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Cancer is considered one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds from plant origin with anti-tumor attributes have been described. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory, and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work, the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin contents (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the Alegría riojana variety, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with crude pepper fruit extracts were determined including protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), among others. In addition, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced their catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H2O2 and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines. [ABSTRACT FROM AUTHOR]

The prognostic role of small intrathoracic nodal metastases in primary patients with lung cancer has been controversial, and it is unclear how their presence should be used for pathologic staging and treatment planning. The intrathoracic lymph nodes from 266 clinical stage I non-small cell carcinoma patients treated at Cedars Sinai Medical Center from 1992 to 2006 were evaluated with immunohistochemistry for keratin AE1/AE3 for the presence of isolated tumor cells and micrometastases, as defined by American Joint Commission on Cancer criteria, correlated with survival using the Kaplan-Meier method and analyzed with power analysis. The English literature from 1995 to 2008 was reviewed to identify best available evidence regarding the prognostic value of isolated tumor cells and micrometastases detected with various immunohistochemistry and molecular methods in non-small cell carcinoma patients. Results were combined with our own data and evaluated with meta-analysis using Comprehensive Meta-analysis 2.0 software (Biostat Inc, Englewood, NJ). Isolated tumor cells and micrometastases were detected in 8 and 67 of 4148 lymph nodes, respectively, and their presence was not significantly associated with survival. Power analysis showed that 3060 cases followed up for 60 months would be needed to achieve 80% power in a study designed to detect survival differences between patients with negative nodes and micrometastases. Meta-analysis of 835 non-small cell carcinoma patients reported in 13 studies showed scanty data to evaluate patients with isolated tumor cells, no significant association between micrometastases and survival and significant data heterogeneity. Current best evidence suggests that non-small cell carcinoma patients should probably not be "upstaged" in the presence of isolated tumor cells and micrometastases. There is no data demonstrating survival benefits for patients treated with adjuvant chemotherapy and/or radiation therapy because of the presence of small nodal metastases., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To study whether isolated tumor cells and micrometastases, as defined by the current American Joint Committee on Cancer criteria for extrapulmonary neoplasms, have prognostic value for patients with resected non-small cell carcinoma of the lung., Methods: Intrathoracic lymph nodes (n = 1063) from 60 patients with non-small cell carcinoma of the lung were studied for the presence of metastases with serial histologic sections and keratin immunostains. Metastases were classified as isolated tumor cells, pN1mi, pN1, pN2mi, and pN2. Isolated tumor cells were smaller than 0.2 mm, while pN1mi and pN2mi measured 0.2 mm to 2 mm. Survival analysis was performed, stratifying by nodal status and stage., Results: Isolated tumor cells were detected in 11 lymph nodes from 5 of 33 pN0 patients and in 9 pN1 and pN2 patients. The lymph nodes from 3 patients were reclassified as pN1mi. No pN2mi were detected. A survival model based on a stratification of the cohort into stages I to III was significant (chi-square = 7.426, df = 2, P =.024) but demonstrated considerable overlap between the survival curves of stage I and II patients. A model stratifying isolated tumor cells and pN1mi into stage I disease was significant (chi-square = 7.985, df = 2, P =.018) and showed no overlap between the survival curves of stage I and II patients. There were no significant survival function differences between patients with pN0, isolated tumor cells, and pN1mi., Conclusions: Patients with non-small cell carcinoma of the lung with isolated tumor cells and pN1mi have similar survivals to those with pN0, consistent with the findings reported for breast cancer patients. Future larger studies of patients with non-small cell carcinoma of the lung are needed to confirm whether current American Joint Committee on Cancer staging criteria should be modified to include the pN1mi category.

