tbuckley/cabot-search huggingface dataset:
Role of 5-alpha-reductase inhibitors in active surveillance of patients with low-risk prostate cancer.
Authors: Andrew Szehsun Chiang, D. Andrew Loblaw, Vibhuti Jethava, Perakaa Sethukavalan, Liying Zhang, Danny Vesprini, Alexandre Mamedov, Robert Nam, Laurence Klotz
Journal: Journal of Clinical Oncology (2012)

14 Background: Active surveillance (AS) is a recognized management option for low-risk prostate cancer. Many institutions use serial PSA values to determine when to reclassify patients into higher risk categories. The impact of 5-alpha-reductase inhibitors (5-ARIs) in this setting has not been well studied. The purpose of this retrospective review was to compare PSA doubling time prior to the initiation of a 5-ARI (pre-5-ARI) to that after the PSA nadir (post-nadir) has been reached. Methods: Between 1996 and 2010, a total of 100 patients with a history of 5-ARI use were captured from our AS database. Of these, twenty-nine had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir doubling times. The majority had stage T1c disease (89.7%) and Gleason scores of six or lower (93.1%). The average PSA at presentation was 6.93 µg/L. More patients were prescribed dutasteride (79.3%) than finasteride (20.7%). PSA doubling time was calculated using the general linear mixed-model method. Statistical analysis was performed using the non-parametric sign test. Results: Median follow-up was 69.5 months (mo). For the twenty-nine patients analyzed, the median pre-5-ARI PSA doubling time was 55.8 mo (6-556.8 mo), while that for the post-nadir values was 25.2 mo (6-231 mo) (p=0.0081). Six patients were ultimately reclassified after an average of 67.7 mo (59-95 mo), due to progression in either PSA doubling time (n=2) or Gleason score (n=4). The median pre-5-ARI and post-nadir doubling times for this group were 48.2 mo (32.4-91.1 mo) and 23.3 mo (6-44.3 mo), respectively. Five of the patients underwent radical prostatectomy, while one underwent radiotherapy with androgen deprivation. Of the six patients, one had biochemical failure after an average post-treatment follow-up of 21.3 mo (0-52 mo). Conclusions: In AS for low-risk prostate cancer, it was found that 5-ARIs significantly decreased PSA doubling time. This effect may be related to preferential suppression of benign prostatic tissue, thereby providing a more accurate depiction of the true cancer-related doubling time. If validated with a larger cohort, 5-ARIs may enhance the utility of PSA doubling time as a biomarker of disease progression in AS.
Recent Trends of Bacteremia in Patients with Hematological Malignancy
Authors: Masanori Seki, Koichiro Maie, Shinichi Ogawa, Naoki Kurita, Yasuhisa Yokoyama, Mamiko Sakata-Yanagimoto, Naoshi Obara, Yuuichi Hasegawa, Norie Ebihara, Shigeru Chiba
Journal: Annals of Oncology (2014)
Motolimod, a selective TLR8 agonist induces apoptosis in monocytic myeloid-derived suppressor cells (M-MDSC)
Authors: Zina J Rutnam, Yushe Dang, Gregory Dietsch, Hailing Lu, Yi Yang, Robert M Hershberg, Mary Disis
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts There is increasing evidence that myeloid-derived suppressor cells (MDSCs) contribute to the progression of cancer by inhibiting tumor-directed immune responses and producing mediators that promote the growth and survival of tumor cells. While present at low numbers in the
mTOR inhibition as a potential treatment for progesterone refractory endometrial hyperplasia
Authors: P. T. Soliman, K. M. Schmeler, R. R. Broaddus, B. M. Slomovitz, W. Wu, D. M. Gershenson, K. H. Lu
Journal: Journal of Clinical Oncology (2005)

