tbuckley/cabot-search huggingface dataset:
The Risk of Relapse in CML Patients Who Discontinued imatinib Can Be Predicted Based on Patients Age and the Results of dPCR Analysis
Authors: Silvia Mori, Elisabetta Vagge, Philipp le Coutre, Elisabetta Abruzzese, Bruno Martino, Ester Pungolino, Chiara Elena, Ivana Pierri, Sarit Assouline, Anna D'Emilio, Antonella Gozzini, Pilar Giraldo, Fabio Stagno, Alessandra Iurlo, Michela Luciani, Giulia De Riso, Kim Dong-Wook, Alessandra Pirola, Anna Petroccione, Agnese Lodolo D'Oria, Patrizia Crivori, Rocco Piazza, Carlo Gambacorti-Passerini
Journal: Blood (2014)
Carcinogenic Effects of Oral Diethylstilbestrol on C3H Male Mice With and Without the Mammary Tumor Virus2
Authors: George H. Gass, Jean Brown, Allan B. Okey
Journal: JNCI Journal of the National Cancer Institute (1974)

Diethylstilbestrol (DES), at 250 parts per billion, was administered in the diet to castrated C3H/An male mice (with the mammary tumor virus) and C3H/Anf male mice (presumably free of the virus). In experiment I, mice of both substralns were observed for mammary tumor formation during 18 months on either DES-containing or control (DES-free) diets; mice in experiment II were observed for 12 months. In groups on control diets, no mammary tumors were found in 80 C3H/An mice, and only 1 tumor was observed in 80 C3H/Anf mice. In groups receiving DES, tumor incidence was 45/80 for C3H/An and 5/80 for C3H/Anf mice. The experiments emphasized that estrogen stimulation of genetically susceptible mice without the mammary tumor virus is not efficient in producing mammary tumors, nor is the virus effective without estrogen.
Second Malignancies as a Consequence of Nucleoside Analog Therapy for Chronic Lymphoid Leukemias
Authors: Bruce D. Cheson, Donald A. Vena, Jane Barrett, Boris Freidlin
Journal: Journal of Clinical Oncology (1999)

The nucleoside analogs fludarabine, 2'-deoxycoformycin (DCF), and 2-chlorodeoxyadenosine (CdA), commonly used in the treatment of patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL), are associated with myelosuppression and profound and prolonged immunosuppression. These complications raise the possibility of an increase in secondary malignancies in patients whose disease already places them at greater risk. The purpose of the present study was to assess the frequency of second tumors in patients with CLL who are treated with fludarabine and in patients with HCL who are treated with DCF and CdA.We reviewed the long-term follow-up data for 2,014 patients treated on National Cancer Institute Group C protocols with fludarabine for relapsed and refractory CLL and with DCF and CdA for HCL using a Second Cancer Report. The numbers of observed and expected secondary tumors were compared.Median follow-up periods for the DCF (n = 409), fludarabine (n = 724), and CdA (n = 979) studies were 6.9, 7.4, and 5.1 years, respectively. The 111 malignancies were most commonly lymphoma (25 patients), prostate (19), lung (15), colorectal (nine), bladder (six), and breast (six), but also CNS, stomach, ovary, head and neck, melanoma, sarcoma, testicular, and myeloid leukemias. Compared with age-adjusted 1994 Surveillance and Epidemiology End-Results rates for the general population, the observed/expected frequencies for DCF, fludarabine, and CdA were 1.43 (95% confidence interval [CI], 0.93 to 2.10), 1.65 (95% CI, 1.04 to 2.47), and 1.50 (95% CI, 1.14 to 1.93), respectively, indicating a significant (at P =.05) increase in risk for patients treated on the latter two protocols compared with a normal population. However, these values are consistent with the increase already associated with these diseases.Despite their immunosuppression, nucleoside analogs can be safely administered to patients with CLL or HCL without a significantly increased risk of secondary malignancies.
Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center.
Authors: E Hu, S Hufford, R Lukes, M Bernstein-Singer, G Sobel, P Gill, L Pinter-Brown, M Rarick, P Rosen, R Brynes
Journal: Journal of Clinical Oncology (1988)

