tbuckley/cabot-search huggingface dataset:
Carcinogenicity of &lt;italic&gt;N&lt;/italic&gt;-Nitrosobis(2-hydroxypropyl)amine and &lt;italic&gt;N&lt;/italic&gt;-Nitrosobis(2-oxopropyl)amine in MRC rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: P Pour, S Salmasi, R Runge, R Gingell, L Wallcave, D Nagel, K Stepan
Journal: JNCI Journal of the National Cancer Institute (1979)

Weekly sc injections of equitoxic doses of N-nitrosobis(2-hydroxypropyl)amine (BHP) and N-nitrosobis(2-oxopropyl)amine (BOP) to Wister-derived MRC rats induced tumors. The incidence, latency, multiplicity, morphologic type, and distribution of these tumors varied according to the compound given. The esophagus was the main target organ for BHP (100%), followed by the respiratory tract (87%), pharynx (80%), colon and liver (each 73%), kidneys (20%), thyroid gland (20%), and urinary bladder and urethra (each 7%). BOP was ineffective in the esophagus and pharynx but induced a higher incidence of tumors in the kidneys (27%), thyroid gland (60%), urinary bladder (33%), and urethra (73%) and fewer neoplasms in the respiratory tract (20%), colon (67%), and liver (53%). In addition, BOP caused a few, apparently primary, prostate squamous cell carcinomas. The results are compared with results of BHP treatment in Sprague-Dawley rats and with results of BHP and BOP treatment in Syrian golden hamsters.
Recurrent and metastatic mesoblastic nephroma in infancy.
Authors: A D Steinfeld, C A Crowley, P A O'Shea, M Tefft
Journal: Journal of Clinical Oncology (1984)

Local recurrence or metastasis of mesoblastic nephroma is extremely uncommon. The first report of a child with mesoblastic nephroma to have both of these problems is presented. The usual course of mesoblastic nephroma is benign, with nephrectomy being curative. Adjuvant treatment is not necessary and may be lethal. However, a review of the five patients who developed locally recurrent and/or metastatic tumor indicates that chemotherapy and radiotherapy are of benefit and can produce long-term disease-free survival.
A phase I study of bortezomib (BTZ) and temozolomide (TMZ) in patients with advanced solid tumors.
Authors: J. Portnow, S. Koehler, M. C. Cristea, W. A. Chow, V. M. Chung, D. Lim, R. Morgan, S. Shibata, P. H. Frankel, T. W. Synold
Journal: Journal of Clinical Oncology (2010)

2563
RTOG 0525: Molecular correlates from a randomized phase III trial of newly diagnosed glioblastoma.
Authors: K. D. Aldape, M. Wang, E. P. Sulman, M. Hegi, H. Colman, G. Jones, A. Chakravarti, M. P. Mehta, D. W. Andrews, L. Long, K. Diefes, L. Heathcock, R. Jenkins, C. J. Schultz, M. R. Gilbert
Journal: Journal of Clinical Oncology (2011)