5080 Background: Complex endometrial hyperplasia (EH) is a pre-malignant lesion that can progress to endometrial cancer (EC). Treatment with oral progesterone results in resolution to normal endometrium in 30–50% of cases. Currently, there are no conservative (i.e. fertility sparing) treatment options for progesterone refractory EH. PTEN mutations are found in 55% of EH and up to 80% of EC. Loss of PTEN leads to constitutive activation of AKT, which in turn phosphorylates the downstream protein mammalian target of rapamycin (mTOR), resulting in cell proliferation. mTOR inhibitors are currently being studied for treatment of endometrial cancer and other solid tumors. The purpose of this study was to determine if mTOR inhibition is a rational target for the treatment of progesterone refractory EH. Methods: Thirty-eight matched pre and post-treatment pairs of paraffin-embedded endometrial biopsies were obtained from patients with EH. Immunohistochemical analysis for PTEN and phospho-mTOR expression was performed on all samples using commercially available monoclonal antibodies. Absence of PTEN was determined if >10% of the glands did not express PTEN. Positive phospho-mTOR was defined as moderate (2+) to strong (3+) staining in at least 20% of the glands. Results: Sixteen patients (42%) had complete resolution of their hyperplasia (responders) and 22 (58%) had persistent hyperplasia despite treatment (non-responders). Following treatment with progesterone, increase in PTEN expression was observed in more responders than non-responders (78% vs. 16%, p=0.04). Positive phospho-mTOR expression was observed in 25/38 (66%) of pre and 24/38 (64%) of post-treatment samples. Increase or persistent positive phospho-mTOR expression was observed in more non-responders than responders (68% vs. 32%, p=0.13). Conclusions: Involution of PTEN negative glands was associated with response to progesterone therapy. Increase or persistent positive phospho-mTOR expression was found in a majority of progesterone refractory endometrial hyperplasias. This finding suggests that there may be a role for mTOR inhibitors in the treatment of progesterone refractory endometrial hyperplasia. No significant financial relationships to disclose.
Cancer risk of aged people with HIV infection and of transplant people
Authors: D. Serraino, P. Piselli, G. Busnach, F. Citterio, L. Fratino, U. Tirelli, P. Burra, E. Arbustini, C. Pradier, R. Giovanni, P. Carrieri
Journal: Journal of Clinical Oncology (2006)

20063 Background: Acquired immunesuppression due to HIV-infection or to anti-rejection therapies following organ transplantation is a well known risk factor for cancer. This increased risk has been well documented for young adults, whereas few data are available on older persons. In this study, we assessed the impact of cancer in HIV-positive persons (HIV+) and in transplant persons (TRP) who were 50 years of age or older. Methods: Data from a multi-cohort study conducted in Italy and France were analysed. Individuals ≥50 years of age were selected from the original study group constituted by 2002 HIV+ seroconverters from Italy, 6072 HIV+ from France and 2755 Italian TRP (1844 kidney, 702 heart, 159 liver and 50 lung TRP). Sex- and age-standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the cancer risk as compared to the general population. Among HIV+, the risk of cancer was also assessed according to treatment with highly active antiretroviral therapies (HAART). Results: This analysis was based on 94 cancers diagnosed in 833 HIV+, and on 154 cancers diagnosed in 1558 TRP ≥50 years of age. The SIRs for all cancers decreased with ageing, ranging from 5.1 (95% CI: 4.0–6.5) in HIV+ aged 50–59 to 2.1 (95% CI: 1.4–3.1) in HIV+ aged 60 or older. In TRP, the SIRs for all cancer were 2.5 (95% CI:2.0–3.1) and 1.6 (95% CI: 1.2–2.0), respectively. In HIV+, the protective effect of HAART was more evident in those aged 50–59 (SIR = 6.8 in never treated and SIR = 2.4 in ever treated) than in HIV+ aged ≥60 (SIR = 2.8 and SIR = 1.6, respectively). This pattern of cancer occurrence was peculiar to virus-related cancers (e.g., Kaposi’s sarcoma, non-Hodgkin’s lymphoma, liver cancer). SIRs for lung cancer in both groups were significantly increased but did not significantly differ according to HAART and/or age. The survival of both HIV+ and TRP was significantly reduced by the diagnosis of cancer, but the difference in survival was not associated with ageing (p = 0.20). Conclusions: Aged individuals with acquired immunesuppression have a cancer pattern similar to younger persons with immunosuppression, but the burden of cancer will increase in absolute terms because of the increasing proportion of older individuals among both HIV+ and TRP. No significant financial relationships to disclose.
Haplotypes of <i>BRCA1</i> and survival of non-small cell lung cancer patients treated with platinum-based chemotherapy
Authors: J. Ryu, E. Shin, J. Lee, Y. Yoo, J. Cho, H. Kim, E. Lee, C. Kim
Journal: Journal of Clinical Oncology (2008)