In the course of our continuing search for new antitumor-antibiotics from marine-derived actinomycete bacteria, four new cytotoxic compounds, designated as daryamides A (1), B (2), and C (3) and (2E,4E)-7-methylocta-2,4-dienoic acid amide (4), were isolated from the culture broth of a marine-derived Streptomyces strain CNQ-085. The structures of these new compounds were assigned by detailed interpretation of spectroscopic data. The relative configuration of 1 was determined by comprehensive NMR analysis, while the absolute configuration of 1 was determined as 4S,5R using the modified Mosher method. The daryamides show weak to moderate cytotoxic activity against the human colon carcinoma cell line HCT-116 and very weak antifungal activities against Candida albicans.

The chemical study of two sponges of the genus Dysidea collected in the Gulf of California has led to the isolation of the new merosesquiterpenes 20-O-acetyl-21-hydroxy-ent-isozonarol (2), 20-O-acetylneoavarol (3), ent-yahazunol (4), and dysienone (5), together with the known compounds 1 and 6-9. The structures of the new metabolites have been established by spectroscopic techniques. The absolute configuration of compounds 5 and 6 has been investigated by application of a procedure developed by Riguera et al. Compounds 2 and 5 showed cytotoxic activity against three human tumor cell lines.

The Gulf of California shell-less mollusc Dolabella auricularia has been found to contain a new 14-membered macrocyclic lactone linked to a 2,4-di-O-methyl-l-alpha-rhamnopyranoside, designated dolastatin 19 (1). The new cancer cell growth inhibitor (1, 8.33 x 10(-8)% yield) was obtained by bioassay (P388 lymphocytic leukemia and human cancer cell lines) directed isolation, accompanied by debromoaplysiatoxin (9.17 x 10(-7)% yield) and anhydrodebromoaplysiatoxin (2.0 x 10(-7)% yield). The structures were determined on the basis of analyses of high-resolution mass spectra and high-field NMR data. All the relative stereochemistry for the chiral centers was designated by utilizing NMR techniques.

Further studies on the seeds of Annona cherimolia have led to the isolation of two pairs of Annonaceous acetogenins, a mixture of epimers of annomolon A (1) and 34-epi-annomolon A (1'), and a mixture of epimers of annomolon B (2) and 34-epi-annomolon B (2'), containing a rare gamma-hydroxymethyl-gamma-lactone moiety and a carbonyl group. Their structures were elucidated on the basis of spectroscopic and chemical methods, and their absolute stereochemistry was solved by preparing their respective per-Mosher ester derivatives. These acetogenins showed substantial cytotoxicity, comparable to that of adriamycin, against a human pancreatic tumor cell line (MIA PaCa-2).

Objectives. Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas. Methods. Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles. FAP expression was evaluated via immunohistochemistry (IHC) in tumor samples (n = 63), adjacent normal tissues (n = 30), and positive controls (n = 2) using semiquantitative systems for intensity (0 = negative; 1 = weak; 2 = moderate; and 3 = strong) and density (none, <25%, 25–75%; >75%) in stromal and tumor/nonstromal cells and using a qualitative overall score (not detected, low, medium, and high). Additionally, RNA sequencing data in publicly available databases were utilized to compare FAP expression in samples (n = 10,626) from various cancer types and evaluate the association between FAP expression and overall survival (OS) in sarcoma (n = 168). Results. The majority of tumor samples had FAP IHC intensity scores ≥2 and density scores ≥25% for stromal cells (77.7%) and tumor cells (50.7%). All desmoid fibromatosis, myxofibrosarcoma, solitary fibrous tumor, and undifferentiated pleomorphic sarcoma samples had medium or high FAP overall scores. Sarcomas were among cancer types with the highest mean FAP expression by RNA sequencing. There was no significant difference in OS in patients with sarcoma with low versus high FAP expression. Conclusion. The majority of the sarcoma samples showed FAP expression by both stromal and tumor/nonstromal cells. Further investigation of FAP as a potential diagnostic and therapeutic target in sarcomas is warranted. [ABSTRACT FROM AUTHOR]

For a searchable version of these abstracts, please visit www.acrabstracts.org. [ABSTRACT FROM AUTHOR]

