tbuckley/cabot-search huggingface dataset:
Synchronous versus metachronous breast cancer: Characteristics of the second tumor
Authors: M. Solh, H. Bu ALI, V. Mittal, K. Bergsman
Journal: Journal of Clinical Oncology (2008)

1107 Background: Synchronous breast cancer is a tumor diagnosed within three months from the diagnosis of the first tumor. There is, currently, no consensus as to it being a totally independent second primary or having the same disease entity as the primary tumor. Our study describes the clinical, histopathologic and prognostic factors of synchronous breast cancer and compares them with metachronous breast cancer. Methods: A retrospective analysis of all patients with synchronous and or metachronous breast cancer treated between January 1991 and March 2004 was done through chart review. Further follow-up data was obtained from the patients’ oncologist's database. Results: Out of a total of 114 patients, 63% had metachronous breast cancer and 37% synchronous. 77.8% of the metachronous group documented a first degree relative with breast cancer compared with 22.2% in the synchronous group (p<0.05). 84% of metachronous tumors and 87% of synchronous tumors involved the contralateral breast. Infiltrating ductal carcinoma was the most common histologic type of the first tumor in both groups. Synchronous breast cancers had a higher incidence of LCIS (16% vs. 4%; p<0.01). This was observed in the second tumor as well (p>0.05). Both first and second tumors of the synchronous group were histologically more aggressive than the metachronous tumors (p<0.05). Both groups were similar regarding the expression of estrogen and progesterone receptors. Both groups were also similar regarding the distribution of tumor stage with 64% of first diagnosed tumors as stage I-II. Synchronous cancer metastasis involved more than one organ (p<0.05). The average lifetime survival from the day of diagnosis for the synchronous group was 4.7 years compared with 12.5 in the metachronous group (p<0.005). Conclusions: Our series shows synchronous breast cancer to be more aggressive than metachronous breast cancer with a poorer outcome. Moreover, the concordance between different tumors within the same patient, in particular for histology, grade, stage and receptor status support the hypothesis of monoclonal origin of synchronous breast cancer. No significant financial relationships to disclose.
Focused Analysis of Exome Sequencing Data for Rare Germline Mutations in Familial and Sporadic Lung Cancer
Authors: Yanhong Liu, Farrah Kheradmand, Caleb F. Davis, Michael E. Scheurer, David Wheeler, Spiridon Tsavachidis, Georgina Armstrong, Claire Simpson, Diptasri Mandal, Elena Kupert, Marshall Anderson, Ming You, Donghai Xiong, Claudio Pikielny, Ann G. Schwartz, Joan Bailey-Wilson, Colette Gaba, Mariza De Andrade, Ping Yang, Susan M. Pinney, Christopher I. Amos, Margaret R. Spitz
Journal: Journal of Thoracic Oncology (2016)
Physical exercise modulates the homeostasis of human regulatory T cells
Authors: Max Weinhold, Alexander Shimabukuro-Vornhagen, Axel Franke, Sebastian Theurich, Patrick Wahl, Michael Hallek, Annette Schmidt, Timo Schinköthe, Joachim Mester, Michael von Bergwelt-Baildon, Wilhelm Bloch
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract #LB-302: Computational identification of oncogenic and tumor suppressor gene networks that related to the cell cycle regulation
Authors: Tomokazu Fukuda, Hideko Sone, Hiromi Akanuma, Hiroyoshi Toyoshiba, Takeharu Yamanaka, Christopher Portier
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Although the importance of cell cycle related oncogene or tumor suppressor genes (e.g. pRB and Cyclin complexes) in the process of the tumorgenesis is well characterized in the clinical and experimental analysis. However, there are still unknown mechanisms for the cell cycle regulation, which is critical step for the progression of the carcinogenesis. For example, it is not fully understood how the cells move to G1 phase from quiescent G0 phase, especially in the mammalian cells. To find out the new gene networks associated with the two transition of the mammalian cell cycle (G0 to G1 and G1 to S phase), we analyzed the linkages between 39 representative oncogene or tumor suppressor genes, which related to the cell cycle regulation, with microarray data obtained from mouse embryonic fibroblasts that synchronized by the serum starvation or hydroxyurea treatment. Analyses with a qualitative algorithm based on Bayesian networks that assume a log-linear relationship between genes have applied, and newly found networks were validated. Results highlighted the importance of two master genes, Cdk7 and Cdkna2 for the re-entry to G1 from G0, and suggested a new network connection from Cdk7 to downstream molecules, including the EGF receptor and N-myc. Profiling of promoter transcription factor binding sites for the downstream molecules suggested that newly identified Cdk7 gene network was mainly mediated through the transcriptional activity of CDK7. Introduction of a recombinant CDK7 with retrovirus resulted in decreased endogenous EGFR and N-myc protein levels. Our results first highlighted the importance of CDK7 for the transition from G0 to G1 caused by the serum stimulation. Furthermore, this study showed the existence of new regulating pathway from CDK7 to EGFR and N-myc, suggesting this analytical approach provides an assessment of regulatory networks in complex mammalian cells, and the process of the carcinogenesis.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-302.
Impact of highly active antiretroviral therapy (HAART) on the incidence and survival in human immunodeficiency virus-infected (HIV) adults with cancer
Authors: R. D. P. Reategui, J. Villena, L. Gutierrez, R. Salazar, J. Vega, J. Collins, R. Chumpitaz, M. d. P. Benites, F. Salas
Journal: Journal of Clinical Oncology (2005)

