Primary primitive neuroectodermal tumor of the cervix

PubMed Central

Li, Bo; Ouyang, Ling; Han, Xue; Zhou, Yang; Tong, Xin; Zhang, Shulang; Zhang, Qingfu

2013-01-01

Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy. PMID:23836982

Promotion of Tumor-Initiating Cells in Primary and Recurrent Breast Tumors

DTIC Science & Technology

2014-10-01

confer stemness . We hypothesize that inhibition of IKK/NF-κB will reduce or eliminate breast camcer TICs, blocking tumorigenesis. Furthermore, we...Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011 Oct;121(10):3804-9. Review...cells and sub- population of cells termed cancer stem cells or tumor-initiating cells (TICs).1 The primary characteristic of TICs is their ability to

Primary malignant small bowel tumors: an atypical abdominal emergency.

PubMed Central

Mitchell, K. J.; Williams, E. S.; Leffall, L. D.

1995-01-01

Primary malignant tumors of the small bowel are uncommon in the United States. They comprise less than 1% of all gastrointestinal malignancies, with an incidence of 2200 cases per year. The clinical presentation of small bowel tumors is frequently insidious and often overlooked by physicians. The low incidence and lack of pathognomonic symptoms are the reasons that the early diagnosis of malignant small bowel tumor is uncommon. To better understand the clinical presentation, diagnostic evaluation, management, and outcome, a review of Howard University patients with primary malignant small bowel tumors between 1970 and 1990 was conducted. Our experience concurs with the reported literature and supports the conclusion that a high index of suspicion is necessary. The diagnosis of a malignant small bowel tumor should be considered in patients with vague chronic abdominal complaints. Images Figure 1 Figure 2 PMID:7752280

Clinical presentation, diagnosis, and pharmacotherapy of patients with primary brain tumors.

PubMed

Newton, H B; Turowski, R C; Stroup, T J; McCoy, L K

1999-01-01

To briefly review the clinical presentation and diagnosis of patients with primary brain tumors, followed by an in-depth survey of the pertinent pharmacotherapy. A detailed search of the neurologic, neurosurgical, and oncologic literature for basic science research, clinical studies, and review articles related to chemotherapy and pharmacotherapy of primary brain tumors. Relevant studies on tissue culture systems, animals, and humans examining the mechanisms of action, pharmacokinetics, clinical pharmacology, and treatment results of chemotherapeutic agents for primary brain tumors. In addition, studies of pharmacologic agents administered for supportive care and symptom control are reviewed. Primary brain tumors derive from cells within the intracranial cavity and generally present with headache, seizure activity, cognitive changes, and weakness. They are diagnosed most efficiently with magnetic resonance imaging. After diagnosis, the most common supportive medications include corticosteroids, gastric acid inhibitors, and anticonvulsants. Chemotherapy is adjunctive treatment for patients with malignant tumors and selected recurrent or progressive benign neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents such as the nitrosoureas, procarbazine, cisplatin, and carboplatin. Other agents used include cyclophosphamide, methotrexate, vincristine, and etoposide. Angiogenesis inhibitors and gene therapy comprise some of the novel therapeutic strategies under investigation. The efficacy of chemotherapy for primary brain tumors remains modest. Novel agents must be discovered that are more specific and attack tumor cells at the molecular level of tumorigenesis. Furthermore, strategies must be developed to counteract the pervasive problem of brain tumor chemoresistance.

Single-cell sequencing deciphers a convergent evolution of copy number alterations from primary to circulating tumor cells.

PubMed

Gao, Yan; Ni, Xiaohui; Guo, Hua; Su, Zhe; Ba, Yi; Tong, Zhongsheng; Guo, Zhi; Yao, Xin; Chen, Xixi; Yin, Jian; Yan, Zhao; Guo, Lin; Liu, Ying; Bai, Fan; Xie, X Sunney; Zhang, Ning

2017-08-01

Copy number alteration (CNA) is a major contributor to genome instability, a hallmark of cancer. Here, we studied genomic alterations in single primary tumor cells and circulating tumor cells (CTCs) from the same patient. Single-nucleotide variants (SNVs) in single cells from both samples occurred sporadically, whereas CNAs among primary tumor cells emerged accumulatively rather than abruptly, converging toward the CNA in CTCs. Focal CNAs affecting the MYC gene and the PTEN gene were observed only in a minor portion of primary tumor cells but were present in all CTCs, suggesting a strong selection toward metastasis. Single-cell structural variant (SV) analyses revealed a two-step mechanism, a complex rearrangement followed by gene amplification, for the simultaneous formation of anomalous CNAs in multiple chromosome regions. Integrative CNA analyses of 97 CTCs from 23 patients confirmed the convergence of CNAs and revealed single, concurrent, and mutually exclusive CNAs that could be the driving events in cancer metastasis. © 2017 Gao et al.; Published by Cold Spring Harbor Laboratory Press.

A multicenter study of primary brain tumor incidence in Australia (2000–2008)

PubMed Central

Dobes, Martin; Shadbolt, Bruce; Khurana, Vini G.; Jain, Sanjiv; Smith, Sarah F.; Smee, Robert; Dexter, Mark; Cook, Raymond

2011-01-01

There are conflicting reports from Europe and North America regarding trends in the incidence of primary brain tumor, whereas the incidence of primary brain tumors in Australia is currently unknown. We aimed to determine the incidence in Australia with age-, sex-, and benign-versus-malignant histology-specific analyses. A multicenter study was performed in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), which has a combined population of >7 million with >97% rate of population retention for medical care. We retrospectively mined pathology databases servicing neurosurgical centers in NSW and ACT for histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008. Data were weighted for patient outflow and data completeness. Incidence rates were age standardized and trends analyzed using joinpoint analysis. A weighted total of 7651 primary brain tumors were analyzed. The overall US-standardized incidence of primary brain tumors was 11.3 cases 100 000 person-years (±0.13; 95% confidence interval, 9.8–12.3) during the study period with no significant linear increase. A significant increase in primary malignant brain tumors from 2000 to 2008 was observed; this appears to be largely due to an increase in malignant tumor incidence in the ≥65-year age group. This collection represents the most contemporary data on primary brain tumor incidence in Australia. Whether the observed increase in malignant primary brain tumors, particularly in persons aged ≥65 years, is due to improved detection, diagnosis, and care delivery or a true change in incidence remains undetermined. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence that can be independent of multiple interstate cancer registries. PMID:21727214

Systemic treatment and primary tumor location in patients with metastatic colorectal cancer.

PubMed

Antoniou, Efstathios; Andreatos, Nikolaos; Margonis, Georgios A; Papalois, Apostolos; Wang, Jaeyun; Damaskos, Christos; Garmpis, Nikolaos; Buettner, Stefan; Deshwar, Amar; Pappas, Vasilios; Weiss, Matthew J; Pawlik, Timothy M; Pikoulis, Emmanouel

2017-01-01

Tumor location (right-sided vs. left-sided) is known to exert a significant influence on the prognosis of primary colorectal cancer (CRC). Given the genetic continuity between primary and metastatic lesions, we aimed to summarize the existing literature on the prognostic implications of primary tumor site as well as to examine the response to chemotherapy by primary tumor location in patients with metastatic CRC (mCRC). A structured review of the literature was performed between 6/1/2016-7/1/2016 using the Pubmed database. Original research articles published between 1/1/2000- 07/01/2016 were considered eligible. The primary endpoints were overall survival (OS)/ progression free survival (PFS) and response to systemic treatment in patients with mCRC. Eleven studies were included. Tumor site was a strong independent predictor of worse OS/PFS in 9 studies, with right-sided tumors having worse prognosis in all cases. Furthermore, 6 studies demonstrated an inferior response to systemic treatment or worse prognosis following the administration of specific regimens among patients with right-sided cancers. As such, there is significant evidence that right-sided lesions are associated with poor outcomes and resistance to systemic treatment. Consequently, primary tumor location should be a consideration, when the administration of systemic therapy is contemplated in mCRC.

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

PubMed

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.

PubMed

Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2018-05-25

Estrogen receptor, coded by the ESR1 gene, is highly expressed in epithelial ovarian cancer. ESR1 gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR1 methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR1 methylation status in primary tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR1 methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 primary tumors) and group B (n = 53 primary tumors and 50 corresponding plasma samples). ESR1 was found methylated in both groups of primary tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR1. A significant agreement for ESR1 methylation was observed between primary tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR1 methylation in primary tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR1 methylation in plasma ctDNA of patients with HGSC. The agreement between ESR1 methylation in primary tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR1 methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Outcomes After Surgical Resection of Primary Non-Myxoma Cardiac Tumors

PubMed Central

Boyacıoğlu, Kamil; Ak, Adnan; Dönmez, Arzu Antal; Çayhan, Burçin; Aksüt, Mehmet; Tunçer, Mehmet Altuğ

2018-01-01

Objective Primary cardiac tumors are rare lesions with different histological type. We reviewed our 17 years of experience in the surgical treatment and clinical results of primary non-myxoma cardiac tumors. Methods Between July 2000 and February 2017, 21 patients with primary cardiac tumor were surgically treated in our institution. The tumors were categorized as benign non-myxomas and malignants. Data including the demographic characteristics, details of the tumor histology and grading, cardiac medical and surgical history, surgical procedure of the patients were obtained from the hospital database. Results Eleven patients were diagnosed with benign non-myxoma tumor (male/female:7/4), ranging in age from 10 days to 74 years (mean age 30.9±26.5 years). Papillary fibroelastoma was the most frequent type (63.6%). There were two early deaths in benign group (all were rhabdomyoma), and mortality rate was 18%. The mean follow-up period was 69.3±58.7 months (range, 3 to 178 months). All survivals in benign group were free of tumor-related symptoms and tumor relapses. Ten patients were diagnosed with malignant tumor (sarcoma/lymphoma:8/2, male/female:3/7), ranging in age from 14 years to 73 years (mean age 44.7±18.9 years). Total resection could be done in only three (30%) patients. The mean follow-up period was 18.7±24.8 months (range, 0-78 months). Six patients died in the first 10 months. Conclusion Complete resection of the cardiac tumors, whenever possible, is the main goal of surgery. Surgical resection of benign cardiac tumors is safe, usually curative and provides excellent long-term prognosis. On the contrary, malignant cardiac tumors still remain highly lethal. PMID:29898146

Bilateral maxillary brown tumors in a patient with primary hyperparathyroidism: Report of a rare entity and review of literature

PubMed Central

Soundarya, N; Sharada, P; Prakash, Nilima; Pradeep, GL

2011-01-01

Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to hyperparathyroidism, resulting in a local destructive phenomenon. The classical “brown tumor” is commonly seen in ends of long bones, the pelvis and ribs. Facial involvement is rare and, when present, usually involves the mandible. We report a case of 60-year-old male with a rare initial presentation of primary hyperparathyroidism with bilateral maxillary brown tumors. The present case represents the third report of the bilateral maxillary brown tumors in a patient with primary hyperparathyroidism. Differential diagnosis is important for the right treatment choice. It should exclude other giant cell lesions that affect the maxillae. PMID:21731279

[Gastrointestinal stromal tumor with primary hepatic unique location--clinical case].

PubMed

Alecu, L; Tulin, A; Ursut, Beatrice; Ursut, B; Oproiu, Al; Obrocea, F; Ionescu, M

2011-01-01

The gastrointestinal stromal tumors are mesenchymal tumors whose primary extradigestive location is very rare (less than 10% primary liver localization). We present a clinical case of primary hepatic location of GIST in a 28 year-old patient. The discovery of this tumor is a chance, the patient presenting for non-specific dyspeptic syndrome and epigastralgia. During the presentation an abdominal ultrasound is performed which identifies an whell-delineated hepatic mass - 5/4 cm. Clinical and paraclinical investigations (CT, EDS, EDI, examination of the intestinal lumen with the videocapsula), confirm the diagnosis of unique hepatic mass of segments III-IV. The diagnosis is confirmed intraoperatory and we perform an atypical liver resection of segments III-IV (with 1 cm safety-margin). The histopatologic exam: GIST.

Strategy in the Surgical Treatment of Primary Spinal Tumors

PubMed Central

Williams, Richard; Foote, Matthew; Deverall, Hamish

2012-01-01

Primary spine tumors are rare, accounting for only 4% of all tumors of the spine. A minority of the more common primary benign lesions will require surgical treatment, and most amenable malignant lesions will proceed to attempted resection. The rarity of malignant primary lesions has resulted in a paucity of historical data regarding optimal surgical and adjuvant treatment and, although we now derive benefit from standardized guidelines of overall care, management of each neoplasm often proceeds on a case-by-case basis, taking into account the individual characteristics of patient operability, tumor resectability, and biological potential. This article aims to provide an overview of diagnostic techniques, staging algorithms and the authors' experience of surgical treatment alternatives that have been employed in the care of selected benign and malignant lesions. Although broadly a review of contemporary management, it is hoped that the case illustrations given will serve as additional “arrows in the quiver” of the treating surgeon. PMID:24353976

Pancreatic islet cell tumor metastasis in multiple endocrine neoplasia type 1: correlation with primary tumor size.

PubMed

Lowney, J K; Frisella, M M; Lairmore, T C; Doherty, G M

1998-12-01

Islet cell tumor (ICT) metastasis is one of the potentially lethal outcomes of multiple endocrine neoplasia type 1 (MEN 1). Management of ICT in patients with MEN 1 is controversial; some advocate resection based on biochemical evidence of progression, whereas others use tumor size to predict the risk of metastasis and the need for resection. This study correlates the size of primary ICT with the presence of metastases. Forty-eight patients with MEN 1 with ICT, from 34 kindreds followed up in our multiple endocrine neoplasia program, were evaluated; 43 of the 48 have been explored for ICT. Metastases to the lymph nodes and liver were documented. Thirty-three percent of patients with pancreatic tumors less than 1 cm in greatest diameter had metastatic disease at surgery and in follow-up, whereas 34.8% of patients with tumors greater than 2 cm in diameter had metastases to lymph nodes or liver. The 2 patients with liver metastases each had primary tumors greater than 2 cm. Follow-up revealed subsequent metastasis in 1 patient. The size of primary tumors in MEN 1 does not correlate with metastatic potential. This is not a good criterion for exploration. Continued follow-up of these patients will be necessary to define the effect of operation on the course of ICT in MEN 1.

Bayesian pretest probability estimation for primary malignant bone tumors based on the Surveillance, Epidemiology and End Results Program (SEER) database.

PubMed

Benndorf, Matthias; Neubauer, Jakob; Langer, Mathias; Kotter, Elmar

2017-03-01

In the diagnostic process of primary bone tumors, patient age, tumor localization and to a lesser extent sex affect the differential diagnosis. We therefore aim to develop a pretest probability calculator for primary malignant bone tumors based on population data taking these variables into account. We access the SEER (Surveillance, Epidemiology and End Results Program of the National Cancer Institute, 2015 release) database and analyze data of all primary malignant bone tumors diagnosed between 1973 and 2012. We record age at diagnosis, tumor localization according to the International Classification of Diseases (ICD-O-3) and sex. We take relative probability of the single tumor entity as a surrogate parameter for unadjusted pretest probability. We build a probabilistic (naïve Bayes) classifier to calculate pretest probabilities adjusted for age, tumor localization and sex. We analyze data from 12,931 patients (647 chondroblastic osteosarcomas, 3659 chondrosarcomas, 1080 chordomas, 185 dedifferentiated chondrosarcomas, 2006 Ewing's sarcomas, 281 fibroblastic osteosarcomas, 129 fibrosarcomas, 291 fibrous malignant histiocytomas, 289 malignant giant cell tumors, 238 myxoid chondrosarcomas, 3730 osteosarcomas, 252 parosteal osteosarcomas, 144 telangiectatic osteosarcomas). We make our probability calculator accessible at http://ebm-radiology.com/bayesbone/index.html . We provide exhaustive tables for age and localization data. Results from tenfold cross-validation show that in 79.8 % of cases the pretest probability is correctly raised. Our approach employs population data to calculate relative pretest probabilities for primary malignant bone tumors. The calculator is not diagnostic in nature. However, resulting probabilities might serve as an initial evaluation of probabilities of tumors on the differential diagnosis list.

Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

PubMed Central

Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

2014-01-01

The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

Clinical significance of tumor cavitation in surgically resected early-stage primary lung cancer.

PubMed

Tomizawa, Kenji; Shimizu, Shigeki; Ohara, Shuta; Fujino, Toshio; Nishino, Masaya; Sesumi, Yuichi; Kobayashi, Yoshihisa; Sato, Katsuaki; Chiba, Masato; Shimoji, Masaki; Suda, Kenichi; Takemoto, Toshiki; Mitsudomi, Tetsuya

2017-10-01

The prognostic impact of tumor cavitation is unclear in patients with early-stage primary lung cancer. The aim of the present study was to examine the clinicopathological features and prognoses of patients with pathological stage I-IIA (p-stage I-IIA) primary lung cancers harboring tumor cavitation. This study was conducted according to the eighth edition of the TNM classification for lung cancer. We examined 602 patients with p-stage I-IIA primary lung cancer out of 890 patients who underwent pulmonary resection from January 2007 through March 2014 and searched for the presence of tumor cavitation, which is defined as the presence of air space within the primary tumor. A total of 59 out of the 602 patients had tumor cavitation (10%). Compared with patients without tumor cavitation, those with tumor cavitation had a significantly higher frequency of the following characteristics: high serum carcinoembryonic antigen (CEA) level (≥5ng/ml, p=0.027), interstitial pneumonia (p=0.0001), high SUVmax value on FDG-PET scan (≥4.2, p=0.023), tumors located in the lower lobe (p=0.024), large tumor size (>3cm, p=0.002), vascular invasion (66% vs 17%, p<0.0001) and non-adenocarcinoma histology (p=0.025). The overall survival period of patients with tumor cavitation was significantly shorter than that of patients without tumor cavitation (log-rank test: p<0.0001, 5-year OS rate: 56% vs 81%). Tumor cavitation was found to be an independent and significant factor associated with poor prognosis in the multivariate analysis (hazard ratio: 1.76, 95% confidence interval: 1.02-3.10, p=0.042). Tumor cavitation is an independent factor for poor prognosis in patients with resected p-stage I-IIA primary lung cancer. Based on our analyses, patients with tumor cavitation should be regarded as a separate cohort that requires more intensive follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

PubMed

Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

2013-10-01

Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice.

