion may jeopardize use of hormonal contraception for pregnancy prevention.  Enrolled in the study were 1793 HIV-negative heterosexual US women recruited from inner-city STD clinics in California Colorado Maryland and New Jersey.  As part of the study participants received counseling encouraging consistent condom use with all male sex partners.  At enrollment 32% of participants had at least one STD.  At the three-month follow-up 188 (75%) of the 249 women who were using hormonal contraception at enrollment were still using this method; only 12% changed from using hormonal methods to condoms for contraception.  In addition 10% of women who were using no contraception or a minimally effective method at enrollment had adopted hormonal contraception use.  Overall consistent condom use increased from 13% at baseline to 36% at follow-up.  By method consistent condom use increased from 8% to 34% among the 208 sterilized women from 10% to 31% among the 249 women who used hormonal methods from 28% to 47% among the 345 condom users from 0% to 33% among the 15 users of barrier methods and from 1% to 30% among the 223 women using no contraception or a minimally effective method.