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Sample records for age tumor stage

  1. Patients with Old Age or Proximal Tumors Benefit from Metabolic Syndrome in Early Stage Gastric Cancer

    PubMed Central

    Zhang, Ying; Liu, Jian-xin; Yu, Hong-mei; Liang, Wei-ping; Jin, Ying; Ren, Chao; He, Ming-ming; Chen, Wei-wei; Luo, Hui-yan; Wang, Zhi-qiang; Zhang, Dong-sheng; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2014-01-01

    Background Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. Methods Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. Results Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P = 0.036). Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P = 0.009 in multivariate analysis) or patients with proximal gastric cancer (P = 0.047 in multivariate analysis). No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P = 0.052 in univariate analysis). Conclusions Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors. PMID:24599168

  2. Ages and Stages: Teen

    MedlinePlus

    ... Pediatrician Ages & Stages Prenatal Baby Toddler Preschool Gradeschool Teen Dating & Sex Fitness Nutrition Driving Safety School Substance Abuse Young Adult Healthy Children > Ages & Stages > Teen Teen Article Body Adolescence can be a rough ...

  3. Stages of Pituitary Tumors

    MedlinePlus

    ... tumors that may spread to bones of the skull or the sinus cavity below the pituitary gland. ... sella (the bone at the base of the skull , where the pituitary gland sits). Recurrent Pituitary Tumors ...

  4. Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and 
ER-Status: Stimulation of Estrogen Signaling Coupled With Breast 
Conserving Surgery

    PubMed Central

    Suba, Zsuzsanna

    2016-01-01

    Abstract: Background Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures. Objective Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking. Method Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients’ age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality. Results Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ER-positive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumor-growth. Conclusion Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer. PMID:27087654

  5. MR imaging in staging of bone tumors

    PubMed Central

    Ehara, Shigeru

    2006-01-01

    For staging of bone tumors, TNM and Enneking’s systems are used with some differences. Magnetic resonance imaging is particularly useful for defining the extent of high-grade tumors, including transcortical and intertrabecular infiltration and periosteal extension. The concepts of compartment and curative surgical margins are important for bone tumor staging. PMID:17098647

  6. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  7. Tumor progression stage: specific losses of heterozygosity.

    PubMed

    Cavenee, W K

    1989-01-01

    The development of human cancer is generally thought to entail a series of events that cause a progressively more malignant phenotype. This hypothesis predicts that tumor cells of the ultimate stage will carry each of the events, cells of the penultimate stage will carry each of the events less the last one and so on. That is to say, a dissection of the pathway form a normal cell to a fully malignant tumor may be viewed as the unraveling of a nested set of aberrations. In experiments designed to elucidate these events, we have compared genotypic combinations at genomic loci defined by restriction endonuclease recognition site variation in normal and tumor tissues from patients with various forms and stages of cancer. The first step, inherited predisposition, is best described for retinoblastoma in which a recessive mutation of a locus residing in the 13q14 region of the genome is unmasked by aberrant, but specific, mitotic chromosomal segregation. A similar mechanism involving the distal short arm of chromosome 17 is apparent in astrocytic tumors and the event is shared by cells in each malignancy stage. This is distinct from a loss of heterozygosity for loci on chromosome 10 which is restricted to the ultimate stage, glioblastoma multiforme. Further, this approach has has been extended to a wide variety of human cancers and shown to be generally applicable. The results suggest a genetic approach to defining degrees of tumor progression and a means for determining the genomic locations of genes involved in the pathway as a prelude to their molecular isolation and characterization. They have provided a molecular genetic-based oncology with clinical utility in differential pathology, in disease groupings for therapeutic purposes and in prenatal identification of latent disease carriers.

  8. Age, stage and senescence in plants

    PubMed Central

    Caswell, Hal; Salguero-Gómez, Roberto

    2013-01-01

    1. Senescence (an increase in the mortality rate or force of mortality, or a decrease in fertility, with increasing age) is a widespread phenomenon. Theories about the evolution of senescence have long focused on the age trajectories of the selection gradients on mortality and fertility. In purely age-classified models, these selection gradients are non-increasing with age, implying that traits expressed early in life have a greater impact on fitness than traits expressed later in life. This pattern leads inevitably to the evolution of senescence if there are trade-offs between early and late performance. 2. It has long been suspected that the stage- or size-dependent demography typical of plants might change these conclusions. In this paper, we develop a model that includes both stage- and age-dependence and derive the age-dependent, stage-dependent and age×stage-dependent selection gradients on mortality and fertility. 3. We applied this model to stage-classified population projection matrices for 36 species of plants, from a wide variety of growth forms (from mosses to trees) and habitats. 4. We found that the age-specific selection gradients within a life cycle stage can exhibit increases with age (we call these contra-senescent selection gradients). In later stages, often large size classes in plant demography, the duration of these contra-senescent gradients can exceed the life expectancy by several fold. 5. Synthesis. The interaction of age- and stage-dependence in plants leads to selection pressures on senescence fundamentally different from those found in previous, age-classified theories. This result may explain the observation that large plants seem less subject to senescence than most kinds of animals. The methods presented here can lead to improved analysis of both age-dependent and stage-dependent demographic properties of plant populations. PMID:23741075

  9. Treatment of Gastrointestinal Carcinoid Tumors by Stage

    MedlinePlus

    ... carcinoid tumors of the stomach. Patients with these conditions who have stomach carcinoid tumors are treated differently from patients without these conditions. Type 1: Patients with high gastrin levels but low levels of stomach acid are said to have type 1 tumors. ...

  10. How Are Lung Carcinoid Tumors Staged?

    MedlinePlus

    ... from the abdomen (diaphragm), the membranes surrounding the space between the lungs (mediastinal pleura), or membranes of ... tumor of any size has grown into the space between the lungs (mediastinum), the heart, the large ...

  11. How Are Gastrointestinal Stromal Tumors Staged?

    MedlinePlus

    ... The cancer has spread to nearby lymph nodes. M categories for GIST M0: The cancer has not ... lungs). Stage grouping Once the T, N, and M categories have been determined, this information is combined, ...

  12. Quest: A New Approach to Molecular Staging of Tumors

    DTIC Science & Technology

    2004-08-01

    200 Words) Towards the goal of molecular diagnosis and staging of NFl-related tumors, we proposed to develop and validate a novel PCR-based method...definitive system for the diagnosis and staging of NFl1-related tumors is a major obstacle to investigating the molecular basis of tumorigenesis, to...develop in individuals with NF1 (4-13). Gains or losses at a particular locus are (reviewed in(4)potential biomarkers for the molecular diagnosis and

  13. Accelerated aging in the tumor microenvironment

    PubMed Central

    Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony

    2011-01-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor micro-environment induces a form of “accelerated aging,” which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy (“self-eating”) in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy “fuel” and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a “mutagenic motor” and allows cancer cells to buffer—at a distance—exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of “accelerated host aging” in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively “cutting off the fuel supply” for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics. PMID:21654190

  14. Tumor LINE-1 Methylation Level in Association with Survival of Patients with Stage II Colon Cancer

    PubMed Central

    Swets, Marloes; Zaalberg, Anniek; Boot, Arnoud; van Wezel, Tom; Frouws, Martine A.; Bastiaannet, Esther; Gelderblom, Hans; van de Velde, Cornelis J. H.; Kuppen, Peter J. K.

    2016-01-01

    Genome-wide DNA hypomethylation is associated with a worse prognosis in early-stage colorectal cancer. To measure genome-wide DNA methylation levels, long interspersed nucleotide element (LINE-1) repeats are used as a surrogate marker. Cohort studies on the clinical impact of genome-wide DNA methylation level in patients with only early-stage colon cancer, are currently lacking. This study aimed to investigate the prognostic value of LINE-1 methylation in a stage II colon cancer cohort (n = 164). Manual needle microdissection of tumor areas was performed on formalin-fixed paraffin-embedded tumor tissue sections followed by DNA extraction. Bisulfite converted DNA was used to assess tumor LINE-1 methylation level by qPCR. Patients with LINE-1 hypomethylated tumors had a significantly worse overall survival compared to patients with a higher level of LINE-1 tumor DNA methylation (HR 1.68, 95% CI 1.03–2.75; p = 0.04). This effect was more prominent in patients aged over 65 years (HR 2.00, 95% CI 1.13–3.52; p = 0.02), although the test for age interaction was not significant. No significant effect on recurrence-free survival was observed. Based on these results, tumor LINE-1 hypomethylation is associated with a worse overall survival in stage II colon cancer. Whether the origin of this causation is cancer-specific or age-related can be debated. PMID:28035987

  15. Current and Future Lymphatic Imaging Modalities for Tumor Staging

    PubMed Central

    Gao, Kuo; Liu, Tiegang; Tariq, Imran; Sajjad, Ashif; Niu, Meiying; Liu, Guokai; Mehmood, Zahid; Tian, Guihua

    2014-01-01

    Tumor progression is supported by the lymphatic system which should be scanned efficiently for tumor staging as well as the enhanced therapeutic outcomes. Poor resolution and low sensitivity is a limitation of traditional lymphatic imaging modalities; thus new noninvasive approaches like nanocarriers, magnetic resonance imaging, positron-emission tomography, and quantum dots are advantageous. Some newer modalities, which are under development, and their potential uses will also be discussed in this review. PMID:24757671

  16. How to analyze tumor stage data in clinical research.

    PubMed

    Hu, Zhi-De; Zhou, Zhi-Rui; Qian, Shi

    2015-04-01

    Tumor staging serves as an important prognostic factor in cancer patient care. It also plays critical roles in cancer-related clinical research. Aimed to shed lights on how to analyze tumor staging related data and deliver proper interpretation, various statistical methods, from categorical data analysis to modeling techniques, were introduced through the examples. General guidelines were discussed for how to choose proper statistical test with key considerations of research aims, study design, measurement scale of data, proper data summary, type of associations, and underlying assumptions of statistical methods.

  17. Relation of Preoperative Thrombocytosis between Tumor Stage and Grade in Patients with Endometrial Cancer

    PubMed Central

    Kaloglu, Songul; Guraslan, Hakan; Tekirdag, Ali Ismet; Dagdeviren, Hediye; Kaya, Cihan

    2014-01-01

    Objective: We aimed to evaluate the predictive value of preoperative thrombocytosis for postoperative tumor stage and tumor grade in patients with endometrial cancer. Materials and Methods: This was a retrospective study carried out in our gynecologic oncology department between January 2000 and December 2011. We reviewed the medical charts of 190 patients diagnosed with endometrial carcinoma and underwent complete staging procedure. The clinicopathologic characteristics of the patients such as; age, gravidity, parity, menopausal status, body mass index, co-morbidities (diabetes, hypertension etc.), stage, grade, histological subtype, depth of myometrial invasion, peritoneal washing cytology and preoperative platelet count were recorded. Endometrioid adenocarcinomas were graded according to the FIGO classification. Blood samples for the measurement of platelet count were obtained 3 days prior to the surgery. Thrombocytosis was defined as a platelet count of 300×109/L. P values less than 0.05 derived from two-tailed tests were considered statistically significant. Results: The mean age of the study population was 55.4 (range 33–80) years. The mean gravidity was 3.8 (range 0–12) and the mean parity was 3.32 (range 0–11). 108 (56,8%) patients were with body mass index of >30 kg/m2. The mean platelet count among women was 288, 6±90.7×109/L (range 105–772×109/L). The majority of the patients were with early stage diseases during the surgeries. 170 (89.5%) of the patients had stage I to II disease, and 20 (10.5%) of them had stage III to IV disease. There were no statistical significance between thrombocytosis and age, gravidity, parity, BMI, cancer grade and stage, histological subtype of the tumor, depth of invasion, cervical involvement, intrauterine tumor volume and peritoneal washing cytology. Conclusion: We found that preoperative platelet count was not correlated with the stage or grade of endometrial cancer. PMID:25610319

  18. Intraoperative methods to stage and localize pancreatic and duodenal tumors.

    PubMed

    Norton, J A

    1999-01-01

    Intraoperative methods to stage and localize tumors have dramatically improved. Advances include less invasive methods to obtain comparable results and precise localization of previously occult tumors. The use of new technology including laparoscopy and ultrasound has provided some of these advances, while improved operative techniques have provided others. Laparoscopy with ultrasound has allowed for improved staging of patients with pancreatic cancer and exclusion of patients who are not resectable for cure. We performed laparoscopy with ultrasound on 50 consecutive patients with adenocarcinoma of the pancreas or liver who appeared to have resectable tumors based on preoperative computed tomography. 22 patients (44%) were found to be unresectable because of tumor nodules on the liver and/or peritoneal surfaces or unsuspected distant nodal or liver metastases. The site of disease making the patient unresectable was confirmed by biopsy in each case. Of the 28 remaining patients in whom laparoscopic ultrasound predicted to be resectable for cure, 26 (93%) had all tumor removed. Thus laparoscopy with ultrasound was the best method to select patients for curative surgery. Intraoperative ultrasound (IOUS) has been a critical method to identify insulinomas that are not palpable. Nonpalpable tumors are most commonly in the pancreatic head. Because the pancreatic head is thick and insulinomas are small, of 9 pancreatic head insulinomas only 3 (33%) were palpable. However, IOUS precisely identified each (100%). Others have recommended blind distal pancreatectomy for individuals with insulinoma in whom no tumor can be identified. However, our data suggest that this procedure is contraindicated as these occult tumors are usually within the pancreatic head. Recent series suggest that previously missed gastrinomas are commonly in the duodenum. IOUS is not able to identify these tumors, but other methods can. Of 27 patients with 31 duodenal gastrinomas, palpation identified 19

  19. Tumor Staging and HPV-Related Oropharyngeal Cancer.

    PubMed

    Wittekindt, Claus; Klussmann, Jens Peter

    The current TNM staging for oropharyngeal cancer (OSCC) was designed empirically for non-HPV-related disease. Emerging evidence suggests it is unsuited for Human papillomavirus (HPV)-related OSCC. Patients with HPV-positive tumors have improved prognosis, despite presenting at advanced stages. These shortcomings of the current staging system have been identified in single- and multi-institutional trials. Patients with HPV related OSCC typically present with advanced N-stages leading to higher stage groupings. A rarity of stages I and II therefore represents the nature of HPV-related OSCC. Concerning prognosis of the patients, N-category and extracapsular spread seem to be of minor importance, whereas advanced T-stages result in unfavourable outcome. Anatomical staging therefore has been implied into different proposals to prognostic risk classifications in HPV-related disease as an additive compound. Prognostic risk groupings are further enhanced by incorporating non-anatomical factors. To summarize, it can be suggested that the current TNM system alone has little prognostic value in HPV-related OSCC.

  20. Mucinous Borderline Ovarian Tumor in Very Old Aged Postmenopausal Woman

    PubMed Central

    Lee, Seung-Hee; Lee, Hae-Hyeog; Lee, Arum; Kim, Yeon-Suk; Jeon, Dong-Su; Kwak, Jeong Ja; Yang, Yo-Sep

    2015-01-01

    Mucinous borderline ovarian tumors (BOTs) occur most often in women between the ages of 20 and 30. Early-stage detection of the condition has a more favorable prognosis. In this case report, the authors present an elderly 93-year old woman who visited our hospital due to severe abdominal pain after being diagnosed with a pelvic mass 2 years ago and not undergoing any treatment since the diagnosis was made. She underwent emergency left salpingo-oophorectomy and was diagnosed with mucinous BOT according to biopsy results. PMID:26793682

  1. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma. PMID:26186252

  2. The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer

    PubMed Central

    Lee, Ming-Ching; Buitrago, Daniel H.; Kadota, Kyuichi; Ujiie, Hideki; Woo, Kaitlin; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2014-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality and has increasingly become a disease of elderly patients. Elderly patients are underrepresented in clinical trials that evaluate treatments for NSCLC. It has been suggested that patients >65 years of age have less robust immune responses to infections, immunizations, and tumors compared with younger patients. With increasing focus and number of immunotherapy clinical trials for NSCLC, we investigated the relationship between patient age and the tumor immune microenvironment in NSCLC. Using tissue microarrays from 1,278 patients with surgically resected Stage I NSCLC (≤65 years [33%], 66–79 years [55%], and ≥80 years [12%]), we determined whether quantitative and qualitative immune cell infiltration in the tumor differed between younger and older patients. Furthermore, we investigated the prognostic value of immune cell infiltration with respect to recurrence in octogenarians. We found that there were no statistically significant differences between older and younger patients in tumoral immune infiltration or effector regulatory immune response ratios (FoxP3/CD3, FoxP3/CD4, and FoxP3/CD8 ratios). In octogenarians, presence of low tumoral CD68+ immune cells was an independent predictor of recurrence. In the uniform cohort of surgically selected and resected Stage I NSCLC patients, tumor immune cell infiltration among the older age group resembled other age groups. Our study provides information that supports inclusion of older age patients selected for surgical resection in neoadjuvant or adjuvant immunotherapy clinical trials for lung cancer. PMID:25941595

  3. The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer.

    PubMed

    Lee, Ming-Ching; Buitrago, Daniel H; Kadota, Kyuichi; Ujiie, Hideki; Woo, Kaitlin; Sima, Camelia S; Travis, William D; Jones, David R; Adusumilli, Prasad S

    2014-11-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality and has increasingly become a disease of elderly patients. Elderly patients are underrepresented in clinical trials that evaluate treatments for NSCLC. It has been suggested that patients >65 years of age have less robust immune responses to infections, immunizations, and tumors compared with younger patients. With increasing focus and number of immunotherapy clinical trials for NSCLC, we investigated the relationship between patient age and the tumor immune microenvironment in NSCLC. Using tissue microarrays from 1,278 patients with surgically resected Stage I NSCLC (≤65 years [33%], 66-79 years [55%], and ≥80 years [12%]), we determined whether quantitative and qualitative immune cell infiltration in the tumor differed between younger and older patients. Furthermore, we investigated the prognostic value of immune cell infiltration with respect to recurrence in octogenarians. We found that there were no statistically significant differences between older and younger patients in tumoral immune infiltration or effector regulatory immune response ratios (FoxP3/CD3, FoxP3/CD4, and FoxP3/CD8 ratios). In octogenarians, presence of low tumoral CD68(+) immune cells was an independent predictor of recurrence. In the uniform cohort of surgically selected and resected Stage I NSCLC patients, tumor immune cell infiltration among the older age group resembled other age groups. Our study provides information that supports inclusion of older age patients selected for surgical resection in neoadjuvant or adjuvant immunotherapy clinical trials for lung cancer.

  4. Early-Stage Breast Cancer in the Octogenarian: Tumor Characteristics, Treatment Choices, and Clinical Outcomes

    PubMed Central

    Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna; Slanetz, Priscilla J.; Houlihan, Mary Jane; Herold, Christina I.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

    2016-01-01

    Background Nodal staging with sentinel node biopsy (SLNB), post-lumpectomy radiotherapy (RT), and endocrine therapy (ET) for estrogen receptor-positive (ER+) tumors is valuable in the treatment of early-stage (stages 1 or 2) breast cancer but used less often for elderly women. Methods This retrospective study investigated women referred for surgical evaluation of biopsy-proven primary early-stage invasive breast cancer from January 2001 to December 2010. Clinicopathologic features, treatment course, and outcomes for women ages 80–89 years and 50–59 years were compared. Results The study identified 178 eligible women ages 80–89 years and 169 women ages 50–59 years. The elderly women more often had grade 1 or 2 disease (p = 0.003) and ER+ tumors (p = 0.007) and less frequently had undergone adjuvant therapies (all p ≤ 0.001). Lumpectomy was performed more commonly for the elderly (92 vs. 83 %, p = 0.02), and axillary surgery was less commonly performed (46 vs. 96 %; p < 0.001). Fewer elderly women had undergone post-lumpectomy RT (42 vs. 89 %; p < 0.001) and ET for ER+ tumors (72 vs. 95 %; p < 0.001). During the median follow-up period of 56 months for the 80- to 89-year old group and 98 months for the 50- to 59-year-old group, death from breast cancer was similar (4 vs. 5 %; p = 0.5). The two groups respectively experienced 7 versus 6 locoregional recurrences and 11 versus 13 distant recurrences. Conclusions The octogenarians had disease survivorship similar to that of the younger women despite less frequent use of adjuvant therapies, likely reflecting lower-risk disease features. Whether increased use of axillary surgery, post-lumpectomy RT, and/or ET for ER+ tumors would further improve outcomes is an important area for further study, but treatment should not be deferred solely on the basis of age. PMID:27364507

  5. Clinical staging in bitches with mammary tumors: Influence of type and histological grade

    PubMed Central

    Gundim, Lígia F.; de Araújo, Camila P.; Blanca, William T.; Guimarães, Ednaldo C.; Medeiros, Alessandra A.

    2016-01-01

    Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas. PMID:27733787

  6. Surgical Approaches for Stage IVA Thymic Epithelial Tumors.

    PubMed

    Shapiro, Mark; Korst, Robert J

    2014-01-14

    Thymic epithelial tumors (TET) are rare mediastinal neoplasms that can metastasize to the pleural space (stage IVA). Complete surgical resection remains the backbone of therapy for patients with early stage TET, however, the role of surgery in the management of patients with stage IVA disease is not fully defined. Published reports in this regard are mainly small, retrospective, and uncontrolled, with unclear inclusion criteria. Surgical options to manage pleural disease include metastasectomy, extrapleural pneumonectomy, and metastasectomy/pleurectomy combined with heated intrapleural chemotherapy. The choice of the most appropriate surgical strategy needs to be individualized according to the quantity and location of disease, the patient's overall condition, as well as operator and institutional expertise. In the majority of cases, metastasectomy of pleural implants will be sufficient to achieve a complete resection. The available literature suggests that in selected patients with stage IVA TET, delivery of neoadjuvant chemotherapy followed by complete resection is a viable treatment option that can be associated with long-term survival.

  7. Development: Ages & Stages--Emerging Physical Skills

    ERIC Educational Resources Information Center

    Poole, Carla; Miller, Susan A.; Church, Ellen Booth

    2005-01-01

    In this article, the authors discuss how children develop their motor skills at different age levels. Newborn's movements are jerky and uncoordinated. Spending lots of floor time with a baby lying on her back or stomach helps her develop coordination, balance, and muscle strength during her earliest months. As locomotion enters a baby's life, she…

  8. Effect of Gibberellic Acid on Crown Gall Tumor Induction in Aging Primary Pinto Bean Leaves 1

    PubMed Central

    Anand, Vinod K.; Bauer, Chris; Heberlein, Gary T.

    1975-01-01

    Gibberellic acid was tested for its effect on tumor induction by Agrobacterium tumefaciens in primary pinto bean (Phaseolus vulgaris) leaves in various stages of development. The hormone was found to promote tumor induction in partially aged leaves but did not effect tumor induction in very young leaves or in fully matured leaves. It is suggested that the natural loss of susceptibility to tumor induction in maturing pinto bean leaves is associated with a concomitant loss of endogenous gibberellins and/or a sensitivity to gibberellins. PMID:16659201

  9. Neighborhood Composition and Cancer among Hispanics: Tumor Stage and Size at Time of Diagnosis

    PubMed Central

    Reyes-Ortiz, Carlos A.; Eschbach, Karl; Zhang, Dong D.; Goodwin, James S.

    2013-01-01

    Background We have previously reported that cancer incidence for lung, female breast, and colon and rectum for Hispanics decreases with increasing percentage of Hispanics at the census tract. In contrast, cervical cancer incidence increases with increasing percentage of Hispanics at the census tract. Methods In this study, we investigate the hypothesis that Hispanics living in census tracts with high percentages of Hispanics are diagnosed with more advanced cancer, with respect to tumor size and stage of diagnosis. Data from the Surveillance, Epidemiology, and End Results registry and the U.S. Census Bureau were used to estimate the odds of diagnosis at a “late” stage (II, III, IV) versus “early” stage (I) and breast cancer tumor size among Hispanics as a function of census tract percent Hispanic. Hispanic ethnicity in the Surveillance, Epidemiology, and End Results registry was identified by medical record review and Hispanic surname lists. The study also used income of Hispanics living in the census tract and controlled for age at diagnosis and gender. Results We found that Hispanics living in neighborhoods with higher density of Hispanic populations were more likely to be diagnosed with late-stage breast, cervical, or colorectal cancer, and to have a larger tumor size of breast cancer. Conclusions Our findings suggest that the benefits of lower cancer incidence in high tract percent Hispanics are partially offset by poorer access and reduced use of screening in conjunction with lower income, poorer health insurance coverage, and language barriers typical of these communities. PMID:18990733

  10. Surveillance programs for stage I nonseminomatous germ cell tumors of the testis.

    PubMed

    Segal, Roanne

    2006-01-01

    Germ cell tumors of the testes constitute approximately 1-2% of all tumors in males 15-35 years of age. Half of those present as clinical stage I disease. The traditional approach was either a retroperitoneal node dissection or radiotherapy. A historical review of the literature suggested that 70% of these patients were cured and did not benefit from further therapy. This coupled with the advent of tumor markers, advanced diagnostic techniques, and cisplatin based chemotherapy led to the consideration for surveillance programs, thereby offering therapy only to those who required it. This article reviews the surveillance programs described in the literature to date with respect to both suitability and program design.

  11. Three-Staged Stereotactic Radiotherapy Without Whole Brain Irradiation for Large Metastatic Brain Tumors

    SciTech Connect

    Higuchi, Yoshinori Serizawa, Toru; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Sato, Makoto; Iwadate, Yasuo; Saeki, Naokatsu

    2009-08-01

    Purpose: To evaluate the efficacy and toxicity of staged stereotactic radiotherapy with a 2-week interfraction interval for unresectable brain metastases more than 10 cm{sup 3} in volume. Patients and Methods: Subjects included 43 patients (24 men and 19 women), ranging in age from 41 to 84 years, who had large brain metastases (> 10 cc in volume). Primary tumors were in the colon in 14 patients, lung in 12, breast in 11, and other in 6. The peripheral dose was 10 Gy in three fractions. The interval between fractions was 2 weeks. The mean tumor volume before treatment was 17.6 {+-} 6.3 cm{sup 3} (mean {+-} SD). Mean follow-up interval was 7.8 months. The local tumor control rate, as well as overall, neurological, and qualitative survivals, were calculated using the Kaplan-Meier method. Results: At the time of the second and third fractions, mean tumor volumes were 14.3 {+-} 6.5 (18.8% reduction) and 10.6 {+-} 6.1 cm{sup 3} (39.8% reduction), respectively, showing significant reductions. The median overall survival period was 8.8 months. Neurological and qualitative survivals at 12 months were 81.8% and 76.2%, respectively. Local tumor control rates were 89.8% and 75.9% at 6 and 12 months, respectively. Tumor recurrence-free and symptomatic edema-free rates at 12 months were 80.7% and 84.4%, respectively. Conclusions: The 2-week interval allowed significant reduction of the treatment volume. Our results suggest staged stereotactic radiotherapy using our protocol to be a possible alternative for treating large brain metastases.

  12. Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection

    PubMed Central

    Jeong, Eugene; Hyun, Seung Hyup; Moon, Seung Hwan; Cho, Young Seok; Kim, Byung-Tae; Lee, Kyung-Han

    2017-01-01

    Abstract Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor 18F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC). Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax. WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52–3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47–3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01–1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups. Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count. PMID:28151879

  13. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages

    SciTech Connect

    Hoshiba, Takashi; Tanaka, Masaru

    2013-09-20

    Highlights: •Models mimicking ECM in tumor with different malignancy were prepared. •Cancer cell proliferation was suppressed on benign tumor ECM. •Benign tumor cell proliferation was suppressed on cancerous ECM. •Chemoresistance of cancer cell was enhanced on cancerous ECM. -- Abstract: Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared “staged tumorigenesis-mimicking matrices” which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  14. Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived from tumor cells at various malignant stages.

    PubMed

    Hoshiba, Takashi; Tanaka, Masaru

    2013-09-20

    Extracellular matrix (ECM) has been focused to understand tumor progression in addition to the genetic mutation of cancer cells. Here, we prepared "staged tumorigenesis-mimicking matrices" which mimic in vivo ECM in tumor tissue at each malignant stage to understand the roles of ECM in tumor progression. Breast tumor cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells, were cultured to form their own ECM beneath the cells and formed ECM was prepared as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF-10A cell proliferation was promoted on the matrices derived from MCF-10A cells. Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only matrices derived from MDA-MB-231 cells. Our results showed that the cells showed different behaviors on staged tumorigenesis-mimicking matrices according to the malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis-mimicking matrices might be a useful in vitro ECM models to investigate the roles of ECM in tumor progression.

  15. One Stage Posterior Minimal Laminectomy and Video-Assisted Thoracoscopic Surgery (VATS) for Removal of Thoracic Dumbbell Tumor

    PubMed Central

    Nam, Kyoung Hyup; Ahn, Hyo Yeoung; Cho, Jeong Su; Kim, Yeoung Dae; Choi, Byung Kwan; Han, In Ho

    2017-01-01

    Objective This study was conducted to assess the surgical results of one-stage posterior minimal laminectomy and video-assisted thoracoscopic surgery (VATS) for the treatment of thoracic dumbbell tumor and to describe its precise technique. In addition, we investigated the technique’s usefulness and limitations. Methods Seven cases of thoracic dumbbell tumor (two men and five women, mean age, 43 years) were analyzed retrospectively. Pathological findings included schwannoma in four patients, neurofibroma in two patients, and hemangioma in one patient. The location of tumors varied from T2/3 to T12/L1. Dumbbell tumors were resected by one-stage operation using posterior laminectomy followed by VATS without instrumentation. Clinical data were reviewed. Results The mean follow-up period was 25 months (range, 3–58 months), and the operative time ranged from 255 to 385 min (mean, 331 min), with estimated blood loss ranging from 110 to 930 mL (mean, 348 mL). The tumor was completely resected without instrumentation and postoperative instability in all cases. Postoperative complications included atelectasis and facial anhydrosis in one case each. Conclusion One-stage posterior minimal laminectomy and VATS may be a safe and less invasive technique for removal of thoracic dumbbell tumor without instability. This method has the advantage of early ambulation and rapid recovery because it reduces blood loss and postoperative pain. PMID:28264248

  16. Two-stage surgical resection of an atypical teratoid rhabdoid tumor occupying the infratentorial and supratentorial compartment in children under two years: Report of two cases

    PubMed Central

    Foreman, Paul M.; Madura, Casey J.; Johnston, James M.; Rocque, Brandon G.

    2016-01-01

    Introduction Atypical teratoid rhabdoid tumors are highly malignant neoplasms that present in young children and can grow to a large size. Maximal safe surgical resection is a mainstay of treatment. Presentation of cases Two cases of children under the age of two with large tumors involving the supratentorial and infratentorial compartments are presented. A two-staged operative approach combining a standard suboccipital approach to the fourth ventricle followed by an infratentorial, supracerebellar approach was utilized for resection. Discussion Maximal safe surgical resection of large tumors in young children is challenging. A staged approach is presented that affords maximal tumor resection while minimizing perioperative morbidity. Conclusion A staged operative approach appears safe and efficacious when resecting large tumors from both the infratentorial and supratentorial compartments in children less than two years of age. PMID:26812670

  17. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.

    PubMed

    Bouchlaka, Myriam N; Sckisel, Gail D; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E; Maverakis, Emanual; Wilkins, Danice E C; Alderson, Kory L; Hsiao, Hui-Hua; Weiss, Jonathan M; Monjazeb, Arta M; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L; Blazar, Bruce R; Wiltrout, Robert H; Redelman, Doug; Taub, Dennis D; Murphy, William J

    2013-10-21

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.

  18. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

    PubMed Central

    Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Maverakis, Emanual; Wilkins, Danice E.C.; Alderson, Kory L.; Hsiao, Hui-Hua; Weiss, Jonathan M.; Monjazeb, Arta M.; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Redelman, Doug; Taub, Dennis D.

    2013-01-01

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice. PMID:24081947

  19. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

    PubMed Central

    Khodapasand, Ehsan; Jafarzadeh, Narges; Farrokhi, Farid; Kamalidehghan, Behnam; Houshmand, Massoud

    2015-01-01

    Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. PMID:25864810

  20. Cyclin D1 and Ki-67 expression correlates to tumor staging in tongue squamous cell carcinoma

    PubMed Central

    de Carli, Marina-Lara; Sperandio, Felipe-Fornias; Hanemann, João-Adolfo-Costa; Pereira, Alessandro-Antônio-Costa

    2015-01-01

    Background The immunohistochemical expression of Cyclin D1 and Ki-67 were analyzed in tongue squamous cell carcinomas (SCC), relating them to the clinical and morphological exhibition of these tumors. Material and Methods Twenty-nine patients fulfilled the inclusion criteria; clinical data included gender, age, ethnicity and use of licit drugs such as alcohol and tobacco. The TNM staging and histopathological differentiation grading was assessed for each case. In addition, T1 patients were gathered with T2 patients; and T3 patients were gathered with T4 patients to assemble two distinct groups: (T1/T2) and (T3/T4). Results The mean follow-up time was 24 months and 30% of the patients died as a consequence of the disease, while 23.3% lived with the disease and 46.7% lived lesion-free. T1 and T2 tumors showed statistically lesser Ki-67 and Cyclin D1 staining when compared to T3 and T4 tumors. Conclusions Ki-67 and Cyclin D1 pose as auxiliary tools when determining the progression of tongue SCC at the time of diagnosis. Key words:Carcinoma, squamous cell, cyclin D, immunohistochemistry, Ki-67 antigen, prognosis. PMID:26449430

  1. Integrin genetic variants and stage-specific tumor recurrence in patients with stage II and III colon cancer.

    PubMed

    Bohanes, P; Yang, D; Loupakis, F; LaBonte, M J; Gerger, A; Ning, Y; Lenz, C; Lenz, F; Wakatsuki, T; Zhang, W; Benhaim, L; El-Khoueiry, A; El-Khoueiry, R; Lenz, H-J

    2015-06-01

    Integrins (ITGs) are key elements in cancer biology, regulating tumor growth, angiogenesis and lymphangiogenesis through interactions of the tumor cells with the microenvironment. Moving from the hypothesis that ITGs could have different effects in stage II and III colon cancer, we tested whether a comprehensive panel of germline single-nucleotide polymorphisms (SNPs) in ITG genes could predict stage-specific time to tumor recurrence (TTR). A total of 234 patients treated with 5-fluorouracil-based chemotherapy at the University of Southern California were included in this study. Whole-blood samples were analyzed for germline SNPs in ITG genes using PCR-restriction fragment length polymorphism or direct DNA sequencing. In the multivariable analysis, stage II colon cancer patients with at least one G allele for ITGB3 rs4642 had higher risk of recurrence (hazard ratio (HR)=4.027, 95% confidence interval (95% CI) 1.556-10.421, P=0.004). This association was also significant in the combined stage II-III cohort (HR=1.975, 95% CI 1.194-3.269, P=0.008). The predominant role of ITGB3 rs4642 in stage II diseases was confirmed using recursive partitioning, showing that ITGB3 rs4642 was the most important factor in stage II diseases. In contrast, in stage III diseases the combined analysis of ITGB1 rs2298141 and ITGA4 rs7562325 allowed to identify three distinct prognostic subgroups (P=0.009). The interaction between stage and the combined ITGB1 rs2298141 and ITGA4 rs7562325 on TTR was significant (P=0.025). This study identifies germline polymorphisms in ITG genes as independent stage-specific prognostic markers for stage II and III colon cancer. These data may help to select subgroups of patients who may benefit from ITG-targeted treatments.

  2. Automatic age-related macular degeneration detection and staging

    NASA Astrophysics Data System (ADS)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  3. Harvey Cushing and pediatric brain tumors at Johns Hopkins: the early stages of development

    PubMed Central

    Pendleton, Courtney; Ahn, Edward S.; Quiñones-Hinojosa, Alfredo

    2015-01-01

    Object Harvey Cushing, credited with pioneering the field of neurosurgery as a distinct surgical subspecialty in the US, was at the forefront of neurooncology, publishing seminal papers on the diagnosis and treatment of pediatric brain tumors during the latter part of his career. However, his contributions to the surgical treatment of these lesions during the early stages of his tenure at the Johns Hopkins Hospital, from 1896 to 1912, remain largely unknown. Methods After obtaining institutional review board approval, and through the courtesy of the Alan Mason Chesney Archives, the authors reviewed the Johns Hopkins Hospital surgical files from the years 1896 to 1912. Patients younger than 18 years of age, presenting with symptoms suspicious for an intracranial tumor, and undergoing surgical intervention by Cushing were selected for further analysis. Results Of the 40 pediatric patients undergoing surgery for suspected intracranial neoplasms, 26 were male. The mean age among the entire sample was 10.1 years. Cushing used three main operative approaches in the surgical treatment of pediatric intracranial neoplasms: infratentorial/suboccipital, subtemporal, and hemisphere flap. Twenty-three patients had negative findings following both the primary and subsequent surgical interventions conducted by Cushing. Postoperative conditions following the primary surgical intervention were improved in 24 patients. Twelve patients (30%) died during their inpatient stay for the primary intervention. The mean time to the last follow-up was 24.9 months; the mean time to death was 10.0 months. Conclusions Cushing strove to maximize exposure while minimizing blood loss in an attempt to increase his ability to successfully treat pediatric brain tumors. His early contributions to the field of pediatric neurooncology demonstrate his commitment to advancing the field of neurosurgery. PMID:21631192

  4. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  5. Efficacy of computed tomography features in predicting stage III thymic tumors

    PubMed Central

    Shen, Yan; Ye, Jianding; Fang, Wentao; Zhang, Yu; Ye, Xiaodan; Ma, Yonghong; Chen, Libo; Li, Minghua

    2017-01-01

    Accurate assessment of the invasion of intrathoracic structures by stage III thymic tumors assists their appropriate management. The present study aimed to evaluate the efficacy of computed tomography (CT) features for the prediction of stage III thymoma invasion. The pre-operative CT images of 66 patients with confirmed stage III thymic tumors were reviewed retrospectively. The CT features of invasion into the mediastinal pleura, lungs, pericardium and great vessels were analyzed, and their sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy were calculated. For mediastinal pleural and pericardial invasion, an absence of space between the tumor and the mediastinal pleura/pericardium with mediastinal pleural/pericardial thickening and pleural/pericardial effusion exhibited a specificity and PPV of 100%, respectively. For lung invasion, a multi-lobular tumor convex to the lung with adjacent lung abnormalities exhibited a specificity and PPV of 91.2 and 81.3%, respectively. For vessel invasion, the specificity and PPV were each 100% for tumors abutting ≥50% of the vessel circumference, and for tumor oppression, deformation and occlusion of the vessel. In conclusion, recognition of the appropriate CT features can serve as a guide to invasion by stage III thymic tumors, and can facilitate the selection of appropriate pre-operative treatment. PMID:28123518

  6. Tumor Heterogeneity of FIGO Stage III Carcinoma of the Uterine Cervix

    SciTech Connect

    Kim, Yong Bae; Lee, Ik Jae; Kim, Song Yih; Kim, Jun Won; Yoon, Hong In; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Suh, Chang Ok; Kim, Gwi Eon

    2009-12-01

    Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high-dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the chi{sup 2} test and Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient.

  7. Old age at diagnosis increases risk of tumor progression in nasopharyngeal cancer

    PubMed Central

    He, Yao-Xuan; Chen, Xiao-Di; Zhang, Guo-Ye; Li, Zhi-Kun; Hong, Jing; Xie, Dan; Cai, Mu-Yan

    2016-01-01

    Age at diagnosis has been found to be a prognostic factor of outcomes in various cancers. However, the effect of age at diagnosis on nasopharyngeal cancer (NPC) progression has not been explored. We retrospectively evaluated the relationship between age and disease progression in 3,153 NPC patients who underwent radiotherapy, chemotherapy, or chemoradiotherapy between 2007 and 2009. Patients were randomly assigned to either a testing cohort or a validation cohort by computer-generated random assignment. X-tile plots determined the optimal cut-point of age based on survival status to be ≤61 vs. >61 years. Further correlation analysis showed that age >61 years was significantly correlated with the tumor progression and therapeutic regimen in both testing and validation cohorts (P <0.05). In the present study, we observed that older age (>61 years) was a strong and independent predictor of poor disease-free survival (DFS) and cancer-specific survival (CSS), in both univariate and multivariate analyses. Age was also found to be a significant prognostic predictor as well (P <0.05) when evaluating patients with the same disease stage. ROC analysis confirmed the predictive value of age on NPC-specific survival in both cohorts (P <0.001) and suggested that age may improve the ability to discriminate outcomes in NPCs, especially regarding tumor progression. In conclusion, our study suggests that older age at NPC diagnosis is associated with a higher incidence of tumor progression and cancer-specific mortality. Age is a strong and independent predictor of poor outcomes and may allow for more tailored therapeutic decision-making and individualized patient counseling. PMID:27463012

  8. Accelerated aging in the tumor microenvironment: connecting aging, inflammation and cancer metabolism with personalized medicine.

    PubMed

    Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E; Pavlides, Stephanos; Whitaker-Menezes, Diana; Pestell, Richard G; Howell, Anthony; Sotgia, Federica

    2011-07-01

    Cancer is thought to be a disease associated with aging. Interestingly, normal aging is driven by the production of ROS and mitochondrial oxidative stress, resulting in the cumulative accumulation of DNA damage. Here, we discuss how ROS signaling, NFκB- and HIF1-activation in the tumor microenvironment induces a form of "accelerated aging," which leads to stromal inflammation and changes in cancer cell metabolism. Thus, we present a unified model where aging (ROS), inflammation (NFκB) and cancer metabolism (HIF1), act as co-conspirators to drive autophagy ("self-eating") in the tumor stroma. Then, autophagy in the tumor stroma provides high-energy "fuel" and the necessary chemical building blocks, for accelerated tumor growth and metastasis. Stromal ROS production acts as a "mutagenic motor" and allows cancer cells to buffer-at a distance-exactly how much of a mutagenic stimulus they receive, further driving tumor cell selection and evolution. Surviving cancer cells would be selected for the ability to induce ROS more effectively in stromal fibroblasts, so they could extract more nutrients from the stroma via autophagy. If lethal cancer is a disease of "accelerated host aging" in the tumor stroma, then cancer patients may benefit from therapy with powerful antioxidants. Antioxidant therapy should block the resulting DNA damage, and halt autophagy in the tumor stroma, effectively "cutting off the fuel supply" for cancer cells. These findings have important new implications for personalized cancer medicine, as they link aging, inflammation and cancer metabolism with novel strategies for more effective cancer diagnostics and therapeutics.

  9. Can Screening With the Ages and Stages Questionnaire Detect Autism?

    PubMed Central

    Hardy, Sarah; Haisley, Lauren; Manning, Courtney; Fein, Deborah

    2015-01-01

    Objective Parents rely on pediatricians to monitor their child’s development. The American Academy of Pediatrics recommends routine developmental screening with both broadband and autism-specific instruments at specified ages. If broadband screeners can detect autism risk, this might minimize the burden of administering autism-specific screens to all children. The current study examines the ability of the Ages and Stages Questionnaire-Third Edition (ASQ-3) to identify children at risk for autism. We looked at ASQ-3 scores of children who screen positive on the Modified Checklist for Autism in Toddlers-Revised, children who continue to screen positive on the M-CHAT-R follow-up interview, and children diagnosed with ASD. Methods 2848 toddlers, aged 16–30 months, were screened with the ASQ-3 and M-CHAT-R across 20 pediatric sites. Children who screened positive on the M-CHAT-R and its follow-up interview were offered a diagnostic evaluation. Results Using the “monitor and/or fail” cutoff on any domain, the ASQ-3 identified 87% of the children who screened positive on the M-CHAT-R with follow-up and 95% (20/21) of those diagnosed with an ASD. “Monitor and/or Fail” on the Communication domain alone also identified 95% of the diagnosed children. Conclusions Scores below the “monitor” cutoff on the Communication domain of the ASQ-3 can indicate initial concern requiring autism-specific follow-up. If these results are confirmed with a sample large enough to separately examine toddlers of different ages and different cultural backgrounds, it may be feasible to implement a two-stage screening strategy, with autism specific screening reserved for those who are positive on a broad band screen. PMID:26348972

  10. Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer

    PubMed Central

    Oh, Tai Young; Shin, Ui Sup; Lee, Hyang Ran; Park, Sun Hoo

    2011-01-01

    Purpose Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. Methods The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. Results Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR ≤ 0.25 group was 92.9% (P = 0.03). Conclusion The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer. PMID:21602965

  11. Two faces of p53: aging and tumor suppression

    PubMed Central

    Rodier, Francis; Campisi, Judith; Bhaumik, Dipa

    2007-01-01

    The p53 tumor suppressor protein, often termed guardian of the genome, integrates diverse physiological signals in mammalian cells. In response to stress signals, perhaps the best studied of which is the response to DNA damage, p53 becomes functionally active and triggers either a transient cell cycle arrest, cell death (apoptosis) or permanent cell cycle arrest (cellular senescence). Both apoptosis and cellular senescence are potent tumor suppressor mechanisms that irreversibly prevent damaged cells from undergoing neoplastic transformation. However, both processes can also deplete renewable tissues of proliferation-competent progenitor or stem cells. Such depletion, in turn, can compromise the structure and function of tissues, which is a hallmark of aging. Moreover, whereas apoptotic cells are by definition eliminated from tissues, senescent cells can persist, acquire altered functions, and thus alter tissue microenvironments in ways that can promote both cancer and aging phenotypes. Recent evidence suggests that increased p53 activity can, at least under some circumstances, promote organismal aging. Here, we discuss the role of p53 as a key regulator of the DNA damage responses, and discuss how p53 integrates the outcome of the DNA damage response to optimally balance tumor suppression and longevity. PMID:17942417

  12. New concepts of staging in gastrointestinal tumors as a basis of diagnosis and multimodal therapy.

    PubMed

    Gretschel, S; Moesta, K T; Hünerbein, M; Lange, T; Gebauer, B; Stroszczinski, C; Bembenek, A; Schlag, P M

    2004-02-01

    The therapy of gastrointestinal tumors is becoming more and more sophisticated and complex. This is due to an improved understanding of the pathogenesis of tumors, a more detailed classification and increasing therapeutic options. The basis of optimized therapeutic concepts is the exact evaluation of tumor spread and exact staging. The following review describes some of the most recent staging concepts in gastrointestinal tumors. Multislice computed tomography (CT), positron emission tomography (PET) and new supraparamagnetic iron oxide contrast agents for magnetic resonance imaging enable an increasing quality of the visualization of tumors and metastases. 3D imaging will be used for planning of surgical interventions in the future. Optical coherence tomography may contribute to an improved tumor staging and, thus, to the safety of limited interventions in early oesophageal- and gastric cancer patients. Laparoscopy and laparoscopic ultrasound become increasingly important for the identification of small metastases in the peritoneum, in lymph nodes and in the liver. The sentinel lymph node concept will contribute to an improved staging and individualized therapy as well.

  13. Bone Mineral Density in Healthy Female Adolescents According to Age, Bone Age and Pubertal Breast Stage

    PubMed Central

    Moretto, M.R; Silva, C.C; Kurokawa, C.S; Fortes, C.M; Capela, R.C; Teixeira, A.S; Dalmas, J.C; Goldberg, T.B

    2011-01-01

    Objectives: This study was designed to evaluate bone mineral density (BMD) in healthy female Brazilian adolescents in five groups looking at chronological age, bone age, and pubertal breast stage, and determining BMD behavior for each classification. Methods: Seventy-two healthy female adolescents aged between 10 to 20 incomplete years were divided into five groups and evaluated for calcium intake, weight, height, body mass index (BMI), pubertal breast stage, bone age, and BMD. Bone mass was measured by bone densitometry (DXA) in lumbar spine and proximal femur regions, and the total body. BMI was estimated by Quetelet index. Breast development was assessed by Tanner’s criteria and skeletal maturity by bone age. BMD comparison according to chronologic and bone age, and breast development were analyzed by Anova, with Scheffe’s test used to find significant differences between groups at P≤0.05. Results: BMD (g·cm-2) increased in all studied regions as age advanced, indicating differences from the ages of 13 to 14 years. This group differed to the 10 and 11 to 12 years old groups for lumbar spine BMD (0.865±0.127 vs 0.672±0.082 and 0.689±0.083, respectively) and in girls at pubertal development stage B3, lumbar spine BMD differed from B5 (0.709±0.073 vs 0.936±0.130) and whole body BMD differed from B4 and B5 (0.867±0.056 vs 0.977±0.086 and 1.040±0.080, respectively). Conclusion: Bone mineralization increased in the B3 breast maturity group, and the critical years for bone mass acquisition were between 13 and 14 years of age for all sites evaluated by densitometry. PMID:21966336

  14. High-Grade Tumor Budding Stratifies Early-Stage Cervical Cancer with Recurrence Risk

    PubMed Central

    Xu, Xia; Guo, Shuang; Wang, Zehua

    2016-01-01

    Objectives This study investigated prognostic significance of tumor budding in early-stage cervical cancer (ESCC) following radical surgery and its contribution to improve the stratification of patients with recurrence risk. Methods The archival medical records and H&E-stained slides of 643 patients with IA2-IIA stage cervical cancer who underwent radical surgery were retrospectively reviewed. Clinicopathological parameters were noted, and tumor buds were counted using immunohistochemistry for each case. The prognostic significance of tumor budding was analyzed. Prediction models that comprised tumor budding were established, and the performance was compared between the novel models and classic criteria via log-rank test and receiver operating characteristic analysis. Results Tumors with high-grade tumor budding (HTB) exhibited a substantially increased risk of recurrence (hazard ratio = 4.287, P < 0.001). Nine predictive models for recurrence were established, in which HTB was combined with recognized risk factors. The model using of at least two risk factors of HTB, tumor size ≥ 4 cm, deep stromal invasion of outer 1/3, and lymphovascular space invasion to stratify patients with an intermediate risk was most predictive of recurrence compared with the classic criteria. Conclusions Tumor budding is an independent, unfavorable, prognostic factor for ESCC patients following radical surgery and holds promise for improved recurrence risk stratification. PMID:27861522

  15. A novel clinicopathological analysis of early stage ovarian Sertoli-Leydig cell tumors at a single institution

    PubMed Central

    Nam, Seon Mi; Kim, Jee Whan; Eoh, Kyung Jin; Kim, Hye Min; Lee, Jung Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun

    2017-01-01

    Objective To evaluate the clinical and pathologic characteristics of patients who were diagnosed with ovarian Sertoli-Leydig cell tumors (SLCTs) in a single institution. Methods The medical records of 11 patients who were pathologically diagnosed with SLCTs beginning in 1995 in a single institute was reviewed. Results The median patient age was 31 years (range, 16 to 70 years). Patient International Federation of Gynecology and Obstetrics stages were IA, IC, and IIB in 3 (27.3%), 6 (54.5%), and 2 (18.2%) patients, respectively. Six patients (54.5%) had grade 3 tumors, 3 patients (27.3%) had grade 2 tumors, and 1 patient (9.1%) had a grade 1 tumor. Four patients without children underwent fertility-sparing surgery, and 7 patients had full staging surgery, including a hysterectomy and bilateral salpingo-oophorectomy, with a laparoscopic approach used in 3. Eight patients underwent pelvic lymph node dissection, and 8 patients were administered adjuvant chemotherapy consisting of bleomycin, etoposide, and cisplatin in 6 cases, a modified bleomycin, etoposide, and cisplatin regimen in 1 case, and a combined paclitaxel and cisplatin regimen in 1 case. Two patients died of disease and were re-diagnosed with Sertoli form endometrioid carcinoma. The other patients remain alive without recurrence at the time of reporting. Conclusion Our findings suggest that regardless of tumor stage or grade, ovarian SLCT patients have a good prognosis. Close observation and unilateral salpingo-oophorectomy would be beneficial for women who still wish to have children, while hysterectomy and bilateral salpingo-oophorectomy with adjuvant chemotherapy would be the optimal treatment in other cases. Furthermore, meticulous pathologic diagnosis is needed to develop a precise treatment strategy. PMID:28217670

  16. Astro research fellowship: Apoptosis as a predictor of tumor response to radiation in stage IB cervical carcinoma

    SciTech Connect

    Wheeler, J.A.; Eifel, P.J.; Allen, P.K.

    1995-07-30

    Levels of apoptosis predict for tumor responsiveness to radiation in various animal systems. To investigate the potential role of apoptosis as a predictor of response in human tumors, a retrospective review was undertaken of patients with adenocarcinoma of the cervix whose primary lesion at presentation measured at least 4 cm and who underwent definitive radiation therapy. A previous report had indicated that roughly half this group of patients should have a long-term relapse free survival. Pretreatment biopsy specimens of 44 patients with Stage IB adenocarcinoma of the cervix, whose primary lesion at presentation measured at least 4 cm in greatest dimension, were scored for apoptosis by two independent investigators without knowledge of the treatment outcome, and the results were averaged. Actuarial methods were used to assess overall survival, disease-free survival, determinate survival, and local control as a function of the baseline level of apoptosis. Patients ranged in age from 21 to 87 years and were treated with definitive radiotherapy between 1964 and 1989. Follow-up for the surviving patients ranged 1 to 278 months, with a mean of 101 months. Patients whose tumors had a baseline level of apoptosis above the median value (2%) had a better overall survival than those with lower levels of apoptosis (p = 0.056). A similar trend for disease-free survival (p = 0.32) and determinate survival (p = 0.27) did not reach statistical significance, perhaps because of the small number of patients. Because only 6 of the 44 patients (13%) had a local tumor failure, it was not possible to establish a correlation between the pretreatment level of apoptosis and the local tumor control by radiation. The baseline level of apoptosis predicted for survival in patients with Stage IB cervical adenocarcinoma. Further investigation of the measurement of apoptosis as a potential predictive assay is warranted in other human tumor systems. 59 refs., 3 figs., 2 tabs.

  17. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  18. Breed- and age-related differences in canine mammary tumors.

    PubMed

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  19. Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression.

    PubMed Central

    de Vries, T. J.; Quax, P. H.; Denijn, M.; Verrijp, K. N.; Verheijen, J. H.; Verspaget, H. W.; Weidle, U. H.; Ruiter, D. J.; van Muijen, G. N.

    1994-01-01

    Degradation of the extracellular matrix and other tissue barriers by proteases like plasminogen activators (PAs) is a prerequisite for neoplastic growth and metastasis. Recently, we reported that highly metastatic behavior of human melanoma cells in nude mice correlates with urokinase-type PA (u-PA) expression and activity and with PA inhibitor type 1 and 2 (PAI-1, PAI-2) expression. Here we report on the occurrence of components of the PA system in the various stages of human melanoma tumor progression in situ. We studied the protein distribution on freshly frozen lesions of common nevocellular nevi (n = 25), dysplastic (= atypical) nevi (n = 16), early primary melanomas (n = 8), advanced primary melanomas (n = 11), and melanoma metastases (n = 17). Tissue-type PA was present in endothelial cells in all lesions, whereas in metastases it could be detected in tumor cells in a minority of the lesions. u-PA, its receptor, PAI-1, and PAI-2 could not be detected in benign and in early stages but appeared frequently in advanced primary melanoma and melanoma metastasis lesions. u-PA was detected in stromal cells and in tumor cells at the invasive front, the u-PA receptor and PAI-2 in tumor cells, and PAI-1 in the extracellular matrix surrounding tumor cells. Localization of the corresponding messenger RNAs and enzyme activities revealed a similar distribution. We conclude that plasminogen activation is a late event in melanoma tumor progression. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8291613

  20. Aging, tumor suppression and cancer: High-wire act!

    SciTech Connect

    Campisi, Judith

    2004-08-15

    Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms.