The reported experience with Hodgkin's disease (HD) in the United States has come primarily from large referral centers that attract a predominantly white population of high socioeconomic status (SES). The majority of these patients had the nodular sclerosis (NS) histologic subtype and asymptomatic stage I/II disease. We have reviewed the records of 178 patients with HD seen within the past 17 years at Los Angeles County-University of Southern California Medical Center (LAC/USC), which is a nonreferral, government-operated facility. Our patient population was found to be heterogeneous, with 38% white, 22% black, and 36% Hispanic. Systemic "B" symptoms were noted in 62% of patients at diagnosis, and 63% had advanced disease (stage III or IV). NS pathologic subtype was present in only 52% of the group. Comparison between the races revealed: (1) Hispanics had a higher incidence of lymphocyte depleted subtype and less NS than whites (P less than .06); (2) whites had equal distribution between stages I/II and III/IV; (3) blacks and Hispanics presented more frequently with stage III/IV (P = .10); and (4) extranodal involvement occurred most often in bone in whites, and was equally distributed between liver, lung, and bone in blacks and Hispanics. We conclude that the lower SES, mixed racial population seen at our institution more closely resembles the reports of HD in Third-World countries and is characterized by advanced symptomatic disease. Further, the clinical pathologic characteristics of HD in the United States may vary significantly, depending upon the precise ethnic and socioeconomic status of the patients being served.
Activity of abiraterone acetate in metastatic patients with castration-resistant prostate cancer (mCRPC) previously treated with ketoconazole: A prospective phase II study from the prostate cancer clinical trials consortium.
Authors: Won Kim, John Wilton, Li Zhang, Amy M. Lin, Lawrence Fong, Terence W. Friedlander, Andrew Caleb Hsieh, Rahul Raj Aggarwal, Tammy J. Rodvelt, Allison Morse, Jeffrey Bozeman, Vivian K. Weinberg, Arturo Molina, James Mohler, Gerald J. Fetterly, Russell Zelig Szmulewitz, Eric Jay Small, Charles J. Ryan
Journal: Journal of Clinical Oncology (2014)

53 Background: Abiraterone acetate (AA), like ketoconazole (keto), inhibits CYP17, the rate-limiting enzyme in androgen biosynthesis. Since patients (pts) with prior keto treatment were excluded from the pivotal phase III AA trials, the utility of AA after keto is not well understood. This prospective study evaluated the efficacy of AA in pts who had received prior keto. Methods: Pts with progressive castration-resistant prostate cancer (mCRPC), prior keto therapy 28 days or more, and normal baseline organ function (including ACTH stimulation) tests were treated with AA 1,000 mg PO daily and prednisone 5 mg PO BID. Pts with prior chemotherapy were excluded. Serum androgen levels, including dehydroepiandrosterone (DHEA), were measured by liquid chromatography/mass spectroscopy (LC/MS) at baseline and during treatment for exploratory analyses. Radiographic progression-free survival (rPFS) was defined as freedom from: death, radiographic progression, or unequivocal clinical progression. Results: Forty two pts were enrolled. Median age was 71. Median prostate-specific antigen (PSA) was 47.5ng/dL. Median duration of prior keto was 38 weeks (range 5 to 207). Treatment with AA resulted in 30% or greater decline in PSA at 12 weeks in 20 pts (48%, 95% CI, 32-63%), and 50% or greater decline in PSA at 12 weeks in 16 pts (38%, 95% CI 24-54%). Median time to PSA progression (TTPP) was 16 weeks (range 4 to 64). Median rPFS was 24 weeks (range 1 to 88). Baseline serum DHEA levels were measured in 40 pts. Nine pts had DHEA less than the limit of quantitation (LOQ, 0.250ng/mL), and 31 pts had DHEA greater than or equal to LOQ. One pt with DHEA less than LOQ (1 out of 9, 11%, 95% CI 0.6-49%) had PSA decline 30% or more at 12 weeks, compared to 17 pts (17 out of 31, 55%, 95% CI 36-72%) with DHEA greater than or equal to LOQ (p=0.028). Median time to pain progression (TTPP) was 8 weeks (range 4 to 32) for pts with DHEA less than LOQ, compared to 18 weeks (range 4 to 64) for pts with DHEA greater than or equal to LOQ (p=0.012). Median rPFS was 12 weeks (range 4 to 24) for pts with DHEA less than LOQ, compared to 36 weeks (range 1 to 88) for pts with DHEA greater tha or equal to LOQ (p = 0.0006). Six pts remain on AA. Conclusions: A significant proportion of pts with prior keto exposure demonstrate clinical response to AA. DHEA levels via LC/MS merits further study as a predictive biomarker in pts treated with androgen synthesis inhibitors. Clinical trial information: NCT01199146.
Transient Carcinoembryonic Antigen (CEA) Elevations Following Resection of Colorectal Cancer: A Limitation in the Use of Serial CEA Levels as an Indicator for Second-Look Surgery&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Robin A. Rittgers, Glenn Steele, Norman Zamcheck, Matthew S. Loewenstein, Paul H. Sugarbaker, Robert J. Mayer, Jacob J. Lokich, James Maltz, Richard E. Wilson
Journal: JNCI Journal of the National Cancer Institute (1978)