Background: Little is known about the genetic characteristics associated with exercise in women undergoing breast cancer surgery. Purpose: In a sample of women who were evaluated prior to breast cancer surgery (n = 310), we evaluated for differences in demographic and clinical characteristics between patients who did and did not exercise on a regular basis and evaluated for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators. Methods: Patients completed an investigator-developed exercise questionnaire. Based on the recommended level of exercise (≥150 minutes/week), survivors were classified into no exercise (NoEx), less exercise (LessEx), or recommended exercise (RecEx) groups. Candidate gene analyses were done to identify relationships between polymorphisms and exercise group membership (i.e., NoEx vs. RecEx). Only 23.5% of the total sample met the recommendations for regular exercise. Results: Compared to the RecEx group (n = 78), patients in the NoEx group (n = 120) had less education; were less likely to report being White or Asia/Pacific Islander; more likely to report a lower household income; had a higher body mass index (BMI), had a poorer functional status; had a higher comorbidity burden; were more likely to self-report high blood pressure; and were more likely to have received neoadjuvant chemotherapy. Polymorphisms in IFNGR1 and NFKB1 were associated with membership in the NoEx group. Conclusions: While they warrant replication, our findings suggest that variations in cytokine-related genes may play a role in exercise behavior, and that clinicians need to assess for barriers to regular exercise and educate patients on its benefits. [ABSTRACT FROM AUTHOR]

After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis—blue mussel and Mytilus californianus—California mussel are the most well‐known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle‐inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle‐inspired biomaterials in various medical applications are summarized for future developments in the field. [ABSTRACT FROM AUTHOR]

Leptospirosis is an emerging infectious disease. Recently, canine and human leptospirosis outbreaks were reported in California and New York, respectively. In this study we evaluated the role that cell death processes play in the inflammatory response to Leptospira. Groups of male C3H/HeJ mice were infected with pathogenic L. interrogans and non-pathogenic L. biflexa for 24 and 72 hours; inflammatory processes were characterized for apoptosis and necroptosis by flowcytometry of spleen cells and were further assessed for expression of biomarkers of necroptosis by western blot. We found that pathogenic L. interrogans promotes apoptosis in myeloid neutrophils and monocytes at 24h and 72h post-infection, whereas L. biflexa promotes apoptosis of myeloid monocytes only at 24h post-infection. It is interesting that the immune cells undergoing the common programmed cell death pathway (apoptosis) are the cell types which were not increased in frequency in spleen of mice infected with L. interrogans (neutrophils) and L. biflexa (monocytes) in our previous study. The same trend was observed with pathogenic L. interrogans inducing necroptosis of myeloid neutrophils in addition to monocytes and macrophages at 24h and/or 72h post-infection, whereas L. biflexa promoted this pro-inflammatory cell death process in monocytes and macrophages only at 24h post-infection. Thus, early apoptosis and necroptosis of these cell types may explain its absence in frequency in spleen. Furthermore, at 24h and 72h, expression of the necroptosis molecular biomarkers p-MLKL, p-RIP1 and p-RIP3 was increased post infection with pathogenic L. interrogans. These data suggest that the underlying cell death processes involved in immune responses to pathogenic Leptospira contribute directly to persistent inflammation during the early stages of leptospirosis. [ABSTRACT FROM AUTHOR]

Presents abstracts of studies on the mechanisms of tumor rejection and modulation of anti-tumor responses presented at the Experimental Biology/ International Unit of Physiological Sciences 2005 Congress in San Diego, California. "Lymphocyte Receptors and Effector Molecules that Control Tumor Immunity," by Mark John Smyth; "Transduction of the Gene Coding for a Human G-Protein Coupled Receptor FPRL1 in Mouse Tumor Cells Increases Host Anti-Tumor Immunity," by Jinyue Hu and others; "Tumor Vaccine Based on Cell Surface Expression of DcR3/TR6," by Quixiu Shi and others.