14503 Background: The BRCA1 has an important role in the processing of DNA damage. This study was conducted to know whether germ-line variations of BRCA1 affect outcome of NSCLC patients treated with platinum combination. Methods: We evaluated four tagging polymorphisms and their haplotypes of BRCA1 and their associations with treatment outcome in 300 NSCLC patients with stage IIIA (16%), IIIB (31%), and IV (53%). Results: Males were 79% and median age was 63 years (range, 28 to 89 years). By histology, squamous cell carcinoma was 139 (46.3%), adenocarcinoma in 137 (45.7%). MST of total patients was 13.0 months. There were no statistically significant associations of tagging polymorphisms (S1613G, IVS13–1893A>C, IVS12–1207C>T and IVS12+112C>A) and overall survival. Among five haplotypes (AACC, AACA, GCTC, GATC and AATC) evaluated, patients with 2 copies of AACC haplotype survived significantly shorter compared to patients with 0 or 1 copy (MST, 8.47 months vs. 14.57 months, log rank P = .0066), even after adjusted for body weight loss, performance status, stage, second line treatment and radiation therapy (HR, 2.097; 95% CI, 1.339 to 3.284). The patients with the 2 copies survived significantly shorter than the other patients in squamous cell carcinoma (MST, 6.8 months vs. 15.3 months, log rank P = 3.6 × 10−5) while no survival difference of between two groups was observed in adenocarcinoma (log rank P = .677). Conclusions: These findings suggest that the AACC haplotype of BRCA1 gene may be an important prognostic marker in NSCLC patients treated with platinum combination. No significant financial relationships to disclose.
Abstract 17514: Prevalence and Clinical, Electrocardiographic and Electrophysiological Characteristics of Ventricular Arrhythmias Originating from the Non-coronary Cusp of the Aorta
Authors: Takumi Yamada, Yung R Lau, Hugh T McElderry, Harish Doppalapudi, Jose Osorio, Vance J Plumb, G. N Kay
Journal: Circulation (2012)

Backgrounds- The aortic root is one of the major sites of idiopathic ventricular arrhythmias (VAs) origins. Some idiopathic VAs can be ablated from the non-coronary aortic cusp (NCC). The purpose o...
BRCA1 and BRCA2 germline mutation carriers have a lower breast density compared to high risk women without such mutations
Authors: P. Sharma, J. R. Klemp, B. F. Kimler, Q. J. Khan, E. J. Smith, C. J. Fabian
Journal: Journal of Clinical Oncology (2007)

1517 Background: High mammographic breast density, a known risk factor for breast cancer is influenced by both genetic and non genetic factors. It is not clear if there are differences in breast densities between BRCA1/2 mutation carriers and high-risk non carriers. The aim of this study was to compare breast density in high-risk women with and without BRCA1/2 mutation. Methods: Women at high risk for development of breast cancer (based on family history, prior precancerous disease or prior breast cancer) who underwent genetic testing at the University of Kansas Breast Cancer Prevention Center between 1998 and 2005 were identified under an IRB approved protocol. BRCA1/2 full sequencing was performed at Myriad Genetic Laboratories. The earliest digitized mammogram of these subjects was identified from a preexisting mammogram database. All mammograms had to be prior to/at least one year from any chemoprevention intervention. For subjects with prior breast cancer, mammogram of the uninvolved breast was used. Breast density was assessed on the left craniocaudal mammographic view by computer assisted method, Cumulus. Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Multiple regression analysis was used to investigate whether differences are due to variables other than mutation status. Results: The study population consisted of 284 high-risk women who underwent BRCA1/2 testing and for whom a mammogram was available. 30 (11%) had BRCA1 and/or 2 deleterious mutation. There was no difference between mutation carriers and non-carriers for BMI, 5 year Gail risk, parity, menopausal status and HRT use. Mutation carriers were younger (median age 42 vs. 46, p=0.020) and more likely to have a positive family history (100% vs. 85%, p=0.020). Older age (p&lt;0.001), higher BMI (p&lt;0.001) and having a BRCA1/2 mutation (p=0.025) were significantly associated with a lower breast density. Conclusion: Among high risk women, possession of a deleterious BRCA1/2 mutation is associated with lower breast density after adjusting for factors known to affect breast density. This suggests that breast density may be governed by genetic factors other than BRCA1/2 mutation status. No significant financial relationships to disclose.
Alloreactivity and Tumor Antigens: Generation of Syngeneic Antilymphoma Killer Lymphocytes by Alloimmunization of Mice With Normal Cells&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: M L Sensi, M Parenza, G Parmiani
Journal: JNCI Journal of the National Cancer Institute (1983)