  1. Transcriptome profile of the early stages of breast cancer tumoral spheroids

    PubMed Central

    Pacheco-Marín, Rosario; Melendez-Zajgla, Jorge; Castillo-Rojas, Gonzalo; Mandujano-Tinoco, Edna; Garcia-Venzor, Alfredo; Uribe-Carvajal, Salvador; Cabrera-Orefice, Alfredo; Gonzalez-Torres, Carolina; Gaytan-Cervantes, Javier; Mitre-Aguilar, Irma B.; Maldonado, Vilma

    2016-01-01

    Oxygen or nutrient deprivation of early stage tumoral spheroids can be used to reliably mimic the initial growth of primary and metastatic cancer cells. However, cancer cell growth during the initial stages has not been fully explored using a genome-wide approach. Thus, in the present study, we investigated the transcriptome of breast cancer cells during the initial stages of tumoral growth using RNAseq in a model of Multicellular Tumor Spheroids (MTS). Network analyses showed that a metastatic signature was enriched as several adhesion molecules were deregulated, including EPCAM, E-cadherin, integrins and syndecans, which were further supported by an increase in cell migration. Interestingly, we also found that the cancer cells at this stage of growth exhibited a paradoxical hyperactivation of oxidative mitochondrial metabolism. In addition, we found a large number of regulated (long non coding RNA) lncRNAs, several of which were co-regulated with neighboring genes. The regulatory role of some of these lncRNAs on mRNA expression was demonstrated with gain of function assays. This is the first report of an early-stage MTS transcriptome, which not only reveals a complex expression landscape, but points toward an important contribution of long non-coding RNAs in the final phenotype of three-dimensional cellular models. PMID:27021602

  2. Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

    PubMed Central

    Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2015-01-01

    The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

  3. Paradoxical role of autophagy in the dysplastic and tumor-forming stages of hepatocarcinoma development in rats.

    PubMed

    Sun, K; Guo, X-L; Zhao, Q-d; Jing, Y-y; Kou, X-r; Xie, X-q; Zhou, Y; Cai, N; Gao, L; Zhao, X; Zhang, S-s; Song, J-r; Li, D; Deng, W-j; Li, R; Wu, M-c; Wei, L-x

    2013-02-21

    Many reports have shown that autophagy has a role as both a promoter and inhibitor in tumor development. However, the mechanism of this paradox is unknown. Tumor development is a multistep process. Therefore, we investigated whether the role of autophagy in hepatocarcinoma formation depended on the stage of tumor development. Based on our results, autophagy inhibition by chloroquine had a tumor-promotive effect in the rat model with N-diethylnitrosamine-induced hepatocarcinogenesis in its dysplastic stage (Ds) and a tumor-suppressive effect in its tumor-forming stage (Ts). In the Ds, autophagy inhibition enhanced cell proliferation, DNA damage and inflammatory cytokines expression in liver. These changes were dependent on the upregulation of reactive oxygen species (ROS) that was resulted from autophagy inhibition, and ultimately accelerated the process of hepatocarcinogenesis. However, in the Ts, autophagy inhibition restrained tumor formation by decreasing tumor cell survival and proliferation. In this stage, autophagy inhibition led to excessive ROS accumulation in the tumor, which promoted cell apoptosis, and prominently suppressed tumor cell metabolism. Taken together, our data suggested that autophagy suppressed hepatocarcinogenesis in the Ds by protecting normal cell stability and promoted hepatocarcinogenesis in the Ts by supporting tumor cells growth. Autophagy always had a role as a protector throughout the process of hepatocarcinoma development.

  4. Paradoxical role of autophagy in the dysplastic and tumor-forming stages of hepatocarcinoma development in rats

    PubMed Central

    Sun, K; Guo, X-l; Zhao, Q-d; jing, Y-y; Kou, X-r; Xie, X-q; Zhou, Y; Cai, N; Gao, L; Zhao, X; Zhang, S-s; Song, J-r; Li, D; Deng, W-j; Li, R; Wu, M-c; Wei, L-x

    2013-01-01

    Many reports have shown that autophagy has a role as both a promoter and inhibitor in tumor development. However, the mechanism of this paradox is unknown. Tumor development is a multistep process. Therefore, we investigated whether the role of autophagy in hepatocarcinoma formation depended on the stage of tumor development. Based on our results, autophagy inhibition by chloroquine had a tumor-promotive effect in the rat model with N-diethylnitrosamine-induced hepatocarcinogenesis in its dysplastic stage (Ds) and a tumor-suppressive effect in its tumor-forming stage (Ts). In the Ds, autophagy inhibition enhanced cell proliferation, DNA damage and inflammatory cytokines expression in liver. These changes were dependent on the upregulation of reactive oxygen species (ROS) that was resulted from autophagy inhibition, and ultimately accelerated the process of hepatocarcinogenesis. However, in the Ts, autophagy inhibition restrained tumor formation by decreasing tumor cell survival and proliferation. In this stage, autophagy inhibition led to excessive ROS accumulation in the tumor, which promoted cell apoptosis, and prominently suppressed tumor cell metabolism. Taken together, our data suggested that autophagy suppressed hepatocarcinogenesis in the Ds by protecting normal cell stability and promoted hepatocarcinogenesis in the Ts by supporting tumor cells growth. Autophagy always had a role as a protector throughout the process of hepatocarcinoma development. PMID:23429287

  5. Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients

    PubMed Central

    Fu, Tao; Liu, Yanliang; Li, Kai; Wan, Weiwei; Pappou, Emmanouil P.; Iacobuzio-Donahue, Christine A.; Kerner, Zachary; Baylin, Stephen B.; Wolfgang, Christopher L.; Ahuja, Nita

    2016-01-01

    We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP−/MLH1-U, or CIMP−/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes. PMID:27880934

  6. Tumor burden as the most important prognostic factor in early stage Hodgkin's disease. Relations to other prognostic factors and implications for choice of treatment

    SciTech Connect

    Specht, L.; Nordentoft, A.M.; Cold, S.; Clausen, N.T.; Nissen, N.I.

    1988-04-15

    Two hundred ninety patients with Hodgkin's disease pathologic stage (PS) I or II were treated in the prospective randomized trial of the Danish National Hodgkin Study with radiotherapy +/- adjuvant combination chemotherapy. The initial tumor burden of each patient was assessed, combining tumor size of each involved region and number of regions involved. Multivariate analyses of prognostic factors including treatment, tumor burden, histologic subtype, pathologic stage, number of involved regions, mediastinal size, systemic symptoms, erythrocyte sedimentation rate (ESR), sex, and age were carried out. With regard to disease-free survival tumor burden was by far the most important prognostic factor for patients treated with adjuvant chemotherapy as well as for patients treated with radiotherapy alone. With regard to survival from Hodgkin's disease only tumor burden and age were independently significant. A combination of tumor burden, histologic subtype, and sex singled out patients with a high relapse rate both after radiotherapy only, and after radiotherapy plus chemotherapy. This combination also singled out patients destined to die from Hodgkin's disease more accurately than other prognostic factors.

  7. Correlation of Positron Emission Tomography/Computed Tomography Scan with Smoking, Tumor Size, Stage and Differentiation in Head and Neck Cancer Patients

    PubMed Central

    Pleitz, Jordan L.; Sinha, Partha; Dressler, Emily V.; Aouad, Rony K.

    2017-01-01

    The goal of this study was to identify associations between positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) in patients presenting with head and neck squamous cell carcinoma (SCC) with tumor site, size, histologic differentiation, smoking, and diabetes. Charts of patients with oropharyngeal and laryngeal SCC who underwent 18F-fluorodeoxyglucose PET/CT scans were reviewed between May 2007 and August 2013. Statistical analyses included modeling log-transformed SUVmax values by tumor site, size, histologic differentiation, smoking status, and diabetes using unadjusted linear regressions. Differences were considered statistically significant for P< 0.05. A total of 111 patients (54 with oropharynx and 57 with larynx cancers) were included, 83 men and 28 women with an average age of 57.5 years old. There was a significantly higher pack-year smoking history (P = 0.005) in the larynx cancer group. While tumor T-stage was found to be significantly different (P < 0.0001), there was no difference in tumor size between the two groups: 3.16 cm and 3.58 cm in the oropharynx and larynx, respectively (P = 0.55). In the oropharynx cohort, SUVmax was associated with both tumor size (P = 0.0001) and stage (P < 0.0002). Interestingly, SUVmax differed by tumor differentiation in the larynx (P = 0.04) but not the oropharynx (P = 0.71). Finally, there was no significant difference in SUVmax relative to diabetes and smoking status. PET/CT SUVmax correlated with both tumor size and stage in oropharyngeal cancer patients, and it correlated only with tumor differentiation but not the size or stage in the larynx. There were no significant differences in SUVmax by diabetes or smoking status. PMID:28217020

  8. A Two-Stage Microfluidic Device for the Isolation and Capture of Circulating Tumor Cells

    NASA Astrophysics Data System (ADS)

    Cook, Andrew; Belsare, Sayali; Giorgio, Todd; Mu, Richard

    2014-11-01

    Analysis of circulating tumor cells (CTCs) can be critical for studying how tumors grow and metastasize, in addition to personalizing treatment for cancer patients. CTCs are rare events in blood, making it difficult to remove CTCs from the blood stream. Two microfluidic devices have been developed to separate CTCs from blood. The first is a double spiral device that focuses cells into streams, the positions of which are determined by cell diameter. The second device uses ligand-coated magnetic nanoparticles that selectively attach to CTCs. The nanoparticles then pull CTCs out of solution using a magnetic field. These two devices will be combined into a single 2-stage microfluidic device that will capture CTCs more efficiently than either device on its own. The first stage depletes the number of blood cells in the sample by size-based separation. The second stage will magnetically remove CTCs from solution for study and culturing. Thus far, size-based separation has been achieved. Research will also focus on understanding the equations that govern fluid dynamics and magnetic fields in order to determine how the manipulation of microfluidic parameters, such as dimensions and flow rate, will affect integration and optimization of the 2-stage device. NSF-CREST: Center for Physics and Chemistry of Materials. HRD-0420516; Department of Defense, Peer Reviewed Medical Research Program Award W81XWH-13-1-0397.

  9. The impact of tumor deposits on colonic adenocarcinoma AJCC TNM staging and outcome.

    PubMed

    Jin, Ming; Roth, Rachel; Rock, Jonathan B; Washington, Mary Kay; Lehman, Amy; Frankel, Wendy L

    2015-01-01

    The definition of tumor deposits (TDs) in colonic adenocarcinoma has been modified in different editions of the AJCC/TNM staging system. Studies have shown that the presence of TD is associated with advanced tumor growth and poor prognosis. Most of these data were obtained in patients with simultaneous lymph node (LN) metastases. Reports focusing on the impact of TD in patients without LN metastasis are limited. We retrospectively restaged all right-sided colonic adenocarcinomas over a 10-year period using criteria from the fifth, sixth, and seventh AJCC edition. We compared the number of tumor nodule interpreted as LN and TD in each edition and evaluated the stage migration caused by TD definition change. We then assessed clinical significance of TD in the AJCC seventh edition by comparing 5-year overall survival of N1c patients versus other N category (N0, N1, N2) patients with similar T and M status. We showed that the average number of tumor nodules interpreted as LNs per case and the number of cases with positive LNs were significantly decreased with the seventh edition compared with fifth/sixth; however, numbers of cases with TDs and <12 LNs were significantly increased with the seventh edition compared with fifth/sixth. These changes, however, resulted in minimal effects on the final stage grouping. Our survival analysis showed that N1c patients had significantly worse survival compared with N0 patients. Although not statistically significant, the hazard ratios indicated that the N1c group might have worse survival than the N1 group and better survival than the N2 group. Therefore, we conclude that TDs predict patient outcome at least similarly to positive LNs.

  10. Role of Adjuvant Radiotherapy for Stage II Thymoma After Complete Tumor Resection

    SciTech Connect

    Chen Yidong

    2010-12-01

    Purpose: To determine whether patients with Masaoka stage II thymoma benefit from adjuvant radiation therapy after complete tumor resection. Methods and Materials: A total of 107 patients with stage II thymoma who underwent complete resection of their tumors between September 1964 and October 2006 were retrospectively analyzed. Sixty-six patients were treated with adjuvant radiotherapy, and 41 patients received surgery alone. Results: Eight patients (7.5%) had a relapse of their disease, including two patients (4.5%) who had surgery alone, and 6 patients (9.5%) who had adjuvant radiation therapy. Disease-free survival rates at 5 and 10 years were 92.3% and 82.6%, respectively, for the surgery-plus-radiation group, and 97.6% and 93.1%, respectively, for the group that underwent surgery alone (p = 0.265). Disease-specific survival rates at 5 and 10 years were 96.4% and 89.3%, respectively, for the surgery-plus-radiation group and 97.5% and 97.5% for the surgery group (p = 0.973). On univariate analysis, patients with type B3 thymomas had the lowest disease-free survival rates among all subtypes (p = 0.001), and patients with large thymomas (>7 cm) had lower disease-specific survival rates than those with small tumors (<7 cm) (p = 0.017). On multivariate analysis, histological type (type B3) thymoma was a significant independent prognostic factor. Conclusions: Adjuvant radiotherapy after complete tumor resection for patients with stage II thymoma did not significantly reduce recurrence rates or improve survival rates. Histological type (type B3) thymoma was a significant independent prognostic factor. Further investigation should be carried out using a multicenter randomized or controlled study.

  11. Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up

    PubMed Central

    Rausei, Stefano; Ruspi, Laura; Galli, Federica; Pappalardo, Vincenzo; Di Rocco, Giuseppe; Martignoni, Francesco; Frattini, Francesco; Rovera, Francesca; Boni, Luigi; Dionigi, Gianlorenzo

    2016-01-01

    Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world. PMID:27678357

  12. Can Locoregional Treatment of the Primary Tumor Improve Outcomes for Women With Stage IV Breast Cancer at Diagnosis?

    SciTech Connect

    Nguyen, David H.A.; Truong, Pauline T.; Alexander, Cheryl; Walter, Caroline V.; Hayashi, Emily; Christie, Jennifer; Lesperance, Mary

    2012-09-01

    Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis. Methods and Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling. Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009). Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease

  13. Integrative Genomic Characterization and a Genomic Staging System for Gastrointestinal Stromal Tumors

    PubMed Central

    Ylipää, Antti; Hunt, Kelly K.; Yang, Jilong; Lazar, Alexander J. F.; Torres, Keila E.; Lev, Dina Chelouche; Nykter, Matti; Pollock, Raphael E.; Trent, Jonathan; Zhang, Wei

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) were historically grouped with leiomyosarcomas (LMSs) based on their morphological similarities, but recently they have been unequivocally established as a distinct type of sarcoma based on the molecular features and response to imatinib treatment. To gain further insight into the genomic differences between GISTs and LMSs, we mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated them with gene expression profiles. Our studies revealed distinct patterns of CNAs between GISTs and LMSs. Losses in chromosomes 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < 0.001), whereas losses in chromosomes 10 and 16 as well as gains in 1q, 14q, and 15q (P < 0.001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, we found several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into four groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were differently expressed in the four groups and the patients had increasingly worse prognosis as the extent of genomic alterations increased. These findings lead us to propose a new tumor-progression genetic staging system termed Genomic Instability Stage (GIS) to complement the current prognostic predictive system based on tumor size, mitotic index (MI), and KIT mutation. PMID:20818650

  14. High incidence of LRAT promoter hypermethylation in colorectal cancer correlates with tumor stage

    PubMed Central

    Pincas, Hanna; Huang, Jianmin; Zachariah, Emmanuel; Zeng, Zhaoshi; Notterman, Daniel A.; Paty, Philip; Barany, Francis

    2015-01-01

    Lecithin:retinol acyltransferase (LRAT) is a major enzyme involved in vitamin A/retinol metabolism, which regulates various physiological processes like cell proliferation and differentiation. LRAT expression is reduced in numerous cancers, yet the underlying mechanisms have remained undefined. We hypothesized that methylation silencing may contribute to decreased LRAT gene expression in colorectal cancer (CRC). LRAT hypermethylation status was analyzed in five CRC cell lines, 167 colorectal tumors, and 69 adjacent normal colonic mucosae, using a quantitative bisulfite/PCR/LDR/Universal Array assay. LRAT transcription levels were determined by real-time RT-PCR in a subset of tumors and matched normal tissues and in CRC cell lines that were treated with a demethylating agent, 5-aza-2′-deoxycytidine. The incidence of LRAT hypermethylation was significantly higher in colorectal tumors than in adjacent normal mucosae (p = 0.0025). Aberrant methylation occurred in 51 % of microsatellite-stable CRCs, in 84 % of microsatellite-unstable CRCs, and in 12 out of 13 colonic polyps. The number of hypermethylated LRAT events was inversely correlated with CRC stage (p < 0.0001). Importantly, LRAT hypermethylation was associated with decreased mRNA level in CRC clinical specimens, and demethylation treatment resulted in LRAT transcriptional reactivation. Our data support the idea that LRAT promoter hypermethylation associates with LRAT gene expression in CRC. The higher frequency of LRAT hypermethylation in colonic polyps and early-stage CRCs indicates that it may occur early in malignant progression. PMID:25260806

  15. Caveolin-1 and Accelerated Host Aging in the Breast Tumor Microenvironment

    PubMed Central

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M.; Quann, Kevin; Bryant, Kelly G.; Molchansky, Alexander; Milliman, Janet N.; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G.; Blagosklonny, Mikhail V.; Lisanti, Michael P.

    2013-01-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1+/+ versus Cav-1−/− age-matched young female mice). Mammary tumors grown in a Cav-1–deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1–deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1–deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1–deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1–deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1–deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues). PMID:22698676

  16. Intraoperative localization of early-stage gastrointestinal tumors using a marking clip detector system.

    PubMed

    Ohdaira, Takeshi; Nagai, Hideo; Shibusawa, Hiroyuki

    2005-01-01

    Intraoperative Tumor site recognition is extremely difficult during laparoscopic surgical treatment of early-stage gastrointestinal carcinoma. A novel marking method that uses both metallic clips and a marking clip detector system (MCDS, Olympus Optical Co., Tokyo, Japan) modified from a metal detector system, was designed by the authors. Metallic clips were applied to the tumor site during preoperative endoscopy, and the clip site was identified intraoperatively using the MCDS. In a basic ex vivo study, three metallic clips were detected easily (100% detection). In a clinical study, the marking site was detected in all gastric cancer patients who underwent laparoscopic subtotal gastrectomy. The mean distance between detected site and clip along the longitudinal bowel axis was 6.4 +/- 2.9 mm. Mean detection time was 18.1 +/- 5.7 seconds. None of the patients in this study experienced complications from this marking technique. MCDS allows accurate identification of tumor sites. This method may be useful for tumor-site identification during laparoscopic gastrectomy.

  17. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer

    PubMed Central

    Eruslanov, Evgeniy B.; Bhojnagarwala, Pratik S.; Quatromoni, Jon G.; Stephen, Tom Li; Ranganathan, Anjana; Deshpande, Charuhas; Akimova, Tatiana; Vachani, Anil; Litzky, Leslie; Hancock, Wayne W.; Conejo-Garcia, José R.; Feldman, Michael; Albelda, Steven M.; Singhal, Sunil

    2014-01-01

    Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of tumor-associated neutrophils (TANs) in the cancer microenvironment is largely unknown. The goal of this study was to provide a phenotypic and functional characterization of TANs in surgically resected lung cancer patients. We found that TANs constituted 5%–25% of cells isolated from the digested human lung tumors. Compared with blood neutrophils, TANs displayed an activated phenotype (CD62LloCD54hi) with a distinct repertoire of chemokine receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial quantities of the proinflammatory factors MCP-1, IL-8, MIP-1α, and IL-6, as well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and neutrophils isolated from distant nonmalignant lung tissue were able to stimulate T cell proliferation and IFN-γ release. Cross-talk between TANs and activated T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL costimulatory molecules on the neutrophil surface, which bolstered T cell proliferation in a positive-feedback loop. Together our results demonstrate that in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather stimulate T cell responses. PMID:25384214

  18. Phenotype and function of tumor-associated neutrophils and their subsets in early-stage human lung cancer.

    PubMed

    Eruslanov, Evgeniy B

    2017-03-10

    Neutrophils accumulate in many types of human and murine tumors and represent a significant portion of tumor-infiltrating myeloid cells. Our current understanding of the role of neutrophils in tumor development has depended primarily on murine models of cancer. However, there are crucial species differences in the evolution of tumors, genetic diversity, immune and inflammatory responses, and intrinsic biology of neutrophils that might have a profound impact on the tumor development and function of neutrophils in mouse versus human tumors. To date, the majority of experimental approaches to study neutrophils in cancer patients have been limited to the examination of circulating blood neutrophils. The phenotype and function of tumor-associated neutrophils (TANs) in humans, particularly in the early stages of tumor development, have not been extensively investigated. Thus, the long-term goal of our work has been to characterize human TANs and determine their specific role in tumor development. Here, we summarize our findings on human TANs obtained from human early stage lung cancer patients. We will describe the phenotypes of different TAN subsets identified in early stage lung tumors, as well as their functional dialog with T cells.

  19. Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis

    PubMed Central

    Court, Colin M; Ankeny, Jacob S; Hou, Shuang; Tseng, Hsian-Rong; Tomlinson, James S

    2016-01-01

    Pancreatic cancer (PC) is the fourth most common cause of cancer-related death in the USA, primarily due to late presentation coupled with an aggressive biology. The lack of adequate biomarkers for diagnosis and staging confound clinical decision-making and delay potentially effective therapies. Circulating tumor cells (CTCs) are a promising new biomarker in PC. Preliminary studies have demonstrated their potential clinical utility, and newer CTC isolation platforms have the potential to provide clinicians access to tumor tissue in a reliable, real-time manner. Such a ‘liquid biopsy’ has been demonstrated in several cancers, and small studies have demonstrated its potential applications in PC. This article reviews the available literature on CTCs as a biomarker in PC and presents the latest innovations in CTC research as well as their potential applications in PC. PMID:26390158

  20. Correlation of serum levo-fucose levels as a biomarker with tumor node metastasis staging in oral cancer patients

    PubMed Central

    Manchil, P. Redwin Dhas; Joy, E. Tatu; Kiran, M. Shashi; Sherubin, J. Eugenia; Khan, M. Farakath; Aravind, B. S.

    2016-01-01

    Background: oral cancer is a result of disordered cellular behavior initiated by various stimuli which is characterized by the alteration of serum glycoproteins consisting of different monosaccharides. One of these is levo-fucose (L-fucose), a methyl pentose. Elevated levels of protein-bound fucose have been reported in various malignancies. Aim: The present study attempted to correlate levels of serum L-fucose as a biomarker with the various tumor node metastasis (TNM) stages of oral cancer. Methodology: The study was carried out on 90 subjects consisting of 30 healthy controls and 60 histopathologically proven oral squamous cell carcinoma (OSCC) cases. The serum fucose level estimation was done based on the method adopted by Winzler. Statistical analysis included independent sample's t-test, one-way ANOVA test, Karl–Pearson correlation test, and Tukey's HSD post hoc test to evaluate the significance and variability of values between groups. Results: Significant elevation in serum fucose levels was noticed among OSCC patients when compared with the controls and a progressive ascent of L-fucose levels were noted as the stage of severity increased. Serum fucose levels were independent of histopathological grading, age, and sex. Conclusion: Serum L-fucose levels were increased in OSCC patients, and a positive correlation was observed between serum L-fucose levels and TNM staging of OSCC. Thus, serum L-fucose can be used as an effective diagnostic and prognostic biomarker in OSCC patients. PMID:27829767

  1. SU-E-J-269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

    SciTech Connect

    Kang, K; Biswas, T; Podder, T

    2015-06-15

    Purpose: This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT. Methods: Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volume (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients. Results: A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week-1 and week-2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p-value > 0.05). Conclusion: Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co-relation between tumor volume reduction and treatment outcome.

  2. Breast Cancer/Stromal Cells Coculture on Polyelectrolyte Films Emulates Tumor Stages and miRNA Profiles of Clinical Samples.

    PubMed

    Daverey, Amita; Brown, Karleen M; Kidambi, Srivatsan

    2015-09-15

    In this study, we demonstrate a method for controlling breast cancer cells adhesion on polyelectrolyte multilayer (PEM) films without the aid of adhesive proteins/ligands to study the role of tumor and stromal cell interaction on cancer biology. Numerous studies have explored engineering coculture of tumor and stromal cells predominantly using transwell coculture of stromal cells cultured onto coverslips that were subsequently added to tumor cell cultures. However, these systems imposed an artificial boundary that precluded cell-cell interactions. To our knowledge, this is the first demonstration of patterned coculture of tumor cells and stromal cells that captures the temporal changes in the miRNA signature as the breast tumor develops through various stages. In our study we used synthetic polymers, namely poly(diallyldimethylammonium chloride) (PDAC) and sulfonated poly(styrene) (SPS), as the polycation and polyanion, respectively, to build PEMs. Breast cancer cells attached and spread preferentially on SPS surfaces while stromal cells attached to both SPS and PDAC surfaces. SPS patterns were formed on PEM surfaces, by either capillary force lithography (CFL) of SPS onto PDAC surfaces or vice versa, to obtain patterns of breast cancer cells and patterned cocultures of breast cancer and stromal cells. In this study, we utilized cancer cells derived from two different tumor stages and two different stromal cells to effectively model a heterogeneous tumor microenvironment and emulate various tumor stages. The coculture model mimics the proliferative index (Ki67 expression) and tumor aggressiveness (HER-2 expression) akin to those observed in clinical tumor samples. We also demonstrated that our patterned coculture model captures the temporal changes in the miRNA-21 and miRNA-34 signature as the breast tumor develops through various stages. The engineered coculture platform lays groundwork toward precision medicine wherein patient-derived tumor cells can be

  3. Comparison of Survival Rates, Tumor Stages, and Localization in between Obese and Nonobese Patients with Gastric Cancer

    PubMed Central

    Dogan, Hakan; Oguz, Basak; Ocak Serin, Sibel; Okuturlar, Yildiz; Gunaldi, Meral; Erismis, Betul; Ozdemir, Bahar; Tural, Deniz; Hursitoglu, Mehmet; Harmankaya, Ozlem; Kumbasar, Abdulbaki

    2016-01-01

    Purpose. In this study we tried to determine the association between body-mass index (BMI), survival rate, and the stage of tumor at the time of diagnosis in patients with gastric cancer. Methods. A total of 270 gastric cancer patients' hospital records were retrospectively evaluated. Patients were grouped according to their BMI at the time of tumor diagnosis. Tumor stages at admission were compared according to their BMI values. Results. There were no differences in OS among BMI subgroups (p = 0.230). The percent of patients with stage III tumor was significantly higher in nonobese while the percent of stage IV tumor was surprisingly higher in obese patients (p was 0.011 and 0.004, resp.). Percent of patients who did not have any surgical intervention was significantly lower in overweight and obese patients than normal and/or underweight patients. Conclusions. At the time of diagnosis, obese patients had significantly higher percent of stage IV tumor than nonobese patients. Despite of that, there were no differences in survival rates among BMI subgroups. Our study results are consistent with “obesity paradox” in gastric cancer patients. We also did not find any relationship between BMI and localization of gastric tumor. PMID:27418926

  4. Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer Patients by Targeted Sequencing

    PubMed Central

    Chen, Ke-Zhong; Lou, Feng; Yang, Fan; Zhang, Jing-Bo; Ye, Hua; Chen, Wei; Guan, Tian; Zhao, Ming-Yu; Su, Xue-Xia; Shi, Rong; Jones, Lindsey; Huang, Xue F.; Chen, Si-Yi; Wang, Jun

    2016-01-01

    Circulating tumor DNA (ctDNA) isolated from peripheral blood has recently been shown to be an alternative source to detect gene mutations in primary tumors; however, most previous studies have focused on advanced stage cancers, and few have evaluated ctDNA detection in early-stage lung cancer. In the present study, blood and tumor samples were collected prospectively from 58 early-stage non-small lung cancer (NSCLC) patients (stages IA, IB, and IIA) and a targeted sequencing approach was used to detect somatic driver mutations in matched tumor DNA (tDNA) and plasma ctDNA. We identified frequent driver mutations in plasma ctDNA and tDNA in EGFR, KRAS, PIK3CA, and TP53, and less frequent mutations in other genes, with an overall study concordance of 50.4% and sensitivity and specificity of 53.8% and 47.3%, respectively. Cell-free (cfDNA) concentrations were found to be significantly associated with some clinical features, including tumor stage and subtype. Importantly, the presence of cfDNA had a higher positive predictive value than that of currently used protein tumor biomarkers. This study demonstrates the feasibility of identifying plasma ctDNA mutations in the earliest stage lung cancer patients via targeted sequencing, demonstrating a potential utility of targeted sequencing of ctDNA in the clinical management of NSCLC. PMID:27555497

  5. Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

    PubMed Central

    Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

    2015-01-01

    Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

  6. Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy

    SciTech Connect

    Calais, G.; Le Floch, O.; Chauvet, B.; Reynaud-Bougnoux, A.; Bougnoux, P. )

    1989-12-01

    In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.

  7. "Life Stage-Specific" Variations in Performance in Response to Age Stereotypes

    ERIC Educational Resources Information Center

    Hehman, Jessica A.; Bugental, Daphne Blunt

    2013-01-01

    In a test of life stage-specific responses to age-based stigma, older (n = 54, ages 62-92) and younger (n = 81, ages 17-22) adults were told that a task (Weschler Adult Intelligence Scale-III block design) required either (a) speed/contemporary knowledge (YA; "youth advantage") or (b) life experience/wisdom (OA; "age…

  8. Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients

    PubMed Central

    Zheng, Xiao; Shi, Liangrong; Wu, Changping; Jiang, Jingting

    2016-01-01

    The detailed understanding of the immunobiology of tumor microenvironment has recently translated into new therapeutic approach against human cancers. Besides the role of immune cells mediating adaptive immune responses, the tumor infiltrating components of the innate immune system including, neutrophils, mast cells, NK cells, and macrophages, also role importantly in anti-tumor immunity. In our present study, we retrospectively analyzed the prognostic value of the densities of tumor infiltrating NK cells and macrophages in esophageal cancer tissues derived from stage II+III patients. Our results showed that the density of the infiltrating NK cells in tumor stroma was significantly associated with nodal status. In addition, the densities of the infiltrating NK cells in tumor nest, and the infiltrating macrophages in tumor nest as well as in tumor stroma, were significantly associated with patients' postoperative prognoses. Furthermore, the combination of infiltrating NK cells in tumor nest and stroma, or the combination of infiltrating macrophages in tumor nest and stroma, could also be used as important prognostic tool in predicting the survival of the stage II+III esophageal cancer patients. PMID:27736796

  9. Targeted labeling of an early-stage tumor spheroid in a chorioallantoic membrane model with upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Kai; Holz, Jasmin A.; Ding, Yadan; Liu, Xiaomin; Zhang, Youlin; Tu, Langping; Kong, Xianggui; Priem, Bram; Nadort, Annemarie; Lambrechts, Saskia A. G.; Aalders, Maurice C. G.; Buma, Wybren Jan; Liu, Yichun; Zhang, Hong

    2015-01-01

    In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb).In vivo detection of cancer at an early-stage, i.e. smaller than 2 mm, is a challenge in biomedicine. In this work target labeling of an early-stage tumor spheroid (~500 μm) is realized for the first time in a chick embryo chorioallantoic membrane (CAM) model with monoclonal antibody functionalized upconversion nanoparticles (UCNPs-mAb). Electronic supplementary information (ESI) available: Details of experimental procedures for the sample preparation and characterization, Chick CAM model, 3-D multicellular tumor spheroids, UCNPs circulating in CAM. See DOI: 10.1039/c4nr05638h

  10. [Predictive value of Ages & Stages Questionnaires for cognitive performance at early years of schooling].

    PubMed

    Schonhaut B, Luisa; Pérez R, Marcela; Castilla F, Ana María; Castro M, Sonia; Salinas A, Patricia; Armijo R, Iván

    2017-02-01

    The Ages and Stages questionnaires (ASQ) has been recently validated in our country for developmental screening. The objective of this study is evaluate the validity of ASQ to predict low cognitive performance in the early years of schooling.

  11. Two-stage microfluidic chip for selective isolation of circulating tumor cells (CTCs).

    PubMed

    Hyun, Kyung-A; Lee, Tae Yoon; Lee, Su Hyun; Jung, Hyo-Il

    2015-05-15

    Over the past few decades, circulating tumor cells (CTCs) have been studied as a means of overcoming cancer. However, the rarity and heterogeneity of CTCs have been the most significant hurdles in CTC research. Many techniques for CTC isolation have been developed and can be classified into positive enrichment (i.e., specifically isolating target cells using cell size, surface protein expression, and so on) and negative enrichment (i.e., specifically eluting non-target cells). Positive enrichment methods lead to high purity, but could be biased by their selection criteria, while the negative enrichment methods have relatively low purity, but can isolate heterogeneous CTCs. To compensate for the known disadvantages of the positive and negative enrichments, in this study we introduced a two-stage microfluidic chip. The first stage involves a microfluidic magnetic activated cell sorting (μ-MACS) chip to elute white blood cells (WBCs). The second stage involves a geometrically activated surface interaction (GASI) chip for the selective isolation of CTCs. We observed up to 763-fold enrichment in cancer cells spiked into 5 mL of blood sample using the μ-MACS chip at 400 μL/min flow rate. Cancer cells were successfully separated with separation efficiencies ranging from 10.19% to 22.91% based on their EpCAM or HER2 surface protein expression using the GASI chip at a 100 μL/min flow rate. Our two-stage microfluidic chips not only isolated CTCs from blood cells, but also classified heterogeneous CTCs based on their characteristics. Therefore, our chips can contribute to research on CTC heterogeneity of CTCs, and, by extension, personalized cancer treatment.

  12. Studies on the mechanism of skin tumor promotion: Evidence for several stages in promotion

    PubMed Central

    Slaga, T. J.; Fischer, S. M.; Nelson, K.; Gleason, G. L.

    1980-01-01

    The effects of nonpromoting and weakly promoting diterpenes on skin tumor promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) were investigated. When phorbol and phorbol 12,13-diacetate (both nonpromoting) were given simultaneously with TPA after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female mice, they had no effect on TPA promotion. However, the nonpromoter 4-O-methyl-TPA and the weak promoter mezerein were found to inhibit TPA promotion in a dose-dependent manner when given simultaneously with TPA. Because mezerein was found to be an effective inhibitor of TPA promotion when given simultaneously and because it induces many biological responses similar to those to TPA, the capacity of mezerein to act as an incomplete promoter in a two-stage promotion protocol was also investigated. Twice-weekly applications of 1,2, or 5 μg of TPA for 2 weeks after DMBA initiation produced 0, 0, and 0.5 papilloma per mouse, respectively, at 20 weeks. When the twice-weekly applications of TPA for 2 weeks were followed by twice-weekly treatments with 2 μg of mezerein for 18 weeks, the number of papillomas per mouse was 2.2, 3.5, and 9.0, respectively. Twice-weekly applications of 2 μg of TPA for 2 weeks followed by twice-weekly treatments with 1, 2, or 4 μg of mezerein for 18 weeks produced 2.1, 3.5, and 6.8 papillomas per mouse, respectively, in DMBA-treated mice. Twice-weekly doses as high as 40 μg of 4-O-methyl-TPA were not effective in producing tumors when given after a limited treatment with TPA; however, 4-O-methyl-TPA had weak activity as a first-stage promoter. The results suggest that although mezerein by itself is a weak promoter and mimics TPA in many biochemical and morphological effects it is a potent second-stage promoter in a two-stage promotion regimen. PMID:6774342

  13. [Central venous catheterization by using ultrasound guidance to patients with terminal stage malignant tumors].

    PubMed

    Yamamoto, Masato; Ono, Akiko; Moriguchi, Kazuko; Kanemoto, Kazuo

    2008-11-01

    Central venous catheterization with ultrasound guidance was performed on 41 patients with terminal stage malignant tumors--112 consecutive insertions at our hospital. We performed a total of 112 consecutive insertions: 30 with the skin marking method and 82 with the real time echo guidance method. Catheter insertion was performed to the internal jugular vein in 24, the supra-clavicular approach of the subclavian vein in 4, the infra-clavicular approach of the subclavian vein in 37 and the femoral vein in 47. The success rate was 85.7% (96/112 insertions), and the mean insertion time was 2.2 minutes. The complication rate was 4.5%: arterial puncture for 3 insertions, and mal-position for 2 insertions. In this examination, it was confirmed that central venous catheterization with ultrasound guidance could be performed safely and briefly in such patients.

  14. Primary stage of photodestruction of malignant cells under photodynamic therapy of tumors

    NASA Astrophysics Data System (ADS)

    Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Tretjakova, Antonina I.

    1996-01-01

    In this work we present the experimental results indicating that under photodynamic therapy the primary stage of the photodestruction of malignant cells is based on the irreversible photodestruction of glycolysis enzymes located, first of all, in mitochondria playing a key role in the energy supply for the tumor cells. It was shown that the formation of complexes between glycolysis enzymes and a sensitizer promotes an effective destruction of the formers. The formation of strong complexes was demonstrated for a number of glycolysis enzymes (glyceraldehyde-2-phosphate dehydrogenase, pyruvate kinase, lactate dehydrogenase) with the use of water-soluble pigments chlorin e6 and tetra(carboxyphenyl)porphyrin (T(CP)P) as sensitizers. The direct correlation was shown between the effectiveness of the photodestruction of enzyme molecules and the enzyme-sensitizer binding constant.

  15. The pursuit of a cholesteatoma by harvey cushing: staged approach to a complex skull base tumor.

    PubMed

    Malekpour, Mahdi; Cohen-Gadol, Aaron A

    2014-10-01

    Objective The evolution of neurosurgical techniques during Harvey Cushing's practice was immense. The authors illustrate this evolution using archived historical records from Harvey Cushing. Setting Historical patient records retained by the Cushing Center at Yale University Department of Neurosurgery. Design The authors present the case of one of Cushing's patients with a cholesteatoma. Results Cushing's surgical treatment of a cholesteatoma extending into the skull base is an example of his meticulous documentation and accelerated surgical techniques. Conclusions This case demonstrates how neurosurgical techniques advanced in the management of complex skull base tumors via a staged approach through the middle and posterior fossae at a time long before the development of modern skull base surgery.

  16. Studies on mechanism of action of anti-tumor-promoting agents: their specificity in two-stage promotion.

    PubMed Central

    Slaga, T J; Klein-Szanto, A J; Fischer, S M; Weeks, C E; Nelson, K; Major, S

    1980-01-01

    The effects of fluocinolone acetonide (FA), retinoic acid (RA), and tosylphenylalanine chloromethyl ketone (TPCK) on two-stage promotion after 7,12-dimethylbenz[a]-anthracene (DMBA) initiation in female Sencar mice were investigated. The two-stage promotion protocol was achieved by twice weekly applications of 2 microgram of 12-O-tetradecanoylphorbol 13-acetate (TPA) for 2 weeks (stage I) followed by twice weekly applications of mezerein for 18 weeks (stage II). Separately stage I and II do not cause any tumors to develop after DMBA initiation. FA was found to be a potent inhibitor of stages I and II but to a greater degree for stage I than for stage II. RA was ineffective in stage I but was a potent inhibitor of stage II; TPCK specifically inhibited stage I but not stage II. FA and TPCK effectively counteract the appearance of the dark basal keratinocytes, whereas RA has no effect. These results provide additional evidence for the importance of dark basal keratinocytes in stage I of promotion and indicate that most of the other biochemical and morphological responses normally associated with promotion (such as polyamines) are actually associated with stage II of promotion. PMID:6769125

  17. Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

    SciTech Connect

    Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Munoz, L.; Tutschka, P.J.; Santos, G.W.; Elfenbein, G.J.; Order, S.E.

    1980-02-01

    Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologous marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.

  18. The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma.

    PubMed

    Jakovic, Ljubomir R; Mihaljevic, Biljana S; Perunicic Jovanovic, Maja D; Bogdanovic, Andrija D; Andjelic, Bosko M; Bumbasirevic, Vladimir Z

    2011-10-01

    Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.

  19. Heterogeneity of Disease Classified as Stage III in Wilms Tumor: A Report From the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)

    SciTech Connect

    Spreafico, Filippo; Gandola, Lorenza; Terenziani, Monica; Collini, Paola; Bianchi, Maurizio; Provenzi, Massimo; Indolfi, Paolo; Pession, Andrea; Nantron, Marilina; Di Cataldo, Andrea; Marchiano, Alfonso; Piva, Luigi

    2012-01-01

    Purpose: We analyzed whether the prognosis can differ among Wilms tumors (WT) labeled as Stage III according to currently adopted classification systems. Methods and Materials: Patients with nonanaplastic Stage III WT consecutively registered in two Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) trials (CNR-92, TW-2003) were the subjects in the present analysis. The steady mainstay of therapy was primary nephrectomy, followed by three-drug chemotherapy with vincristine, dactinomycin, doxorubicin, and abdominal radiotherapy (RT). Results: Ninety-nine WT patients met the criteria for classification as Stage III according to a revised version of the National Wilms Tumor Study-3 staging system (51 patients in CNR-92, 48 patients in TW-2003). Regional lymph nodes (LN) were not biopsied in 16 patients. After a median follow-up of 66 months, the 4-year disease-free survival (DFS) and overall survival (OS) rates were 85% {+-} 4% and 92% {+-} 3%, respectively, for the whole group. For 38 children with positive LN, the 4-year DFS rate was 73% {+-} 7%, as opposed to 98% {+-} 2% for the 45 children with Stage III WT according to the other criteria but with negative biopsied LN (p = 0.001). The subgroup with the worst prognosis consisted of children more than 2 years old with positive LN (DFS 67% {+-} 8%). A delay between surgery and RT > 30 days had an adverse impact on the abdominal tumor relapse rate. Conclusions: This study provides further evidence that Stage III tumors with LN metastases might be distinguished from WTs meeting the other criteria for classification as Stage III. The worse outcome of the former may warrant a prospective study on the effects of intensified therapy. A subclassification of Stage III tumors is discussed.

  20. Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies

    PubMed Central

    Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

    2016-01-01

    Background Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. Methods PubMed, Cochrane’s Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Results Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55–1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Conclusion Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors. PMID:27524907

  1. Age, Tumor Characteristics, and Treatment Regimen as Event Predictors in Ewing: A Children's Oncology Group Report

    PubMed Central

    Marina, Neyssa; Granowetter, Linda; Grier, Holcombe E.; Womer, Richard B.; Randall, R. Lor; Marcus, Karen J.; McIlvaine, Elizabeth; Krailo, Mark

    2015-01-01

    Purpose. To associate baseline patient characteristics and relapse across consecutive COG studies. Methods. We analyzed risk factors for LESFT patients in three randomized COG trials. We evaluated age at enrollment, primary site, gender, tumor size, and treatment (as randomized). We estimated event-free survival (EFS, Kaplan-Meier) and compared risk across groups (log-rank test). Characteristics were assessed by proportional hazards regression with the characteristic of interest as the only component. Confidence intervals (CI) for RR were derived. Factors related to outcome at level 0.05 were included in a multivariate regression model. Results. Between 12/1988 and 8/2005, 1444 patients were enrolled and data current to 2001, 2004, or 2008 were used. Patients were with a median age of 12 years (0–45), 55% male and 88% Caucasian. The 5-year EFS was 68.3% ± 1.3%. In univariate analysis age, treatment, and tumor location were identified for inclusion in the multivariate model, and all remained significant (p < 0.01). Since tumor size was not collected in the last study, the other two were reanalyzed. This model identified age, treatment, tumor location, and tumor size as significant predictors. Conclusion. Age > 18 years, pelvic tumor, size > 8 cms, and chemotherapy without ifosfamide/etoposide significantly predict worse outcome. AEWS0031 is NCT00006734, INT0091 and INT0054 designed before 1993 (unregistered). PMID:26508901

  2. Assessing the effects of metabolism of environmental agents on cancer tumor development by a two-stage model of carcinogenesis.

    PubMed Central

    Tan, W Y; Singh, K P

    1987-01-01

    By combining the Michaelis-Menten kinetics of metabolism with the two-stage model of Moolgavkar and Knudson (1981) and the extended two-stage model of carcinogenesis proposed by Tan and Gastardo (1985), this paper proceeds to investigate the effects of metabolism of carcinogens on cancer tumor development. It is shown that the nonlinear kinetics of metabolism of carcinogens affect the dose-response relationship mainly through the mutation rates. If the initiator is affected by metabolism, then the metabolism of promoters has very little or negligible effects of the expected incidences and the number of tumors. PMID:3691427

  3. A transition in transcriptional activation by the glucocorticoid and retinoic acid receptors at the tumor stage of dermal fibrosarcoma development.

    PubMed Central

    Vivanco, M D; Johnson, R; Galante, P E; Hanahan, D; Yamamoto, K R

    1995-01-01

    In transgenic mice harboring the bovine papillomavirus genome, fibrosarcomas arise along an experimentally accessible pathway in which normal dermal fibroblasts progress through two pre-neoplastic stages, mild and aggressive fibromatosis, followed by a final transition to the tumor stage. We found that the glucocorticoid receptor (GR) displays only modest transcriptional regulatory activity in cells derived from the three non-tumor stages, whereas it is highly active in fibrosarcoma cells. Upon inoculation into mice, the aggressive fibromatosis cells progress to tumor cells that have high GR activity; thus, the increased transcriptional regulatory activity of GR correlates with the cellular transition to the tumor stage. The intracellular levels of GR, as well as its hormone-dependent nuclear translocation and specific DNA binding activities, are unaltered throughout the progression. Strikingly, the low GR activity observed in the pre-neoplastic stages cannot be overcome by exogenous GR introduced by co-transfection. Moreover, comparisons of primary embryo fibroblasts and their transformed derivatives revealed a similar pattern--modest GR activity, unresponsive to overexpressed GR protein, in the normal cells was strongly increased in the transformed cells. Likewise, the retinoic acid receptor (RAR) displayed similar differential activity in the fibrosarcoma pathway. Thus, the oncogenic transformation of fibroblasts, and likely other cell types, is accompanied by a striking increase in the activities of transcriptional regulators such as GR and RAR. We suggest that normal primary cells have a heretofore unrecognized capability to limit the magnitude of induction of gene expression. Images PMID:7774580

  4. Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis

    PubMed Central

    McLeod, Donald S.A.; Jonklaas, Jacqueline; Brierley, James D.; Ain, Kenneth B.; Cooper, David S.; Fein, Henry G.; Haugen, Bryan R.; Ladenson, Paul W.; Magner, James; Ross, Douglas S.; Skarulis, Monica C.; Steward, David L.; Xing, Mingzhao; Litofsky, Danielle R.; Maxon, Harry R.

    2015-01-01

    Background: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. Objective: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. Methods: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R2). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. Results: The best five alternate papillary cancer systems had age cut-points of 45–50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50–55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003–0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). Conclusions: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation. PMID:26203804

  5. StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

    PubMed

    Sen, Manimala; Katragadda, Shanmukh; Ravichandran, Aarthi; Deshpande, Gouri; Parulekar, Minothi; Nayanala, Swetha; Vittal, Vikram; Shen, Weiming; Phooi Nee Yong, Melanie; Jacob, Jemima; Parchuru, Sravanthi; Dhanuskodi, Kalpana; Eyring, Kenneth; Agrawal, Pooja; Agarwal, Smita; Shanmugam, Ashwini; Gupta, Satish; Vishwanath, Divya; Kumari, Kiran; Hariharan, Arun K; Balaji, Sai A; Liang, Qiaoling; Robolledo, Belen; Gauribidanur Raghavendrachar, Vijayashree; Oomer Farooque, Mohammed; Buresh, Cary J; Ramamoorthy, Preveen; Bahadur, Urvashi; Subramanian, Kalyanasundaram; Hariharan, Ramesh; Veeramachaneni, Vamsi; Sankaran, Satish; Gupta, Vaijayanti

    2017-04-03

    Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages.

  6. The Tumor-Log Odds of Positive Lymph Nodes-Metastasis Staging System, a Promising New Staging System for Gastric Cancer after D2 Resection in China

    PubMed Central

    Wang, Zhi-qiang; Ren, Chao; Wang, De-shen; Zhang, Dong-sheng; Luo, Hui-yan; Li, Yu-hong; Xu, Rui-hua

    2012-01-01

    Background In this study, we established a hypothetical tumor-lodds-metastasis (TLM) and tumor-ratio-metastasis (TRM) staging system. Moreover, we compared them with the 7th edition of American Joint Committee on Cancer tumor-nodes-metastasis (AJCC TNM) staging system in gastric cancer patients after D2 resection. Methods A total of 1000 gastric carcinoma patients receiving treatment in our center were selected for the analysis. Finally, 730 patients who received D2 resection were retrospectively studied. Patients were staged using the TLM, TRM and the 7th edition AJCC TNM system. Survival analysis was performed with a Cox regression model. We used two parameters to compare the TNM, TRM and TLM staging system, the −2log likelihood and the hazard ratio. Results The cut points of lymph node ratio (LNR) were set as 0, 0–0.3, 0.3–0.6, 0.6–1.0. And for the log odds of positive lymph nodes (LODDS), the cut points were established as≤−0.5, −0.5-0, 0-0.5, >0.5. There were significant differences in survival among patients in different LODDS classifications for each pN or LNR groups. When stratified by the LODDS classifications, the prognosis was highly homologous between those in the according pN or LNR classifications. Multivariate analysis showed that TLM staging system was better than the TRM or TNM system for the prognostic evaluation. Conclusions The TLM system was superior to the TRM or TNM system for prognostic assessment of gastric adenocarcinoma patients after D2 resection. PMID:22348125

  7. Incorporation of perineural invasion of gastric carcinoma into the 7th edition tumor-node-metastasis staging system.

    PubMed

    Jiang, Nan; Deng, Jing-Yu; Liu, Yong; Ke, Bin; Liu, Hong-Gen; Liang, Han

    2014-09-01

    The aim of this study was to determine the prognostic value of perineural invasion (PNI) in patients with gastric cancer who underwent curative resection. We retrospectively analyzed 518 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. Patients with PNI had a significantly larger tumors (≥5.0 cm), lymphatic venous invasion (positive), deeper tumor invasion (T4), more number of lymph node metastases (N3), and higher tumor stage (III). Regarding survival, multivariate analysis showed that PNI emerged as an independent prognostic factor for survival (hazard ratio (HR) = 1.901, P < 0.001). We incorporated the PNI into the 7th edition tumor-node-metastasis (TNM) staging system. Comparing with the 7th edition staging system, the redefinition of TPNI stage had higher -2loglikelihood value (-2loglikelihood = 3,492.259) and lower HR and 95 % confidence interval (CI) (HR = 1.955, 95 % CI = 1.630-2.343); redefinition of NPNI and TNMIIIPNI stage both had lower -2loglikelihood value (-2loglikelihood = 3,306.608; -2loglikelihood = 2,535.151) and higher HR and 95 % CI (HR = 1.879, 95 % CI = 1.720-2.053; HR = 2.268, 95 % CI = 1.900-2.707), which represented the optimum prognostic stratification, together with better homogeneity, discriminatory ability. Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer and it should be incorporated into TNM staging.

  8. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    PubMed Central

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    ABSTRACT Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with tumor-associated antigens (TAA) gp100 and tyrosinase after radical lymph node dissection. Skin-test infiltrating lymphocytes (SKILs) obtained from delayed-type hypersensitivity skin-test biopsies were analyzed for the presence of TAA-specific CD8+ T cells by tetrameric MHC-peptide complexes and by functional TAA-specific T cell assays, defined by peptide-recognition (T2 cells) and/or tumor-recognition (BLM and/or MEL624) with specific production of Th1 cytokines and no Th2 cytokines. Results: Ninety-seven patients were analyzed: 21 with stage IIIA, 34 with stage IIIB, and 42 had stage IIIC disease. Tetramer-positive CD8+ T cells were present in 68 patients (70%), and 24 of them showed a response against all 3 epitopes tested (gp100:154–162, gp100:280–288, and tyrosinase:369–377) at any point during vaccinations. A functional T cell response was found in 62 patients (64%). Rates of peptide-recognition of gp100:154–162, gp100:280–288, and tyrosinase:369–377 were 40%, 29%, and 45%, respectively. Median recurrence-free survival and distant metastasis-free survival of the whole study population were 23.0 mo and 36.8 mo, respectively. Conclusions: DC vaccination induces a functional TAA-specific T cell response in the majority of stage III melanoma patients, indicating it is more effective in stage III than in stage IV melanoma patients. Furthermore, performing multiple cycles of vaccinations enhances the chance of a broader immune response. PMID:27622047

  9. The Relationship among Pubertal Stage, Age, and Drinking in Adolescent Boys and Girls

    ERIC Educational Resources Information Center

    Faden, Vivian B.; Ruffin, Beverly; Newes-Adeyi, Gabriella; Chen, Chiung

    2010-01-01

    This study used data from the Third National Household and Nutrition Examination Survey (NHANES) to examine the association between pubertal status (Tanner staging for boys and girls and menarche for girls) and alcohol use in a nationally representative sample of youths ages 12 to 17. Logistic regression was used to model the relationship. In…

  10. Minuteman Stage III Operational Surveillance Program Seven-Year Testing Bondline Aging Study,

    DTIC Science & Technology

    1985-12-01

    Liner Gel Fraction at Various Motor Locations ......... . . 25 14 Liner Moisture at Various Motor Locations ............. ... 26 6 15 Motor TC 30005 ...PageI ,,. 18 Shore A Hardness Gradient of ANB-3066 Propellant at the Forward Equator ........ ...................... .. 30 19 Motor TC 30005 ...75 I 2 Matrix for Minuteman Stage III Bondline Aging Program ........ 76 3 Motor TC 30005 Material Properties Data, Forward

  11. Developmental Screening Using the Ages and Stages Questionnaire: Standardized versus Real-World Conditions

    ERIC Educational Resources Information Center

    San Antonio, Marianne C.; Fenick, Ada M.; Shabanova, Veronika; Leventhal, John M.; Weitzman, Carol C.

    2014-01-01

    Developmental screens are often used in nonstandardized conditions, such as pediatric waiting rooms, despite validation under standardized conditions. We examined the reproducibility of the Ages and Stages Questionnaire (ASQ), a developmental screening instrument commonly used in pediatric practices, under standardized versus nonstandardized…

  12. Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

    PubMed Central

    Sanoff, Hanna K.; Stitzenberg, Karyn B.; Baron, John A.; Lund, Jennifer L.; Sandler, Robert S.

    2017-01-01

    Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute's Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n = 6, 862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50–69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50–69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years. PMID:28239395

  13. From stage to age in variable environments: life expectancy and survivorship.

    PubMed

    Tuljapurkar, Shripad; Horvitz, Carol C

    2006-06-01

    Stage-based demographic data are now available on many species of plants and some animals, and they often display temporal and spatial variability. We provide exact formulas to compute age-specific life expectancy and survivorship from stage-based data for three models of temporal variability: cycles, serially independent random variation, and a Markov chain. These models provide a comprehensive description of patterns of temporal variation. Our formulas describe the effects of cohort (birth) environmental condition on mortality at all ages, and of the effects on survivorship of environmental variability experienced over the course of life. This paper complements existing methods for time-invariant stage-based data, and adds to the information on population growth and dynamics available from stochastic demography.

  14. Contribution of diffusion weighted MRI to diagnosis and staging in gastric tumors and comparison with multi-detector computed tomography

    PubMed Central

    Fatih Özbay, Mehmet; Çallı, İskan; Doğan, Erkan; Çelik, Sebahattin; Batur, Abdussamet; Bora, Aydın; Yavuz, Alpaslan; Bulut, Mehmet Deniz; Özgökçe, Mesut; Çetin Kotan, Mehmet

    2017-01-01

    Abstract Background Diagnostic performance of Diffusion-Weighted magnetic resonance Imaging (DWI) and Multi-Detector Computed Tomography (MDCT) for TNM (Tumor, Lymph node, Metastasis) staging of gastric cancer was compared. Patients and methods We used axial T2-weighted images and DWI (b-0,400 and b-800 s/mm2) protocol on 51 pre-operative patients who had been diagnosed with gastric cancer. We also conducted MDCT examinations on them. We looked for a signal increase in the series of DWI images. The depth of tumor invasion in the stomach wall (tumor (T) staging), the involvement of lymph nodes (nodal (N) staging), and the presence or absence of metastases (metastatic staging) in DWI and CT images according to the TNM staging system were evaluated. In each diagnosis of the tumors, sensitivity, specificity, positive and negative accuracy rates of DWI and MDCT examinations were found through a comparison with the results of the surgical pathology, which is the gold standard method. In addition to the compatibilities of each examination with surgical pathology, kappa statistics were used. Results Sensitivity and specificity of DWI and MDCT in lymph node staging were as follows: N1: DWI: 75.0%, 84.6%; MDCT: 66.7%, 82%;N2: DWI: 79.3%, 77.3%; MDCT: 69.0%, 68.2%; N3: DWI: 60.0%, 97.6%; MDCT: 50.0%, 90.2%. The diagnostic tool DWI seemed more compatible with the gold standard method (surgical pathology), especially in the staging of lymph node, when compared to MDCT. On the other hand, in T staging, the results of DWI and MDCT were better than the gold standard when the T stage increased. However, DWI did not demonstrate superiority to MDCT. The sensitivity and specificity of both imaging techniques for detecting distant metastasis were 100%. Conclusions The diagnostic accuracy of DWI for TNM staging in gastric cancer before surgery is at a comparable level with MDCT and adding DWI to routine protocol of evaluating lymph nodes metastasis might increase diagnostic accuracy

  15. Age-stage, two-sex life table of Parapoynx crisonalis (Lepidoptera: Pyralidae) at different temperatures.

    PubMed

    Chen, Qi; Li, Ni; Wang, Xing; Ma, Li; Huang, Jian-Bin; Huang, Guo-Hua

    2017-01-01

    Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage-specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C.

