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Trpkov K.,University of Calgary | Grignon D.J.,Indiana University | Amin M.B.,Cedars Sinai Medical Center | Billis A.,University of Campinas | And 9 more authors.
American Journal of Surgical Pathology | Year: 2013

The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a Z65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus, "the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in <10% of radical nephrectomy specimens. Copyright © 2013 by Lippincott Williams & Wilkins.


PubMed | Anderson Cancer Center Houston, New York University and Association of Chinese American Physicians Flushing
Type: Review | Journal: American journal of cancer research | Year: 2016

Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.


Sonego M.,Italian National Cancer Institute | Schiappacassi M.,Italian National Cancer Institute | Lovisa S.,Italian National Cancer Institute | Dall'Acqua A.,Italian National Cancer Institute | And 22 more authors.
EMBO Molecular Medicine | Year: 2013

Stathmin is a p53-target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG-EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG-EOC cells carrying a p53 mutant (p53MUT) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53MUT by DNA-PKCS, eventually modulating p53MUT stability and transcriptional activity. Inhibition of stathmin or DNA-PKCS impaired p53MUT-dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA-PKCS, p53MUT overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells. © 2013.


Smitha S.,Cochin University of Science and Technology | Haseena V.S.,Cochin University of Science and Technology | Narayanan T.N.,Rice University | Reena Mary A.P.,Cochin University of Science and Technology | And 8 more authors.
Materials Express | Year: 2012

Multimodal imaging agents that combine magnetic and fluorescent imaging capabilities are desirable for the high spatial and temporal resolution. In the present work, we report the synthesis of multifunctional fluorescent ferrofluids using iron oxide as the magnetic core and rhodamine B as fluorochrome shell. The core-shell structure was designed in such a way that fluorescence quenching due to the inner magnetic core was minimized by an intermediate layer of silica. The intermediate passive layer of silica was realized by a novel method which involves the esterification reaction between the epoxy group of prehydrolysed 3-Glyidoxypropyltrimethoxysilane and the surfactant over iron oxide. The as-synthesized ferrofluids have a high saturation magnetization in the range of 62-65 emu/g and were found to emit light of wavelength 640 nm (λexcitation = 446 nm). Time resolved life time decay analysis showed a bi-exponential decay pattern with an increase in the decay life time in the presence of intermediate silica layer. Cytotoxicity studies confirmed the cell viability of these materials. The in vitro MRI imaging illustrated a high contrast when these multimodal nano probes were employed and the R2 relaxivity of these sample was found to be 334 mM-1s-1 which reveals its high potential as a T2 contrast enhancing agent. © 2012 by American Scientific Publishers. All rights reserved.


PubMed | University Utrecht, Netherlands Cancer Institute, Anderson Cancer Center Houston, Medical College of Wisconsin and 4 more.
Type: | Journal: Frontiers in oncology | Year: 2016

An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented.


PubMed | Anderson Cancer Center Houston, Houston Methodist Hospital Houston, Texas Childrens Cancer and Hematology Centers Houston and Baylor College of Medicine
Type: Journal Article | Journal: International journal of clinical and experimental pathology | Year: 2014

Precursor B acute lymphoblastic leukemia (B-ALL) is the most common cancer in children and overall, has an excellent prognosis. However, the Philadelphia chromosome translocation (Ph+), t(9;22)(q34;q11), is present in a small subset of patients and confers poor outcomes. CD25 (IL-2 receptor alpha chain) expression has been associated with Ph+ B-ALL in adults, but no similar study has been performed in pediatric B-ALL.A retrospective analysis of 221 consecutive pediatric patients with a diagnosis of B-ALL (blood and/or bone marrow) from 2009 to 2012 was performed to determine an association between Ph+ B-ALL and CD25 expression. A threshold of 25% was used to define positive cases for CD25 expression by flow cytometry.There were 221 patients with a diagnosis of B-ALL ranging from 2 to 22 years (median, 6 years). Eight (3.6%) B-ALL patients were positive for the Philadelphia chromosome translocation (Ph+ B-ALL) and 213 were negative (Ph-negative B-ALL). CD25 expression was observed in 6 of 8 (75%) Ph+ B-ALL patients and 6 of 213 (2.8%) Ph-negative B-ALL patients. CD25 expression was significantly higher in Ph+ B-ALL compared to Ph-negative B-ALL, with median CD25 expression of 64% (range 0-93%) and 0.1% (range 0-91%), respectively (P 0.0002). Therefore, CD25 expression as a predictor of Ph+ B-ALL had 75% sensitivity, 97% specificity, 50% positive predictive value and 99% negative predictive value.CD25 expression is a specific and relatively sensitive marker for the identification of Ph+ B-ALL in the pediatric population.