PubMed

Xu, Chengming; Ruan, Banjun; Jiang, Yinghao; Xue, Ting; Wang, Zhenyu; Lu, Huanyu; Wei, Ming; Wang, Shan; Ye, Zicheng; Zhai, Dongsheng; Wang, Li; Lu, Zifan

2017-06-24

Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation. Copyright © 2017 Elsevier Inc. All rights reserved.

Top 50 most cited articles on primary tumors of the spine.

PubMed

Alan, Nima; Cohen, Jonathan; Ozpinar, Alp; Agarwal, Nitin; Kanter, Adam S; Okonkwo, David O; Hamilton, D Kojo

2017-08-01

Citation analysis was performed in order to identify the top 50 most cited articles pertaining to the field of primary spinal tumors. This collection of articles highlights important trends in the neurosurgical literature. We searched the Thomson Reuters Web of Knowledge in order to identify articles pertaining to primary tumors of the spine. Impertinent articles were removed. The top 50 most cited articles were identified. Thereafter, article characteristics were determined including article type, article topic, level of evidence, and citation rate. The selected articles were published between 1951 and 2008. The most productive year was 1997 with 6 publications. The top 50 articles were published in twenty-two different journals, most commonly in Neurosurgery (12), Journal of Neurosurgery (8), and Spine (6). The most frequently cited article was by Tomita et al. written in 1997 which described total en bloc spondylectomy as a novel surgical technique in management of primary tumors of the vertebral column. We identified the 50 most-cited articles in the field of primary spinal tumors. This collection of articles serves as a reference for recognizing impactful studies in the field. Copyright © 2017. Published by Elsevier Ltd.

Primary yolk sac tumor of the urachus.

PubMed

Romero-Rojas, Alfredo Ernesto; Messa-Botero, Oscar Alberto; Melo-Uribe, Mario Alexander; Díaz-Pérez, Julio Alexander; Chinchilla-Olaya, Sandra Isabel

2011-10-01

Neoplasms originating from the urachus are rare. The most common urachal malignancy is adenocarcinoma, whereas extragonadal germ cell tumors, primarily of the urachus, are an extremely rare finding. To describe a primary yolk sac tumor (YST) of the urachus in an adult. A 44-year-old woman presented with 6 months of pelvic pain associated with a sensation of progressive mass growth. At the time of tumor resection, the tumor was found to be attached by a pedicle to the dome of the bladder, with no injury to the adjacent organs. Pathological study showed a neoplasm with epithelioid cells, pseudocysts, a myxomatous background, and Schiller-Duval body formations. Immunohistochemistry stains showed positivity to AE1/AE3, α-1-fetoprotein, and α-1-antitrypsin and negativity to other markers. An unusual case of a YST in the urachus is presented. This is the first reported adult case based on the authors' bibliographic search.

The degree of intratumor mutational heterogeneity varies by primary tumor sub-site

PubMed Central

Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I.; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B.; Grandis, Jennifer Rubin; Thomas, Sufi Mary

2016-01-01

In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies. PMID:27034009

The degree of intratumor mutational heterogeneity varies by primary tumor sub-site.

PubMed

Ledgerwood, Levi G; Kumar, Dhruv; Eterovic, Agda Karina; Wick, Jo; Chen, Ken; Zhao, Hao; Tazi, Loubna; Manna, Pradip; Kerley, Spencer; Joshi, Radhika; Wang, Lin; Chiosea, Simion I; Garnett, James David; Tsue, Terance Ted; Chien, Jeremy; Mills, Gordon B; Grandis, Jennifer Rubin; Thomas, Sufi Mary

2016-05-10

In an era where mutational profiles inform treatment options, it is critical to know the extent to which tumor biopsies represent the molecular profile of the primary and metastatic tumor. Head and neck squamous cell carcinoma (HNSCC) arise primarily in the mucosal lining of oral cavity and oropharynx. Despite aggressive therapy the 5-year survival rate is at 50%. The primary objective of this study is to characterize the degree of intratumor mutational heterogeneity in HNSCC. We used multi-region sequencing of paired primary and metastatic tumor DNA of 24 spatially distinct samples from seven patients with HNSCC of larynx, floor of the mouth (FOM) or oral tongue. Full length, in-depth sequencing of 202 genes implicated in cancer was carried out. Larynx and FOM tumors had more than 69.2% unique SNVs between the paired primary and metastatic lesions. In contrast, the oral tongue HNSCC had only 33.3% unique SNVs across multiple sites. In addition, HNSCC of the oral tongue had fewer mutations than larynx and FOM tumors. These findings were validated on the Affymetrix whole genome 6.0 array platform and were consistent with data from The Cancer Genome Atlas (TCGA). This is the first report demonstrating differences in mutational heterogeneity varying by subsite in HNSCC. The heterogeneity within laryngeal tumor specimens may lead to an underestimation of the genetic abnormalities within tumors and may foster resistance to standard treatment protocols. These findings are relevant to investigators and clinicians developing personalized cancer treatments based on identification of specific mutations in tumor biopsies.

Primary Tumor and MEF Cell Isolation to Study Lung Metastasis.

PubMed

Dong, Shengli; Maziveyi, Mazvita; Alahari, Suresh K

2015-05-20

In breast tumorigenesis, the metastatic stage of the disease poses the greatest threat to the affected individual. Normal breast cells with altered genotypes now possess the ability to invade and survive in other tissues. In this protocol, mouse mammary tumors are removed and primary cells are prepared from tumors. The cells isolated from this procedure are then available for gene profiling experiments. For successful metastasis, these cells must be able to intravasate, survive in circulation, extravasate to distant organs, and survive in that new organ system. The lungs are the typical target of breast cancer metastasis. A set of genes have been discovered that mediates the selectivity of metastasis to the lung. Here we describe a method of studying lung metastasis from a genetically engineered mouse model.. Furthermore, another protocol for analyzing mouse embryonic fibroblasts (MEFs) from the mouse embryo is included. MEF cells from the same animal type provide a clue of non-cancer cell gene expression. Together, these techniques are useful in studying mouse mammary tumorigenesis, its associated signaling mechanisms and pathways of the abnormalities in embryos.

KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue.

PubMed

Mostert, Bianca; Jiang, Yuqiu; Sieuwerts, Anieta M; Wang, Haiying; Bolt-de Vries, Joan; Biermann, Katharina; Kraan, Jaco; Lalmahomed, Zarina; van Galen, Anne; de Weerd, Vanja; van der Spoel, Petra; Ramírez-Moreno, Raquel; Verhoef, Cornelis; Ijzermans, Jan N M; Wang, Yixin; Gratama, Jan-Willem; Foekens, John A; Sleijfer, Stefan; Martens, John W M

2013-07-01

Although anti-EGFR therapy has established efficacy in metastatic colorectal cancer, only 10-20% of unselected patients respond. This is partly due to KRAS and BRAF mutations, which are currently assessed in the primary tumor. To improve patient selection, assessing mutation status in circulating tumor cells (CTCs), which possibly better represent metastases than the primary tumor, could be advantageous. We investigated the feasibility of KRAS and BRAF mutation detection in colorectal CTCs by comparing three sensitive methods and compared mutation status in matching primary tumor, liver metastasis and CTCs. CTCs were isolated from blood drawn from 49 patients before liver resection using CellSearch™. DNA and RNA was isolated from primary tumors, metastases and CTCs. Mutations were assessed by co-amplification at lower denaturation temperature-PCR (Transgenomic™), real-time PCR (EntroGen™) and nested Allele-Specific Blocker (ASB-)PCR and confirmed by Sanger sequencing. In 43 of the 49 patients, tissue RNA and DNA was of sufficient quantity and quality. In these 43 patients, discordance between primary and metastatic tumor was 23% for KRAS and 7% for BRAF mutations. RNA and DNA from CTCs was available from 42 of the 43 patients, in which ASB-PCR was able to detect the most mutations. Inconclusive results in patients with low CTC counts limited the interpretation of discrepancies between tissue and CTCs. Determination of KRAS and BRAF mutations in CTCs is challenging but feasible. Of the tested methods, nested ASB-PCR, enabling detection of KRAS and BRAF mutations in patients with as little as two CTCs, seems to be superior. Copyright © 2012 UICC.

Quantitative Primary Tumor Indocyanine Green Measurements Predict Osteosarcoma Metastatic Lung Burden in a Mouse Model.

PubMed

Fourman, Mitchell S; Mahjoub, Adel; Mandell, Jon B; Yu, Shibing; Tebbets, Jessica C; Crasto, Jared A; Alexander, Peter E; Weiss, Kurt R

2018-03-01

Current preclinical osteosarcoma (OS) models largely focus on quantifying primary tumor burden. However, most fatalities from OS are caused by metastatic disease. The quantification of metastatic OS currently relies on CT, which is limited by motion artifact, requires intravenous contrast, and can be technically demanding in the preclinical setting. We describe the ability for indocyanine green (ICG) fluorescence angiography to quantify primary and metastatic OS in a previously validated orthotopic, immunocompetent mouse model. (1) Can near-infrared ICG fluorescence be used to attach a comparable, quantitative value to the primary OS tumor in our experimental mouse model? (2) Will primary tumor fluorescence differ in mice that go on to develop metastatic lung disease? (3) Does primary tumor fluorescence correlate with tumor volume measured with CT? Six groups of 4- to 6-week-old immunocompetent Balb/c mice (n = 6 per group) received paraphyseal injections into their left hindlimb proximal tibia consisting of variable numbers of K7M2 mouse OS cells. A hindlimb transfemoral amputation was performed 4 weeks after injection with euthanasia and lung extraction performed 10 weeks after injection. Histologic examination of lung and primary tumor specimens confirmed ICG localization only within the tumor bed. Mice with visible or palpable tumor growth had greater hindlimb fluorescence (3.5 ± 2.3 arbitrary perfusion units [APU], defined as the fluorescence pixel return normalized by the detector) compared with those with a negative examination (0.71 ± 0.38 APU, -2.7 ± 0.5 mean difference, 95% confidence interval -3.7 to -1.8, p < 0.001). A strong linear trend (r = 0.81, p < 0.01) was observed between primary tumor and lung fluorescence, suggesting that quantitative ICG tumor fluorescence is directly related to eventual metastatic burden. We did not find a correlation (r = 0.04, p = 0.45) between normalized primary tumor fluorescence and CT volumetric measurements. We

Primary Tumors of the Osseous Chest Wall and Their Management.

PubMed

Thomas, Mathew; Shen, K Robert

2017-05-01

Primary osseous tumors of the chest wall are uncommon neoplasms. They occur in a wide variety of pathologic forms, most of which can be distinguished by unique radiologic appearance. Management of these tumors depends on the diagnosis and stage. Adequate surgical resection is critical in achieving the best outcomes for most of these tumors. Chemotherapy and radiation may have an adjuvant role. Surgeons considering resection of any chest wall tumor should have a sound knowledge of the principles of resection and reconstruction. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

PubMed

Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

2018-01-01

Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

PubMed

Worch, Jennifer; Ranft, Andreas; DuBois, Steven G; Paulussen, Michael; Juergens, Heribert; Dirksen, Uta

2018-06-01

The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations. © 2018 Wiley Periodicals, Inc.

Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

NASA Astrophysics Data System (ADS)

Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

2016-08-01

The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

Primary hepatic carcinoid tumor: case report and literature review

PubMed Central

Camargo, Éden Sartor; Viveiros, Marcelo de Melo; Corrêa, Isaac José Felippe; Robles, Laercio; Rezende, Marcelo Bruno

2014-01-01

Primary hepatic carcinoid tumors are extremely rare neoplasms derived from hormone-producing neuroendocrine cells. It is difficult to make their diagnosis before biopsy, surgical resection or necropsy. A recent publication described only 94 cases of these tumors. There is no sex predilection and apparently it has no association with cirrhosis or preexisting hepatic disease. The most effective treatment is hepatectomy, and resection is determined by size and location of the lesions. PMID:25628206

Primary mesenchymal or mixed-cell-origin lung tumors in four dogs.

PubMed

Watson, A D; Young, K M; Dubielzig, R R; Biller, D S

1993-03-15

Primary lung tumors of mesenchymal or mixed cell origin were diagnosed in 4 dogs with clinical and radiographic abnormalities indicating an intrathoracic mass. Each dog had 1 large intrapulmonary lesion, and 1 dog also had nodules scattered throughout all lung lobes. Two dogs were euthanatized; 1 had a biphasic pulmonary blastoma; and the other had a pulmonary chondroblastic osteosarcoma with intrapulmonary metastases. The masses in the other 2 dogs were hamartomas (lipomatous in 1, microcystic in the other), which were resected. Both dogs survived more than 1 year after surgery. Primary lung tumors are uncommon in dogs and are generally malignant (adenocarcinomas or carcinomas). Tumors of connective tissue or mixed cell origin are rare, but the outcome is potentially good after surgical removal.

Advances in evaluation of primary brain tumors.

PubMed

Chen, Wei; Silverman, Daniel H S

2008-07-01

The evaluation of primary brain tumor is challenging. Neuroimaging plays a significant role. At diagnosis, imaging is needed to establish a differential diagnosis, provide prognostic information, as well as direct biopsy. After the initial treatment, imaging is needed to distinguish recurrent disease from treatment-related changes such as radiation necrosis. In low-grade gliomas, this also includes monitoring anaplastic transformation into high-grade tumors. Recently, targeted treatments have been an extremely active area of research. Evaluation in clinical trials of such targeted treatments demands advanced roles of imaging such as treatment planning, monitoring response, and predicting treatment outcomes. Current clinical gold standard magnetic resonance imaging provides superior structural detail but poor specificity in identifying viable tumors in treated brain with surgery/radiation/chemotherapy. (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is capable of identifying anaplastic transformation and has prognostic value. The sensitivity and specificity of FDG in evaluating recurrent tumor and treatment-induced changes can be significantly improved by coregistration with magnetic resonance imaging and potentially by delayed imaging 3 to 8 hours after injection. Amino acid PET tracers can be more sensitive than FDG in imaging some recurrent tumors, in particular recurrent low-grade tumors. They are also promising for differentiating between recurrent tumors and treatment-induced changes. Newer PET tracers to image important aspects of tumor biology have been actively studied. Tracers for imaging membrane transport such as (18)F-choline have shown promise in differential diagnosis. (18)F-labeled nucleotide analogs such as 3'-deoxy-3'-[(18)F]-fluorothymidine (FLT) and (18)F-FMAU have been developed to image proliferation. The use of FLT has demonstrated prognostic power in predicting treatment response in patients treated with an antiangiogenic

[The role of whole body 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in the management of unknown primary tumors].

PubMed

Wu, Zhi-Jian; Zhang, Yong-Xue; Wei, Hao; Jia, Qing

2007-08-28

To assess the role of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in the management of unknown primary primary (CUP) with metastatic loci. Thirty-four patients of CUP with metastatic loci who had undergone unsuccessful conventional diagnostic work-up underwent (18)F-FDG PET/CT. The images thus obtained were analyzed with visual and semi-quantitative methods. Histopathology, cytology, and/or follow-up were used to evaluate the PET/CT results. In 20 of the 34 patients (18)F-FDG PET/CT showed focal tracer accumulations corresponding to potential primary tumor sites located in the lung (n = 9), colon (n = 3), rectum (n = 2), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), breast (n = 1), and ovary (n = 2). The detection rate of primary tumor by (18)F-FDG PET/CT was 50.0% (17/34), the primary tumors were identified in the lung (n = 8), colon (n = 2), rectum (n = 1), pancreas (n = 1), right aryepiglottic wall (n = 1), esophagus (n = 1), ovary (n = 2), and breast (n = 1). The false positive rate was 8.8% (3/34) with the diagnosis of primary tumor in the lung (n = 1), colon (n = 1), and rectum (n = 1) to be identified as false. In 14 of the 34 patients, (18)F-FDG PET/CT did not reveal lesions suspected to be the primary tumor sites in 13 patients, and it was impossible to identify one lesion as the most likely primary tumor in one patient due to the presence of multiple hot spots in several organs. The (18)F-FDG PET/CT findings affected the medical management in 17 of the 34 (50.0%) patients due to the finding of primary sites and/or additional metastases. (18)F-FDG PET/CT has relevant impact on the therapeutic management of patients with unknown primary tumor. It is recommended that (18)F-FDG PET/CT be performed in the patient with unknown primary tumor after unsuccessful conventional diagnostic workup.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

PubMed

Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

2018-02-23

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P <0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

[Colorectal cancer the importance of primary tumor location].

PubMed

Ryska, M; Bauer, J

2017-01-01

Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

PubMed

Dondossola, Eleonora; Dobroff, Andrey S; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-23

Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell-mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery.

[Extraoseus Ewings Sarcoma, Primary Affection of Uterine Cervix--Case Report].

PubMed

Bílek, O; Holánek, M; Zvaríková, M; Fabian, P; Robešová, B; Procházková, M; Adámková Krákorová, D

2015-01-01

Ewing's sarcoma is usually diagnosed in adolescents and young adults, peak of incidence is around 15 years of age. Primary localization is mostly in the skeleton of long bones and chest wall. Primary extraosseous involvement rarely occurs, incidence increases with age. We present a case report of a 57-year-old patient with locally advanced tumors of the cervix, clinical stage IIB. Due to histological and molecular genetic examination revealing EWS -ERG fusion gene, Ewing's sarcoma was diagnosed. CT revealed pathological pelvic lymphadenopathy and multiple pulmonary bilateral methastases, scintigraphy did not prove any affection of skeleton. The patient underwent a two-stage intensive chemotherapy regimens VIDE (vincristine, ifosfamide, doxorubicin, etoposide) and VAI (vincristine, actinomycin D, ifosfamide). During the second phase, concomitant radiotherapy of pelvis was aplied. According to PET/CT, complete remission was achieved. Whole-lung irradiation was applied in consolidation of the result. Primary Ewing's sarcoma of the cervix is an extremely rare disease. To our knowledge, only 12 cases was presented until this time. The average age at time of dia-gnosis was 35 years. Unlike the previous reports, we initially diagnosed distant metastases. The treatment was led according to the protocol Ewing 2008 designed for primary skeletal Ewing's sarcoma. Currently, 18 months after the therapy, the patient is without signs of disease. However, long-term follow-up is necessary.