  16. Cancer biology for individualized therapy: Correlation of growth fraction index in native-state histoculture with tumor grade and stage

    SciTech Connect

    Vescio, R.A.; Connors, K.M. ); Youngkin, T. ); Bordin, G.M.; Robb, J.A. ); Umbreit, J.N. ); Hoffman, R.M. Univ. of California, San Diego )

    1990-01-01

    There is a need for individualization of all aspects of cancer therapy. Because of significant heterogeneity within a tumor class, there is a need to develop an in vitro test to accurately gauge tumor aggressiveness. Current methodologies such as flow cytometry, which lacks unambiguous interpretation of cell-proliferative data, and determination of the thymidine-labeling index, which measures nucleotide uptake in a nonphysiological state, have not reproducibly attained this goal. The authors have developed an in vitro native-state three-dimensional gel-supported histoculture system that allows the growth of all human solid tumor types for relatively long time periods. The native-state system was used to identify the percent of cells capable of incorporating ({sup 3}H)thymidine over a 4-day period, which we term the growth fraction index (GFI). They have compared the ability of cancer tissue to proliferate in native-state culture to the stage and histological grade of four major types of human carcinomas: breast, ovarian, colon, and lung. Eighty percent of tumor explants could be evaluated, even when sent from across the country. They have determined that the GFI correlates with tumor stage and grade for breast and ovarian carcinoma. These results suggest the applicability of gel-supported three-dimensional native-state histoculture for prognostic purpose in patients with breast and ovarian cancers and demonstrate the clinical relevance of the native-state histoculture system.

  17. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    PubMed

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

  18. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer

    PubMed Central

    Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A.; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T.; Aguilera, Renato J.; Dickerson, Erin B.; Torabi, Alireza; Dwivedi, Alok K.; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A.; Nahleh, Zeina

    2017-01-01

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation. PMID:28031536

  19. Caveolin-1 and accelerated host aging in the breast tumor microenvironment: chemoprevention with rapamycin, an mTOR inhibitor and anti-aging drug.

    PubMed

    Mercier, Isabelle; Camacho, Jeanette; Titchen, Kanani; Gonzales, Donna M; Quann, Kevin; Bryant, Kelly G; Molchansky, Alexander; Milliman, Janet N; Whitaker-Menezes, Diana; Sotgia, Federica; Jasmin, Jean-François; Schwarting, Roland; Pestell, Richard G; Blagosklonny, Mikhail V; Lisanti, Michael P

    2012-07-01

    Increasing chronological age is the most significant risk factor for human cancer development. To examine the effects of host aging on mammary tumor growth, we used caveolin (Cav)-1 knockout mice as a bona fide model of accelerated host aging. Mammary tumor cells were orthotopically implanted into these distinct microenvironments (Cav-1(+/+) versus Cav-1(-/-) age-matched young female mice). Mammary tumors grown in a Cav-1-deficient tumor microenvironment have an increased stromal content, with vimentin-positive myofibroblasts (a marker associated with oxidative stress) that are also positive for S6-kinase activation (a marker associated with aging). Mammary tumors grown in a Cav-1-deficient tumor microenvironment were more than fivefold larger than tumors grown in a wild-type microenvironment. Thus, a Cav-1-deficient tumor microenvironment provides a fertile soil for breast cancer tumor growth. Interestingly, the mammary tumor-promoting effects of a Cav-1-deficient microenvironment were estrogen and progesterone independent. In this context, chemoprevention was achieved by using the mammalian target of rapamycin (mTOR) inhibitor and anti-aging drug, rapamycin. Systemic rapamycin treatment of mammary tumors grown in a Cav-1-deficient microenvironment significantly inhibited their tumor growth, decreased their stromal content, and reduced the levels of both vimentin and phospho-S6 in Cav-1-deficient cancer-associated fibroblasts. Since stromal loss of Cav-1 is a marker of a lethal tumor microenvironment in breast tumors, these high-risk patients might benefit from treatment with mTOR inhibitors, such as rapamycin or other rapamycin-related compounds (rapalogues).

  20. Staging of cervical cancer based on tumor heterogeneity characterized by texture features on 18F-FDG PET images

    NASA Astrophysics Data System (ADS)

    Mu, Wei; Chen, Zhe; Liang, Ying; Shen, Wei; Yang, Feng; Dai, Ruwei; Wu, Ning; Tian, Jie

    2015-07-01

    The aim of the study is to assess the staging value of the tumor heterogeneity characterized by texture features and other commonly used semi-quantitative indices extracted from 18F-FDG PET images of cervical cancer (CC) patients. Forty-two patients suffering CC at different stages were enrolled in this study. Firstly, we proposed a new tumor segmentation method by combining the intensity and gradient field information in a level set framework. Secondly, fifty-four 3D texture features were studied besides of SUVs (SUVmax, SUVmean, SUVpeak) and metabolic tumor volume (MTV). Through correlation analysis, receiver-operating-characteristic (ROC) curves analysis, some independent indices showed statistically significant differences between the early stage (ES, stages I and II) and the advanced stage (AS, stages III and IV). Then the tumors represented by those independent indices could be automatically classified into ES and AS, and the most discriminative feature could be chosen. Finally, the robustness of the optimal index with respect to sampling schemes and the quality of the PET images were validated. Using the proposed segmentation method, the dice similarity coefficient and Hausdorff distance were 91.78   ±   1.66% and 7.94   ±   1.99 mm, respectively. According to the correlation analysis, all the fifty-eight indices could be divided into 20 groups. Six independent indices were selected for their highest areas under the ROC curves (AUROC), and showed significant differences between ES and AS (P  <  0.05). Through automatic classification with the support vector machine (SVM) Classifier, run percentage (RP) was the most discriminative index with the higher accuracy (88.10%) and larger AUROC (0.88). The Pearson correlation of RP under different sampling schemes is 0.9991   ±   0.0011. RP is a highly stable feature and well correlated with tumor stage in CC, which suggests it could differentiate ES and AS with high

  1. Transitions in Physiologic Coupling: Sleep Stage and Age Dependence of Cardio-respiratory Phase Synchronization

    NASA Astrophysics Data System (ADS)

    Bartsch, Ronny P.; Ivanov, Plamen Ch.

    2012-02-01

    Recent studies have focused on various features of cardiac and respiratory dynamics with the aim to better understand key aspects of the underlying neural control of these systems. We investigate how sleep influences cardio-respiratory coupling, and how the degree of this coupling changes with transitions across sleep stages in healthy young and elderly subjects. We analyze full night polysomnographic recordings of 189 healthy subjects (age range: 20 to 90 years). To probe cardio-respiratory coupling, we apply a novel phase synchronization analysis method to quantify the adjustment of rhythms between heartbeat and breathing signals. We investigate how cardio-respiratory synchronization changes with sleep-stage transitions and under healthy aging. We find a statistically significant difference in the degree of cardio-respiratory synchronization during different sleep stages for both young and elderly subjects and a significant decline of synchronization with age. This is a first evidence of how sleep regulation and aging influence a key nonlinear mechanism of physiologic coupling as quantified by the degree of phase synchronization between the cardiac and respiratory systems, which is of importance to develop adequate modeling approaches.

  2. CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer.

    PubMed

    Chen, Viola J; Oermann, Eric; Vahdat, Saloomeh; Rabin, Jennifer; Suy, Simeng; Yu, Xia; Collins, Sean P; Subramaniam, Deepa; Banovac, Filip; Anderson, Eric; Collins, Brian T

    2012-01-01

    Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21-111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3-13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12-72 months) follow-up, the 3 year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1-2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

  3. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    PubMed

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  4. Aging and insulin signaling differentially control normal and tumorous germline stem cells

    PubMed Central

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-01-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC–male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. PMID:25470527

  5. Gene Expression in Wilms’ Tumor Mimics the Earliest Committed Stage in the Metanephric Mesenchymal-Epithelial Transition

    PubMed Central

    Li, Chi-Ming; Guo, Meirong; Borczuk, Alain; Powell, Charles A.; Wei, Michelle; Thaker, Harshwardhan M.; Friedman, Richard; Klein, Ulf; Tycko, Benjamin

    2002-01-01

    Wilms’ tumor (WT) has been considered a prototype for arrested cellular differentiation in cancer, but previous studies have relied on selected markers. We have now performed an unbiased survey of gene expression in WTs using oligonucleotide microarrays. Statistical criteria identified 357 genes as differentially expressed between WTs and fetal kidneys. This set contained 124 matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush KT, Nigam SK: Changes in global gene expression patterns during development and maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649–5654) to establish genes with stage-specific expression in the developing rat kidney. Mapping between the two data sets showed that WTs systematically overexpressed genes corresponding to the earliest stage of metanephric development, and underexpressed genes corresponding to later stages. Automated clustering identified a smaller group of 27 genes that were highly expressed in WTs compared to fetal kidney and heterologous tumor and normal tissues. This signature set was enriched in genes encoding transcription factors. Four of these, PAX2, EYA1, HBF2, and HOXA11, are essential for cell survival and proliferation in early metanephric development, whereas others, including SIX1, MOX1, and SALL2, are predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or reduced (SALL2) in cells at other developmental stages. These data imply that the blastema in WTs has progressed to the committed stage in the mesenchymal-epithelial transition, where it is partially arrested in differentiation. The WT-signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the imprinted gene NNAT and the metastasis-associated transcription factor E1AF. PMID:12057921

  6. Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of Recurrence in Stage IV Wilms Tumor

    SciTech Connect

    Kirkland, Robert S.; Nanda, Ronica H.; Alazraki, Adina; Esiashvili, Natia

    2015-06-01

    Purpose: Chest computed tomography (CT) is currently accepted as the main modality for initial disease staging and response assessment in Wilms tumor (WT). However, there is great variability in the number and size of lung metastases at the time of diagnosis and after induction chemotherapy. There is a lack of clinical evidence as to how this variability in tumor burden affects choice of therapy and disease outcome. This study sought to evaluate a previously proposed lung metastases risk stratification system based on CT findings and clinical outcomes in stage IV WT patients. Methods and Materials: Thirty-five pediatric patients with a diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT scans between 1997 and 2012 were included in the analysis. Patients were divided into low-, intermediate-, and high-risk categories based on the size and number of pulmonary metastases before and after 6 weeks of chemotherapy. Association of the lung risk groups with lung recurrence-free survival and overall survival at each time point was analyzed with relevant covariates. Results: Risk group distribution both at diagnosis and after induction chemotherapy was not influenced by tumor histology. Initial risk grouping suggested an association with disease-free survival at 5 years (P=.074); however, the most significant correlation was with postinduction chemotherapy disease status (P=.027). In patients with an intermediate or high burden of disease after 6 weeks of chemotherapy, despite receiving whole-lung and boost irradiation, survival outcomes were poorer. Conclusions: Pulmonary tumor burden in stage IV WT on chest CT can predict disease outcome. Patients with intermediate- or low-risk disease, especially after induction therapy, have a higher risk for recurrence. After prospective validation, this method may become a valuable tool in adaptation of therapy to improve outcome.

  7. Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.

    PubMed

    Sayed, Ramy K A; de Leonardis, Erika Chacin; Guerrero-Martínez, José A; Rahim, Ibtissem; Mokhtar, Doaa M; Saleh, Abdelmohaimen M; Abdalla, Kamal E H; Pozo, María J; Escames, Germaine; López, Luis C; Acuña-Castroviejo, Darío

    2016-10-01

    The gastrocnemius muscle (GM) of young (3months) and aged (12months) female wild-type C57/BL6 mice was examined by light and electron microscopy, looking for the presence of structural changes at early stage of the aging process. Morphometrical parameters including body and gastrocnemius weights, number and type of muscle fibers, cross section area (CSA), perimeter, and Feret's diameter of single muscle fiber, were measured. Moreover, lengths of the sarcomere, A-band, I-band, H-zone, and number and CSA of intermyofibrillar mitochondria (IFM), were also determined. The results provide evidence that 12month-old mice had significant changes on skeletal muscle structure, beginning with the reduction of gastrocnemius weight to body weight ratio, compatible with an early loss of skeletal muscle function and strength. Moreover, light microscopy revealed increased muscle fibers size, with a significant increase on their CSA, perimeter, and diameter of both type I and type II muscle fibers, and a reduction in the percentage of muscle area occupied by type II fibers. Enhanced connective tissue infiltrations, and the presence of centrally nucleated muscle fibers, were also found in aged mice. These changes may underlie an attempt to compensate the loss of muscle mass and muscle fibers number. Furthermore, electron microscopy discovered a significant age-dependent increase in the length of sarcomeres, I and H bands, and reduction on the overlapped actin/myosin length, supporting contractile force loss with age. Electron microscopy also showed an increased number and CSA of IFM with age, which may reveal more endurance at 12months of age. Together, mice at early stage of aging already show significant changes in gastrocnemius muscle morphology and ultrastructure that are suggestive of the onset of sarcopenia.

  8. Aging Effects on Cardiac and Respiratory Dynamics in Healthy Subjects across Sleep Stages

    PubMed Central

    Schumann, Aicko Y.; Bartsch, Ronny P.; Penzel, Thomas; Ivanov, Plamen Ch.; Kantelhardt, Jan W.

    2010-01-01

    Study Objectives: Respiratory and heart rate variability exhibit fractal scaling behavior on certain time scales. We studied the short-term and long-term correlation properties of heartbeat and breathing-interval data from disease-free subjects focusing on the age-dependent fractal organization. We also studied differences across sleep stages and night-time wake and investigated quasi-periodic variations associated with cardiac risk. Design: Full-night polysomnograms were recorded during 2 nights, including electrocardiogram and oronasal airflow. Setting: Data were collected in 7 laboratories in 5 European countries. Participants: 180 subjects without health complaints (85 males, 95 females) aged from 20 to 89 years. Interventions: None. Measurements and Results: Short-term correlations in heartbeat intervals measured by the detrended fluctuation analysis (DFA) exponent α1 show characteristic age dependence with a maximum around 50–60 years disregarding the dependence on sleep and wake states. Long-term correlations measured by α2 differ in NREM sleep when compared with REM sleep and wake, besides weak age dependence. Results for respiratory intervals are similar to those for α2 of heartbeat intervals. Deceleration capacity (DC) decreases with age; it is lower during REM and deep sleep (compared with light sleep and wake). Conclusion: The age dependence of α1 should be considered when using this value for diagnostic purposes in post-infarction patients. Pronounced long-term correlations (larger α2) for heartbeat and respiration during REM sleep and wake indicate an enhanced control of higher brain regions, which is absent during NREM sleep. Reduced DC possibly indicates an increased cardiovascular risk with aging and during REM and deep sleep. Citation: Schumann AY; Bartsch RP; Penzel T; Ivanov PC; Kantelhardt JW. Aging effects on cardiac and respiratory dynamics in healthy subjects across sleep stages. SLEEP 2010;33(7):943-955. PMID:20614854

  9. Age-stage, two-sex life table of Parapoynx crisonalis (Lepidoptera: Pyralidae) at different temperatures

    PubMed Central

    Chen, Qi; Li, Ni; Wang, Xing; Ma, Li; Huang, Jian-Bin; Huang, Guo-Hua

    2017-01-01

    Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage–specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C. PMID:28264022

  10. The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma.

    PubMed

    Bruna, Flavia; Arango-Rodríguez, Martha; Plaza, Anita; Espinoza, Iris; Conget, Paulette

    2017-01-01

    Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC. OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch. At papilloma stage, the vehicle or 3×10(6) allogenic bone marrow-derived MSCs were locally administered. Four weeks later, the lesions were studied according to: volume, stratification (histology), proliferation (Ki-67), apoptosis (Caspase 3 cleaved), vasculature (ASMA), inflammation (Leukocyte infiltrate), differentiation (CK1 and CK4) and gene expression profile (mRNA). Tumors found in individuals that received MSCs were smaller than those presented in the vehicle group (87±80 versus 54±62mm(3), p<0.05). The rate of proliferation was two times lower and the apoptosis was 2.5 times higher in lesions treated with MSCs than in untreated ones. While the laters presented dedifferentiated cells, the former maintained differentiated cells (cytokeratin and gene expression profile similar to normal tissue). Thus, MSC administration at papilloma stage precludes tumor growth and epithelial dedifferentiation of OSCC.

  11. Effect of Two-Stage Aging on Microstructure of 7075 Aluminum Alloys

    DTIC Science & Technology

    1981-04-01

    which particular microstructural characteristic is of greatest significance in the stress corrosion behavior of 7075 in a high strength condition. 2...is expected that RRA may provide less improvement in the stress corrosion behavior of 7050 than of I I 7075 . Data from these tests would allow...I v h EFFECT OF TWO-STAGE AGING ON MICROSTRUCTURE OF 7075 ALUMINUM ALLOYS RE- 627 "Final Report E April 1981 "by 7! Jonn M. Papazian OT i. Prepared

  12. Regional staging of white matter signal abnormalities in aging and Alzheimer's disease.

    PubMed

    Lindemer, Emily R; Greve, Douglas N; Fischl, Bruce R; Augustinack, Jean C; Salat, David H

    2017-01-01

    White matter lesions, quantified as 'white matter signal abnormalities' (WMSA) on neuroimaging, are common incidental findings on brain images of older adults. This tissue damage is linked to cerebrovascular dysfunction and is associated with cognitive decline. The regional distribution of WMSA throughout the cerebral white matter has been described at a gross scale; however, to date no prior study has described regional patterns relative to cortical gyral landmarks which may be important for understanding functional impact. Additionally, no prior study has described how regional WMSA volume scales with total global WMSA. Such information could be used in the creation of a pathologic 'staging' of WMSA through a detailed regional characterization at the individual level. Magnetic resonance imaging data from 97 cognitively-healthy older individuals (OC) aged 52-90 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were processed using a novel WMSA labeling procedure described in our prior work. WMSA were quantified regionally using a procedure that segments the cerebral white matter into 35 bilateral units based on proximity to landmarks in the cerebral cortex. An initial staging was performed by quantifying the regional WMSA volume in four groups based on quartiles of total WMSA volume (quartiles I-IV). A consistent spatial pattern of WMSA accumulation was observed with increasing quartile. A clustering procedure was then used to distinguish regions based on patterns of scaling of regional WMSA to global WMSA. Three patterns were extracted that showed high, medium, and non-scaling with global WMSA. Regions in the high-scaling cluster included periventricular, caudal and rostral middle frontal, inferior and superior parietal, supramarginal, and precuneus white matter. A data-driven staging procedure was then created based on patterns of WMSA scaling and specific regional cut-off values from the quartile analyses. Individuals with Alzheimer's disease

  13. Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2.

    PubMed

    Hu, Ruyi; Liu, Wenming; Qiu, Xingfeng; Lin, Zhenghe; Xie, Yan; Hong, Xingya; Paerhati, Reyila; Qi, Zhongquan; Zhuang, Guohong; Liu, Zhongchen

    2016-03-01

    Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC.

  14. Expression of tumor necrosis factor-α-induced protein 8 in stage III gastric cancer and the correlation with DcR3 and ERK1/2

    PubMed Central

    HU, RUYI; LIU, WENMING; QIU, XINGFENG; LIN, ZHENGHE; XIE, YAN; HONG, XINGYA; PAERHATI, REYILA; QI, ZHONGQUAN; ZHUANG, GUOHONG; LIU, ZHONGCHEN

    2016-01-01

    Tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) is a recently identified protein that is considered to be associated with various malignancies, including esophageal, breast and pancreatic cancer; however, the importance of TIPE in gastric cancer (GC) remains unknown. Decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor superfamily that is expressed in digestive system neoplasms. The expression of DcR3 is regulated by the mitogen-activated protein kinase (MAPK)/MAPK kinase/extracellular signal-regulated kinase (ERK) signaling pathway. Reverse transcription-polymerase chain reaction was performed to detect the expression of TIPE, ERK and DcR3 in the pathological and tumor-adjacent normal gastric tissues of 30 patients that demonstrated stage III gastric adenocarcinoma. The expression and distribution of the TIPE protein was examined using immunohistochemistry, and the clinical significance and expression levels of DcR3 and ERK1/2 were evaluated. The expression of TIPE, ERK1/2 and DcR3 in the tumor tissues of GC was significantly increased compared with paracarcinoma tissues (P<0.05). In addition, TIPE expression positively correlated with DcR3 and ERK1 levels (r=0.538 and r=0.462, respectively; P<0.05). There was no statistical difference between tumor tissues from patients with varying age, gender, differentiation or lymph node metastasis (P>0.05). TIPE may be vital in the progression of GC. TIPE may be associated with the expression of DcR3 and ERK1/2, which may be involved in the cell apoptosis of GC. The present study elucidates the potential function of TIPE as a novel marker and therapeutic target for GC. PMID:26998086

  15. KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions

    PubMed Central

    Yang, Yizeng; Katz, Jonathan P.

    2016-01-01

    ABSTRACT The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context. PMID:26934576

  16. KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions.

    PubMed

    Yang, Yizeng; Katz, Jonathan P

    2016-04-02

    The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context.

  17. Age estimation by dental developmental stages in children and adolescents in Iceland.

    PubMed

    Vidisdottir, Sigridur Rosa; Richter, Svend

    2015-12-01

    Studies have shown that it is necessary to create a database for dental maturity for every population and compare it to others. The present study is the first one for dental development in the Icelandic population the age range being 4-24 years. It will help in forensic dental age estimation and will also help dentists, physicians, anthropologists, archaeologists and other professionals who rely on developmental age assessment in children and adolescents. In this present retrospective cross-sectional study, dental maturity was determined in 1100 Icelandic children and adolescents from orthopantomograms (OPGs). The first 100 were used for a pilot study and the remaining 1000 for the main study. A total of 23 subjects were excluded. The sample consisted of 508 girls and 469 boys from the age of 4-24 years and a dental developmental scoring system was used as a standard for determination of dental maturity stages. A total of 200 OPGs were studied both on the left and right side and the remaining on the right side. Dental maturity was established for all teeth and both genders, when the sample permitted, from the beginning of crown formation to the root apex closure. The Cronbach's Alpha reliability test showed high reliability, R=0.982. Girls in Iceland reach dental maturity root completed (stage 10, Rc) at 17.81 years of age for the maxillary and at 18.47 years for the mandibular teeth. Boys reach dental maturity root completed (stage 10, Rc) at 18.00 years of age in the maxilla and 17.63 in the mandible. There was no significant difference between left and right side (r=0.95-1.00) and there was no gender difference, except in root formation in maxillary and mandibular canines where girls reached root completed earlier than boys. A reliable database has been established in Iceland for tooth development in the age range of 4-24 years, which is compatible with international studies. These results will help forensic odontologists and other professionals to estimate with

  18. Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

    ClinicalTrials.gov

    2016-01-13

    Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  19. PROSPECTIVE COMPARISON OF TUMOR STAGING USING COMPUTED TOMOGRAPHY VERSUS MAGNETIC RESONANCE IMAGING FINDINGS IN DOGS WITH NASAL NEOPLASIA: A PILOT STUDY.

    PubMed

    Lux, Cassie N; Culp, William T N; Johnson, Lynelle R; Kent, Michael; Mayhew, Philipp; Daniaux, Lise A; Carr, Alaina; Puchalski, Sarah

    2017-02-24

    Identification of nasal neoplasia extension and tumor staging in dogs is most commonly performed using computed tomography (CT), however magnetic resonance imaging (MRI) is routinely used in human medicine. A prospective pilot study enrolling six dogs with nasal neoplasia was performed with CT and MRI studies acquired under the same anesthetic episode. Interobserver comparison and comparison between the two imaging modalities with regard to bidimensional measurements of the nasal tumors, tumor staging using historical schemes, and assignment of an ordinal scale of tumor margin clarity at the tumor-soft tissue interface were performed. The hypotheses included that MRI would have greater tumor measurements, result in higher tumor staging, and more clearly define the tumor soft tissue interface when compared to CT. Evaluation of bone involvement of the nasal cavity and head showed a high level of agreement between CT and MRI. Estimation of tumor volume using bidimensional measurements was higher on MRI imaging in 5/6 dogs, and resulted in a median tumor volume which was 18.4% higher than CT imaging. Disagreement between CT and MRI was noted with meningeal enhancement, in which two dogs were positive for meningeal enhancement on MRI and negative on CT. One of six dogs had a higher tumor stage on MRI compared to CT, while the remaining five agreed. Magnetic resonance imaging resulted in larger bidimensional measurements and tumor volume estimates, along with a higher likelihood of identifying meningeal enhancement when compared to CT imaging. Magnetic resonance imaging may provide integral information for tumor staging, prognosis, and treatment planning.

  20. p53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancer.

    PubMed

    Esrig, D; Spruck, C H; Nichols, P W; Chaiwun, B; Steven, K; Groshen, S; Chen, S C; Skinner, D G; Jones, P A; Cote, R J

    1993-11-01

    Seventy-three transitional cell carcinomas of the bladder were analyzed by immunohistochemistry for p53 nuclear accumulation, and the results were compared to mutations detected in the p53 gene by single strand conformational polymorphism analysis (SSCP) and DNA sequence analysis. Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections. A highly significant association between the presence of p53 mutations and p53 nuclear reactivity as detected by immunohistochemistry was found (P = 0.0001). Of 32 tumors that demonstrated p53 mutations by SSCP, 27 (84%) showed p53 nuclear reactivity. Of the five cases that did not demonstrate p53 nuclear reactivity, four had mutations in exon 5. However, of 41 tumors with no evidence of p53 mutation by molecular analysis, 12 (29%) showed p53 immunoreactivity. This indicates that immunohistochemical methods may be more sensitive than SSCP in detecting p53 mutations or that discordant cases represent tumors with accumulation of wild type p53 protein, without mutations at the p53 locus. Of the 15 tumors that were found to have mutations at exon 8, 13 demonstrated high-intensity homogeneous p53 nuclear reactivity by immunohistochemistry, and all mutations located at codon 280 demonstrated high-intensity homogeneous immunoreactivity. However, three of three tumors with exon 6 mutations demonstrated low-level p53 immunoreactivity, and four of six tumors with mutations in exon 5 showed no detectable p53 nuclear reactivity. This indicates that the heterogeneity of immunoreactivity observed when analyzing p53 nuclear accumulation may be related to the site of the p53 gene mutation. Information on tumor grade, stage, lymph node status, disease-free interval, and overall survival were available in 54 patients who had undergone cystectomy. A significant association was observed between p53 alterations (detected by immunohistochemistry and SSCP) and histological tumor grade (P = 0.003) and stage (P = 0

  1. Age estimation from stages of epiphyseal union in the presacral vertebrae.

    PubMed

    Cardoso, Hugo F V; Ríos, Luis

    2011-02-01

    The presacral vertebrae have various secondary centers of ossification, whose timing of fusion can be used for age estimation of human skeletal remains up to the middle to the latter third decade. However, detailed information about the age at which these secondary centers of ossification fuse has been lacking. In this study, the timing of epiphyseal union in presacral vertebrae was studied in a sample of modern Portuguese skeletons (57 females and 47 males) between the ages of 9 and 30, taken from the Lisbon documented skeletal collection. A detailed photographic record of these epiphyses and the age ranges for the different stages of epiphyseal union are provided. Partial union of epiphyses was observed from 11 to 27 years of age. In general, centers of ossification begin to fuse first in the cervical and lumbar vertebrae, followed by centers of ossification in the thoracic region. The first center of ossification to complete fusion is usually that of the mammillary process in lumbar vertebrae. This is usually followed by that of the transverse process, spinous transverse process, and annular ring, regardless of vertebra type. There were no statistically significant sex differences in timing of fusion, but there was a trend toward early maturation in females for some vertebra or epiphyses. Bilateral epiphyses did not show statistically significant differences in timing of fusion. This study offers information on timing of fusion of diverse epiphyseal locations useful for age estimation of complete or fragmented human skeletal remains.

  2. Primary Tumor Site as a Predictor of Treatment Outcome for Definitive Radiotherapy of Advanced-Stage Oral Cavity Cancers

    SciTech Connect

    Lin, Chien-Yu; Wang, Hung-Ming; Kang, Chung-Jan; Lee, Li-Yu; Huang, Shiang-Fu; Fan, Kang-Hsing; Chen, Eric Yen-Chao

    2010-11-15

    Purpose: To evaluate the outcome of definitive radiotherapy (RT) for oral cavity cancers and to assess prognostic factors. Methods and Materials: Definitive RT was performed on 115 patients with oral cavity cancers at Stages III, IVA, and IVB, with a distribution of 6%, 47%, and 47%, respectively. The median dose of RT was 72Gy (range, 62-76Gy). Cisplatin-based chemotherapy was administered to 95% of the patients. Eleven patients underwent salvage surgery after RT failure. Results: Eight-eight (76.5%) patients responded partially and 23 (20%) completely; of the patients who responded, 18% and 57%, respectively, experienced a durable effect of treatment. The 3-year overall survival, disease-specific survival, and progression-free survival were 22%, 27%, and 25%, respectively. The 3-year PFS rates based on the primary tumor sites were as follows: Group I (buccal, mouth floor, and gum) 51%, Group II (retromolar and hard palate) 18%, and Group III (tongue and lip) 6% (p < 0.0001). The 3-year progression-free survival was 41% for N0 patients and 19% for patients with N+ disease (p = 0.012). The T stage and RT technique did not affect survival. The patients who underwent salvage surgery demonstrated better 3-year overall survival and disease-specific survival (53% vs. 19%, p = 0.015 and 53% vs. 24%, p = 0.029, respectively). Subsite group, N+, and salvage surgery were the only significant prognostic factors for survival after multivariate analysis. Conclusion: The primary tumor site and neck stage are prognostic predictors in advanced-stage oral cancer patients who received radical RT. The primary tumor extension and RT technique did not influence survival.

  3. Age and petrology of alkalic postshield and rejuvenated-stage lava from Kauai, Hawaii

    USGS Publications Warehouse

    Clague, D.A.; Dalrymple, G.B.

    1988-01-01

    At the top of the Waimea Canyon Basalt on the island of Kauai, rare flows of alkalic postshield-stage hawaiite and mugearite overlie tholeiitic flows of the shield stage. These postshield-stage flows are 3.92 Ma and provide a younger limit for the age of the tholeiitic shield stage. The younger Koloa Volcanics consist of widespread alkalic rejuvenated-stage flows and vents of alkalic basalt, basanite, nephelinite, and nepheline melilitite that erupted between 3.65 and 0.52 Ma. All the flows older than 1.7 Ma occur in the west-northwestern half of the island and all the flows younger than 1.5 Ma occur in the east-southeastern half. The lithologies have no spatial or chronological pattern. The flows of the Koloa Volcanics are near-primary magmas generated by variable small degrees of partial melting of a compositionally heterogeneous garnet-bearing source that has about two-thirds the concentration of P2O5, rare-earth elements, and Sr of the source of the Honolulu Volcanics on the island of Oahu. The same lithology in the Koloa and Honolulu Volcanics is generated by similar degrees of partial melting of distinct source compositions. The lavas of the Koloa Volcanics can be generated by as little as 3 percent to as much as 17 percent partial melting for nepheline melilitite through alkalic basalt, respectively. Phases that remain in the residue of the Honolulu Volcanics, such as rutile and phlogopite, are exhausted during formation of the Koloa Volcanics at all but the smallest degrees of partial melting. The mantle source for Kauai lava becomes systematically more depleted in 87Sr/86Sr as the volcano evolves from the tholeiitic shield stage to the alkalic postshield stage to the alkalic rejuvenated stage: at the same time, the lavas become systematically more enriched in incompatible trace elements. On a shorter timescale, the lavas of the Koloa Volcanics display the same compositional trends, but at a lower rate of change. The source characteristics of the Koloa

  4. Raman spectroscopic detection of early stages in DMBA-induced tumor evolution in hamster buccal pouch model: an exploratory study

    NASA Astrophysics Data System (ADS)

    Ghanate, Avinash D.; Kumar, G.; Talathi, Sneha; Maru, G. B.; Krishna, C. Murali

    2010-12-01

    Oral cancers are the serious health problem in developing as well as developed world, and more so in India and other south Asian countries. Survival rate of these cancers, despite advances in treatment modalities are one of the poorest which is attributed to lack of reliable screening and early detection methods. The hamster buccal pouch (HBP)carcinogenesis model closely mimics human oral cancers. Optical spectroscopy methods are sensitive enough to detect subtle biochemical changes and thus hold great potential in early detection of cancers. However, efficacy of these techniques in classifying of sequential evolution of tumors has never been tested. Therefore, in this study, we have explored the feasibility of Raman spectroscopic classification of different stages of cancers in hamster model. Strong vibrational modes of lipids (1440, 1654, and 1746 cm-1) are seen in control tissue spectra, whereas strong protein bands are seen in spectra of DMBA treated tissues. These differences were exploited to classify control and treated tissues using Linear Discriminant Analysis (LDA), Principle Component Analysis (PCA)-Limit test, Factorial Discriminant Analysis (FDA), Quadratic Discriminant Analysis (QDA), PLS-DA and non- linear decision tree methods. All these techniques have shown good classification between spectra of different stages of tumor evolution and results were further successfully verified by leave-one-out and single blinded methods. Thus findings of this study, first of its kind,demonstrate the feasibility of Raman spectroscopic detection of early changes in tumor evolution.

  5. Raman spectroscopic detection of early stages in DMBA-induced tumor evolution in hamster buccal pouch model: an exploratory study

    NASA Astrophysics Data System (ADS)

    Ghanate, Avinash D.; Kumar, G.; Talathi, Sneha; Maru, G. B.; Krishna, C. Murali

    2011-08-01

    Oral cancers are the serious health problem in developing as well as developed world, and more so in India and other south Asian countries. Survival rate of these cancers, despite advances in treatment modalities are one of the poorest which is attributed to lack of reliable screening and early detection methods. The hamster buccal pouch (HBP)carcinogenesis model closely mimics human oral cancers. Optical spectroscopy methods are sensitive enough to detect subtle biochemical changes and thus hold great potential in early detection of cancers. However, efficacy of these techniques in classifying of sequential evolution of tumors has never been tested. Therefore, in this study, we have explored the feasibility of Raman spectroscopic classification of different stages of cancers in hamster model. Strong vibrational modes of lipids (1440, 1654, and 1746 cm-1) are seen in control tissue spectra, whereas strong protein bands are seen in spectra of DMBA treated tissues. These differences were exploited to classify control and treated tissues using Linear Discriminant Analysis (LDA), Principle Component Analysis (PCA)-Limit test, Factorial Discriminant Analysis (FDA), Quadratic Discriminant Analysis (QDA), PLS-DA and non- linear decision tree methods. All these techniques have shown good classification between spectra of different stages of tumor evolution and results were further successfully verified by leave-one-out and single blinded methods. Thus findings of this study, first of its kind,demonstrate the feasibility of Raman spectroscopic detection of early changes in tumor evolution.

  6. Comparative analysis of BRAF, NRAS and c-KIT mutation status between tumor tissues and autologous tumor cell-lines of stage III/IV melanoma.

    PubMed

    Knol, Anne-Chantal; Pandolfino, Marie-Christine; Vallée, Audrey; Nguyen, Frédérique; Lella, Virginie; Khammari, Amir; Denis, Marc; Puaux, Anne-Laure; Dréno, Brigitte

    2015-01-01

    In the last decade, advances in molecular biology have provided evidence of the genotypic heterogeneity of melanoma. We analysed BRAF, NRAS and c-KIT alterations in tissue samples from 63 stage III/IV melanoma patients and autologous cell-lines, using either allele-specific or quantitative PCR. The expression of BRAF V600E protein was also investigated using an anti-BRAF antibody in the same tissue samples. 81% of FFPE samples and tumor cell-lines harboured a genetic alteration in either BRAF (54%) or NRAS (27%) oncogenes. There was a strong concordance (100%) between tissue samples and tumor cell-lines. The BRAF V600E mutant-specific antibody showed high sensitivity (96%) and specificity (100%) for detecting the presence of a BRAF V600E mutation. The correlation was of 98% between PCR and immunohistochemistry results for BRAF mutation. These results suggest that BRAF and NRAS mutation status of tumor cells is not affected by culture conditions.

  7. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years.

    PubMed

    Braak, Heiko; Thal, Dietmar R; Ghebremedhin, Estifanos; Del Tredici, Kelly

    2011-11-01

    Two thousand three hundred and thirty two nonselected brains from 1- to 100-year-old individuals were examined using immunocytochemistry (AT8) and Gallyas silver staining for abnormal tau; immunocytochemistry (4G8) and Campbell-Switzer staining were used for the detection ofβ-amyloid. A total of 342 cases was negative in the Gallyas stain but when restaged for AT8 only 10 were immunonegative. Fifty-eight cases had subcortical tau predominantly in the locus coeruleus, but there was no abnormal cortical tau (subcortical Stages a-c). Cortical involvement (abnormal tau in neurites) was identified first in the transentorhinal region (Stage 1a, 38 cases). Transentorhinal pyramidal cells displayed pretangle material (Stage 1b, 236 cases). Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI. Pretangles restricted to subcortical sites were seen chiefly at younger ages. Of the total cases, 1,031 (44.2%) had β-amyloid plaques. The first plaques occurred in the neocortex after the onset of tauopathy in the brainstem. Plaques generally developed in the 40s in 4% of all cases, culminating in their tenth decade (75%). β-amyloid plaques and NFTs were significantly correlated (p < 0.0001). These data suggest that tauopathy associated with sporadic Alzheimer disease may begin earlier than previously thought and possibly in the lower brainstem rather than in the transentorhinal region.

  8. Bringing the law to the gerontological stage: a different look at movies and old age.

    PubMed

    Doron, Israel

    2006-01-01

    Films often portray the complexities of real-life aging issues, showing how they are apparently handled outside of and around the law or legal issues. Furthermore, films considering the aged and the social issues associated with aging also reveal how the law actually functions as a framework around and within which people develop customs, habits, and behaviors related to the issue of old age. Exposing these hidden socio-legal boundaries allows us to better understand both the films concerned and the place of law within our aging society. In an attempt to better understand these issues, this article deconstructs five relatively modern and well-known films. All feature aged protagonists, and all tell their stories against a background of legal issues that are only alluded to, and remain hidden "behind the scenes." Two main questions are addressed by this analysis: First, to what extent does the reality of old age as described in the films considered here reflect familiar social phenomena identified by empirical studies? And, second, to what extent does the legal infrastructure embedded in the narrative of these films reflect the legal regulations that govern the aged in today's society. The conclusions that arose from the analysis of the cinematic and the legal reality expressed in the films demonstrate that the current level of discourse on major issues in social gerontology ignores the importance and relevance of law. Therefore, it behooves us to "bring the Law to the gerontological stage," where the current situation as it actually exists can be analyzed and perhaps even changed.

  9. Survival of patients with colorectal cancer in Austria by sex, age, and stage.

    PubMed

    Haidinger, Gerald; Waldhoer, Thomas; Hackl, Monika; Vutuc, Christian

    2006-10-01

    This paper for the first time presents Austrian data on survival of patients, diagnosed from 1998 through 2002, with colon cancer and with rectal cancer. Cumulative relative survival rates were calculated by age, standardized for all ages and stages combined, and by age groups (< 50 years, 50-64 years, and =65 years) according to stages (localized, regional metastases and distant metastases). In carcinoma of the colon 5-year relative survival was 66 % in males and 64 % in females. In carcinoma of the rectum 5-year relative survival was 64 % in males and 67 % in females. Compared to the earlier results from the Tyrol (based on patients diagnosed from 1990 through 1994) the 5-year survival of patients with colon cancer increased from 55 % to 66 % in males and from 58 % to 64 % in females. In patients with rectal cancer 5-year survival increased from 44 % to 64 % in males and from 46 % to 67 % in females. This increase in part can be explained by a positive effect of early detection and of better treatment.

  10. Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage

    PubMed Central

    GARNIER, AGNÈS; ILMER, MATTHIAS; BECKER, KRISTINA; HÄBERLE, BEATE; VON SCHWEINITZ, DIETRICH; KAPPLER, ROLAND; BERGER, MICHAEL

    2016-01-01

    The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription-quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characterizing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time

  11. Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.

    PubMed

    Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

    2014-04-01

    In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.

  12. Reference values of blood parameters in beef cattle of different ages and stages of lactation.

    PubMed Central

    Doornenbal, H; Tong, A K; Murray, N L

    1988-01-01

    Reference (normal) values for 12 blood serum components were determined for 48 Shorthorn cows (2-10 years old) and their 48 calves, 357 crossbred cows (12-14 years old), 36 feedlot bulls and 36 feedlot steers. In addition, hemoglobin, hematocrit, triiodothyronine, thyroxine and cortisol levels were determined for the crossbred cows, and feedlot bulls and steers. Reference values were tabulated according to sex, age and stage of lactation. Serum concentrations of urea, total protein and bilirubin, and serum activity of aspartate aminotransferase and lactate dehydrogenase increased with age (P less than 0.05), while calcium, phosphorus and alkaline phosphatase decreased with age (P less than 0.05) from birth to the age of ten years. The Shorthorn cows had the highest levels of glucose at parturition (P less than 0.05) with decreasing levels during lactation. Creatinine concentration decreased during lactation and increased during postweaning. Both lactate dehydrogenase and aspartate aminotransferase levels increased (P less than 0.05) during lactation. Urea and uric acid were present at higher concentrations in lactating than nonlactating cows (P less than 0.05). The values reported, based on a wide age range and large number of cattle, could serve as clinical guides and a basis for further research. PMID:3349406

  13. Variation in Honey Bee Gut Microbial Diversity Affected by Ontogenetic Stage, Age and Geographic Location

    PubMed Central

    Hroncova, Zuzana; Havlik, Jaroslav; Killer, Jiri; Doskocil, Ivo; Tyl, Jan; Kamler, Martin; Titera, Dalibor; Hakl, Josef; Mrazek, Jakub; Bunesova, Vera; Rada, Vojtech

    2015-01-01

    Social honey bees, Apis mellifera, host a set of distinct microbiota, which is similar across the continents and various honey bee species. Some of these bacteria, such as lactobacilli, have been linked to immunity and defence against pathogens. Pathogen defence is crucial, particularly in larval stages, as many pathogens affect the brood. However, information on larval microbiota is conflicting. Seven developmental stages and drones were sampled from 3 colonies at each of the 4 geographic locations of A. mellifera carnica, and the samples were maintained separately for analysis. We analysed the variation and abundance of important bacterial groups and taxa in the collected bees. Major bacterial groups were evaluated over the entire life of honey bee individuals, where digestive tracts of same aged bees were sampled in the course of time. The results showed that the microbial tract of 6-day-old 5th instar larvae were nearly equally rich in total microbial counts per total digestive tract weight as foraging bees, showing a high percentage of various lactobacilli (Firmicutes) and Gilliamella apicola (Gammaproteobacteria 1). However, during pupation, microbial counts were significantly reduced but recovered quickly by 6 days post-emergence. Between emergence and day 6, imago reached the highest counts of Firmicutes and Gammaproteobacteria, which then gradually declined with bee age. Redundancy analysis conducted using denaturing gradient gel electrophoresis identified bacterial species that were characteristic of each developmental stage. The results suggest that 3-day 4th instar larvae contain low microbial counts that increase 2-fold by day 6 and then decrease during pupation. Microbial succession of the imago begins soon after emergence. We found that bacterial counts do not show only yearly cycles within a colony, but vary on the individual level. Sampling and pooling adult bees or 6th day larvae may lead to high errors and variability, as both of these stages may

  14. Transformation resistance in a premature aging disorder identifies a tumor-protective function of BRD4.

    PubMed

    Fernandez, Patricia; Scaffidi, Paola; Markert, Elke; Lee, Ji-Hyeon; Rane, Sushil; Misteli, Tom

    2014-10-09

    Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS) provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis.

  15. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

    PubMed

    Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

    2017-01-10

    In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

  16. Role of computed tomography angiography in detection and staging of small bowel carcinoid tumors

    PubMed Central

    Bonekamp, David; Raman, Siva P; Horton, Karen M; Fishman, Elliot K

    2015-01-01

    Small-bowel carcinoid tumors are the most common form (42%) of gastrointestinal carcinoids, which by themselves comprise 70% of neuroendocrine tumors. Although primary small bowel neoplasms are overall rare (3%-6% of all gastrointestinal neoplasms), carcinoids still represent the second most common (20%-30%) primary small-bowel malignancy after small bowel adenocarcinoma. Their imaging evaluation is often challenging. State-of-the-art high-resolution multiphasic computed tomography together with advanced postprocessing methods provides an excellent tool for their depiction. The manifold interactive parameter choices however require knowledge of when to use which technique. Here, we discuss the imaging appearance and evaluation of duodenal, jejunal and ileal carcinoid tumors, including the imaging features of the primary tumor, locoregional mesenteric nodal metastases, and distant metastatic disease. A protocol for optimal lesion detection is presented, including the use of computed tomography enterography, volume acquisition, computed tomography angiography and three-dimensional mapping. Imaging findings are illustrated with a series of challenging cases which illustrate the spectrum of possible disease in the small bowel and mesentery, the range of possible appearances in the bowel itself on multiphase data and extraluminal findings such as the desmoplastic reaction in mesentery and hypervascular liver metastases. Typical imaging pitfalls and pearls are illustrated. PMID:26435774

  17. Hyperandrogenism produced by ovarian tumors in women at different life stages.

    PubMed

    Fux-Otta, Carolina; Szafryk de Mereshian, Paula; López de Corominas, Mónica; Fuster, Margarita; López, Carlos R

    2014-01-01

    Objetivo: evaluar las diferentes manifestaciones del hiperandrogenismo tumoral de origen ovárico en distintos grupos etarios. Diseño: reporte de casos.Lugar de trabajo: centros académicos.Pacientes: son reportadas tres pacientes con exceso de andrógenos. Resultados: describimos una paciente de 10 años con hiperandrogenemia y signos de masculinización secundarios a un tumor de células de Leydig; otra paciente, en edad fértil, con un tumor carcinoide de ovario asociado a hiperplasia estromal que se manifestó con signos de masa abdominal y de virilización. El tercer caso una mujer, en etapa postmenopáusica con alopecia severa, tenía un tumor de células esteroideas, raro en este grupo etario. onclusión: la evaluación de una mujer con signos y síntomas de virilización debe incluir una detallada historia clínica, examen físico y apropiados dosajes hormonales, especialmente si existe dificultad en establecer su origen cuando los estudios imagenológicos son normales.

  18. Photoacoustic microscopy of arteriovenous shunts and blood diffusion in early-stage tumors

    PubMed Central

    Yeh, Chenghung; Liang, Jinyang; Zhou, Yong; Hu, Song; Sohn, Rebecca E.; Arbeit, Jeffrey M.; Wang, Lihong V.

    2016-01-01

    Abstract. Angiogenesis in a tumor region creates arteriovenous (AV) shunts that cause an abnormal venous blood oxygen saturation (sO2) distribution. Here, we applied optical-resolution photoacoustic microscopy to study the AV shunting in vivo. First, we built a phantom to image sO2 distribution in a vessel containing converged flows from two upstream blood vessels with different sO2 values. The phantom experiment showed that the blood from the two upstream vessels maintained a clear sO2 boundary for hundreds of seconds, which is consistent with our theoretical analysis using a diffusion model. Next, we xenotransplanted O-786 tumor cells in mouse ears and observed abnormal sO2 distribution in the downstream vein from the AV shunts in vivo. Finally, we identified the tumor location by tracing the sO2 distribution. Our study suggests that abnormal sO2 distribution induced by the AV shunts in the vessel network may be used as a new functional benchmark for early tumor detection. PMID:26882446

  19. Photoacoustic microscopy of arteriovenous shunts and blood diffusion in early-stage tumors

    NASA Astrophysics Data System (ADS)

    Yeh, Chenghung; Liang, Jinyang; Zhou, Yong; Hu, Song; Sohn, Rebecca E.; Arbeit, Jeffrey M.; Wang, Lihong V.

    2016-02-01

    Angiogenesis in a tumor region creates arteriovenous (AV) shunts that cause an abnormal venous blood oxygen saturation (sO2) distribution. Here, we applied optical-resolution photoacoustic microscopy to study the AV shunting in vivo. First, we built a phantom to image sO2 distribution in a vessel containing converged flows from two upstream blood vessels with different sO2 values. The phantom experiment showed that the blood from the two upstream vessels maintained a clear sO2 boundary for hundreds of seconds, which is consistent with our theoretical analysis using a diffusion model. Next, we xenotransplanted O-786 tumor cells in mouse ears and observed abnormal sO2 distribution in the downstream vein from the AV shunts in vivo. Finally, we identified the tumor location by tracing the sO2 distribution. Our study suggests that abnormal sO2 distribution induced by the AV shunts in the vessel network may be used as a new functional benchmark for early tumor detection.

  20. Photoacoustic microscopy of arteriovenous shunts and blood diffusion in early-stage tumors.

    PubMed

    Yeh, Chenghung; Liang, Jinyang; Zhou, Yong; Hu, Song; Sohn, Rebecca E; Arbeit, Jeffrey M; Wang, Lihong V

    2016-02-01

    Angiogenesis in a tumor region creates arteriovenous (AV) shunts that cause an abnormal venous blood oxygen saturation ( sO2 ) distribution. Here, we applied optical-resolution photoacoustic microscopy to study the AV shunting in vivo. First, we built a phantom to image sO2 distribution in a vessel containing converged flows from two upstream blood vessels with different sO2 values. The phantom experiment showed that the blood from the two upstream vessels maintained a clear sO2 boundary for hundreds of seconds, which is consistent with our theoretical analysis using a diffusion model. Next, we xenotransplanted O-786 tumor cells in mouse ears and observed abnormal sO2 distribution in the downstream vein from the AV shunts in vivo. Finally, we identified the tumor location by tracing the sO2 distribution. Our study suggests that abnormal sO2 distribution induced by the AV shunts in the vessel network may be used as a new functional benchmark for early tumor detection.

  1. Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies

    PubMed Central

    Bettegowda, Chetan; Sausen, Mark; Leary, Rebecca J.; Kinde, Isaac; Wang, Yuxuan; Agrawal, Nishant; Bartlett, Bjarne R.; Wang, Hao; Luber, Brandon; Alani, Rhoda M.; Antonarakis, Emmanuel S.; Azad, Nilofer S.; Bardelli, Alberto; Brem, Henry; Cameron, John L.; Lee, Clarence C.; Fecher, Leslie A.; Gallia, Gary L.; Gibbs, Peter; Le, Dung; Giuntoli, Robert L.; Goggins, Michael; Hogarty, Michael D.; Holdhoff, Matthias; Hong, Seung-Mo; Jiao, Yuchen; Juhl, Hartmut H.; Kim, Jenny J.; Siravegna, Giulia; Laheru, Daniel A.; Lauricella, Calogero; Lim, Michael; Lipson, Evan J.; Marie, Suely Kazue Nagahashi; Netto, George J.; Oliner, Kelly S.; Olivi, Alessandro; Olsson, Louise; Riggins, Gregory J.; Sartore-Bianchi, Andrea; Schmidt, Kerstin; Shih, le-Ming; Oba-Shinjo, Sueli Mieko; Siena, Salvatore; Theodorescu, Dan; Tie, Jeanne; Harkins, Timothy T.; Veronese, Silvio; Wang, Tian-Li; Weingart, Jon D.; Wolfgang, Christopher L.; Wood, Laura D.; Xing, Dongmei; Hruban, Ralph H.; Wu, Jian; Allen, Peter J.; Schmidt, C. Max; Choti, Michael A.; Velculescu, Victor E.; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas; Diaz, Luis A.

    2014-01-01

    The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction–based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer. PMID:24553385

  2. Immunomodulation by MYB is associated with tumor relapse in patients with early stage colorectal cancer

    PubMed Central

    Millen, Rosemary; Malaterre, Jordane; Cross, Ryan S.; Carpinteri, Sandra; Desai, Jayesh; Tran, Ben; Darcy, Phillip; Gibbs, Peter; Sieber, Oliver; Zeps, Nikolajs; Waring, Paul; Fox, Stephen; Pereira, Lloyd; Ramsay, Robert G.

    2016-01-01

    ABSTRACT The presence of tumor immune infiltrating cells (TILs), particularly CD8+ T-cells, is a robust predictor of outcome in patients with colorectal cancer (CRC). We revisited TIL abundance specifically in patients with microsatellite stable (MSS) CRC without evidence of lymph node or metastatic spread. Examination of the density of CD8+ T-cells in primary tumors in the context of other pro-oncogenic markers was performed to investigate potential regulators of TILs. Two independent cohorts of patients with MSS T2-4N0M0 CRC, enriched for cases with atypical relapse, were investigated. We quantified CD8+ and CD45RO+ -TILs, inflammatory markers, NFkBp65, pStat3, Cyclo-oxygenase-2 (COX2) and GRP78 as well as transcription factors (TF), β-catenin and MYB. High CD8+ TILs correlated with a better relapse-free survival in both cohorts (p = 0.002) with MYB and its target gene, GRP78 being higher in the relapse group (p = 0.001); no difference in pSTAT3 and p65 was observed. A mouse CRC (CT26) model was employed to evaluate the effect of MYB on GRP78 expression as well as T-cell infiltration. MYB over-expressing in CT26 cells increased GRP78 expression and the analysis of tumor-draining lymph nodes adjacent to tumors showed reduced T-cell activation. Furthermore, MYB over-expression reduced the efficacy of anti-PD-1 to modulate CT26 tumor growth. This high MYB and GRP78 show a reciprocal relationship with CD8+ TILs which may be useful refining the prediction of patient outcome. These data reveal a new immunomodulatory function for MYB suggesting a basis for further development of anti-GRP78 and/or anti-MYB therapies. PMID:27622014

  3. Tanespimycin and tipifarnib exhibit synergism in inducing apoptosis in melanoma cell lines from later stages of tumor progression.

    PubMed

    Bentke, Anna; Małecki, Jędrzej; Ostrowska, Barbara; Krzykowska-Petitjean, Katarzyna; Laidler, Piotr

    2013-10-01

    Many anticancer strategies rely on efficient induction of apoptosis. The need for development of drug combinations with a strong pro-apoptotic activity is of particular interest in melanoma resistant to currently available chemotherapeutic regimes. We studied the pro-apoptotic properties of combination of tanespimycin+tipifarnib in five melanoma cell lines representing various stages of tumor progression. Our results show that in cells derived from vertical- and metastatic-phase the combination of tested drugs is strongly cytotoxic and efficient in inducing apoptosis, as evidenced by activation of caspase-9 and caspase-3 and enhanced fragmentation of DNA.

  4. Tumor microRNA-29a expression and the risk of recurrence in stage II colon cancer.

    PubMed

    Weissmann-Brenner, Alina; Kushnir, Michal; Lithwick Yanai, Gila; Aharonov, Ranit; Gibori, Hadas; Purim, Ofer; Kundel, Yulia; Morgenstern, Sara; Halperin, Marissa; Niv, Yaron; Brenner, Baruch

    2012-06-01

    There is emerging evidence for the prognostic role of various microRNA (miRNA) molecules in colon cancer. The aim of this study was therefore to compare the miRNA profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. The study population included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies between 1995 and 2005 without adjuvant therapy and for whom reliable miRNA expression data were available. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples. Initial profiling, using microarrays, was done in order to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23, 21%) and those who did not (good prognosis group, n=87, 79%) in the entire group and within each stage. The results showed that in stage I, none of the 903 miRNAs tested showed differential expression between patients with good prognosis compared with those with poor prognosis. In contrast, in stage II, one miRNA, miR-29a, showed a clear differential expression between the groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival (DFS), on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar impact of this miR on DFS. In conclusion, this study demonstrated a significant impact of miR-29a on the risk of recurrence in patients with stage II but not in patients with stage I colon cancer. Based on these results, a validation study is planned.

  5. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age.

    PubMed

    Brown, Linda Morris; Devesa, Susan S; Chow, Wong-Ho

    2008-08-20

    Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22,759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100,000 person-years (95% confidence interval [CI] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100,000 person-years (95% CI = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% CI = 0.13 to 0.21) to 0.74 per 100,000 person-years (95% CI = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.

  6. Primary liver tumors in pediatric patients: proper imaging technique for diagnosis and staging.

    PubMed

    Rozell, Joseph M; Catanzano, Tara; Polansky, Stanley M; Rakita, Dmitry; Fox, Lindsay

    2014-08-01

    Liver tumors in children are rare and comprise a diverse set of both benign and malignant lesions, most of which are not clinically detected until they are large and often difficult to resect. Technological advances in diagnostic imaging have greatly influenced the surgical planning of these lesions and ultimately the clinical outcome. The intent of this article is to present an imaging algorithm for the effective and efficient workup of liver tumors in pediatric patients. This includes the appropriate timing and use of various imaging modalities, such as conventional radiographs, ultrasound, computed tomography, and magnetic resonance imaging. This article also addresses the use of sedation, intravenous contrast agents, and the benefits and limitations of specific imaging modalities. An overview of the radiologic and pathologic findings in common liver lesions in pediatric patients, as well as individual case examples demonstrating the use of the proposed workup algorithm, is provided.