The possibility of obtaining a syngeneic antitumor effect by immunization with normal allogeneic cells was investigated by tests of the lytic activity of peritoneal exudate cells (PEC) of BALB/c mice immunized with lymphoid cells of either a single strain or a pool of six different allogeneic strains on the syngeneic Moloney virus-induced lymphoma YC8 target and on one of its clones designated YC8-D1. Significant cytotoxicity on both targets but not on two other BALB/c lymphomas was obtained with PEC of BALB/c mice singly immunized to the non-H-2-incompatible but H-2-compatible DBA/2 or B10.D2 lymphoid cells. The lack of lysis of YC8 cells by PEC of BALB/c mice immune to B10.A (H-2k,d) suggests that the in vitro killing was restricted by Kd-IEd region products of the major histocompatibility complex. Pool immunization was effective in generating antitumor cytotoxic lymphocytes only when DBA/2 lymphoid cells were included in the pool. The pattern of reactivity of effectors elicited in (BALB/c x DBA/2)F1 and in (BALB/c x B10.D2)F1 mice by immunization with DBA/2 and B10.D2 cells showed that at least two sets of antigens are recognized on YC8 targets, one shared by DBA/2 and B10.D2 tissues and the other expressed by DBA/2 cells only. Cold target blocking experiments indicated that the same effectors recognized non-H-2 antigens of DBA/2 and the cross-reacting YC8 determinants. The antitumor effect was mediated by T-cells, since it was abrogated by treatment of effectors with anti-Thy 1.2 serum plus complement. These data indicate that determinants defined by cytotoxic T-lymphocytes are expressed on the BALB/c lymphoma YC8 and cross-react with non-H-2 antigens of DBA/2 and B10.D2 strains.
Experimental Aerosol Transmission of Yaba Virus in Monkeys&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lauren G. Wolfe, Richard A. Griesemer, Robert L. Farrell
Journal: JNCI Journal of the National Cancer Institute (1968)

Aerosol transmission of Yaba virus was demonstrated by tumor formation in 5 of 12 rhesus and 1 of 3 cynomolgus monkeys. Solitary or multiple pulmonary tumors were found in 5 of 14 monkeys necropsied between 2 and 16 weeks post exposure. In a sixth animal a large deforming nasal tumor and multiple subcutaneous tumors occurred. Compared to Yaba virus-induced subcutaneous tumors, the onset of tumor formation was delayed and the course was prolonged in aerosol-exposed monkeys. The susceptibility of individual monkeys to aerosol transmission could not be correlated with the dose of virus retained in the lung or with the interval between exposure and euthanasia. Horizontal transmission to cagemates was not observed. The pulmonary and nasal tumors were similar morphologically to Yaba virus-induced subcutaneous tumors. The sites of the initial proliferative response were demonstrated in the alveolar septa. Occasionally, bronchi and bronchioles were compressed and bronchioles, lymphatics, and blood vessels were invaded. Ultrastructurally, sites of viral replication were seen in granular pneumonocytes and in cells similar to those composing Yaba virus-induced subcutaneous histiocytomas. It was concluded that aerosolized Yaba virus is potentially hazardous to man.
Safety of panitumumab, a fully human monoclonal antibody against the epidermal growth factor receptor (EGFr), in patients (pts) with metastatic colorectal cancer (mCRC) across clinical trials
Authors: M. Peeters, E. Van Cutsem, J. Berlin, J. R. Hecht, R. Ruiz, L. Navale, R. Amado, N. J. Meropol
Journal: Journal of Clinical Oncology (2007)