Marine microbes produce extracellular reactive oxygen species (ROS) such as superoxide and hydrogen peroxide (H2O2) as a result of regulated and nonregulated physiological and metabolic reactions. ROS production can be a sink and cryptic recycling flux of dissolved oxygen that may rival other key fluxes in the global oxygen cycle; however, the low abundance and high turnover rate of ROS makes this figure difficult to constrain. One key step in determining the disparity between the gross production of ROS and the net sink of dissolved oxygen lies in understanding the degradation pathways of H2O2 in the marine water column. In this study, we use isotope‐labeling techniques to determine the redox fate of H2O2 in a range of marine environments off the West Coast of California. We find that H2O2 reduction is greater than or equal to H2O2 oxidation at most sampled depths, with notable exceptions in some surface and intermediate water depths. The observation that H2O2 oxidation can exceed reduction in the dark ocean indicates the presence of an oxidizing decay pathway that is not among the known suite of microbially mediated enzymatic pathways (i.e., catalase and peroxidase), pointing to an abiotic and/or a nonenzymatic decay pathway at intermediate water depths. These results highlight the complexity and heterogeneity of ROS decay pathways in natural waters and their unconstrained regulation of oxygen levels within the ocean. [ABSTRACT FROM AUTHOR]

The article focuses on the various problems with big information technology (IT), discussed in the 19th International Molecular Medicine Tri-Conference held at the Moscone Center in San Francisco, California, from February 19–23, 2012. It also discusses the problems regarding circulating tumor cells (CTCs). Topics include high-content screening and dedicated processors for genome assembly along with high-content analysis.

The article offers information on the research on how normal brain functions contribute to pediatric brain tumors may help physicians fight a lethal childhood cancer. Topics discussed include the most common form of high-grade glioma in childhood, is the leading cause of pediatric brain tumor deaths; focuses on effect of electrical activity of brain on the tumor cells to develop a new class of drug ; and views on cellular mechanisms of neurodevelopment and neuroplasticity.

Discusses the role of surrounding tissue in cancer progression. Evidence that the "microenvironment" of a cancer cell determines its tumorigenic or malignant potential; Example of the type of cancers mutated BRCA1 genes can cause; Reference to research by Mina Bissell and colleagues of the Lawrence Berkeley National Laboratory in California, where three-dimensional models simulating real tissue structures within the body were developed; Work on tumor development at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts; Discussion of how normal cells react to the presence of cancer cells that results in a state of cell proliferation and extracellular matrix degradation; Comments from Lisa Coussens of the University of California, San Francisco; Study at the Vanderbilt University School of Medicine into stromal signals that contribute to cancer progression; Comment of Lawrence Berkeley's Mary Helen Barcellos-Hoff on the role of transforming growth factor β (TGF-β) cytokine; Comment of Valerie Weaver, University of Pennsylvania in Philadelphia, on microarray analysis.

Pomegranate is an old plant made up by flowers, roots, fruits and leaves, native to Central Asia and principally cultivated in the Mediterranean and California (although now widespread almost all over the globe). The current use of this precious plant regards not only the exteriority of the fruit (employed also for ornamental purpose) but especially the nutritional and, still potential, health benefits that come out from the various parts composing this one (carpellary membranes, arils, seeds and bark). Indeed, the phytochemical composition of the fruit abounds in compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) presenting a significant biological and nutraceutical value. For these reasons, pomegranate interest is increased over the years as the object of study for many research groups, particularly in the pharmaceutical sector. Specifically, in-depth studies of its biological and functional properties and the research of new formulations could be applied to a wide spectrum of diseases including neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review, considering the increasing scientific and commercial interest of nutraceuticals, we reported an update of the investigations concerning the health-promoting properties of pomegranate and its bioactive compounds against principal human pathologies. [ABSTRACT FROM AUTHOR]

The article discusses a study on a procedure could provide an option for the treatment of locally advanced pancreatic cancer. Presented at the Society of Interventional Radiology's 37th Annual Scientific Meeting in San Francisco, California, the study suggested the procedure that is based on using electrical micropulses to rupture tumor cells. The researchers termed the procedure as irreversible electroporation (IRE).