  7. Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: Impact of tumor volume

    SciTech Connect

    Basaki, Kiyoshi . E-mail: basaki-rad@umin.ac.jp; Abe, Yoshinao; Aoki, Masahiko; Kondo, Hidehiro; Hatayama, Yoshiomi; Nakaji, Shigeyuki

    2006-02-01

    Purpose: To investigate the impact of tumor volume on overall survival in patients with Stage III non-small-cell lung cancer (NSCLC) treated with definitive radiation therapy (RT). Methods and Materials: Between May 1997 and February 2003, 71 patients with Stage III NSCLC were treated with radiation therapy of 60 Gy or more. The total target dose was between 60 and 77 Gy (average, 66.3 Gy). Chemotherapy was used in 45 cases. The primary tumor and nodal volume were identified in pretreatment computed tomography scans. Univariate and multivariate analyses were used to evaluate the impact of tumor volume on survival after RT. Results: The overall 2-year survival rate was 23%, with a median survival time of 14 months. The median survival times were 10 months and 19 months with large primary tumor volume more than median volume and smaller primary tumor volume, respectively. At a univariate analysis, the total tumor volume (TTV) (p < 0.0003) and the primary tumor volume (p < 0.00008) were significant and the nodal volume was not. At multivariate analyses, both the TTV and the primary tumor volume were significant prognostic factors. Conclusion: The primary tumor volume as well as TTV is a significant prognostic factor on survival in patients with Stage III NSCLC treated with RT and should be recorded in clinical results when the survivals are compared among clinical studies.

  8. Biomarkers in Tissue Samples From Patients With High-Risk Wilms Tumor

    ClinicalTrials.gov

    2016-05-17

    Clear Cell Sarcoma of the Kidney; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Rhabdoid Tumor of the Kidney; Stage I Wilms Tumor; Stage II Wilms Tumor; Stage III Wilms Tumor; Stage IV Wilms Tumor; Stage V Wilms Tumor

  9. Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease

    PubMed Central

    Hallan, Stein I.; Matsushita, Kunihiro; Sang, Yingying; Mahmoodi, Bakhtawar K.; Black, Corri; Ishani, Areef; Kleefstra, Nanne; Naimark, David; Roderick, Paul; Tonelli, Marcello; Wetzels, Jack F.M.; Astor, Brad C.; Gansevoort, Ron T.; Levin, Adeera; Wen, Chi-Pang; Coresh, Josef

    2014-01-01

    Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) of age on the association of estimated GFR and albuminuria with clinical risk examining both relative and absolute risk. Design, Setting, Participants We investigated 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australesia, Europe, and North/South America conducted during 1972–2011 with mean follow-up time of 5.8 years (range 0–31 years). Main Outcome Measures Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholestserol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. Results Mortality (112,325 deaths) and ESRD (8,411 events) risk were higher at lower eGFR and higher albuminuria in every age category. In general/high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age: e.g., adjusted HRs (95% CI) at eGFR 45 vs. 80 ml/min/1.73m2 were 3.50 (2.55–4.81), 2.21 (2.02–2.41), 1.59 (1.42–1.77), and 1.35 (1.23–1.48) in age categories 18–54, 55–64, 65–74 and 75+ years, respectively (P-values for age interaction <0.05). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0–12.8], 12.2 [10.3–14.3], 13.3 [9.0–18.6], and 27.2 [13.5–45.5] excess deaths per 1,000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age were less evident, while differences in absolute risk were higher in the older age categories (7.5 [95% CI, 4.3–11.9], 12.2 [7.9–17

  10. [Cervical cancer staging - preoperative assessment of tumor extent (a review of the most recent ultrasound studies)].

    PubMed

    Fischerová, D

    2014-12-01

    For treatment planning of cervical cancer it is necessary preoperatively to determine the presence and size of residual tumour after the biopsy, the tumour topography within the cervix and the parametrial and lymph node status. According to current data, ultrasound is comparably accurate with magnetic resonance imaging in view of tumour presence and local extent assessment. Ultrasound, if compared with the magnetic resonance imaging, does not have known contraindications and it is a broadly available diagnostic test. Currently no advanced imaging technique exists that can reliably detect infiltrated lymph nodes in the clinically early stage of the disease, as it often manifests as micrometastatic involvement in non-enlarged lymph nodes. The sensitivity of lymph node detection using ultrasound in the early stage is around 40%, but the specificity is high (96%). For daily practice, this means that a negative ultrasound finding should be always verified by surgical staging based on systematic lymphadenectomy, while positive ultrasound finding usually changes the treatment strategy.

  11. [Testosterone production by tumor tissue in partial androgen deficiency in aged men (PADAM)].

    PubMed

    Pecherskiĭ, A V; Semiglazov, V F; Komiakov, B K; Guliev, B G; Gorelov, A I; Novikov, A I; Pecherskiĭ, V I; Simonov, N N; Guliaev, A V; Samusenko, I A

    2005-01-01

    The aim of the study was examination of cause-effect relationships between PADAM, extragonadal production of androgens and high proliferative activity in aged men. The study group included 15 patients aged between 53 and 79 years with prostatic cancer (n = 5), urinary bladder cancer (n = 5) and cancer of the rectum (n = 5). Control samples of tissues of the prostatic gland, urinary bladder and rectum were obtained from dead bodies of men at the age between 18 and 29 years killed in the accidents at the age from 18 to 29 years. Testosterone levels in the tissues of peritumor zone of the prostate, in tumor tissue of patients with cancer of the prostate, urinary bladder and the rectum were higher than in blood serum. In prostatic cancer, testosterone in the tumor tissue was higher than in the tissues of prostatic peritumor zone. The values of Histochemical score AR of the peritumor zone in prostatic cancer patients were higher than those of the control group. It was detected that ER, PR, bcl-2, Ki-67 and p53 in prostatic tissue of young controls were absent while in patients with prostatic cancer these factors were expressed in the peritumor zone. In cancer of the urinary bladder, peritumor zone showed expression of PR, bcl-2, Ki-67 and p53, while no such expression was in the controls. ER, bcl-2, Ki-67 and p53 were registered in the peritumor zone of patients with cancer of the rectum but the controls had neither ER, bcl-2 nor p53 while Ki-67 expression in rectal cancer was higher than in the controls. The results of the study suggest that testosterone production by some tumors and tissues of the peritumor zone accompanied with high proliferative activity and dysregulation of the cell cycle is secondary to PADAM. These changes arise to compensate testicular deficiency and are manifestations of metabolic syndrome (X-syndrome). In this situation immune system fails to utilize all atypical cells.

  12. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    PubMed Central

    Schick, Tina; Altay, Lebriz; Viehweger, Eva; Hoyng, Carel B.; den Hollander, Anneke I.; Felsch, Moritz; Fauser, Sascha

    2016-01-01

    Background Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. Methods In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. Results Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). Conclusion The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was

  13. Some implications of Scale Relativity theory in avascular stages of growth of solid tumors in the presence of an immune system response.

    PubMed

    Buzea, C Gh; Agop, M; Moraru, Evelina; Stana, Bogdan A; Gîrţu, Manuela; Iancu, D

    2011-08-07

    We present a traveling-wave analysis of a reduced mathematical model describing the growth of a solid tumor in the presence of an immune system response in the framework of Scale Relativity theory. Attention is focused upon the attack of tumor cells by tumor-infiltrating cytotoxic lymphocytes (TICLs), in a small multicellular tumor, without necrosis and at some stage prior to (tumor-induced) angiogenesis. For a particular choice of parameters, the underlying system of partial differential equations is able to simulate the well-documented phenomenon of cancer dormancy and propagation of a perturbation in the tumor cell concentration by cnoidal modes, by depicting spatially heterogeneous tumor cell distributions that are characterized by a relatively small total number of tumor cells. This behavior is consistent with several immunomorphological investigations. Moreover, the alteration of certain parameters of the model is enough to induce soliton like modes and soliton packets into the system, which in turn result in tumor invasion in the form of a standard traveling wave. In the same framework of Scale Relativity theory, a very important feature of malignant tumors also results, that even in avascular stages they might propagate and invade healthy tissues, by means of a diffusion on a Newtonian fluid.

  14. Circulating Tumor DNA in Predicting Outcomes in Patients With Stage IV Head and Neck Cancer or Stage III-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-19

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  15. Interstitial radiation therapy for early-stage nasal vestibule cancer: A continuing quest for optimal tumor control and cosmesis

    SciTech Connect

    Levendag, Peter C. . E-mail: p.levendag@erasmusmc.nl; Nijdam, Wideke M.; Moolenburgh, Sanne E. van; Tan, Lisa; Noever, Inge R.T.T.; Rooy, Peter van; Mureau, Marc; Jansen, Peter P.; Munte, Kai; Hofer, Stefan O.P.

    2006-09-01

    Introduction: This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR). Methods and Materials: Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by a panel. Finally, full hospital costs are computed. Results: A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to Euro 5772 ($7044). Conclusion: Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to Euro 5772 ($7044 US). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.

  16. Two-stage model of radon-induced malignant lung tumors in rats: effects of cell killing

    NASA Technical Reports Server (NTRS)

    Luebeck, E. G.; Curtis, S. B.; Cross, F. T.; Moolgavkar, S. H.

    1996-01-01

    A two-stage stochastic model of carcinogenesis is used to analyze lung tumor incidence in 3750 rats exposed to varying regimens of radon carried on a constant-concentration uranium ore dust aerosol. New to this analysis is the parameterization of the model such that cell killing by the alpha particles could be included. The model contains parameters characterizing the rate of the first mutation, the net proliferation rate of initiated cells, the ratio of the rates of cell loss (cell killing plus differentiation) and cell division, and the lag time between the appearance of the first malignant cell and the tumor. Data analysis was by standard maximum likelihood estimation techniques. Results indicate that the rate of the first mutation is dependent on radon and consistent with in vitro rates measured experimentally, and that the rate of the second mutation is not dependent on radon. An initial sharp rise in the net proliferation rate of initiated cell was found with increasing exposure rate (denoted model I), which leads to an unrealistically high cell-killing coefficient. A second model (model II) was studied, in which the initial rise was attributed to promotion via a step function, implying that it is due not to radon but to the uranium ore dust. This model resulted in values for the cell-killing coefficient consistent with those found for in vitro cells. An "inverse dose-rate" effect is seen, i.e. an increase in the lifetime probability of tumor with a decrease in exposure rate. This is attributed in large part to promotion of intermediate lesions. Since model II is preferable on biological grounds (it yields a plausible cell-killing coefficient), such as uranium ore dust. This analysis presents evidence that a two-stage model describes the data adequately and generates hypotheses regarding the mechanism of radon-induced carcinogenesis.

  17. The Living Stage Improvisational Theatre Demonstration Project for Orthopedically Handicapped Children, Ages 4-8. Overview, 1978-1981.

    ERIC Educational Resources Information Center

    Alexander, Robert; Haynes, Wendy

    The Living Stage Improvisational Theatre Demonstration Project (Washington, D.C.) conducts weekly workshops to enhance the creative expression and self esteem of orthopedically handicapped children, aged 4 to 8 years. The Living Stage program is designed to demonstrate that methods of improvisational theatre can have a positive impact on parental…

  18. Tumoral CD10 Expression Correlates with High-Grade Histology and Increases Risk of Recurrence in Patients with Stage I Lung Adenocarcinoma

    PubMed Central

    Kadota, Kyuichi; Buitrago, Daniel; Lee, Ming-Ching; Villena-Vargas, Jonathan; Sima, Camelia S.; Jones, David R.; Travis, William D.; Adusumilli, Prasad S.

    2015-01-01

    Objective CD10 (neutral endopeptidase) is expressed in various normal and tumor cells, and its biological function can be controlled through enzymatic activity and signaling pathways. We investigated whether CD10 expression predicted disease recurrence and whether it correlated with histologic subtypes of stage I lung adenocarcinoma. Material and Methods We reviewed tumor slides of resected pathologic stage I lung adenocarcinomas (1995–2009). Tumors were classified according to the IASLC/ATS/ERS classification. CD10 immunohistochemistry was performed using tissue microarrays (n = 915). We combined the intensity (0–3) and distribution scores (0–2) for CD10 to create a total score (0–5). Risk of recurrence was estimated using competing risks methods. Results In the training cohort (n = 313), risk of recurrence of patients with high tumoral CD10 (score > 1, n = 57) was significantly higher (5-year cumulative incidence of recurrence [CIR], 37%) than in those with low CD10 (score ≤ 1; n = 256; 5-year CIR, 16%; P < 0.001); this finding was confirmed in the validation cohort (n = 602, P = 0.036). High tumoral CD10 was associated with higher risk of recurrence in acinar (P = 0.007) and papillary predominant tumors (P = 0.022). High tumoral CD10 was most frequently identified in micropapillary predominant (41%) and solid predominant tumors (34%). On multivariate analysis of intermediate-grade tumors, high tumoral CD10 remained a significant independent risk factor of recurrence (hazard ratio, 1.88; P = 0.025). Conclusion In stage I lung adenocarcinoma, tumoral CD10 correlated with high-grade histology and was an independent predictor of recurrence in intermediate-grade tumors. PMID:26141216

  19. The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment.

    PubMed

    Stoll, Elizabeth A; Horner, Philip J; Rostomily, Robert C

    2013-10-01

    Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as 'critical nodes' in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy.

  20. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression.

    PubMed

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

    2016-05-03

    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2.

  1. Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.

    PubMed

    Giráldez, María Dolores; Lozano, Juan José; Cuatrecasas, Míriam; Alonso-Espinaco, Virginia; Maurel, Joan; Mármol, Maribel; Hörndler, Carlos; Ortego, Javier; Alonso, Vicente; Escudero, Pilar; Ramírez, Gina; Petry, Christoph; Lasalvia, Luis; Bohmann, Kerstin; Wirtz, Ralph; Mira, Aurea; Castells, Antoni

    2013-03-01

    Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5'fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

  2. Study of Kidney Tumors in Younger Patients

    ClinicalTrials.gov

    2016-11-18

    Clear Cell Sarcoma of the Kidney; Congenital Mesoblastic Nephroma; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Wilms Tumor; Stage II Renal Cell Cancer; Stage II Wilms Tumor; Stage III Renal Cell Cancer; Stage III Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Wilms Tumor; Stage V Wilms Tumor

  3. TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors.

    PubMed

    Sakai, Eiji; Fukuyo, Masaki; Matsusaka, Keisuke; Ohata, Ken; Doi, Noriteru; Takane, Kiyoko; Matsuhashi, Nobuyuki; Fukushima, Junichi; Nakajima, Atsushi; Kaneda, Atsushi

    2016-06-01

    Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma-carcinoma sequence, some CRC develop through flat lesions, so-called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate-methylation with KRAS mutation and low-methylation with absence of oncogene mutation. Intermediate-methylation LST were mostly granular type LST (LST-G) and low-methylation LST were mostly non-granular LST (LST-NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non-synonymous mutations, although there was no significant difference in the frequency of total mutations between LST-G and LST-NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST-G but 26% (13/50) of LST-NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma-carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST-NG.

  4. [Utilization of Werner syndrome mouse model in studying premature aging and tumor].

    PubMed

    Jia, Shu-Ting; Yang, Shi-Hua; Luo, Ying

    2009-08-01

    Werner syndrome (WS) is a rare autosomal recessive genetic disease in human. It is considered as a good model disease in studying human premature syndrome. Werner protein (WRN) is a nuclear protein mutated in WS. Recent biochemical and genetic studies indicated that WRN plays important roles in DNA replication, DNA repair, and telomere maintenance. Here, we reviewed the molecular genetics of WS and the importance of telomere and WRN in the development of WS. Knocking out both telomerase and Wrn genes in mouse faithfully manifests human WS. The mouse model provides a unique genetic platform to explore the crosstalk of premature aging and tumor.

  5. Adaptation of the Ages and Stages Questionnaire for Remote Aboriginal Australia.

    PubMed

    D'Aprano, Anita; Silburn, Sven; Johnston, Vanessa; Robinson, Gary; Oberklaid, Frank; Squires, Jane

    2016-04-01

    A key challenge to providing quality developmental care in remote Aboriginal primary health care (PHC) centers has been the absence of culturally appropriate developmental screening instruments. This study focused on the cross-cultural adaptation of the Ages and Stages Questionnaires, 3rd edition (ASQ-3), with careful attention to language and culture. We aimed to adapt the ASQ-3 for use with remote dwelling Australian Aboriginal children, and to investigate the cultural appropriateness and feasibility of the adapted ASQ-3 for use in this context. We undertook a qualitative study in two remote Australian Aboriginal communities, using a six-step collaborative adaptation process. Aboriginal Health Workers (AHWs) were trained to use the adapted ASQ-3, and follow-up interviews examined participants' views of the cultural acceptability and usefulness of the adapted instrument. The adapted ASQ-3 was found to have high face validity and to be culturally acceptable and relevant to parents, AHWs, and early childhood development experts.

  6. Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.

    PubMed Central

    Maass, G; Schmidt, W; Berger, M; Schilcher, F; Koszik, F; Schneeberger, A; Stingl, G; Birnstiel, M L; Schweighoffer, T

    1995-01-01

    Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:7777545

  7. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

    PubMed Central

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J.; Strausberg, Robert L.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Gibbs, Peter

    2017-01-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing–based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID:27384348

  8. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-06

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

  9. Effect of tumor characteristics and duplication of the muscularis mucosae on the endoscopic staging of superficial Barrett esophagus-related neoplasia.

    PubMed

    Mandal, Rajni V; Forcione, David G; Brugge, William R; Nishioka, Norman S; Mino-Kenudson, Mari; Lauwers, Gregory Y

    2009-04-01

    Endoscopic mucosal resection (EMR) is being advocated as a diagnostic, staging, and therapeutic technique for the management of Barrett esophagus (BE)-related neoplasia. With the emergence of new endoluminal therapy including EMR for the treatment of BE-related superficial adenocarcinomas, accurate staging has become crucial to select patients for different treatment arms. Intramucosal adenocarcinomas can be successfully treated by endoluminal techniques, whereas submucosal invasive tumors with a greater risk of lymph node metastasis are likely candidates for esophagectomy. Endoscopic ultrasound (EUS) is used to stage superficial BE-related neoplasms, yet endoscopic staging can be incongruent to that obtained after pathologic examination. In this study, we sought to determine morphologic factors, which may influence EUS staging in 35 cases with intramucosal adenocarcinoma diagnosed by subsequent EMR, focusing on tumor characteristics and structural changes associated with BE. Among the latter duplication of the muscularis mucosae, either fragmented or well-organized, was seen in 64% of 11 cases that were overstaged as having submucosal invasion by EUS, compared with 38% of those accurately staged. A greater vertical thickness of the tumor was also associated with overstaging by EUS (1.61+/-0.75 mm in the discordant vs. 1.16+/-0.67 mm in the concordant groups, P=0.028). The results illustrate how morphologic factors may affect EUS staging of superficial esophageal adenocarcinomas. EUS alone is not sufficient for staging these neoplasms precisely, and to accurately stratify patients into different treatment arms, EMR should play a role as a complementary staging modality.

  10. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some throat ...

  11. Survival of enteric pathogens during butterhead lettuce growth: crop stage, leaf age, and irrigation.

    PubMed

    Van der Linden, Inge; Cottyn, Bart; Uyttendaele, Mieke; Vlaemynck, Geertrui; Heyndrickx, Marc; Maes, Martine

    2013-06-01

    The survival of Salmonella enterica serovar Thompson and Escherichia coli O157 was investigated on growing butterhead lettuce plants in the plant-growth chamber and greenhouse. All inoculation tests were made under conditions that approximate the greenhouse conditions for butterhead lettuce cultivation in Flanders (Belgium). The survival and proliferation of the pathogens on the leaves was determined at days 0, 4, and 8 after inoculation using standard plating techniques on selective medium. In the growth chamber, the extent to which both pathogens were able to multiply on the lettuce leaves was influenced by crop stage and leaf age. On young plants, the older leaves supported pathogen survival better. On nearly mature plants, pathogen population sizes were significantly higher on the old and young leaves compared with middle-aged leaves (p<0.001). In the greenhouse, the environmental regimen with high fluctuations in temperature and relative humidity was less conducive to the survival of E. coli O157, though its survival on nearly mature lettuce was enhanced by overhead irrigation. The moist conditions between the folded inner leaves are likely contributing to the survival of enteric pathogens in the lettuce head. Butterhead lettuce grown in greenhouses with a sprinkle irrigation system may present a potential health hazard when contaminated near harvest. Experimental design (growth chamber versus greenhouse) largely influences enteric pathogen behavior on growing lettuce plants.

  12. Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer

    PubMed Central

    Liu, Chang; Eng, Cathy; Shen, Jianjun; Lu, Yue; Takata, Yoko; Mehdizadeh, Amir; Chang, George J.; Rodriguez-Bigas, Miguel A.; Li, Yanan; Chang, Ping; Mao, Yixiang; Hassan, Manal M.; Wang, Fangyu; Li, Donghui

    2016-01-01

    Purpose The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer. Results 145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0.002). The reduced expression was significantly related to increased risk of tumor recurrence and risk of death. As a predictor for tumor recurrence, ROC analysis revealed the AUC (95% CI) was 0.72 (0.59-0.85, P=0.001) for lower level of miR-4772-3p compared to 0.63 (0.51-0.75, P=0.062) for tumor site and 0.65 (0.51-0.78,P=0.034) for lymph node status. Among 66/84 patients who received FOLFOX adjuvant therapy, 9/10 (90%) patients with a lower level and 10/56 (18%) patients with a higher level of miR-4772-3p had tumor recurrence (P<0.001). Materials and Methods Blood samples were prospectively collected from84 patients with stage II/III colon cancer after tumor resection and before adjuvant therapy. Serum exosomal miRNA profiles were determined by RNA sequencing. Differentially expressed mature miRNAs were identified between patients with or without tumor recurrence. The top hits were validated in individual RNA samples using quantitative real-time reverse transcription PCR. Conclusions Reduced expression of serum exosomal miR-4772-3p is a prognostic biomarker for tumor recurrence in stage II and stage III colon cancer patients. The predictive value of this marker for response to FOLFOX adjuvant therapy needs further investigation. PMID:27788488

  13. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine

    PubMed Central

    Kristofco, Lauren A.; Cruz, Luis Colon; Haddad, Samuel P.; Behra, Martine L; Chambliss, C. Kevin; Brooks, Bryan W.

    2016-01-01

    Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4–10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72 h studies were conducted at 1–4, 4–7 and 7–10 dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10 dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p < 0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4–10 dpf). 10 dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7 dpf larvae with an environmentally realistic lowest observed effect concentration of 200 ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0–4 dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more

  14. Age matters: Developmental stage of Danio rerio larvae influences photomotor response thresholds to diazinion or diphenhydramine.

    PubMed

    Kristofco, Lauren A; Cruz, Luis Colon; Haddad, Samuel P; Behra, Martine L; Chambliss, C Kevin; Brooks, Bryan W

    2016-01-01

    Because basic toxicological data is unavailable for the majority of industrial compounds, High Throughput Screening (HTS) assays using the embryonic and larval zebrafish provide promising approaches to define bioactivity profiles and identify potential adverse outcome pathways for previously understudied chemicals. Unfortunately, standardized approaches, including HTS experimental designs, for examining fish behavioral responses to contaminants are rarely available. In the present study, we examined movement behavior of larval zebrafish over 7 days (4-10 days post fertilization or dpf) during typical daylight workday hours to determine whether intrinsic activity differed with age and time of day. We then employed an early life stage approach using the Fish Embryo Test (FET) at multiple developmental ages to evaluate whether photomotor response (PMR) behavior differed with zebrafish age following exposure to diazinon (DZN), a well-studied orthophosphate insecticide, and diphenhydramine (DPH), an antihistamine that also targets serotonin reuptake transporters and the acetylcholine receptor. 72h studies were conducted at 1-4, 4-7 and 7-10dpf, followed by behavioral observations using a ViewPoint system at 4, 7 and 10dpf. Distance traveled and swimming speeds were quantified; nominal treatment levels were analytically verified by isotope-dilution LC-MSMS. Larval zebrafish locomotion displayed significantly different (p<0.05) activity profiles over the course of typical daylight and workday hours, and these time of day PMR activity profiles were similar across ages examined (4-10dpf). 10dpf zebrafish larvae were consistently more sensitive to DPH than either the 4 or 7dpf larvae with an environmentally realistic lowest observed effect concentration of 200ng/L. Though ELS and FET studies with zebrafish typically focus on mortality or teratogenicity in 0-4dpf organisms, behavioral responses of slightly older fish were several orders of magnitude more sensitive to DPH. Our

  15. Haploinsufficiency of the Myc regulator Mtbp extends survival and delays tumor development in aging mice

    PubMed Central

    Grieb, Brian C.; Boyd, Kelli; Mitra, Ramkrishna; Eischen, Christine M.

    2016-01-01

    Alterations of specific genes can modulate aging. Myc, a transcription factor that regulates the expression of many genes involved in critical cellular functions was shown to have a role in controlling longevity. Decreased expression of Myc inhibited many of the deleterious effects of aging and increased lifespan in mice. Without altering Myc expression, reduced levels of Mtbp, a recently identified regulator of Myc, limit Myc transcriptional activity and proliferation, while increased levels promote Myc-mediated effects. To determine the contribution of Mtbp to the effects of Myc on aging, we studied a large cohort of Mtbp heterozygous mice and littermate matched wild-type controls. Mtbp haploinsufficiency significantly increased longevity and maximal survival in mice. Reduced levels of Mtbp did not alter locomotor activity, litter size, or body size, but Mtbp heterozygous mice did exhibit elevated markers of metabolism, particularly in the liver. Mtbp+/− mice also had a significant delay in spontaneous cancer development, which was most prominent in the hematopoietic system, and an altered tumor spectrum compared to Mtbp+/+ mice. Therefore, the data suggest Mtbp is a regulator of longevity in mice that mimics some, but not all, of the properties of Myc in aging. PMID:27803394

  16. X-Ray Computed Tomography: Semiautomated Volumetric Analysis of Late-Stage Lung Tumors as a Basis for Response Assessments

    PubMed Central

    Bendtsen, C.; Kietzmann, M.; Korn, R.; Mozley, P. D.; Schmidt, G.; Binnig, G.

    2011-01-01

    Background. This study presents a semiautomated approach for volumetric analysis of lung tumors and evaluates the feasibility of using volumes as an alternative to line lengths as a basis for response evaluation criteria in solid tumors (RECIST). The overall goal for the implementation was to accurately, precisely, and efficiently enable the analyses of lesions in the lung under the guidance of an operator. Methods. An anthropomorphic phantom with embedded model masses and 71 time points in 10 clinical cases with advanced lung cancer was analyzed using a semi-automated workflow. The implementation was done using the Cognition Network Technology. Results. Analysis of the phantom showed an average accuracy of 97%. The analyses of the clinical cases showed both intra- and interreader variabilities of approximately 5% on average with an upper 95% confidence interval of 14% and 19%, respectively. Compared to line lengths, the use of volumes clearly shows enhanced sensitivity with respect to determining response to therapy. Conclusions. It is feasible to perform volumetric analysis efficiently with high accuracy and low variability, even in patients with late-stage cancer who have complex lesions. PMID:21747819

  17. High risk of development of renal cell tumor in end-stage kidney disease: the role of microenvironment.

    PubMed

    Nagy, Anetta; Walter, Eva; Zubakov, Dmitry; Kovacs, Gyula

    2016-07-01

    End-stage renal disease (ESRD) and acquired cystic renal disease (ACRD) are associated with high risk of development of renal cell tumors (RCT) displaying unusual phenotype and genotype. The underlying molecular mechanism is not yet known. To explore the molecular microenvironment, we have established the expression profile of ESRD/ACRD kidneys. RNA extracted from normal and ESRD/ACRD kidneys and distinct types of RCT was subjected to Affymetrix HG U133 micro array analysis. A gene expression signature indicated cancer-related biological processes in the remodeling of ESRD/ACRD kidneys. Quantitative RT-PCR studies confirmed a specific gene signature including a functional group of inflammatory cytokines and also cytokeratins associated with stem cell characteristics of epithelial cells. Several of the signature genes including the SCEL were expressed in ESRD/ACRD-associated papillary RCT as well. Immunohistological analysis confirmed the expression of CXCL8 and its receptor CXCR2 as well as the expression of SCEL in hyperplastic tubular, cystic, and papillary structures and RCTs in ESRD/ACRD kidney. Our data indicates that ESRD/ACRD is a novel disease and the inflammatory microenvironment altered plasticity, and stem cell characteristics of epithelial cells may be associated with the high risk of tumor development.

  18. Expression of Rab1A is upregulated in human lung cancer and associated with tumor size and T stage

    PubMed Central

    Qin, Xiaoyu; Huang, Tinglei; Huang, Bo; Zhang, Yanjie; Jiang, Bin

    2016-01-01

    Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined. The results demonstrated that Rab1A was significantly overexpressed in the different histological types of lung cancer as compared to non-cancerous tissues, and Rab1A expression was correlated with tumor volume and stage. In a large panel of lung cancer cell lines, high Rab1A expression was observed as compared to a normal lung/bronchus epithelial cell line. However, Rab1A protein levels were not correlated with mTORC1 (P-S6K1), mTORC2 (P-AKT), MEK (P-ERK), JNK (P-c-Jun) or p38MAPK (P-MK2) signaling. Rab1A knockdown had no effect on mTOR signaling or cell growth. These data suggested that Rab1A may be involved in the pathogenesis of human lung cancer in an mTOR- and MAPK-independent manner. PMID:27902464

  19. Tumor necrosis factor receptors support murine hematopoietic progenitor function in the early stages of engraftment.

    PubMed

    Pearl-Yafe, Michal; Mizrahi, Keren; Stein, Jerry; Yolcu, Esma S; Kaplan, Ofer; Shirwan, Haval; Yaniv, Isaac; Askenasy, Nadir

    2010-07-01

    Tumor necrosis factor (TNF) family receptors/ligands are important participants in hematopoietic homeostasis, in particular as essential negative expansion regulators of differentiated clones. As a prominent injury cytokine, TNF-alpha has been traditionally considered to suppress donor hematopoietic stem and progenitor cell function after transplantation. We monitored the involvement of TNF receptors (TNF-R) 1 and 2 in murine hematopoietic cell engraftment and their inter-relationship with Fas. Transplantation of lineage-negative (lin(-)) bone marrow cells (BMC) from TNF receptor-deficient mice into wild-type recipients showed defective early engraftment and loss of durable hematopoietic contribution upon recovery of host hematopoiesis. Consistently, cells deficient in TNF receptors had reduced competitive capacity as compared to wild-type progenitors. The TNF receptors were acutely upregulated in bone marrow (BM)-homed donor cells (wild-type) early after transplantation, being expressed in 60%-75% of the donor cells after 6 days. Both TNF receptors were detected in fast cycling, early differentiating progenitors, and were ubiquitously expressed in the most primitive progenitors with long-term reconstituting potential (lin(-)c-kit(+) stem cell antigen (SCA)-1(+)). BM-homed donor cells were insensitive to apoptosis induced by TNF-alpha and Fas-ligand and their combination, despite reciprocal inductive cross talk between the TNF and Fas receptors. The engraftment supporting effect of TNF-alpha is attributed to stimulation of progenitors through TNF-R1, which involves activation of the caspase cascade. This stimulatory effect was not observed for TNF-R2, and this receptor did not assume redundant stimulatory function in TNFR1-deficient cells. It is concluded that TNF-alpha plays a tropic role early after transplantation, which is essential to successful progenitor engraftment.

  20. Aging-associated B7-DC+ B cells enhance anti-tumor immunity via Th1 and Th17 induction.

    PubMed

    Tomihara, Kei; Shin, Takako; Hurez, Vincent J; Yagita, Hideo; Pardoll, Drew M; Zhang, Bin; Curiel, Tyler J; Shin, Tahiro

    2012-02-01

    Because most patients with cancer are aged and because immunological functions are altered during aging, it is important to account for aging-associated immunological alterations in the design of new cancer immunotherapies. We thus compared immune populations in young and aged mice and found that B7-DC(+) (PD-L2/CD273) B cells, a minor population in young mice, were significantly increased in aged mice. Induction of both Th1 and Th17 cells was significantly augmented by B7-DC(+) B cells from aged mice, and this effect was blocked with anti-B7-DC antibodies in vitro and in vivo. Moreover, retardation of tumor growth in aged mice was largely B7-DC dependent. Tumor growth in young mice was significantly inhibited by immunization with B7-DC(+) B cells from aged mice owing to increased induction of tumor antigen-specific cytotoxic T lymphocytes. These data indicate that B7-DC(+) B cells could play an important role in aging-associated cancer immunopathology as well as in other aging-associated diseases and further suggest that B7-DC(+) B cells have potential for future cancer immunotherapy.

  1. ASSOCIATION BETWEEN HUMAN PAPILLOMAVIRUS AND COLORECTAL ADENOCARCINOMA AND ITS INFLUENCE ON TUMOR STAGING AND DEGREE OF CELL DIFFERENTIATION

    PubMed Central

    PICANÇO-JUNIOR, Olavo Magalhães; OLIVEIRA, Andre Luiz Torres; FREIRE, Lucia Thereza Mascarenhas; BRITO, Rosangela Baia; VILLA, Luisa Lina; MATOS, Délcio

    2014-01-01

    Background Colorectal cancer is one of the most common types of neoplasia among the worldwide adult population. Among neoplasms of the gastrointestinal tract, it is ranked second in relation to prevalence and mortality, but its etiology is only known in around 5% of the cases. It is believed that 15% of malignant diseases are related to viral oncogenesis. Aim To correlate the presence of HPV with the staging and degree of cell differentiation among patients with colorectal adenocarcinoma. Methods A retrospective case-control study was conducted on 144 patients divided between a test group of 79 cases of colorectal cancer and a control group to analyze 144 patients aged 25 to 85 years (mean, 57.85 years; standard deviation, 15.27 years and median, 58 years). Eighty-six patients (59.7%) were male. For both groups, tissue samples from paraffin blocks were subjected to DNA extraction followed by the polymerase chain reaction using generic and specific primers for HPV 16 and 18. Dot blot hybridization was also performed with the aim of identifying HPV DNA. Results The groups were shown to be homogenous regarding sex, age and site of HPV findings in the samples analyzed. Out of the 41 patients with HPV, 36 (45.6%) were in the cases and five (7.7%) were in the control group (p<0.001). All the HPV cases observed comprised HPV 16, and HPV 18 was not shown in any of the cases studied. There were no significant differences in comparisons of sex, age and site regarding the presence of HPV in either of the groups. It was not observe any significant difference in relation to staging or degree of cell differentiation among the patients with colorectal cancer. Conclusion Human papillomavirus type 16 is present in individuals with colorectal carcinoma. However, its presence was unrelated to staging or degree of differentiation. PMID:25184765

  2. ADAPTING A PARENT-COMPLETED, SOCIOEMOTIONAL QUESTIONNAIRE IN CHINA: THE AGES & STAGES QUESTIONNAIRES: SOCIAL-EMOTIONAL.

    PubMed

    Bian, Xiaoyan; Xie, Huichao; Squires, Jane; Chen, Chieh-Yu

    2017-03-01

    The Ages & Stages Questionnaire: Social-Emotional (ASQ:SE; Squires, Bricker, & Twombly, 2002a), developed in the United States, was translated and adapted for use in China. Lack of valid and reliable instruments for identifying social and emotional delays in young children is a worldwide issue. Professionals in China have recently focused efforts on developing methods for early identification of social, emotional, and behavioral issues in the birth-to-5 population. Following the guidelines of the International Test Commission, the ASQ:SE was translated into Simplified Chinese (ASQ:SE-C) to collect a normative sample of 2,528 children across China. Data were analyzed to evaluate the psychometric properties of the ASQ:SE-C, using both classical test theory and item response theory, including generating cutoff points appropriate for the Chinese sample. A panel of Chinese experts was surveyed to assess face validity and estimated utility of the newly adapted tool. Discussions of research findings and implications for future studies are provided.

  3. Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro

    SciTech Connect

    Shimada, Y.; Kaji, K.; Ito, H.; Noda, K.; Matsuo, M. )

    1990-01-01

    We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in aged cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro.

  4. Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

    PubMed Central

    Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

    2016-01-01

    There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

  5. The Impact of Tumor Size on Outcomes After Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Allibhai, Zishan; Taremi, Mojgan; Bezjak, Andrea; Brade, Anthony; Hope, Andrew J.; Sun, Alexander; Cho, B.C. John

    2013-12-01

    Purpose: Stereotactic body radiation therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC) offers excellent control rates. Most published series deal mainly with small (usually <4 cm), peripheral, solitary tumors. Larger tumors are associated with poorer outcomes (ie, lower control rates, higher toxicity) when treated with conventional RT. It is unclear whether SBRT is sufficiently potent to control these larger tumors. We therefore evaluated and examined the influence of tumor size on treatment outcomes after SBRT. Methods and Materials: Between October 2004 and October 2010, 185 medically inoperable patients with early (T1-T2N0M0) NSCLC were treated on a prospective research ethics board-approved single-institution protocol. Prescription doses were risk-adapted based on tumor size and location. Follow-up included prospective assessment of toxicity (as per Common Terminology Criteria for Adverse Events, version 3.0) and serial computed tomography scans. Patterns of failure, toxicity, and survival outcomes were calculated using Kaplan-Meier method, and the significance of tumor size (diameter, volume) with respect to patient, treatment, and tumor factors was tested. Results: Median follow-up was 15.2 months. Tumor size was not associated with local failure but was associated with regional failure (P=.011) and distant failure (P=.021). Poorer overall survival (P=.001), disease-free survival (P=.001), and cause-specific survival (P=.005) were also significantly associated with tumor size (with tumor volume more significant than diameter). Gross tumor volume and planning target volume were significantly associated with grade 2 or worse radiation pneumonitis. However, overall rates of grade ≥3 pneumonitis were low and not significantly affected by tumor or target size. Conclusions: Currently employed stereotactic body radiation therapy dose regimens can provide safe effective local therapy even for larger solitary NSCLC tumors (up to 5.7 cm

  6. Analysis of Molecular Markers by Anatomic Tumor Site in Stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance)

    PubMed Central

    Sinicrope, Frank A.; Mahoney, Michelle R.; Yoon, Harry H.; Smyrk, Thomas C.; Thibodeau, Stephen N.; Goldberg, Richard M.; Nelson, Garth D.; Sargent, Daniel J.; Alberts, Steven R.

    2015-01-01

    PURPOSE To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas. Experimental Design In a randomized trial of adjuvant FOLFOX + cetuximab, BRAFV600E and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N=3,018) in relationship to tumor location including subsite. Cox models were used to assess clinical outcome including overall survival (OS). RESULTS KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Non-mutated BRAF or KRAS tumors progressively decreased from sigmoid to transverse (all p<0.0001). Significantly poorer OS was found for mutant KRAS in distal [HR, 1.98 (1.49–2.63); p<.0001] vs proximal [1.25 (0.97–1.60), p=.079] cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal vs distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (padjusted=.043) and MMR (padjusted=.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: padjusted=0.001). CONCLUSIONS Mutations in BRAF or KRAS codon 12 were enriched in proximal cancers whereas non-mutated BRAF/KRAS were increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location. PMID:26187617

  7. Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

    SciTech Connect

    Fujisawa, Koichi; Terai, Shuji; Hirose, Yoshikazu; Takami, Taro; Yamamoto, Naoki; Sakaida, Isao

    2011-10-22

    Highlights: {yields} Zebrafish SMP30/RGN mRNA expression decreases with aging. {yields} Decreased expression was observed in liver tumors as compared to the surrounding area. {yields} SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish by administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.

  8. Disability Stage Is an Independent Risk Factor for Mortality in Medicare Beneficiaries 65 Years of Age and Older

    PubMed Central

    Hennessy, Sean; Kurichi, Jibby E.; Pan, Qiang; Streim, Joel E.; Bogner, Hillary; Xie, Dawei; Stineman, Margaret G.

    2015-01-01

    Background Stages of activity limitation based on activities of daily living (ADLs) and instrumental activities of daily living (IADLs) have been found to predict mortality in those age 70 years and above but have not been examined in Medicare beneficiaries age 65 years and older using routinely collected data. Objective To examine the association between functional stages based on activities of ADLs and IADLs with three-year mortality in Medicare beneficiaries age 65 years and older, accounting for baseline sociodemographics, heath status, smoking, subjective health, and psychological well-being. Design Cohort study using the Medicare Current Beneficiary Survey (MCBS) and associated health care utilization data. Setting Community administered survey. Participants We included 9698 Medicare beneficiaries 65 years of age and older who entered the MCBS in 2005–07. Main outcome measures Death within three years of cohort entry. Results The overall mortality rate was 3.6 per 100 person years, and three-year cumulative mortality was 10.3%. Unadjusted three-year mortality was monotonically associated with both ADL stage and IADL stag. Adjusted three-year mortality was associated with ADL and IADL stages, except that in some models the hazard ratio for stage III (which includes persons with atypical activity limitation patterns) was numerically lower than that for stage II. Conclusion We found nearly monotonic relationships between ADL and IADL stage and adjusted three-year mortality. These findings could aid in the development of population health approaches and metrics for evaluating the success of alternative economic, social, or health policies on the longevity of older adults with activity limitations. PMID:26003869

  9. Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of Neuroendocrine Tumors

    PubMed Central

    Deppen, Stephen A.; Liu, Eric; Blume, Jeffrey D.; Clanton, Jeffrey; Shi, Chanjuan; Jones-Jackson, Laurie B.; Lakhani, Vipul; Baum, Richard P.; Berlin, Jordan; Smith, Gary T.; Graham, Michael; Sandler, Martin P.; Delbeke, Dominique; Walker, Ronald C.

    2017-01-01

    Our purpose was to evaluate safety and efficacy of 68Ga-DOTATATE PET/CT compared with 111In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. Methods 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after 68Ga-DOTATATE injection. Added value was determined by changes in treatment plan when 68Ga-DOTATATE PET/CT results were added to all prior imaging, including 111In-pentetreotide. Interobserver reproducibility of 68Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. Results 68Ga-DOTATATE PET/CT and 111In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). 68Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. 68Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by 111In-pentetreotide. Conclusion 68Ga-DOTATATE PET/CT was equivalent or superior to 111In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. 68Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with 111In-pentetreotide, 68Ga-DOTATATE imaging should be used instead of 111In-pentetreotide imaging where available. PMID:26769865

  10. Three-Dimensional Ground Glass Opacity Ratio in CT Images Can Predict Tumor Invasiveness of Stage IA Lung Cancer

    PubMed Central

    Yu, Woo Sik; Hong, Sae Rom; Lee, Jin Gu; Lee, Jae Seok; Jung, Hee Suk; Kim, Dae Joon; Chung, Kyung Young

    2016-01-01

    Purpose We investigated the relationship between various parameters, including volumetric parameters, and tumor invasiveness according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification. Materials and Methods We retrospectively reviewed 99 patients with completely resected stage IA lung adenocarcinoma. The correlation between several parameters [one-dimensional ground glass opacity (1D GGO) ratio, two-dimensional (2D) GGO ratio, three-dimensional (3D) GGO ratio, 1D solid size, 2D solid size, and 3D solid size] and tumor invasiveness according to IASLC/ATS/ERS classification was investigated using receiver operating characteristic (ROC) analysis. Adenocarcinoma in situ and minimally invasive adenocarcinoma were referred to as noninvasive adenocarcinoma. Results The areas under the curve (AUC) to predict invasive adenocarcinoma for the 1D, 2D, and 3D GGO ratios were 0.962, 0.967, and 0.971, respectively. The optimal cut-off values for the 1D, 2D, and 3D GGO ratios were 38%, 62%, and 74%, respectively. The AUC values for 1D, 2D, and 3D solid sizes to predict invasive adenocarcinoma were 0.933, 0.944, and 0.903, respectively. The optimal cut-off values for 1D, 2D, and 3D solid sizes were 1.2 cm, 1.5 cm2, and 0.7 cm3, respectively. The difference in the ROC curves for 3D GGO ratio and 3D solid size was significant (p=0.01). Conclusion Computed tomography image-related parameters based on GGO were well correlated with and predictive of invasiveness according to IASLC/ATS/ERS classification. 3D GGO ratio was more strongly correlated with pathologic invasiveness than 3D solid size. PMID:27401643

  11. Dense and Non-dense Mammographic Area and Risk of Breast Cancer by Age and Tumor Characteristics

    PubMed Central

    Bertrand, Kimberly A.; Scott, Christopher G.; Tamimi, Rulla M.; Jensen, Matthew R.; Pankratz, V. Shane; Norman, Aaron D.; Visscher, Daniel W.; Couch, Fergus J.; Shepherd, John; Chen, Yunn-Yi; Fan, Bo; Wu, Fang-Fang; Ma, Lin; Beck, Andrew H.; Cummings, Steven R.; Kerlikowske, Karla; Vachon, Celine M.

    2015-01-01

    Background Mammographic density (MD) is a strong breast cancer risk factor. We previously reported associations of percent MD with larger and node-positive tumors across all ages, and estrogen receptor (ER)-negative status among women ages <55 years. To provide insight into these associations, we examined the components of percent MD (dense area (DA) and non-dense area (NDA) with breast cancer subtypes. Methods Data were pooled from six studies including 4095 breast cancers and 8558 controls. DA and NDA were assessed from digitized film-screen mammograms and standardized across studies. Breast cancer odds by density phenotypes and age according to histopathological characteristics and receptor status were calculated using polytomous logistic regression. Results DA was associated with increased breast cancer risk [odds ratios (OR) for quartiles: 0.65, 1.00(Ref), 1.22, 1.55; p-trend <0.001] and NDA was associated with decreased risk [ORs for quartiles: 1.39, 1.00(Ref), 0.88, 0.72; p-trend <0.001] across all ages and invasive tumor characteristics. There were significant trends in the magnitude of associations of both DA and NDA with breast cancer by increasing tumor size (p-trend<0.001) but no differences by nodal status. Among women <55 years, DA was more strongly associated with increased risk of ER+ vs. ER− tumors [p-heterogeneity (het) = 0.02] while NDA was more strongly associated with decreased risk of ER− vs. ER+ tumors [p-het = 0.03]. Conclusions DA and NDA have differential associations with ER+ vs. ER− tumors that vary by age. Impact DA and NDA are important to consider when developing age- and subtype-specific risk models. PMID:25716949

  12. A novel highly potent trivalent TGF-β receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.

    PubMed

    Qin, Tai; Barron, Lindsey; Xia, Lu; Huang, Haojie; Villarreal, Maria M; Zwaagstra, John; Collins, Cathy; Yang, Junhua; Zwieb, Christian; Kodali, Ravindra; Hinck, Cynthia S; Kim, Sun Kyung; Reddick, Robert L; Shu, Chang; O'Connor-McCourt, Maureen D; Hinck, Andrew P; Sun, Lu-Zhe

    2016-12-27

    The effects of transforming growth factor beta (TGF-β) signaling on prostate tumorigenesis has been shown to be strongly dependent on the stage of development, with TGF-β functioning as a tumor suppressor in early stages of disease and as a promoter in later stages. To study in further detail the paradoxical tumor-suppressive and tumor-promoting roles of the TGF-β pathway, we investigated the effect of systemic treatment with a TGF-β inhibitor on early stages of prostate tumorigenesis. To ensure effective inhibition, we developed and employed a novel trivalent TGF-β receptor trap, RER, comprised of domains derived from the TGF-β type II and type III receptors. This trap was shown to completely block TβRII binding, to antagonize TGF-β1 and TGF-β3 signaling in cultured epithelial cells at low picomolar concentrations, and it showed equal or better anti-TGF-β activities than a pan TGF-β neutralizing antibody and a TGF-β receptor I kinase inhibitor in various prostate cancer cell lines. Systemic administration of RER inhibited prostate tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN) lesions in the prostate glands of Pten conditional null mice. These results provide evidence that TGF-β acts as a promoter rather than a suppressor in the relatively early stages of this spontaneous prostate tumorigenesis model. Thus, inhibition of TGF-β signaling in early stages of prostate cancer may be a novel therapeutic strategy to inhibit the progression as well as the metastatic potential in patients with prostate cancer.

  13. A novel highly potent trivalent TGF-β receptor trap inhibits early-stage tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands

    PubMed Central

    Qin, Tai; Barron, Lindsey; Xia, Lu; Huang, Haojie; Villarreal, Maria M.; Zwaagstra, John; Collins, Cathy; Yang, Junhua; Zwieb, Christian; Kodali, Ravindra; Hinck, Cynthia S.; Kim, Sun Kyung; Reddick, Robert L.; Shu, Chang; O’Connor-McCourt, Maureen D.; Hinck, Andrew P.; Sun, Lu-Zhe

    2016-01-01

    The effects of transforming growth factor beta (TGF-β) signaling on prostate tumorigenesis has been shown to be strongly dependent on the stage of development, with TGF-β functioning as a tumor suppressor in early stages of disease and as a promoter in later stages. To study in further detail the paradoxical tumor-suppressive and tumor-promoting roles of the TGF-β pathway, we investigated the effect of systemic treatment with a TGF-β inhibitor on early stages of prostate tumorigenesis. To ensure effective inhibition, we developed and employed a novel trivalent TGF-β receptor trap, RER, comprised of domains derived from the TGF-β type II and type III receptors. This trap was shown to completely block TβRII binding, to antagonize TGF-β1 and TGF-β3 signaling in cultured epithelial cells at low picomolar concentrations, and it showed equal or better anti-TGF-β activities than a pan TGF-β neutralizing antibody and a TGF-β receptor I kinase inhibitor in various prostate cancer cell lines. Systemic administration of RER inhibited prostate tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN) lesions in the prostate glands of Pten conditional null mice. These results provide evidence that TGF-β acts as a promoter rather than a suppressor in the relatively early stages of this spontaneous prostate tumorigenesis model. Thus, inhibition of TGF-β signaling in early stages of prostate cancer may be a novel therapeutic strategy to inhibit the progression as well as the metastatic potential in patients with prostate cancer. PMID:27863384

  14. Impact of Pretreatment Tumor Growth Rate on Outcome of Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

    SciTech Connect

    Atallah, Soha; Cho, B.C. John; Allibhai, Zishan; Taremi, Mojgan; Giuliani, Meredith; Le, Lisa W.; Brade, Anthony; Sun, Alexander; Bezjak, Andrea; Hope, Andrew J.

    2014-07-01

    Purpose: To determine the influence of pretreatment tumor growth rate on outcomes in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Methods and Materials: A review was conducted on 160 patients with T1-T2N0M0 NSCLC treated with SBRT at single institution. The patient's demographic and clinical data, time interval (t) between diagnostic and planning computed tomography (CT), vital status, disease status, and cause of death were extracted from a prospectively kept database. Differences in gross tumor volume between diagnostic CT (GTV1) and planning CT (GTV2) were recorded, and growth rate was calculated by use of specific growth rate (SGR). Kaplan-Meier curves were constructed for overall survival (OS). Differences between groups were compared with a log-rank test. Multivariate analyses were performed by use of the Cox proportional hazard model with SGR and other relevant clinical factors. Cumulative incidence was calculated for local, regional, and distant failures by use of the competing risk approach and was compared with Gray's test. Results: The median time interval between diagnostic and planning CT was 82 days. The patients were divided into 2 groups, and the median SGR was used as a cut-off. The median survival times were 38.6 and 27.7 months for the low and high SGR groups, respectively (P=.03). Eastern Cooperative Oncology Group performance status (P=.01), sex (P=.04), SGR (P=.03), and GTV2 (P=.002) were predictive for OS in multivariable Cox regression analysis and, except sex, were similarly predictive for failure-free survival (FFS). The 3-year cumulative incidences of regional failure were 19.2% and 6.0% for the high and low SGR groups, respectively (P=.047). Conclusion: High SGR was correlated with both poorer OS and FFS in patients with early-stage NSCLC treated with SBRT. If validated, this measurement may be useful in identifying patients most likely to benefit from adjuvant

  15. Increased Serum Insulin Exposure Does Not Affect Age or Stage of Pancreatic Adenocarcinoma Diagnosis in Patients with Diabetes Mellitus

    PubMed Central

    Chao, David T.; Shah, Nilesh H.; Zeh, Herbert J.; Bahary, Nathan; Whitcomb, David C.; Brand, Randall E.

    2015-01-01

    Objectives In considering whether medications that increase insulin levels accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC patients with diabetes mellitus (DM) who used exogenous insulin or insulin-stimulating medications should have an earlier age of diagnosis or present with more advanced disease. Methods Patients enrolled in our PC registry from 6/1/2003 to 5/31/2012 were stratified according to treatment solely with insulin, insulin-stimulating medications, or insulin-independent medications. Age of PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed among the cohorts. Results Of 122 DM patients (mean age: 67.4 ± 10.2 years), the mean age of PC diagnosis within the insulin-only (n=40), insulin-stimulating (n=11), insulin-independent (n=71), and non-DM (n=321) cohorts were 68.7 ± 10.5 years, 69.6 ± 10.8 years, 66.3 ± 9.7 years, and 65.5 ± 10.5 years, respectively. No significant difference among the age of PC diagnosis was observed based on duration or type of DM treatment. There was no correlation between PC stage and increased insulin exposure. Conclusions Anti-DM medications that increase exposure to insulin do not appear to accelerate PC development using outcomes of mean age of PC diagnosis, PC stage, or duration between DM and PC diagnoses. PMID:26418902

  16. Testosterone related to age and life-history stages in male baboons and geladas

    PubMed Central

    Beehner, Jacinta C.; Gesquiere, Laurence; Seyfarth, Robert M.; Cheney, Dorothy L.; Alberts, Susan C.; Altmann, Jeanne

    2013-01-01

    Despite significant advances in our knowledge of how testosterone mediates life-history trade-offs, this research has primarily focused on seasonal species. We know comparatively little about the relationship between testosterone and life-history stages for non-seasonally breeding species. Here we examine testosterone profiles across the lifespan of males from three non-seasonally breeding primates: yellow baboons (Papio cynocephalus or P. hamadryas cynocephalus), chacma baboons (Papio ursinus or P. h. ursinus), and geladas (Theropithecus gelada). First, we predict that testosterone profiles will track the reproductive profiles of each taxon across their respective breeding years. Second, we evaluate age-related changes in testosterone to determine whether several life-history transitions are associated with these changes. Subjects include males (>2.5 years) from wild populations of each taxon from whom we had fecal samples for hormone determination. Although testosterone profiles across species were broadly similar, considerable variability was found in the timing of two major changes: (1) the attainment of adult levels of testosterone, and (2) the decline in testosterone after the period of maximum production. Attainment of adult testosterone levels was delayed by one year in chacmas compared with yellows and geladas. With respect to the decline in testosterone, geladas and chacmas exhibited a significant drop after three years of maximum production, while yellows declined so gradually that no significant annual drop was ever detected. For both yellows and chacmas, increases in testosterone production preceded elevations in social dominance rank. We discuss these differences in the context of ecological and behavioral differences exhibited by these taxa. PMID:19712676

  17. Deficiency of protein kinase Calpha in mice results in impairment of epidermal hyperplasia and enhancement of tumor formation in two-stage skin carcinogenesis.

    PubMed

    Hara, Takeshi; Saito, Yuriko; Hirai, Takaaki; Nakamura, Kenji; Nakao, Kazuki; Katsuki, Motoya; Chida, Kazuhiro

    2005-08-15

    We generated a mouse strain lacking protein kinase Calpha (PKCalpha) and evaluated the significance of the enzyme in epithelial hyperplasia and tumor formation. PKCalpha-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. Tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCalpha suppresses tumor promotion. However, the severity of epidermal hyperplasia induced by topical TPA treatment was markedly reduced. In mutant mice, the number of 5-bromo-2'-deoxyuridine-labeled epidermal basal keratinocytes increased 16 to 24 hours after topical TPA treatment as in the case of wild-type mice, but significantly decreased at 36 and 48 hours. Furthermore, the regenerating epithelium induced by skin wound significantly decreased in thickness but was not structurally impaired. The enhanced tumor formation may not be associated with epidermal hyperplasia. The induction levels of epidermal growth factor (EGF) receptor ligands, tumor growth factor alpha (TGF-alpha), and heparin-binding EGF-like growth factor, in the skin of mutant mice by TPA treatment were significantly lower than those in the skin of wild-type mice. PKCalpha may regulate the supply of these EGF receptor ligands in basal keratinocytes, resulting in a reduced epidermal hyperplasia severity in the mutant mice. We propose that PKCalpha positively regulates epidermal hyperplasia but negatively regulates tumor formation in two-stage skin carcinogenesis.

