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  • 1
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 12, No. 11_Supplement ( 2013-11-01), p. B191-B191
    Abstract: Purpose: To evaluate whether PIK3CA mutations and/or PTEN loss predict better clinical outcomes to phase I trials of PI3K/AKT/mTOR inhibition-based therapies in patients with metastatic, recurrent or refractory cervical cancers. Methods: Outcome analyses were conducted on 36 consecutive patients with advanced cervical cancers who were initially seen in a designated Phase I clinic at MD Anderson Cancer Center from 1/1/2006 to 6/30/2012, and tested for PIK3CA mutations and/or PTEN loss in a CLIA-certified molecular diagnostic laboratory, in accordance with the IRB guidelines. All data were obtained from patients’ electronic medical records. Results: All patients (n=36) had received at least one systemic therapy before the referral. Approximately 50% of tested patients (n=18/36) harbored PIK3CA mutations (n=9/34, 26% including seven E545K, one E542K, and one E545K/D549H in squamous cell carcinoma [7/19, 37%], adenocarcinoma [1/12, 8%] and small cell carcinoma [1/1, 100%]) and/or PTEN loss (n=12, 63%). Six patients were removed from further analyses because they did not enroll to a phase I study (n=2) or had only one negative result while the other test was not done (n=4). At their initial phase I therapy, the patients with PIK3CA mutations and/or PTEN loss (n=18) achieved four PR and seven SD ≥ 6 months (61% CR/PR/SD≥6months) with a median progression-free survival (PFS) of 6.7 months, compared to one CR and one SD ≥ 6 months (17% CR/PR/SD≥6months, p=0.026) with a median PFS of 2.5 months (p=0.001) in patients without PIK3CA mutations and/or PTEN loss (n=12). Analyses in patients receiving mTOR inhibitor-based phase I regimens showed that patients with PIK3CA mutations and/or PTEN loss (n=10) achieved three PR and four SD ≥ 6 months (70% CR/PR/SD≥6months) with a median PFS of 6.6 months, compared to one SD ≥ 6 months (17% CR/PR/SD≥6months, p=0.119) with a median PFS of 3.2 months (p=0.014) in patients without PIK3CA mutations and/or PTEN loss who received mTOR inhibitor-based phase I regimens (n=6); or one PR and three SD ≥ 6 months (50% CR/PR/SD≥6months, p=0.63) with a median PFS of 5.3 months (p=0.86) in patients with PIK3CA mutations and/or PTEN loss who did not receive mTOR inhibitor-based phase I regimens (n=8). Conclusions: The most frequent PIK3CA mutation in patients with advanced cervical cancers was E545K. Matched therapy using mTOR inhibitor-based regimens led to dramatic clinical responses, and a significantly longer PFS in patients with PIK3CA mutations and/or PTEN loss. Thus, targeting aberrant PI3K pathway is warranted for further evaluation in patients with advanced cervical cancers. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B191. Citation Format: Ming-Mo Hou, Xiaochun Liu, Sarina A. Piha-Paul, Filip Janku, Jennifer Wheler, Aung Naing, Diane Bodurka, Kathleen Schmeler, Karen Lu, Ralph Zinner, David Hong, Funda Meric-Bernstam, Razelle Kurzrock, Siqing Fu. Target-matched therapies in patients with advanced cervical cancers harboring PIK3CA mutations and/or PTEN loss. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B191.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2062135-8
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2013
    In:  Contributions to Mineralogy and Petrology Vol. 165, No. 4 ( 2013-4), p. 641-662
    In: Contributions to Mineralogy and Petrology, Springer Science and Business Media LLC, Vol. 165, No. 4 ( 2013-4), p. 641-662
    Type of Medium: Online Resource
    ISSN: 0010-7999 , 1432-0967
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 1616-0
    detail.hit.zdb_id: 1458979-5
    detail.hit.zdb_id: 2075437-1
    detail.hit.zdb_id: 2075439-5
    detail.hit.zdb_id: 2075450-4
    SSG: 13
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  • 3
    In: American Journal of Nephrology, S. Karger AG, Vol. 37, No. 3 ( 2013), p. 199-207