Metformin selectively affects human glioblastoma tumor-initiating cell viability

PubMed Central

Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirana; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2013-01-01

Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect. PMID:23255107

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

PubMed Central

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

2015-01-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

Advising potential recipients on the use of organs from donors with primary central nervous system tumors.

PubMed

Warrens, Anthony N; Birch, Rhiannon; Collett, David; Daraktchiev, Maren; Dark, John H; Galea, George; Gronow, Katie; Neuberger, James; Hilton, David; Whittle, Ian R; Watson, Christopher J E

2012-02-27

Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.

Anesthetic implications of primary cardiac tumors in infants and children.

PubMed

Kussman, Barry D; Devavaram, Prabhakar; Hansen, Dolly D; Dinardo, James A; Forbess, Joseph M; Mehrota, Ramji; McGowan, Francis X

2002-10-01

To determine the degree of hemodynamic and airway compromise in infants and children undergoing anesthesia for primary cardiac tumors. Retrospective study. Tertiary-care, academic children's hospital. Patients <18 years old who had undergone anesthesia and surgery for resection or biopsy of a primary cardiac tumor (n = 25). None. Charts were reviewed for intraoperative complications, defined as (1) hypotension (20% decrease from baseline) during or after induction; (2) failure to gain airway control by insertion of an airway or endotracheal intubation, inability to ventilate after administration of a muscle relaxant, need for change in patient position, rigid bronchoscopy, or cardiopulmonary bypass for adequate oxygenation; and (3) new arrhythmias. Hypotension during induction occurred in 4 patients (16%), 3 of whom were hemodynamically unstable preoperatively. Hypotension after induction was found in 2 (8%) patients. Hypotension occurred more frequently in patients with obstruction to blood flow and arrhythmia (n = 3), obstruction to blood flow only (n = 1), and arrhythmia only (n = 1). No patient had airway difficulty related to the tumor, although one intrapericardial tumor mimicked an anterior mediastinal mass. New arrhythmias occurred in 3 (12%) patients. The subgroup of patients at greatest risk are patients with a combination of obstruction to blood flow and arrhythmias. Despite the alarming diagnosis, the intraoperative course tends to be fairly stable in most cases. Extensive pericardial tumors may produce the same airway concerns as anterior mediastinal masses, but airway complications do not seem to be a problem with intrachamber tumors. Copyright 2002, Elsevier Science (USA). All rights reserved.

Tumor-Like Presentation of Primary Angiitis of the Central Nervous System.

PubMed

de Boysson, Hubert; Boulouis, Grégoire; Dequatre, Nelly; Godard, Sophie; Néel, Antoine; Arquizan, Caroline; Detante, Olivier; Bloch-Queyrat, Coralie; Zuber, Mathieu; Touzé, Emmanuel; Bienvenu, Boris; Aouba, Achille; Guillevin, Loïc; Naggara, Olivier; Pagnoux, Christian

2016-09-01

We aimed to describe the clinical and imaging features of patients with tumor-like presentation of primary angiitis of the central nervous system. We retrospectively analyzed 10 patients enrolled in the French primary angiitis of the central nervous system cohort, who initially presented tumor-like brain lesions and compared them with other patients within the cohort. The 10 patients with tumor-like presentation in the cohort were younger and had more seizures at diagnosis than the other 75 patients (median of 37 [30-48] years versus 46 [18-79] years; P=0.008; 9 [90%] with seizures versus 22 [29%], P<0.001; respectively). All 10 patients had a biopsy (stereotactic procedure in 7 and open-wedge surgery in 3). Histological findings suggestive of vasculitis were observed in 9 patients in whom conventional cerebral angiography and magnetic resonance angiography were negative. In the remaining patient, vascular imaging demonstrated diffuse bilateral large- and medium-sized vessel involvement (biopsy did not reveal vasculitis). All patients with tumor-like presentation received glucocorticoids, combined with cyclophosphamide in 9 cases. With a median follow-up of 27 (12-130) months, 5 (50%) patients relapsed, but achieved remission again after treatment intensification. Patients with tumor-like presentation of primary angiitis of the central nervous system represent a subgroup characterized with mainly small-sized vessel disease that requires histological confirmation because vascular imaging is often normal. Although relapses are not uncommon, global outcomes are good under treatment with glucocorticoids and cyclophosphamide. © 2016 American Heart Association, Inc.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

PubMed

Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

The membrane mucin MUC4 is elevated in breast tumor lymph node metastases relative to matched primary tumors and confers aggressive properties to breast cancer cells.

PubMed

Workman, Heather C; Miller, Jamie K; Ingalla, Ellen Q; Kaur, Rouminder P; Yamamoto, Diane I; Beckett, Laurel A; Young, Lawrence Jt; Cardiff, Robert D; Borowsky, Alexander D; Carraway, Kermit L; Sweeney, Colleen; Carraway, Kermit L

2009-01-01

Previous studies indicate that overexpression of the membrane-associated mucin MUC4 is potently anti-adhesive to cultured tumor cells, and suppresses cellular apoptotic response to a variety of insults. Such observations raise the possibility that MUC4 expression could contribute to tumor progression or metastasis, but the potential involvement of MUC4 in breast cancer has not been rigorously assessed. The present study aimed to investigate the expression of the membrane mucin MUC4 in normal breast tissue, primary breast tumors and lymph node metastases, and to evaluate the role of MUC4 in promoting the malignant properties of breast tumor cells. MUC4 expression levels in patient-matched normal and tumor breast tissue was initially examined by immunoblotting lysates of fresh frozen tissue samples with a highly specific preparation of anti-MUC4 monoclonal antibody 1G8. Immunohistochemical analysis was then carried out using tissue microarrays encompassing patient-matched normal breast tissue and primary tumors, and patient-matched lymph node metastases and primary tumors. Finally, shRNA-mediated knockdown was employed to assess the contribution of MUC4 to the cellular growth and malignancy properties of JIMT-1 breast cancer cells. Immunoblotting and immunohistochemistry revealed that MUC4 levels are suppressed in the majority (58%, p < 0.001) of primary tumors relative to patient-matched normal tissue. On the other hand, lymph node metastatic lesions from 37% (p < 0.05) of patients expressed higher MUC4 protein levels than patient-matched primary tumors. MUC4-positive tumor emboli were often found in lymphovascular spaces of lymph node metastatic lesions. shRNA-mediated MUC4 knockdown compromised the migration, proliferation and anoikis resistance of JIMT-1 cells, strongly suggesting that MUC4 expression actively contributes to cellular properties associated with breast tumor metastasis. Our observations suggest that after an initial loss of MUC4 levels during the

Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?

PubMed

Donnem, Tom; Hu, Jiangting; Ferguson, Mary; Adighibe, Omanma; Snell, Cameron; Harris, Adrian L; Gatter, Kevin C; Pezzella, Francesco

2013-08-01

Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10-30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.

Tumor inoculation site affects the development of cancer cachexia and muscle wasting.

PubMed

Matsuyama, Tatsuzo; Ishikawa, Takeshi; Okayama, Tetsuya; Oka, Kaname; Adachi, Satoko; Mizushima, Katsura; Kimura, Reiko; Okajima, Manabu; Sakai, Hiromi; Sakamoto, Naoyuki; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Handa, Osamu; Takagi, Tomohisa; Kokura, Satoshi; Naito, Yuji; Itoh, Yoshito

2015-12-01

The phenotype and severity of cancer cachexia differ among tumor types and metastatic site in individual patients. In this study, we evaluated if differences in tumor microenvironment would affect the development of cancer cachexia in a murine model, and demonstrated that body weight, adipose tissue and gastrocnemius muscle decreased in tumor-bearing mice. Interestingly, a reduction in heart weight was observed in the intraperitoneal tumor group but not in the subcutaneous group. We evaluated 23 circulating cytokines and members of the TGF-β family, and found that levels of IL-6, TNF-α and activin A increased in both groups of tumor-bearing mice. Eotaxin and G-CSF levels in the intraperitoneal tumor group were higher than in the subcutaneous group. Atrogin 1 and MuRF1 mRNA expressions in the gastrocnemius muscle increased significantly in both groups of tumor-bearing mice, however, in the myocardium, expression of these mRNAs increased in the intraperitoneal group but not in subcutaneous group. Based on these results, we believe that differences in microenvironment where tumor cells develop can affect the progression and phenotype of cancer cachexia through alterations in various circulating factors derived from the tumor microenvironment. © 2015 UICC.

Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

PubMed

Kim, Hoon; Zheng, Siyuan; Amini, Seyed S; Virk, Selene M; Mikkelsen, Tom; Brat, Daniel J; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E; Cohen, Mark L; Van Meir, Erwin G; Scarpace, Lisa; Laird, Peter W; Weinstein, John N; Lander, Eric S; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S; Verhaak, Roel G W

2015-03-01

Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. © 2015 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is the link?

PubMed Central

Germano, Isabelle; Swiss, Victoria; Casaccia, Patrizia

2010-01-01

The discovery of brain tumor-derived cells (BTSC) with the properties of stem cells has led to the formulation of the hypothesis that neural stem cells could be the cell of origin of primary brain tumors (PBT). In this review we present the most common molecular changes in PBT, define the criteria of identification of BTSC and discuss the similarities between the characteristics of these cells and those of the endogenous population of neural stem cells (NPCs) residing in germinal areas of the adult brain. Finally, we propose possible mechanisms of cancer initiation and progression and suggest a model of tumor initiation that includes intrinsic changes of resident NSC and potential changes in the microenvironment defining the niche where the NSC reside. PMID:20045420

Second primary cancers following borderline ovarian tumors.

PubMed

Sanci, Muzaffer; Gultekin, Emre; Cingillioglu, Basak; Gultekin, Ozge Elmastas; Ozvural, Seyfettin; Emirdar, Volkan; Yildirim, Yusuf

2011-06-01

Several studies have reported an increased risk of second primary cancers subsequent to invasive epithelial ovarian cancer. However, there is no adequate data regarding such risk in borderline ovarian tumors (BOTs). The aim of this study was to evaluate the risk of subsequent second primary cancers among women with BOTs. BOT patients treated in our center between December 1985 and April 2009 were retrospectively screened for developing second primary cancer during follow-up period. There were 96 women diagnosed with BOT. Mean age at the time of diagnosis was 47 ± 14.3, ranging from 19 to 79. Eighty-eight (91.6%) patients had stage I disease, two patients (2.1%) had stage II and six (6.2%) had stage III. Twenty-five (26.0%) patients received platinum-based adjuvant chemotherapy. Mean follow-up time was 96.5 ± 442 months (range: 9-280 months). There were ten (10.4%) recurrences. Only one patient developed second primary cancer. Second primary cancer observed in this case was basal cell carsinoma of the eyelid, which was diagnosed 2 years after primary disease. There were no patients with common women's cancers such as breast and colorectal cancers. These findings do not suggest increased risk of subsequent cancers in patients with BOT. However, population-based studies are needed for evaluating exact risk of developing second primary malignancies in women with BOTs.

Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

PubMed

Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

2014-01-01

Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

Association of Primary Tumor Site With Mortality in Patients Receiving Bevacizumab and Cetuximab for Metastatic Colorectal Cancer.

PubMed

Aljehani, Mayada A; Morgan, John W; Guthrie, Laurel A; Jabo, Brice; Ramadan, Majed; Bahjri, Khaled; Lum, Sharon S; Selleck, Matthew; Reeves, Mark E; Garberoglio, Carlos; Senthil, Maheswari

2018-01-01

Biologic therapy (BT) (eg, bevacizumab or cetuximab) is increasingly used to treat metastatic colorectal cancer (mCRC). Recent investigations have suggested that right- or left-sided primary tumor origin affects survival and response to BT. To evaluate the association of tumor origin with mortality in a diverse population-based data set of patients receiving systemic chemotherapy (SC) and bevacizumab or cetuximab for mCRC. This population-based nonconcurrent cohort study of statewide California Cancer Registry data included all patients aged 40 to 85 years diagnosed with mCRC and treated with SC only or SC plus bevacizumab or cetuximab from January 1, 2004, through December 31, 2014. Patients were stratified by tumor origin in the left vs right sides. Treatment with SC or SC plus bevacizumab or cetuximab. Mortality hazards by tumor origin (right vs left sides) were assessed for patients receiving SC alone or SC plus bevacizumab or cetuximab. Subgroup analysis for patients with wild-type KRAS tumors was also performed. A total of 11 905 patients with mCRC (6713 men [56.4%] and 5192 women [43.6%]; mean [SD] age, 60.0 [10.9] years) were eligible for the study. Among these, 4632 patients received SC and BT. Compared with SC alone, SC plus bevacizumab reduced mortality among patients with right- and left-sided mCRC, whereas SC plus cetuximab reduced mortality only among patients with left-sided tumors and was associated with significantly higher mortality for right-sided tumors (hazard ratio [HR], 1.31; 95% CI, 1.14-1.51; P < .001). Among patients treated with SC plus BT, right-sided tumor origin was associated with higher mortality among patients receiving bevacizumab (HR, 1.31; 95% CI, 1.25-1.36; P < .001) and cetuximab (HR, 1.88; 95% CI, 1.68-2.12; P < .001) BT, compared with left-sided tumor origin. In patients with wild-type KRAS tumors (n = 668), cetuximab was associated with reduced mortality among only patients with left-sided mCRC compared

Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations

PubMed Central

King, Kathryn S.; Prodanov, Tamara; Kantorovich, Vitaly; Fojo, Tito; Hewitt, Jacqueline K.; Zacharin, Margaret; Wesley, Robert; Lodish, Maya; Raygada, Margarita; Gimenez-Roqueplo, Anne-Paule; McCormack, Shana; Eisenhofer, Graeme; Milosevic, Dragana; Kebebew, Electron; Stratakis, Constantine A.; Pacak, Karel

2011-01-01

Purpose To present data on the high rate of SDHB mutations in patients with metastatic pheochromocytoma/paraganglioma whose initial tumor presentation began in childhood or adolescence. Patients and Methods From 2000 to 2010, 263 patients with pheochromocytoma/paraganglioma were evaluated through the National Institutes of Health (NIH), Bethesda, MD. Of the 263 patients, 125 patients were found to have metastatic disease; of these 125 patients, 32 patients presented with a tumor before 20 years of age. An additional 17 patients presented with a tumor before 20 years of age but demonstrated no development of metastatic disease. Genetic testing for mutations in the VHL, MEN, and SDHB/C/D genes was performed on patients without previously identified genetic mutations. Results Of the 32 patients who presented with metastatic disease and had their primary tumor in childhood or adolescence, sequence analysis of germline DNA showed SDHB mutations in 23 patients (71.9%), SDHD mutations in three patients (9.4%), VHL mutations in two patients (6.3%), and an absence of a known mutation in four patients (12.5%). The majority of these 32 patients (78.1%) presented with primary tumors in an extra-adrenal location. Conclusion The majority of patients with metastatic pheochromocytoma/paraganglioma who presented with a primary tumor in childhood/adolescence had primary extra-adrenal tumors and harbored SDHB mutations. Except for primary tumors located in the head and neck where SDHD genetic testing is advised, we recommend that patients who present with metastatic pheochromocytoma/paraganglioma with primary tumor development in childhood or adolescence undergo SDHB genetic testing before they undergo testing for other gene mutations, unless clinical presentation or family history suggests a different mutation. PMID:21969497

PRC2/EED-EZH2 Complex Is Up-Regulated in Breast Cancer Lymph Node Metastasis Compared to Primary Tumor and Correlates with Tumor Proliferation In Situ

PubMed Central

Yu, Hongxiang; Simons, Diana L.; Segall, Ilana; Carcamo-Cavazos, Valeria; Schwartz, Erich J.; Yan, Ning; Zuckerman, Neta S.; Dirbas, Frederick M.; Johnson, Denise L.; Holmes, Susan P.; Lee, Peter P.

2012-01-01

Background Lymph node metastasis is a key event in the progression of breast cancer. Therefore it is important to understand the underlying mechanisms which facilitate regional lymph node metastatic progression. Methodology/Principal Findings We performed gene expression profiling of purified tumor cells from human breast tumor and lymph node metastasis. By microarray network analysis, we found an increased expression of polycomb repression complex 2 (PRC2) core subunits EED and EZH2 in lymph node metastatic tumor cells over primary tumor cells which were validated through real-time PCR. Additionally, immunohistochemical (IHC) staining and quantitative image analysis of whole tissue sections showed a significant increase of EZH2 expressing tumor cells in lymph nodes over paired primary breast tumors, which strongly correlated with tumor cell proliferation in situ. We further explored the mechanisms of PRC2 gene up-regulation in metastatic tumor cells and found up-regulation of E2F genes, MYC targets and down-regulation of tumor suppressor gene E-cadherin targets in lymph node metastasis through GSEA analyses. Using IHC, the expression of potential EZH2 target, E-cadherin was examined in paired primary/lymph node samples and was found to be significantly decreased in lymph node metastases over paired primary tumors. Conclusions/Significance This study identified an over expression of the epigenetic silencing complex PRC2/EED-EZH2 in breast cancer lymph node metastasis as compared to primary tumor and its positive association with tumor cell proliferation in situ. Concurrently, PRC2 target protein E-cadherin was significant decreased in lymph node metastases, suggesting PRC2 promotes epithelial mesenchymal transition (EMT) in lymph node metastatic process through repression of E-cadherin. These results indicate that epigenetic regulation mediated by PRC2 proteins may provide additional advantage for the outgrowth of metastatic tumor cells in lymph nodes. This opens

Are Mammographically Occult Additional Tumors Identified More Than 2 Cm Away From the Primary Breast Cancer on MRI Clinically Significant?