LBA2000 Background: Formalin-fixed, paraffin embedded GBM tumor tissue, adequate for conventional MGMT methylation analyses, was required for entry onto the RTOG 0525 clinical trial. Methods: Four prognostic biomarkers were evaluated on a training set of 220 retrospectively obtained GBM samples, consisting of IDH1 mutation, the glioma-CpG island methylator phenotype (G-CIMP), a microarray-based mRNA panel and a novel MGMT promoter methylation assay. For each biomarker, 2 (IDH1 and mRNA) or 3 subgroups (G-CIMP and MGMT) were defined based on associations with overall survival. All combinations (36 possible) of each of the 4 biomarker-derived subgroups were then defined and compared with survival data and then consolidated into 4 risk groups. Once created in the training set, this model was applied to the RTOG 0525 samples (n=763) for external validation. Results: Application of the molecular risk classification to RTOG 0525 samples (left table) showed a highly significant survival association (p&lt;0.001). When compared to the recursive partitioning analysis (RPA, table on right), this composite molecular classifier better identified patients with long term survival and appears to improve resolution by revealing an additional distinct risk group. The molecular classifier was prognostic in each of the treatment arms individually. Conclusions: Four distinct biomarkers or biomarker panels were tested in GBM. These biomarkers were compared with clinical outcome in a training set to optimize a method to combine them into a classifier. This classifier was then validated on a large sample set from a large phase III clinical trial. This composite panel may represent an improvement over the existing RPA with respect to risk stratification of patients for GBM. Additionally, it has the potential to impact future clinical trial designs and provide enhanced opportunities for personalization of therapy for GBM. Support: NCI U10 CA2121661, U10 CA37422, P50 CA127001. [Table: see text]
Maximal sniff nasal inspiratory pressure in Brazilian healthy subjects: A multicentre study
Authors: Guilherme Augusto de Freitas Fregonezi, Palomma Russelly Saldanha Araujo, Armele de Fátima Dornelas de Andrade, Marlene Moreno, Ester Silva, Jasiel Frutuoso Nascimento, Larissa de Andrade Carvalho, Ana Gabriela Leal Cavalcanti, Viviane Cerezer Silva, Vanessa Resqueti
Journal: European Respiratory Journal (2011)

Objective:  To propose reference values of SNIP for Brazilian population.   Methods:  This study was conducted in three centers in Brazil, Natal-RN, Recife-PE and Piracicaba-SP. Subject were evaluated in relation to anthropometrics parameters, physical activity profile and maximal sniff nasal inspiratory pressure follow recommendations of ATS/ERS Statement on Respiratory Muscle Testing. SNIP was measured from FRC in the sitting positions using a catheter through a plug occluding one nostril during 10 maximal sniffs through the contra-lateral nostril. For each test the largest pressure measured in cmH2O was taken into account. Correlation and multiple linear regressions were used to predicted male and female SNIP equations. Results were compared with previous published studies.   Results:  We studied 244 subjects (114 male and 130 female) distributed in different age grouped 20-80 years old. We found a significantly negative correlation between SNIP and age for male and female (p   Conclusions:  The results of this study provide reference equations of SNIP for health Brazilian population from 20 to 80 years old.  Financial support: CNPq.
Immunologic Reactivity to Weak Transplantation Antigens: Factors Which Favor Sensitization Rather Than Tolerance2
Authors: J. Wayne Streilein, Joan S. Streilein
Journal: JNCI Journal of the National Cancer Institute (1973)

This study of the immunologic reactivity of Syrian hamsters to weak histoantigenic differences revealed that 20% of LSH hamsters normally displayed a penchant for becoming tolerant of MHA strain antigens, as evidenced by prolonged acceptance of MHA skin allografts. The incidence of tolerance was greatly increased by an initial exposure of normal LSH hosts to MHA cells devoid of putative immunologic reactivity directed at LSH antigens. Conversely, it was rendered almost negligible by pretreatment of normal LSH animals with MHA lymphoid cells capable of mounting a mild graft-versus-host response: Animals so treated were rendered highly sensitized to MHA transplantation antigens. In addition, under appropriate experimental conditions, the strongly histoincompatible CB strain antigens could interact with MHA antigens so that LSH animals became highly immunized to the MHA antigens. LSH hosts challenged with either lymphoid cells or skin allografts from (CB X MHA)F1 donors rejected subsequent MHA skin grafts in brisk secondset fashion; more importantly, LSH animals were similarly hyperimmunized when disparate MHA and CB determinants were expressed on different cell populations administered as an admixture or in individual portions into separate tissue sites. These observations may have implications for two experimental and/or clinical situations in which the development of tolerance or immunity to weak antigens may determine therapeutic success or failure: organ transplantation and/or tumor resistance.
Tobacco Causes Human Cancers—A Concept Founded on Epidemiology and an Insightful Experiment Now Requires Translation Worldwide
Authors: Lawrence A. Loeb
Journal: Cancer Research (2016)