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 An experimental model of CIN was established in rats. Serum creatinine, blood urea nitrogen, plasma cystatin C, urinary N-acetyl-β-glucosaminidase, and urinary & #947;-glutamyl transpeptidase were measured to evaluate kidney function. Apoptosis was assessed by transmission electron microscopy, transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and poly-ADP-ribose polymerase cleavage. Fork-head box O1 transcriptional factor (FoxO1) mRNA expression was evaluated by quantitative real-time PCR. Phospho-p38 mitogen-activated protein kinase (MAPK) protein expression was assessed by immunohistochemistry and Western blotting. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 TMP significantly attenuated the resulting renal dysfunction and renal tubular cell apo-ptosis. Mechanistically, TMP decreased the expression of phospho-p38 MAPK protein and attenuated the increased FoxO1 mRNA and nuclear protein expression. In addition, TMP inhibited inducible nitric oxide synthase and Bax protein expression while it upregulated Bcl-2. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 In summary, this study demonstrated the protective role of TMP against CIN and indicated the effects of TMP may be mediated by the inhibition of p38 MAPK and FoxO1 pathways. Thus, TMP may be a new potential therapeutic agent to prevent CIN.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1468523-1
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2013-01-23)
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2615211-3
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2013
    In:  Frontiers of Medicine Vol. 7, No. 1 ( 2013-3), p. 143-146
    In: Frontiers of Medicine, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2013-3), p. 143-146
    Type of Medium: Online Resource
    ISSN: 2095-0217 , 2095-0225
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2617113-2
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e13534-e13534
    Abstract: e13534 Background: Patients with metastatic cervical cancers have a poor prognosis and few effective therapies available. Thus, access to a phase I trial may provide a viable option. Methods: Outcomes of 54 consecutive patients with metastatic cervical cancers seen in a phase I clinic at MD Anderson Cancer Center from 1/1/2006 to 12/31/2012 were reviewed in accordance with the MD Anderson IRB guidelines. Results: The 54 patients included Caucasians (n=34, 63%), Hispanics (n=9, 17%), African Americans (n=7, 13%), and others (n=4, 7%). Pathological diagnoses were squamous cell carcinoma (n=33, 60%), adenocarcinoma (n=12, 22%), adenosquamous (n=3, 6%), poorly differentiated carcinoma (n=2, 4%), small cell carcinoma (n=2, 4%), clear cell carcinoma (n=1, 2%), and melanoma (n=1, 2%). Initial staging was as follows: I (n=16, 30%), II (n=11, 20%), III (n=11, 20%), and IV (n=16, 30%). Prior treatment included surgery (n=23, 43%), radiotherapy (n=41, 76%), and systemic chemotherapy (n=54, 100%) including one regimen (n=30, 55%), two (n=15, 28%) and more (n=9, 17%). At their initial visit to the phase I clinic, the median age was 47 years. The majority of patients had ECOG PS 0-1 (n=45, 83%), and MDACC prognostic scores 0-1 (n=48, 89%). Almost all the 54 referred patients were enrolled into a phase I trial (n=52, 96%). Initial phase I trials these patients had received led to one CR, five PR, and 12 SD ≥ 6 months (CR/PR/SD≥6 months=35%). Of the patients who progressed on their first protocols, 11 patients (21%) were enrolled into a second protocol, leading to 36% of PR/SD≥6 months (n=4). Among those enrolled into a third (n=4) and a fourth (n=1) study, no CR/PR/SD≥6 months was achieved. The median overall survival in these 54 referred patients was 10.6 months. Among 36 patients who underwent molecular marker studies, 15 were found to harbor PIK3CA mutations and/or PTEN loss (42%) and achieved 60% of CR/PR/SD≥6 months (3 PR and 6 SD≥6 months). Conclusions: Aberrant PI3K pathway was frequently identified in advanced cervical cancers, and the high rate of CR/PR/SD≥6 months was observed in these patients treated under a phase I trial, suggesting that phase I trials, especially mutation matched regimens, may provide potential benefits to these patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e13575-e13575
    Abstract: e13575 Background: Mucositis is a well-known side effect of mTOR inhibitor (temsirolimus) treatment of cancer patients, limiting the use of mTOR inhibitors. We investigated whether combination treatment of temsirolimus with another agent that was not known to cause mucositis would result in a higher or lower incidence of mucositis. We further investigated if there was an association between the severity of mucositis and tumor response to the temsirolimus-based combination treatment. Methods: This retrospective data review was approved by IRB and conducted in the department of Investigational Cancer Therapeutics at MD Anderson Cancer Center. We reviewed the electronic medical records of 87 patients who were enrolled in temsirolimus-based combination phase I trials (n=3), including physician notes from the date they enrolled on the study to the date they came off treatments. We first examined the incidence of mucositis