In a previous study, other investigators recommended second-look surgery for colorectal cancer primarily on the basis of plasma carcinoembryonic antigen (CEA) rises and prepared a nomogram for ready recognition of these "significant" increases. We found 25 patients whose CEA levels met the recommended criteria for significance; however, in 9 of these patients the rises were transient. Eight had no clinical evidence of recurrent cancer and they might have had negative second-look surgery had this been done because of CEA rises alone. The use of the CEA nomogram merely eliminated laboratory variation as a cause of the CEA rise. It did not, however, rule out biologic causes of CEA rises, other than that of cancer, especially benign liver disease. We were unable to differentiate benign from malignant rises on the basis of CEA changes alone. Preoperative CEA values helped to separate the two rises. Transient rises usually began earlier. Malignant CEA rises were more likely to be exponential. The rate of rise alone did not discriminate between the two rises. Thus, although serial CEA levels were helpful in making the decision for reexploration, they did not substitute for complete clinical assessment.
Pathology of the Esophagus
Authors: N A Shepherd
Journal: Gut (2001)

Pathology of the Esophagus . K Takubo (Pp 299; illustrated). Japan: Educa, 2000. ISBN 4 87006 011 6.

While the oesophagus has provided much interest to physicians and surgeons, particularly since the advent of endoscopy, manometry, and pH monitoring, to many pathologists it remained a muscular tube of relative pathological disinterest. Perhaps compared with the stomach and the intestines there is a relative paucity of interesting pathological conditions to study. Barrett's oesophagus has certainly …
Disorganization of Mouse Bladder Epithelium Induced by 2-Acetylaminofluorene and 4-Ethylsulfonylnaphthalene-1-sylfonamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Patricia E. Levi, Judy C. Knowles, Diana M. Cowen, Margery Wood, Edward H. Cooper
Journal: JNCI Journal of the National Cancer Institute (1971)

A comparison has been made of the changes induced in mouse bladder epithelium during the early stages of feeding with 2 bladder carcinogens [2-acetylaminofluorene (AAF) and 4-ethyIsulfonylnaphthaIene-1-Sulfonamide (ENS)]. ENS increased cell proliferation and inhibited cell differentiation, as shown by the loss of special organelles, lysosome activity, polyploidy, and alkaline phosphatase activity. At the same time, the mitochondria underwent degenerative change. Part of these effects was secondary to the rising pH and increased crystalluria accompanying ENS feeding. AAF was more insidious, causing little proliferative change, but there was increased lysosomal activity and later mitochondrial degeneration.
Response of children with high-risk acute lymphoblastic leukemia treated with and without cranial irradiation: a report from the Children's Cancer Group.
Authors: J Nachman, H N Sather, J M Cherlow, M G Sensel, P S Gaynon, J N Lukens, L Wolff, M E Trigg
Journal: Journal of Clinical Oncology (1998)

PURPOSE Intensified intrathecal (i.t.) chemotherapy without cranial radiation therapy (CRT) prevents CNS relapse in children with low-risk and intermediate-risk acute lymphoblastic leukemia (ALL). In the current study, high-risk ALL patients who achieved a rapid early response (RER) to induction chemotherapy were randomized to receive intensive systemic chemotherapy and presymptomatic CNS therapy that consisted of either i.t. methotrexate (MTX) and CRT or intensified i.t. MTX alone. PATIENTS AND METHODS Children (n = 636) with high-risk ALL (aged 1 to 9 years and WBC count &gt; or = 50,000/microL or age &gt; or = 10 years, excluding those with lymphomatous features) who achieved an RER (&lt; or = 25% marrow blasts on day 7) to induction therapy and lacked CNS disease at diagnosis were randomized to receive systemic therapy with either i.t. MTX and CRT (regimen A, n = 317) or intensified i.t. MTX alone (regimen B, n = 319). RESULTS Interim analysis in July 1993 revealed 3-year event-free survival (EFS) estimates of 82.1% +/- 4.0% (SD)and 70.4% +/- 4.2% for patients treated on regimens A and B, respectively (P = .004). As of January 1996, outcome had changed: 5-year EFS estimates were 69.1% +/- 3.4% and 75.0% +/- 2.7% for regimens A and B, respectively (P = 0.50). Marrow relapses comprised 57 events on regimen A and 43 events on regimen B. Fewer late events occurred on regimen B. CONCLUSION For high-risk pediatric ALL patients who show an RER to induction therapy and are treated with systemic Children's Cancer Group (CCG)-modified Berlin-Frankfurt-Munster (BFM) chemotherapy, presymptomatic CNS therapy that consists of either i.t. MTX plus CRT or intensified i.t. MTX alone results in a similar 5-year EFS outcome. Furthermore, intensified i.t. MTX may protect against late bone marrow relapse.
Tumor Incidence and Development of Autoimmune Hemolytic Anemia in Two Breeding Lines of the NZB Mouse Strain That Differ in Chromosome Breakage&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Ingrid Emerit, Josué Feingold, Ariette Levy, Etienne Martin, Edouard Housset
Journal: JNCI Journal of the National Cancer Institute (1980)