The article discusses the development of biotechnology nanoworms used to image tumor cells. The nanoworms consist of about 10 dextran-coated nanospheres of iron oxide which are superparamagnetic. The elongated nanostructures accumulated in the tumor cells and remained longer than nanospheres. The research was directed by Michael Sailor’s group at the University of California San Diego in collaboration with the Massachusetts Institute of Technology and the University of California at Santa Barbara. The research is published in the vol. 20, 2008 issue of “Advanced Materials.”

The article profiles Benjamin Bonavida, an Immunology professor at the University of California at Los Angeles (UCLA) David Geffen School of Medicine in California. His earlier research at UCLA were mostly about the mechanism of cell-mediated cytotoxicity. But during the last 10 years, his research focused on the immunobiology of cancer, specifically on the molecular mechanisms underlying resistance of tumor cells to cytotoxic stimuli.

Tumor growth and metastasis in nasopharyngeal carcinoma (NPC) patients recent research stated that intracellular Hsp70 is a stress protein as the main factor for the growth, invasion and metastasis of NPC. To analyze intracellular Hsp70 protein expression of NPC patients which correlate with staging of NPC as clinical manifestation. Formalin-fixed paraffin-embedded biopsy specimens from 20 NPCs histopathology and clinically. The expression of intracellular Hsp70 was obtained using monoclonal antibody of Anti Human Hsp70 from Santa Cruz Biotechnology, California, USA. The assessment of the staining was performed with Remmele methode by Histopathologies doctor Consultant. 20 NPC patients met the inclusion and exclusion criteria. The data showed a negative intracellular of Hsp70 expression by 15% for all sample that consist of 1 patient of stage I, II, III, and none for stage IV. Then, followed by 25% of mild positive intracellular Hsp70 expression which consisted of 0 patient of stage I and III, 2 patients of stage II, and 3 patients of stage IV. Followed by 50% of moderate positive intracellular Hsp70 expression which consisted of 0 patient of stage I and II, 1 patient of stage III, and 9 patients of stage IV. Spearman test results test scored p = 0.001 with a correlation coefficient of 0.671. The correlation of intracellular Hsp70 protein expression with stage (I, II, III, and IV) in NPC patients was significant (p < 0.05). There was a correlation between increased intracellular Hsp70 expression and the stage of patients with nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

From ASCO, we report on metastatic castrate-resistant prostate cancer and locally advanced/metastatic renal cell carcinoma. From IHS, we report on complementary and alternative medicine use by patients and practitioners, the effects of biological hemp-derived cannabidiol on PTSD in military veterans, and more. [ABSTRACT FROM AUTHOR]

The article offers information on the abstracts of the several research studies. Discussed are the topics of the research studies which include "Glycine/Sarcosine Ratio As Novel Biomarker For Alcohol-Induced Liver Fibrosis Under Sumoylation Control"; "Increased Chemokines, Chemokine Receptors, And Neurodegeneration In Postmortem Human Alcoholic Brain" and "The Role Of Microglia-Expressed Trem2 In Ethanol-Induced Neuroimmune Activation"

We present sessions on hepatocellular carcinoma and colorectal and pancreatic cancers from ASCO GI. Key sessions from SABCS covered dose intensification, new trial data, and ovarian suppression to preserve fertility. [ABSTRACT FROM AUTHOR]

The article offers information on the chemical structure of saxitoxin. Researchers of the University of California report that the chemical structure of a potent nerve poison is associated with red tides and tainted shellfish. Chemistry professor Henry Rapoport and two former associates John L. Wong and Rudolph Oesterlin, worked on this laboratory analytical studies of complete formula for the deadly saxitoxin molecule for over a period of 10-years. Description and precautions of saxitoxin is also offered.

The article offers information on bridge between the fields of bioethics and environmental ethics along with the control of cancer. Topics discussed include Cancer Registry of Greater California gathers individual-level data and uses these data for cancer surveillance; improvements in care and survivorship, and advocacy; and population based collections of samples becomes essential to understand biologic development and progression of cancer tumors.