4138 Background: Panitumumab is indicated in pts with EGFr-expressing mCRC refractory to chemotherapy. We present a summary of safety with panitumumab monotherapy in mCRC pts across 10 clinical trials. Methods: Data were pooled from pts enrolled in 10 clinical trials (including 2 extension studies). Pts received at least 1 dose of panitumumab at 2.5 mg/kg QW, 6 mg/kg Q2W, or 9 mg/kg Q3W. Adverse events were graded using NCI-CTC or CTCAE criteria. Results: A total of 920 mCRC pts were included in this analysis: 60% were male; 88% were white; median age (range) was 61 (20, 88) years. All pts had prior therapy; 77% had failed prior fluoropyrimidine, irinotecan, and/or oxaliplatin. Most (80%) pts received panitumumab 6 mg/kg Q2W; 17% and 3% of pts received panitumumab 2.5 mg/kg QW and 9 mg/kg Q3W, respectively. Median (range) follow-up time was 21 (1–124) weeks. A total of 7264 panitumumab infusions were administered with a median (range) of 5 (1–94) infusions/pt. Treatment-related adverse events (AE) were experienced by 94% (grade = 3, 20%) of pts. All pts had = 1 AE. The most common AEs were skin-related and GI toxicities ( table ). Skin-related AEs resulted in discontinuation in 2% of pts. Overall, 12% of pts discontinued panitumumab due to toxicity. Four (0.4%) pts had grade = 3 infusion reactions. In pts with postdose samples (n = 613), increased and persistent postdose levels of anti-panitumumab antibodies were detected in 0.5% of pts by ELISA and in 4.6% of pts by Biacore assay. Conclusions: Skin toxicity was common, but rarely treatment-limiting. Most AEs were mild to moderate and infrequently resulted in discontinuation. Infusion reactions and formation of anti-panitumumab antibodies were rare. The safety profile of 9 mg/kg Q3W panitumumab appeared consistent with other dosages; however, because of the small pt size further evaluation is needed. Panitumumab at 2.5 mg/kg QW and 6 mg/kg Q2W was well tolerated across 10 clinical studies. [Table: see text] No significant financial relationships to disclose.
Preclinical testing using tumors from genetically engineered mouse mammary models
Authors: L. Varticovski, M. G. Hollingshead, M. R. Anver, A. I. Robles, J. E. Green, K. W. Hunter, G. Merlino, N. Nunez, S. D. Hursting, P. S. Steeg, C. J. Barrett
Journal: Journal of Clinical Oncology (2006)

10067 Background: Mouse models have been used extensively in preclinical testing of anticancer drugs. However, few of these models reflect the progression of human disease, and even fewer predict the performance of these drugs in clinical trials. Testing anticancer therapies in genetically engineered mouse (GEM) holds the promise of improving preclinical models and guiding the design of clinical trials. Unfortunately, the use of tumor-bearing GEM is hampered by the difficulty in simultaneously obtaining sufficient numbers of animals with the same stage of tumor development. The additional complexity in testing breast cancer therapies in the mouse is that all 10 mammary glands can develop tumors, frequently at different times. Methods: To circumvent the variable tumor latency and lack of synchrony in GEM, we transplanted tumor fragments or cell suspensions from multiple mammary tumor-bearing GEM into the mammary fat pad or subcutaneously into naïve syngeneic, immunodeficient athymic nude, or scid mice. Results: Tumors transplanted as fragments or cell suspensions derived from anterior mammary gland grew faster than the posterior tumors for serial passages without any significant morphologic differences. Cell suspensions using fresh or frozen cells were equally effective in generating tumors, and increasing the numbers of transplanted cells resulted in faster tumor growth. The transplantation strategy was reproducible in multiple breast cancer mouse models, including MMTV-PyMT, -Her2/neu, -wnt1/p53, BRCA1/p53, and others. Metastatic disease in the lungs was evident after removing the primary tumors at different rates for each mouse model. The transplanted primary tumors and the tumors arising in the original GEM had similar morphologic appearance and sensitivity to several chemotherapeutic and novel molecular targeted agents. Conclusions: We have established transplantable synchronous mammary tumors from GEM which also develop metastatic disease. These valuable mouse models are suitable for studying tumor-host interactions, tumor progression, and preclinical testing in a well-characterized molecular and genetic background. Testing these GEM tumors for conventional and novel molecular targeted therapies will be discussed. No significant financial relationships to disclose.