PubMed

Goodman, Sarah; Mango, Victoria; Friedlander, Lauren; Desperito, Elise; Wynn, Ralph; Ha, Richard

2018-06-08

To evaluate the clinical significance of mammographically occult additional tumors identified more than 2cm away from the primary breast cancer on preoperative magnetic resonance imaging (MRI). An Institutional Review Board approved review of consecutive preoperative breast MRIs performed from 1/1/08 to 12/31/14, yielded 667 patients with breast cancer. These patients underwent further assessment to identify biopsy proven mammographically occult breast tumors located more than 2cm away from the edge of the primary tumor. Additional MRI characteristics of the primary and secondary tumors and pathology were reviewed. Statistical analysis was performed using SPSS (v. 24). Of 667 patients with breast cancer, 129 patients had 150 additional ipsilateral mammographically occult tumors that were more than 2cm away from the edge of the primary tumor. One hundred twelve of 129 (86.8%) patients had one additional tumor and 17/129 (13.2%) had two or more additional tumors. In 71/129 (55.0%), additional tumors were located in a different quadrant and in 58/129 (45.0%) additional tumors were in the same quadrant but ≥2cm away. Overall, primary tumor size was significantly larger (mean 1.87± 1.25 cm) than the additional tumors (mean 0.79 ± 0.61cm, p < 0.001). However, in 20/129 (15.5%) the additional tumor was larger and in 26/129 (20.2%) the additional tumor was ≥1cm. The primary tumor was significantly more likely to be invasive (81.4%, 105/129) compared to additional tumors (70%, 105/150, p = 0.03). In 9/129 (7.0%) patients, additional tumors yielded unsuspected invasive cancer orhigher tumor grade. The additional tumor was more likely to be nonmass lesion type (37.3% vs 24% p = 0.02) and focus lesion type (10% vs 0.08%, p < 0.001) compared to primary tumor. Mammographically occult additional tumors identified more than 2cm away from the primary breast tumor on MRI are unlikely to be surgically treated if undiagnosed and may be clinically significant. Copyright �

SU-F-R-13: Decoding 18F-FDG Uptake Heterogeneity for Primary and Lymphoma Tumors by Using Texture Analysis in PET Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Yin, Y

Purpose: To explore 18F-FDG uptake heterogeneity of primary tumor and lymphoma tumor by texture features of PET image and quantify the heterogeneity difference between primary tumor and lymphoma tumor. Methods: 18 patients with primary tumor and lymphoma tumor in lung cancer were enrolled. All patients underwent whole-body 18F-FDG PET/CT scans before treatment. Texture features, based on Gray-level Co-occurrence Matrix, second and high order matrices are extracted from code using MATLAB software to quantify 18F-FDG uptake heterogeneity. The relationships of volume between energy, entropy, correlation, homogeneity and contrast were analyzed. Results: For different cases, tumor heterogeneity was not the same. Texturemore » parameters (contrast, entropy, and correlation) of lymphoma were lower than primary tumor. On the contrast, the texture parameters (energy, homogeneity and inverse different moment) of lymphoma were higher than primary tumor. Significantly, correlations were observed between volume and energy (primary, r=−0.194, p=0.441; lymphoma, r=−0.339, p=0.582), homogeneity (primary, r=−0.146, p=0.382; lymphoma, r=−0.193, p=0.44), inverse difference moment (primary, r=−0.14, p=0.374; lymphoma, r=−0.172, p=0.414) and a positive correlation between volume and entropy (primary, r=0.233, p=0.483; lymphoma, r=0.462, p=0.680), contrast (primary, r=0.159, p=0.399; lymphoma, r=0.341, p=0.584), correlation (primary, r=0.027, p=0.165; lymphoma, r=0.046, p=0.215). For the same patient, energy for primary and lymphoma tumor is equal. The volume of lymphoma is smaller than primary tumor, but the homogeneity were higher than primary tumor. Conclusion: This study showed that there were effective heterogeneity differences between primary and lymphoma tumor by FDG-PET image texture analysis.« less

Hotspot mutation panel testing reveals clonal evolution in a study of 265 paired primary and metastatic tumors.

PubMed

Goswami, Rashmi S; Patel, Keyur P; Singh, Rajesh R; Meric-Bernstam, Funda; Kopetz, E Scott; Subbiah, Vivek; Alvarez, Ricardo H; Davies, Michael A; Jabbar, Kausar J; Roy-Chowdhuri, Sinchita; Lazar, Alexander J; Medeiros, L Jeffrey; Broaddus, Russell R; Luthra, Rajyalakshmi; Routbort, Mark J

2015-06-01

We used a clinical next-generation sequencing (NGS) hotspot mutation panel to investigate clonal evolution in paired primary and metastatic tumors. A total of 265 primary and metastatic tumor pairs were sequenced using a 46-gene cancer mutation panel capable of detecting one or more single-nucleotide variants as well as small insertions/deletions. Mutations were tabulated together with tumor type and percentage, mutational variant frequency, time interval between onset of primary tumor and metastasis, and neoadjuvant therapy status. Of note, 227 of 265 (85.7%) tumor metastasis pairs showed identical mutation calls. Of the tumor pairs with identical mutation calls, 160 (60.4%) possessed defining somatic mutation signatures and 67 (25.3%) did not exhibit any somatic mutations. There were 38 (14.3%) cases that showed at least one novel mutation call between the primary and metastasis. Metastases were almost two times more likely to show novel mutations (n = 20, 7.5%) than primary tumors (n = 12, 4.5%). TP53 was the most common additionally mutated gene in metastatic lesions, followed by PIK3CA and SMAD4. PIK3CA mutations were more often associated with metastasis in colon carcinoma samples. Clinical NGS hotspot panels can be useful in analyzing clonal evolution within tumors as well as in determining subclonal mutations that can expand in future metastases. PIK3CA, SMAD4, and TP53 are most often involved in clonal divergence, providing potential targets that may help guide the clinical management of tumor progression or metastases. ©2015 American Association for Cancer Research.

Analysis of imaging characteristics of primary malignant bone tumors in children

PubMed Central

Sun, Yingwei; Liu, Xueyong; Pan, Shinong; Deng, Chunbo; Li, Xiaohan; Guo, Qiyong

2017-01-01

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a

Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more.

PubMed

Bonadonna, G; Veronesi, U; Brambilla, C; Ferrari, L; Luini, A; Greco, M; Bartoli, C; Coopmans de Yoldi, G; Zucali, R; Rilke, F

1990-10-03

In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.

Relation between primary tumor FDG avidity and site of first distant metastasis in patients with breast cancer.

PubMed

Lim, Chae Hong; Moon, Seung Hwan; Cho, Young Seok; Im, Young-Hyuck; Choe, Yearn Seong; Kim, Byung-Tae; Lee, Kyung-Han

2016-08-01

Identification of tumor imaging features associated with metastatic pattern may allow better understanding of cancer dissemination. Here, we investigated how primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of breast cancer metastasis.Subjects were 264 patients with advanced breast cancer who underwent positron emission tomography/computed tomography at diagnosis and had metastasis at presentation (n = 193) or metastatic relapse after surgery (n = 71). Primary tumor FDG avidity (maximum SUV [SUVmax] ≥10.1) was compared with histology and first metastatic sites.The most common site of first metastasis was the bone, occurring in 62.7% of patients with metastasis at presentation and 38.0% of those with metastatic relapse. First metastasis to lung occurred in 30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In patients with metastasis at presentation, primary tumors were FDG avid in 98/193 cases, and this was associated with more frequent first metastasis to lung (37.8% vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were FDG avid in 31/71 cases, and this was associated with more frequent first metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P = 0.008). In patients with metastasis relapse, primary tumors that were FDG avid but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%; P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung and liver, which suggests that tumor cells with heightened glycolytic activity better colonize these organs.

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

PubMed

Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Horswell, Stuart; Chambers, Tim; O'Brien, Tim; Lopez, Jose I; Watkins, Thomas B K; Nicol, David; Stares, Mark; Challacombe, Ben; Hazell, Steve; Chandra, Ashish; Mitchell, Thomas J; Au, Lewis; Eichler-Jonsson, Claudia; Jabbar, Faiz; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Stewart, Aengus; Xing, Wei; Smith, Jonathan C; Escudero, Mickael; Huffman, Adam; Matthews, Nik; Elgar, Greg; Phillimore, Ben; Costa, Marta; Begum, Sharmin; Ward, Sophia; Salm, Max; Boeing, Stefan; Fisher, Rosalie; Spain, Lavinia; Navas, Carolina; Grönroos, Eva; Hobor, Sebastijan; Sharma, Sarkhara; Aurangzeb, Ismaeel; Lall, Sharanpreet; Polson, Alexander; Varia, Mary; Horsfield, Catherine; Fotiadis, Nicos; Pickering, Lisa; Schwarz, Roland F; Silva, Bruno; Herrero, Javier; Luscombe, Nick M; Jamal-Hanjani, Mariam; Rosenthal, Rachel; Birkbak, Nicolai J; Wilson, Gareth A; Pipek, Orsolya; Ribli, Dezso; Krzystanek, Marcin; Csabai, Istvan; Szallasi, Zoltan; Gore, Martin; McGranahan, Nicholas; Van Loo, Peter; Campbell, Peter; Larkin, James; Swanton, Charles

2018-04-19

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

High fidelity of driver chromosomal alterations among primary and metastatic renal cell carcinomas: implications for tumor clonal evolution and treatment.

PubMed

Kouba, Eril J; Eble, John N; Simper, Novae; Grignon, David J; Wang, Mingsheng; Zhang, Shaobo; Wang, Lisha; Martignoni, Guido; Williamson, Sean R; Brunelli, Matteo; Luchini, Claudio; Calió, Anna; Cheng, Liang

2016-11-01

Recent studies have demonstrated considerable genomic heterogeneity in both primary and metastatic renal cell carcinoma (RCC). This mutational diversity has serious implications for the development and implementation of targeted molecular therapies. We evaluated 39 cases of primary RCC tumors with their matched metastatic tumors to determine if the hallmark chromosomal anomalies of these tumors are preserved over the course of disease progression. Thirty-nine matched pairs of primary and metastatic RCCs (20 clear cell RCC, 16 papillary RCC, and 3 chromophobe RCC) were analyzed. All clear cell RCC and papillary RCC tumors were evaluated for chromosome 3p deletion, trisomy 7 and 17 using fluorescence in situ hybridization. Chromophobe RCC tumors were evaluated for genetic alterations in chromosomes 1, 2, 6, 10, and 17. Of the 20 clear cell RCC tumors, 18 primary tumors (90%) showed a deletion of chromosome 3p and were disomic for chromosomes 7 and 17. All molecular aberrations were conserved within the matched metastatic tumor. Of the 16 papillary RCC tumors, 10 primary tumors (62%) showed trisomy for both chromosomes 7 and 17 without 3p deletion. These molecular aberrations and others were conserved in the paired metastatic tumors. Of the three chromophobe RCC tumors, multiple genetic anomalies were identified in chromosomes 1, 2, 6, 10, and 17. These chromosomal aberrations were conserved in the matched metastatic tumors. Our results demonstrated genomic fidelity among the primary and metastatic lesions in RCCs. These findings may have important clinical and diagnostic implications.

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

PubMed Central

Blumenthal, Laura; VandenBoom, Timothy; Melian, Edward; Peterson, Anthony; Hutchens, Kelli A.

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC. PMID:26594171

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

PubMed

Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

2015-06-01

A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

Primary perivascular epithelioid cell tumors of the liver: CT/MRI findings and clinical outcomes.

PubMed

O'Malley, Martin E; Chawla, Tanya P; Lavelle, Lisa P; Cleary, Sean; Fischer, Sandra

2017-06-01

The purpose of our study was to describe the CT and MRI features of primary PEComas of the liver and to document the associated clinical outcomes. Retrospective study included 20 patients with primary hepatic perivascular epithelioid cell tumors (PEComa) with pathology and clinical outcomes for correlation. Study group included 20 patients: 16 women, 4 men; mean age 53 (range 35-77) years. Initial pathology diagnoses were classic angiomyolipoma (AML) (n = 11), epithelioid AML (n = 7), and PEComa not otherwise specified (n = 2). Mean tumor size was 5.1 (range 1.3-15.0) cm. CT/MRI features included well-defined margins 20/20 (100%), arterial enhancement 18/19 (95%), subcapsular location 17/20 (85%), heterogeneous 16/20 (80%), dysmorphic vessels 14/20 (70%), fat 13/20 (65%), hemorrhage 4/20 (20%), cystic components 4/20 (20%), and calcification 1/20 (5%). At the time of discovery, 18 patients were asymptomatic and their tumors were incidentally detected on imaging, and 2 patients were symptomatic. Ultimately, 18 tumors were benign and 2 developed metastases. On CT/MRI, most primary hepatic PEComas were well-defined, arterial enhancing, subcapsular, heterogeneous masses that often had dysmorphic vessels and contained fat. Most tumors were benign but complications included local symptoms, bleeding, and malignant change.

Epidemiology of primary brain tumors: current concepts and review of the literature.

PubMed Central

Wrensch, Margaret; Minn, Yuriko; Chew, Terri; Bondy, Melissa; Berger, Mitchel S.

2002-01-01

The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines. PMID:12356358

Computed tomography findings of ovarian metastases from colon cancer: comparison with primary malignant ovarian tumors.

PubMed

Choi, Hyuck Jae; Lee, Joo-Hyuk; Seo, Sang-Soo; Lee, Sun; Kim, Seok Ki; Kim, Joo-Young; Lee, Jong Seok; Park, Sang-Yoon; Kim, Young Hoon

2005-01-01

The computed tomography (CT) findings of ovarian metastases from colon cancer were evaluated and were compared with those of primary malignant ovarian tumors. Sixteen patients with 21 masses from colon cancer and 20 patients with 31 primary malignant ovarian tumors were included in this study. The CT findings (laterality, size, margin, shape, mass characteristic, strong enhancement of cyst wall, enhancement of solid portion, amount of ascites, peritoneal seeding, lymph node enlargement, and metastasis) and ages of the patients in both groups were compared. Univariate analysis, the Pearson chi test, and the independent-samples t test were used to distinguish them. A smooth margin of the tumor (odds ratio=24.3, 95% confidence interval: 2.9-204.2) and cystic nature of the mass (Pearson chi=12.96, P=0.005) were strong predictors of ovarian metastasis from colon cancer. Ovarian metastases from colon cancer show a smooth margin and more cystic nature on CT compared with primary malignant ovarian tumors.

[A rare primary tumor of the mediastinum: pleomorphic liposarcoma].

PubMed

Msaad, S; Yangui, I; Ayedi, L; Ketata, W; Sellami, T; Ayoub, A; Jlidi, R

2007-12-01

Liposarcoma of the mediastinum is a rare tumor with various histologic features. We report a case of mediatinal pleomorphic liposarcoma in a 37-year-old man who complained of chest pain. Computed tomography showed an anterior expansive process within the mediastinum. Histological diagnosis was established by a trans-thoracic computed tomography guided core-needle biopsy. Despite a first cure of chemotherapy with gemcitabin/cisplatin, disease progression led to death 3 months after diagnosis. Mediastinal pleomorphic liposarcoma is an exceptional invading tumor affecting the middle-aged adult. This tumor, usually giant, becomes symptomatic by compression of mediastinal structures. Surgery is the best treatment when possible. The role of radiotherapy and chemotherapy are discussed. Prognosis depends both on the quality of resection and the grade malignancy.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

PubMed

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

Polyclonal origin of parathyroid tumors is common and is associated with multiple gland disease in primary hyperparathyroidism.

PubMed

Shi, Yuhong; Azimzadeh, Pedram; Jamingal, Sarada; Wentworth, Shannon; Ferlitch, Janice; Koh, James; Balenga, Nariman; Olson, John A

2018-01-01

Parathyroid tumors are mostly considered monoclonal neoplasms, the rationale for focused parathyroidectomy in primary hyperparathyroidism. We reported that flow sorting parathyroid tumor cells and methylation-sensitive polymerase chain reaction (me-PCR) of polymorphic human androgen receptor gene and phosphoglycerate kinase gene alleles in deoxyribonucleic acid reveals that ≤35% of parathyroid tumors are polyclonal. We sought to confirm these findings and assess for clinical relevance. Parathyroid tumors from 286 female primary hyperparathyroidism patients were analyzed for clonal status. Tumor clonal status was compared with clinical variables and operative findings. Statistical analysis was performed and significance was established at P < .05. In the study, 176 (62%) patients were informative for human androgen receptor gene and/or phosphoglycerate kinase gene. Assignment of clonal status was made in 119 (68%) tumors, of which 64 (54%) were monoclonal and 55 (46%) were polyclonal. Comparison of tumor clonal status to clinical variables in patients with complete operative data (N = 82) showed that while clinical features were the same between tumor types, patients with polyclonal tumors more often had multiple gland disease (risk ratio 4.066, confidence interval, 1.016-16.26; P = .039) potentially missed at unilateral neck exploration. This work confirms that primary hyperparathyroidism is often the result of polyclonal tumors and that parathyroid tumor clonal status may be associated with multiple gland disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary intra-abdominal malignant fibrous histiocytoma: a highly aggressive tumor.