  18. Validity of the Fine Motor Area of the 12-Month Ages and Stages Questionnaire in Infants Following Major Surgery

    ERIC Educational Resources Information Center

    Smith, Cally; Wallen, Margaret; Walker, Karen; Bundy, Anita; Rolinson, Rachel; Badawi, Nadia

    2012-01-01

    The Ages and Stages Questionnaires (ASQ) are parent-report screening tools to identify infants at risk of developmental difficulties. The purpose of this study was to examine validity and internal reliability of the fine motor developmental area of the ASQ, 2nd edition (ASQ2-FM) for screening 12-month-old infants following major surgery. The…

  19. Steep Dose-Response Relationship for Stage I Non-Small-Cell Lung Cancer Using Hypofractionated High-Dose Irradiation by Real-Time Tumor-Tracking Radiotherapy

    SciTech Connect

    Onimaru, Rikiya Fujino, Masaharu; Yamazaki, Koichi; Onodera, Yuya; Taguchi, Hiroshi; Katoh, Norio; Hommura, Fumihiro; Oizumi, Satoshi; Nishimura, Masaharu; Shirato, Hiroki

    2008-02-01

    Purpose: To investigate the clinical outcomes of patients with pathologically proven, peripherally located, Stage I non-small-cell lung cancer who had undergone stereotactic body radiotherapy using real-time tumor tracking radiotherapy during the developmental period. Methods and Materials: A total of 41 patients (25 with Stage T1 and 16 with Stage T2) were admitted to the study between February 2000 and June 2005. A 5-mm planning target volume margin was added to the clinical target volume determined with computed tomography at the end of the expiratory phase. The gating window ranged from {+-}2 to 3 mm. The dose fractionation schedule was 40 or 48 Gy in four fractions within 1 week. The dose was prescribed at the center of the planning target volume, giving more than an 80% dose at the planning target volume periphery. Results: For 28 patients treated with 48 Gy in four fractions, the overall actuarial survival rate at 3 years was 82% for those with Stage IA and 32% for those with Stage IB. For patients treated with 40 Gy in four fractions within 1 week, the overall actuarial survival rate at 3 years was 50% for those with Stage IA and 0% for those with Stage IB. A significant difference was found in local control between those with Stage IB who received 40 Gy vs. 48 Gy (p = 0.0015) but not in those with Stage IA (p = 0.5811). No serious radiation morbidity was observed with either dose schedule. Conclusion: The results of our study have shown that 48 Gy in four fractions within 1 week is a safe and effective treatment for peripherally located, Stage IA non-small-cell lung cancer. A steep dose-response curve between 40 and 48 Gy using a daily dose of 12 Gy delivered within 1 week was identified for Stage IB non-small-cell lung cancer in stereotactic body radiotherapy using real-time tumor tracking radiotherapy.

  20. Learning Multiple Band-Pass Filters for Sleep Stage Estimation: Towards Care Support for Aged Persons

    NASA Astrophysics Data System (ADS)

    Takadama, Keiki; Hirose, Kazuyuki; Matsushima, Hiroyasu; Hattori, Kiyohiko; Nakajima, Nobuo

    This paper proposes the sleep stage estimation method that can provide an accurate estimation for each person without connecting any devices to human's body. In particular, our method learns the appropriate multiple band-pass filters to extract the specific wave pattern of heartbeat, which is required to estimate the sleep stage. For an accurate estimation, this paper employs Learning Classifier System (LCS) as the data-mining techniques and extends it to estimate the sleep stage. Extensive experiments on five subjects in mixed health confirm the following implications: (1) the proposed method can provide more accurate sleep stage estimation than the conventional method, and (2) the sleep stage estimation calculated by the proposed method is robust regardless of the physical condition of the subject.

  1. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. Stages of Wilms Tumor

    MedlinePlus

    ... Social worker . Some cancer treatments cause side effects months or years after treatment has ended. Side effects ... begin during or after treatment and continue for months or years are called late effects . Late effects ...

  3. Conflict-Specific Aging Effects Mainly Manifest in Early Information Processing Stages-An ERP Study with Different Conflict Types.

    PubMed

    Korsch, Margarethe; Frühholz, Sascha; Herrmann, Manfred

    2016-01-01

    Aging is usually accompanied by alterations of cognitive control functions such as conflict processing. Recent research suggests that aging effects on cognitive control seem to vary with degree and source of conflict, and conflict specific aging effects on performance measures as well as neural activation patterns have been shown. However, there is sparse information whether and how aging affects different stages of conflict processing as indicated by event related potentials (ERPs) such as the P2, N2 and P3 components. In the present study, 19 young and 23 elderly adults performed a combined Flanker conflict and stimulus-response-conflict (SRC) task. Analysis of the reaction times (RTs) revealed an increased SRC related conflict effect in elderly. ERP analysis furthermore demonstrated an age-related increase of the P2 amplitude in response to the SRC task. In addition, elderly adults exhibited an increased P3 amplitude modulation induced by incongruent SRC and Flanker conflict trials.

  4. How Are Wilms Tumors Diagnosed?

    MedlinePlus

    ... Tumor Early Detection, Diagnosis, and Staging How Are Wilms Tumors Diagnosed? Wilms tumors are usually found when a ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  5. Bringing the Law to the Gerontological Stage: A Different Look at Movies and Old Age

    ERIC Educational Resources Information Center

    Doron, Israel

    2006-01-01

    Films often portray the complexities of real-life aging issues, showing how they are apparently handled outside of and around the law or legal issues. Furthermore, films considering the aged and the social issues associated with aging also reveal how the law actually functions as a framework around and within which people develop customs, habits,…

  6. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  7. Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats.

    PubMed

    Möller, Frank Josef; Pemp, Daniela; Soukup, Sebastian T; Wende, Kathleen; Zhang, Xiajie; Zierau, Oliver; Muders, Michael H; Bosland, Maarten C; Kulling, Sabine E; Lehmann, Leane; Vollmer, Günter

    2016-08-01

    There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened.

  8. Survival Analyses for Patients With Surgically Resected Pancreatic Neuroendocrine Tumors by World Health Organization 2010 Grading Classifications and American Joint Committee on Cancer 2010 Staging Systems.

    PubMed

    Yang, Min; Ke, Neng-wen; Zeng, Lin; Zhang, Yi; Tan, Chun-lu; Zhang, Hao; Mai, Gang; Tian, Bo-le; Liu, Xu-bao

    2015-12-01

    In 2010, World Health Organization (WHO) reclassified pancreatic neuroendocrine tumors (p-NETs) into 4 main groups: neuroendocrine tumor G1 (NET G1), neuroendocrine tumor G2 (NET G2), neuroendocrine carcinoma G3 (NEC G3), mixed adeno and neuroendocrine carcinoma (MANEC). Clinical value of these newly updated WHO grading criteria has not been rigorously validated. The authors aimed to evaluate the clinical consistency of the new 2010 grading classifications by WHO and the 2010 tumor-node metastasis staging systems by American Joint Committee on Cancer (AJCC) on survivals for patients with surgically resected p-NETs. Moreover, the authors would validate the prognostic value of both criteria for p-NETs.The authors retrospectively collected the clinicopathologic data of 120 eligible patients who were all surgically treated and histopathologically diagnosed as p-NETs from January 2004 to February 2014 in our single institution. The new WHO criteria were assigned to 4 stratified groups with a respective distribution of 62, 35, 17, and 6 patients. Patients with NET G1 or NET G2 obtained a statistically better survival compared with those with NEC G3 or MANEC (P < 0.001). Survivals of NET G1 was also better than those of NET G2 (P = 0.023), whereas difference of survivals between NEC G3 and MANEC present no obvious significance (P = 0.071). The AJCC 2010 staging systems were respectively defined in 61, 36, 12, and 11 patients for each stage. Differences of survivals of stage I with stage III and IV were significant (P < 0.001), as well as those of stage II with III and IV (P < 0.001); whereas comparisons of stage I with stage II and stage III with IV were not statistically significant (P = 0.129, P = 0.286; respectively). Together with radical resection, these 2 systems were both significant in univariate and multivariate analysis (P < 0.05).The newly updated WHO 2010 grading classifications and the AJCC 2010 staging systems could consistently reflect the clinical outcome

  9. Correlation between Ultrasound Reflection Intensity and Tumor Ablation Ratio of Late-Stage Pancreatic Carcinoma in HIFU Therapy: Dynamic Observation on Ultrasound Reflection Intensity

    PubMed Central

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma. PMID:24453916

  10. Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

    PubMed

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

  11. Adaptive Memory of Human NK-like CD8+ T-Cells to Aging, and Viral and Tumor Antigens

    PubMed Central

    Pita-López, María Luisa; Pera, Alejandra; Solana, Rafael

    2016-01-01

    Human natural killer (NK)-like CD8+ T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8+ T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8+ T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8+KIR+ T-cells, innate CD8+ T-cells, CD8+CD28−KIR+ T-cells or NKT-like CD8+CD56+ cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8+ T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8+ T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8+ T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation (“adaptation”) of the NK-like CD8+ T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity. PMID:28066426

  12. Adaptive Memory of Human NK-like CD8(+) T-Cells to Aging, and Viral and Tumor Antigens.

    PubMed

    Pita-López, María Luisa; Pera, Alejandra; Solana, Rafael

    2016-01-01

    Human natural killer (NK)-like CD8(+) T-cells are singular T-cells that express both T and NK cell markers such as CD56; their frequencies depend on their differentiation and activation during their lifetime. There is evidence of the presence of these innate CD8(+) T-cells in the human umbilical cord, highlighting the necessity of investigating whether the NK-like CD8(+) T-cells arise in the early stages of life (gestation). Based on the presence of cell surface markers, these cells have also been referred to as CD8(+)KIR(+) T-cells, innate CD8(+) T-cells, CD8(+)CD28(-)KIR(+) T-cells or NKT-like CD8(+)CD56(+) cells. However, the functional and co-signaling significance of these NK cell receptors on NK-like CD8(+) T-cells is less clear. Also, the diverse array of costimulatory and co-inhibitory receptors are spatially and temporally regulated and may have distinct overlapping functions on NK-like CD8(+) T-cell priming, activation, differentiation, and memory responses associated with different cell phenotypes. Currently, there is no consensus regarding the functional properties and phenotypic characterization of human NK-like CD8(+) T-cells. Environmental factors, such as aging, autoimmunity, inflammation, viral antigen re-exposure, or the presence of persistent tumor antigens have been shown to allow differentiation ("adaptation") of the NK-like CD8(+) T-cells; the elucidation of this differentiation process and a greater understanding of the characteristics of these cells could be important for their eventual in potential therapeutic applications aimed at improving protective immunity. This review will attempt to elucidate an understanding of the characteristics of these cells with the goal toward their eventual use in potential therapeutic applications aimed at improving protective immunity.

  13. Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

    PubMed Central

    Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

    2014-01-01

    Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

  14. Tumor Necrosis Factor Gene Polymorphisms in Advanced Non-exudative Age-related Macular Degeneration

    PubMed Central

    Bonyadi, Mohammad Hossein Jabbarpoor; Bonyadi, Morteza; Ahmadieh, Hamid; Fotuhi, Nikoo; Shoeibi, Nasser; Saadat, Saeed; Yagubi, Zakieh

    2015-01-01

    Purpose: To investigate tumor necrosis factor (TNF)-α gene polymorphisms in advanced dry-type age-related macular degeneration (AMD) in a population from Northeastern Iran. Methods: In this case-control study, 50 patients with geographic macular atrophy and 73 gender-matched controls were enrolled. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood. Polymerase chain reaction was performed to analyze 2 candidate single nucleotide polymorphisms in the TNF-α gene, namely −1031 thymine (T)/cytosine (C) and −308 guanine (G)/adenine (A). Results: The distribution of the - 1031 T/C genotype was TT, 62%; TC, 36%; CC, 2% in the patients and TT, 60%; TC, 36%; CC, 4% in the controls (P = 0.94). Genotype analysis of TNF-α −308 also revealed no significant difference in distribution between patients (G, 78%; GA, 22%; AA, 0%) and controls (GG, 74%; GA, 23%; AA, 3%) (P = 0.51). None of the haplotypes nor alleles of studied TNF-α polymorphisms were significantly associated with advanced dry-type AMD. Conclusion: The findings of this study show that polymorphisms in the TNF-α gene, do not play an important role in dry-type AMD in the studied population. PMID:26425318

  15. Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer (NSCLC) patients and survivors with metachronous second primary tumor (MST)

    PubMed Central

    Ding, Xingchen; Wang, Linlin; Liu, Xijun; Sun, Xindong; Yu, Jinming; Meng, Xue

    2017-01-01

    Abstract Rationale: The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Patient concerns: Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. Diagnoses The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. Interventions: The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). Outcomes: The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. Lessons: This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors. PMID:28272214

  16. Outcomes of Patients With Revised Stage I Clear Cell Sarcoma of Kidney Treated in National Wilms Tumor Studies 1-5

    SciTech Connect

    Kalapurakal, John A.; Perlman, Elizabeth J.; Seibel, Nita L.; Ritchey, Michael; Dome, Jeffrey S.; Grundy, Paul E.

    2013-02-01

    Purpose: To report the clinical outcomes of children with revised stage I clear cell sarcoma of the kidney (CCSK) using the National Wilms Tumor Study Group (NWTS)-5 staging criteria after multimodality treatment on NWTS 1-5 protocols. Methods and Materials: All CCSK patients enrolled in the National Wilms Tumor Study Group protocols had their pathology slides reviewed, and only those determined to have revised stage I tumors according to the NWTS-5 staging criteria were included in the present analysis. All patients were treated with multimodality therapy according to the NWTS 1-5 protocols. Results: A total of 53 children were identified as having stage I CCSK. All patients underwent primary surgery with radical nephrectomy. The chemotherapy regimens used were as follows: regimen A, C, F, or EE in 4 children (8%); regimen DD or DD4A in 33 children (62%); regimen J in 4 children (8%); and regimen I in 12 children (22%). Forty-six patients (87%) received flank radiation therapy (RT). Seven children (13%) did not receive flank RT. The median delay between surgery and the initiation of RT was 9 days (range, 3-61). The median RT dose was 10.8 Gy (range, 10-36). The flank RT doses were as follows: 10.5 or 10.8 Gy in 25 patients (47%), 11-19.9 Gy in 2 patients (4%), 20-29.9 Gy in 9 patients (17%), and 30-40 Gy in 10 patients (19%). The median follow-up for the entire group was 17 years (range, 2-36). The relapse-free and cancer-specific survival rate was 100% at the last follow-up examination. Conclusions: The present results have demonstrated that children with revised stage I CCSK using the NWTS-5 staging criteria have excellent survival rates despite the use of varying RT doses and chemotherapy regimens in the NWTS 1-5 protocols.

  17. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically-resected stage I-IIIA non-small cell lung cancers

    PubMed Central

    Drilon, Alexander; Sugita, Hirofumi; Sima, Camelia S.; Zauderer, Marjorie; Rudin, Charles M.; Kris, Mark G.; Rusch, Valerie W.; Azzoli, Christopher G.

    2014-01-01

    Introduction While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene (TSG) promoter methylation in early-stage non-small cell lung cancers (NSCLCs), few studies have investigated this question prospectively. Methods Primary tumor tissue from patients with resected pathologic stage I-IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse-transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual TSGs (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. Results 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (66%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p=0.03). The total number of genes with methylated promoters did not correlate with RFS (p=0.89) or OS (p=0.55). Conclusions Contrary to data established by previous retrospective series, TSG promoter methylation (CDKN2A, CDH13, RASSF1,APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs. PMID:25122424

  18. Class I versus Class III radical hysterectomy in stage IB1 (tumor ≤ 2 cm) cervical cancer: a matched cohort study

    PubMed Central

    Wang, Wei; Shang, Chun-liang; Du, Qi-qiao; Wu, Di; Liang, Yan-chun; Liu, Tian-yu; Huang, Jia-ming; Yao, Shu-zhong

    2017-01-01

    Background & Aims: The long-term oncological outcome of Class I hysterectomy to treat stage IB1 cervical cancer is unclear. The aim of the present study was to compare the surgical and long-term oncological outcomes of Class I hysterectomy and Class III radical hysterectomy for treatment of stage IB1 cervical cancer (tumor ≤ 2 cm). Methods: Seventy stage IB1 cervical cancer patients (tumor ≤ 2 cm) underwent Class I hysterectomy and 577 stage IB1 cervical cancer patients (tumor ≤ 2 cm) underwent Class III radical hysterectomy were matched with known risk factors for recurrence by greedy algorithm. Clinical, pathologic and follow-up data were retrospectively collected. Five-year survival outcomes were assessed using Kaplan-Meier model. Results: After matching, a total of 70 patient pairs (Class I - Class III) were included. The median follow-up times were 75 (range, 26-170) months in the Class III group and 75 (range, 27-168) months in the Class I group. The Class I and Class III group had similar 5-year recurrence-free survival rates (RFS) (98.6% vs. 97.1%, P = 0.56) and overall survival rates (OS) (100.0% vs. 98.5%, P = 0.32). Compared with the Class III group, the Class I group resulted in significantly shorter operating time, less intra-operative blood loss, less intraoperative complications, less postoperative complications, and shorter hospital stay. Conclusions: These findings suggest that Class I hysterectomy is an oncological safe alternative to Class III radical hysterectomy in treatment of stage IB1 cervical cancer (tumor ≤ 2 cm) and Class I hysterectomy is associated with fewer perioperative complication and earlier recovery.

  19. Variation in body condition indices of crimson finches by sex, breeding stage, age, time of day, and year

    PubMed Central

    Milenkaya, Olga; Weinstein, Nicole; Legge, Sarah; Walters, Jeffrey R.

    2013-01-01

    Body condition indices are increasingly applied in conservation to assess habitat quality, identify stressed populations before they decline, determine effects of disturbances, and understand mechanisms of declines. To employ condition indices in this manner, we need first to understand their baseline variability and sources of variation. Here, we used crimson finches (Neochmia phaeton), a tropical passerine, to describe the variation in seven commonly used condition indices by sex, age, breeding stage, time of day, and year. We found that packed cell volume, haemoglobin, total plasma protein, and scaled mass were all significantly affected by an interaction between sex and breeding stage. Furcular fat varied by sex and breeding stage and also trended by year, scaled mass showed a positive trend with age and varied by time of day, and haemoglobin additionally varied by year. Pectoral muscle scores varied and heterophil to lymphocyte ratio trended only by year. Year effects might reflect a response to annual variation in environmental conditions; therefore, those indices showing year effects may be especially worthy of further investigation of their potential for conservation applications. Pectoral muscle scores and heterophil to lymphocyte ratio may be particularly useful due to the lack of influence of other variables on them. For the other indices, the large variation that can be attributed to individual covariates, such as sex and breeding stage, suggests that one should not interpret the physiological condition of an individual as measured by these indices from their absolute value. Instead, the condition of an individual should be interpreted relative to conspecifics by sex, breeding stage, and possibly age. PMID:27293604

  20. White matter integrity and reaction time intraindividual variability in healthy aging and early-stage Alzheimer disease.

    PubMed

    Jackson, Jonathan D; Balota, David A; Duchek, Janet M; Head, Denise

    2012-02-01

    Aging and early-stage Alzheimer disease (AD) have been shown to be associated with increased RT intraindividual variability (IIV, as reflected by the coefficient of variation) and an exaggeration of the slow tail of the reaction time (RT) distribution in attentional control tasks, based on ex-Gaussian analyses. The current study examined associations between white matter volume, IIV, and ex-Gaussian RT distribution parameters in cognitively normal aging and early-stage AD. Three RT attention tasks (Stroop, Simon, and a consonant-vowel odd-even switching task) in conjunction with MRI-based measures of cerebral and regional white matter volume were obtained in 133 cognitively normal and 33 early-stage AD individuals. Larger volumes were associated with less IIV and less slowing in the tail of the RT distribution, and larger cerebral and inferior parietal white matter volumes were associated with faster modal reaction time. Collectively, these results support a role of white matter integrity in IIV and distributional skewing, and are consistent with the hypothesis that IIV and RT distributional skewing are sensitive to breakdowns in executive control processes in normal and pathological aging.

  1. Plasma Ghrelin Concentrations Were Altered with Oestrous Cycle Stage and Increasing Age in Reproductively Competent Wistar Females

    PubMed Central

    Saffrey, M. Jill; Taylor, Victoria J.

    2016-01-01

    Changes in appetite occur during the ovarian cycle in female mammals. Research on appetite-regulatory gastrointestinal peptides in females is limited, because reproductive changes in steroid hormones present additional experimental factors to control for. This study aimed to explore possible changes in the orexigenic (appetite-stimulating) gastrointestinal peptide hormone ghrelin during the rodent oestrous cycle. Fed and fasted plasma and stomach tissue samples were taken from female Wistar rats (32–44 weeks of age) at each stage of the oestrous cycle for total ghrelin quantification using radioimmunoassay. Sampling occurred during the dark phase when most eating takes place in rats. Statistical analysis was by paired-samples t-test, one-way ANOVA on normally distributed data, with Tukey post-hoc tests, or Kruskal-Wallis if not. GLM univariate analysis was used to assess main effects and interactions in ghrelin concentrations in the fed or fasted state and during different stages of the ovarian cycle, with age as a covariate. No consistent fed to fasted ghrelin increases were measured in matched plasma samples from the same animals, contrary to expectations. Total ghrelin concentrations did not significantly change between cycle stages with ANOVA, in either fed or fasted plasma or in stomach tissue. This was despite significantly decreased fasted stomach contents at oestrus (P = 0.028), suggesting decreased food intake. There was however a significant interaction in ghrelin plasma concentrations between fed and fasted proestrus rats and a direct effect of age with rats over 37 weeks old having lower circulating concentrations of ghrelin in both fed and fasted states. The biological implications of altered ghrelin plasma concentrations from 37 weeks of age are as yet unknown, but warrant further investigation. Exploring peripheral ghrelin regulatory factor changes with increasing age in reproductively competent females may bring to light potential effects on

  2. APPLYING TEP MEASUREMENTS TO ASSESS THE AGING STAGE OF MARAGING 250 STEEL

    SciTech Connect

    Snir, Y.; Gelbstein, Y.; Pinkas, M.; Yeheskel, O.; Landau, A.

    2008-02-28

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 deg. C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni{sub 3}(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  3. Applying Tep Measurements to Assess the Aging Stage of Maraging 250 Steel

    NASA Astrophysics Data System (ADS)

    Snir, Y.; Pinkas, M.; Gelbstein, Y.; Yeheskel, O.; Landau, A.

    2008-02-01

    Thermoelectric power (TEP) measurements had been proved as an effective method for evaluating the metallurgical state of various alloys. The current work was conducted in order to evaluate the influence of the aging state of Maraging 250 steel on TEP values. Commercial Maraging 250 steel was aged at 500 °C for 0.5-6 hours (hrs). TEP, hardness (Rc) and ultrasonic (US) measurements, were preformed on the as received and aged specimens. XRD measurements were used to identify the formation of precipitates (mainly Ni3(Ti,Mo)), reverted austenite and to evaluate changes in the microstrain caused by the precipitation process. A correlation was found between the TEP and the various measurements as a function of the aging time.

  4. Predicting age-related differences in visual information processing using a two-stage queuing model.

    PubMed

    Ellis, R D; Goldberg, J H; Detweiler, M C

    1996-05-01

    Recent work on age-related differences in some types of visual information processing has qualitatively stated that younger adults are able to develop parallel processing capability, while older adults remain serial processors. A mathematical model based on queuing theory was used to quantitatively predict and parameterize age-related differences in the perceptual encoding and central decision-making aspects of a multiple-frame search task. Statistical results indicated main effects for frame duration, display load, age group, and session of practice. Comparison of the full model and a restricted model indicated an efficient contribution of the encoding speed parameter. The best-fitting parameter set indicated that (1) younger participants processed task information with a two-channel parallel system, while older participants were serial processors; and (2) perceptual encoding had a large impact on age-related differences in task performance. Results are discussed with implications for human factors design principles.

  5. [Morphofunctional status of gonadotropic cells of the adenohypophysis at early stages of age involution].

    PubMed

    Kozak, M V; Teplyĭ, D L

    2007-01-01

    Action of alpha-tocopherol, emoxipinum on functional status of gonadotropic cells was investigated at deficiency of sexual hormones in male and female rats of Wistar line. The alpha-tocopherol slows down aging of gonadotropic cells after gonadectomy.

  6. Dental and Chronological Ages as Determinants of Peak Growth Period and Its Relationship with Dental Calcification Stages

    PubMed Central

    Litsas, George; Lucchese, Alessandra

    2016-01-01

    Purpose: To investigate the relationship between dental, chronological, and cervical vertebral maturation growth in the peak growth period, as well as to study the association between the dental calcification phases and the skeletal maturity stages during the same growth period. Methods: Subjects were selected from orthodontic pre-treatment cohorts consisting of 420 subjects where 255 were identified and enrolled into the study, comprising 145 girls and 110 boys. The lateral cephalometric and panoramic radiographs were examined from the archives of the Department of Orthodontics, Aristotle University of Thessaloniki, Greece. Dental age was assessed according to the method of Demirjian, and skeletal maturation according to the Cervical Vertebral Maturation Method. Statistical elaboration included Spearman Brown formula, descriptive statistics, Pearson’s correlation coefficient and regression analysis, paired samples t-test, and Spearman’s rho correlation coefficient. Results: Chronological and dental age showed a high correlation for both gender(r =0.741 for boys, r = 0.770 for girls, p<0.001). The strongest correlation was for the CVM Stage IV for both males (r=0.554) and females (r=0.68). The lowest correlation was for the CVM Stage III in males (r=0.433, p<0.001) and for the CVM Stage II in females (r=0.393, p>0.001). The t-test revealed statistically significant differences between these variables (p<0.001) during the peak period. A statistically significant correlation (p<0.001) between tooth calcification and CVM stages was determined. The second molars showed the highest correlation with CVM stages (CVMS) (r= 0.65 for boys, r = 0.72 for girls). Conclusion: Dental age was more advanced than chronological for both boys and girls for all CVMS. During the peak period these differences were more pronounced. Moreover, all correlations between skeletal and dental stages were statistically significant. The second molars showed the highest correlation whereas the

  7. The IASLC Lung Cancer Staging Project: Proposals for Coding T Categories for Subsolid Nodules and Assessment of Tumor Size in Part-Solid Tumors in the Forthcoming Eighth Edition of the TNM Classification of Lung Cancer.

    PubMed

    Travis, William D; Asamura, Hisao; Bankier, Alexander A; Beasley, Mary Beth; Detterbeck, Frank; Flieder, Douglas B; Goo, Jin Mo; MacMahon, Heber; Naidich, David; Nicholson, Andrew G; Powell, Charles A; Prokop, Mathias; Rami-Porta, Ramón; Rusch, Valerie; van Schil, Paul; Yatabe, Yasushi

    2016-08-01

    This article proposes codes for the primary tumor categories of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and a uniform way to measure tumor size in part-solid tumors for the eighth edition of the tumor, node, and metastasis classification of lung cancer. In 2011, new entities of AIS, MIA, and lepidic predominant adenocarcinoma were defined, and they were later incorporated into the 2015 World Health Organization classification of lung cancer. To fit these entities into the T component of the staging system, the Tis category is proposed for AIS, with Tis (AIS) specified if it is to be distinguished from squamous cell carcinoma in situ (SCIS), which is to be designated Tis (SCIS). We also propose that MIA be classified as T1mi. Furthermore, the use of the invasive size for T descriptor size follows a recommendation made in three editions of the Union for International Cancer Control tumor, node, and metastasis supplement since 2003. For tumor size, the greatest dimension should be reported both clinically and pathologically. In nonmucinous lung adenocarcinomas, the computed tomography (CT) findings of ground glass versus solid opacities tend to correspond respectively to lepidic versus invasive patterns seen pathologically. However, this correlation is not absolute; so when CT features suggest nonmucinous AIS, MIA, and lepidic predominant adenocarcinoma, the suspected diagnosis and clinical staging should be regarded as a preliminary assessment that is subject to revision after pathologic evaluation of resected specimens. The ability to predict invasive versus noninvasive size on the basis of solid versus ground glass components is not applicable to mucinous AIS, MIA, or invasive mucinous adenocarcinomas because they generally show solid nodules or consolidation on CT.

  8. Collecting Tumor Samples From Patients With Gynecological Tumors

    ClinicalTrials.gov

    2016-10-26

    Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell

  9. [Wilms' tumor. Its multidisciplinary management].

    PubMed

    Rivera Luna, R; Martínez Guerra, G; Ruano Aguilar, J; Cárdenas Cardoz, R; Lanche Guevara, T

    1992-01-01

    A total of 115 children with a histopathological diagnosis of Wilms' tumor were studied. The average age was three years. An abdominal tumor was the most frequent clinical manifestations, with a predominating clinicopathological stage II. The most important prognostic factors were the clinical stage and histological subvariety. A five year disease free period during the early stages was very favorable. On the other hand, advances stages and unfavorable histopathology established a poor prognosis. In our experience, stages I and II and favorable histology should not receive radiotherapy but instead brief chemotherapy. The global five year survival was 82%. All the patients with an unfavorable histology occupied stages II and IV. a comparison of disease free survival between stages I and II against III and IV showed statistical significance (p 0.01). Statistical significance also appeared upon comparison between unfavorable versus favorable (p 0.01) histology. Emphasis is placed upon multidisciplinary management of this type of malignant neoplasias.

  10. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

    PubMed

    Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

    2016-10-01

    Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-xL, and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-xL overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

  11. Another stage of development: Biological degeneracy and the study of bodily ageing.

    PubMed

    Mason, Paul H; Maleszka, Ryszard; Dominguez D, Juan F

    2016-12-21

    Ageing is a poorly understood process of human development mired by a scientific approach that struggles to piece together distributed variable factors involved in ongoing transformations of living systems. Reconfiguring existing research paradigms, we review the concept of 'degeneracy', which has divergent popular and technical definitions. The technical meaning of degeneracy refers to the structural diversity underlying functional plasticity. Degeneracy is a distributed system property that can be observed within individual brains or across different brains. For example, dementias with similar behavioural anomalies can result from a diverse range of cellular "faults", which is an example of degeneracy because the symptoms are similar in spite of different underlying mechanisms. Degeneracy is a valuable epistemological tool that can transformatively enhance scientific models of bodily ageing. We propose that movement science is one of the first areas that can productively integrate degeneracy into models of bodily ageing. We also propose model organisms such as eusocial honey bees in which degeneracy can be studied at the molecular and cellular level. Developing a vocabulary for thinking about how distributed variable factors are interlinked is important if we are to understand bodily ageing not as a single entity, but as the heterogeneous construction of changing biological, social, and environmental processes.

  12. Long-term Survival and Clinical Benefit from Adoptive T-cell Transfer in Stage IV Melanoma Patients Is Determined by a Four-Parameter Tumor Immune Signature.

    PubMed

    Melief, Sara M; Visconti, Valeria V; Visser, Marten; van Diepen, Merel; Kapiteijn, Ellen H W; van den Berg, Joost H; Haanen, John B A G; Smit, Vincent T H B M; Oosting, Jan; van der Burg, Sjoerd H; Verdegaal, Els M E

    2017-02-01

    The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early-stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyses, and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas database. We identified four parameters that were associated with a better survival: CD8(+) T cells, galectin-9(+) dendritic cells (DC)/DC-like macrophages, a high M1/M2 macrophage ratio, and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit. Cancer Immunol Res; 5(2); 170-9. ©2017 AACR.

  13. Circulating tumor DNA in early-stage breast cancer: personalized biomarkers for occult metastatic disease and risk of relapse?

    PubMed

    af Hällström, Taija M; Puhka, Maija; Kallioniemi, Olli

    2015-08-01

    The availability of blood-based markers to predict response of a solid tumor to treatment, estimate patient prognosis and diagnose relapse well before clinical symptoms arise, is a long-standing hope in clinical oncology. Ideally, assays designed to provide such information should be inexpensive (at least in the foreseeable future), simple, and, of course, predictive of the clinical evolution of the disease. While early research focused on circulating glycosylated tumor-derived protein biomarkers, the focus is now rapidly shifting to new opportunities, such as circulating tumor cells, extracellular vesicles, micro-RNAs and cancer-derived cell-free DNA a.k.a. circulating tumor-derived DNA (ctDNA).

  14. Experience of curing serious obstruction of advanced-stage upper digestive tract tumor using laser under endoscope

    NASA Astrophysics Data System (ADS)

    Mu, Hai-Bin; Zhang, Man-Ling; Zhang, Xiao-Qiang; Zhang, Feng-Qiu; Kong, De-Jia; Tang, Li-Bin

    1998-11-01

    The patients who suffer from upper digestive tract tumor, such as cancer of esophagus, cancer of cardia, all have serious obstruction and fail to get nutrition and can not bear the strike of the radiotherapy and chemotherapy. In order to reduce the obstruction symptom and suffering of the patients and to prolong their life time, since 1989, our hospital used the laser to cure the upper digestive tract tumor 11 cases with serious obstruction and got remarkable curative effect.

  15. Sterol and triterpene derivatives from plants inhibit the effects of a tumor promoter, and sitosterol and betulinic acid inhibit tumor formation in mouse skin two-stage carcinogenesis.

    PubMed

    Yasukawa, K; Takido, M; Matsumoto, T; Takeuchi, M; Nakagawa, S

    1991-01-01

    A single topical application of 1 microgram of 12-O-tetradecanoylphorbol- 13-acetate (TPA) to the ears of mice was shown to induce edema, and this TPA-induced inflammation was inhibited by 4-methylsterol and triterpene derivatives. The ED50 of these compounds against TPA-induced inflammation was 0.1-3 mumol. Phytosterols had only slight inhibitory effects. Furthermore, application of 5 micrograms TPA to mouse skin rapidly caused accumulation of ornithine decarboxylase (ODC). Similarly, sitosterol and lupane-type triterpene derivatives markedly inhibited this TPA-induced ODC accumulation. In addition, 5 mumol betulinic acid markedly inhibited the promoting effect of 2.5 micrograms TPA applied twice weekly on skin tumor formation in mice initiated with 50 micrograms of 7,12-dimethylbenz[a]anthracene, and 5 mumol of sitosterol caused slight suppression. Thus, the inhibitory effects of sterol and triterpene derivatives on TPA-induced inflammation roughly parallelled their inhibitory activities against tumor promotion.

  16. Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence

    PubMed Central

    Jin, Jing; Jung, Hae Yoen; Lee, Kyu Ho; Yi, Nam-Joon; Suh, Kyung-Suk; Jang, Ja-June; Lee, Kyoung-Bun

    2016-01-01

    Background: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. Methods: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. Results: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015). Conclusions: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs. PMID:27086597

  17. Aging and Surveillance Program MINUTEMAN II/III Stage II Program Progress.

    DTIC Science & Technology

    1985-11-01

    130 Firing Adapters Used to Fire VECP Igniters 58 132 Squib Arrangement Used in Both KR80000 Safe and Arm and FFTFs 59 133 Bladder Permeation vs Age...hydrolytic liner degradation as the primary mechanism leading ; . " to failure for the motor. Kinetic projections for service life ranged from 14 to 17...the igniter following assembly . In general, propellant in the bulk of the web is slightly harder than that measured in the fin. Propellant in the slot

  18. Angiogenic inhibitors for older patients with advanced colorectal cancer: Does the age hold the stage?

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Lutrino, Eufemia Stefania; Ferrari, Laura; Casagrande, Mariaelena; Cardellino, Giovanni Gerardo; Rosati, Gerardo; Fasola, Gianpiero

    2013-01-01

    Although major progress has been achieved in the treatment of advanced colorectal cancer (CRC) with the employment of antiangiogenic agents, several questions remain on the use of these drugs in older patients. Since cardiovascular, renal and other comorbidities are common in the elderly, an accurate assessment of the patients’ conditions should be performed before a treatment decision is made. Since most CRC patients enrolled in clinical trials testing antiangiogenic drugs were aged < 65 years, the efficacy and tolerability of these agents in elderly patients has not been adequately explored. Data suggest that patients with advanced CRC derive similar benefit from bevacizumab treatment regardless of age, but the advantage of other antiangiogenic drugs in the same class of patients appears more blurred. Literature data suggest that specific antiangiogenic-related toxicities such as hypertension or arterial thromboembolic events may be higher in the elderly than in the younger patients. In addition, it should be emphasized that the patients included in the clinical studies discussed herein were selected and therefore may not be representative of the usual elderly population. Advanced age alone should not discourage the use of bevacizumab. However, a careful patients’ selection and watchful monitoring of toxicities are required to optimize the use of antiangiogenics in this population. PMID:23847406

  19. Mammary tumors

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported.

  20. The Prognostic Impact of Molecular Subtypes and Very Young Age on Breast Conserving Surgery in Early Stage Breast Cancer

    PubMed Central

    McGuire, Kandace; Alco, Gul; Nur Pilanci, Kezban; Koksal, Ulkuhan I; Elbüken, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Sarsenov, Dauren; Öztürk, Alper; İğdem, Şefik; Okkan, Sait; Eralp, Yeşim; Dincer, Maktav; Ozmen, Vahit

    2016-01-01

    Background Premenopausal breast cancer with a triple-negative phenotype (TNBC) has been associated with inferior locoregional recurrence free survival (LRFS) and overall survival (OS) after breast conserving surgery (BCS). The aim of this study is to analyze the association between age, subtype, and surgical treatment on survival in young women (≤40 years) with early breast cancer in a population with a high rate of breast cancer in young women. Methods Three hundred thirty-two patients ≤40 years old with stage I-II invasive breast cancer who underwent surgery at a single institution between 1998 and 2012 were identified retrospectively. Uni- and multivariate analysis evaluated predictors of LRFS, OS, and disease free survival (DFS). Results Most patients (64.2%) underwent BCS. Mean age and follow-up time were 35 (25 ± 3.61) years, and 72 months (range, 24–252), respectively. In multivariate analysis, multicentricity/multifocality and young age (<35 years) independently predicted for poorer DFS and OS. Those aged 35–40 years had higher LRFS and DFS than those <35 in the mastectomy group (p=0.007 and p=0.039, respectively). Patients with TNBC had lower OS compared with patients with luminal A subtype (p=0.042), and those who underwent BCS had higher OS than patients after mastectomy (p=0.015). Conclusion Young age (< 35 years) is an independent predictor of poorer OS and DFS as compared with ages 35–40, even in countries with a lower average age of breast cancer presentation. In addition, TNBC in the young predicts for poorer OS. BCS can be performed in young patients with TNBC, despite their poorer overall survival. PMID:27433412

  1. MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans.

    PubMed

    Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M A; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F; Hellberg, Josephine; Thornton, Janet M; Gems, David

    2014-02-01

    In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality.

  2. MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

    PubMed Central

    Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M.A.; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F.; Hellberg, Josephine; Thornton, Janet M.; Gems, David

    2014-01-01

    In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality. PMID:24531613

  3. Psychometric properties of the Brazilian-adapted version of the Ages and Stages Questionnaire in public child daycare centers.

    PubMed

    Filgueiras, Alberto; Pires, Pedro; Maissonette, Silvia; Landeira-Fernandez, J

    2013-08-01

    Well-designed screening assessment instruments that can evaluate child development in public daycare centers represent an important resource to help improve the quality of these programs, as an early detection method for early developmental delay. The Ages and Stages Questionnaire, 3rd edition (ASQ-3), comprises a series of 21 questionnaires designed to screen developmental performance in the domains of communication, gross motor skills, fine motor skills, problem solving, and personal-social ability in children aged 2 to 66 months. The purpose of the present work was to translate and adapt all of the ASQ-3 questionnaires for use in Brazilian public child daycare centers and to explore their psychometric characteristics with both Classical Test Theory and Rating Scale analyses from the Rasch model family. A total of 18 Ages & Stages Questionnaires - Brazilian translation (ASQ-BR) questionnaires administered at intervals from 6 to 60 months of age were analyzed based on primary caregiver evaluations of 45,640 children distributed in 468 public daycare centers in the city of Rio de Janeiro. The results indicated that most of the ASQ-BR questionnaires had adequate internal consistency. Exploratory factor analyses yielded a one-factor solution for each domain of all of the ASQ-BR questionnaires. The only exception was the personal-social domain in some of the questionnaires. Item Response Theory based on Rating Scale analysis (infit and outfit mean squares statistics) indicated that only 44 of 540 items showed misfit problems. In summary, the ASQ-BR questionnaires are psychometrically sound developmental screening instruments that can be easily administered by primary caregivers.

  4. The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

    NASA Astrophysics Data System (ADS)

    (Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

    2011-08-01

    Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than

  5. Battling regional (stage III) lung cancer: bumpy road of a cancer survivor in the immunotherapy age.

    PubMed

    Hao, Zhonglin; Biddinger, Paul; Schroeder, Carsten; Tariq, Khurram

    2016-07-07

    A 58-year-old woman, a heavy smoker, was diagnosed with stage III squamous cell lung cancer. She was treated with concurrent chemotherapy and radiotherapy, with partial response. 2 months later, she had haemoptysis caused by brisk bleeding from the radiated right upper lobe. Fortunately, her bleed was self-limited. 4 months later, a rapidly enlarging renal mass was discovered and turned out to be metastatic from the lung primary. Second-line chemotherapy with docetaxel and ramucirumab did not have effects on the renal mass after 2 cycles. Despite not being eligible for a durvalumab trial because of lack of PD-L1 expression, she had a meaningful response to nivolumab. Once every 2 weeks, infusion of nivolumab resulted in rapid tumour shrinkage in multiple areas. In the next few months, she experienced a variety of side effects, some of which were potentially life-threatening. She had disease progression 9 months into treatment.

  6. An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer

    PubMed Central

    Nixon, Iain J.; Wang, Laura Y.; Migliacci, Jocelyn C.; Eskander, Antoine; Campbell, Michael J.; Aniss, Ahmad; Morris, Lilah; Vaisman, Fernanda; Corbo, Rossana; Momesso, Denise; Vaisman, Mario; Carvalho, Andre; Learoyd, Diana; Leslie, William D.; Nason, Richard W.; Kuk, Deborah; Wreesmann, Volkert; Morris, Luc; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Pathak, K. Alok; Shen, Wen T.; Sywak, Mark; Kowalski, Luis; Freeman, Jeremy; Perrier, Nancy; Shah, Jatin P.

    2016-01-01

    Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions. Methods: A total of 9484 patients were included from 10 institutions. Tumor (T), nodes (N), and metastasis (M) data and age were provided for each patient. The group was stratified by AJCC/UICC stage using age 45 years and age 55 years as cutoffs. The Kaplan–Meier method was used to calculate outcomes for disease-specific survival (DSS). Concordance probability estimates (CPE) were calculated to compare the degree of concordance for each model. Results: Using age 45 years as a cutoff, 10-year DSS rates for stage I–IV were 99.7%, 97.3%, 96.6%, and 76.3%, respectively. Using age 55 years as a cutoff, 10-year DSS rates for stage I–IV were 99.5%, 94.7%, 94.1%, and 67.6%, respectively. The change resulted in 12% of patients being downstaged, and the downstaged group had a 10-year DSS of 97.6%. The change resulted in an increase in CPE from 0.90 to 0.92. Conclusions: A change in the cutoff age in the current AJCC/UICC staging system from 45 years to 55 years would lead to a downstaging of 12% of patients, and would improve the statistical validity of the model. Such a change would be clinically relevant for thousands of patients worldwide by preventing overstaging of patients with low-risk disease while providing a more realistic estimate of prognosis for those who remain high risk. PMID:26914539

  7. Apolipoprotein D takes center stage in the stress response of the aging and degenerative brain☆

    PubMed Central

    Dassati, Sarah; Waldner, Andreas; Schweigreiter, Rüdiger

    2014-01-01

    Apolipoprotein D (ApoD) is an ancient member of the lipocalin family with a high degree of sequence conservation from insects to mammals. It is not structurally related to other major apolipoproteins and has been known as a small, soluble carrier protein of lipophilic molecules that is mostly expressed in neurons and glial cells within the central and peripheral nervous system. Recent data indicate that ApoD not only supplies cells with lipophilic molecules, but also controls the fate of these ligands by modulating their stability and oxidation status. Of particular interest is the binding of ApoD to arachidonic acid and its derivatives, which play a central role in healthy brain function. ApoD has been shown to act as a catalyst in the reduction of peroxidized eicosanoids and to attenuate lipid peroxidation in the brain. Manipulating its expression level in fruit flies and mice has demonstrated that ApoD has a favorable effect on both stress resistance and life span. The APOD gene is the gene that is upregulated the most in the aging human brain. Furthermore, ApoD levels in the nervous system are elevated in a large number of neurologic disorders including Alzheimer's disease, schizophrenia, and stroke. There is increasing evidence for a prominent neuroprotective role of ApoD because of its antioxidant and anti-inflammatory activity. ApoD emerges as an evolutionarily conserved anti-stress protein that is induced by oxidative stress and inflammation and may prove to be an effective therapeutic agent against a variety of neuropathologies, and even against aging. PMID:24612673

  8. Sedimentation processes and new age constraints on rifting stages in Lake Baikal: results of deep-water drilling

    NASA Astrophysics Data System (ADS)

    Kuzmin, M. I.; Karabanov, E. B.; Prokopenko, A. A.; Gelety, V. F.; Antipin, V. S.; Williams, D. F.; Gvozdkov, A. N.

    With this paper we present a first attempt to combine the direct results on lithology, composition and age dating in the boreholes BDP-93, BDP-96 and BDP-97 with geological and seismic data from the areas where those sections were drilled. The sedimentary environments represented by the BDP boreholes are markedly different and possess characteristic lithological features. The results of the deep drilling provide the essential means for testing numerous age models used in geological reconstructions of the Lake Baikal rifting dynamics. Neither the basin-wide unconformity interpreted from seismic data, nor the interpreted change from shallow-water to deep-water facies at the boundary of the seismic stratigraphic complexes were found in the BDP-96 boreholes on Academician Ridge. Also, lithology does not support the proposed reconstructions of intense lake level fluctuations and transgressions during the Pliocene at Academician Ridge. The continuous deep-water hemipelagic sedimentation at Academician Ridge has existed for the past 5Ma. The beginning of an intense rifting phase of the Neobaikalian sub-stage and related drastic changes in sedimentation processes were interpreted on seismic sections as the basin-wide unconformity B10. Different age estimates for this boundary ranged from Late Pliocene (3.5Ma) to Plio-Pleistocene boundary. As shown by BDP-96 borehole, B10 is associated with a lithological change from diatomaceous ooze to dense silty clay and not with an erosional contact. The new age for this boundary in BDP-96 is approximately 2.5Ma. This new age constraint suggests that the upper sedimentary strata of Northern Baikal (1.5-1.7km thick) have formed during the past 2.5Ma with average sedimentation rates of 60-70cm/ka. The BDP-93 boreholes at Buguldeika suggest that uplift in Primorsky Range took place prior to 1.07-1.31Ma, a date which exceeds the age of previous geological models.

  9. Age-stage, two-sex life table of Brontispa longissima (Gestro) (Coleoptera: Hispidae) feeding on four palm plant varieties.

    PubMed

    Jin, Tao; Lin, Yu-Ying; Jin, Qi-An; Wen, Hai-Bo; Peng, Zheng-Qiang

    2012-10-01

    The life history of Brontispa longissima (Gestro) (Coleoptera: Hispidae), reared under laboratory conditions on leaves of coconut (Cocos nucifera L.), royal palm [Roystonea regia (Kunth) O.F.Cook], bottle palm [Hyophorbe lagenicaulis (L. Bailey) H.E.Moore], and fishtail palm (Caryota ochlandra Hance) was analyzed using age-stage, two-sex life table. Means and standard errors of population growth parameters were calculated using the jackknife method. Moreover, survival rate and fecundity data were applied to project the population for revealing the different stage structure. The mean intrinsic rates of population growth when reared on each respective leaf type were 0.032, 0.031, 0.019, and 0.044. Individuals reared on C. nucifera achieved the highest net reproduction rate at 114.5 offspring per female. The mean generation times of B. longissima ranged from 93.2 d (reared on C. ochlandrai) to 161.5 d (reared on H. lagenicaulis). Projections from survival rate and fecundity data indicated that B. longissima populations can row considerably faster on C. ochlandra than on the other three host plants. The results validate the two-stage life history approach taken, providing an essential tool for developing and testing future control strategies.

  10. Age-Stage, Two-Sex Life Table Characteristics of Aedes albopictus and Aedes Aegypti in Penang Island, Malaysia.

    PubMed

    Maimusa, Hamisu A; Ahmad, Abu Hassan; Kassim, Nur Faeza A; Rahim, Junaid

    2016-03-01

    The life table developmental attributes of laboratory colonies of wild strains of Aedes albopictus and Aedes aegypti were analyzed and compared based on the age-stage, two-sex life table. Findings inclusive in this study are: adult preoviposition periods, total preoviposition period, mean intrinsic rate of increase (r), mean finite rate of increase (λ), net reproductive rates (R0), and mean generation time (T). The total preadult development time was 9.47 days for Ae. albopictus and 8.76 days for Ae. aegypti. The life expectancy was 19.01 days for Ae. albopictus and 19.94 days for Ae. aegypti. Mortality occurred mostly during the adult stage. The mean development time for each stage insignificantly correlated with temperature for Ae. albopictus (r  =  -0.208, P > 0.05) and (r  =  -0.312, P > 0.05) for Ae. aegypti. The population parameters suggest that Ae. albopictus and Ae. aegypti populations are r-strategists characterized by a high r, a large R0, and short T. This present study provides the first report to compare the life parameters of Ae. albopictus and Ae. aegypti strains from Penang island, Malaysia.

  11. Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

    PubMed

    Yasukawa, K; Yu, S; Yamanouchi, S; Takido, M; Akihisa, T; Tamura, T

    1995-04-01

    We have found that several lupane-type triterpenes, including lupeol, its acetate, betulin and betulinic acid, inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, and that betulinic acid inhibits tumor promotion in two-stage carcinogenesis in mice. Among seven lupane-type triterpenes assayed, these compounds inhibited the inflammatory activity induced by TPA in mice. The 50 % inhibitory dose of these compounds for TPA-induced inflammation was 0.4-4.0 μmol. Furthermore, topical application of lupeol, lupeol 3-acetate and betulin markedly suppressed the tumor-promoting effect of TPA (1 μg/mouse) in mouse skin initiated with 7,12-dimethyl-benz[a]anthracene (50 μg/mouse), at a grade corresponding to that of betulinic acid.

  12. Inhibitory effect of α-lipoic acid on thioacetamide-induced tumor promotion through suppression of inflammatory cell responses in a two-stage hepatocarcinogenesis model in rats.

    PubMed

    Fujii, Yuta; Segawa, Risa; Kimura, Masayuki; Wang, Liyun; Ishii, Yuji; Yamamoto, Ryuichi; Morita, Reiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2013-09-25

    To investigate the protective effect of α-lipoic acid (a-LA) on the hepatocarcinogenic process promoted by thioacetamide (TAA), we used a two-stage liver carcinogenesis model in N-diethylnitrosamine (DEN)-initiated and TAA-promoted rats. We examined the modifying effect of co-administered a-LA on the liver tissue environment surrounding preneoplastic hepatocellular lesions, with particular focus on hepatic macrophages and the mechanism behind the decrease in apoptosis of cells surrounding preneoplastic hepatocellular lesions during the early stages of hepatocellular tumor promotion. TAA increased the number and area of glutathione S-transferase placental form (GST-P)(+) liver cell foci and the numbers of proliferating and apoptotic cells in the liver. Co-administration with a-LA suppressed these effects. TAA also increased the numbers of ED2(+), cyclooxygenase-2(+), and heme oxygenase-1(+) hepatic macrophages as well as the number of CD3(+) lymphocytes. These effects were also suppressed by a-LA. Transcript levels of some inflammation-related genes were upregulated by TAA and downregulated by a-LA in real-time RT-PCR analysis. Outside the GST-P(+) foci, a-LA reduced the numbers of apoptotic cells, active caspase-8(+) cells and death receptor (DR)-5(+) cells. These results suggest that hepatic macrophages producing proinflammatory factors may be activated in TAA-induced tumor promotion. a-LA may suppress tumor-promoting activity by suppressing the activation of these macrophages and the subsequent inflammatory responses. Furthermore, a-LA may suppress tumor-promoting activity by suppressing the DR5-mediated extrinsic pathway of apoptosis and the subsequent regeneration of liver cells outside GST-P(+) foci.

  13. SU-E-T-630: Predictive Modeling of Mortality, Tumor Control, and Normal Tissue Complications After Stereotactic Body Radiotherapy for Stage I Non-Small Cell Lung Cancer

    SciTech Connect

    Lindsay, WD; Berlind, CG; Gee, JC; Simone, CB

    2015-06-15

    Purpose: While rates of local control have been well characterized after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC), less data are available characterizing survival and normal tissue toxicities, and no validated models exist assessing these parameters after SBRT. We evaluate the reliability of various machine learning techniques when applied to radiation oncology datasets to create predictive models of mortality, tumor control, and normal tissue complications. Methods: A dataset of 204 consecutive patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) at the University of Pennsylvania between 2009 and 2013 was used to create predictive models of tumor control, normal tissue complications, and mortality in this IRB-approved study. Nearly 200 data fields of detailed patient- and tumor-specific information, radiotherapy dosimetric measurements, and clinical outcomes data were collected. Predictive models were created for local tumor control, 1- and 3-year overall survival, and nodal failure using 60% of the data (leaving the remainder as a test set). After applying feature selection and dimensionality reduction, nonlinear support vector classification was applied to the resulting features. Models were evaluated for accuracy and area under ROC curve on the 81-patient test set. Results: Models for common events in the dataset (such as mortality at one year) had the highest predictive power (AUC = .67, p < 0.05). For rare occurrences such as radiation pneumonitis and local failure (each occurring in less than 10% of patients), too few events were present to create reliable models. Conclusion: Although this study demonstrates the validity of predictive analytics using information extracted from patient medical records and can most reliably predict for survival after SBRT, larger sample sizes are needed to develop predictive models for normal tissue toxicities and more advanced

  14. Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome

    PubMed Central

    Yamanoi, Kazuhiro; Arai, Eri; Tian, Ying; Takahashi, Yoriko; Miyata, Sayaka; Sasaki, Hiroki; Chiwaki, Fumiko; Ichikawa, Hitoshi; Sakamoto, Hiromi; Kushima, Ryoji; Katai, Hitoshi; Yoshida, Teruhiko; Sakamoto, Michiie; Kanai, Yae

    2015-01-01

    The aim of this study was to clarify the significance of DNA methylation alterations during gastric carcinogenesis. Single-CpG resolution genome-wide DNA methylation analysis using the Infinium assay was performed on 109 samples of non-cancerous gastric mucosa (N) and 105 samples of tumorous tissue (T). DNA methylation alterations in T samples relative to N samples were evident for 3861 probes. Since N can be at the precancerous stage according to the field cancerization concept, unsupervised hierarchical clustering based on DNA methylation levels was performed on N samples (βN) using the 3861 probes. This divided the 109 patients into three clusters: A (n = 20), B1 (n = 20), and B2 (n = 69). Gastric carcinomas belonging to Cluster B1 showed tumor aggressiveness more frequently than those belonging to Clusters A and B2. The recurrence-free and overall survival rates of patients in Cluster B1 were lower than those of patients in Clusters A and B2. Sixty hallmark genes for which βN characterized the epigenetic clustering were identified. We then focused on DNA methylation levels in T samples (βT) of the 60 hallmark genes. In 48 of them, including the ADAM23, OLFM4, AMER2, GPSM1, CCL28, DTX1 and COL23A1 genes, βT was again significantly correlated with tumor aggressiveness, and the recurrence-free and/or overall survival rates. Multivariate analyses revealed that βT was a significant prognostic factor, being independent of clinicopathological parameters. These data indicate that DNA methylation profiles at the precancerous stage may be inherited by gastric carcinomas themselves, thus determining tumor aggressiveness and patient outcome. PMID:25740824

  15. Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study

    PubMed Central

    Li, Jun; Yang, Shengke; Hu, Junjie; Liu, Hao; Du, Feng; Yin, Jie; Liu, Sai; Li, Ci; Xing, Shasha; Yuan, Jiatian; Lv, Bo; Fan, Jun; Leng, Shusheng; Zhang, Xin; Wang, Bing

    2016-01-01

    We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients. PMID:26934317

  16. Inferring Positions of Tumor and Nodes in Stage III Lung Cancer From Multiple Anatomical Surrogates Using Four-Dimensional Computed Tomography

    SciTech Connect

    Malinowski, Kathleen T.; Pantarotto, Jason R.; Senan, Suresh

    2010-08-01

    Purpose: To investigate the feasibility of modeling Stage III lung cancer tumor and node positions from anatomical surrogates. Methods and Materials: To localize their centroids, the primary tumor and lymph nodes from 16 Stage III lung cancer patients were contoured in 10 equal-phase planning four-dimensional (4D) computed tomography (CT) image sets. The centroids of anatomical respiratory surrogates (carina, xyphoid, nipples, mid-sternum) in each image set were also localized. The correlations between target and surrogate positions were determined, and ordinary least-squares (OLS) and partial least-squares (PLS) regression models based on a subset of respiratory phases (three to eight randomly selected) were created to predict the target positions in the remaining images. The three-phase image sets that provided the best predictive information were used to create models based on either the carina alone or all surrogates. Results: The surrogate most correlated with target motion varied widely. Depending on the number of phases used to build the models, mean OLS and PLS errors were 1.0 to 1.4 mm and 0.8 to 1.0 mm, respectively. Models trained on the 0%, 40%, and 80% respiration phases had mean ({+-} standard deviation) PLS errors of 0.8 {+-} 0.5 mm and 1.1 {+-} 1.1 mm for models based on all surrogates and carina alone, respectively. For target coordinates with motion >5 mm, the mean three-phase PLS error based on all surrogates was 1.1 mm. Conclusions: Our results establish the feasibility of inferring primary tumor and nodal motion from anatomical surrogates in 4D CT scans of Stage III lung cancer. Using inferential modeling to decrease the processing time of 4D CT scans may facilitate incorporation of patient-specific treatment margins.