Presents abstracts of studies on molecular targets in diet and cancer, presented at the Experimental Biology/International Union of Physiological Sciences 2005 congress held in San Diego, California. "Inhibitory Effect of Prolonged-Butyrate Treatment on Migration and Invasion of HT1080 Tumor Cells," by Huawei Zeng and Mary Briske-Anderson; "Omega-3 Fatty Acids Attenuate Breast Cancer Growth Through Activation of a Sphingomyelinase-Madiated Pathway," by Rafat Siddiqui, Min Wu et al.; "The Green Tea Compound EGCG Regulates Wnt Signaling Through the HBP1 Transcriptional Repressor," by Jiyoung Kim, Amy S. Yee et al.

Presents abstracts of studies on soy and cancer, presented at the Experimental Biology/International Union of Physiological Sciences 2005 congress held in San Diego, California. "Soybean Saponins Inhibit Tumor Cell Invasion by Regulating Expressions of MMPs and Secretion of TIMP-2 in Human Fibrosarcoma HT1080 Cells," by Ji-Hye Kang, Mi-Kyung Sung et al.; "Regulation of Expression of Heat Shock Proteins in Mammary Tumor Cells Exposed to Isoflavones," by Jong-Sang Kim, Jang Hoon Kim et al.; "Identification and Characterization of Soy Peptides With Topoisomerase Inhibitory Activity," by Elvira Gonzales De Mejia, Wenyi Wang et al.

Presents abstracts of studies on glycobiology and glycans in disease, presented at the Experimental Biology/International Union of Physiological Sciences 2005 convention held in San Diego, California. "Effects of Lectins on Viability of Human Colon Cell Lines: A Multiparameter Approach," by Eileen L. Heinrich, Lily Welty et al.; "Fructose Enhances Migration and Invasion of Human Breast Tumor Cells," by R. Jean Hine, J. S. Stanley et al.; "Betaine, a Novel Antithrombotic Agent in the Effective Management of Peripheral Arterial Occlusive Disease," by Omer Iqbal, Jallal Messadek et al.

Multiple long-term studies have demonstrated a propensity for breast cancer recurrences to develop near the site of the original breast cancer. Recognition of this local recurrence pattern laid the foundation for the development of accelerated partial breast irradiation (APBI) approaches designed to limit the radiation treatment field to the site of the malignancy. However, there is a paucity of data regarding the efficacy of APBI in general, and intraoperative radiotherapy (IORT), in particular, for the management of ductal carcinoma in situ (DCIS). As a result, use of APBI, remains controversial. A prospective nonrandomized trial was designed to determine if patients with pure DCIS considered eligible for concurrent IORT based on preoperative mammography and contrast-enhanced magnetic resonance imaging (CE-MRI) could be successfully treated using IORT with minimal need for additional therapy due to inadequate surgical margins or excessive tumor size. Between November 2007 and June 2014, 35 women underwent bilateral digital mammography and bilateral breast CE-MRI prior to selection for IORT. Patients were deemed eligible for IORT if their lesion was ≤4 cm in maximal diameter on both digital mammography and CE-MRI, pure DCIS on minimally invasive breast biopsy or wide local excision, and considered resectable with clear surgical margins using breast-conserving surgery (BCS). Postoperatively, the DCIS lesion size determined by imaging was compared with lesion size and surgical margin status obtained from the surgical pathology specimen. Thirty-five patients completed IORT. Median patient age was 57 years (range 42-79 years) and median histologic lesion size was 15.6 mm (2-40 mm). No invasive cancer was identified. In more than half of the patients in our study (57.1%), MRI failed to detect a corresponding lesion. Nonetheless, 30 patients met criteria for negative margins (i.e., margins =2 mm) whereas five patients had positive margins (<2 mm). Two of the five patients with positive margins underwent mastectomy due to extensive imaging-occult DCIS. Three of the five patients with positive margins underwent successful re-excision at a subsequent operation prior to subsequent whole breast irradiation. A total of 14.3% (5/35) of patients required some form of additional therapy. At 36 months median follow-up (range of 2-83 months, average 42 months), only two patients experienced local recurrences of cancer (DCIS only), yielding a 5.7% local recurrence rate. No deaths or distant recurrences were observed. Imaging-occult DCIS is a challenge for IORT, as it is for all forms of breast-conserving therapy. Nonetheless, 91.4% of patients with DCIS were successfully managed with BCS and IORT alone, with relatively few patients requiring additional therapy. [ABSTRACT FROM AUTHOR]

The article offers information on the 2015 PanAmerican Society for Pigment Cell Research (PASPCR) that will be held in Orange, California from September 27 to 30.