PubMed

Salemis, Nikolaos S; Gourgiotis, Stavros; Tsiambas, Evangelos; Panagiotopoulos, Nikolaos; Karameris, Andreas; Tsohataridis, Efstathios

2010-12-01

Malignant fibrous histiocytoma (MFH) is the most common soft-tissue sarcoma of late adult life occurring predominantly in the extremities. Primary intra-abdominal MFH is a very rare occurrence. The aim of this study is to describe a very rare case of an intra-abdominal MFH with a highly aggressive clinical course. A 67-year-old male was referred to our department with a 2-week history of dull lower abdominal pain and a gradually enlarging right lower abdominal mass, which he first noticed 2 months prior to admission. Computed tomography (CT) scan demonstrated a mass in the right iliac fossa. On exploratory laparotomy, a tumor was found in the right iliac fossa attached to the parietal lateral peritoneum without any evidence of invasion into the adjacent structures. Complete excision of the tumor with clear margins was performed. Histological and immunohistochemical examinations showed a MFH. One month after surgery, while on adjuvant chemotherapy, the patient was readmitted with dyspnea and a slightly palpable mass in the area of the previous radical resection. CT scan revealed local tumor recurrence along with multiple pulmonary metastatic deposits. Unfortunately, despite treatment, the patient died of progressive disease 5 weeks later. Primary intra-abdominal MFH is a very rare but aggressive malignancy with a high tendency of local recurrence and metastatic spread. Early detection and complete surgical excision with clear margins is the treatment of choice. In some cases, however, the tumor can exhibit a highly aggressive clinical course despite radical surgery and adjuvant therapy.

Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillett, N.A.; Muggenburg, B.A.; Mewhinney, J.A.

1988-11-01

Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of /sup 238/PuO/sub 2/. Initial deposition of /sup 238/PuO/sub 2/ in the respiratory tract was followed by translocation of a portion of the /sup 238/Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to /sup 238/PuO/sub 2/, 112 dogs died or were killed 4000 days after /sup 238/Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become moremore » pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that /sup 238/Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of /sup 238/Pu.« less

CUP Syndrome-Metastatic Malignancy with Unknown Primary Tumor.

PubMed

Zaun, Gregor; Schuler, Martin; Herrmann, Ken; Tannapfel, Andrea

2018-03-09

2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP. This review is based on pertinent publications retrieved by a selective search in PubMed with an emphasis on articles from the past decade. The current guidelines and recommendations of specialty societies were also considered in the evaluation. CUP most commonly manifests itself as metastases to the lymph nodes, lungs, liver, or bones. With the aid of imaging studies, including functional hybrid imaging and further medical examination, a primary tumor can be discovered in up to 40% of patients initially diagnosed with CUP. Immunohistochemistry guided by histomorphology often enables precise characterization of the lesion and can be supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The most commonly detected types of primary tumor are cancers of the lung, pancreas, liver, and biliary system. For patients with local metastases, surgical resection or radiotherapy with curative intent is usually indicated, sometimes in the framework of a multimodal treatment concept. The median 2-year survival of patients with disseminated CUP is only 20%. For such patients, specific types of systemic therapy are recommended on the basis of the diagnostic characterization of the disease. Immune-modulatory antibodies can be effective, particularly in the treatment of CUP that has been characterized with biomarkers, but should still be considered experimental at present. A combination of conventional and innovative diagnostic methods enables the provision of highly refined therapeutic strategies to patients with CUP who are undergoing treatment in interdisciplinary cancer centers.

Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

PubMed

Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

2007-08-01

Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

Primary tumor resection in metastatic breast cancer: A propensity-matched analysis, 1988-2011 SEER data base.

PubMed

Vohra, Nasreen A; Brinkley, Jason; Kachare, Swapnil; Muzaffar, Mahvish

2018-03-02

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988-2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score-matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score-matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity-matched analysis. © 2018 Wiley Periodicals, Inc.

Intratumoral hemorrhage because of primary spinal mixed germ cell tumor presenting with atypical radiological features in an adult.

PubMed

Yamamoto, Junkoh; Takahashi, Mayu; Nakano, Yoshiteru; Saito, Takeshi; Kitagawa, Takehiro; Ueta, Kunihiro; Miyaoka, Ryo; Nakamura, Eiichiro; Nishizawa, Shigeru

2013-10-01

Germ cell tumors are known to arise in the central nervous system, usually in the intracranial regions. However, primary spinal mixed germ cell tumors are extremely rare. This is the first reported case of intratumoral hemorrhage because of a primary spinal mixed germ cell tumor consisting of germinoma and immature teratoma in the conus medullaris of an adult patient that presented with rapid changes on magnetic resonance image (MRI). We report this rare case and discuss the clinical manifestations of an intramedullary spinal mixed germ cell tumor in adult. A case report. A 42-year-old woman experienced buttock numbness, and a spinal cord tumor was observed on the conus medullaris on MRI. The patient was scheduled for an operation in 1 month, but she developed sudden-onset neurologic deterioration. Rapid progression of the tumor was observed on follow-up MRI. The tumor was removed by emergency surgery and was identified as a primary mixed germinoma and immature teratoma. The patient received adjuvant chemotherapy and radiotherapy after gross total resection. The neurologic deficit of the patient was relieved, and recurrence of the tumor was not observed 26 months after the surgery. We present this rare case and emphasize the necessity of precise diagnosis and early treatment of primary spinal germ cell tumor. Close observation on MRI is required after surgery, and adjuvant chemotherapy and radiotherapy should be considered according to the pathologic features. Copyright © 2013 Elsevier Inc. All rights reserved.

Ribonuclease binase inhibits primary tumor growth and metastases via apoptosis induction in tumor cells.

PubMed

Mironova, Nadezhda L; Petrushanko, Irina Y; Patutina, Olga A; Sen'kova, Aexandra V; Simonenko, Olga V; Mitkevich, Vladimir A; Markov, Oleg V; Zenkova, Marina A; Makarov, Alexander A

2013-07-01

Exogenous ribonucleases are known to inhibit tumor growth via apoptosis induction in tumor cells, allowing to consider them as promising anticancer drugs for clinical application. In this work the antitumor potential of binase was evaluated in vivo and the mechanism of cytotoxic effect of binase on tumor cells was comprehensively studied in vitro. We investigated tumoricidal activity of binase using three murine tumor models of Lewis lung carcinoma (LLC), lymphosarcoma RLS 40 and melanoma B-16. We show for the first time that intraperitoneal injection of binase at a dose range 0.1-5 mg/kg results in retardation of primary tumor growth up to 45% in LLC and RLS 40 and inhibits metastasis up to 50% in LLC and RLS 40 and up to 70% in B-16 melanoma. Binase does not exhibit overall toxic effect and displays a general systemic and immunomodulatory effects. Treatment of RLS 40-bearing animals with binase together with polychemotherapy revealed that binase decreases the hepatotoxicity of polychemotherapy while maintaining its antitumor effect. It was demonstrated that the cytotoxic effect of binase is realized via the induction of the intrinsic and extrinsic apoptotic pathways. Activation of intrinsic apoptotic pathway is manifested by a drop of mitochondrial potential, increase in calcium concentration and inhibition of respiratory activity. Subsequent synthesis of TNF-α in the cells under the action of binase triggers extrinsic apoptotic pathway through the binding of TNF with cell-death receptors and activation of caspase 8. Thus binase is a potential anticancer therapeutics inducing apoptosis in cancer cells.

Primary osseous tumors of the pediatric spinal column: review of pathology and surgical decision making.

PubMed

Ravindra, Vijay M; Eli, Ilyas M; Schmidt, Meic H; Brockmeyer, Douglas L

2016-08-01

Spinal column tumors are rare in children and young adults, accounting for only 1% of all spine and spinal cord tumors combined. They often present diagnostic and therapeutic challenges. In this article, the authors review the current management of primary osseous tumors of the pediatric spinal column and highlight diagnosis, management, and surgical decision making.

Long-term primary culture of mouse mammary tumor cells: production of virus.

PubMed

Young, L J; Cardiff, R D; Ashley, R L

1975-05-01

Long-term primary cultures of mouse mammary tumor cells proved an excellent source of mouse mammary tumor virus (MMTV). Virus purified from these primary cultures had the same morphologic biochemical, immunologic, and biologic characteristics as MMTV. Quantitation of MMTV-protein equivalents released into the medium was measured by the radioimmunoassay for MMTV. Peak production levels were 20-40 mug MMTV protien equivalents/75-cm-2 flask/24 hours. These cultures produced MMTV for as long as 90 days. MMTV cultivation depended on the initial cell-plating density and hormones. Maximal MMTV release was obtained at a plating density of 1 times 10-6 cells/cm-2 in the presence of insulin and hydrocortisone. Insulin alone gave basal levels of MMTV, and hydrocortisone alone increased MMTV release only three-fold, but insulin and hydrocortisone together effected an eightfold increase in MMTV release. This suggested that hydrocortisone had a primary effect on MMTV release and insulin acted synergistically with hydrocortisone to maximize MMTV release.

Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer

DTIC Science & Technology

2006-07-01

surrounding bone microenvironment were investigated by purifying endothelial cells from tumor-burdened and non-tumor burdened spines . 4T1...of Balb/c mice. Fresh resected tissue (normal fat pad, primary tumor tissue or the metastatic sites spine , femur and lung) was obtained and cell... Hedgehog signalling pathway: Lasp1, CREBBP/EP300 inhibitory protein 1 and FoxP1. Of interest as well are a number of differentially regulated ESTs

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

PubMed

Zhang, Rong-Xin; Ma, Wen-Juan; Gu, Yu-Ting; Zhang, Tian-Qi; Huang, Zhi-Mei; Lu, Zhen-Hai; Gu, Yang-Kui

2017-07-27

It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Surgical Treatment of Metastatic Ovarian Tumors From Extragenital Primary Sites.

PubMed

Sal, Veysel; Demirkiran, Fuat; Topuz, Samet; Kahramanoglu, Ilker; Yalcin, Ibrahim; Bese, Tugan; Sozen, Hamdullah; Tokgozoglu, Nedim; Salihoglu, Yavuz; Turan, Hasan; Iyibozkurt, Cem; Kolomuc, Tugba; Sofiyeva, Nigar; Berkman, Sinan; Arvas, Macit

2016-05-01

The purpose of this study was to investigate the outcomes and prognostic factors of metastasectomy in patients with metastatic ovarian tumors from extragenital primary sites. All patients with pathologically confirmed metastatic ovarian tumors between January 1997 and June 2015 were included in this study. A total of 131 patients were identified. The data were obtained from the patients' medical records. Clinicopathological features were evaluated by both univariate and multivariate analyses. The primary sites were colorectal region (53.4%), stomach (26%), and breast (13%). Preoperative serum CA 125 and CA 19-9 levels were elevated in 29.4% and 39.8% of the patients, respectively. Cytoreductive surgery was performed in 41.2% of the patients. Seventy-three (55.7%) patients had no residual disease after surgery. Sixty-six (49.6%) patients had combined metastases at the time of the surgery to sites including the liver, pancreas, lung, bone, lymph nodes, bladder, or the intestine. With a median follow-up of 33 months, the median survival time was 22 months. The estimated 5-year survival probability is 0.26. On univariate analysis, primary cancer site, combined metastasis outside the ovaries, residual disease, preoperative serum CA 125 and CA 19-9 levels, and histologic type were significant parameters for overall survival. Furthermore, residual disease, preoperative serum CA 19-9 level, and primary cancer site were found to be independent prognostic factors on multivariate analysis. The most common primary sites for ovarian metastasis are gastrointestinal tract. Metastasectomy may have beneficial effects on survival, especially if the residual disease is less than 5 mm. Prospective studies warranted to evaluate the value of metastasectomy in patients with ovarian metastasis.

BRAF/NRAS mutation frequencies among primary tumors and metastases in patients with melanoma.

PubMed

Colombino, Maria; Capone, Mariaelena; Lissia, Amelia; Cossu, Antonio; Rubino, Corrado; De Giorgi, Vincenzo; Massi, Daniela; Fonsatti, Ester; Staibano, Stefania; Nappi, Oscar; Pagani, Elena; Casula, Milena; Manca, Antonella; Sini, Mariacristina; Franco, Renato; Botti, Gerardo; Caracò, Corrado; Mozzillo, Nicola; Ascierto, Paolo A; Palmieri, Giuseppe

2012-07-10

The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues. In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites. BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples. In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.

Tumor associated CD70 expression is involved in promoting tumor migration and macrophage infiltration in GBM.

PubMed

Ge, Haitao; Mu, Luyan; Jin, Linchun; Yang, Changlin; Chang, Yifan Emily; Long, Yu; DeLeon, Gabriel; Deleyrolle, Loic; Mitchell, Duane A; Kubilis, Paul S; Lu, Dunyue; Qi, Jiping; Gu, Yunhe; Lin, Zhiguo; Huang, Jianping

2017-10-01

Tumor migration/metastasis and immunosuppression are major obstacles in effective cancer therapy. Incidentally, these 2 hurdles usually coexist inside tumors, therefore making therapy significantly more complicated, as both oncogenic mechanisms must be addressed for successful therapeutic intervention. Our recent report highlights that the tumor expression of a TNF family member, CD70, is correlated with poor survival for primary gliomas. In this study, we investigated how CD70 expression by GBM affects the characteristics of tumor cells and the tumor microenvironment. We found that the ablation of CD70 in primary GBM decreased CD44 and SOX2 gene expression, and inhibited tumor migration, growth and the ability to attract monocyte-derived M2 macrophages in vitro. In the tumor microenvironment, CD70 was associated with immune cell infiltrates, such as T cells; myeloid-derived suppressor cells; and monocytes/macrophages based on the RNA-sequencing profile. The CD163+ macrophages were far more abundant than T cells were. This overwhelming level of macrophages was identified only in GBM and not in low-grade gliomas and normal brain specimens, implying their tumor association. CD70 was detected only on tumor cells, not on macrophages, and was highly correlated with CD163 gene expression in primary GBM. Additionally, the co-expression of the CD70 and CD163 genes was found to correlate with decreased survival for patients with primary GBM. Together, these data suggest that CD70 expression is involved in promoting tumor aggressiveness and immunosuppression via tumor-associated macrophage recruitment/activation. Our current efforts to target this molecule using chimeric antigen receptor T cells hold great potential for treating patients with GBM. © 2017 UICC.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

PubMed

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

[Gynecological malignant tumor related multiple primary malignant neoplasms: clinical analysis of 30 cases].

PubMed

Shi, Li; Zhou, Shulin; Jiang, Yi; Wan, Yicong; Ma, Jingjing; Fu, Shilong; Cheng, Wenjun

2014-03-01

To investigate the clinical features of gynecological malignant tumor related multiple primary malignant neoplasms (MPMN). Apply retrospective and comprehensive analysis to the clinical data of 30 patients with gynecological malignant tumor related MPMN. Synchronous MPMN were found in 9 patients. Their average age was 50.2 years old and their median age was 49 years old. The neoplasms were located at ovary, uterus, cervix, breast and intestine. Metachronous MPMN were found in 21 patients. Their average age was 57.7 and their median age was 57 years old. The median interval between the first and the second primary malignant neoplasm was 4.0 years. The neoplasms were located at breast, ovary, uterus, gastrointestinal tract, uterine cervix, lung etc. In 30 cases, 26 of them were treated by surgical operation and further adjunctive treatment of chemotherapy and (or) radiotherapy was conducted as per the neoplasm staging and its pathological results. The rest 4 patients (first primary malignant neoplasms were excised from 3 of them and another one was not treated by surgical operation) received adjunctive treatment of chemotherapy and (or) radiotherapy. Followed ups, which varied from 6 to 60 months, were made to 29 patients and 20 out of the 29 were alive.5-year survival rate of patients with gynecological malignant tumor related MPMN was 47.8%, 2-year survival rate was 73.9%, and 1-year survival rate was 88.6%. Pay more attention to the patients with gynecological malignant tumor related MPMN, examine the high-risk patients with malignant tumor comprehensively, identify whether it is recurrence, metastasis or new growth of malignant neoplasm, and further ensure early diagnosis and proper treatment, avoiding misdiagnosis and missed diagnosis.

Local control of metastatic lung tumors treated with SBRT of 48 Gy in four fractions: in comparison with primary lung cancer.

PubMed

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro; Shinkai, Tetsu; Kubo, Yoshiro; Sugawara, Yoshifumi; Inoue, Takeshi; Sakai, Shinya; Aono, Shoji; Takahashi, Tadaaki; Semba, Takatoshi; Uwatsu, Kotaro

2010-02-01

The optimal dose of stereotactic body radiotherapy (SBRT) for metastatic lung tumors has not been clarified. Local control rates of metastatic lung tumors treated with SBRT of 48 Gy in four fractions, which is one of the common dose schedules for Stage I primary lung cancer in Japan, were examined. Between 2006 and 2008, 12 metastatic lung tumors (colorectal cancer, 7; others, 5) in 10 patients and 56 lesions of Stage I primary lung cancer (T1, 43; T2, 13) in 52 patients were treated with SBRT of 48 Gy in four fractions at the isocenter. Two-year overall survival rates were 86% for patients with metastatic lung tumors and 96% for patients with Stage I primary lung cancer (P = 0.4773). One- and 2-year local control rates were 48% and 25% for metastatic lung tumors, and 91% and 88% for Stage I primary lung cancer, respectively (P < 0.0001). The local control rates after SBRT of 48 Gy in four fractions were significantly worse in metastatic lung tumors compared with Stage I primary lung cancer. In SBRT, metastatic lung tumors should be clearly differentiated from primary lung cancer and should be given higher doses.

Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram.

PubMed

Policeni, Fabiana; Pakalniskis, Brittany; Yang, Limin

2016-01-01

Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs) are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient's left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI) was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT) to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI.

Primary epithelioid trophoblastic tumor with a synchronous breast carcinoma detected only with FDG-PET/CT Scan.

PubMed

Kara, T; Ozcan Kara, P; Baba, F; Celik, C; Kara Gedik, G

2011-01-01

Epithelioid trophoblastic tumor is a recently described, rare and distinctive type of gestational trophoblastic tumor. We report the case of a 31-year old patient who had a full-term pregnancy 18 months before presentation. She had a right axillary lymph node metastasis and was referred for FDG-PET/CT scan for evaluation of distant metastasis and to detect primary malignancy. The axillary lymph node biopsy revealed metastatic breast carcinoma. FDG-PET/CT revealed increased uptake of right axillary lymph node, soft tissue density lesion with a diameter of 24 mm on left cervical region with increased FDG uptake, increased uptake on cervical region and left inguinal lymph node with increased uptake. Pelvic MRI imaging and ultrasonography were negative for malignancy in cervical region. Biopsy of the lesion was consistent with epithelioid trophoblastic tumor in cervical region. Gestational trophoblastic tumor was not suspected because she had no signs such as abnormal vaginal bleeding. FDG-PET/CT demonstrated the primary lesion in cervical region. We report a rare case of primary epithelioid trophoblastic tumor detected only with FDG-PET/CT scan which synchronized with breast carcinoma. Copyright © 2010 Elsevier España, S.L. and SEMNIM. All rights reserved.