Increased chromosome breakage observed in NZB mice was studied. Breeding experiments with mice selected according to breakage frequencies provided evidence that the proportion of mice with high breakage (HB) and low breakage (LB) figures in the progeny depends on the phenotype of the parents. Selective breeding for the "chromosome breakage" characteristic was successful and resulted in the separation of a breeding line with LB incidence. However, the selection could not be continued beyond the fourth generation for the mice with HB incidence because of lethal factors. Comparative studies of HB mice from the HB line and LB mice from the LB line showed significant differences for tumor incidence and positivity of the Coombs' test.
Snake venom leads to injury similar to acute lung injury revealing the needing of anti-inflammatory therapy
Authors: Rodolfo P. Vieira, Manoel C. Oliveira-Junior, Vanessa R. Silva, Paula N. Nonaka, Stella R. Zamuner, Camila A.A. Silva, Ronaldo A. Silva, Celso R.F. Carvalho, Luis V.F. Oliveira
Journal: European Respiratory Journal (2013)

The majority of studies show that ophidian accidents may lead to death due to respiratory failure by paralysis of respiratory muscle a despite of venom effects on neuromuscular junctions. However, the present study investigated the time-line effects of Crotalus durissus terrificus snake venom in the mechanical, inflammatory and immunological lung response. Forty male Swiss mice were distributed in Control, 3 hours, 6 hours, 12 hours and 24 hours groups (n = 8). Crotalus durissus terrificus venom (CdtV) (0.6 g/g) was intra-muscularly injected and the animals were studied after 3, 6, 12 and 24 hours after CdtV injection. The pulmonary mechanics, the airway and parenchyma inflammation and the expression of 8-isoprostane, Gp91Phox, iNOS, ICAM-1 and NF-kB by airway epithelium was analyzed. Furthermore, primary mouse tracheo-bronchial epithelial cells, human BEAS-2B and A549 cells were stimulated with 0,1g, 1g and 10g of CdtV for 24 hours and the levels of TNF-alpha, IL-6 and IL-13 were measured by ELISA. CdtV increased the static and dynamic pulmonary elastance (p0.01), resistance (p0.01) and viscoelastic properties (p0.01). CdtV increased the neutrophils and mononuclear cells density in airways wall and lung parenchyma (p0.05). CdtV increased the epithelial expression of NF-kB, Gp91phox, iNOS, 8-isoprostane and ICAM-1 (p0.01). Mouse primary tracheo-bronchial epithelial cells, BEAS-2B and A549 confirmed that CdtV activates epithelial cells, since that CdtV induces the release of IL-6, IL-13 and TNF-alpha (p0.01). We conclude that CdtV induces a direct pulmonary injury with participation of epithelial cells.
Solitary plasmacytoma of bone: treatment, progression, and survival.
Authors: L Y Chak, R S Cox, D G Bostwick, R T Hoppe
Journal: Journal of Clinical Oncology (1987)

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.
Comparative Virulence of the Mammary Tumor Agent From Different Sources; Qualitative and Quantative Differences&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Katherine P. Hummel, C.C. Little
Journal: JNCI Journal of the National Cancer Institute (1963)

The virulence of the mammary tumor agent (MTA) in males and parous and virgin females of 4 high-tumor strains, C3H, RIII, A, and DBA/1, was compared by inoculation of groups of young female mice of low-tumor strain BALB/c with blood derived from the 12 groups of donors. The qualitative nature of the MTA difference was determined by observation of tumor rates (incidence and mean tumor age) in female offspring of the inoculated mice. In both inoculated BALB/c mice and their offspring, the groups with MTA derived from strain C3H mice had more tumors at younger ages than groups with MTA derived from the other high-tumor strains. These observations are evidence that the MTA carried in the blood of strain C3H mice differs in quality from that in mice of strains RIII, A, and DBA/1; it is a more virulent form, inducing early development and a high incidence of mammary gland tumors in the BALB/c mice. The groups of BALB/c mice inoculated with blood from multiparous females had higher tumor rates than those with MTA from virgin females and males, but tumor rates in the offspring of the 3 groups were not different. This observation is interpreted as evidence that, although there is more MTA in the blood of multiparous females, it has not been changed in a detectable qualitative way by the hormonal output of the donor.
Efficacy of gabapentin on pruritus induced by interleukin-2 (IL-2) treatment in patients with metastatic renal cell carcinoma and melanoma
Authors: S. Lee, V. Rusciano, J. P. Dutcher
Journal: Journal of Clinical Oncology (2007)