  17. VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

    PubMed

    Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

    2015-07-01

    Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics.

  18. Support Vector Machine-Based Prediction of Local Tumor Control After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Klement, Rainer J.; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Guckenberger, Matthias

    2014-03-01

    Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED{sub ISO}) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED{sub ISO} and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED{sub ISO}, age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP

  19. Up-regulating telomerase and tumor suppressors: focusing on anti-aging interventions at the population level.

    PubMed

    Hartwig, Fernando Pires; Bertoldi, Daniel; Larangeira, Martin; Wagner, Mônica Silveira

    2014-02-01

    Most human populations are undergoing a demographic transition regarding their age structure. This transition is reflected in chronic non-communicable diseases featuring among the main contributors to burden of disease. Considering that the aging process is a major risk factor for such conditions, understanding the mechanisms underlying aging and age-related diseases is critical to develop strategies to impact human health at population and/or individual-levels. Two different aspects of aging process (namely, telomere shortening and DNA damage accumulation) were shown to interact in positively impacting mice median survival. However, strategies aimed at translating such knowledge into actual human health benefits have not yet been discussed. In this manuscript, we present potential exposures that are suited for population-level interventions, and contextualize the roles of population (based on behavioral exposures) and individual-level (based on small-molecule administration) anti-aging interventions in different levels of disease prevention. We suggest that exposures such as moderate wine consumption, reducing calorie intake and active lifestyle are potentially useful for primordial and primary prevention, while small-molecules that activate telomerase and/or tumor suppression responses are more suited for secondary and tertiary prevention (although important for primary prevention in specific population subgroups). We also indicate the need of studying the impacts, on aging and age-related diseases, of different combinations of these exposures in well-conducted randomized controlled trials, and propose Mendelian randomization as a valuable alternative to gather information in human populations regarding the effects of potential anti-aging interventions.

  20. Low Ki67/high ATM protein expression in malignant tumors predicts favorable prognosis in a retrospective study of early stage hormone receptor positive breast cancer

    PubMed Central

    Feng, Xiaolan; Li, Haocheng; Kornaga, Elizabeth N.; Dean, Michelle; Lees-Miller, Susan P.; Riabowol, Karl; Magliocco, Anthony M.; Morris, Don; Watson, Peter H.; Enwere, Emeka K.; Bebb, Gwyn; Paterson, Alexander

    2016-01-01

    Introduction This study was designed to investigate the combined influence of ATM and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods 532 formalin-fixed paraffin-embedded specimens of resected primary breast tumors were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using fluorescence and brightfield immunohistochemistry respectively, and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p = 0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Conclusions These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. PMID:27741524

  1. Can Wilms Tumor Be Found Early?

    MedlinePlus

    ... Wilms Tumor Early Detection, Diagnosis, and Staging Can Wilms Tumor Be Found Early? Wilms tumors are usually found ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  2. Genome-wide DNA methylation profiles reveal novel candidate genes associated with meat quality at different age stages in hens

    PubMed Central

    Zhang, Meng; Yan, Feng-Bin; Li, Fang; Jiang, Ke-Ren; Li, Dong-Hua; Han, Rui-Li; Li, Zhuan-Jan; Jiang, Rui-Rui; Liu, Xiao-Jun; Kang, Xiang-Tao; Sun, Gui-Rong

    2017-01-01

    Poultry meat quality is associated with breed, age, tissue and other factors. Many previous studies have focused on distinct breeds; however, little is known regarding the epigenetic regulatory mechanisms in different age stages, such as DNA methylation. Here, we compared the global DNA methylation profiles between juvenile (20 weeks old) and later laying-period (55 weeks old) hens and identified candidate genes related to the development and meat quality of breast muscle using whole-genome bisulfite sequencing. The results showed that the later laying-period hens, which had a higher intramuscular fat (IMF) deposition capacity and water holding capacity (WHC) and less tenderness, exhibited higher global DNA methylation levels than the juvenile hens. A total of 2,714 differentially methylated regions were identified in the present study, which corresponded to 378 differentially methylated genes, mainly affecting muscle development, lipid metabolism, and the ageing process. Hypermethylation of the promoters of the genes ABCA1, COL6A1 and GSTT1L and the resulting transcriptional down-regulation in the later laying-period hens may be the reason for the significant difference in the meat quality between the juvenile and later laying-period hens. These findings contribute to a better understanding of epigenetic regulation in the skeletal muscle development and meat quality of chicken. PMID:28378745

  3. Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology

    NASA Astrophysics Data System (ADS)

    Wendel, Marco; Bazhenova, Lyudmila; Boshuizen, Rogier; Kolatkar, Anand; Honnatti, Meghana; Cho, Edward H.; Marrinucci, Dena; Sandhu, Ajay; Perricone, Anthony; Thistlethwaite, Patricia; Bethel, Kelly; Nieva, Jorge; van den Heuvel, Michel; Kuhn, Peter

    2012-02-01

    Circulating tumor cell (CTC) counts are an established prognostic marker in metastatic prostate, breast and colorectal cancer, and recent data suggest a similar role in late stage non-small cell lung cancer (NSCLC). However, due to sensitivity constraints in current enrichment-based CTC detection technologies, there are few published data about CTC prevalence rates and morphologic heterogeneity in early-stage NSCLC, or the correlation of CTCs with disease progression and their usability for clinical staging. We investigated CTC counts, morphology and aggregation in early stage, locally advanced and metastatic NSCLC patients by using a fluid-phase biopsy approach that identifies CTCs without relying on surface-receptor-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. HD-CTCs were analyzed in blood samples from 78 chemotherapy-naïve NSCLC patients. 73% of the total population had a positive HD-CTC count (>0 CTC in 1 mL of blood) with a median of 4.4 HD-CTCs mL-1 (range 0-515.6) and a mean of 44.7 (±95.2) HD-CTCs mL-1. No significant difference in the medians of HD-CTC counts was detected between stage IV (n = 31, range 0-178.2), stage III (n = 34, range 0-515.6) and stages I/II (n = 13, range 0-442.3). Furthermore, HD-CTCs exhibited a uniformity in terms of molecular and physical characteristics such as fluorescent cytokeratin intensity, nuclear size, frequency of apoptosis and aggregate formation across the spectrum of staging. Our results demonstrate that despite stringent morphologic inclusion criteria for the definition of HD-CTCs, the HD-CTC assay shows high sensitivity in the detection and characterization of both early- and late-stage lung cancer CTCs. Extensive studies are warranted to investigate the prognostic value of CTC profiling in early-stage lung cancer. This finding has implications for the design of extensive studies examining screening, therapy and surveillance in

  4. Neurosurgical procedures, spinal nerve roots - one stage removal of thoracic dumb-bell tumor: role of spinal evoked potential.

    PubMed

    Srivastava, Dharmendra Kumar; Singh, Deepak; Tiwari, Bhuwan Chandra; Awasthi, Namarata; Hussain, Nuzhat

    2014-02-01

    We report a rare case of benign thoracic dumb-bell tumor in the upper posterior mediastinum, which was successfully removed by posterolateral thoracotomy and foraminotomy, using intraoperative monitoring of spinal motor-evoked potentials. This technique has many advantages including minimal morbidity and mortality, a single incision, one-step complete resection with adequate exposure, spinal stabilization, avoidance of laminectomy, nerve root identification, and good predicted postoperative function.

  5. KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia.

    PubMed

    Huang, Conway C; Liu, Zhaoli; Li, Xingnan; Bailey, Sarah K; Nail, Clinton D; Foster, K Wade; Frost, Andra R; Ruppert, J Michael; Lobo-Ruppert, Susan M

    2005-12-01

    KLF4 is induced upon growth-arrest in vitro and during epithelial maturation in vivo, and is essential for proper cell fate specification of post-mitotic cells. In spite of a normal role in post-mitotic cells, expression is upregulated and constitutive in certain tumor types. KLF4 functions as an oncogene in vitro, and enforced expression in basal cells of mouse skin rapidly induces lesions similar to hyperplasia, dysplasia and squamous cell carcinoma (SCC). Here we used conditional expression to characterize early steps in KLF4-mediated tumor initiation. In contrast to SCC-like lesions that result when using a conditional, keratin 14 promoter-dependent strategy, lower conditional expression achieved using a MMTV promoter induced only epidermal cycling within morphologically normal skin, a process we termed occult cell turnover. Surprisingly, KLF4-induced hyperplastic lesions showed increased transgene-derived mRNA and protein in maturing, PCNA-negative cells, a property of endogenous KLF4. In contrast, hyperplastic lesions induced by GLI1, a control, showed uniform transgene expression. In KLF4-induced dysplasia and SCC the complementarity of KLF4 and PCNA was replaced by concordance of the two proteins. These studies show that KLF4 transcripts are normally suppressed in cycling cells in a promoter-independent fashion, consistent with a post-transcriptional control, and reveal loss of this control in the transition from hyperplasia to dysplasia. Like the mouse tumors, human cutaneous SCCs and adjacent dysplasias frequently showed maturation-independence of KLF4, with co-expression of KLF4 and PCNA. A smaller subset of human SCCs showed complementarity of KLF4 and PCNA, similar to hyperplastic mouse skin. The results identify parallels between a mouse model and human primary tumors, and show that successive increases of KLF4 in the nuclei of basal keratinocytes leads to occult cell turnover followed by hyperplasia, dysplasia, and invasive SCC.

  6. Staged liver resection for perihilar liver tumors using a tourniquet in the umbilical fissure and sequential portal vein embolization on the fourth postoperative day (a modified ALTPS).

    PubMed

    Robles Campos, Ricardo; Brusadin, Roberto; López Conesa, Asunción; Parrilla Paricio, Pascual

    2014-12-01

    Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) achieves the hypertrophy of the future liver remnant in seven days. We achieved the same hypertrophy placing a tourniquet in the parenchimal transection line associating a right portal vein ligation (associating liver tourniquet and right portal vein ligation for staged hepatectomy-ALTPS). In perihiliar tumors a«non touch» technique should be performed. ALPPS y ALTPS do not comply with this technical aspect because a dissection of the hilum is carried out in both procedures during the portal dissection. To avoid this problem we devised a new method called sequential ALTPS. It consists of placing a tourniquet in the umbilical fissure without ligation of the right portal vein during the first stage. Subsequently, on the 4(th) postoperative day we perform a percutaneous right portal vein embolization. We present the first case of this new technique in which we have obtained a hypertrophy of 77% of the future liver remnant seven days after portal vein embolization. In the second stage a right trisectionectomy was performed with inferior vena cava resection with a goretex graft replacement.

  7. Work-family conflict among members of full-time dual-earner couples: an examination of family life stage, gender, and age.

    PubMed

    Allen, Tammy D; Finkelstein, Lisa M

    2014-07-01

    Based on cross-sectional data from the 2008 National Study of the Changing Workforce, this study investigates relationships between gender, age, and work-family conflict across 6 family life stages. Participants were 690 married/partnered employees who worked 35 or more hours a week. Results indicated a small but negative relationship between age and work-family conflict. Work-family conflict was also associated with family stage, with the least amount of conflict occurring during the empty nest stage and the most occurring when the youngest child in the home was 5 years of age or younger. Gender differences were also observed. Specifically, men reported more work interference with family than did women when the youngest child in the home was a teen. Women overall reported more family interference with work than did men. Results concerning age and gender revealed a different pattern demonstrating that family stage is not simply a proxy for age. Age had a main effect on work-to-family conflict that was monotonic in nature and on family to-work conflict that was linear in nature. In conclusion, the results indicate gender, age, and family stage each uniquely relate to work-family conflict.

  8. The Expression of Glyceraldehyde-3-Phosphate Dehydrogenase Associated Cell Cycle (GACC) Genes Correlates with Cancer Stage and Poor Survival in Patients with Solid Tumors

    PubMed Central

    Wang, Dunrui; Moothart, Daniel R.; Lowy, Douglas R.; Qian, Xiaolan

    2013-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is often used as a stable housekeeping marker for constant gene expression. However, the transcriptional levels of GAPDH may be highly up-regulated in some cancers, including non-small cell lung cancers (NSCLC). Using a publically available microarray database, we identified a group of genes whose expression levels in some cancers are highly correlated with GAPDH up-regulation. The majority of the identified genes are cell cycle-dependent (GAPDH Associated Cell Cycle, or GACC). The up-regulation pattern of GAPDH positively associated genes in NSCLC is similar to that observed in cultured fibroblasts grown under conditions that induce anti-senescence. Data analysis demonstrated that up-regulated GAPDH levels are correlated with aberrant gene expression related to both glycolysis and gluconeogenesis pathways. Down-regulation of fructose-1,6-bisphosphatase (FBP1) in gluconeogenesis in conjunction with up-regulation of most glycolytic genes is closely related to high expression of GAPDH in the tumors. The data presented demonstrate that up-regulation of GAPDH positively associated genes is proportional to the malignant stage of various tumors and is associated with an unfavourable prognosis. Thus, this work suggests that GACC genes represent a potential new signature for cancer stage identification and disease prognosis. PMID:23620736

  9. Total Gross Tumor Volume Is an Independent Prognostic Factor in Patients Treated With Selective Nodal Irradiation for Stage I to III Small Cell Lung Cancer

    SciTech Connect

    Reymen, Bart; Van Loon, Judith; Baardwijk, Angela van; Wanders, Rinus; Borger, Jacques; Dingemans, Anne-Marie C.; Bootsma, Gerben; Pitz, Cordula; Lunde, Ragnar; Geraedts, Wiel; Lambin, Philippe; De Ruysscher, Dirk

    2013-04-01

    Purpose: In non-small cell lung cancer, gross tumor volume (GTV) influences survival more than other risk factors. This could also apply to small cell lung cancer. Methods and Materials: Analysis of our prospective database with stage I to III SCLC patients referred for concurrent chemo radiation therapy. Standard treatment was 45 Gy in 1.5-Gy fractions twice daily concurrently with carboplatin-etoposide, followed by prophylactic cranial irradiation (PCI) in case of non-progression. Only fluorodeoxyglucose (FDG)-positron emission tomography (PET)-positive or pathologically proven nodal sites were included in the target volume. Total GTV consisted of post chemotherapy tumor volume and pre chemotherapy nodal volume. Survival was calculated from diagnosis (Kaplan-Meier ). Results: A total of 119 patients were included between May 2004 and June 2009. Median total GTV was 93 ± 152 cc (7.5-895 cc). Isolated elective nodal failure occurred in 2 patients (1.7%). Median follow-up was 38 months, median overall survival 20 months (95% confidence interval = 17.8-22.1 months), and 2-year survival 38.4%. In multivariate analysis, only total GTV (P=.026) and performance status (P=.016) significantly influenced survival. Conclusions: In this series of stage I to III small cell lung cancer patients treated with FDG-PET-based selective nodal irradiation total GTV is an independent risk factor for survival.

  10. Dental age assessment of adolescents and emerging adults in United Kingdom Caucasians using censored data for stage H of third molar roots.

    PubMed

    Boonpitaksathit, Teelana; Hunt, Nigel; Roberts, Graham J; Petrie, Aviva; Lucas, Victoria S

    2011-10-01

    The root of the third permanent molar is the only dental structure that continues development after completion of growth of the second permanent molar. It is claimed that the lack of a clearly defined end point for completion of growth of the third permanent molar means that this tooth cannot be used for dental age assessment. The aim of this study was to estimate the mean age of attainment of the four stages (E, F, G, and H) of root development of the third molar. The way in which the end point of completion of stage H can be identified is described. A total of 1223 dental panoramic tomographs (DPTs) available in the archives of the Eastman Dental Hospital, London, were used for this study. The ages of the subjects ranged from 12.6 to 24.9 years with 63 per cent of the sample being female. Demirjan's tooth development stages (TDSs), for the first and second molars, were applied to the third molars by a single examiner. For each of stages E, F, and G and for stage H censored data, the mean ages of the males and females were compared, separately within each tooth morphology type using the two sample t-test (P < 0.01). The same test was used to compare the mean ages of the upper and lower third molars on each side, separately for each gender. The mean age of attainment and the 99 per cent confidence interval (CI) for each TDS were calculated for each third molar. The final stage H data were appropriately censored to exclude data above the age of completion of root growth. The results showed that, for each gender, the age in years at which individuals attained each of the four TDSs was approximately normally distributed. The mean age for appropriately censored data was always lower than the corresponding mean age of the inappropriately censored data for stage H (male UR8 19.57, UL8 19.53, LL8 19.91, and LR8 20.02 and female UR8 20.08, UL8 20.13, LL8 20.78, and LR8 20.70). This inappropriately censored data overestimated the mean age for stage H. The appropriately

  11. Regular physical activity is associated with improved small artery distensibility in young to middle-age stage 1 hypertensives.

    PubMed

    Saladini, Francesca; Benetti, Elisabetta; Mos, Lucio; Mazzer, Adriano; Casiglia, Edoardo; Palatini, Paolo

    2014-12-01

    The aim of the present study was to investigate the association of physical activity with small artery elasticity in the early stage of hypertension. We examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure 145.6±10.3/92.5±5.8 mmHg), divided into two categories of physical activity, sedentary (n=264) and non-sedentary (n=102) subjects. The augmentation index was measured using the Specaway DAT System. Small artery compliance (C2) was measured by applanation tonometry, at the radial artery, with an HDI CR2000 device. After 6 years of follow-up, arterial distensibility assessment was repeated in 151 subjects. Heart rate was lower in active than in sedentary subjects (71.2±8.9 vs 76.6±9.7 bpm, p<0.001). After adjusting for age, sex, heart rate, smoking, and blood pressure, C2 was higher (8.0±2.6 vs 6.4±3.0 ml/mmHg × 100, p=0.008) in non-sedentary than in sedentary patients. The augmentation index was smaller in the former (8.8±20.1 vs 16.8±26.5%, p=0.044) but the difference lost statistical significance after further adjustment for blood pressure. After 6 years, C2 was still higher in the non-sedentary than sedentary subjects. In addition, an improvement in the augmentation index accompanied by a decline in total peripheral resistance was found in the former. These data show that regular physical activity is associated with improved small artery elasticity in the early phase of hypertension. This association persists over time and is independent of blood pressure and heart rate.

  12. Influence of histological degree of seminiferous tubular degeneration and stage of seminiferous cycle on the proliferation of spermatogonia in aged Syrian hamster (Mesocricetus auratus).

    PubMed

    Bernal-Mañas, C M; Cortes, S; Morales, E; Horn, R; Seco-Rovira, V; Beltran-Frutos, E; Ferrer, C; Canteras, M; Pastor, L M

    2014-08-01

    The ageing testis is associated with germ loss in the seminiferous epithelium and a decrease in spermatogonia proliferation. In this work, we study whether the stages of the seminiferous epithelium cycle and/or the degree of histological tubular degeneration resulting from ageing is related with this decrease in spermatogonia proliferation. Eleven hamsters were used, five aged 6 months and six aged 24 months. In both groups, the proliferative activity was studied by BrdU immunostaining. The number of BrdU-positive and BrdU-negative cells was measured, providing the overall proliferation index in adult and aged testes. The mean number of BrdU-positive cells was also determined for each degree of histological degeneration of seminiferous epithelium, and a spermatogonia proliferation index was obtained for each stage of the seminiferous cycle. Ageing caused an overall decrease in the BrdU-positive cell percentage and a decrease in the number of BrdU-positive cells in the tubular sections with hypospermatogenesis, the sloughing of germ cells and maturation arrest, these changes being similar in both young and old animals. The spermatogonia proliferation index was only seen to be significantly lower in ageing hamster in stages VII-VIII of the seminiferous epithelium cycle. In conclusion, the overall decrease in proliferation observed in aged seminiferous epithelium is correlated with an increase in the number of degenerated sections of the seminiferous tubules, and this decrease is a phenomenon which occurs in specific stages of the seminiferous cycle.

  13. Correlating planned radiation dose to the cochlea with primary site and tumor stage in patients with head and neck cancer treated with intensity-modulated radiation therapy

    SciTech Connect

    Zhang, Jeanette; Qureshi, Muhammad M.; Kovalchuk, Nataliya; Truong, Minh Tam

    2014-04-01

    The aim of the study was to determine tumor characteristics that predict higher planned radiation (RT) dose to the cochlea in patients with head and neck cancer (HNC) treated with intensity-modulated radiotherapy (IMRT). From 2004 to 2012, 99 patients with HNC underwent definitive IMRT to a median dose of 69.96 Gy in 33 fractions, with the right and left cochlea-vestibular apparatus contoured for IMRT optimization as avoidance structures. If disease involvement was adjacent to the cochlea, preference was given to tumor coverage by prescription dose. Descriptive statistics were calculated for dose-volume histogram planning data, and mean planning dose to the cochlea (from left or right cochlea, receiving the greater amount of RT dose) was correlated to primary site and tumor stage. Mean (standard deviation) cochlear volume was 1.0 (0.60) cm{sup 3} with maximum and mean planned doses of 31.9 (17.5) Gy and 22.1 (13.7) Gy, respectively. Mean planned dose (Gy) to cochlea by tumor site was as follows: oral cavity (18.6, 14.4), oropharynx (21.7, 9.1), nasopharynx (36.3, 10.4), hypopharynx (14.9, 7.1), larynx (2.1, 0.62), others including the parotid gland, temporal bone, and paranasal sinus (33.6, 24.0), and unknown primary (25.6, 6.7). Average mean planned dose (Gy) to the cochlea in T0-T2 and T3-T4 disease was 22.0 and 29.2 Gy, respectively (p = 0.019). By site, a significant difference was noted for nasopharynx and others (31.6 and 50.7, p = 0.012) but not for oropharynx, oral cavity, and hypopharynx. Advanced T category predicted for higher mean cochlear dose, particularly for nasopharyngeal, parotid gland, temporal bone, and paranasal sinus HNC sites.

  14. TARP vaccination is associated with slowing in PSA velocity and decreasing tumor growth rates in patients with Stage D0 prostate cancer.

    PubMed

    Wood, Lauren V; Fojo, Antonio; Roberson, Brenda D; Hughes, Meghan S B; Dahut, William; Gulley, James L; Madan, Ravi A; Arlen, Philip M; Sabatino, Marianna; Stroncek, David F; Castiello, Luciano; Trepel, Jane B; Lee, Min-Jung; Parnes, Howard L; Steinberg, Seth M; Terabe, Masaki; Wilkerson, Julia; Pastan, Ira; Berzofsky, Jay A

    2016-08-01

    T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks. 41 patients enrolled with median on-study duration of 75 weeks at the time of this analysis. Seventy-two percent of patients reaching 24 weeks and 74% reaching 48 weeks had a decreased Slope Log(PSA) compared to their pre-vaccination baseline (p = 0.0012 and p = 0.0004 for comparison of overall changes in Slope Log(PSA), respectively). TARP vaccination also resulted in a 50% decrease in median tumor growth rate (g): pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p = 0.003). 80% of subjects exhibited new vaccine-induced TARP-specific IFNγ ELISPOT responses but they did not correlate with decreases in Slope Log(PSA). Thus, vaccination with TARP peptides resulted in significant slowing in PSA velocity and reduction in tumor growth rate in a majority of patients with PSA biochemical recurrence.

  15. Plasma 25-Hydroxyvitamin D3 and Bladder Cancer Risk According to Tumor Stage and FGFR3 Status: A Mechanism-Based Epidemiological Study

    PubMed Central

    2012-01-01

    Background Previous evidence suggests that 25-hydroxyvitamin D3 [25(OH)D3] protects against several cancers. However, little is known regarding urothelial bladder cancer (UBC). We analyzed the association between plasma 25(OH)D3 and overall risk of UBC, as well as according to stage and FGFR3 molecular subphenotypes. Methods Plasma concentrations of 25(OH)D3 in 1125 cases with UBC and 1028 control subjects were determined by a chemiluminescence immunoassay. FGFR3 mutational status and expression in tumor tissue were assessed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression adjusting for potential confounders. Analyses were further stratified by tumor invasiveness and grade, FGFR3 expression, and smoking status. Cell proliferation was measured in human UBC cell lines cultured with 1α,25-dihydroxyvitamin D3. Results A statistically significantly increased risk of UBC was observed among subjects presenting the lowest concentrations of 25(OH)D3 (ORadj = 1.83; 95% CI = 1.19 to 2.82; P = .006), showing a dose–response effect (P trend = .004). The association was stronger for patients with muscle-invasive tumors, especially among low-FGFR3 expressers (ORadj = 5.94; 95% CI = 1.72 to 20.45; P = .005). The biological plausibility of these associations is supported by the fact that, in vitro, 1α,25-dihydroxyvitamin D3 upregulates FGFR3 expression in UBC cell lines with low levels of wild-type FGFR3. Conclusion These findings support a role of vitamin D in the pathogenesis of UBC and show that 25(OH)D3 levels are associated with FGFR3 expression in the tumor. Because FGFR3 mutation and overexpression are markers of better outcome, our findings suggest that individuals with low levels of plasma 25(OH)D3 may be at high risk of more aggressive forms of UBC. PMID:23108201

  16. Predictive Value of Stemness Factor Sox2 in Gastric Cancer Is Associated with Tumor Location and Stage

    PubMed Central

    Kang, Qian; Li, Ai-Qin; Jin, Peng; Wang, Xin; He, Yu-Qi; Li, Na; Cheng, Tao; Sheng, Jian-Qiu

    2017-01-01

    Cancer stem cells (CSCs) are thought to be the "root" of cancer. Although stemness-related factors ALDH1A1 and Sox2 have been used as markers to identify gastric CSCs, the expression pattern and significance of these factors in gastric cancer have not been sufficiently demonstrated. In this study, the expressions of ALDH1A1 and Sox2 were detected by immunohistochemistry in 122 gastric cancer specimens. And the correlation between Sox2 or ALDH1A1 expression and clinicopathological parameters and overall survival data were analyzed. The positive rate of ALDH1A1 expression was 60%, but there was no significant difference between survival rates of ALDH1A1-positive and ALDH1A1-negative patients. Sox2 was expressed in 42% of specimens and was associated with poor prognosis of patients (P = 0.015). Stratified analysis showed that Sox2 expression correlated with shorter lifespan only in patients with cardiac gastric cancers (P = 0.002) or stage I or II gastric cancers (P = 0.002); but not in patients with non-cardiac cancers (P = 0.556) or stage III or IV gastric cancers (P = 0.121). Analysis on a database cohort validated the correlation between Sox2 expression and poor prognosis in stage II cancer. Also, expression of Sox2 was associated with lymphnode metastasis in patients with cardiac gastric cancer (P = 0.037). A multivariate analysis revealed that Sox2 was an independent prognostic factor in cardiac gastric cancer. Our results indicate that predictive value of Sox2 in gastric cancer is associated with cardiac cancer location and with early cancer stages (I and II). PMID:28046028

  17. Palynology, geochemistry and Re-Os age of the Lower-Middle Pennsylvanian stage boundary, central Appalachian basin, USA

    NASA Astrophysics Data System (ADS)

    Geboy, N.; Tripathy, G. R.; Ruppert, L. F.; Eble, C. F.; Blake, B. M.; Hannah, J. L.; Stein, H. J.

    2014-12-01

    Wales and Germany and therefore has implications across the Carboniferous Euramerican Belt. Further, the Betsie has been interpreted to represent the Lower-Middle Pennsylvanian stage boundary in North America, making this directly measured age an important marker not only within the CAB but also for refinement of the Carboniferous timescale.

  18. High Expression of KIF20A Is Associated with Poor Overall Survival and Tumor Progression in Early-Stage Cervical Squamous Cell Carcinoma

    PubMed Central

    Gu, Haifeng; Li, Min; Liu, Zhimin; Feng, Yanling; Zheng, Nianzhen; Xie, Chuanmiao; Zhang, Yanna

    2016-01-01

    Background The kinesin family member 20a (KIF20A) protein has been implicated in the development and progression of many human cancers; however, its precise function and role in cervical cancer remain largely unclear. This study aimed to investigate the expression profile and prognostic value of KIF20A in patients with early-stage cervical squamous cell carcinoma. Methods We examined the mRNA and protein levels of KIF20A in eight cervical cancer cell lines and eight paired cervical cancer samples, compared with normal cervical epithelial cells and adjacent normal cervical tissues, respectively. Immunohistochemistry was performed to detect the expression of KIF20A in paraffin-embedded specimens from 169 early-stage cervical squamous cell carcinoma patients. Statistical analyses were applied to analyze the association between KIF20A expression and clinical variables, as well with patient survival. Results The mRNA and protein expression levels of KIF20A were significantly elevated in cervical cancer cell lines and lesions compared with normal cells and corresponding normal tissues (P < 0.05). Immunohistochemistry analysis in 169 cervical cancer cases revealed that increased KIF20A expression was strongly associated with human papillomavirus (HPV) infection (P = 0.008), clinical stage (P = 0.001), tumor recurrence (P = 0.016), vital status (P < 0.001), the property of the surgical margin (P = 0.032), the lymphovascular space involvement (P = 0.014), and pelvic lymph node metastasis (P = 0.001). The overall survival and disease-free survival of patients with high levels of KIF20A expression were significantly poorer than those with low KIF20A expression. KIF20A was an independent survival prognostic factor, as evidenced by univariate and multivariate analysis. Conclusions Our results illustrate that elevated KIF20A expression correlates with HPV infection, clinical stage, tumor recurrence, lymphovascular space involvement, pelvic lymph node metastasis, and poor outcome

  19. The New Immortalized Uroepithelial Cell Line HBLAK Contains Defined Genetic Aberrations Typical of Early Stage Urothelial Tumors

    PubMed Central

    Hoffmann, Michèle J.; Koutsogiannouli, Evangelia; Skowron, Margaretha A.; Pinkerneil, Maria; Niegisch, Günter; Brandt, Artur; Stepanow, Stefanie; Rieder, Harald; Schulz, Wolfgang A.

    2016-01-01

    Background: Cell culture models of normal urothelial cells are important for studying differentiation, disease mechanisms and anticancer drug development. Beyond primary cultures with their limitations in lifespan, interindividual heterogeneity and supply, few conditionally immortalized cell lines with limited applicability due to partial transformation or impaired differentiation capacity are available. We describe characteristics of the new spontaneously immortalized cell line HBLAK derived from a primary culture of uroepithelial cells. Objective: To characterize utility and limitations of HBLAK cells as an urothelial cell culture model. Methods: Differentiation markers were investigated by immunofluorescence and RT-PCR, genetic changes by standard karyotyping, array-CGH, PCR, RT-PCR and exome sequencing; expression of p53 and p21 by Western blotting. Results: HBLAK cells proliferated for >50 passages without senescing. They expressed cytokeratins of basal urothelial cells. Terminal differentiation markers appeared only after induction of differentiation by specific protocols. The karyotype was stable, with few chromosomal changes, especially gains of chromosomes 5 and 20 and a chromosome 9p21 deletion resulting in p16INK4A loss. A C228T TERT promoter mutation was present, but no other mutation typical of urothelial carcinoma. TP53 was wild-type and the cell cycle was arrested in response to genomic stress. Conclusions: HBLAK cells retain some differentiation potential and respond to cytotoxic agents similar to normal urothelial cells, but contain genetic changes contributing to immortalization in urothelial tumors. HBLAK may be valuable for evaluating the tumor specificity of novel cancer drugs, but may also be applied as an urothelial in vitro carcinogenesis model. PMID:28035326

  20. IMMMUNOPHENOTYPE OF SPONTANEOUS HEMATOLYMPHOID TUMORS OCCURRING IN YOUNG AND AGING FEMALE CD-1 MICE

    PubMed Central

    Rehg, Jerold E.; Rahija, Richard; Bush, Dorothy; Bradley, Alys; Ward, Jerrold M.

    2015-01-01

    A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1 mice, but the cellular lineage of CD-1 mouse neoplasms has not be published. In this study, immunohistochemistry (IHC) was used to characterize the cellular lineage of spontaneous hematolymphoid neoplasms arising in young female CD-1 mice used as health monitoring sentinels and aging female CD-1 mice used as controls in 80 wk carcinogenesis studies. Lymphoblastic lymphomas of T-cell and B-cell lineage were common in mice 12 mo or less of age, whereas a wide range of non-lymphoblastic B-cell lymphomas and lymphoblastic T-cell lymphomas were common in mice > 12 mo old. Renal hyaline droplets positive for lysozyme were observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA-BCL) and a myeloid leukemia. Endogenous ecotropic MuLV genes have been recovered from CD-1 mice, but MuLV protein expression has not been previously demonstrated. We reported for the first time the expression of MuLV protein by IHC in lymphomas and some normal tissues of both young and aging CD-1 mice. This report should help to differentiate spontaneous lymphomas and leukemias in CD-1 mice from those induced by chemicals and other methods. PMID:26224701

  1. Tumor Markers

    MedlinePlus

    ... types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma Tissue analyzed: Blood How used: To assess stage, ... NSE) Cancer types: Small cell lung cancer and neuroblastoma Tissue analyzed: Blood How used: To help in ...

  2. One stage curative resection of double intestinal neuroendocrine tumors with thirty-two bilobar liver metastases. A case report.

    PubMed

    Mirarchi, Mariateresa; De Raffele, Emilio; Cuicchi, Dajana; Lecce, Ferdinando; Cruciani, Giorgio; Cola, Bruno

    2015-01-01

    Neuroendocrine tumours (NETs) of the midgut are often multifocal and have a noticeable attitude to metastasize to locoregional lymph nodes and liver. Surgery is the only curative treatment for metastatic NETs of the midgut, even though only a minority of patients are candidates to radical surgical resection. The optimal timing for surgical resection in case of synchronous presentation of primary intestinal neoplasms and resectable LM is still controversial, especially when LM are multiple and/or involve multiple liver segments. Even though a staged approach with initial intestinal resection followed by liver resection is still preferred, recent studies have shown favourable results for simultaneous procedures, which have the striking advantage of avoiding a second laparotomy, with morbidity and mortality rates comparable to staged resections. We report here the case of a patient with double midgut well-differentiated NET and thirty-two synchronous bilobar LM who received successful simultaneous curative right hemicolectomy and radical but conservative liver resection and radiofrequency thermal ablation with the guidance of intraoperative ultrasonography. He is alive without evidence of recurrence 48 months after surgery.

  3. Is cancer a metabolic rebellion against host aging? In the quest for immortality, tumor cells try to save themselves by boosting mitochondrial metabolism.

    PubMed

    Ertel, Adam; Tsirigos, Aristotelis; Whitaker-Menezes, Diana; Birbe, Ruth C; Pavlides, Stephanos; Martinez-Outschoorn, Ubaldo E; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2012-01-15

    Aging drives large systemic reductions in oxidative mitochondrial function, shifting the entire body metabolically towards aerobic glycolysis, a.k.a, the Warburg effect. Aging is also one of the most significant risk factors for the development of human cancers, including breast tumors. How are these two findings connected? One simplistic idea is that cancer cells rebel against the aging process by increasing their capacity for oxidative mitochondrial metabolism (OXPHOS). Then, local and systemic aerobic glycolysis in the aging host would provide energy-rich mitochondrial fuels (such as L-lactate and ketones) to directly "fuel" tumor cell growth and metastasis. This would establish a type of parasite-host relationship or "two-compartment tumor metabolism", with glycolytic/oxidative metabolic-coupling. The cancer cells ("the seeds") would flourish in this nutrient-rich microenvironment ("the soil"), which has been fertilized by host aging. In this scenario, cancer cells are only trying to save themselves from the consequences of aging, by engineering a metabolic mutiny, through the amplification of mitochondrial metabolism. We discuss the recent findings of Drs. Ron DePinho (MD Anderson) and Craig Thomspson (Sloan-Kettering) that are also consistent with this new hypothesis, linking cancer progression with metabolic aging. Using data mining and bioinformatics approaches, we also provide key evidence of a role for PGC1a/NRF1 signaling in the pathogenesis of (1) two-compartment tumor metabolism, and (2) mitochondrial biogenesis in human breast cancer cells.

  4. Multi-stage uplift of the Rocky Mountains: new age constraints on the Telluride Conglomerate and regional compilation of apatite fission track ages

    NASA Astrophysics Data System (ADS)

    Donahue, M. S.; Karlstrom, K. E.; Gonzales, D. A.; Pecha, M.; McKeon, R. E.

    2011-12-01

    The Telluride Conglomerate, exposed on the western flanks of Oligocene caldera complexes of the San Juan Mountains of Colorado, has historically been considered an Eocene alluvial deposit overlying the "Rocky Mountain erosion surface" and pre-dating Oligocene volcanism. Measured sections show that the Telluride preserves an unroofing sequence with basal units dominated by Paleozoic sedimentary clasts transitioning into upper units dominated by locally derived Proterozoic basement mixed with previously unrecognized andesitic Oligocene volcanics. Paleoflow directions and thicknesses of the preserved unit indicate the Telluride Conglomerate was deposited by a large, high-energy WNW- flowing braided river system. Detrital zircon analysis indicates minimum ages for individual grains within the Telluride Conglomerate of 28.0 to 31.5 Ma. This, plus the entrained volcanic clasts, redefines the unit as being of Oligocene age and indicates that conglomeratic deposition overlapped with regional San Juan volcanism and just predated major caldera eruptions at 28.4 Ma (San Juan and Uncompahgre) and 27.6 Ma (Silverton). We interpret the deposition of the Telluride Conglomerate to be the depositional response to regional uplift and erosion related to early stages of San Juan magmatism. These units have undergone significant post-depositional tectonism: the Telluride Conglomerate is found at ~9,000ft elevation near Telluride, CO, but is at ~13,000' at its westernmost exposure at Mt. Wilson. We attribute this differential uplift to be associated with faulting, pluton emplacement, and additional mantle driven uplift associated with the emplacement and cooling of the Wilson Stock in the last 20-22 Ma as documented by Miocene cooling seen in apatite helium (AHe) ages. This cooling fits into our regional compilation of published apatite fission track (AFT) and AHe data showing temporally and spatially partitioned Cenozoic cooling indicative of multistage uplift of the Rocky Mountain

  5. Assessment of Choroidal Microstructure and Subfoveal Thickness Change in Eyes With Different Stages of Age-Related Macular Degeneration

    PubMed Central

    Lu, Linna; Xu, Shiqiong; He, Fangling; Liu, Yan; Zhang, Yidan; Wang, Jing; Wang, Zhiliang; Fan, Xianqun

    2016-01-01

    Abstract Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes. The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages. The study was a retrospective, cross-sectional case series. The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD. All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography. The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes. One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P < 0.001). Choroidal thickness was greater in early AMD eyes than in intermediate/late AMD eyes (P < 0.001). Mean percentage of Sattler layer area in each group showed a similar tendency. Microstructure of the choroid showed reduced vascular density of Sattler layer areas in late AMD eyes compared with normal eyes. Decreasing subfoveal choroidal thickness and percentage of Sattler layer area were demonstrated in the progression of AMD. The choroidal change was related to atrophy of the microstructural changes of underlying capillaries and medium-sized vessels. PMID:26962799

  6. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice

    PubMed Central

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  7. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice.

    PubMed

    Huang, Hu; Liu, Ying; Wang, Lei; Li, Wen

    2017-01-01

    The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and

  8. The Anti-Aging and Tumor Suppressor Protein Klotho Enhances Differentiation of a Human Oligodendrocytic Hybrid Cell Line

    PubMed Central

    Chen, Ci-Di; Liang, Jennifer; Hixson, Kathryn; Zeldich, Ella; Abraham, Carmela R.

    2016-01-01

    Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats, and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here, we examined the signaling pathways induced by Klotho in MO3.13, a human oligodendrocytic hybrid cell line. We show that exogenous Klotho affects the ERK and Akt signaling pathways, decreases the proliferative abilities and enhances differentiation of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80 % of the differentially expressed genes being downregulated. Using gene set enrichment analysis, we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging, and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain and other malignancies. PMID:24907942

  9. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    PubMed

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

  10. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: Contested discourses of ageing

    PubMed Central

    Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-01-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a ‘natural’ and a ‘normal’ paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses

  11. The experiences of close persons caring for people with chronic kidney disease stage 5 on conservative kidney management: contested discourses of ageing.

    PubMed

    Low, Joe; Myers, Jason; Smith, Glenn; Higgs, Paul; Burns, Aine; Hopkins, Katherine; Jones, Louise

    2014-11-01

    Chronic kidney disease stage 5 is a global health challenge in the context of population ageing across the world. The range of treatment options available to patients at all ages has increased and includes transplantation and dialysis. However, these options are often seen as inappropriate for older frailer patients who are now offered the option of conservative kidney management, which is presented as a non-invasive alternative to dialysis, involving symptom management and addressing psychosocial needs. In this study, we conducted qualitative interviews with 26 close persons caring for someone with chronic kidney disease stage 5 in the United Kingdom to investigate how conservative kidney management interacted with implicit ideas of ageing, in both the experience of conservative kidney management and the understanding of the prognosis and future care of the kidney disease. Our findings highlighted participant confusion about the nature of conservative kidney management, which stems from an initial lack of clarity about how conservative kidney management differed from conventional treatments for chronic kidney disease stage 5. In particular, some respondents were not aware of the implicit palliative nature of the intervention or indeed the inevitable end-of-life issues. Although these findings can be situated within the context of communication failure, we would further argue that they also bring to the surface tensions in the discourses surrounding ageing and old age, drawing on the use of a 'natural' and a 'normal' paradigm of ageing. In the context of chronic kidney disease stage 5, more patients are being dialysed at older ages, but conservative kidney management is being advanced as a better option than dialysis in terms of quality of life and experience. However, in doing so, conservative kidney management implicitly draws on a notion of older age that echoes natural ageing rather than advocate a more interventionist approach. The role of discourses of ageing

  12. Developmental screening in a Canadian First Nation (Mohawk): psychometric properties and adaptations of ages & stages questionnaires (2nd edition)

    PubMed Central

    2014-01-01

    Background The need for early intervention tools adapted to the First Nation culture is well documented. However, standards derived from First Nation communities are absent from the literature. This study examines the psychometric properties of an adaptation of a caregiver-completed screening tool, the Ages & Stages Questionnaires (ASQ), for the Mohawk population. Methods Participants who completed the questionnaires include 17 teachers, along with the parents of 282 children (130 girls and 152 boys) between the ages of 9 and 66 months who attend the Child and Family Center Mohawk Territory, Quebec. Results For the internal consistency of the four questionnaires (36-, 42-, 48- and 54-month intervals), Cronbach’s alphas varied between .61 and .84. Five results were below 0.60: “gross motor” (Q36 and Q42), “problem solving” (Q36) and “personal-social” (Q36 and Q42). A comparison of the results shows that parents and teachers agreed in 85% of the cases concerning the referral of the child for further evaluation. Moreover, the group discussion with the parents revealed that the use of the questionnaire was appreciated and was deemed appropriate for use within the community. Conclusion The results show that the ASQ is a screening test that may be appropriate for use with children from communities that are seemingly very different in terms of geographic, climatic and cultural backgrounds. This preliminary study with the Child and Family Center appears to support further study and the use of the ASQ with the Mohawk population. PMID:24467769

  13. Comparing adult hippocampal neurogenesis in mammalian species and orders: influence of chronological age and life history stage.

    PubMed

    Amrein, Irmgard; Isler, Karin; Lipp, Hans-Peter

    2011-09-01

    Adult hippocampal neurogenesis is a prominent event in rodents. In species with longer life expectancies, newly born cells in the adult dentate gyrus of the hippocampal formation are less abundant or can be completely absent. Several lines of evidence indicate that the regulatory mechanisms of adult neurogenesis differ between short- and long-lived mammals. After a critical appraisal of the factors and problems associated with comparing different species, we provide a quantitative comparison derived from seven laboratory strains of mice (BALB, C57BL/6, CD1, outbred) and rats (F344, Sprague-Dawley, Wistar), six other rodent species of which four are wild-derived (wood mouse, vole, spiny mouse and guinea pig), three non-human primate species (marmoset and two macaque species) and one carnivore (red fox). Normalizing the number of proliferating cells to total granule cell number, we observe an overall exponential decline in proliferation that is chronologically equal between species and orders and independent of early developmental processes and life span. Long- and short-lived mammals differ with regard to major life history stages; at the time points of weaning, age at first reproduction and average life expectancy, long-lived primates and foxes have significantly fewer proliferating cells than rodents. Although the database for neuronal differentiation is limited, we find indications that the extent of neuronal differentiation is subject to species-specific selective adaptations. We conclude that absolute age is the critical factor regulating cell genesis in the adult hippocampus of mammals. Ontogenetic and ecological factors primarily influence the regulation of neuronal differentiation rather than the rate of cell proliferation.

  14. Changes in sex and non-sex hormones and distribution of erythrocyte antigens in reproductive age women with tumors of body of uterus in Adjara.

    PubMed

    Nakashidze, I; Kotrikadze, N; Diasamidze, A; Nagervadze, M; Ramishvili, L

    2013-04-01

    The aim the research was to study the hormonal state of reproductive age women with tumors of body of uterus. The quantitative changes of sex steroid hormones: progesterone (P), estradiol (E), testosterone (T), gonadotropine -Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were investigated. Distribution of ABO blood group antigens and Rh-Hr systems genetic variants in the blood of women living in Adjara Region was also studied. For study was used reproductive age women's blood with benign (fibromioma) and malignant (endometrial cancer) tumors of body of uterus (the middle age was 20-45 years). The determination of hormones was made by the enzymatic analysis method (ELAIZA). For the research of blood groups, were used the immunoserologic methods. The study have revealed that in blood of reproductive age women with benign and malignant tumors of body of uterus, level of estradiol was increased while levels of progesterone and testosterone were sharply reduced. Amount of Follicle-stimulating hormone and Luteinizing hormone were also increased. It's significant that, both hormones were sharply increased in case of cancer of body of uterus, in comparison with control group and benign tumor. According to distribution of ABO blood group phenotypes - O (I) phenotypic group of ABO system has its highest frequency in blood of women with cancer of body of uterus. Cancer of body of uterus is associated with O (I) phenotypic groups; benign tumor of body of uterus - with A(II) and AB(IV) phenotypic groups. Women with cc and EE genetic variants of Rh-Hr system have sensitivity to the development of benign and malignant tumors of body of uterus; women with ee genetic variant have lower sensitivity towards body of uterus cancer and sharply expressed sensitivity to uterus benign tumors. In women with malignant tumors of body of uterus the frequency of distribution of Rh-Hr system CC genetic variant was sharply reduced.

  15. High Radiation Dose May Reduce the Negative Effect of Large Gross Tumor Volume in Patients With Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Zhao Lujun; West, Brady T.; Hayman, James A.; Lyons, Susan; Cease, Kemp; Kong, F.-M. . E-mail: Fengkong@med.umich.edu

    2007-05-01

    Purpose: To determine whether the effect of radiation dose varies with gross tumor volume (GTV) in patients with stage I/II non-small cell lung cancer (NSCLC). Methods and Materials: Included in the study were 114 consecutive patients with medically inoperable stage I/II NSCLC treated with three-dimensional conformal radiotherapy between 1992 and 2004. The median biologic equivalent dose (BED) was 79.2 Gy (range, 58.2-124.5 Gy). The median GTV was 51.8 cm{sup 3} (range, 2.1-727.8 cm{sup 3}). The primary endpoint was overall survival (OS). Kaplan-Meier estimation and Cox regression models were used for survival analyses. Results: Multivariate analysis showed that there was a significant interaction between radiation dose and GTV (p < 0.001). In patients with BED {<=}79.2 Gy (n = 68), the OS medians for patients with GTV >51.8 cm{sup 3} and {<=}51.8 cm{sup 3} were 18.2 and 23.9 months, respectively (p 0.015). If BED was >79.2 Gy (n = 46), no significant difference was found between GTV groups (p = 0.681). For patients with GTV >51.8 cm{sup 3} (n = 45), the OS medians in those with BED >79.2 Gy and {<=}79.2 Gy were 30.4 and 18.2 months, respectively (p < 0.001). If GTV was {<=}51.8 cm{sup 3} (n = 45), the difference was no longer significant (p = 0.577). Conclusion: High-dose radiation is more important for patients with larger tumors and may be effective in reducing the adverse outcome associated with large GTV. Further prospective studies are needed to confirm this finding.

  16. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  17. Application of in situ hybridization probes for MLH-1 and MSH-2 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemistry and tumor stage.

    PubMed

    Korabiowska, Monika; Cordon-Cardo, Carlos; Jaenckel, Fredericke; Stachura, Jerzy; Fischer, Gösta; Brinck, Ulrich

    2004-12-01

    Defects in DNA mismatch-repair genes MLH1 and MSH2 reported primarily in hereditary nonpolyposis colorectal carcinoma are present in many sporadic tumors, including malignant melanomas. The main aim of this study was to investigate the expression of these genes in malignant melanomas in relation to tumor stage. An experiment was performed on paraffin-embedded tissue microarrays of malignant melanomas applying in situ hybridization with probes produced by our research group and immunohistochemical techniques. In situ hybridization demonstrated MLH1 expression in 45 of 59 melanomas and MSH2 expression in 51 of 59 melanomas. Immunohistochemistry detected MLH1 expression in 46 of 59 melanomas and MSH2 expression in 50 of 59 melanomas. Down-regulation of expression of both DNA mismatch repair genes in malignant melanomas was observed. The findings obtained by in situ hybridization and immunohistochemistry correlated significantly. Our study demonstrates the suitability of in situ hybridization with MLH1 and MSH2 probes for paraffin-embedded tissue. Tissue microarrays can be used successfully in both in situ hybridization and immunohistochemistry to analyze the expression of DNA mismatch-repair genes.

  18. Prognostic value of isolated tumor cells and micrometastases of lymph nodes in early-stage breast cancer: a French sentinel node multicenter cohort study.

    PubMed

    Houvenaeghel, Gilles; Classe, Jean-Marc; Garbay, Jean-Rémy; Giard, Sylvia; Cohen, Monique; Faure, Christelle; Hélène, Charytensky; Belichard, Catherine; Uzan, Serge; Hudry, Delphine; Azuar, Pierre; Villet, Richard; Penault Llorca, Frédérique; Tunon de Lara, Christine; Goncalves, Anthony; Esterni, Benjamin

    2014-10-01

    To define the prognostic value of isolated tumor cells (ITC), micrometastases (pN1mi) and macrometastases in early stage breast cancer (ESBC). We conducted a retrospective multicenter cohort study at 13 French sites. All the eligible patients who underwent SLNB from January 1999 to December 2008 were identified, and appropriate data were extracted from medical records and analyzed. Among 8001 patients, including 70% node-negative (n = 5588), 4% ITC (n = 305), 10% pN1mi (n = 794) and 16% macrometastases (n = 1314) with a median follow-up of 61.3 months, overall survival (OS) and recurrence-free survival (RFS) rates at 84 months were not statistically different in ITC or pN1mi compared to tumor-free nodes. Axillary recurrence (AR) was significantly more frequent in ITC (1.7%) and pN1mi (1.5%) compared to negative nodes (0.6%). Survival and AR rates of single macrometastases were not different from those of ITC or pN1mi. In case of 2 macrometastases or more, survival rates decreased and recurrence rates increased significantly. Micrometastases and ITC do not have a negative prognostic value. Single macrometastases might have an intermediate prognostic value while 2 macrometastases or more are associated with poorer prognosis.

  19. AB266. Expression of long noncoding RNA lncRNA-n336928 is correlated with tumor stage and grade and overall survival in bladder cancer

    PubMed Central

    Chen, Tao; Wu, Changli; Hu, Hailong

    2016-01-01

    Background Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. Up to date, quite a few lncRNAs have been implicated as promising biomarkers for tumor early detection and prognosis monitoring. Methods In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n=3).Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P<0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P<0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Conclusions our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer

  20. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    PubMed

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  1. Radiation Dose to the Brachial Plexus in Head-and-Neck Intensity-Modulated Radiation Therapy and Its Relationship to Tumor and Nodal Stage

    SciTech Connect

    Truong, Minh Tam; Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya; Orlina, Lawrence; Willins, John

    2012-09-01

    Purpose: The purpose of this retrospective study was to determine tumor factors contributing to brachial plexus (BP) dose in head-and-neck cancer (HNC) patients treated with intensity-modulated radiotherapy (IMRT) when the BP is routinely contoured as an organ at risk (OAR) for IMRT optimization. Methods and Materials: From 2004 to 2011, a total of 114 HNC patients underwent IMRT to a total dose of 69.96 Gy in 33 fractions, with the right and left BP prospectively contoured as separate OARs in 111 patients and the ipsilateral BP contoured in 3 patients (total, 225 BP). Staging category T4 and N2/3 disease were present in 34 (29.8%) and 74 (64.9%) patients, respectively. During IMRT optimization, the intent was to keep the maximum BP dose to {<=}60 Gy, but prioritizing tumor coverage over achieving the BP constraints. BP dose parameters were compared with tumor and nodal stage. Results: With a median follow-up of 16.2 months, 43 (37.7%) patients had {>=}24 months of follow-up with no brachial plexopathy reported. Mean BP volume was 8.2 {+-} 4.5 cm{sup 3}. Mean BP maximum dose was 58.1 {+-} 12.2 Gy, and BP mean dose was 42.2 {+-} 11.3 Gy. The BP maximum dose was {<=}60, {<=}66, and {<=}70 Gy in 122 (54.2%), 185 (82.2%), and 203 (90.2%) BP, respectively. For oropharynx, hypopharynx, and larynx sites, the mean BP maximum dose was 58.4 Gy and 63.4 Gy in T0-3 and T4 disease, respectively (p = 0.002). Mean BP maximum dose with N0/1 and N2/3 disease was 52.8 Gy and 60.9 Gy, respectively (p < 0.0001). Conclusions: In head-and-neck IMRT, dose constraints for the BP are difficult to achieve to {<=}60 to 66 Gy with T4 disease of the larynx, hypopharynx, and oropharynx or N2/3 disease. The risk of brachial plexopathy is likely very small in HNC patients undergoing IMRT, although longer follow-up is required.

  2. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-07-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats.

  3. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    ClinicalTrials.gov

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  4. Signs and Symptoms of Wilms Tumor

    MedlinePlus

    ... Detection, Diagnosis, and Staging Signs and Symptoms of Wilms Tumor Wilms tumors can be hard to find early ... Your Child’s Doctor About Wilms Tumor? More In Wilms Tumor About Wilms Tumor Causes, Risk Factors, and Prevention ...

  5. Expression of RNA-binding motif 10 is associated with advanced tumor stage and malignant behaviors of lung adenocarcinoma cancer cells.

    PubMed

    Guan, Guofang; Li, Ranwei; Tang, Wenfang; Liu, Tiecheng; Su, Zhenzhong; Wang, Yan; Tan, Jingjin; Jiang, Shan; Wang, Ke

    2017-03-01

    This study assessed RNA-binding motif 10 expression in lung adenocarcinoma tissues and examined the role and mechanism of RNA-binding motif 10 in the regulation of lung adenocarcinoma malignancy. Lung adenocarcinoma and corresponding adjacent non-tumor lung tissues from 41 patients were subjected to reverse transcription-polymerase chain reaction and Western blot assessment to detect RNA-binding motif 10 expression. Recombinant lentivirus carrying RNA-binding motif 10 complementary DNA was used to infect lung adenocarcinoma cell lines, A549 and H1299 cells. Complementary DNA microarray was used to profile RNA-binding motif 10-regulated genes. Levels of RNA-binding motif 10 messenger RNA and protein were significantly lower in lung adenocarcinoma tissues than those in paired non-tumor tissues (p < 0.001). Reduced RNA-binding motif 10 expression was found to be associated with an advanced tumor stage. RNA-binding motif 10 overexpression inhibited viability and colony formation capacity of lung adenocarcinoma cell lines and induced cell-cycle arrest at G0/G1 phase in A549 cells and at S phase in H1299 cells. Complementary DNA microarray analysis identified 304 upregulated and 386 downregulated genes induced by RNA-binding motif 10 overexpression, which may be involved in cancer, focal adhesion, peroxisome proliferator-activated receptor-regulated gene pathway, cytokine-cytokine receptor interaction, mitogen-activated protein kinase signaling, complement and coagulation cascades, platelet amyloid precursor protein pathway, extracellular matrix-receptor interaction, and small cell lung cancer-related genes. Expression of FGF2, EGFR, WNT5A, NF-κB, and RAP1A was downregulated, whereas expression of AKT2, BIRC3, and JUN was upregulated. RNA-binding motif 10 messenger RNA and protein were reduced in lung adenocarcinoma tissues, and RNA-binding motif 10 overexpression inhibited lung adenocarcinoma cancer cell malignant behavior in vitro. Molecularly, RNA-binding motif

  6. Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma.