during the course of study and its severity. We assessed patient response to the study treatment with severity of the mucositis. Results: The overall incidence of mucositis in the 3 temsirolimus-based combination trials was 46%, similar to the published data for the single agent of 41%. The grades of mucositis were: for grade 1 (n=14), grade 2 (n=17) and grade 3 (n=9). No grade 4 mucositis was observed. Neither gender nor ethnicity altered the incidence of mucositis. The median onset time was 14 days after the start of the studies. Of 87 patients, 20 responded to the study treatments with at least stable disease for longer than 6 months or a partial or complete response. The incidence of the mucositis was not associated with the response to temsirolimus-based treatment. Severity of mucositis did not correlate with response to the temsirolimus-based regimen. (grades 1/2 vs. ≥ grade 3; p=0.512). Conclusions: The incidence of mucositis did not increase significantly in patients who received a temsirolimus-based regimen compared to single-agent temsirolimus. Severity of mucositis did not correlate with tumor response to the temsirolimus-based regimen. Future study is warranted to optimize management for mTOR inhibitor-induced mucositis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 26_suppl ( 2013-09-10), p. 9-9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 26_suppl ( 2013-09-10), p. 9-9
    Abstract: 9 Background: Traditionally, breast cancer-related lymphedema is considered to be mainly due to the mechanical injury from cancer surgery. Recent research identified that inflammation-infection may be one of the important predictors for lymphedema. This pilot study aimed to explore the associations between lymphatic and pro-inflammatory candidate gene variations and lymphedema. Methods: A prospective, longitudinal, repeated-measure, and comparative design was used to recruit 178 breast cancer survivors. To ensure the accuracy of lymphedema phenotype, lymphedema was classified into lymphedema of arm and breast. Arm lymphedema must have been validated by infra-red perometer and a bioimpedance device. Breast lymphedema was validated by an observational scale since no objective measure is available. Saliva samples were collected for DNA extraction. Candidate Gene Association Research Method was used to examine the eight genes known for inflammation and lymphatic specific growth factors: cytokines (IL1A, IL6, IL8, IL10, IL13) and PTGS2 (COX2), and lymphatic specific growth factors [VEGF-C and D]. Descriptive statistics, Chi-Squared tests for contingency tables and one-way analysis of variance for continuous variables were used to compare the genotypes for each of these genes in patients with and without lymphedema. Odds ratios of developing lymphedema are estimated. Results: Among 178 survivors, 39 women were confirmed to have arm lymphedema and 43 women had breast lymphedema. Five genes were significantly associated with breast cancer-related lymphedema. Specific single nucleic polymorphisms (SNPs) for lymphatic specific growth factors VEGF-C (rs4604006) and cytokine IL13 (rs1800925) were related to arm lymphedema. Specific SNPs of cytokine IL1A (rs1800587) and PTGS2 (COX2) (rs20417) were associated with breast lymphedema. Conclusions: Our findings provided preliminary data on genetic susceptibility as a risk factor for breast cancer-related lymphedema. Findings of our study may serve as a preliminary foundation for a priori recognition of genetic risk that may facilitate lymphedema risk prediction prior to surgery and raises the potential for early intervention for a high-risk group.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 9
    Online Resource
    Online Resource
    Institute of Electrical and Electronics Engineers (IEEE) ; 2013
    In:  IEEE Transactions on Image Processing Vol. 22, No. 10 ( 2013-10), p. 3766-3778
    In: IEEE Transactions on Image Processing, Institute of Electrical and Electronics Engineers (IEEE), Vol. 22, No. 10 ( 2013-10), p. 3766-3778
    Type of Medium: Online Resource
    ISSN: 1057-7149 , 1941-0042
    Language: Unknown
    Publisher: Institute of Electrical and Electronics Engineers (IEEE)
    Publication Date: 2013
    detail.hit.zdb_id: 2034319-X
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  • 10
    In: The Analyst, Royal Society of Chemistry (RSC), Vol. 138, No. 12 ( 2013), p. 3388-
    Type of Medium: Online Resource
    ISSN: 0003-2654 , 1364-5528
    Language: English
    Publisher: Royal Society of Chemistry (RSC)
    Publication Date: 2013
    detail.hit.zdb_id: 1472713-4
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