Abstract The recognition that tobacco smoke is carcinogenic led to the most significant and successful effort at reducing cancer incidence in human history. A major milestone of this effort was the publication in Cancer Research by Wynder and colleagues, which demonstrated the ability of tobacco tars to produce tumors in mice. This study provided a powerful link between the epidemiology of cancer and mechanisms of carcinogenesis. This commentary asserts that we have a moral obligation to translate our success in reducing lung cancer in the United States to the 1.25 billion smokers throughout the rest of the world. Cancer Res; 76(4); 765–6. ©2016 AACR. See related article by Wynder et al., Cancer Res 1953;13:855–64.
Antibodies to the FVIII light chain that neutralize FVIII procoagulant activity are present in plasma of nonresponder patients with severe hemophilia A and in normal polyclonal human IgG
Authors: Alexandre Moreau, Sébastien Lacroix-Desmazes, Natalie Stieltjes, Evgueni Saenko, Srini V. Kaveri, Roseline D'Oiron, Yvette Sultan, Dorothea Scandella, Michel D. Kazatchkine
Journal: Blood (2000)
Efficacy of sequential methotrexate, fluorouracil, and leucovorin rescue: due to the 24-hour interval? The leucovorin-fluorouracil combination? Both?
Authors: D S Martin
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.8.1512 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2072152 Efficacy of sequential methotrexate, fluorouracil, and leucovorin rescue: due to the 24-hour interval? The leucovorin-fluorouracil combination? Both? D S MartinxD S MartinSearch for articles by this author https://doi.org/10.1200/JCO.1991.9.8.1512 PDF "Efficacy of sequential methotrexate, fluorouracil, and leucovorin rescue: due to the 24-hour interval? The leucovorin-fluorouracil combination? Both?." Journal of Clinical Oncology, 9(8), pp. 1512–1513© 1991 by American Society of Clinical Oncology
Clinical staging in carcinoma cervix: Does it correlate with pathological staging?
Authors: P. Jain, A. Goel
Journal: Journal of Clinical Oncology (2008)

16570 Background: Cervical cancer is a clinically staged malignancy according to FIGO Staging System. The 1994 revision of FIGO staging system is the currently internationally accepted staging system. Being a subjective method, with inter observer variations, it has certain limitations. The surgico pathological TNM staging is however a more accurate and objective method of staging. The purpose of the present article is to compare the clinical FIGO stage with post operative TNM stage in sixty two cases of carcinoma cervix treated with surgery. Materials and Methods: Sixty two patients of early cervical carcinoma were treated with surgery from Jan. 2002 to Dec. 2007 in the department of surgical oncology at Mahavir Cancer Sansthan. A retrospective analysis of these cases was performed. All the patients underwent a thorough clinical evaluation and were staged as per FIGO staging system pre operatively. A punch biopsy was taken from the growth. An ultrasound of the whole abdomen was done in all the cases. After appropriate pre operative work up all the patients underwent type III radical hysterectomy with bilateral pelvic lymph node dissection. Para aortic lymph node sampling was done in 27 cases. The clinical stage was then compared with the pathological TNM stage post operatively. A comparison was also made between the ultrasonography findings and histopathology. The pre operative histology from punch biopsy was compared to the final histology. 28 patients (45%) received adjuvant radiation therapy. All the patients were followed up regularly as per guidelines with a median follow up of 12 months (Range 3–42m). Results: On comparison of FIGO & TNM Stage, there was a discrepancy between the two in 18 patients (29%). 10 (16%) patients got upstaged whereas in 8 (13%) patients the disease was down staged. In 3 patients the disease got up staged because of metastasis in pelvic lymph node. 5 patients got up staged due to microscopic vaginal involvement. Tumor size led to upstaging in 2 patients. All upstaged patients required Adjuvant Radiotherapy. Conclusion: Clinical staging being observer dependent is not an objective method of staging and significant discrepancies have been observed between the two staging systems. No significant financial relationships to disclose.
Exemestane in advanced and recurrent endometrial carcinoma. A phase II study
Authors: B. Nordstrom, T. Salmi, M. Mirza, V. Abeler, G. Kristensen
Journal: Journal of Clinical Oncology (2006)