6033 Background: Cancer is a frequent complication of HIV infection.HAART has been widely used and has a positive impact on survival of AIDS, however its impact on incidence and survival of cancer in HIV patients is still unclear. Method: We performed a retrospective analysis of clinical data of HIV patients diagnosed in Hospital Nacional Guillermo Almenara Lima-Peru, collected from Jan 1992 to December 2002. 2422 HIV-seropositive patients were analized, representing 8738 person-years. HAART was introduced in our institution since 1998. Incidence was calculated as number of cases per 1000 person/year Results: During this 11 years observation period, 101 newly diagnosed cases of cancer were reported. The cancer incidence in the pre HAART period (1992–1997) was 19.87 compared with 8.56 (p<0.001) in post HAART era. Kaposi’s sarcoma incidence declined from 8.21 to 3.89 (p=0.012), also Non Hodgkin Lymphoma (NHL) incidence was significant lower after HAART use from 8.64 to 1.86 (p<0.001) as well as in Cerebral Lymphoma (3.02 to 0.15; p<0.001). No significant changes were observed in cervical or other tumors. Median overall survival of cancer patients with no HAART was 2 months compared with non reached median survival of HAART treated cancer patients, and the 5 years survival was 17% versus 61%(p<0.001).A superior 5 years survival for patients with HAART and antitumor therapy in comparison with cancer patients with HAART and no cancer treatment was also observed (70% vs 51% p<0.033). Conclusions: In our serie, incorporation of HAART as standard treatment in HIV patients produced a reduction in the incidence of Kaposi’ Sarcoma and NHL. We also observed an improvement in 5 years survival in patients diagnosed of HIV and cancer, treated with HAART, with or without the use of antineoplastic treatment. Our data demonstrated the benefit of using an aggressive treatment of HIV infection as well as for the cancer in the outcome of these patients. No significant financial relationships to disclose.
Survival for children with medulloblastoma following tumor recurrence or progression
Authors: L. Gargan, A. Mulne, R. D. Elterman, B. E. Weprin, N. J. Winick, D. C. Bowers
Journal: Journal of Clinical Oncology (2005)

1556 Background: Despite improvement in therapies, a substantial number of children with medulloblastoma experience tumor progression. The objectives of this single institution report are to report the 5 year post-progression survival and to identify prognostic factors for survival among children with progressive or recurrent medulloblastoma. Methods: The relationship between post-progression survival and demographic, tumor, and treatment factors were examined among 46 patients (22 females; mean age at diagnosis = 6.5 years; mean age at progression = 8.4 years) with recurrent medulloblastoma. Differences were calculated by Kaplan-Meier log rank analysis. Results: The probability of 5 year post-progression survival among patients in this study with progressive medulloblastoma was 26.3%. Twenty-two (48%) patients had local recurrence only, 5 (11%) had local + distant recurrence, and 19 (41%) had distant recurrence only. Patients with local recurrence only had a significantly prolonged post-progression survival compared to those with local + distant and distant recurrence (p = 0.039). The 17 patients treated with radiation therapy (RT) following progression had prolonged PPS (p = 0.003). Other categorical variables, including patient sex, age < 3 years at diagnosis, age < 6 years at diagnosis, age at progression, interval from diagnosis to progression, initial tumor stage, initial adjuvant therapy, and treatment with chemotherapy or autologous stem cell transplant following progression, were not associated with prolonged post-progression survival. Conclusions: Although the post-progression survival is poor for children with recurrent medulloblastoma, certain patients groups differ appreciably in their likelihood of post-progression survival. Patients with who have a local recurrence only and those who receive RT following progression have prolonged post-progression survival. No significant financial relationships to disclose.
Long-term exposure to air pollution and asthma hospitalizations in elderly adults: A cohort study
Authors: Zorana Andersen, Klaus Bønnelykke, Martin Hvidberg, Steen Jensen, Matthias Ketzel, Steffen Loft, Mette Sørensen, Anne Tjønneland, Kim Overvad, Ole Raaschou-Nielsen
Journal: European Respiratory Journal (2011)