Temporalis myofascial flap for primary cranial base reconstruction after tumor resection.

PubMed

Eldaly, Ahmed; Magdy, Emad A; Nour, Yasser A; Gaafar, Alaa H

2008-07-01

To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Retrospective case series. Tertiary referral center. Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Flap survival, postoperative complications, and donor site morbidity. Patients included 37 males and 4 females ranging in age from 10 to 65 years. Two patients received preoperative and 18 postoperative radiation therapy. Patient follow-up ranged from 4 to 39 months. The whole temporalis muscle was used in 26 patients (63.4%) and only part of a coronally split muscle was used in 15 patients (36.6%). Nine patients had primary donor site reconstruction using a Medpor((R)) (Porex Surgical, Inc., Newnan, GA) temporal fossa implant; these had excellent aesthetic results. There were no cases of complete flap loss. Partial flap dehiscence was seen in six patients (14.6%); only two required surgical débridement. None of the patients developed cerebrospinal leaks or meningitis. One patient was left with complete paralysis of the temporal branch of the facial nerve. Three patients (all had received postoperative irradiation) developed permanent trismus. The temporalis myofascial flap was found to be an excellent reconstructive alternative for a wide variety of skull base defects following tumor ablation. It is a very reliable, versatile flap that is usually available in the operative field with relatively low donor site aesthetic and functional morbidity.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Chien-Yu; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan

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-yearmore » 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.« less

Does Radiotherapy for the Primary Tumor Benefit Prostate Cancer Patients with Distant Metastasis at Initial Diagnosis?

PubMed Central

Cho, Yeona; Chang, Jee Suk; Rha, Koon Ho; Hong, Sung Joon; Choi, Young Deuk; Ham, Won Sik; Kim, Jun Won; Cho, Jaeho

2016-01-01

Purpose/Objectives Treatment of the primary tumor reportedly improves survival in several types of metastatic cancer. We herein evaluated the efficacy and toxicity of radiotherapy for the primary tumor in prostate cancer with metastasis. Materials/Methods The study cohort included 140 men with metastatic prostate cancer at initial diagnosis. Metastatic sites were divided into 4 groups as follows: solitary bone, 2–4 bones, ≥5 bones, and visceral organs. Patient, tumor, and treatment characteristics, and clinical outcomes were compared between patients treated with (prostate radiotherapy [PRT] group) or without radiotherapy to the primary tumor. Results Patients in PRT group presented with a statistically significantly younger age (p = .02), whereas other characteristics showed no significant difference. Overall survival (OS) and biochemical failure-free survival (BCFFS) were improved in PRT patients (3-year OS: 69% vs. 43%, p = 0.004; 3-year BCFFS: 52% vs. 16%, p = 0.002). Multivariate analysis identified PRT as a significant predictor of both OS (hazard ratio [HR] = 0.43, p = 0.015). None of the 38 PRT patients experienced severe (grade ≥3) genitourinary or gastrointestinal toxicity. Conclusions Our data suggest that radiotherapy to the primary tumor was associated with improved OS and BCFFS in metastatic prostate cancer. The results of this study warrant prospective controlled clinical trials of this approach in stage IV prostate cancer patients with limited extent of bone metastasis and good performance status. PMID:26807740

Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1

PubMed Central

Smith, Melissa E.; Cimica, Velasco; Chinni, Srinivasa; Jana, Suman; Koba, Wade; Yang, Zhixia; Fine, Eugene; Zagzag, David; Montagna, Cristina; Kalpana, Ganjam V.

2011-01-01

Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16Ink4a and p21CIP. RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered, Ini1+/− mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in Ini1+/− mice. In a PET-guided longitudinal study, we found that treating Ini1+/− mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased CCND1 copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that Ini1+/− mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which is essential for developing effective treatment strategies against these aggressive tumors. PMID:21173237

Primary Tr1 cells from metastatic melanoma eliminate tumor-promoting macrophages through granzyme B- and perforin-dependent mechanisms.

PubMed

Yan, Hongxia; Zhang, Ping; Kong, Xue; Hou, Xianglian; Zhao, Li; Li, Tianhang; Yuan, Xiaozhou; Fu, Hongjun

2017-04-01

In malignant melanoma, tumor-associated macrophages play multiple roles in promoting tumor growth, such as inducing the transformation of melanocytes under ultraviolet irradiation, increasing angiogenesis in melanomas, and suppressing antitumor immunity. Because granzyme B- and perforin-expressing Tr1 cells could specifically eliminate antigen-presenting cells of myeloid origin, we examined whether Tr1 cells in melanoma could eliminate tumor-promoting macrophages and how the interaction between Tr1 cells and macrophages could affect the growth of melanoma cells. Tr1 cells were characterized by high interleukin 10 secretion and low Foxp3 expression and were enriched in the CD4 + CD49b + LAG-3 + T-cell fraction. Macrophages derived from peripheral blood monocytes in the presence of modified melanoma-conditioned media demonstrated tumor-promoting capacity, exemplified by improving the proliferation of cocultured A375 malignant melanoma cells. But when primary Tr1 cells were present in the macrophage-A375 coculture, the growth of A375 cells was abrogated. The conventional CD25 + Treg cells, however, were unable to inhibit macrophage-mediated increase in tumor cell growth. Further analyses showed that Tr1 cells did not directly eliminate A375 cells, but mediated the killing of tumor-promoting macrophages through the secretion of granzyme B and perforin. The tumor-infiltrating interleukin 10 + Foxp3 - CD4 + T cells expressed very low levels of granzyme B and perforin, possibly suggested the downregulation of Tr1 cytotoxic capacity in melanoma tumors. Together, these data demonstrated an antitumor function of Tr1 cells through the elimination of tumor-promoting macrophages, which was not shared by conventional Tregs.

Prevalence estimates for primary brain tumors in the United States by age, gender, behavior, and histology.

PubMed

Porter, Kimberly R; McCarthy, Bridget J; Freels, Sally; Kim, Yoonsang; Davis, Faith G

2010-06-01

Prevalence is the best indicator of cancer survivorship in the population, but few studies have focused on brain tumor prevalence because of previous data limitations. Hence, the full impact of primary brain tumors on the healthcare system in the United States is not completely described. The present study provides an estimate of the prevalence of disease in the United States, updating an earlier prevalence study. Incidence data for 2004 and survival data for 1985-2005 were obtained by the Central Brain Tumor Registry of the United States from selected regions, modeled under 2 different survival assumptions, to estimate prevalence rates for the year 2004 and projected estimates for 2010. The overall incidence rate for primary brain tumors was 18.1 per 100 000 person-years with 2-, 5-, 10-, and 20-year observed survival rates of 62%, 54%, 45%, and 30%, respectively. On the basis of the sum of nonmalignant and averaged malignant estimates, the overall prevalence rate of individuals with a brain tumor was estimated to be 209.0 per 100 000 in 2004 and 221.8 per 100 000 in 2010. The female prevalence rate (264.8 per 100 000) was higher than that in males (158.7 per 100 000). The averaged prevalence rate for malignant tumors (42.5 per 100 000) was lower than the prevalence for nonmalignant tumors (166.5 per 100 000). This study provides estimates of the 2004 (n = 612 770) and 2010 (n = 688 096) expected number of individuals living with primary brain tumor diagnoses in the United States, providing more current and robust estimates for aiding healthcare planning and patient advocacy for an aging US population.

Epilepsy in patients with primary brain tumors: The impact on mood, cognition, and HRQOL.

PubMed

Rahman, Z; Wong, C H; Dexter, M; Olsson, G; Wong, M; Gebsky, V; Nahar, N; Wood, A; Byth, K; King, M; Bleasel, A B

2015-07-01

A primary brain tumor (PBT) is often a fatal disease of the nervous system and has a serious impact on health-related quality of life (HRQOL). Presence of epilepsy and adverse reactions from tumor and epilepsy treatments may cause additional decline in HRQOL. We aimed to study the impact of epileptic seizures on cognition, mood, and HRQOL in patients with brain tumor-related epilepsy. Patients were grouped on an ordinal scale according to epilepsy burden from none to severe based on the presence of epileptic seizures and seizure frequency: L1, no epilepsy; L2, with epilepsy, seizure-free in the last 6 months with antiepileptic drugs; and L3, with epilepsy, at least one seizure in the last 6 months with AEDs. Health-related quality of life was measured by Functional Assessment of Cancer Therapy-Brain (FACT-Br) and Quality of Life in Epilepsy-31 (QOLIE-31) tools, cognition by the Montreal Cognitive Assessment (MoCA) tool and Frontal Assessment Battery (FAB), mood by the Hospital Anxiety and Depression Scale (HADS), activities of daily living (ADLs) by the Barthel Index (BI), and performance status by the Karnofsky Performance Status (KPS) scale in patients with primary brain tumors at least one month following neurosurgery with or without radiotherapy and chemotherapy. Eighty-one patients with a diagnosis of primary brain tumors were recruited. Sixty-eight percent of patients were diagnosed with primary brain tumor-related epilepsy, 50.61% patients had cognitive impairment, 33% had abnormal scores in the anxiety scale, and 34% had abnormal scores in the depression scale. There were no statistically significant differences in these scores among L1, L2, and L3 groups. There were statistically significant differences in duration of disease and KPS and BI scores between L1 and L3 groups. The L3 group has significantly longer duration of disease and scored low in both the BI and KPS scale when compared to the L1 group. All patients with primary brain tumors scored

[Echocardiography in diagnosis of primary cardiac tumors in pediatrics].

PubMed

Erdmenger Orellana, Julio; Vázquez, Clara; Ortega Maldonado, Jesús

2005-01-01

We report the experience in the diagnosis of primary cardiac tumor during the period from 1999 to 2004, 8500 studies were revised echocardiographic carried out. We found 21 patients, 11 of female sex (55%). In 15/21 (71%), the age of presentation was less than 1 year. In 9/21 the tumor was multiple (42.8%), lodged in the ventricle right in 2/21 (9.5%), in the ventricle left 3 (14.2%), 8 in the septum interventricular (38%) and 4 compromised the auriculas. They were classified like rabdomiomas 14 (66%), 5 associates with sclerosis tuberosa, 4 mixomas (19%), 2 fibromas (9.5%) and 1 rabdomiosarcoma (4.7%). In five patients the diagnosis was prenatal. The global mortality went of 9.5%. The echocardiograpy is a good diagnosis method in our series the rabdomioma occupied the first place in frequency.

Thermal ablation of intrahepatic cholangiocarcinoma: Safety, efficacy, and factors affecting local tumor progression.

PubMed

Takahashi, Edwin A; Kinsman, Kristin A; Schmit, Grant D; Atwell, Thomas D; Schmitz, John J; Welch, Brian T; Callstrom, Matthew R; Geske, Jennifer R; Kurup, A Nicholas

2018-06-04

To evaluate the safety and oncologic efficacy of percutaneous thermal ablation of intrahepatic cholangiocarcinoma (ICC) and identify risk factors for local tumor progression (LTP). Retrospective review of an institutional tumor ablation registry demonstrated that 20 patients (9 males, 11 females; mean age 62.5 ± 15.8 years) with 50 ICCs (mean size 1.8 ± 1.3 cm) were treated with percutaneous radiofrequency ablation (RFA) or microwave ablation (MWA) between 2006 and 2015. Thirty-eight of the treated ICCs (76%) were metastases that developed after surgical resection of the primary tumor. Patient demographics, procedure technical parameters, and clinical outcomes were reviewed. A Cox proportional hazards model was used to examine the risk of LTP by ablation modality. Survival analyses were performed using the Kaplan-Meier method. Mean imaging follow-up time was 41.5 ± 42.7 months. Forty-four (88%) ICCs were treated with RFA, and 6 (12%) with MWA. Eleven (22%) cases of LTP developed in 5 (25%) patients. The median time to LTP among these 11 tumors was 7.1 months (range, 2.3-22.9 months). Risk of LTP was not significantly different for ICCs treated with MWA compared to RFA (HR 2.72; 95% CI 0.58-12.84; p = 03.21). Median disease-free survival was 8.2 months (1.1-70.4 months), and median overall survival was 23.6 months (7.4-122.5 months). No major complication occurred. Percutaneous thermal ablation is a safe and effective treatment for patients with ICCs and may be particularly valuable in unresectable patients, or those who have already undergone hepatic surgery. Tumor size and ablation modality were not associated with LTP, whereas primary tumors and superficially located tumors were more likely to subsequently recur.

Effect of gibberellic Acid on crown gall tumor induction in aging primary pinto bean leaves.

PubMed

Anand, V K; Bauer, C; Heberlein, G T

1975-06-01

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.

Breed-specific incidence rates of canine primary bone tumors — A population based survey of dogs in Norway

PubMed Central

Anfinsen, Kristin P.; Grotmol, Tom; Bruland, Oyvind S.; Jonasdottir, Thora J.

2011-01-01

This is one of few published population-based studies describing breed specific rates of canine primary bone tumors. Incidence rates related to dog breeds could help clarify the impact of etiological factors such as birth weight, growth rate, and adult body weight/height on development of these tumors. The study population consisted of dogs within 4 large/giant breeds; Irish wolfhound (IW), Leonberger (LB), Newfoundland (NF), and Labrador retriever (LR), born between January 1st 1989 and December 31st 1998. Questionnaires distributed to owners of randomly selected dogs — fulfilling the criteria of breed, year of birth, and registration in the Norwegian Kennel Club — constituted the basis for this retrospective, population-based survey. Of the 3748 questionnaires received by owners, 1915 were completed, giving a response rate of 51%. Forty-three dogs had been diagnosed with primary bone tumors, based upon clinical examination and x-rays. The breeds IW and LB, with 126 and 72 cases per 10 000 dog years at risk (DYAR), respectively, had significantly higher incidence rates of primary bone tumors than NF and LR (P < 0.0001). Incidence rates for the latter were 11 and 2 cases per 10 000 DYAR, respectively. Pursuing a search for risk factors other than body size/weight is supported by the significantly different risks of developing primary bone tumors between similarly statured dogs, like NF and LB, observed in this study. Defining these breed-specific incidence rates enables subsequent case control studies, ultimately aiming to identify specific etiological factors for developing primary bone tumors. PMID:22210997

Drug screening of cancer cell lines and human primary tumors using droplet microfluidics.

PubMed

Wong, Ada Hang-Heng; Li, Haoran; Jia, Yanwei; Mak, Pui-In; Martins, Rui Paulo da Silva; Liu, Yan; Vong, Chi Man; Wong, Hang Cheong; Wong, Pak Kin; Wang, Haitao; Sun, Heng; Deng, Chu-Xia

2017-08-22

Precision Medicine in Oncology requires tailoring of therapeutic strategies to individual cancer patients. Due to the limited quantity of tumor samples, this proves to be difficult, especially for early stage cancer patients whose tumors are small. In this study, we exploited a 2.4 × 2.4 centimeters polydimethylsiloxane (PDMS) based microfluidic chip which employed droplet microfluidics to conduct drug screens against suspended and adherent cancer cell lines, as well as cells dissociated from primary tumor of human patients. Single cells were dispersed in aqueous droplets and imaged within 24 hours of drug treatment to assess cell viability by ethidium homodimer 1 staining. Our results showed that 5 conditions could be screened for every 80,000 cells in one channel on our chip under current circumstances. Additionally, screening conditions have been adapted to both suspended and adherent cancer cells, giving versatility to potentially all types of cancers. Hence, this study provides a powerful tool for rapid, low-input drug screening of primary cancers within 24 hours after tumor resection from cancer patients. This paves the way for further technological advancement to cutting down sample size and increasing drug screening throughput in advent to personalized cancer therapy.

Contemporary Role of Radiotherapy in the Management of Primary Penile Tumors and Metastatic Disease.

PubMed

Crook, Juanita

2016-11-01

Squamous cell cancer of the penis is a radiocurable malignancy all too often managed solely by partial or total penectomy. Effective management of the primary tumor while preserving penile morphology and function is a priority. External radiotherapy and brachytherapy have a role to play in the definitive management of the primary tumor. Surgical nodal staging remains a cornerstone of management because it is the strongest predictor of survival, and inguinal status determines pelvic management. Postoperative radiotherapy of the regional nodes for high-risk pathology is indicated. Chemoradiotherapy should be considered as neoadjuvant treatment for unresectable nodes or as definitive management. Copyright © 2016 Elsevier Inc. All rights reserved.

Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma

PubMed Central

González-Gómez, P.; de la Fuente, M.; Hernández-Laín, Aurelio; Mira, H.; Sánchez-Gómez, P.; Garcia-Fuentes, M.