5042 Background: Most entrometrial adenocarcinomas of the endometrioid type express estrogen receptors and are potentially hormone sensitive. The aim of this phase II study was to evaluate the responsiveness of these tumors to treatment with Exemestane, an aromatase inhibitor. Methods: So far, 31 patients have been recruited to this ongoing study. Patients had to have a measurable tumor. Evaluation of response by CT was performed every 3 months. Evaluation of estrogen receptors (ER) was performed by immunohistochemistry and was positive in 17 patients, negative in 5 and not performed in 6 of the 28 patients evaluable for response. Treatment was given with Exemestane 25 mg orally daily. Results: Radiotherapy had been given as part of the initial therapy to 16 patients. Before inclusion into the study, 22 patients had received chemotherapy and 7 of these had also received hormonal treatment with gestagens for relapse. Response to Exemestane treatment was evaluable in 28 patients. In 17 patients with ER positive tumors, 1 showed a complete response, 1 partial response and 6 have had stable disease for 3+ months (3 patients), 6+ months (2) and 9+ months (1). The treatment was well tolerated with no major toxicity. Updated response rates will be presented. Conclusions: Treatment with Exemestane orally showed effect in patients with ER positive tumors in this heavily pre-treated group of patients with endometrioid adenocarcinoma of the endometrium. No significant financial relationships to disclose.
A phase II study of intravenous (IV) milataxel (M) for the treatment of non-small cell lung cancer (NSCLC) refractory to platinum-based therapy
Authors: T. Mekhail, P. Serwatowski, A. Dudek, C. Belani, R. Jankowska, K. J. Pandya, S. Arnold, J. Brahmer, B. Gitlitz, R. Govindan
Journal: Journal of Clinical Oncology (2006)

7098 Background: M (TL139, MAC-321) is a novel taxane that has shown activity when administered IV or orally in both taxane-resistant and susceptible nude mouse xenograft models. The current study is an open-label study in previously treated patients (pts) with locally advanced, metastatic, or recurrent NSCLC to determine response rate. Methods: Pts with cytologically or histologically confirmed NSCLC must have received 1 or 2 prior regimens including prior platinum, and may have received prior paclitaxel or docetaxel. Good performance status (ECOG 0 or 1), and adequate hematologic, hepatic and renal function were required. Pts with clinically active brain metastases were excluded. Pts were treated with M 35 mg/m 2 as a 4 hr IV infusion every 3 weeks. The primary end point was objective response rate. Results: A total of 46 pts were treated: 21 (46%) female pts and 25 (54%) male pts. Mean age was 59 (range 41–85), ECOG was PS 0 in 13 (28%) pts, PS 1 in 31 (67%) pts and unknown in 2 (4%) pts. The number of prior chemotherapy regimens was &gt; 1 in 21 (46%) pts. Twenty-five (54%) pts had one prior taxane and 7 (15%) pts had both paclitaxel and docetaxel previously. The median number of cycles was 3 (range 1–14). Nine (20%) pts required dose reduction. Five (11%) pts discontinued treatment due to adverse events. A total of 25 (54%) pts reported drug related grade 3 or 4 adverse events. Non-hematologic grade 3 or 4 drug-related events occurring in more than 1 pt included: neuropathy 4 (9%) pts, neutropenic fever 3 (7%) pts, arthralgia 2 (4%) pts. There was no treatment related mortality. Objective responses were confirmed in 4 (9%) pts (3 PR, 1 CR). Three pts with response (including pt with CR) had received prior docetaxel. PR duration was 175, 250, and 315 days. Pt with CR received 4 cycles of M and discontinued due to the CR. Pt remained in CR at day 504. Conclusions: Milataxel 35 mg/m 2 as a 4 hr IV infusion every 3 weeks provided durable responses in heavily pretreated pts including pts who had previously received taxanes. No significant financial relationships to disclose.
Bortezomib, bendamustine, and rituximab in patients (pts) with relapsed (rel) or refractory (ref) follicular lymphoma (FL): Dose-finding results of the VERTICAL study
Authors: J. Matous, J. Letzer, P. Rosen, S. Noga, N. Fowler, S. Smith, B. Amin, H. Shi, S. Parasuraman, B. Cheson
Journal: Journal of Clinical Oncology (2009)