Background Lung cancer is the leading cause of morbidity and death worldwide. Although the available lung cancer animal models have been informative and further propel our understanding of human lung cancer, they still do not fully recapitulate the complexities of human lung cancer. The pathogenesis of lung cancer remains highly elusive because of its aggressive biologic nature and considerable heterogeneity, compared to other cancers. The association of Cul4 A amplification with aggressive tumor growth and poor prognosis has been suggested. Our previous study suggested that Cul4 A is oncogenic in vitro, but its oncogenic role in vivo has not been studied. Methods Viral delivery approaches have been used extensively to model cancer in mouse models. In our experiments, we used Cre-recombinase induced overexpression of the Cul4A gene in transgenic mice to study the role of Cul4A on lung tumor initiation and progression and have developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. Results Here we show that the use of a recombinant adenovirus expressing Cre-recombinase (' Adeno Cre') to induce Cul4A overexpression in the lungs of mice allows controls of the timing and multiplicity of tumor initiation. Following our mouse models, we are able to study the potential role of Cul4A in the development and progression in pulmonary adenocarcinoma as well. Conclusion Our findings indicate that Cul4A is oncogenic in vivo, and this mouse model is a tool in understanding the mechanisms of Cul4A in human cancers and for testing experimental therapies targeting Cul4A. [ABSTRACT FROM AUTHOR]

Objectives To estimate the impact of p21-activated kinase 1 expression on recurrence and survival of patients with non-metastatic clear cell renal cell carcinoma after surgical resection. Methods We retrospectively enrolled 254 patients (187 in the training cohort and 67 in the validation cohort) with non-metastatic clear cell renal cell carcinoma undergoing nephrectomy at a single institution. Clinicopathological features, overall survival and recurrence-free survival were recorded. p21-activated kinase 1 intensities were assessed by immunohistochemistry of patients' specimens. The Kaplan-Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on overall survival and recurrence-free survival. The concordance index was calculated to assess predictive accuracy. Results In both cohorts, elevated p21-activated kinase 1 expression in tumor tissues positively correlated with advanced T stage and Fuhrman grade. High p21-activated kinase 1 expression indicated poor survival and early recurrence of patients with non-metastatic clear cell renal cell carcinoma, especially with early T1-2 stage disease. After backward elimination, p21-activated kinase 1 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of the traditional University of California Integrated Staging System and Mayo Clinic stage, size, grade and necrosis prognostic models was improved when p21-activated kinase 1 expression was added. Conclusions Elevated expression of p21-activated kinase 1 seems to be an independent adverse prognostic biomarker for recurrence and survival in patients with non-metastatic clear cell renal cell carcinoma after nephrectomy. [ABSTRACT FROM AUTHOR]

Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. Purpose This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine). Methods Eighteen patients with advanced solid tumors received aldoxorubicin 230 or 350 mg/m (equivalent in drug load to doxorubicin at doses of 170 or 260 mg/m, respectively) once every 21 days. Blood samples were taken in cycle 1 before aldoxorubicin infusion, and at 5, 15, 30, and 60 min, and at 2, 4, 8, 12, 16, 24, 48, and 72 h after infusion. Urine samples were taken in cycle 1 at 24, 48, and 72 h after infusion. Limited blood sampling was done in cycle 3, before aldoxorubicin infusion, and at 60 min and at 2, 4, and 8 h after infusion. Results The long mean half-life (20.1-21.1 h), narrow mean volume of distribution (3.96-4.08 L/m), and slow mean clearance rate (0.136-0.152 L/h/m) suggest that aldoxorubicin is stable in circulation and does not accumulate readily in body compartments outside of the bloodstream. Very little doxorubicin and its major metabolite doxorubicinol, which has been implicated in doxorubicin-associated cardiotoxicity, are excreted in urine. This might explain the lack of cardiotoxicity observed thus far with aldoxorubicin. Conclusions Our findings support dosing and administration schemas used in an ongoing phase 3 clinical study of aldoxorubicin in soft tissue sarcoma, and phase 2 clinical studies in small cell lung cancer, glioblastoma, and Kaposi's sarcoma. [ABSTRACT FROM AUTHOR]