Background:  Exposure to air pollution in early life contributes to the burden of childhood asthma, but it is not clear whether lifetime exposure to air pollution can lead to asthma onset or progression in adulthood. We studied the effect of exposure to traffic-related air pollution over 35 years on the risk for hospitalization for asthma in elderly.   Methods:  We followed 57 053 participants in the Danish Diet, Cancer and Health cohort, aged 50-65 years at baseline (1993-1997), for first hospital admission for asthma until 2006. Annual levels of nitrogen dioxide (NO 2 ) were estimated at all residential addresses since 1971. We modelled the association between NO 2  and hospitalization for asthma using Cox regression in people with and without previous hospitalizations for asthma, and assessed effect modification by co-morbid conditions.   Findings:  During 9.9 years9 mean follow-up, 977 of 53 695 eligible people (1.9%) were admitted to hospital for asthma: 821 (1.5%) admissions were among 53 143 people who had not and 176 (31.9%) among 552 people who had been hospitalized for asthma before baseline. NO 2  levels were positively associated with risk for asthma hospitalization in the full cohort (hazard ratio and 95% confidence interval per inter-quartile range, 5.8 μg/m 3 : 1.12; 1.04-1.22), and in people without previous asthma hospitalization (1.10; 1.01-1.20), with the strongest effects for people with a history of asthma hospitalization (1.41; 1.15-2.07). Enhanced associations between NO 2  and admissions for asthma were observed for people with COPD (1.30; 1.07-1.52).   Interpretation:  Air pollution is a risk factor for progression and/or onset of asthma in late adulthood.
miR-892b Silencing Activates NF-κB and Promotes Aggressiveness in Breast Cancer
Authors: Lili Jiang, Liang Yu, Xin Zhang, Fangyong Lei, Lan Wang, Xiangxia Liu, Shu Wu, Jinrong Zhu, Geyan Wu, Lixue Cao, Aibin Liu, Libing Song, Jun Li
Journal: Cancer Research (2016)

The strength and duration of NF-κB signaling is tightly controlled at multiple levels under physiologic conditions, but the mechanism underlying constitutive activation of the NF-κB pathway in cancer remains unclear. In this study, we investigated miRNA-mediated regulation of the NF-κB cascade in breast cancer. We report that miR-892b expression was significantly downregulated in human breast cancer specimens and correlated with poor patient survival. Overexpression of miR-892b in breast cancer cells significantly decreased tumor growth, metastatic capacity, and the ability to induce angiogenesis, whereas miR-892b depletion enhanced these properties, in vitro and in vivo. Furthermore, we demonstrate that miR-892b attenuated NF-κB signaling by directly targeting and suppressing multiple mediators of NF-κB, including TRAF2, TAK1, and TAB3, and thus, miR-892b silencing in breast cancer cells sustains NF-κB activity. Moreover, miR-892b downregulation was attributed to aberrant hypermethylation of its promoter. Taken together, our results provide insight into a new mechanism by which NF-κB signaling becomes constitutively activated in breast cancer and suggest a tumor-suppressive role for miR-829b, prompting further investigation into miRNA mimics for cancer therapy.
Comparison of Radiosensitivity Between Human Hematopoietic Cell Lines Derived From Patients With Down's Syndrome and From Normal Persons2
Authors: C. C. Huang, A. Banerjee, J. C. Tan, Y. Hou
Journal: JNCI Journal of the National Cancer Institute (1977)