8550 Background: FL is an incurable indolent B-cell non-Hodgkin's lymphoma. Survival has improved in the past decade with the introduction of rituximab (Rituxan, R), but response decreases with repeated exposure. Bortezomib (Velcade, V) plus R was active and generally well tolerated in rel/ref FL [de Vos ASH 2006 Abs694], and bendamustine hydrochloride (Treanda, B) plus R has also shown activity in heavily pretreated FL [Robinson JCO 2008]. The current single-arm, multi-center study evaluates the efficacy and safety of VBR in pts with rel/ref FL. Here we report the safety of dose escalation of B in combination with VR. Methods: Pts with relapsed FL with ≥4 prior doses of R (no prior V or B), ≥1 measurable tumor mass, no active central nervous system lymphoma, KPS ≥50%, adequate hematologic, renal and hepatic function, and no peripheral neuropathy ≥G2 were eligible. Pts received five 35d cycles of V 1.6 mg/m 2 (d1, 8, 15, 22), B 50, 70, or 90 mg/m 2 (d1, 2) and R 375 mg/m 2 (d1, 8, 15, 22, cycle 1; d1, cycles 2–5). B dose escalation continued based on cycle 1 dose-limiting toxicities (DLTs), defined as: treatment-related platelet count &lt;25,000/mm 3 for &gt;7 days or any platelet count &lt;10,000/mm 3 ; G4 neutropenia for &gt;7 days; any treatment-related ≥G3 non-hematologic toxicity other than inadequately treated nausea, vomiting, or diarrhea; or any toxicity resulting in &gt;1 week treatment delay. Results: Sixteen pts (4 at B 50 mg/m 2 , 6 each at B 70 and 90 mg/m 2 ) with a median of 3 prior therapies (range 1–13; 31% prior stem-cell transplantation) have been treated (15 evaluable for DLT); median age was 54.5 (44–80) yrs. There was one DLT at B 70 mg/m 2 (severe rash; pt discontinued), and one DLT at 90 mg/m 2 (G3 thrombocytopenia requiring cycle 2 d1 delay). Hematologic AEs were manageable and included 4 (25%) ≥G3 neutropenia and 1 (6%) G4 thrombocytopenia. Non-hematologic AEs ≥G3 in &gt;1 pt were diarrhea (31%), fatigue (25%), vomiting (13%), and nausea (13%). Peripheral neuropathy was reported in 6 pts (38%; 1 G3). Evidence of antitumor activity has been observed. Conclusions: Enrollment is continuing in the phase II portion of the study with B 90 mg/m 2 , the highest planned dose. [Table: see text]
Correlation of thymidine phosphorylase (TP), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) expression in primary and metastatic sites with response to capecitabine plus irinotecan in patients with colorectal cancer
Authors: N. J. Meropol, P. J. Gold, R. B. Diasio, Y.-M. Chen, T. Godfrey, T. Hill, A. J. Kovatich, K. A. Lund, E. Mitchell, R. Schwarting
Journal: Journal of Clinical Oncology (2004)