2015-01-01

Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133+, Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy. PMID:25860932

Immune response in melanoma: an in-depth analysis of the primary tumor and corresponding sentinel lymph node

PubMed Central

Ma, Michelle W.; Medicherla, Ratna C.; Qian, Meng; de Miera, Eleazar Vega-Saenz; Friedman, Erica B.; Berman, Russell S.; Shapiro, Richard L.; Pavlick, Anna C.; Ott, Patrick A.; Bhardwaj, Nina; Shao, Yongzhao; Osman, Iman; Darvishian, Farbod

2013-01-01

The sentinel lymph node is the initial site of metastasis. Down-regulation of anti-tumor immunity plays a role in nodal progression. Our objective was to investigate the relationship between immune modulation and sentinel lymph node positivity, correlating it with outcome in melanoma patients. Lymph node/primary tissues from melanoma patients prospectively accrued and followed at New York University Medical Center were evaluated for the presence of regulatory T-cells (Foxp3+) and dendritic cells (conventional: CD11c+, mature: CD86+) using immunohistochemistry. Primary melanoma immune cell profiles from sentinel lymph node-positive/-negative patients were compared. Logistic regression models inclusive of standard-of-care/immunologic primary tumor characteristics were constructed to predict the risk of sentinel lymph node positivity. Immunological responses in the positive sentinel lymph node were also compared to those in the negative non-sentinel node from the same nodal basin and matched negative sentinel lymph node. Decreased immune response was defined as increased regulatory T-cells or decreased dendritic cells. Associations between the expression of these immune modulators, clinicopathologic variables, and clinical outcome were evaluated using univariate/multivariate analyses. Primary tumor conventional dendritic cells and regression were protective against sentinel lymph node metastasis (odds ratio=0.714, 0.067; P=0.0099, 0.0816, respectively). Anti-tumor immunity was down-regulated in the positive sentinel lymph node with an increase in regulatory T-cells compared to the negative non-sentinel node from the same nodal basin (P=0.0005) and matched negative sentinel lymph node (P=0.0002). The positive sentinel lymph node also had decreased numbers of conventional dendritic cells compared to the negative sentinel lymph node (P<0.0001). Adding sentinel lymph node regulatory T-cell expression improved the discriminative power of a recurrence risk assessment model

SU-E-I-100: Heterogeneity Studying for Primary and Lymphoma Tumors by Using Multi-Scale Image Texture Analysis with PET-CT Images

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Dengwang; Wang, Qinfen; Li, H

Purpose: The purpose of this research is studying tumor heterogeneity of the primary and lymphoma by using multi-scale texture analysis with PET-CT images, where the tumor heterogeneity is expressed by texture features. Methods: Datasets were collected from 12 lung cancer patients, and both of primary and lymphoma tumors were detected with all these patients. All patients underwent whole-body 18F-FDG PET/CT scan before treatment.The regions of interest (ROI) of primary and lymphoma tumor were contoured by experienced clinical doctors. Then the ROI of primary and lymphoma tumor is extracted automatically by using Matlab software. According to the geometry size of contourmore » structure, the images of tumor are decomposed by multi-scale method.Wavelet transform was performed on ROI structures within images by L layers sampling, and then wavelet sub-bands which have the same size of the original image are obtained. The number of sub-bands is 3L+1.The gray level co-occurrence matrix (GLCM) is calculated within different sub-bands, thenenergy, inertia, correlation and gray in-homogeneity were extracted from GLCM.Finally, heterogeneity statistical analysis was studied for primary and lymphoma tumor using the texture features. Results: Energy, inertia, correlation and gray in-homogeneity are calculated with our experiments for heterogeneity statistical analysis.Energy for primary and lymphomatumor is equal with the same patient, while gray in-homogeneity and inertia of primaryare 2.59595±0.00855, 0.6439±0.0007 respectively. Gray in-homogeneity and inertia of lymphoma are 2.60115±0.00635, 0.64435±0.00055 respectively. The experiments showed that the volume of lymphoma is smaller than primary tumor, but thegray in-homogeneity and inertia were higher than primary tumor with the same patient, and the correlation with lymphoma tumors is zero, while the correlation with primary tumor isslightly strong. Conclusion: This studying showed that there were effective

Zone-specific remodeling of tumor blood vessels affects tumor growth.

PubMed

Tilki, Derya; Kilic, Nerbil; Sevinc, Sema; Zywietz, Friedrich; Stief, Christian G; Ergun, Suleyman

2007-11-15

Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet. By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones. The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative. The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. (c) 2007 American Cancer Society.

Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

PubMed

Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

2018-06-01

Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

Feasibility of Primary Tumor Culture Models and Preclinical Prediction Assays for Head and Neck Cancer: A Narrative Review

PubMed Central

Dohmen, Amy J. C.; Swartz, Justin E.; Van Den Brekel, Michiel W. M.; Willems, Stefan M.; Spijker, René; Neefjes, Jacques; Zuur, Charlotte L.

2015-01-01

Primary human tumor culture models allow for individualized drug sensitivity testing and are therefore a promising technique to achieve personalized treatment for cancer patients. This would especially be of interest for patients with advanced stage head and neck cancer. They are extensively treated with surgery, usually in combination with high-dose cisplatin chemoradiation. However, adding cisplatin to radiotherapy is associated with an increase in severe acute toxicity, while conferring only a minor overall survival benefit. Hence, there is a strong need for a preclinical model to identify patients that will respond to the intended treatment regimen and to test novel drugs. One of such models is the technique of culturing primary human tumor tissue. This review discusses the feasibility and success rate of existing primary head and neck tumor culturing techniques and their corresponding chemo- and radiosensitivity assays. A comprehensive literature search was performed and success factors for culturing in vitro are debated, together with the actual value of these models as preclinical prediction assay for individual patients. With this review, we aim to fill a gap in the understanding of primary culture models from head and neck tumors, with potential importance for other tumor types as well. PMID:26343729

Changes in Signal Intensity of the Dentate Nucleus and Globus Pallidus in Pediatric Patients: Impact of Brain Irradiation and Presence of Primary Brain Tumors Independent of Linear Gadolinium-based Contrast Agent Administration.

PubMed

Tamrazi, Benita; Nguyen, Binh; Liu, Chia-Shang J; Azen, Colleen G; Nelson, Mary B; Dhall, Girish; Nelson, Marvin D

2018-05-01

Purpose To determine whether whole-brain irradiation, chemotherapy, and primary brain pathologic conditions affect magnetic resonance (MR) imaging signal changes in pediatric patients independent of the administration of gadolinium-based contrast agents (GBCAs). Materials and Methods This institutional review board-approved, HIPAA-compliant study included 144 pediatric patients who underwent intravenous GBCA-enhanced MR imaging examinations (55 patients with primary brain tumors and whole-brain irradiation, 19 with primary brain tumors and chemotherapy only, 52 with primary brain tumors without any treatment, and 18 with neuroblastoma without brain metastatic disease). The signal intensities (SIs) in the globus pallidus (GP), thalamus (T), dentate nucleus (DN), and pons (P) were measured on unenhanced T1-weighted images. GP:T and DN:P SI ratios were compared between groups by using the analysis of variance and were analyzed relative to group, total cumulative number of doses of GBCA, age, and sex by using multivariable linear models. Results DN:P ratio for the radiation therapy group was greater than that for the other groups except for the group of brain tumors treated with chemotherapy (P < .05). The number of GBCA doses was correlated with the DN:P ratio for the nontreated brain tumor group (P < .0001). The radiation therapy-treated brain tumor group demonstrated higher DN:P ratios than the nontreated brain tumor group for number of doses less than or equal to 10 (P < .0001), whereas ratios in the nontreated brain tumor group were higher than those in the radiation therapy-treated brain tumor group for doses greater than 20 (P = .05). The GP:T ratios for the brain tumor groups were greater than that for the neuroblastoma group (P = .01). Conclusion Changes in SI of the DN and GP that are independent of the administration of GBCA occur in patients with brain tumors undergoing brain irradiation, as well as in patients with untreated primary brain tumors. © RSNA

Clear cell renal cell carcinoma: a comparative study of histological and chromosomal characteristics between primary tumors and their corresponding metastases.

PubMed

Dagher, Julien; Kammerer-Jacquet, Solène-Florence; Dugay, Frédéric; Beaumont, Marion; Lespagnol, Alexandra; Cornevin, Laurence; Verhoest, Grégory; Bensalah, Karim; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine

2017-07-01

Clear cell renal cell carcinoma (ccRCC) has a poor prognosis with a 50% risk of metastases. Little is known about the phenotypic and molecular profiles of metastases regarding their corresponding primary tumors. This study aimed to screen phenotypic and genotypic differences between metastases and their corresponding primary tumors. We selected four cases with available frozen material. The histological, immunohistochemical (VEGFA, CD31, SMA, Ki67, p53, PAR-3), FISH (VHL gene), next-generation sequencing (VHL and c-MET genes), multiplex ligation-dependent probe amplification, and array-(comparative genomic hybridization) CGH analyses were realized. Metastases were nodal, hepatic (synchronous), adrenal, and pulmonary (metachronous). High-grade tumor cells were significantly more frequent in metastases (p = 0.019). Metastases and high-grade zones of primary tumors shared similar characteristics compared to low-grade zones: a lower microscopic vascular density (43.5 vs 382.5 vessels/mm 2 ; p = 0.0027), a higher expression of VEGF (73 vs 10%, p = 0.045), Ki67 (37.6 vs 8.3%; p = 0.011), and p53 (54 vs 10.6%; p = 0.081), and a cytoplasmic and membranous PAR-3 staining. Metastases exhibited more chromosomal imbalances than primary tumors in total (18.75 ± 6.8; p = 0.044) with more genomic gains (13.5 ± 7; p = 0.013). The loss of chromosome 9 and gain of Xq were found in both primary tumors and metastases but gains of loci or chromosomes 2p, 3q, 5, 8q, 12, and 20 were only found in metastases. The VHL gene status was similar in each tumor couple. Although metastases and primary tumors share common histological features, this study highlights chromosomal differences specific to metastases which could be involved in ccRCC metastatic evolution.

Lack of relevant information for tumor staging in pathology reports of primary cutaneous melanoma.

PubMed

Busam, K J

2001-05-01

For the T classification of primary cutaneous melanoma, the current American Joint Committee on Cancer staging (AJCC) system relies on tumor thickness and level of invasion. A new T classification has been proposed based on thickness and ulceration. The slides and reports of 135 departmental pathology consultations of patients referred to a major cancer center with a diagnosis of primary cutaneous invasive malignant melanoma were examined. Whether the outside pathology reports contained information on tumor thickness, level of invasion, and ulceration was recorded. Dermatopathologists had issued 76.3% of the reports and general surgical pathologists, 24.3%. Information provided was as follows: tumor thickness, 97.8%; Clark level, 71.9%; and presence or absence of ulceration, 28.1%. Of the 97 melanomas with no comment on ulceration, 17 were indeed ulcerated. Thus, the lack of a comment on ulceration cannot be equated with the absence of ulceration. The present study documents that many pathology reports on melanomas lack sufficient information for AJCC staging. Therefore, review of outside pathology material is necessary not only to confirm or revise the tumor diagnosis but also to provide clinicians with histologic parameters required for AJCC staging.

Brain tumor - children

MedlinePlus

... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

The isoform A of reticulon-4 (Nogo-A) in cerebrospinal fluid of primary brain tumor patients: influencing factors.

PubMed

Koper, Olga Martyna; Kamińska, Joanna; Milewska, Anna; Sawicki, Karol; Mariak, Zenon; Kemona, Halina; Matowicka-Karna, Joanna

2018-05-18

The influence of isoform A of reticulon-4 (Nogo-A), also known as neurite outgrowth inhibitor, on primary brain tumor development was reported. Therefore the aim was the evaluation of Nogo-A concentrations in cerebrospinal fluid (CSF) and serum of brain tumor patients compared with non-tumoral individuals. All serum results, except for two cases, obtained both in brain tumors and non-tumoral individuals, were below the lower limit of ELISA detection. Cerebrospinal fluid Nogo-A concentrations were significantly lower in primary brain tumor patients compared to non-tumoral individuals. The univariate linear regression analysis found that if white blood cell count increases by 1 × 10 3 /μL, the mean cerebrospinal fluid Nogo-A concentration value decreases 1.12 times. In the model of multiple linear regression analysis predictor variables influencing cerebrospinal fluid Nogo-A concentrations included: diagnosis, sex, and sodium level. The mean cerebrospinal fluid Nogo-A concentration value was 1.9 times higher for women in comparison to men. In the astrocytic brain tumor group higher sodium level occurs with lower cerebrospinal fluid Nogo-A concentrations. We found the opposite situation in non-tumoral individuals. Univariate linear regression analysis revealed, that cerebrospinal fluid Nogo-A concentrations change in relation to white blood cell count. In the created model of multiple linear regression analysis we found, that within predictor variables influencing CSF Nogo-A concentrations were diagnosis, sex, and sodium level. Results may be relevant to the search for cerebrospinal fluid biomarkers and potential therapeutic targets in primary brain tumor patients. Nogo-A concentrations were tested by means of enzyme-linked immunosorbent assay (ELISA).

Primary small-bowel malignancy: update in tumor biology, markers, and management strategies.

PubMed

Shenoy, Santosh

2014-12-01

Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies. Relevant articles from PubMed/Medline and Embase searches were collected using the phrases "small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma". Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma. Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.

Differential Impact of Close Surgical Margin on Local Recurrence According to Primary Tumor Size in Oral Squamous Cell Carcinoma.

PubMed

Jang, Jeon Yeob; Choi, Nayeon; Ko, Young-Hyeh; Chung, Man Ki; Son, Young-Ik; Baek, Chung-Hwan; Baek, Kwan-Hyuck; Jeong, Han-Sin

2017-06-01

The extent of surgical safety margin (gross tumor border to resection margin) in oral cancer surgery remains unclear, and no study has determined the differential impact of close surgical margin and microscopic extension according to primary tumor size in oral cancers. We retrospectively analyzed the clinical data of 325 patients with surgically treated oral cavity squamous cell carcinomas to determine the effect of a close surgical margin (<5 mm) (cSM 5 ) on local recurrence. In addition, the depth of microscopic tumor infiltration was determined in 90 available surgical specimens. The cSM 5 was not related to the risk of local tumor recurrence in early-stage oral cancer, while it significantly increased the rate of local tumor recurrence in resectable advanced-stage oral cancers (hazard ratio 3.157, 95 % confidence interval 1.050-9.407, p = 0.041). Addition of postoperative adjuvant radiation to early-stage tumors with cSM 5 did not further reduce the local recurrence rate compared to surgery alone. The depth of microscopic tumor extension from the gross tumor border was significantly associated with primary tumor thickness (ρ = 0.390, p < 0.001) and tumor sizes (ρ = 0.308, p = 0.003), which was a median (range) of 0.84 (0.14-2.32) mm in T1, 1.06 (0.20-4.34) mm in T2, and 1.77 (0.13-4.70) mm in T3-4. The cSM 5 was a significant risk factor for local recurrence only in advanced oral cancers, but not in early-stage tumors, where microscopic tumor extension was not beyond 3 mm in T1 tumors. Thus, the extent of surgical safety margin can be redefined according to the primary tumor size.

Epidemiology of pediatric primary malignant central nervous system tumors in Iran: a 10 year report of National Cancer Registry.

PubMed

Beygi, Sara; Saadat, Soheil; Jazayeri, Seyed Behzad; Rahimi-Movaghar, Vafa

2013-08-01

CNS tumors are the leading cause of cancer related deaths among children and adolescents. Nonetheless, the incidence of pediatric CNS tumors in developing countries is poorly understood. We aimed to provide epidemiologic features of primary malignant CNS tumors in Iranian children 0-19 years of age using National Cancer Registry (NCR) data bank. The data recorded by NCR over a 10 year period (2000-2010) were reviewed. Of 1948 tumor cases, 93.3% were located in brain, 5.1% were found in the spinal cord & cauda equina, and 1.6% affected cranial nerves and other parts of the nervous system. The overall average annual age specific incidence rate was 1.43 per 100,000. Males were more likely to develop CNS tumors (1.65 per 100,000) compared to females (1.21 per 100,000, p<0.01). Children under 5 years of age had the highest age specific incidence rate (1.86 per 100,000). Astrocytic tumors with the incidence rate of 0.61 per 100,000 were the most frequent specific histology followed by embryonal (0.38 per 100,000), and ependymal tumors (0.10 per 100,000). With regard to the histological distribution of tumors, some unique features including the high proportion of unspecified malignant neoplasms (7.6%) were noted. The overall incidence rate was markedly lower than western findings. Major differences were also observed in incidence rates of specific histologies. Although the discrepancies may be attributable to diversity in classification schemes and registration practices, a real ethnic and geographical variation in predisposition to development of pediatric CNS cancers is strongly suggested. Copyright © 2013 Elsevier Ltd. All rights reserved.

Primary Culture System for Germ Cells from Caenorhabditis elegans Tumorous Germline Mutants

PubMed Central

Vagasi, Alexandra S.; Rahman, Mohammad M.; Chaudhari, Snehal N.; Kipreos, Edward T.

2017-01-01

The Caenorhabditis elegans germ line is an important model system for the study of germ stem cells. Wild-type C. elegans germ cells are syncytial and therefore cannot be isolated in in vitro cultures. In contrast, the germ cells from tumorous mutants can be fully cellularized and isolated intact from the mutant animals. Here we describe a detailed protocol for the isolation of germ cells from tumorous mutants that allows the germ cells to be maintained for extended periods in an in vitro primary culture. This protocol has been adapted from Chaudhari et al., 2016. PMID:28868332

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

PubMed

Jiang, Meng-Jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

2015-09-01

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common.Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes.Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients.

Epidemiology of primary brain tumors in the Middle Eastern population in California, USA 2001-2005.

PubMed

Nasseri, Kiumarss; Mills, John R

2009-01-01

The fast growing Middle Eastern (ME) population has rarely been studied in the U.S.. The purpose of this study was to compare the epidemiology of primary brain tumors in this ethnic population with the non-Hispanic, non-Middle Eastern White (NHNMW) in California. ME cases were identified by surname in the California cancer registry and ME population estimates were based on ancestry. Data for 683 cases of primary brain tumors (429 benign, 238 malignant, 16 uncertain) in the ME and 15,589 cases (8352 benign, 6812 malignant, 425 uncertain) in the NHNMW were available for this study. ME patients were significantly (p < 0.05) younger and their age-adjusted incidence rates per 100,000 for benign tumors of 10.0 in men and 17.6 in women were higher than similar rates of 7.3 and 10.6 in the NHNMW group (p < 0.05). Rates for malignant tumors were similar. Meningioma was the main histology responsible for the observed increase in patients over 40 years of age. Also increased were benign tumors of the pituitary and pineal glands. The overall mortality in patients with benign tumors was significantly lower than malignant tumors. This study presents a significantly high incidence of benign meningioma in the ME population in California. This may be due to higher susceptibility or exposure of this ethnic group to the risk factor(s) for this neoplasm. Considering the reported causal association of benign meningioma with childhood radiation exposure from Israel, exposure to this risk factor in this ethnic group needs to be evaluated in future studies.