Seven hematopoietic cell lines, four derived from the peripheral blood of patients with Down's syndrome (DS) and three from normal persons, were irradiated with 100, 150, 300, and 500 rads from a 60Co source and harvested for cell count and chromosome aberration studies every 12 hours for 72 hours post irradiation. Cell growth inhibition and an increase in chromosome aberration were observed in all the cell lines at each dose level and time interval. No significant difference was observed in the effects between DS and normal cell lines. The most common types of aberrations in the 12-hour samples were chromosome and/or chromatid breaks. In the later samples, chromatid exchanges were predominant. The results of the variance analyses on the induced chromosome aberrations in six lines (three DS and three normal lines) showed radiation dosage to be the largest component of total variance, following postirradiation duration and cell lines. The samples harvested 24 and 36 hours post irradiation generally showed greater effects than the samples of other harvest durations. The cell line variance could only be attributed to the differences among and between individual cell lines rather than the difference between DS and normal cell lines.
The role of growth factor support following neutropenic events in early stage breast cancer (BC) patients treated with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC): A sub-analysis of BCIRG 001
Authors: C. L. Vogel, J. R. Mackey, M. Martin
Journal: Journal of Clinical Oncology (2004)

677 Background: TAC significantly improves disease-free and overall survival over FAC (HR 0.70, 0.68, respectively) and is emerging as one of the most active adjuvant treatments in patients (pts) with node positive early stage (BC) (Martin, SABCS 2003 #43). TAC is generally well tolerated but is associated with a higher incidence of febrile neutropenia (FN) vs FAC. ASCO clinical practice guidelines recommend secondary prophylaxis with G-CSF after FN in a prior cycle to maintain dose intensity. Methods: Pts with node-positive BC were randomized to TAC (75/50/500 mg/m2 q3wk x 6) or FAC (500/50/500 mg/m2 q3wk x 6). Corticosteroid premedication and prophylactic ciprofloxacin were given with TAC, but not with FAC. In case of FN (≥ gr 2 fever with gr 4 neutropenia), pts were treated with G-CSF for all subsequent cycles. This retrospective sub-group analysis compares the incidence of FN for cycles treated without and with G-CSF. Results: 1491 patients were accrued with 1480 evaluable for safety (TAC 744, FAC 736). A similar number of cycles were delivered in both arms (TAC 4010; FAC 4007). FN: TAC 183 pts (24.7% pts, 5.4% cycles), FAC 18 pts (2.5% pts, 0.5% cycles) with at least half the FN occurring in the first cycle (TAC: 97/183 pts; FAC 9/18 pts). G-CSF was administered to 250 TAC pts and 93 FAC pts. Among these, G-CSF was used as secondary prophylaxis for 87% (TAC) and 44% (FAC) of pts. The rate of FN (per cycle) without vs with G-CSF (+G) among all pts was: TAC 187/3114 (6.0%) vs TAC+G 28/896 (3.1%); FAC 19/3704 (0.5%) vs FAC+G 1/303 (0.3%). There were no septic deaths during treatment with either TAC or FAC, regardless of the use of GCSF. Conclusions: Among pts treated with TAC, the use of G-CSF decreased the incidence of neutropenic complications, although it remained higher than for pts treated with FAC. For pts experiencing a neutropenic event with TAC, secondary prophylaxis with G-CSF is appropriate. The impact of G-CSF on other clinical safety parameters will also be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Aventis
Does race impact survival in VA patients with gastric cancer?
Authors: S. Ali, U. Navaneethan, M. S. Beg, M. M. Safa
Journal: Journal of Clinical Oncology (2008)