3056 Background: IL-2 treatment causes pruritus, but the pathogenic mechanism is not well understood. Its relation to histamine is controversial, and it does not seem to correlate with the eosinophilia induced by IL-2. Direct stimulation of pain nerve fibers, such as A-delta and C fibers by the cytokines induced by IL-2 treatment has been proposed as a possible cause of pruritus. Stabilizing the nerve membrane or nerve synapses by pharmacologic means may improve pruritus, and we have used gabapentin for this purpose. Here we evaluate its efficacy. Methods: 54 patients, 34 Male, 20 female, were treated with IL-2 from January, 2005 to December, 2006. Among 30 patients who complained of pruritus, 17 patients were given gabapentin. Concurrent follow up notes of these 17 patients were reviewed. They were interviewed immediately following IL-2 treatment and retrospectively using a specific IRB approved questionaire, which quantified pruritus according to CTCAE 3.0 criteria, before and after the administration of gabapentin. The CTCAE grading scale is 0 to 3, from none, localized, widespread, to widespread pruritus interfering with daily activities. Data was analyzed with paired student T-test using SPSS 13.0 for data analysis. Results: 15 patients had renal cell carcinoma and 2 had melanoma. Mean age was 56 years. 12 patients were male and 5 were female. Gabapentin was started in hospital in 9 patients and outpatient in 8. Mean initial dose of gabapentin was 865 mg/day, and the mean time for gabapentin to provide symptom relief was 1.088 hours after each dose. According to CTCAE scale, the mean pruritus before gabapentin was 2.41 and it decreased to 0.65 after gabapentin treatment. Paired student T-test for the difference of means before and after the treatment was statistically significant (p &lt; 0.0005). Conclusions: Pruritus induced by IL-2 infusion responds well to gabapentin, which stabilizes nerve fibers and synapses. Although other confounding causes of pruritus cannot be excluded, the major mechanism is likely due to direct or indirect effect of IL-2, which then stimulates the nerve fibers. Thus, we propose gabapentin as an effective treatment against pruritus induced by IL-2. No significant financial relationships to disclose.
Convergence of eicosanoid and integrin biology: 12-lipoxygenase seeks a partner
Authors: Keqin Tang, Yinlong Cai, Sangeeta Joshi, Elizabeth Tovar, Stephanie C. Tucker, Krishna Rao Maddipati, John D. Crissman, William T. Repaskey, Kenneth V. Honn
Journal: Molecular Cancer (2015)

Integrins and enzymes of the eicosanoid pathway are both well-established contributors to cancer. However, this is the first report of the interdependence of the two signaling systems. In a screen for proteins that interacted with, and thereby potentially regulated, the human platelet-type 12-lipoxygenase (12-LOX, ALOX12), we identified the integrin β4 (ITGB4). Using a cultured mammalian cell model, we have demonstrated that ITGB4 stimulation leads to recruitment of 12-LOX from the cytosol to the membrane where it physically interacts with the integrin to become enzymatically active to produce 12(S)-HETE, a known bioactive lipid metabolite that regulates numerous cancer phenotypes. The net effect of the interaction was the prevention of cell death in response to starvation. Additionally, regulation of β4-mediated, EGF-stimulated invasion was shown to be dependent on 12-LOX, and downstream Erk signaling in response to ITGB4 activation also required 12-LOX. This is the first report of an enzyme of the eicosanoid pathway being recruited to and regulated by activated β4 integrin. Integrin β4 has recently been shown to induce expansion of prostate tumor progenitors and there is a strong correlation between stage/grade of prostate cancer and 12-LOX expression. The 12-LOX enzymatic product, 12(S)-HETE, regulates angiogenesis and cell migration in many cancer types. Therefore, disruption of integrin β4-12LOX interaction could reduce the pro-inflammatory oncogenic activity of 12-LOX. This report on the consequences of 12-LOX and ITGB4 interaction sets a precedent for the linkage of integrin and eicosanoid biology through direct protein-protein association.