Both solid and hematologic malignancies may be complicated by coagulopathies. Disseminated intravascular coagulation (DIC) in the presence of pancreatic cancer is generally unrecognized and may have fatal consequences. The diagnosis of DIC in a patient with advanced cancer is a poor prognostic indicator. Presented here is a case study consisting of two patients presenting with a new diagnosis of pancreatic cancer complicated by DIC. Aggressive supportive treatment in addition to systemic chemotherapy consisting of gemcitabine and nab-paclitaxel was initiated and DIC was controlled. An early diagnosis of DIC and the administration of systemic chemotherapy with a high response rate and an ability to reduce tumor bulk rapidly may offer some patients the probability of recovery. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background A substantial proportion of solid tumors carry the BRAF V600E mutation, which causes activation of the MEK/MAPK pathway and is a poor prognostic indicator. Patients with locally advanced human cancers are often treated with external beam radiation therapy. Given the association of Raf overactivation with radioresistance, we hypothesized that, in BRAF V600E-mutated carcinomas, there would be combinatorial activity between radiation and PLX4720, a specific BRAF V600E-inhibitor. Methods Two BRAF V600E-mutated cancer cell lines and one BRAF-V600E wildtype (WT) cancer cell line were obtained. We performed cell viability assays and clonogenic assays using combinations of radiation and PLX4720. We assessed MEK and MAPK phosphorylation at different PLX4720 concentrations with western blotting, and cell cycle progression was evaluated by flow cytometry. Results Our results show combinatorial, additive activity between radiation and PLX4720 in BRAF V600E-mutated cell lines, but not in the BRAF WT line. In BRAF V600E-mutated cells, there was a PLX4720 concentration-dependent decrease in MEK and MAPK phosphorylation. In cells with BRAF V600E mutations, PLX4720 caused cell cycle arrest at G1, and, when combined with radiation, caused a combined G1 and G2 cell cycle arrest; this pattern of cell cycle effects was not seen in the BRAF WT cell line. Conclusions These data suggest additive, combinatorial activity between radiation and PLX4720 in cancers carrying BRAF V600E mutations. Our data has potential for translation into the multimodality treatment of BRAF V600E-mutated cancers. [ABSTRACT FROM AUTHOR]

Purpose: To determine the feasibility of dose-rounding rituximab by looking at the potential deviation from the prescribed dose to the dose rounded to the nearest vial size. Methods: This study is a retrospective chart review of all rituximab orders prescribed for hematologic or oncologic indications over a period of 24 months. The feasibility of dose-rounding rituximab to the nearest vial size was evaluated by looking at the potential deviation of the prescribed dose to the rounded dose. Physician opinion towards dose rounding rituximab was assessed through a survey. Results: From October 2008 through September 2010, 2028 orders of rituximab were prescribed and processed. Ninety-nine percent of all rituximab doses fell within 10% dose deviation if rounded to the nearest 100-mg vial size and 66.1% of all rituximab orders fell within 5% dose deviation. All responding physicians were comfortable with at least a 5% dose deviation, projecting a yearly savings of approximately US$37,000 through rounding down and capturing additional cost of approximately US$43,000 through rounding up. Conclusion: The projected savings of dose-rounding rituximab to the nearest vial size resulted in both substantial financial savings and reduced unnecessary wastage of unused drug. [ABSTRACT FROM AUTHOR]