4645 Background: Prior studies have found racial disparities in the use of treatment and survival in gastric cancer. The aim of this study was to assess the influence of race on the treatment and outcome of patients with cancer of the stomach at the VA. Methods: We searched the VA Central Cancer Registry (VACCR) for all stomach cancer cases from 1995–2006 using ICD codes 160- 169. The data was transformed, analyzed using SPSS v.13.0. Results: There were a total of 6,453 patients with gastric adenocarcinoma, of which 6,296 patients were analyzed. There were 1,769 (28.9%) black and 4,527 (71.9%) white patients with gastric cancer. Baseline characteristics between white and black patients were similar (see table). Staging information was available for 3,606 (57.3%) patients. The incidence of metastatic disease was similar in black versus white patients (46.5% vs. 44.13%, p=0.19). There was also no difference in median survival in patients of either race (see table). The use of surgery was similar in both races with non metastatic disease. In metastatic disease surgery, chemotherapy or radiotherapy was also similar. In Cox-regression analysis considering variables including age, race, stage and treatment, only age, surgery, chemotherapy and absence of metastatic disease were found to be independent predictors of survival, while race did not influence the survival. Conclusion: In the VA system, black veterans with adenocarcinoma of the stomach are as likely to undergo surgical resection, chemo and radiotherapy for metastatic gastric cancer as white veterans. Although, there was no difference in the median survival and the incidence of metastatic disease between black and white patients, the median survival outcome was uniformly poor in patients with gastric cancer. In the presence of equal access medical system, the treatment and outcomes do not differ much between black and white veterans with regard to cancers of the stomach. Baseline Characteristics Characteristic Number of patients (N=6296) P Value Blacks N=1,769 Whites N=4,527 Age (Years) 67.4 68.94 P=0.17 Stage (n=3,606, 57.3%) Non metastatic disease 548 (27.5%) 1,442 (72.5%) P=0.19 Metastatic disease 477 (29.5%) 1,139 (70.5%) P=0.19 Survival (Months) Non metastatic disease 14.13 13.03 P=0.49 Metastatic disease 3.0 2.83 P=0.47 No significant financial relationships to disclose.
Role of Computed Tomography in Staging and Management of Gastrointestinal Lymphoma
Authors: George Blackledge, Jonathan K Best, Derek Crowther
Journal: Journal of the Royal Society of Medicine (1979)

Twenty-six computed tomography (CT) examinations in 18patients with histologically proven gastrointestinal lymphomas are reported. Fourteen CT examinations were performed at the time of initial presentation, the others being performed during the course of the disease. CT did not help in the diagnosis of the disease but it is effective in assessing the extent and thus the stage of the disease. A normal CT scan during follow up is associated with good prognosis. CT may be of help in planning treatment, especially radiotherapy. It is an investigation easily tolerated by patients and can be used in circumstances where other investigations would be impossible.
A phase I, pharmacokinetic and pharmacodynamic study of sorafenib (S), a multi-targeted kinase inhibitor in combination with temsirolimus (T), an mTOR inhibitor in patients with advanced solid malignancies
Authors: A. Patnaik, A. Ricart, J. Cooper, K. Papadopoulos, M. Beeram, C. Mita, M. M. Mita, D. Hufnagel, E. Izbicka, A. W. Tolcher
Journal: Journal of Clinical Oncology (2007)

3512 Background: The combination of S and T is hypothesized to maximize pathway inhibition by concurrently targeting parallel signaling mechanisms and will abrogate potential resistance mechanisms directed towards the MAPK pathway through increased signaling via the survival pathway involving PI3K/Akt. Methods: Eligible patients (pts) were treated with escalating continuous oral doses of S (200 and 400 mg BID) and weekly T IV (15 mg, 25 mg). S began on day 8 of course 1 to permit PK evaluations of T. PD studies in PBMCs were performed serially in pts. Results: To date, 24 evaluable pts have received 85 courses [median 3;range1–12] in the following S/T dose cohorts; cohort 1: 200 mg/15 mg (n=6), cohort 2: 400 mg/15 mg (n=11), cohort 3: 400 mg/25 mg (n=6), and cohort 4: 200 mg/25 mg (n=1). Patients demographics were males/female 11/13, median age 54.5 [range 27–71] and PS of 0/1/2 : n=9/13/2. Dose limiting toxicities (DLT) were grade 3 typhlitis in 1/6 pts in cohort 1, and mucositis in 1/6 pts in cohort 2. Expansion of cohort 2 to 11 patients resulted in 4 additional DLTs (hand foot syndrome (HFS) x 2 pts, thrombycytopenia/rash x 1 pt, creatinine elevation x 1 pt). 3 of 6 pts in cohort 3 experienced DLT (HFS x 2 pts, thrombocytopenia x 1 pt). PK analyses show no evidence of S effect on T kinetics while C ss,min values of S are consistent with those reported in single-agent studies (S 200mg BID median C ss,min 4.42 μg/mL [SD 3.05], S 400 mg BID median C ss,min 5.11 μg/mL [SD 4.35]). Apparent downregulation of 4E-BP1 and activated forms of p70S6 kinase and ERK was observed in some patients following treatment. Partial responses have occurred in NHL (1 pt) and papillary thyroid cancer (1 pt) and prolonged SD (&gt; 12 mo) has been observed in RCC (1 pt). Conclusions: The combination of S and T demonstrate significant mucocutaneous toxicity at full doses of S, however preliminary PK analyses show no evidence of drug-drug interactions. Characterization of an intermediate dose of S 200 mg BID/T 25 mg IV is ongoing. [Table: see text]