    PubMed

    Siiskonen, Hanna; Poukka, Mari; Bykachev, Andrey; Tyynelä-Korhonen, Kristiina; Sironen, Reijo; Pasonen-Seppänen, Sanna; Harvima, Ilkka T

    2015-12-01

    The role of mast cells in cutaneous melanoma remains unclear. Tryptase and chymase are serine proteinases and major proteins in mast cell secretory granules. Therefore, this study aimed to investigate the presence of tryptase and chymase mast cells in benign and malignant cutaneous melanocytic lesions and in lymph node metastases of melanomas. The presence of positively stained mast cells was correlated with clinicopathological characteristics in invasive melanomas. Paraffin-embedded sections of 28 benign (13 intradermal, 10 compound, and five junctional nevi) and 26 dysplastic nevi, 15 in-situ melanomas, 36 superficially (pT1, Breslow's thickness<1 mm), and 49 deeply (pT4, Breslow's thickness>4 mm) invasive melanomas and 30 lymph node metastases were immunohistochemically stained for mast cell tryptase and chymase, and immunopositive cells were counted using the hotspot counting method. The mean count of tryptase and chymase mast cells was lower in invasive melanomas compared with in-situ melanomas and dysplastic and benign nevi. In deeply invasive melanomas, the difference was statistically significant compared with dysplastic nevi (P=0.003 for tryptase and P=0.009 for chymase) and in-situ melanomas (0.043 for tryptase). Low numbers of tryptase mast cells were associated with poor overall survival (P=0.031) in deeply invasive melanomas and with a more advanced stage (T1b, P=0.008) in superficially invasive melanomas. Low numbers of chymase mast cells were associated with microsatellites (P=0.017) in deeply invasive melanomas. The results suggest that these serine proteinases of mast cells may be protective in the pathogenesis of melanoma.

  7. TGFβ1 overexpression is associated with improved survival and low tumor cell proliferation in patients with early-stage pancreatic ductal adenocarcinoma

    PubMed Central

    Glazer, Evan S.; Welsh, Eric; Pimiento, Jose M.; Teer, Jamie K.; Malafa, Mokenge P.

    2017-01-01

    The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene. Average log2 mRNA expression of TGFβ1 in patients with high expression was 11.6 ± 0.2 and 10.5 ± 0.6 in patients with low expression (P<0.001). Low TGFβ1 expression is associated with shorter median survival compared with high TGFβ1 expression (17 versus at least 60 months; P=0.005). Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67) expression have shorter median survival versus those with lowerMKI67 expression (16 versus 20 months; P=0.026). TGFβ1 and MKI67 are inversely associated (P=0.009). On multivariate analysis, improved survival is associated with TGFβ1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant radiotherapy (P=0.017), whereas positive surgical margins are associated with worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for PDAC, high TGFβ1 expression may counteract the worse survival associated with high proliferation. PMID:27895310

  8. [Combined spinal epidural anesthesia during endoprosthetic surgeries for bone tumors in old-age children].

    PubMed

    Matinian, N V; Saltanov, A I

    2005-01-01

    Thirty-five patients (ASA II-III) aged 12 to 17 years, diagnosed as having osteogenic sarcoma and Ewing's sarcoma localizing in the femur and tibia, were examined. Surgery was performed as sectoral resection of the affected bone along with knee joint endoprosthesis. Surgical intervention was made under combined spinal and epidural anesthesia (CSEA) with sedation, by using the methods for exact dosing of propofol (6-4 mg/kg x h). During intervention, a child's respiration remains is kept spontaneous with oxygen insufflation through a nasal catheter. CSEA was performed in two-segmental fashion. The epidural space was first catheterized. After administration of a test dose, 0.5% marcaine spinal was injected into dermatomas below the subarachnoidal space, depending on body weight (3.0-4.0 ml). Sensory blockade developed following 3-5 min and lasted 90-120 min, thereafter a local anesthetic (bupivacaine) or its mixture plus promedole was epidurally administered. ??Anesthesia was effective in all cases, motor blockade. During surgery, there was a moderate arterial hypotension that did not require the use of vasopressors. The acid-alkali balance suggested the adequacy of spontaneous respiration. The only significant complication we observed was atony of the bladder that requires its catheterization till the following day. An epidural catheter makes it possible to effect adequate postoperative analgesia.

  9. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    ClinicalTrials.gov

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  10. A relationship to survival is seen by combining the factors of mismatch repair status, tumor location and age of onset in colorectal cancer patients

    PubMed Central

    Li, Pan; Xiao, Zhitao; Braciak, Todd A.; Ou, Qingjian; Chen, Gong; Oduncu, Fuat S.

    2017-01-01

    Background The progression of colorectal cancer (CRC) may differ depending on the location of the tumor and the age of onset of the disease. Previous studies also suggested that the molecular basis of CRC varies with tumor location, which could affect the clinical management of patients. Therefore, we performed survival analysis looking at different age groups and mismatch repair status (MMR) of CRC patients according to primary tumor location in an attempt to identify subgroups of CRC that might help in the prognosis of disease. Methods A group of 2233 patients operated on to remove their CRC tumors were analyzed (521 with right colon cancer, 740 with left colon cancer and 972 with rectal cancer). The expression of four MMR genes was assessed by immunohistochemistry (IHC), independent of clinical criteria. From the data collected, a predictive model for overall survival (OS) could be constructed for some associations of tumor location and age of onset using Kaplan-Meier, logistic and Cox regression analysis. Results When tumor location was considered as the lone factor, we found no statistical difference in overall survival (OS) between right cancer (68%), left cancer (67%) or rectal cancer tumor locations (71%) (HR: 1.17, 95%CI (confidence interval): 0.97–1.43, P = 0.057). When age of onset was considered, middle age (40–59 years) and older (60–85 years) patients were found to have higher OS than younger onset cancer (20–39 years) patients (69% vs 71% vs 59%, HR: 1.07, 95% confidence interval (CI): 0.91–1.25, P = 0.008). When both age of onset and tumor location were considered in combination as disease factors, we found that the subgroup of patients with left colon cancer from middle age (69%) and older (67%) aged patients had higher OS than younger (54%) patients (HR: 0.89, 95%CI: 0.68–1.16, P = 0.048). However in patients with right colon cancers, we found no statistical difference is OS between younger, middle age or older grouped patients (60% vs

  11. Sustained expression of a neuron-specific isoform of the Taf1 gene in development stages and aging in mice

    SciTech Connect

    Jambaldorj, Jamiyansuren; Makino, Satoshi; Munkhbat, Batmunkh; Tamiya, Gen

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer We identified the mouse homologue of neuron-specific TAF1 (N-Taf1). Black-Right-Pointing-Pointer Taf1 mRNA was expressed in most tissues and cell lines. Black-Right-Pointing-Pointer N-Taf1 mRNA was expressed in the brain and Neuroblastoma N2a cell lines. Black-Right-Pointing-Pointer Taf1 and N-Taf1 showed different expression profile in development stage and aging. -- Abstract: TATA-box binding protein associated factor 1 (TAF1) protein is the largest and the essential component of the TFIID complex in the pathway of RNA polymerase II-mediated gene transcription, and it regulates transcription of a large number of genes related to cell division. The neuron-specific isoform of the TAF1 gene (N-TAF1), which we reported previously, may have an essential role in neurons through transcriptional regulation of many neuron-specific genes. In the present study, we cloned the full-length cDNA that encodes the mouse homologue of N-TAF1 (N-Taf1) protein. By carrying out of real time RT-PCR, we investigated the expression analysis of the N-Taf1 mRNA in mouse tissues and cell lines. As well as the human N-TAF1, the N-Taf1 showed limited expression in the brain and neuroblastoma, whereas Taf1 expressed elsewhere. Furthermore, in mouse embryo head or mouse brain, mRNA expression of TAF1 changes dramatically during development but N-Taf1 showed sustained expression. Our result suggests that the N-Taf1 gene has an important role in non-dividing neuronal cell rather than in cell division and proliferation during neurogenesis.

  12. Circulation of HIV antigen in blood according to stage of infection, risk group, age and geographic origin.

    PubMed

    Goudsmit, J; Paul, D A

    1987-12-01

    Human immunodeficiency virus antigen (HIV-ag) was determined by enzyme immunoassay (EIA) in HIV-antibody (anti-HIV) positive as well as pre-anti-HIV seroconversion sera and the results analysed according to stage of infection, risk group, age and geographic origin. Eleven (19%) of 58 homosexual men tested showed HIV-ag in a serum taken 3-4 months before or one at the time of anti-HIV seroconversion. In another eight (14%) HIV-ag persisted after seroconversion and half of them developed AIDS or AIDS-related complex (ARC) in contrast to none of the other 50 anti-HIV seroconversions. Two (13%) of 16 haemophiliacs tested had HIV-ag only in the first anti-HIV seropositive sample. HIV-ag was present in 86% (30/35) of Dutch homosexual men with AIDS, in 32% (7/22) of men with ARC and in 17% (24/145) of men with persistent generalized lymphadenopathy (PGL) or without symptoms. Three percent (2/60) of sera of asymptomatic i.v. drug users from Amsterdam were HIV-ag positive. Ten percent (1 of 10) of sera from Central Africans with 'Slim Disease' were HIV-ag positive. Among infected children from the USA or Europe 89-100% (8/9 and 2/2) of AIDS cases, 67-100% (6/9 and 3/3) of children with ARC and 75% (3/4) of asymptomatic children were HIV-ag positive. The HIV-ag EIA appears to be able to identify HIV infection earlier than the available anti-HIV assays in a significant number of cases. Since persistence of HIV-ag, except possibly in African cases, is strongly associated with clinical deterioration, HIV-ag appears to be a suitable marker for, independent of their clinical status, selecting individuals for antiviral therapy and also for monitoring the efficiency of such therapy.

  13. The rates of change of the stochastic trajectories of acceleration variability are a good predictor of normal aging and of the stage of Parkinson's disease

    PubMed Central

    Torres, Elizabeth B.

    2013-01-01

    The accelerometer data from mobile smart phones provide stochastic trajectories that change over time. This rate of change is unique to each person and can be well-characterized by the continuous two-parameter family of Gamma probability distributions. Accordingly, on the Gamma plane each participant can be uniquely localized by the shape and the scale parameters of the Gamma probability distribution. The scatter of such points contains information that can unambiguously separate the normal controls (NC) from those patients with Parkinson's disease (PD) that are at a later stage of the disease. In general normal aging seems conducive of more predictable patterns of variation in the accelerometer data. Yet this trend breaks down in PD where the statistical signatures seem to be a more relevant predictor of the stage of the disease. Those patients at a later stage of the disease have more random and noisier patterns than those in the earlier stages, whose statistics resemble those of the older NC. Overall the peak rates of change of the stochastic trajectories of the accelerometer are a good predictor of the stage of PD and of the age of a “normally” aging individual. PMID:23882193

  14. Generation Changes over the Period of 1986-2006 in the Physical Fitness of Boys Aged 7-19 from Eastern Poland at Particular Stages of Education

    ERIC Educational Resources Information Center

    Saczuk, Jerzy; Wasiluk, Agnieszka; Zalech, Miroslaw

    2012-01-01

    Study aim: To assess the size of secular trends in the physical fitness of boys from eastern Poland taking into consideration stages of education. Material and methods: The physical fitness results of boys aged 7-19 years living in eastern regions of Poland were analyzed: 3188 students were examined in 1986 while in 2006 the research included 10…

  15. Palliative resection of the primary tumor is associated with improved overall survival in incurable stage IV colorectal cancer: A nationwide population-based propensity-score adjusted study in the Netherlands.

    PubMed

    't Lam-Boer, Jorine; Van der Geest, Lydia G; Verhoef, Cees; Elferink, Marloes E; Koopman, Miriam; de Wilt, Johannes H

    2016-11-01

    As the value of palliative primary tumor resection in stage IV colorectal cancer (CRC) is still under debate, the purpose of this population-based study was to investigate if palliative primary tumor resection as the initial treatment after diagnosis was associated with improved overall survival. All patients with stage IV colorectal adenocarcinoma (2008-2011) were selected from the Netherlands Cancer Registry, and patients undergoing treatment with curative intent (i.e., metastasectomy, radiofrequency ablation and/or hyperthermic intraperitoneal chemotherapy), or best supportive care were excluded. After propensity score matching, a multivariable Cox proportional hazard model was performed to determine the association between treatment strategy and mortality. From a total group of 10,371 patients with stage IV CRC, 2,746 patients (26%) underwent an elective palliative resection of the primary tumor, whether or not followed by systemic therapy, and 3,345 patients (32%) were initially treated with palliative systemic therapy. After propensity score matching, median overall survival in these groups was 17.2 months (95% CI 16.3-18.1) and 11.5 months (95% CI 11.0-12.0), respectively. In Cox regression analysis, primary tumor resection was significantly associated with improved overall survival (hazard ratio of death = 0.44 [95% CI 0.35-0.55], p < 0.001). This large population-based study shows an overall survival benefit for patients with incurable stage IV CRC who underwent primary tumor resection as the initial treatment after diagnosis, compared to patients who started systemic therapy with the primary tumor in situ. This result is an argument in favor of resection of the primary tumor, even when patients have little to no symptoms.

  16. Multi-stage uplift of the Colorado Plateau and the age of Grand Canyon and precursor canyons

    NASA Astrophysics Data System (ADS)

    Karlstrom, K. E.; Lee, J. P.; Kelley, S. A.; Crow, R.

    2012-12-01

    Debates about the age of Grand Canyon link to debates about the timing of surface uplift(s) of the Colorado Plateau- Rocky Mountain (CP-RM) region. One "old Grand Canyon" model proposes that a paleocanyon of almost the same depth and location as today's Grand Canyon was carved by a NE-flowing "California" paleoriver 80-70 Ma, then was re-used at ~55 Ma by a SW-flowing "Arizona" paleoriver. This model postulates the CP-RM region was uplifted to near modern elevations during the Laramide orogeny. A second model postulates a 17 Ma Grand Canyon; this time corresponds to Basin and Range extension and postulated mantle-driven surface uplift. The "young Grand Canyon" model postulates that >2/3 of modern Grand Canyon was carved by W-flowing Colorado River that became integrated to the Gulf of California at 5-6 Ma during Neogene mantle-driven uplift of the CP/RM region. Thermochronologic data are poised to substantially resolve these debates. Our thermochronology dataset combines published and new apatite fission-track and helium analyses, and joint thermal history modeling using both systems. This dataset reveals three major cooling episodes: 1) a multi-stage Sevier-Laramide contraction episode from about 90 Ma to 50 Ma with structural relief on upwarps on the order 0.5-1 km, compatible with a similar magnitude of surface uplift; 2) 30-20 Ma cooling that was associated with denudation and northward cliff retreat of most of the Mesozoic section from Grand Canyon region; 3) <10 Ma cooling that is best documented in eastern Grand Canyon as part of a general pattern of decreasing age of cooling/denudation to the NE. Combined geologic and thermochronologic data define the age and 3-D geometry of Cenozoic paleotopography that led to Grand Canyon carving. Combined AHe and AFT data indicate 2-4 km of sedimentary rocks covered the Grand Canyon region until about 40 Ma, negating the California River model. These strata were not removed from the Marble Canyon area until after about

  17. The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors

    PubMed Central

    2013-01-01

    Background VEGF may play a role in the pathogenesis of cancer disease, for example in cell growth, proliferation and angiogenesis. In this study, we investigated plasma levels of this cytokine in comparison to plasma levels of a new biomarker - HE4 and the established tumor marker CA125 in ovarian cancer patients (100) as compared to control groups: patients with a benign ovarian tumor (80) and healthy subjects (50). Methods Plasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method. Results The results showed that levels of VEGF, CA125 and HE4 were significantly higher in ovarian cancer (OC) patients as compared to the both control groups. VEGF has demonstrated as high as comparative markers values of the diagnostic sensitivity (SE), specificity (SP), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in early stages of cancer tested groups. The combined use of parameters studied resulted in the increase in the diagnostic criteria values and the AUC. Conclusions These findings suggest the usefulness of VEGF in the early diagnostics of ovarian cancer, especially in combination with CA125 and HE4, as a new biomarkers panel. Additionally, VEGF is the most useful tool in the diagnostics of locally advanced ovarian cancer without metastases. Investigated cytokine presented similar to HE4 usefulness in differentiation of OC according to its histopathlogical sub-type, and could be used especially in the diagnostics of endometrioid epithelial OC. PMID:23819707

  18. Behavioral deficits during early stages of aging in Caenorhabditis elegans result from locomotory deficits possibly linked to muscle frailty.

    PubMed

    Glenn, Charles F; Chow, David K; David, Lawrence; Cooke, Carol A; Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Goldberg, Ilya G; Wolkow, Catherine A

    2004-12-01

    Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments.

  19. Screening accuracy of the parent-completed Ages and Stages Questionnaires - second edition as a broadband screener for motor problems in preschoolers with autism spectrum disorders.

    PubMed

    Vanvuchelen, Marleen; Van Schuerbeeck, Lise; Braeken, Marijke Aka

    2017-01-01

    Children with autism spectrum disorders are at risk for motor problems. However, this area is often overlooked in the developmental evaluation in autism diagnostic clinics. An alternative can be to identify children who should receive intensive motor assessment by using a parent-based screener. The aim of this study was to examine whether the Ages and Stages Questionnaires - second edition may be used to identify gross and fine motor problems in children. High-functioning children with autism spectrum disorder (n = 43, 22-54 m) participated in this study. Sensitivity, specificity, predictive values and areas under the receiver operating characteristic curve were calculated by comparing the Ages and Stages Questionnaires - second edition scores to the developmental evaluation of the Peabody Developmental Motor Scale - second edition. The results revealed that both the Ages and Stages Questionnaires - second edition gross and fine motor domain may be used to identify children without motor problems. In contrast, sensitivity analyses revealed the likelihood of under screening motor problems in this population. The Ages and Stages Questionnaires - second edition met only the criteria of a fair to good accuracy to identify poor gross motor (sensitivity = 100%) and below-average fine motor development (sensitivity = 71%) in this sample. Hence, the capacity of the Ages and Stages Questionnaires - second edition to identify motor problems in preschoolers with autism spectrum disorder appears to be limited. It is recommended to include a formal standardized motor test in the diagnostic procedure for all children with autism spectrum disorder.

  20. The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.

    PubMed

    Nunomura, Akihiko; Tamaoki, Toshio; Motohashi, Nobutaka; Nakamura, Masao; McKeel, Daniel W; Tabaton, Massimo; Lee, Hyoung-Gon; Smith, Mark A; Perry, George; Zhu, Xiongwei

    2012-03-01

    Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approachto identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinicaldementia rating score and postmortem brain pathologic diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that, although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD.

  1. Hypothalamic tumor

    MedlinePlus

    ... occur at any age. They are often more aggressive in adults than in children. In adults, tumors ... The treatment depends on how aggressive the tumor is, and whether it is a glioma or another type of cancer. Treatment may involve combinations of surgery, radiation , ...

  2. Tumor Suppressor and Aging Biomarker p16INK4a Induces Cellular Senescence without the Associated Inflammatory Secretory Phenotype*

    PubMed Central

    Coppé, Jean-Philippe; Rodier, Francis; Patil, Christopher K.; Freund, Adam; Desprez, Pierre-Yves; Campisi, Judith

    2011-01-01

    Cellular senescence suppresses cancer by preventing the proliferation of cells that experience potentially oncogenic stimuli. Senescent cells often express p16INK4a, a cyclin-dependent kinase inhibitor, tumor suppressor, and biomarker of aging, which renders the senescence growth arrest irreversible. Senescent cells also acquire a complex phenotype that includes the secretion of many cytokines, growth factors, and proteases, termed a senescence-associated secretory phenotype (SASP). The SASP is proposed to underlie age-related pathologies, including, ironically, late life cancer. Here, we show that ectopic expression of p16INK4a and another cyclin-dependent kinase inhibitor, p21CIP1/WAF1, induces senescence without a SASP, even though they induced other features of senescence, including a stable growth arrest. Additionally, human fibroblasts induced to senesce by ionizing radiation or oncogenic RAS developed a SASP regardless of whether they expressed p16INK4a. Cells induced to senesce by ectopic p16INK4a expression lacked paracrine activity on epithelial cells, consistent with the absence of a functional SASP. Nonetheless, expression of p16INK4a by cells undergoing replicative senescence limited the accumulation of DNA damage and premature cytokine secretion, suggesting an indirect role for p16INK4a in suppressing the SASP. These findings suggest that p16INK4a-positive cells may not always harbor a SASP in vivo and, furthermore, that the SASP is not a consequence of p16INK4a activation or senescence per se, but rather is a damage response that is separable from the growth arrest. PMID:21880712

  3. Fertility sparing surgery for stage IA type I and G2 endometrial cancer in reproductive-aged patients: evidence-based approach and future perspectives.

    PubMed

    Vitale, Salvatore Giovanni; Rossetti, Diego; Tropea, Alessandro; Biondi, Antonio; Laganà, Antonio Simone

    2017-02-10

    Fertility-sparing surgery (FSS) in reproductive-age patients affected by endometrial cancer (EC) gained growing attention in the last decade, although the first reports were already published in 1990-2000s. Nevertheless, only few patients undergoing FSS for stage I, type I EC had been reported in each case series, without a robust multicenter study. In the available literature there are even fewer reported cases of conservative treatment of Stage IA and G2 EC. Considering these important gaps in our current knowledge, the purpose of this review was to summarize the available evidence about conservative treatments for stage IA type I and G2 EC, to improve the pretreatment counseling for reproductive-age patients. According to our overview, women who have low-risk disease (G1 or G2, endometrioid histotype confined to the endometrium) are candidates for progestin therapy. In addition, FSS could be considered a valid option for reproductive-aged patients with stage IA type I and G2 EC. Nevertheless, we solicit new trials to clarify the medium- and long-term outcomes in this kind of patients.

  4. Impact of Age, Race and Socio-economic Status on Temporal Trends in Late-Stage Prostate Cancer Diagnosis in Florida

    PubMed Central

    Goovaerts, Pierre; Xiao, Hong; Gwede, Clement K.; Tan, Fei; Huang, Youjie; Adunlin, Georges; Ali, Askal

    2015-01-01

    Individual-level data from the Florida Cancer Data System (1981–2007) were analysed to explore temporal trends of prostate cancer late-stage diagnosis, and how they vary based on race, income and age. Annual census-tract rates were computed for two races (white and black) and two age categories (40–65, >65) before being aggregated according to census tract median household incomes. Joinpoint regression and a new disparity statistic were applied to model temporal trends and detect potential racial and socio-economic differences. Multi-dimensional scaling was used as an innovative way to visualize similarities among temporal trends in a 2-D space. Analysis of time-series indicated that late-stage diagnosis was generally more prevalent among blacks, for age category 40–64 compared to older patients covered by Medicare, and among classes of lower socio-economic status. Joinpoint regression also showed that the rate of decline in late-stage diagnosis was similar among older patients. For younger patients, the decline occurred at a faster pace for blacks with rates becoming similar to whites in the late 90s, in particular for higher incomes. Both races displayed distinct spatial patterns with higher rates of late-stage diagnosis in the Florida Panhandle for whites whereas high rates clustered in South-eastern Florida for blacks. PMID:26644992

  5. Impact of Age, Race and Socio-economic Status on Temporal Trends in Late-Stage Prostate Cancer Diagnosis in Florida.

    PubMed

    Goovaerts, Pierre; Xiao, Hong; Gwede, Clement K; Tan, Fei; Huang, Youjie; Adunlin, Georges; Ali, Askal

    2015-11-01

    Individual-level data from the Florida Cancer Data System (1981-2007) were analysed to explore temporal trends of prostate cancer late-stage diagnosis, and how they vary based on race, income and age. Annual census-tract rates were computed for two races (white and black) and two age categories (40-65, >65) before being aggregated according to census tract median household incomes. Joinpoint regression and a new disparity statistic were applied to model temporal trends and detect potential racial and socio-economic differences. Multi-dimensional scaling was used as an innovative way to visualize similarities among temporal trends in a 2-D space. Analysis of time-series indicated that late-stage diagnosis was generally more prevalent among blacks, for age category 40-64 compared to older patients covered by Medicare, and among classes of lower socio-economic status. Joinpoint regression also showed that the rate of decline in late-stage diagnosis was similar among older patients. For younger patients, the decline occurred at a faster pace for blacks with rates becoming similar to whites in the late 90s, in particular for higher incomes. Both races displayed distinct spatial patterns with higher rates of late-stage diagnosis in the Florida Panhandle for whites whereas high rates clustered in South-eastern Florida for blacks.

  6. Serum alpha-fetoprotein subfractions identified by Ricinus communis agglutinin I in hepatic malignancies, yolk sac tumor, benign hepatic diseases, and fetal stage.

    PubMed

    Ishiguro, T; Takahashi, Y

    1989-01-01

    Using Ricinus communis agglutinin I (RCA-I) affinity crossed-line immunoelectrophoresis, alpha-fetoprotein (AFP) subfractions were studied in sera from patients with primary hepatic cancer (PHC), hepatic metastasis of gastric cancer (HMGC), yolk sac tumor (YST), acute or chronic hepatitis or hepatic cirrhosis. Fetal AFP subfractions were also examined in amniotic fluids or in culture fluids of fetal tissues. RCA-I non-reactive subfraction was commonly found in PHC, HMGC, YST, benign hepatic diseases, and fetal stage. RCA-I weakly reactive (WR) or strongly reactive (SR) subfraction was noted only in malignant diseases. RCA-I has a specific affinity to terminal galactose in oligosaccharide, and the presence of sialic acid on galactose residue(s) inhibits the affinity with RCA-I. Therefore, common AFP subfraction non-reactive with RCA-I was assumed to be galactosialyl form, while RCA-I WR and SR subfractions found only in malignancies were monogalactosyl and digalactosyl, respectively. Clinically this approach to detect the RCA-I WR or SR subfraction facilitates a differential diagnosis of AFP-producing malignancies and benign conditions.

  7. Stages of Adolescence

    MedlinePlus

    ... Español Text Size Email Print Share Stages of Adolescence Page Content Article Body Adolescence, these years from puberty to adulthood, may be roughly divided into three stages: early adolescence, generally ages eleven to fourteen; middle adolescence, ages ...

  8. Stages of Pancreatic Neuroendocrine Tumors

    MedlinePlus

    ... illnesses and treatments will also be taken. Blood chemistry studies : A procedure in which a blood sample ... checked to measure the amount of VIP. Blood chemistry studies : A procedure in which a blood sample ...

  9. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    ClinicalTrials.gov

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  10. Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor

    ClinicalTrials.gov

    2016-11-28

    Adult Renal Wilms Tumor; Beckwith-Wiedemann Syndrome; Childhood Renal Wilms Tumor; Diffuse Hyperplastic Perilobar Nephroblastomatosis; Hemihypertrophy; Stage I Renal Wilms Tumor; Stage II Renal Wilms Tumor; Stage III Renal Wilms Tumor; Stage IV Renal Wilms Tumor; Stage V Renal Wilms Tumor

  11. Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal carcinoma distant normal tissue highlights arm specific enrichment and expansion across tumor stages.

    PubMed

    Ruan, Xiaoyang; Liu, Hongfang; Boardman, Lisa; Kocher, Jean-Pierre A

    2014-01-01

    Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the overall extent of LOH in normal tissue and their significance to tumorigenesis remain unknown, as existing studies are largely based on selected microsatellite markers. Here we present the first autosome-wide study of LOH in IDC and distant normal tissue using informative loci deduced from SNP array-based and sequencing-based techniques. We show a consistently high LOH concurrence rate in IDC (mean = 24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33) histologically normal tissue contains genomic instability that can be a potential marker of increased IDC risk. Concurrent LOH is more frequent in fragile site related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm level shows distant normal tissue has low level but non-random enrichment of LOH (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r = 0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific LOH enrichment was independently observed in tumor samples from 548 IDC patients when stratified by tumor size based T stages. Fine LOH structure from sequencing data indicates LOH in low order tissues non-randomly overlap (∼67%) with LOH that usually has longer tract length (the length of genomic region affected by LOH) in high order tissues. The consistent observations from multiple datasets suggest progressive LOH in the development of IDC potentially through arm-specific pile up effect with discernible signature in normal tissue. Our finding also suggests that LOH detected in IDC by comparing to paired adjacent or distant normal tissue are more likely underestimated.

  12. Effects of leaf age within growth stages of pepper and sorghum plants on leaf thickness, water, chlorophyll, and light reflectance. [in spectral vegetation discrimination

    NASA Technical Reports Server (NTRS)

    Gausman, H. W.; Cardenas, R.; Berumen, A.

    1974-01-01

    Pepper and sorghum plants (characterized by porous and compact leaf mesophylls, respectively) were used to study the influence of leaf age on light reflectance. Measurements were limited to the upper five nodal positions within each growth stage, since upper leaves make up most of the reflectance surfaces remotely sensed. The increase in leaf thickness and water content with increasing leaf age was taken into consideration, since each of these factors affects the reflectance as well as the selection of spectral wavelength intervals for optimum discrimination of vegetation.

  13. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  14. Early stages of salmon calcitonin aggregation: effect induced by ageing and oxidation processes in water and in the presence of model membranes.

    PubMed

    Gaudiano, Maria Cristina; Colone, Marisa; Bombelli, Cecilia; Chistolini, Pietro; Valvo, Luisa; Diociaiuti, Marco

    2005-06-30

    The natural ageing- and hydrogen peroxide-induced aggregation of salmon calcitonin were studied in water and in the presence of dipalmitoylphosphatidylcholine (DPPC) liposomes. The early stages of the aggregation process at low protein concentration were investigated by means of Circular Dichroism spectroscopy (CD) and conventional and immunogold labelling Transmission Electron Microscopy (TEM). In buffered water solution, salmon calcitonin showed a two-stage conformational variation related to fibril formation and phase-separation of larger aggregates. A first stage, characterised by small conformational changes but a decrease in dichroic band intensity, was followed by a second stage, 6 days after, leading to higher conformational variations and aggregations. Salmon calcitonin showed a distinct modification in the secondary structure and aggregate morphology in the presence of hydrogen peroxide with respect to natural ageing, indicating that the two aggregation processes (natural and chemical-induced) followed a distinct mechanism. The oxidised forms of the peptide were separated by liquid chromatography. The same study was performed in the presence of DPPC liposomes. The results obtained by conventional and immunogold labelling TEM evidenced that salmon calcitonin in buffered water solution essentially does not enter the liposomes but forms around them a fibril network characterised by the same conformational changes after 6 days. The oxidised sample in the presence of liposomes showed a "fibrils hank", separated from liposomes. The presence of liposomes did not affect either the aggregation or the conformational modifications yet observed by TEM and CD in water solution.

  15. New K-Ar ages and the geologic evidence against rejuvenated-stage volcanism at Haleakalā, East Maui, a postshield-stage volcano of the Hawaiian island chain

    USGS Publications Warehouse

    Sherrod, David R.; Nishimitsu, Yoshitomo; Tagami, Takahiro

    2003-01-01

    The age of the Kula/Hāna boundary is ca. 0.15–0.12 Ma; thus, volcanic quiescence of only ∼0.03 m.y. separates the two formations, much shorter than the previously known limit of 0.25–0.30 m.y. The brevity of this hiatus, coupled with coincident vent loci and broadly similar geochemical characteristics for the Hāna and the upper part of the Kula Volcanics, indicates that the Hāna Volcanics unit comprises deposits of postshield-stage volcanism that has waned substantially since ca. 0.4–0.3 Ma. Haleakalā has not yet begun a classically defined rejuvenated stage. Our findings support recent numerical modeling of plume-lithosphere interactions that predict that Haleakalā is near the end of its postshield growth.

  16. DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging.

    PubMed

    Olivieri, Fabiola; Albertini, Maria Cristina; Orciani, Monia; Ceka, Artan; Cricca, Monica; Procopio, Antonio Domenico; Bonafè, Massimiliano

    2015-11-03

    A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development.

  17. Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats

    PubMed Central

    Kensara, Osama Adnan; El-Shemi, Adel Galal; Mohamed, Amr Mohamed; Refaat, Bassem; Idris, Shakir; Ahmad, Jawwad

    2016-01-01

    Colorectal cancer (CRC) is one of the most prevalent cancers and has a high mortality rate. Insensitivity and the limited therapeutic efficacy of its standard chemotherapeutic drug, 5-fluorouracil (5-FU), represents an important challenge in CRC treatment. The robust antitumor properties of thymoquinone (TQ), the main bioactive constituent of Nigella sativa, have recently been demonstrated on different cancers. We investigated whether TQ could potentiate the chemopreventive effect of 5-FU to eradicate the early stages of CRC and elucidated its underlying mechanisms. An intermediate-term (15 weeks) model of colorectal tumorigenesis was induced in male Wistar rats by azoxymethane (AOM), and the animals were randomly and equally divided into five groups: control, AOM, AOM/5-FU, AOM/TQ, and AOM/5-FU/TQ. TQ (35 mg/kg/d; 3 d/wk) was given during the seventh and 15th weeks post-AOM injection, while 5-FU was given during the ninth and tenth weeks (12 mg/kg/d for 4 days; then 6 mg/kg every other day for another four doses). At week 15, the resected colons were subjected to macroscopic, histopathological, molecular, and immunohistochemical examinations. Interestingly, 5-FU/TQ combination therapy resulted in a more significant reduction on AOM-induced colorectal tumors and large aberrant crypts foci than treatment with the individual drugs. Mechanistically, 5-FU and TQ remarkably cooperated to repress the expression of procancerous Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF, and TBRAS and upregulate the expression of anti-tumorigenesis DKK-1, CDNK-1A, TGF-β1, TGF-βRII, Smad4, and GPx. Overall, our findings present the first report describing the in vivo enhancement effect of combined TQ and 5-FU against early stages of CRC; however, further studies are required to determine the value of this combination therapy in an advanced long-term model of CRC and also to realize its clinical potential. PMID:27468227

  18. Epithelial-to-mesenchymal transition leads to disease-stage differences in circulating tumor cell detection and metastasis in pre-clinical models of prostate cancer

    PubMed Central

    Lowes, Lori E.; Goodale, David; Xia, Ying; Postenka, Carl; Piaseczny, Matthew M.; Paczkowski, Freeman; Allan, Alison L.

    2016-01-01

    Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the “gold standard” clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable to CellSearch® (EpCAM-based) and one detecting CTCs semi-independent of EMT status via combined staining with EpCAM/HLA (human leukocyte antigen). In vivo differences in CTC generation, kinetics, metastasis and EMT status were determined using 4 PCa models with progressive epithelial (LNCaP, LNCaP-C42B) to mesenchymal (PC-3, PC-3M) phenotypes. Assay validation demonstrated that the CellSearch®-based assay failed to detect a significant number (~40-50%) of mesenchymal CTCs. In vivo, PCa with an increasingly mesenchymal phenotype shed greater numbers of CTCs more quickly and with greater metastatic capacity than PCa with an epithelial phenotype. Notably, the CellSearch®-based assay captured the majority of CTCs shed during early-stage disease in vivo, and only after establishment of metastases were a significant number of undetectable CTCs present. This study provides important insight into the influence of EMT on CTC generation and subsequent metastasis, and highlights that novel technologies aimed at capturing mesenchymal CTCs may only be useful in the setting of advanced metastatic disease. PMID:27764810

  19. Inhibitory effect of phytoglycoprotein on tumor necrosis factor-{alpha} and interleukin-6 at initiation stage of colon cancer in 1,2-dimethylhydrazine-treated ICR mice

    SciTech Connect

    Lee, Sei-Jung; Lim, Kye-Taek

    2007-12-01

    This study was carried out to investigate the chemopreventive potentials of plant originated glycoprotein (UDN glycoprotein, 116 kDa) isolated from the stems of Ulmus davidiana Nakai (UDN) on aberrant crypt foci (ACF) formation in 1,2-dimethylhydrazine (DMH)-treated ICR mice. UDN glycoprotein was administered to mice at 0.01% and 0.02% levels for 5 weeks. The mice were treated with 20 mg/kg DMH twice a week for 2 weeks in presence of UDN glycoprotein and killed at week 6. We found that UDN glycoprotein has inhibitory effects on the frequency of colonic aberrant crypt foci (ACF), activation of colonic proliferating cell nuclear antigen (PCNA), and release of plasma lactate dehydrogenase (LDH) in DMH-treated mice. In addition, UDN glycoprotein has anti-oxidative effects on the formation of plasma thiobarbituric acid reactive substances (TBARS) and the production of plasma inducible nitric oxide (NO) in DMH-treated mouse. Also, 0.02% UDN glycoprotein suppressed the DNA binding activities of nuclear factor-kappa B (NF-{kappa}B) and activator protein-1 (AP-1), accompanying the inhibitions of its subunits (p50, p65, c-Jun, and c-Fos), pro-inflammatory proteins [inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)], and pro-inflammatory cytokines [tumor necrosis factor (TNF)-{alpha} and interleukin (IL)-6] on DMH-stimulated ACF formation. On the basis of these results, we assume that UDN glycoprotein may be useful for colon cancer prevention at initiation stage.

  20. An Alternative to Farmer Age as an Indicator of Life-Cycle Stage: The Case for a Farm Family Age Index

    ERIC Educational Resources Information Center

    Burton, Rob J. F.

    2006-01-01

    In studies of farming, the age of the principal decision-maker (PDM) has been associated with numerous farm structural and managerial features and has been widely accepted as a good indicator of the influence of life-cycle factors on decision-making. As such, it has become an important aspect of many quantitative studies of agricultural change.…

  1. Aging

    PubMed Central

    Park, Dong Choon

    2013-01-01

    Aging is initiated based on genetic and environmental factors that operate from the time of birth of organisms. Aging induces physiological phenomena such as reduction of cell counts, deterioration of tissue proteins, tissue atrophy, a decrease of the metabolic rate, reduction of body fluids, and calcium metabolism abnormalities, with final progression onto pathological aging. Despite the efforts from many researchers, the progression and the mechanisms of aging are not clearly understood yet. Therefore, the authors would like to introduce several theories which have gained attentions among the published theories up to date; genetic program theory, wear-and-tear theory, telomere theory, endocrine theory, DNA damage hypothesis, error catastrophe theory, the rate of living theory, mitochondrial theory, and free radical theory. Although there have been many studies that have tried to prevent aging and prolong life, here we introduce a couple of theories which have been proven more or less; food, exercise, and diet restriction. PMID:24653904

  2. Evaluation of microscopic tumor extension in early-stage cervical cancer: quantifying subclinical uncertainties by pathological and magnetic resonance imaging findings

    PubMed Central

    Sanuki, Naoko; Urabe, Shogo; Matsumoto, Hideo; Ono, Asami; Komatsu, Eiji; Kamei, Noritaka; Maeda, Toru

    2013-01-01

    We performed a detailed analysis of hysterectomy specimens of uterine cervical cancer to determine the appropriate length of uterine body to include within the clinical target volume. Between 2008 and 2011, 54 patients with uterine cervical carcinoma underwent hysterectomy. Those with quality pre-operative magnetic resonance imaging (MRI) data were included for analysis. Tumor sizes measured by MRI and microscopy were compared with regard to brachytherapy-oriented parameters. Detailed descriptive analysis focusing on the extent of tumor involvement was also performed. A total of 31 specimens were analyzed. The median maximal tumor length measured by MRI was slightly shorter than microscopic length (19 vs. 24 mm, respectively), while the maximal radius was almost identical. No tumors with a maximal size <2 cm by MRI (n = 6) extended to the uterine body ≥ 1/3. The majority of maximal tumor length underestimation on MRI was within 1 cm. Precise tumor delineation can be made by MRI. For patients with tumors <2 cm on MRI, treating the entire uterine body length may not be necessary. A 1-cm margin around an MRI-based gross tumor seems to be adequate to cover the actual tumor involvement. PMID:23381955

  3. Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage.

    PubMed Central

    Shibata, M A; Liu, M L; Knudson, M C; Shibata, E; Yoshidome, K; Bandey, T; Korsmeyer, S J; Green, J E

    1999-01-01

    The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax. C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax+/- genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax+/- or bax-/- mice compared with bax+/+ mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma. PMID:10329616

  4. The effect of pre-existing mental health comorbidities on the stage at diagnosis and timeliness of care of solid tumor malignances in a Veterans Affairs (VA) medical center.

    PubMed

    Wadia, Roxanne J; Yao, Xiaopan; Deng, Yanhong; Li, Jia; Maron, Steven; Connery, Donna; Gunduz-Bruce, Handan; Rose, Michal G

    2015-09-01

    There are limited data on the impact of mental health comorbidities (MHC) on stage at diagnosis and timeliness of cancer care. Axis I MHC affect approximately 30% of Veterans receiving care within the Veterans Affairs (VA) system. The purpose of this study was to compare stage at diagnosis and timeliness of care of solid tumor malignancies among Veterans with and without MHC. We performed a retrospective analysis of 408 charts of Veterans with colorectal, urothelial, and head/neck cancer diagnosed and treated at VA Connecticut Health Care System (VACHS) between 2008 and 2011. We collected demographic data, stage at diagnosis, medical and mental health co-morbidities, treatments received, key time intervals, and number of appointments missed. The study was powered to assess for stage migration of 15-20% from Stage I/II to Stage III/IV. There was no significant change in stage distribution for patients with and without MHC in the entire study group (p = 0.9442) and in each individual tumor type. There were no significant differences in the time intervals from onset of symptoms to initiation of treatment between patients with and without MHC (p = 0.1135, 0.2042 and 0.2352, respectively). We conclude that at VACHS, stage at diagnosis for patients with colorectal, urothelial and head and neck cancers did not differ significantly between patients with and without MHC. Patients with MHC did not experience significant delays in care. Our study indicates that in a medical system in which mental health is integrated into routine care, patients with Axis I MHC do not experience delays in cancer care.

  5. Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes.

    PubMed

    Pareja, Rene; Rendón, Gabriel J; Vasquez, Monica; Echeverri, Lina; Sanz-Lomana, Carlos Millán; Ramirez, Pedro T

    2015-06-01

    Radical trachelectomy is the treatment of choice in women with early-stage cervical cancer wishing to preserve fertility. Radical trachelectomy can be performed with a vaginal, abdominal, or laparoscopic/robotic approach. Vaginal radical trachelectomy (VRT) is generally not offered to patients with tumors 2cm or larger because of a high recurrence rate. There are no conclusive recommendations regarding the safety of abdominal radical trachelectomy (ART) or laparoscopic radical trachelectomy (LRT) in such patients. Several investigators have used neoadjuvant chemotherapy in patients with tumors 2 to 4cm to reduce tumor size so that fertility preservation may be offered. However, to our knowledge, no published study has compared outcomes between patients with cervical tumors 2cm or larger who underwent immediate radical trachelectomy and those who underwent neoadjuvant chemotherapy followed by radical trachelectomy. We conducted a literature review to compare outcomes with these 2 approaches. Our main endpoints for evaluation were oncological and obstetrical outcomes. The fertility preservation rate was 82.7%, 85.1%, 89%; and 91.1% for ART (tumors larger than >2cm), ART (all sizes), NACT followed by surgery and VRT (all sizes); respectively. The global pregnancy rate was 16.2%, 24% and 30.7% for ART, VRT, and NACT followed by surgery; respectively. The recurrence rate was 3.8%, 4.2%, 6%, 7.6% and 17% for ART (all sizes), VRT (all sizes), ART (tumors>2cm), NACT followed by surgery, and VRT (tumors>2cm). These outcomes must be considered when offering a fertility sparing technique to patients with a tumor larger than 2cm.

  6. Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non-Small-Cell Lung Cancer: A Competing Risks Analysis.

    PubMed

    Eguchi, Takashi; Bains, Sarina; Lee, Ming-Ching; Tan, Kay See; Hristov, Boris; Buitrago, Daniel H; Bains, Manjit S; Downey, Robert J; Huang, James; Isbell, James M; Park, Bernard J; Rusch, Valerie W; Jones, David R; Adusumilli, Prasad S

    2017-01-20

    Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

  7. Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

    ClinicalTrials.gov

    2017-04-12

    Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell

  8. Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

    ClinicalTrials.gov

    2016-04-14

    Childhood Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Clear Cell Sarcoma of the Kidney; Papillary Renal Cell Carcinoma; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Renal Wilms Tumor; Stage II Renal Cell Cancer; Stage II Renal Wilms Tumor; Stage III Renal Cell Cancer; Stage III Renal Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Renal Wilms Tumor

  9. Wnt3a expression is associated with MMP-9 expression in primary tumor and metastatic site in recurrent or stage IV colorectal cancer

    PubMed Central

    2014-01-01

    Background The wnt/β-catenin signaling pathway is known to affect in cancer oncogenesis and progression by interacting with the tumor microenvironment. However, the roles of wnt3a and wnt5a in colorectal cancer (CRC) have not been thoroughly studied. In the present study, we investigated the expression of wnt protein and the concordance rate in primary tumor and metastatic sites in CRC. To determine the relationship of wnt proteins with invasion related protein, we also analyzed the association between wnt protein expression and the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor-2 (VEGFR-2). Methods Tumor tissue was obtained from eighty-three paraffin- embedded blocks which were using resected tissue from both the primary tumor and metastatic sites for each patient. We performed immunohistochemical staining for wnt3a, wnt5a, β-catenin, MMP-9 and VEGFR-2. Results Wnt3a, wnt5a, β-catenin, and MMP-9 expression was high; the proteins were found in over 50% of the primary tumors, but the prevalence was lower in tissue from metastatic sites. The concordance rates between the primary tumor and metastatic site were 76.2% for wnt5a and 79.4% for wnt3a and β-catenin, but VEGFR-2 was expressed in 67.4% of the metastatic sites even when not found in the primary tumor. Wnt3a expression in primary tumors was significantly associated with lymph node involvement (p = 0.038) and MMP-9 expression in the primary tumor (p = 0.0387), mesenchyme adjacent to tumor (p = 0.022) and metastatic site (p = 0.004). There was no other relationship in the expression of these proteins. Vascular invasion in primary tumor tissue may be a potential prognostic marker for liver metastasis, but no significant association was observed among the wnt protein, MMP-9, and VEGFR-2 for peritoneal seeding. In survival analysis, β-catenin expression was significantly correlated with overall survival (p = 0.05). Conclusions Wnt3a and wnt5a

  10. Advanced maternal age and the risk of Down syndrome characterized by the meiotic stage of the chromosomal error: A population-based study

    SciTech Connect

    Yoon, P.W.; Khoury, M.J.; Freeman, S.B.

    1996-03-01

    The identification of DNA polymorphisms makes it possible to classify trisomy 21 according to the parental origin and stage (meiosis I [MI], meiosis II [MII], or postzygotic mitotic) of the chromosomal error. Studying the effect of parental age on these subgroups could shed light on parental exposures and their timing. From 1989 through 1993, 170 infants with trisomy 21 and 267 randomly selected control infants were ascertained in a population-based, case-control study in metropolitan Atlanta. Blood samples for genetic studies were obtained from case infants and their parents. Using logistic regression, we independently examined the association between maternal and paternal age and subgroups of trisomy 21 defined by parental origin and meiotic stage. The distribution of trisomy 21 by origin was 86% maternal (75% MI and 25% MII), 9% paternal (50% MI and 50% MII), and 5% mitotic. Compared with women <25 years of age, women {>=}40 years old had an odds ratio of 5.2 (95% confidence interval, 1.0-27.4) for maternal MI (MMI) errors and 51.4 (95% confidence interval, 2.3-999.0) for maternal MII (MMII) errors. Birth-prevalence rates for women {>=}40 years old were 4.2/1,000 births for MMI errors and 1.9/1,000 births for MMII errors. These results support an association between advanced maternal age and both MMI and MMII errors. The association with MI does not pinpoint the timing of the error; however, the association with MII implies that there is at least one maternal age-related mechanism acting around the time of conception. 16 refs., 1 fig., 2 tabs.

  11. Sleep fragmentation and sepsis differentially impact blood-brain barrier integrity and transport of tumor necrosis factor-α in aging.

    PubMed

    Opp, Mark R; George, Amrita; Ringgold, Kristyn M; Hansen, Kim M; Bullock, Kristin M; Banks, William A

    2015-11-01

    The factors by which aging predisposes to critical illness are varied, complex, and not well understood. Sepsis is considered a quintessential disease of old age because the incidence and mortality of severe sepsis increases in old and the oldest old individuals. Aging is associated with dramatic changes in sleep quality and quantity and sleep increasingly becomes fragmented with age. In healthy adults, sleep disruption induces inflammation. Multiple aspects of aging and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis factor-α (TNF), a cytokine involved in sleep regulation and neuroimmune processes, exerts some of its effects on the CNS by crossing the blood-brain barrier (BBB). In this study we examined the impact of sepsis, sleep fragmentation, and aging on BBB disruption and TNF transport into brain. We used the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that were either undisturbed or had their sleep disrupted. There was a dichotomous effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and increased TNF transport in young mice but not in aged mice, whereas sleep fragmentation disrupted the BBB and increased TNF transport in aged mice, but not in young mice. Combining sleep fragmentation and CLP did not produce a greater effect on either of these BBB parameters than did either of these manipulations alone. These results suggest that the mechanisms by which sleep fragmentation and sepsis alter BBB functions are fundamentally different from one another and that a major change in the organism's responses to those insults occurs with aging.

  12. Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection.

    PubMed

    Balliet, Renee M; Capparelli, Claudia; Guido, Carmela; Pestell, Timothy G; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Whitaker-Menezes, Diana; Chiavarina, Barbara; Pestell, Richard G; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P

    2011-12-01

    Increasing chronological age is the most significant risk factor for cancer. Recently, we proposed a new paradigm for understanding the role of the aging and the tumor microenvironment in cancer onset. In this model, cancer cells induce oxidative stress in adjacent stromal fibroblasts. This, in turn, causes several changes in the phenotype of the fibroblast including mitochondrial dysfunction, hydrogen peroxide production, and aerobic glycolysis, resulting in high levels of L-lactate production. L-lactate is then transferred from these glycolytic fibroblasts to adjacent epithelial cancer cells and used as "fuel" for oxidative mitochondrial metabolism.  Here, we created a new pre-clinical model system to directly test this hypothesis experimentally. To synthetically generate glycolytic fibroblasts, we genetically-induced mitochondrial dysfunction by knocking down TFAM using an sh-RNA approach.  TFAM is mitochondrial transcription factor A, which is important in functionally maintaining the mitochondrial respiratory chain. Interestingly, TFAM-deficient fibroblasts showed evidence of mitochondrial dysfunction and oxidative stress, with the loss of certain mitochondrial respiratory chain components, and the over-production of hydrogen peroxide and L-lactate. Thus, TFAM-deficient fibroblasts underwent metabolic reprogramming towards aerobic glycolysis.  Most importantly, TFAM-deficient fibroblasts significantly promoted tumor growth, as assayed using a human breast cancer (MDA-MB-231) xenograft model. These increases in glycolytic fibroblast driven tumor growth were independent of tumor angiogenesis. Mechanistically, TFAM-deficient fibroblasts increased the mitochondrial activity of adjacent epithelial cancer cells in a co-culture system, as seen using MitoTracker. Finally, TFAM-deficient fibroblasts also showed a loss of caveolin-1 (Cav-1), a known breast cancer stromal biomarker. Loss of stromal fibroblast Cav-1 is associated with early tumor recurrence, metastasis

  13. Comparison of the effectiveness of high and low LET radiations for the proportion of survivals with liver tumors at every age in (C57BL/6N x C3H/HeN) F1 mice.

    PubMed

    Nitta, Yumiko; Satoh, Kenichi; Suga, Shinji; Endo, Satoru; Nitta, Kohsaku

    2006-07-01

    To investigate the late effects of neutrons at the energy below 1 MeV on the liver carcinogenesis as a function of age, one-week old mice were exposed to 1.0 Gy monoenergetic neutrons (0.317, 0.525 and 1.026 MeV) or 137Cs gamma rays. Survival and carcinogenesis were examined by 18 months of age. Following radiation, tumor incidences in liver, Harderian gland, lung, ovary and pituitary gland were compared. The proportion of the lifespan with liver tumors exposed to neutrons to that exposed to gamma rays was calculated as a function of age. Survival rates among the three groups exposed to neutrons of different energies were not significantly different from one another but shorter than those treated with gamma rays for both sexes. With regard to liver tumor incidence evaluated at 18 months of age, the effectiveness of neutrons to gamma rays was 2.54 for females, and 2.08 for males by the factor. Levels of estrogen in the serum were similar between mice bearing liver tumors and those devoid of tumors. In conclusion, all three energies of neutrons induced similar effectiveness with respect to liver carcinogenicity. Proportions of the lifespan with liver tumors of neutron-exposed to gamma-exposed were shorter in females than males along with ages over 12 months. To obtain this factor at every age contributed for the evaluation of the biological effectiveness of radiations with the parameter of tumor incidence and latency simultaneously.

  14. Testicular germ cell tumors: pathogenesis, diagnosis and treatment.

    PubMed

    Winter, Christian; Albers, Peter

    2011-01-01

    Testicular germ cell tumors represent the most common solid malignancy of young men aged 15-40 years. Histopathologically, testicular germ cell tumors are divided into two major groups: pure seminoma and nonseminoma. The pathogenesis of testicular germ cell tumors remains unknown; however, cryptorchidism is the main risk factor, and molecular studies have shown strong evidence of an association between genetic alterations and testicular germ cell tumors. In cases of suspicion for testicular germ cell tumor, a surgical exploration with orchiectomy is obligatory. After completion of diagnostic procedures, levels of serum tumor markers and the clinical stage based on the International Union Against Cancer tumor-node-metastasis classification should be defined. Patients with early-stage testicular germ cell tumors are treated by individualized risk stratification within a multidisciplinary approach. The individual management (surveillance, chemotherapy or radiotherapy) has to be balanced according to clinical features and the risk of short-term and long-term toxic effects. Treatment for metastatic tumors is based on risk stratification according to International Germ Cell Cancer Collaborative Group classification and is performed with cisplatin-based chemotherapy and residual tumor resection in cases of residual tumor lesion. High-dose chemotherapy represents a curative option for patients with second or subsequent relapses.

  15. InCVAX - A novel strategy for treatment of late-stage, metastatic cancers through photoimmunotherapy induced tumor-specific immunity

    PubMed Central

    Zhou, Feifan; Li, Xiaosong; Naylor, Mark F.; Hode, Tomas; Nordquist, Robert E.; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel S.K.; Du, Nan; Shi, Lei; Wang, Xiuli; Chen, Wei R.

    2015-01-01

    A novel, promising potential cancer vaccine strategy was proposed to use a two-injection procedure for solid tumors to prompt the immune system to identify and systemically eliminate the primary and metastatic cancers. The two-injection procedure consists of local photothermal application on a selected tumor intended to liberate whole cell tumor antigens, followed by a local injection of an immunoadjuvant that consists of a semi-synthetic functionalized glucosamine polymer, N-dihydro-galacto-chitosan (GC), which is intended to activate antigen presenting cells and facilitate an increased uptake of tumor antigens. This strategy is thus proposed as an in situ autologous cancer vaccine (inCVAX) that may activate antigen presenting cells and expose them to tumor antigens in situ, with the intention of inducing a systemic tumor specific T-cell response. Here, the development of inCVAX for the treatment of metastatic cancers in the past decades are systematically reviewed. The antitumor immune responses of local photothermal treatment and immunological stimulation with GC are also discussed. This treatment approach is also commonly referred to as laser immunotherapy (LIT). PMID:25633839

  16. Induction of GST-P-positive proliferative lesions facilitating lipid peroxidation with possible involvement of transferrin receptor up-regulation and ceruloplasmin down-regulation from the early stage of liver tumor promotion in rats.