3520 Background: In preclinical models, expression of three enzymes involved in the metabolism and antitumor activity of capecitabine, an orally administered prodrug of 5-fluorouracil (5-FU), impact cytotoxicity: TP (final step in conversion of capecitabine to 5-FU), DPD (5-FU degradation), and TS (5-FU target). This study was undertaken to determine whether expression of these enzymes in primary tumors and/or metastatic sites predicts response to capecitabine in patients (pts) with colorectal cancer (CRC). Methods: 67 chemotherapy-naïve (except adjuvant therapy) pts with measurable metastatic CRC were treated with irinotecan 125 (15 pts, cohort 1) or 100 (52 pts, cohort 2) mg/m2 intravenously on days (d) 1 and 8, plus capecitabine orally 1000 (cohort 1) or 900 (cohort 2) mg/m2 twice daily on d2–15, every 21 d. Starting doses were reduced after the first 15 pts because of toxicity (Gold et al. ASCO 2003). Paraffin-embedded tumor samples from primary and metastatic sites (49 pts) were assessed for expression of TP, TS, and DPD by immunohistochemistry (IHC) (Roche Diagnostics antibodies) and mRNA quantification (Roche Diagnostics kits). Results: Mean age was 61.8 years (range 40–81), 37M/30F. Objective response rate (confirmed at >4 weeks, RECIST criteria) was 42% (7 pts cohort 1, 21 pts cohort 2). Grade 3–4 adverse events in >5% of pts in cohort 2 were (#pts): diarrhea (18), dehydration (7), hand-foot syndrome (4), deep vein thrombosis (3), nausea (4), vomiting (4). Response rate was 62% vs. 20% in pts with TP+ vs. TP- primary tumors (p=0.01), and 61% vs. 14% in pts with TP+ vs. TP- metastatic tumors (p=0.04). Similarly, response was more likely in primary tumors with ≥mean levels of TP mRNA (75% vs. 37%, p=0.03). There was no relationship between TS or DPD expression (IHC or mRNA) in primary or metastatic sites and likelihood of response. Conclusions: These data support the hypothesis that TP expression may be useful as a predictive marker for response in CRC pts treated with an active combination of capecitabine plus irinotecan. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MDR Global Systems, LLC; Roche Labs Hoffman LaRoche; MDR Global Systems, LLC; Pfizer; Roche Hoffman LaRoche Roche; Roche Integrated Cancer Care Unit Roche
A phase I study of a hypomethylating agent azacitidine in combination with carboplatin in patients with platinum resistant epithelial ovarian cancer
Authors: S. Fu
Journal: Journal of Clinical Oncology (2006)

5087 Background: Hypermethylation is a common event associated with inactivation of a variety of genes and pathways involved in tumorigenesis and progression as well as drug resistance. Previous evidence displayed that hypomethylating agents could resensitize epithelial ovarian cancer cells to platinum treatment through reexpression of platinum sensitivity-related genes. Therefore, it is of great interest to use a hypomethylating agent to resensitize platinum resistant epithelial ovarian cancer cells to platinum treatment. Methods: This proof-of-concept study used a modified dose-escalation schema (3+3 design). All patients, who have progressed within the 6 months after a platinum-based regimen, are eligible if they have a pathologically confirmed epithelial ovarian cancer. All patients receive subcutaneous injection of azacitidine 75 mg/m 2 /day for 5 days on days 1–5 and intravenous infusion of carboplatin once on day 2 of each treatment cycle (28 days). Azacitidine is maintained at the same dosage during dose-escalation of carboplatin from AUC4 to AUC5. Results: Six patients have received a total of 16 cycles of treatment. There was no grade 2 or higher toxicity observed. Three patients were evaluable for response: 1 patient, who received 6 cycles of treatment, achieved complete response by CA125 criteria and stable disease by imaging criteria; 1 patient, who received 5 cycles of treatment, displayed stable disease; and the 3rd patient, who received 2 cycles of treatment, showed mixed response by imaging criteria. Conclusions: Preliminary data showed that a regimen of azacitidine 75 mg/m 2 /day for 5 days plus carboplatin AUC 5 on day 2 was well tolerated in patients with extensive prior treatment. No significant financial relationships to disclose.