PubMed | Anderson Cancer Center Houston, Michael bakey Va Medical Center Houston, War Related Illness and Injury Study Center and Baylor College of Medicine
Type: Journal Article | Journal: Sexual medicine | Year: 2015

U.S. veterans of recent wars in Iraq and Afghanistan may be at greater risk for sexual dysfunction due to injuries, mental health conditions, medications used to treat those conditions, and psychosocial factors.To explore the perceptions of recent Veterans about sexual health and dysfunction, contributing factors, its impact and solutions.Qualitative study.Eight men who screened positive for sexual dysfunction at initial presentation to a postdeployment clinic at a Veterans Affairs medical center.Patients who screened positive for sexual dysfunction and indicated an interest in participating were contacted and scheduled for an in-person private interview with a researcher. Interviews were semistructured, utilizing open-ended and follow-up probe questions to elicit the individuals perspective about sexual dysfunction and its cause, impact and solutions. Interviews were recorded, transcribed and analyzed for themes.These heterosexual men discussed a range of sexual dysfunction in their activities including lack of desire, erectile dysfunction, delayed orgasm, premature ejaculation, and distraction. They also discussed the importance of setting or context and changes over time to their sexual health and function. The men shared their ideas about contributory factors, including normal aging, medication side effects, injury and a possible role for combat deployment more generally. Reported solutions for sexual dysfunction included medications, herbal remedies, and new positions and approaches to sexual activity. Participants reported discussing sexual dysfunction with their health-care providers and what was helpful. Finally, the men expressed in their own words the significant impact of sexual dysfunction on their self-perception, their partners, and their relationships.Sexual dysfunction in recent combat veterans can have important negative effects on their health and relationships. Our findings elucidate perceived contributory factors and preferred solutions, which can be applied by health-care providers to improve the management of sexual dysfunction in these patients.


Abdullah F.,Morzak Clinic | Abdullah F.,Anderson Cancer Center Houston | Rashid R.M.,Morzak Center | Rashid R.M.,Anderson Cancer Center Houston
Journal of Drugs in Dermatology | Year: 2010

The use of herbal medications in dermatologic disease has become common practice among consumers. In this paper, the authors review and discuss the existing evidence-based botanical modalities in the peer-reviewed literature with a particular focus on various presentations of alopecia. To maximize potential clinical application, this review has been limited human studies. The goal of the study was to provide a thorough evaluation of the current understanding of the use of non-pharmaceutical botanical products in the management of hair loss. Copyright © 2010 Journal of Drugs in Dermatology.


Peters K.M.,University of Sydney | Brooks B.E.,Anderson Cancer Center Houston | Schumacher M.A.,Anderson Cancer Center Houston | Schumacher M.A.,Duke University | And 5 more authors.
PLoS ONE | Year: 2011

Structures of the multidrug-binding repressor protein QacR with monovalent and bivalent cationic drugs revealed that the carboxylate side-chains of E90 and E120 were proximal to the positively charged nitrogens of the ligands ethidium, malachite green and rhodamine 6G, and therefore may contribute to drug neutralization and binding affinity. Here, we report structural, biochemical and in vivo effects of substituting these glutamate residues. Unexpectedly, substitutions had little impact on ligand affinity or in vivo induction capabilities. Structures of QacR(E90Q) and QacR(E120Q) with ethidium or malachite green took similar global conformations that differed significantly from all previously described QacR-drug complexes but still prohibited binding to cognate DNA. Strikingly, the QacR(E90Q)-rhodamine 6G complex revealed two mutually exclusive rhodamine 6G binding sites. Despite multiple structural changes, all drug binding was essentially isoenergetic. Thus, these data strongly suggest that rather than contributing significantly to ligand binding affinity, the role of acidic residues lining the QacR multidrug-binding pocket is primarily to attract and guide cationic drugs to the "best available" positions within the pocket that elicit QacR induction. © 2011 Peters et al.


PubMed | Georgetown University, Anderson Cancer Center Houston and Baylor College of Medicine
Type: Journal Article | Journal: International journal of molecular epidemiology and genetics | Year: 2014

Males have excess advanced liver disease and cirrhosis risk including from chronic hepatitis C virus (HCV) infection though the reasons are unclear.To examine the role variants in genes involved in androgen and estrogen biosynthesis and metabolism play in HCV-related liver disease risk in males.We performed a cross-sectional study evaluating single nucleotide polymorphisms (SNPs) in 16 candidate genes involved in androgen and estrogen ligand and receptor synthesis and risk of advanced hepatic fibrosis (F3/F4-F4) and inflammation (A2/A3-A3). We calculated adjusted odds ratios (ORs) using logistic regression and used multifactor dimensionality reduction (MDR) analysis to assess for gene-environment interaction.Among 466 chronically HCV-infected males, 59% (n = 274) had advanced fibrosis and 54% (n = 252) had advanced inflammation. Nine of 472 SNPs were significantly associated with fibrosis risk; 4 in AKR1C3 (e.g., AKR1C3 rs2186174: ORadj = 2.04, 95% CI 1.38-3.02), 1 each in AKR1C2 and ESR1, and 1 in HSD17B6. Four SNPs were associated with inflammation risk, 2 in SRD5A1 (e.g., SRD5A1 rs248800: ORadj = 1.86, 95% CI 1.20-2.88) and 1 each in AKR1C2 and AKR1C3. MDR analysis identified a single AKR1C3 locus (rs2186174) as the best model for advanced fibrosis; while a 4-locus model with diabetes, AKR1C2 rs12414884, SRD5A1 rs6555406, and SRD5A1 rs248800 was best for inflammation.The consistency of our findings suggests AKR1C isoenzymes 2 and 3, and potentially SRD5A1, may play a role in progression of HCV-related liver disease in males. Future studies are needed to validate these findings and to assess if similar associations exist in females.

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