    PubMed

    Mizukami, Sayaka; Ichimura, Ryohei; Kemmochi, Sayaka; Taniai, Eriko; Shimamoto, Keisuke; Ohishi, Takumi; Takahashi, Miwa; Mitsumori, Kunitoshi; Shibutani, Makoto

    2010-04-01

    To elucidate the role of metal-related molecules in hepatocarcinogenesis, we examined immunolocalization of transferrin receptor (Tfrc), ceruloplasmin (Cp) and metallothionein (MT)-1/2 in relation to liver cell foci positive for glutathione-S-transferase placental form (GST-P) in the early stage of tumor promotion by fenbendazole (FB), phenobarbital, piperonyl butoxide or thioacetamide in a rat two-stage hepatocarcinogenesis model. To estimate the involvement of oxidative stress responses to the promotion, immunolocalization of 4-hydroxy-2-nonenal, malondialdehyde and acrolein was similarly examined. Our findings showed that MT-1/2 immunoreactivity was not associated with the cellular distribution of GST-P and proliferating cell nuclear antigen, suggesting no role of MT-1/2 in hepatocarcinogenesis. We also found enhanced expression of Tfrc after treatment with strong tumor-promoting chemicals. With regard to Cp, the population showing down-regulation was increased in the GST-P-positive foci in relation to tumor promotion. Up-regulation of Tfrc and down-regulation of Cp was maintained in GST-P-positive neoplastic lesions induced after long-term promotion with FB, suggesting the expression changes occurring downstream of the signaling pathway involved in the formation of GST-P-positive lesions. Furthermore, enhanced accumulation of lipid peroxidation end products was observed in the GST-P-positive foci by promotion. Post-initiation treatment with peroxisome proliferator-activated receptor alpha agonists did not enhance any such distribution changes in GST-P-negative foci. The results thus suggest that facilitation of lipid peroxidation is involved in the induction of GST-P-positive lesions by tumor promotion from an early stage, and up-regulation of Tfrc and down-regulation of Cp may be a signature of enhanced oxidative cellular stress in these lesions.

  17. Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants

    PubMed Central

    Singer, Michael A; Amir, Nancy; Herro, Angela; Porbandarwalla, Salman S; Pollard, Joseph

    2012-01-01

    Low vision devices in the past have been mainly extraocular. There are now four new devices in different stages of development and implementation that are currently available. Three of them, the Implantable Miniature Telescope (IMT, VisionCare Ophthalmic Technologies, Saratoga, CA), Intraocular Lens for Visually Impaired People (IOL-VIP, IOL-VIP System, Soleko, Pontecorvo, Italy), and Lipschitz Mirror Implant (LMI, Optolight Vision Technology, Herzlia, Israel) are implanted into the anterior segment while the Argus II (Second Sight Medical Products, Sylmar, CA) is implanted into the posterior segment. The goal of these devices is to increase the patient quality of life which has been measured by Visual Functioning Questionnaire (VFQ) scales. The IMT is the only device that has been shown to increase the VFQ score by seven points at 6 months compared to baseline. It is the only FDA-approved device in the US while the Argus has been approved in Europe. Each of these prosthetics has potential benefits for patients. PMID:22259233

  18. Improving quality of life in patients with end-stage age-related macular degeneration: focus on miniature ocular implants.

    PubMed

    Singer, Michael A; Amir, Nancy; Herro, Angela; Porbandarwalla, Salman S; Pollard, Joseph

    2012-01-01

    Low vision devices in the past have been mainly extraocular. There are now four new devices in different stages of development and implementation that are currently available. Three of them, the Implantable Miniature Telescope (IMT, VisionCare Ophthalmic Technologies, Saratoga, CA), Intraocular Lens for Visually Impaired People (IOL-VIP, IOL-VIP System, Soleko, Pontecorvo, Italy), and Lipschitz Mirror Implant (LMI, Optolight Vision Technology, Herzlia, Israel) are implanted into the anterior segment while the Argus II (Second Sight Medical Products, Sylmar, CA) is implanted into the posterior segment. The goal of these devices is to increase the patient quality of life which has been measured by Visual Functioning Questionnaire (VFQ) scales. The IMT is the only device that has been shown to increase the VFQ score by seven points at 6 months compared to baseline. It is the only FDA-approved device in the US while the Argus has been approved in Europe. Each of these prosthetics has potential benefits for patients.

  19. Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests

    PubMed Central

    Ledo, Alicia

    2015-01-01

    Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies. PMID:26581110

  20. Psychosocial impact of illness intrusiveness moderated by self-concept and age in end-stage renal disease.

    PubMed

    Devins, G M; Beanlands, H; Mandin, H; Paul, L C

    1997-11-01

    This study assesses whether a person's self-concept as a "chronic kidney patient" differentially moderates the psychosocial impact of illness intrusiveness--illness-induced lifestyle disruptions--across the life span. Renal transplant (n = 52) and maintenance dialysis patients (n = 49) completed the illness Intrusiveness Ratings Scale, a semantic-differential self-concept measure, and structured interviews measuring psychosocial well-being and emotional distress. Across ages, distress rose with increasing illness intrusiveness when self-concept was similar, but not dissimilar, to the chronic kidney patient stereotype. The relation between illness intrusiveness and psychosocial well-being differed significantly between younger and older respondents depending on whether they construed themselves as similar versus dissimilar to the chronic kidney patient. Although self-definition moderates the psychosocial impact of chronic disease, this varies across the life span and across affect states.

  1. [Neuromuscular status of children of different gestational age on the stage of transition from intrauterine immersion to the earth's gravity].

    PubMed

    2012-01-01

    The work was aimed at describing the neuromuscular status of premature baby in the context of the ontogenetic and zero gravity model using the results of superficial interference electromyography (IEMG). Throughout six postnatal weeks, IEMG of premature babies is similar to EMG of full-term child on the first days of extrauterine life; IEMG is characterized by a "simplified" temporal structure, low amplitude and frequency, IEMG dynamics of fullterm child is slow in contrast to premature baby; the reason seems to be maximum long intrauterine life during which the motor system gets better prepared and maturates. On the other hand, complexity and high amplitude of premature baby IEMG as compared with full-term child of the same postconceptual age are associated with the inevitable sensory stimulation after birth. Abilitation procedures provided to premature baby could be adapted to the purposes of post-flight rehabilitation of cosmonauts.

  2. Quantitative pteridine fluorescence analysis: A possible age-grading technique for the adult stages of the blow fly Calliphora vicina (Diptera: Calliphoridae).

    PubMed

    Bernhardt, Victoria; Hannig, Laura; Kinast, Ronja; Verhoff, Marcel A; Rothweiler, Florian; Zehner, Richard; Amendt, Jens

    2017-03-04

    Age estimation of adult flies could extend the possible window of time for calculating the minimal postmortem interval (PMImin) by means of entomological methods. Currently, this is done by estimating the time required by necrophagous Diptera to reach certain juvenile developmental landmarks, and the method only works until the end of metamorphosis and emergence of the adult fly. Particularly at indoor crime scenes, being able to estimate the age of trapped adult flies would be an important tool with which to extend the calculable PMI beyond the developmental period. Recently, several promising age-dependent morphological and physiological characteristics of adult insects have been investigated in medical and forensic entomology, but the results are still preliminary and restricted to a few species. We examined adults of the forensically relevant blow fly species Calliphora vicina and investigated the fluorescence levels of pteridine, a group of metabolites that accumulates in the eyes during aging. From Day 1 to Day 25 post-emergence, flies were kept at three different temperature regimes (20°C, 25°C, and fluctuating temperatures in the context of a field study) and 12:12 L:D. From Day 1 until Day 7, the fluorescence of pteridine was determined on a daily basis, and thereafter, every three days. The achieved fly age was multiplied with the relevant temperature and converted into accumulated degree-days (ADD). The fluorescence level of pteridine increased linear with increasing ADD (females: R(2)=0.777; males: R(2)=0.802). The difference between sexes was significant (p<0.001). Neither head weight nor temperature had an effect on pteridine fluorescence. Because the variation in pteridine fluorescence increased with increasing ADD, it seems favorable to combine several aging methods for more precise results. In context, we emphasize that different body parts of the same specimen can be used to analyze cuticular hydrocarbons (legs), pteridine fluorescence (head

  3. Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient.

    PubMed

    Kawano, S; Tatsumi, E; Yoneda, N; Yamaguchi, N; Goji, J; Ito, H; Nagai, T; Nishikori, M; Okamura, A; Koiwai, O

    1995-01-01

    A 66-year-old male patient was admitted with dyspnea; physical examination revealed petechiae and systemic lymphadenopathy. Laboratory findings showed leukemia. The blasts in the peripheral blood were negative for cytochemical myeloperoxidase, and had condensed nuclear chromatin with a nucleolus. The histological diagnosis of the biopsied neck lymph node was lymphoblastic lymphoma. The leukemia cells expressed CD2, CD6, CD7, CD13low, CD56, beta chain of IL-2 receptorlow (IL-2R beta), and HLA-DR antigens, but not other pan-T (CD5, CD3, CD4, and CD8); pan-B (CD10, CD19, CD20, and CD24); natural killer (NK) (CD16, CD57); or myeloid (CD33) antigens. Electronmicroscopy revealed convoluted nuclei with conspicuous nucleoli and peripherally condensed heterochromatin. Membrane-bound granules containing an electron dense matrix were observed in the cytoplasm, indicating the NK cell nature of the neoplastic cells. While terminal deoxynucleotidyl transferase (TdT) and cytoplasmic CD3 were not detected by immunofluorescence on fixed smears, Northern blot analysis revealed the gene expression of CD3 epsilon, CD3 zeta, and TdT. Gene rearrangement analysis revealed that the beta, gamma, and delta chains of T-cell receptor (TCR) and immunoglobulin heavy chain (IgH) were of germline genotype. While the overall interpretation of the phenotype and genotype was difficult, the derivation of an immature stage of NK lineage was strongly suggested, based predominantly on the electronmicroscopic features. Despite initially successful chemotherapy, the patient died 14 months after initial presentation.

  4. Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina.

    PubMed

    Zurita, Alfredo E; Taglioretti, Matías; DE Los Reyes, Martín; Cuadrelli, Francisco; Poire, Daniel

    2016-06-07

    A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorín Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa.

  5. Highly retentive core domains in K-feldspar preserve argon ages from high temperature stages of granite exhumation

    NASA Astrophysics Data System (ADS)

    Forster, Marnie; Lister, Gordon

    2016-04-01

    Retentive core domains are characterized by diffusion parameters that imply K-feldspar should be able to retain argon even at temperatures near or above the granite solidus. In this case it should be possible to date granite emplacement using argon geochronology, and the same answer should be obtained as by using other methods. We present one case study where this is the case, from the elevated Capoas granite stock on Palawan, in the Philippines, and another where it is not, from the South Cyclades Shear Zone, on Ios, Greece. We attempt to determine the factors such as the role of fluid ingress in triggering the in situ recrystallization that can eliminate and/or modify the core domains, leading to relatively youthful ages. Thermochronology is still possible, because less retentive diffusion domains exist, but different methods need to be applied to interpret the data. The work also demonstrates that K-feldspar can be sufficiently retentive as to allow direct dating of processes that reduce the dimensions of diffusion domains, e.g., cataclased and/or recrystallized K-feldspar in fault rock and/or mylonite. These are important developments in the methodology of 40Ar/39Ar geochronology, but to further advance we need to clarify the nature of these highly retentive core domains. In particular, we need better understand how they are modified by microstructural processes during deformation and metamorphism. We need also to assess the role of any crystal structural changes during step-heating in vacuo.

  6. Use of nano-sized clay crystallites to restore adhesion among tumor and aging stem cells - a molecular simulations approach

    PubMed Central

    Ahmed, Habib-ur-Rehman; Abduljauwad, Sahel N

    2016-01-01

    Adhesion of cells to the ECM is key to the regulation of cellular morphology, migration, proliferation, survival, and differentiation. The decrease in or loss of the cell’s ability of mutual adhesiveness has been considered as one of the specific abnormalities in the surface properties of malignant cells. A change in the association of plasma membrane with cytoskeletal structures also seems to have a close relation with these abnormalities. Similar to the role of adhesions in tumor cells, stem cells’ self-renewal is also tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. This study has demonstrated through molecular simulations the potential use of smectite (Na-montmorillonite) clay crystallites to create adhesions among tumor and stem cells. High electrostatic energies and cohesive energy densities measured in the simulations after the sorption of clay crystallites on cell-cell and cell-ECM complexes validate the concept of using these crystallites for the purposes. As results of this study are quite promising and clay crystallites could be considered as an option to restore adhesions in tumor and stem cells, other confirmatory tests and live cell culture studies are in process for the final validation. PMID:28078181

  7. TH-C-12A-02: Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Stage I and II Peripheral Lung Tumors with Unflattened Beams

    SciTech Connect

    Huang, B; Lu, J; Chen, J; Chen, C; Lin, P; Kuang, Y

    2014-06-15

    Purpose: The full arcs strategy used in SBRT with RapidArc and unflattened (FFF) beams in large and heterogeneous peripheral non-smallcell lung cancer (NSCLC) appears to be suboptimal as it increases the disadvantageous dose to the contralateral lung, which potentially increases the toxicity to surrounding tissues. In this study, we investigated, for the first time, the dose delivery strategies using partial arcs (PA) and the fully rotational arcs with avoidance sectors (FAAS) for SBRT with FFF beams in peripheral NSCLC patients. Methods: Eighteen patients with NSCLC (stage I and II) were selected for this study. Nine patients with a GTV <= 10cc were designated as the small tumor group. The remaining nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OAR), total MU, out-of-field dose, and delivery time were analyzed. Delta4 and Portal dosimetry were employed to evaluate the delivery accuracy. Results: or the small tumor group, the FAAS plans significantly achieved a better conformity index, the lower total MU and out-of-field dose, a shorter treatment time, and the reduced doses to cord, heart, and lung (p < 0.05). But the target doses were slightly higher than that delivered by PA plans. For the large tumor group, the PA plans significantly attained a better conformity index and a shorter treatment time (p < 0.05). Furthermore, all plans achieved a high pass rate, with all the gamma indices greater than 97% at the Γ{sub 3mm,} {sub 3%} threshold. Conclusion: This study suggests that FAAS strategy is more beneficial for small tumor patients undergoing lung SBRT with FFF beams. However, for large tumor patients, PA strategy is recommended. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.

  8. Competence for Regeneration during Tobacco Internodal Development (Involvement of Plant Age, Cell Elongation Stage, and Degree of Polysomaty).

    PubMed Central

    Gilissen, LJW.; Van Staveren, M. J.; Hakkert, J. C.; Smulders, MJM.

    1996-01-01

    This study deals with internodal development in vegetative plants of Nicotiana tabacum cv Samsun NN and its reflection in changes of the cellular competence for regeneration. During elongation of the internodes, the cells of the epidermis, subepidermis, and cortex exclusively expanded and increased their DNA content cell type specifically, generally from 2C to 4C. Cells with the 8C DNA content were found mainly among the cortex cells of mature internodes. The frequency of shoot regeneration (directly from subepidermal and epidermal cells together) on thin cell layer explants increased to an optimum along with elongation of the internodes and decreased in mature internodes along with aging. The frequencies of diploid shoots among the regenerants from elongating and mature internodes were high (88 and 75% on the average, respectively), indicating that most cells that had achieved the 4C DNA content generally retained the G2 phase of the diploid cell cycle. Shoots regenerated from explants of young plant material mainly had a vitrified appearance. The occurrence of this type of malformed growth was already determined by the physiological state of the cells in the internode and did not interfere with their acquisition of competence. Vitrification was unrelated to the degree of polysomaty of the internodal tissue. Using the occurrence of tetraploid root regenerants (from intermediate cortex-derived callus), up to a frequency of 50%, we show that the position in the plant where a majority of the 4C cortex cells switched to the G1 phase of the tetraploid cell cycle was at the transition from the elongation phase to the mature phase. PMID:12226359

  9. Natural growth and diet of known-age pallid sturgeon (Scaphirhynchus albus) early life stages in the upper Missouri River basin, Montana and North Dakota

    USGS Publications Warehouse

    Braaten, P.J.; Fuller, D.B.; Lott, R.D.; Haddix, T.M.; Holte, L.D.; Wilson, R.H.; Bartron, M.L.; Kalie, J.A.; DeHaan, P.W.; Ardren, W.R.; Holm, R.J.; Jaeger, M.E.

    2012-01-01

    Prior to anthropogenic modifications, the historic Missouri River provided ecological conditions suitable for reproduction, growth, and survival of pallid sturgeon Scaphirhynchus albus. However, little information is available to discern whether altered conditions in the contemporary Missouri River are suitable for feeding, growth and survival of endangered pallid sturgeon during the early life stages. In 2004 and 2007, nearly 600 000 pallid sturgeon free embryos and larvae were released in the upper Missouri River and survivors from these releases were collected during 2004–2010 to quantify natural growth rates and diet composition. Based on genetic analysis and known-age at release (1–17 days post-hatch, dph), age at capture (dph, years) could be determined for each survivor. Totals of 23 and 28 survivors from the 2004 and 2007 releases, respectively, were sampled. Growth of pallid sturgeon was rapid (1.91 mm day-1) during the initial 13–48 dph, then slowed as fish approached maximum length (120–140 mm) towards the end of the first growing season. The diet of young-of-year pallid sturgeon was comprised of Diptera larvae, Diptera pupae, and Ephemeroptera nymphs. Growth of pallid sturgeon from ages 1–6 years was about 48.0 mm year-1. This study provides the first assessment of natural growth and diet of young pallid sturgeon in the wild. Results depict pallid sturgeon growth trajectories that may be expected for naturally produced wild stocks under contemporary habitat conditions in the Missouri River and Yellowstone River.

  10. Late-Stage HIMU-Type Volcanism on the Walvis Ridge: Not just Part of an Age-Progressive Tristan-Gough Hotspot Track

    NASA Astrophysics Data System (ADS)

    Homrighausen, S.; Hoernle, K.; Hauff, F.; Portnyagin, M.; Werner, R.; Geldmacher, J.; Garbe-Schoenberg, C. D.

    2015-12-01

    The Walvis Ridge forms the NE portion of the Tristan-Gough hotspot track. It links the Etendeka large igneous province (LIP) in Africa, initially connected to the Parana LIP in South America, to the Guyot Province, that ends at the active volcanic islands of Tristan da Cunha and Gough. After the plume head stage, the hotspot changed from a ridge-centered plume tail, forming the Walvis Ridge and Rio Grande Rise (130-60 Ma), to an intraplate setting resulting in the geochemical distinct Tristan and Gough subtracks (Rohde et al. 2013; Geology 41). New major and trace element and radiogenic isotope data have been generated from 36 new dredge locations on the Walvis Ridge during R/V Sonne cruises SO233 and SO234. Based on the bathymetric data, we have identified tectonic structures and subsidence rates which indicate a complex geodynamic interplay of the Walvis Ridge formation and westward migration of the Mid Atlantic Ridge and the Rio Grande Rise. Our new results confirm that the age-progressive basement of the Walvis Ridge reflects only the enriched Gough component with no evidence of the Tristan component being present (Hoernle et al., 2015; Nat. Comm.). Superimposed large seamounts (including ridge- and guyot-like structures), especially in the SE portion of the Walvis Ridge, belong to a later-stage of alkalic volcanism with distinct HIMU incompatible element and Sr-Nd-Pb-Hf isotopic composition. The HIMU late-stage volcanism (206Pb/204Pb up to 20.8) is similar in composition to St. Helena and a late-stage (Eocene) sample from the Rio Grande Rise (Rohde et al., 2013; Tectonophysics 604). The new geochemical, bathymetric and existing age data indicate a magmatic reactivation c. 20-40 Ma after the formation of the Walvis Ridge basement, which may be related to passage of the Walvis Ridge over a batch of upwelling St. Helena type plume material. Our new results indicate a more complex formation of the Walvis Ridge than previously thought, which included two major

  11. Intratubular trophoblasts in the contralateral testis caused elevation of serum human chorionic gonadotropin following complete remission of stage II testicular tumor: a case report.

    PubMed

    Nitta, Satoshi; Kawai, Koji; Onozawa, Mizuki; Ando, Satoshi; Miyazaki, Jun; Nagata, Chigusa; Noguchi, Masayuki; Yamasaki, Kazumitsu; Uchida, Katsunori; Iwamoto, Teruaki; Nishiyama, Hiroyuki

    2013-01-01

    We report the case of a 22-year-old male who had a history of metastatic right testicular tumor successfully treated with chemotherapy and surgery. Twenty-one months after the initial treatment, the serum human chorionic gonadotropin started to increase gradually, but whole body imaging including the left testis revealed no abnormal finding except testicular microlithiasis. A biopsy of the left testis revealed intratubular germ cell neoplasia, unclassified type. After the human chorionic gonadotropin level reached 6.6 mIU/ml, he underwent left high orchiectomy. Histology demonstrated a small malignant germ cell tumor as well as intratubular germ cell neoplasia, unclassified type, both of which were negative for human chorionic gonadotropin staining. Besides these lesions, there were tiny foci of human chorionic gonadotropin-immunoreactive intratubular trophoblasts. Serum human chorionic gonadotropin normalized immediately after the orchiectomy, and he had no sign of recurrence at 6 months. The present case will provide new insight into the diagnosis of testicular tumor recurrence with isolated elevation of a serum tumor marker.

  12. Treatment of Cavernous Sinus Tumors with Linear Accelerator Radiosurgery

    PubMed Central

    Chang, Steven D.; Doty, James R.; Martin, David P.; Hancock, Steven L.; Adler, John R.

    1999-01-01

    Since 1989, 79 patients with benign or malignant cavernous sinus tumors, have been treated at Stanford University with linear accelerator (linac) radiosurgery. Radiosurgery has been used as (1) a planned second-stage procedure for residual tumor following surgery, (2) primary treatment for patients whose medical conditions preclude surgery, (3) palliation of malignant lesions, and (4) definitive treatment for small, well-localized, poorly accessible tumors. Mean patient age was 52 years (range, 18 to 88); there were 28 males and 51 females. Sixty-one patients had benign tumors; 18 had malignant tumors. Mean tumor volume was 6.8 cm3 (range 0.5 to 22.5 cm3) covered with an average of 2.3 isocenter (range, 1 to 5). Radiation dose averaged 17.1 Gy. Mean follow-up was 46 months. Tumor control or shrinkage, or both, varied with pathology. Radiographic tumor improvement was most pronounced in malignant lesions, with greater than 85% showing reduction in tumor size; benign tumors (meningiomas and schwannomas) had a 63% control rate and 37% shrinkage rate, with none enlarging. We concluded that stereotactic radiosurgery is a valuable tool in managing cavernous sinus tumors. There was excellent control and stabilization of benign tumors and palliation of malignant lesions. ImagesFigure 1Figure 2 PMID:17171089

  13. Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

    PubMed Central

    Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  14. Computed Tomography-Based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients With Mass-like Consolidation After Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Dunlap, Neal E.; Yang Wensha; McIntosh, Alyson; Sheng, Ke; Benedict, Stanley H.; Read, Paul W.; Larner, James M.

    2012-12-01

    Purpose: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. Methods and Materials: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. Results: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade {>=}2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). Conclusion: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will

  15. The Articular Morphology of the First Carpometacarpal Joint Does Not Differ between Men and Women, but Changes with Aging and Early Stage Osteoarthritis

    PubMed Central

    Halilaj, Eni; Moore, Douglas C.; Laidlaw, David H.; Got, Christopher J.; Weiss, Arnold-Peter C.; Ladd, Amy L.; Crisco, Joseph J.

    2014-01-01

    The increased prevalence of thumb carpometacarpal (CMC) joint osteoarthritis (OA) in women has been previously linked to the articular morphology of the trapezium. However, studies report conflicting results on how the articular shapes of male and female trapezia compare to one another, mainly because their findings are based on data from older cadaver specimens. The purpose of this in vivo study was to dissociate the effect of sex from that of aging and early OA by using cohorts of healthy young and healthy older subjects, as well as patients with early stage OA. Computed tomography scans from 68 healthy subjects and 87 arthritic subjects were used to obtain 3-D bone models. The trapezial and metacarpal articular surfaces were manually delineated on scaled bone models, to remove the effect of size, and then were compared between sex, age, and health groups by using polar histograms of curvature and average curvature values. We found no sex differences, but significant age-group and health-group differences, in the articular surfaces of both bones. The older healthy subjects had higher curvature in the concave and lower curvature in the convex directions of both the trapezial and metacarpal saddles than the healthy young subjects. Subjects with early OA had significantly different metacarpal and trapezial articular shapes from healthy subjects. These findings suggest that aging and OA affect the articular shape of the CMC joint, but that, in contrast to previously held beliefs, inherent sex differences are not responsible for the higher incidence of CMC OA in women. PMID:24909332

  16. The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

    SciTech Connect

    Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

    2010-12-01

    Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score {>=}70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p < 0.005) and use of radiation only (p {<=} 0.001) were associated with inferior survival independent of other factors. Patient selection for CMT was affected by age ({>=}70, p < 0.001), comorbidity (severity index [SI]> 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p < 0.001) and SI (p < 0.001) compared with Groups 2 and 3. Group 3 patients were the oldest with the most unfavorable comorbidity profile. Comorbidity scores (SI >2; p = 0.006) and age ({>=}70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

  17. Modeling the Effects of Constant and Variable Temperatures on the Vital Rates of an Age-, Stage-, and Sex-Structured Population by Means of the SANDY Approach.

    PubMed

    Nachman, G; Gotoh, T

    2015-06-01

    We present a general and flexible mathematical model (called SANDY) that can be used to describe many biological phenomena, including the phenology of arthropods. In this paper, we demonstrate how the model can be fitted to vital rates (i.e., rates associated with development, survival, hatching, and oviposition) of the two-spotted spider mite (Tetranychus urticae (Koch)) exposed to different constant temperatures ranging from 15°C to 37.5°C. SANDY was incorporated into an age-, stage- and sex-structured dynamic model, which was fitted to cohort life-tables of T. urticae conducted at five constant temperatures (15, 20, 25, 30, and 35°C). Age- and temperature-dependent vital rates for the three main stages (eggs, immatures, and adults) constituting the life-cycle of mites were adequately described by the SANDY model. The modeling approach allows for simulating the growth of a population in a variable environment. We compared the predicted net reproductive rate (R0) and intrinsic rate of natural increase (rm) at fluctuating temperatures with empirical values obtained from life-table experiments conducted at temperatures that changed with a daily amplitude (±0, ±3, ±6, ±9, and ±12°C) around an average of 22°C. Results show that R0 decreases with increasing amplitude, while rm is more robust to variable temperatures. An advantage of SANDY is that the same simple mathematical expression can be applied to describe all the vital rates. Besides, the approach is not confined to modeling the influence of a single factor on population growth but allows for incorporating the combined effect of several limiting factors, provided that the combined effect of the factors is multiplicative.

  18. A Decade of Experience in Developing Preclinical Models of Advanced- or Early-Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic Chemotherapy, and the Tumor Microenvironment.

    PubMed

    Kerbel, Robert S

    2015-01-01

    The clinical circumstance of treating spontaneous metastatic disease, after resection of primary tumors, whether advanced/overt or microscopic in nature, is seldom modeled in mice and may be a major factor in explaining the frequent discordance between preclinical and clinical therapeutic outcomes where the trend is "overprediction" of positive results in preclinical mouse model studies. To evaluate this hypothesis, a research program was initiated a decade ago to develop multiple models of metastasis in mice, using variants of human tumor cell lines selected in vivo for enhanced spontaneous metastatic aggressiveness after surgical resection of established orthotopic primary tumors. These models have included breast, renal, and colorectal carcinomas; ovarian cancer (but without prior surgery); and malignant melanoma. They have been used primarily for experimental therapeutic investigations involving various antiangiogenic drugs alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The various translational studies undertaken have revealed a number of clinically relevant findings. These include the following: (i) the potential of metronomic chemotherapy, especially when combined with a vascular endothelial growth factor pathway targeting drug to successfully treat advanced metastatic disease; (ii) the development of relapsed spontaneous brain metastases in mice with melanoma or breast cancer whose systemic metastatic disease is successfully controlled for a period with a given therapy; (iii) foreshadowing the failure of adjuvant antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in contrast to the modest successes of antiangiogenic antibodies plus chemotherapy in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of angiogenesis as a determinant of intrinsic resistance or minimal responsiveness to antiangiogenic therapy

  19. Renal primitive neuroectodermal tumors.

    PubMed

    Bartholow, Tanner; Parwani, Anil

    2012-06-01

    Primitive neuroectodermal tumors exist as a part of the Ewing sarcoma/primitive neuroectodermal tumor family. These tumors most commonly arise in the chest wall and paraspinal regions; cases with a renal origin are rare entities, but have become increasingly reported in recent years. Although such cases occur across a wide age distribution, the average age for a patient with a renal primitive neuroectodermal tumor is the mid- to late 20s, with both males and females susceptible. Histologically, these tumors are characterized by pseudorosettes. Immunohistochemically, CD99 is an important diagnostic marker. Clinically, these are aggressive tumors, with an average 5-year disease-free survival rate of only 45% to 55%. Given that renal primitive neuroectodermal tumor bears many similarities to other renal tumors, it is important to review the histologic features, immunostaining profile, and genetic abnormalities that can be used for its correct diagnosis.

  20. Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma.

    PubMed

    Pedersen, Nicklas Juel; Jensen, David Hebbelstrup; Lelkaitis, Giedrius; Kiss, Katalin; Charabi, Birgitte; Specht, Lena; von Buchwald, Christian

    2017-02-14

    It is challenging to identify at diagnosis those patients with early oral squamous cell carcinoma (OSCC), who have a poor prognosis and those that have a high risk of harboring occult lymph node metastases. The aim of this study was to develop a standardized and objective digital scoring method to evaluate the predictive value of tumor budding. We developed a semi-automated image-analysis algorithm, Digital Tumor Bud Count (DTBC), to evaluate tumor budding. The algorithm was tested in 222 consecutive patients with early-stage OSCC and major endpoints were overall (OS) and progression free survival (PFS). We subsequently constructed and cross-validated a binary logistic regression model and evaluated its clinical utility by decision curve analysis. A high DTBC was an independent predictor of both poor OS and PFS in a multivariate Cox regression model. The logistic regression model was able to identify patients with occult lymph node metastases with an area under the curve (AUC) of 0.83 (95% CI: 0.78-0.89, P <0.001) and a 10-fold cross-validated AUC of 0.79. Compared to other known histopathological risk factors, the DTBC had a higher diagnostic accuracy. The proposed, novel risk model could be used as a guide to identify patients who would benefit from an up-front neck dissection.

  1. Analysis of the effect of age on the prognosis of breast cancer.

    PubMed

    Cluze, C; Colonna, M; Remontet, L; Poncet, F; Sellier, E; Seigneurin, A; Delafosse, P; Bossard, N

    2009-09-01

    To explore the effect of age at diagnosis on relative survival from breast cancer at different cancer stages and grades, using appropriate statistical modeling of time-varying and non-linear effects of that prognostic covariate. Data on 4,791 female invasive breast cancers diagnosed between 1990 and 1997 were obtained from a French cancer registry. The effect of age on relative survival was studied using an approach based on excess rate modeling. Different models testing non-linear and non-proportional effects of age were explored for each grade and each stage. In the whole population, the effect of age was not linear and varied with the time elapsed since diagnosis. When analyzing the different sub-groups according to grade and stage, age did not have a significant effect on relative survival in grade 1 or stage 3 tumors. In grade 2 and stage 4 tumors, the excess mortality rate increased with age, in a linear way. In grade 3 tumors, age was a time-dependent factor: older women had higher excess rates than younger ones during the first year after diagnosis whereas the inverse phenomenon was observed 5 years after diagnosis. Our findings suggest that when taking into account grade and stage, the time-varying impact of young age at diagnosis is limited to grade 3 tumors, without evidence of worst prognosis at 5 years for the youngest women.

  2. CNS and spinal tumors.

    PubMed

    Furtado, Andre D; Panigrahy, Ashok; Fitz, Charles R

    2016-01-01

    Primary CNS tumors consist of a diverse group of neoplasms originating from various cell types in the CNS. Brain tumors are the most common solid malignancy in children under the age of 15 years and the second leading cause of cancer death after leukemia. The most common brain neoplasms in children differ consistently from those in older age groups. Pediatric brain tumors demonstrate distinct patterns of occurrence and biologic behavior according to sex, age, and race. This chapter highlights the imaging features of the most common tumors that affect the child's CNS (brain and spinal cord).

  3. The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes.

    PubMed

    Ksiaa, Feryel; Ziadi, Sonia; Mokni, Moncef; Korbi, Sadok; Trimeche, Mounir

    2010-04-01

    JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

  4. HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy.

    PubMed

    Campbell, Marcia R; Amin, Dhara; Moasser, Mark M

    2010-03-01

    The human epidermal growth family (HER) of tyrosine kinase receptors underlies the pathogenesis of many types of human cancer. The oncogenic functions of three of the HER proteins can be unleashed through amplification, overexpression, or mutational activation. This has formed the basis for the development of clinically active targeted therapies. However, the third member HER3 is catalytically inactive, not found to be mutated or amplified in cancers, and its role and functions have remained shrouded in mystery. Recent evidence derived primarily from experimental models now seems to implicate HER3 in the pathogenesis of several types of cancer. Furthermore, the failure to recognize the central role of HER3 seems to underlie resistance to epidermal growth factor receptor (EGFR)- or HER2-targeted therapies in some cancers. Structural and biochemical studies have now greatly enhanced our understanding of signaling in the HER family and revealed the previously unrecognized activating functions embodied in the catalytically impaired kinase domain of HER3. This renewed interest and mechanistic basis has fueled the development of new classes of HER3-targeting agents for cancer therapy. However, identifying HER3-dependent tumors presents a formidable challenge and the success of HER3-targeting approaches depends entirely on the development and power of predictive tools.

  5. Stage IV and age over 45 years are the only prognostic factors of the International Prognostic Score for the outcome of advanced Hodgkin lymphoma in the Spanish Hodgkin Lymphoma Study Group series.

    PubMed

    Guisado-Vasco, Pablo; Arranz-Saez, Reyes; Canales, Miguel; Cánovas, Araceli; Garcia-Laraña, José; García-Sanz, Ramón; Lopez, Andrés; López, José Luis; Llanos, Marta; Moraleda, José Maria; Rodriguez, José; Rayón, Consuelo; Sabin, Pilar; Salar, Antonio; Marín-Niebla, Ana; Morente, Manuel; Sánchez-Godoy, Pedro; Tomás, José Francisco; Muriel, Alfonso; Abraira, Victor; Piris, Miguel A; Garcia, Juán F; Montalban, Carlos

    2012-05-01

    The International Prognostic Score (IPS) is the most widely used system to date for identifying risk groups for the outcome of patients with advanced Hodgkin lymphoma, although important limitations have been recognized. We analyzed the value of the IPS in a series of 311 patients with advanced classical Hodgkin lymphoma (cHL) (Ann Arbor stage III, IV or stage II with B symptoms and/or bulky masses) treated with first-line chemotherapy including adriamycin (adriamycin, bleomycin, vinblastine, dacarbazine [ABVD] or equivalent variants). In univariate and multivariate analyses, stage IV disease and age ≥ 45 years were the only factors with independent predictive significance for overall survival (OS) (p = 0.002 and p < 0.001, respectively). Stage IV was still significant for freedom from progression (FFP) (p = 0.001) and age ≥ 45 years was borderline significant (p = 0.058). IPS separates prognostic groups, as in the original publication, but this is mainly due to the high statistical significance of stage IV and age ≥ 45 years. Moreover, the combination of these two factors enables a simpler system to be constructed that separates groups with different FFP and OS. In conclusion, in our series, stage IV and age ≥ 45 years are the key prognostic factors for the outcome of advanced cHL.

  6. SU-E-J-266: Cone Beam Computed Tomography (CBCT) Inter-Scan and Inter-Observer Tumor Volume Variability Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-Small Cell Lung Cancer (NSCLC)

    SciTech Connect

    Hou, Y; Aileen, C; Kozono, D; Killoran, J; Wagar, M; Lee, S; Hacker, F; Aerts, H; Lewis, J; Mak, R

    2015-06-15

    Purpose: Quantification of volume changes on CBCT during SBRT for NSCLC may provide a useful radiological marker for radiation response and adaptive treatment planning, but the reproducibility of CBCT volume delineation is a concern. This study is to quantify inter-scan/inter-observer variability in tumor volume delineation on CBCT. Methods: Twenty earlystage (stage I and II) NSCLC patients were included in this analysis. All patients were treated with SBRT with a median dose of 54 Gy in 3 to 5 fractions. Two physicians independently manually contoured the primary gross tumor volume on CBCTs taken immediately before SBRT treatment (Pre) and after the same SBRT treatment (Post). Absolute volume differences (AVD) were calculated between the Pre and Post CBCTs for a given treatment to quantify inter-scan variability, and then between the two observers for a given CBCT to quantify inter-observer variability. AVD was also normalized with respect to average volume to obtain relative volume differences (RVD). Bland-Altman approach was used to evaluate variability. All statistics were calculated with SAS version 9.4. Results: The 95% limit of agreement (mean ± 2SD) on AVD and RVD measurements between Pre and Post scans were −0.32cc to 0.32cc and −0.5% to 0.5% versus −1.9 cc to 1.8 cc and −15.9% to 15.3% for the two observers respectively. The 95% limit of agreement of AVD and RVD between the two observers were −3.3 cc to 2.3 cc and −42.4% to 28.2% respectively. The greatest variability in inter-scan RVD was observed with very small tumors (< 5 cc). Conclusion: Inter-scan variability in RVD is greatest with small tumors. Inter-observer variability was larger than inter-scan variability. The 95% limit of agreement for inter-observer and inter-scan variability (∼15–30%) helps define a threshold for clinically meaningful change in tumor volume to assess SBRT response, with larger thresholds needed for very small tumors. Part of the work was funded by a Kaye

  7. Efficacy of Intensity Modulated Radiation Therapy After Surgery in Early Stage of Esophageal Carcinoma;

    ClinicalTrials.gov

    2016-07-30

    Esophageal Neoplasm; Esophageal Cancer TNM Staging Primary Tumor (T) T2; Esophageal Cancer TNM Staging Primary Tumor (T) T3; Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0; Esophageal Cancer TNM Staging Distal Metastasis (M) M0

  8. What Should You Ask Your Doctor about Lung Carcinoid Tumors?

    MedlinePlus

    ... Staging What Should You Ask Your Doctor About Lung Carcinoid Tumors? It is important to have honest, ... Your Doctor About Lung Carcinoid Tumors? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  9. Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB.

    PubMed

    Sharma, Sanjay; Dominguez, Ana Lucia; Lustgarten, Joseph

    2006-01-01

    It has been well established that there is a decline in immune function with age resulting in a diminished capacity to respond to infections or tumors. Although many studies have demonstrated the efficacy of autologous dendritic cells (DC) vaccines in stimulating an anti-tumor immune response in the young, almost none of these reports consider the effect that aging has on the immune system or test whether DC-vaccination is effective in old hosts. In this study we compared the efficacy of DC-vaccination in young and old mice. Our results showed that DC-vaccination in young animals induced an anti-tumor response resulting in approximately 60% tumor growth inhibition, while minimal protection was observed in old animals. DC vaccination plus rIL-2 further enhanced the anti-tumor response in young animals (approximately 70-75% inhibition), while ineffective in old animals. In contrast, co-administration of anti-OX-40 or anti-4-1BB mAbs vigorously enhanced the anti-tumor immune response in both young (approximately 85-90% inhibition) and old mice (approximately 70-75% inhibition). Our data indicate that although old mice have a decline in immune function, they have the capacity to develop strong anti-tumor responses as long as they are provided with efficient co-stimulation.

  10. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  11. The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas.

    PubMed

    Sunaoshi, Masaaki; Amasaki, Yoshiko; Hirano-Sakairi, Shinobu; Blyth, Benjamin J; Morioka, Takamitsu; Kaminishi, Mutsumi; Shang, Yi; Nishimura, Mayumi; Shimada, Yoshiya; Tachibana, Akira; Kakinuma, Shizuko

    2015-09-01

    Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age-at-exposure and their underlying mechanisms remain unclear. We assessed genome-wide DNA copy number and mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). Although T-cell lymphoma incidence was similar, loss of heterozygosity at Cdkn2a on chromosome 4 and at Ikaros on chromosome 11 was more frequent in the two older groups, while loss at the Pten locus on chromosome 19 was more frequent in the infant-irradiated group. Cdkn2a and Ikaros mutation/loss was a common feature of the young adult-irradiation group, with Ikaros frequently (50%) incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik12, which lacks two DNA binding zinc-finger domains). Conversely, Pten mutations were more frequent after early irradiation (60%) than after young adult-irradiation (30%). Homozygous Pten mutations occurred without DNA copy number change after irradiation starting in infancy, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Our findings demonstrate that while deletions on chromosomes 4 and 11 affecting Cdkn2a and Ikaros are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after irradiation from infancy suffer a second hit in Pten by mis-segregation or recombination. This is the first report showing an influence of age-at-exposure on genomic alterations of tumor suppressor genes and their relative involvement in radiation-induced T-cell lymphoma. These data are important for considering the risks

  12. Tumor suppressor SET9 guides the epigenetic plasticity of breast cancer cells and serves as an early-stage biomarker for predicting metastasis.

    PubMed

    Montenegro, M F; Sánchez-Del-Campo, L; González-Guerrero, R; Martínez-Barba, E; Piñero-Madrona, A; Cabezas-Herrera, J; Rodríguez-López, J N

    2016-11-24

    During the course of cancer progression, neoplastic cells undergo dynamic and reversible transitions between multiple phenotypic states, and this plasticity is enabled by underlying shifts in epigenetic regulation. Our results identified a negative feedback loop in which SET9 controls DNA methyltransferase-1 protein stability, which represses the transcriptional activity of the SET9 promoter in coordination with Snail. The modulation of SET9 expression in breast cancer cells revealed a connection with E2F1 and the silencing of SET9 was sufficient to complete an epigenetic program that favored epithelial-mesenchymal transition and the generation of cancer stem cells, indicating that SET9 plays a role in modulating breast cancer metastasis. SET9 expression levels were significantly higher in samples from patients with pathological complete remission than in samples from patients with disease recurrence, which indicates that SET9 acts as a tumor suppressor in breast cancer and that its expression may serve as a prognostic marker for malignancy.

  13. Impact of multiple caregiving roles on elevated depressed mood in early-stage breast cancer patients and same-age controls

    PubMed Central

    Bailey, Ellen H.; Pérez, Maria; Aft, Rebecca L.; Liu, Ying; Schootman, Mario; Jeffe, Donna B.

    2010-01-01

    The effect of caregiving roles on risk of elevated depressed mood over 12 months was examined in early-stage (0–IIA) breast cancer patients and same-aged women without breast cancer. Women were interviewed 4–6 weeks, 6 months, and 12 months following definitive surgical treatment (patients) or routine screening mammogram (controls). The Center for Epidemiologic Studies-Depression Scale was administered at each interview and dichotomized for analysis (<16 [little/no depressed mood] vs. ≥16 [elevated depressed mood]). Participants were categorized as having no caregiving responsibilities, care-giving for children or other persons, or caregiving for both children and others (multiple caregiving roles). Two multivariable marginal logistic regression models with repeated measures were fit (one each for patients and controls) to examine the effect of caregiving roles on elevated depressed mood, using generalized estimating equations to account for intra-individual correlations. Of 1096 participants (mean age 58; 76% white), 1019 with caregiving data were included in the analysis. Compared with baseline, patients with multiple caregiving roles (23/521 patients) were at increased risk of elevated depressed mood at 6 months (adjusted odds ratio [aOR], 7.20; 95% confidence interval [CI], 1.17–44.46; P = 0.034), and controls with multiple caregiving roles (15/498 controls) were at decreased risk of elevated depressed mood at 12-month follow-up (aOR, 0.12; 95% CI, 0.02–0.97; P = 0.047). Patients with multiple caregiving roles were more likely while controls were less likely to report elevated depressed mood over time, suggesting a need to identify patients with multiple caregiving roles early during their treatment. PMID:19936914

  14. Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS): Theory of a High-Sensitivity Methodology for the Detection of Early-Stage Tumors in Tissues

    NASA Astrophysics Data System (ADS)

    Choi, S.; Mandelis, A.; Guo, X.; Lashkari, B.; Kellnberger, S.; Ntziachristos, V.

    2015-06-01

    In the field of medical diagnostics, biomedical photoacoustics (PA) is a non-invasive hybrid optical-ultrasonic imaging modality. Due to the unique hybrid capability of optical and acoustic imaging, PA imaging has risen to the frontiers of medical diagnostic procedures such as human breast cancer detection. While conventional PA imaging has been mainly carried out by a high-power pulsed laser, an alternative technology, the frequency domain biophotoacoustic radar (FD-PAR) is under intensive development. It utilizes a continuous wave optical source with the laser intensity modulated by a frequency-swept waveform for acoustic wave generation. The small amplitude of the generated acoustic wave is significantly compensated by increased signal-to-noise ratio (several orders of magnitude) using matched-filter and pulse compression correlation processing in a manner similar to radar systems. The current study introduces the theory of a novel FD-PAR modality for ultra-sensitive characterization of functional information for breast cancer imaging. The newly developed theory of wavelength-modulated differential PA spectroscopy (WM-DPAS) detection has been introduced to address angiogenesis and hypoxia monitoring, two well-known benchmarks of breast tumor formation. Based on the WM-DPAS theory, this modality efficiently suppresses background absorptions and is expected to detect very small changes in total hemoglobin concentration and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. An experimental system design for the WM-DPAS is presented and preliminary single-ended laser experimental results were obtained and compared to a limiting case of the developed theoretical formalism.

  15. 2003-2013, a valuable study: Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in stage IV breast cancer.

    PubMed

    Lin, Mao; Liang, Shuzhen; Jiang, Feng; Xu, Jiongyuan; Zhu, Weibing; Qian, Wei; Hu, Yong; Zhou, Zhanchun; Chen, Jibing; Niu, Lizhi; Xu, Kecheng; Lv, Youyong

    2017-03-01

    Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. After the patients had received low-dose chemotherapy, those in the treatment group also received the DC-CIK therapy, which was repeated four times in a fortnight to form one cycle. At least three cycles of DC-CIK therapy were given. Immune function was measured in treatment group patients' sera. Disease-free survival (DFS) and Overall survival (OS) after the diagnosis of stage IV breast cancer was assessed after a 10-year follow-up. The result demonstrated that immune function is obviously enhanced after DC-CIK therapy. By Cox regression analysis, DC-CIK therapy reduced the risk of disease progression (p<0.01) with an increased OS (p<0.01). After low-dose chemotherapy, active immunization with DC-CIK immunotherapy is a potentially effective approach for the control of tumour growth in stage IV breast cancer patients.

  16. Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

    SciTech Connect

    Bogen, K T

    2007-05-11

    A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p pharmacokinetic and 2 harmacokinetic 2-stage

  17. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  18. Trends in 'cure' fraction from colorectal cancer by age and tumour stage between 1975 and 2000, using population-based data, Osaka, Japan.

    PubMed

    Ito, Yuri; Nakayama, Tomio; Miyashiro, Isao; Sugimoto, Tomoyuki; Ioka, Akiko; Tsukuma, Hideaki; Abdel-Rahman, Manar E; Rachet, Bernard

    2012-10-01

    Since the 1960s, Japan has experienced a striking increase in the incidence of colorectal cancer, now the second most common cancer in the country. Meanwhile, the management of colorectal cancer has changed dramatically with the implementation of, for example, screening, endoscopy and adjuvant chemotherapy. It is therefore of interest to monitor the long-term trends in population 'cure' in Japan. We analysed 33 885 colorectal cancer cases diagnosed between 1975 and 2000 in Osaka. We applied the multivariable mixture cure model to estimate cure fraction and median survival time (MST) for 'uncured' patients, by sex, age, stage, period at diagnosis and subsite. For colon cancer, the cure fraction increased by about 25%, while MST for the uncured was prolonged from 8 to 12 months. The cure fraction was 5% higher in men than in women, while MST was similar in both. The cure fraction also increased for localized and regional tumours. For rectal cancer, the cure fraction increased by about 25-30%, but remained lower than for colon cancer. From the late 1970s, the cure fraction for colorectal cancer increased dramatically due to better management of detection and care for colorectal cancer. This improvement was obtained at the cost of shorter MST for uncured patients.

  19. Age-related changes in protein metabolism of beech (Fagus sylvatica L.) seeds during alleviation of dormancy and in the early stage of germination.

    PubMed

    Ratajczak, Ewelina; Kalemba, Ewa M; Pukacka, Stanislawa

    2015-09-01

    The long-term storage of seeds generally reduces their viability and vigour. The aim of this work was to evaluate the effect of long-term storage on beech (Fagus sylvatica L.) seeds at optimal conditions, over 9 years, on the total and soluble protein levels and activity of proteolytic enzymes, including endopeptidases, carboxypeptidases and aminopeptidases, as well as free amino acid levels and protein synthesis, in dry seeds, after imbibition and during cold stratification leading to dormancy release and germination. The same analyses were conducted in parallel on seeds gathered from the same tree in the running growing season and stored under the same conditions for only 3 months. The results showed that germination capacity decreased from 100% in freshly harvested seeds to 75% in seeds stored for 9 years. The levels of total and soluble proteins were highest in freshly harvested seeds and decreased significantly during storage, these proportions were retained during cold stratification and germination of seeds. Significant differences between freshly harvested and stored seeds were observed in the activities of proteolytic enzymes, including endopeptidases, aminopeptidases and carboxypeptidases, and in the levels of free amino acids. The neosynthesis of proteins during dormancy release and in the early stage of seed germination was significantly weaker in stored seeds. These results confirm the importance of protein metabolism for seed viability and the consequences of its reduction during seed ageing.

  20. Dissociation of mitogenesis and late-stage promotion of tumor cell phenotype by phorbol esters: mitogen-resistant variants are sensitive to promotion.

    PubMed Central

    Colburn, N H; Wendel, E J; Abruzzo, G

    1981-01-01

    The JB-6 mouse epidermal cell line has been used as a model system for studying the mechanism of late-stage promoter-dependent preneoplastic progression. The studies reported here are concerned with determining whether there is a requirement for mitogenic stimulation in promotion of anchorage independence and tumorigenicity in JB-6 cells. Such a requirement would predict that variants selected for 12-O-tetradecanoylphorbol 13-acetate (TPA) mitogen resistance would also be promotion resistant. Promotion-responsive cell lines have been selected for resistance to TPA-induced mitogenic stimulation at plateau density by cotreatment with colchicine and removal of mitogen-responsive colchicine-detached cells. The selected TPA-resistant population of cells showed a mitogenic response that was diminished by a factor of four but showed no diminution in the promotion-of-anchorage-independence response to TPA. Mitogen-resistant clonal lines derived from the selected population fell into three phenotypic classes when assayed in soft agar: (i) anchorage-independent transformants; (ii) variants resistant to promotion of anchorage independence by TPA; and (iii) variants sensitive to promotion by TPA. The existence of the latter class (i.e., the mitogen-resistant promotable variants) indicates a lack of obligatory causal relationship between TPa-induced mitogenesis and late-stage promotion and, thereby suggests that the two events can be dissociated. Images PMID:6947266

  1. Habits of sun exposure and risk of malignant melanoma: an analysis of incidence rates in Norway 1955-1977 by cohort, sex, age, and primary tumor site

    SciTech Connect

    Magnus, K.

    1981-11-15

    Incidence data on malignant melanoma of the skin in Norway from 1955-1977, comprising a total of 5108 new cases, were analyzed according to cohort, sex, age, and primary tumor site. A continuous increase in incidence of approximately 7% per year was observed for both sexes during the study period. For trunk and lower limb melanomas, the increase and cohort variations in incidence were much greater than for face and neck melanoma. A difference between these site groups was also observed in the shape of the cohort curves of age-specific rates. This indicated that the trend in carcinogenic exposure through life was different for the face--neck and the trunk--lower limb. For the generations born 1930-1949, the incidence of malignant melanoma per area unit of skin was greater for the trunk and lower limb than for the face--neck. It is suggested that not only the cumulated dose, but also the intensity of solar radiation may be significant in the cause of malignant melanoma.

  2. Coping and quality of life in patients with skin tumors in the follow-up stage: The mediating role of body image and psychological morbidity.

    PubMed

    Pereira, M Graça; Baia, Vânia; Machado, José C

    2016-01-01

    This study examined the relationships between coping style, body image, psychological morbidity, and quality of life. A total of 58 patients who were diagnosed with skin tumors, had been submitted to surgery, and were in the follow-up phase answered the following instruments: dermatology life quality index (DLQI), hospital anxiety and depression scales (HADS), body image scale (BIS), and the mini mental adjustment to cancer scale (Mini-MAC). The results showed that patients with a higher use of the coping styles of helplessness/hopelessness, anxious preoccupation, and cognitive avoidance reported a worse quality of life. Body image mediated the relationship between the coping styles of anxious preoccupation, helplessness/hopelessness, and quality of life. Psychological morbidity mediated the relationship between helplessness/hopelessness and quality of life. Therefore, even in the follow-up phase, it is important that health professionals are aware of the patient's emotional distress and body image to identify those at a higher risk of having a poorer quality of life.

  3. Non-randomized confirmatory trial of modified radical hysterectomy for patients with tumor diameter 2 cm or less FIGO Stage IB1 uterine cervical cancer: Japan Clinical Oncology Group Study (JCOG1101).

    PubMed

    Kunieda, Futoshi; Kasamatsu, Takahiro; Arimoto, Takahide; Onda, Takashi; Toita, Takafumi; Shibata, Taro; Fukuda, Haruhiko; Kamura, Toshiharu

    2015-01-01

    A non-randomized confirmatory trial was started in Japan to evaluate the efficacy of modified radical hysterectomy in patients with tumor diameter 2 cm or less FIGO Stage IB1 uterine cervical cancer, for which the current standard is radical hysterectomy. This study began in January 2013 and a total of 240 patients will be accrued from 37 institutions within 3 years. The primary endpoint is 5-year survival. The secondary endpoints are overall survival, relapse-free survival, local relapse-free survival, percent completion of modified radical hysterectomy, percent local relapse, percent pathological parametrial involvement, days until self-urination and residual urine disappearance, blood loss, operation time, percent post-operative radiation therapy, adverse events and severe adverse events. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000009726 (http://www.umin.ac.jp/ctr/).

  4. Inhibitory effect of the rhizomes of Alpinia officinarum on TPA-induced inflammation and tumor promotion in two-stage carcinogenesis in mouse skin.

    PubMed

    Yasukawa, Ken; Sun, Yi; Kitanaka, Susumu; Tomizawa, Naoyuki; Miura, Motofumi; Motohashi, Shigeyasu

    2008-07-01

    The methanol extract of galangal (the rhizomes of Alpinia officinarum L.) exhibited remarkable antitumor-promoting activity on an in vivo two-stage carcinogenesis test of mice using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. Seven diarylheptanoids (1-7) were isolated and identified from the active fraction of the methanol extracts of the galangal. These compounds, 1-7, were evaluated for their inhibitory effects on TPA-induced inflammation (1 microg/ear) in mice. These compounds (1-7) tested showed marked anti-inflammatory effects, with a 50% inhibitory dose of 0.8-2.7 micromol/ear.

  5. Tuberous sclerosis complex 1: an epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice.

    PubMed

    Kladney, Raleigh D; Cardiff, Robert D; Kwiatkowski, David J; Chiang, Gary G; Weber, Jason D; Arbeit, Jeffrey M; Lu, Zhi Hong

    2010-11-01

    The phosphoinositide 3-kinase (PI3K) pathway regulates mammalian cell growth, survival, and motility and plays a major pathogenetic role in human prostate cancer (PCa). However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)-mediated cell growth signal transduction in PCa have yet to be elucidated in detail. Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1), a potent negative regulator of mTORC1 signaling. Epithelial inactivation was not immediately tumorigenic, but Tsc1-deficient mice developed prostatic intraepithelial neoplasia (mPIN) in lateral and anterior prostates by 6 months of age, with increasing disease penetrance over time. Lateral prostate lesions in 16- to 22-month-old mutant mice progressed to two types of more advanced lesions, adenomatous gland forming lesion (Type 1) and atypical glands embedded in massively expanded reactive stroma (Type 2). Both Type 1 and Type 2 lesions contained multiple foci of microinvasive carcinoma. Epithelial neoplastic and atypical stromal lesions persisted despite 4 weeks of RAD001 chemotherapy. Rapalogue resistance was not due to AKT or extracellular signal-regulated kinase 1/2 activation. Expression of the homeobox gene Nkx3.1 was lost in Tsc1-deficient mPIN, and it cooperated with TSC1 loss in mPIN initiation in doubly mutant Tsc1:Nkx3.1 prostatic epithelial knockout mice. Thus, TSC1 inactivation distal to PI3K and AKT activation is sufficient to activate a molecular signaling cascade producing prostatic neoplasia and focal carcinogenesis.