Impact of Surgical Resection of the Primary Tumor on Overall Survival in Patients With Metastatic Pheochromocytoma or Sympathetic Paraganglioma.

PubMed

Roman-Gonzalez, Alejandro; Zhou, Shouhao; Ayala-Ramirez, Montserrat; Shen, Chan; Waguespack, Steven G; Habra, Mouhammed A; Karam, Jose A; Perrier, Nancy; Wood, Christopher G; Jimenez, Camilo

2018-07-01

To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS). Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known. We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information. A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8-183.2 months vs 36 months, 95% CI 27.2-44.8 months; P < 0.001].Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5-105.4 months vs 36 months, 95% CI 29.7-42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion. Primary tumor resection in patients with metastatic PPG appeared to be

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Faisal; Loma Linda University Medical Center, Department of Radiation Oncology, Loma Linda, CA; Sarkar, Vikren

Purpose: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. Materials and methods: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipsemore » treatment planning software. Patients were treated with a median radiation dose of 45 Gy (range: 37.5 to 50 Gy) to the primary volume and 45 Gy (range: 45 to 64.8 Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). Results: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45 Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

PubMed Central

2014-01-01

Background Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs. Methods Tumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells. Results The cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria. Conclusions This study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis

Primary benign tumors in chiropractic practice and the importance of x-ray diagnosis: A report of two cases

PubMed Central

Pelletier, Jacques C.

1987-01-01

Two cases of primary benign bone tumors were diagnosed radiographically in a chiropractic practice. Although primary osseous tumors are somewhat uncommon, their potential presence emphasizes the importance of x-ray diagnosis as an essential adjunct to chiropractic practice. This procedure may preclude underlying lesions before considering treatment of seemingly uncomplicated injuries. Two such cases are presented: unicameral bone cyst and osteochondroma. ImagesFigure 1Figure 2Figure 3

Dynamic Contrast-enhanced Magnetic Resonance Imaging for Differentiating Between Primary Tumor, Metastatic Node and Normal Tissue in Head and Neck Cancer.

PubMed

Chen, Liangliang; Ye, Yufeng; Chen, Hanwei; Chen, Shihui; Jiang, Jinzhao; Dan, Guo; Huang, Bingsheng

2018-06-01

To study the difference of the Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) parameters among the primary tumor, metastatic node and peripheral normal tissue of head and neck cancer. Consecutive newly-diagnosed head and neck cancer patients with nodal metastasis between December 2010 and July 2013 were recruited, and 25 patients (8 females; 24~63,mean 43±11 years old) were enrolled. DCE-MRI was performed in the primary tumor region including the regional lymph nodes on a 3.0-T MRI system. Three quantitative parameters: Ktrans (volume transfer constant), ve (volume fraction of extravascular extracellular space) and kep (the rate constant of contrast transfer) were calculated for the largest node. A repeated-measure ANOVA with a Greenhouse-Geisser correction and post hoc tests using the Bonferroni correction were used to evaluate the differences in Ktrans, ve and kep among primary tumors, metastatic nodes and normal tissue. The values of both Ktrans and ve of normal tissue differed significantly from those of nodes (both P < 0.001) and primary tumors (both P < 0.001) respectively, while no significant differences of Ktrans and ve were observed between nodes and primary tumors (P = 0.075 and 0.365 respectively). The kep values of primary tumors were significantly different from those of nodes (P = 0.001) and normal tissue (P = 0.002), while no significant differences between nodes and normal tissue (P > 0.999). The DCE-MRI parameters were different in the tumors, metastatic nodes and normal tissue in head and neck cancer. These findings may be useful in the characterization of head and neck cancer.

Alcohol Devitalization and Replantation for Primary Malignant Bone Tumors of the Knee Joint

PubMed Central

ZHANG, Xihai; CHEN, Ge; WANG, Jun; TANG, Lian; YIN, Yiran

2017-01-01

Background: This paper is aimed at studying the therapeutic effects of in situ replantation of alcohol-devitalized bone segments to treat malignant bone tumors of the knee joint. Methods: We retrospectively analyzed clinical data for 45 patients from January 2013 to January 2016 who underwent replantation following alcohol-devitalization of bone segments and 40 who underwent prosthesis implantation. The two groups were comparable in basal clinical biometric data, including gender, age, tumor type and location, Enneking staging, and maximum tumor diameter. Radical tumor resection was combined with neoadjuvant chemotherapy following the two-implantation procedures. Results: The median follow-up time was 25 months, and the outcomes were compared. We found no differences in the length of bone lesions, surgery time, intraoperative blood loss, amount of postoperative drainage, and perioperative complications, which were just three for each method. We also found no significant differences in limb function scores, internal fixation imaging scores, tumor-free survival rate, and overall survival rate between the two groups. Replantation following alcohol-devitalization of tumor-bearing bone segment demonstrated similar clinical outcomes compared with prosthesis implantation in the treatment of primary malignant bone tumors of the knee joint. Conclusion: Both therapies enjoy good application safety and effectiveness. Because alcohol devitalization is inexpensive and easy to apply in the clinic, it should be considered a preferred method in the treatment of bone tumors. PMID:29308374

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors.

PubMed

Kundu, Bornali; Penwarden, Amy; Wood, Joel M; Gallagher, Thomas A; Andreoli, Matthew J; Voss, Jed; Meier, Timothy; Nair, Veena A; Kuo, John S; Field, Aaron S; Moritz, Chad; Meyerand, M Elizabeth; Prabhakaran, Vivek

2013-04-01

Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume. Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas. There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD. Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor

Clinicopathological feature and prognosis of primary hepatic gastrointestinal stromal tumor.

PubMed

Liu, Zhen; Tian, Yangzi; Liu, Shushang; Xu, Guanghui; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei; Feng, Fan

2016-09-01

Compared to gastric gastrointestinal stromal tumor (GIST), hepatic GIST is very rare in clinic. Reports on clinicopathological feature and prognosis of this rare disease are limited in literature. The purpose of this study was, therefore, to summarize clinical and pathological features as well as prognosis of the primary hepatic GIST. One case of primary hepatic GIST from our center and 22 cases reported in MEDLINE or China National Knowledge Infrastructure (CNKI) were enrolled into this study. Clinicopathological features as well as survival data of hepatic GIST were analyzed and compared with 297 gastric GISTs and 59 small intestinal GISTs from our center. Majority of the 22 cases (95.7%) of hepatic GIST was larger than 5 cm in size, and 75.0% of the tumors were over 5/50 HPF in mitotic index. Most of the hepatic GISTs (85.7%) displayed spindle cell shape in morphology. All of the hepatic GIST (100%) enrolled in this study were classified as high-risk category by the National Institute of Health (NIH) risk classification. The 5-year median disease-free survival (DFS) time was 24.0 months and 5-year disease-specific survival (DSS) rate was 33.3%, respectively. Distribution of clinicopathological features was significantly different among hepatic, gastric, and small intestinal GIST. The DFS and DSS of hepatic GIST were significantly lower than those of the other two groups. Majority of the hepatic GIST is large in size and highly malignant. Prognosis of the primary hepatic GIST is worse than that of gastric GIST and small intestinal GIST. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Outcome of supratentorial intraaxial extra ventricular primary pediatric brain tumors: A prospective study

PubMed Central

Patibandla, Mohana Rao; Bhattacharjee, Suchanda; Uppin, Megha S.; Purohit, Aniruddh Kumar

2014-01-01

Introduction: Tumors of the central nervous system (CNS) are the second most frequent malignancy of childhood and the most common solid tumor in this age group. CNS tumors represent approximately 17% of all malignancies in the pediatric age range, including adolescents. Glial neoplasms in children account for up to 60% of supratentorial intraaxial tumors. Their histological distribution and prognostic features differ from that of adults. Aims and Objectives: To study clinical and pathological characteristics, and to analyze the outcome using the Engel's classification for seizures, Karnofsky's score during the available follow-up period of minimum 1 year following the surgical and adjuvant therapy of supratentorial intraaxial extraventricular primary pediatric (SIEPP) brain tumors in children equal or less than 18 years. Materials and Methods: The study design is a prospective study done in NIMS from October 2008 to January 2012. All the patients less than 18 years of age operated for SIEPP brain tumors proven histopathologically were included in the study. All the patients with recurrent or residual primary tumors or secondaries were excluded from the study. Post operative CT or magnetic resonance imaging (MRI) is done following surgery. Results and Analysis: There were 2, 8 and 20 patients in the age range of 0-2 years, >2-10 years and 10-18 years, respectively. There were 21 male patients and 9 female patients. Out of 30 patients, 16 had lesion in the temporal lobe, 6 in frontal lobe, 4 in thalamus, 3 in parietal lobe and 1 in occipital lobe. Out of 30 patients, 11 patients had malignant lesions and nineteen patients had benign lesions. Gross total excision could be achieved in 19 patients and subtotal in 11 patients. Seven patients had mortality and four of the remaining 23 patients had increased deficits postoperatively. Remaining 19 patients either improved or remained same. Conclusions: SIEPP brain tumors have male preponderance, occur in 95% of patients in

Management of the Primary Tumor and Limited Metastases in Patients With Metastatic Pancreatic Cancer.

PubMed

Herman, Joseph M; Hoffman, John P; Thayer, Sarah P; Wolff, Robert A

2015-05-01

New combinations of cytotoxic chemotherapy have been proven to increase response rates and survival times compared with single-agent gemcitabine for patients with metastatic pancreatic cancer. These responses have been dramatic for a subset of patients, therefore raising questions about the management of limited metastatic disease with surgery or other ablative methods. Similarly, for patients having a complete radiographic response to chemotherapy in the metastatic compartment, whether to consider local therapy in the form of radiation or surgery for the primary tumor is now an appropriate question. Therefore, collaboration among experts in surgery, medical oncology, and radiation oncology has led to the development of guiding principles for local therapies to the primary intact pancreatic tumor for patients with limited metastatic disease and those who have had a significant response after systemic therapy.

Quality of Life in Patients With Primary and Metastatic Brain Tumors in the Literature as Assessed by the FACT-Br.

PubMed

Chiu, Nicholas; Chiu, Leonard; Zeng, Liang; Zhang, Liying; Cella, David; Popovic, Marko; Chow, Ronald; Lam, Henry; Poon, Michael; Chow, Edward

2012-12-01

The Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a quality of life (QOL) assessment tool that was originally developed for use in patients with primary brain tumors. However, the tool has also been used to assess QOL in patients with metastatic brain tumors. The purpose of this study is to compare the differences in QOL responses as assessed by the FACT-Br in patients with primary and metastatic brain neoplasms. A systematic literature search was conducted using the OvidSP platform in MEDLINE (1946 to July Week 2 2012) and EMBASE (1980 to 2012 Week 28). Articles in which the FACT-Br was used as a QOL assessment for patients with malignant brain tumors (both primary and metastatic) were included in the study. The weighted means of FACT-Br subscale and overall scores were calculated for the studies. To compare these scores, weighted analysis of variance was conducted and PROC GLM was performed for the data. A P-value of < 0.05 was considered statistically significant. A total of 23 studies (four in brain metastases, 18 in primary brain tumors and 1 in a mixed sample) using the FACT-Br for assessment of QOL were identified. Social and functional well-being were significantly better in patients with primary brain tumors (weighted mean score of 22.2 vs. 10.7, P = 0.0026, 16.9 vs. 6.2, P = 0.0025, respectively). No other scale of the FACT-Br was significantly different between the two groups and the performance status of patients included in both groups was similar. Patients with primary brain cancer seemed to have better social and functional well-being scores than those with metastatic brain tumors. Other QOL domains were similar between these two groups. However, the heterogeneity in the included studies and the low sample size of included samples in patients with metastatic brain tumors could have confounded our findings.

Primary Ewing's Sarcoma of the temporal bone in an infant.

PubMed

Goudarzipour, Kourosh; Shamsian, Shahin; Alavi, Samin; Nourbakhsh, Kazem; Aghakhani, Roxana; Eydian, Zahra; Arzanian, Mohammad Taghi

2015-04-01

Introduction : Ewing's sarcoma is the second most common primary malignant tumor of bone found in children after Osteosarcoma. It accounts for 4-9% of primary malignant bone tumors and it affects bones of the skull or face in only 1-4% of cases. Hence it rarely affects the head and neck. Subject and Method : In this case report, we describe a case of primary Ewing's sarcoma occurring in the temporal bone. The tumor was surgically excised, and the patient underwent chemotherapy for ten months. Results : Neither recurrence nor distant metastasis was noted in these 10 months after surgery but about 18 months after surgery our patient was expired. Conclusion : Although the prognosis of Ewing's sarcoma is generally poor because of early metastasis to the lungs and to other bones, a review of the article suggested that Ewing's sarcoma occurring in the skull can often be successfully managed by intensive therapy with radical excision and chemotherapy. This result was supported by the case reported here.

THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

PubMed Central

Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635

Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

NASA Astrophysics Data System (ADS)

Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

1996-12-01

The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu Yongpeng; Li Hongzhen; Miki, Jun

2006-04-01

In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferativemore » capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.« less

Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer

PubMed Central

Hoshina, Seigo; Takayanagi, Toshiaki; Tominaga, Takeshi

1994-01-01

Angiogenesis is an independent prognostic indicator in breast cancer. In this report, the relationship between expression of vascular endothclial growth factor (VEGF; a selective mitogen for endothelial cells) and the microvessel density was examined in 103 primary breast cancers. The expression of VEGF was evaluated by immunocytochemical staining using anti‐VEGF antibody. The microvessel density, which was determined by immunostaining for factor VIII antigen, in VEGF‐rich tumors was clearly higher than that in VEGF‐poor tumors (P<0.01). There was a good correlation between VEGF expression and the increment of microvessel density. Furthermore, postoperative survey demonstrated that the relapse‐free survival rate of VEGF‐rich tumors was significantly worse than that of VEGF‐poor tumors. It was suggested that the expression of VEGF is closely associated with the promotion of angiogenesis and with early relapse in primary breast cancer. PMID:7525523

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

Clinical, Biologic, and Prognostic Differences on the Basis of Primary Tumor Site in Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

PubMed Central

Vo, Kieuhoa T.; Matthay, Katherine K.; Neuhaus, John; London, Wendy B.; Hero, Barbara; Ambros, Peter F.; Nakagawara, Akira; Miniati, Doug; Wheeler, Kate; Pearson, Andrew D.J.; Cohn, Susan L.; DuBois, Steven G.

2014-01-01

Purpose Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear. Patients and Methods Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS). Results Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003). Conclusion Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences. PMID:25154816

Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

PubMed

Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

2013-07-09

Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors.

PubMed

Singh, Harmeet; Li, Ying; Fuller, Peter J; Harrison, Craig; Rao, Jyothsna; Stephens, Andrew N; Nie, Guiying

2013-01-01

Objective. The high temperature requirement factor A3 (HtrA3) is a serine protease homologous to bacterial HtrA. Four human HtrAs have been identified. HtrA1 and HtrA3 share a high degree of domain organization and are downregulated in a number of cancers, suggesting a widespread loss of these proteases in cancer. This study examined how extensively the HtrA (HtrA1-3) proteins are downregulated in commonly used cancer cell lines and primary ovarian tumors.Methods. RT-PCR was applied to various cancer cell lines (n=17) derived from the ovary, endometrium, testes, breast, prostate, and colon, and different subtypes of primary ovarian tumors [granulosa cell tumors (n=19), mucinous cystadenocarcinomas (n=6), serous cystadenocarcinomas (n=8)] and normal ovary (n = 9). HtrA3 protein was localized by immunohistochemistry.Results. HtrA3 was extensively downregulated in the cancer cell lines examined including the granulosa cell tumor-derived cell lines. In primary ovarian tumors, the HtrA3 was significantly lower in serous cystadenocarcinoma and granulosa cell tumors. In contrast, HtrA1 and HtrA2 were expressed in all samples with no significant differences between the control and tumors. In normal postmenopausal ovary, HtrA3 protein was localized to lutenizing stromal cells and corpus albicans. In serous cystadenocarcinoma, HtrA3 protein was absent in the papillae but detected in the mesenchymal cyst wall.Conclusion. HtrA3 is more extensively downregulated than HtrA1-2 in cancer cell lines. HtrA3, but not HtrA1 or HtrA2, was decreased in primary ovarian serous cystadenocarcinoma and granulosa cell tumors. This study provides evidence that HtrA3 may be the most relevant HtrA associated with ovarian malignancy.

The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.

PubMed

Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.

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 ...

Primary hyperparathyroidism associated with a giant cell tumor: One case in the distal radius.

PubMed

Ouzaa, M R; Bennis, A; Iken, M; Abouzzahir, A; Boussouga, M; Jaafar, A

2015-10-01

Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive lesions) that usually disappear after normalization of calcium and phosphate levels. It rarely occurs simultaneously with a giant cell tumor. The authors report one case of a localized form at the distal radius in a patient being followed for primary hyperparathyroidism. The diagnostic challenges related to the clinical and radiological similarities of these two pathological entities are discussed, as they can lead to delays in therapeutic management. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

PubMed Central

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol; Rogers, Lisa; Peereboom, David M.

2017-01-01

Abstract Background. Complete prevalence proportions illustrate the burden of disease in a population. This study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y). Methods. Complete prevalence proportions were estimated using a novel regression method extended from the Completeness Index Method, which combines survival and incidence data from multiple sources. In this study, two datasets, CBTRUS and SEER, were used to calculate complete prevalence estimates of interest. Results. Complete prevalence for malignant primary brain tumors was 47.59/100000 population (22.31, 48.49, and 57.75/100000 for child, AYA, and adult populations). The most prevalent cancers by age were childhood leukemia (36.65/100000), AYA melanoma of the skin (66.21/100000), and adult female breast (1949.00/100000). The most prevalent CBTRUS histologies in children and AYA were pilocytic astrocytoma (6.82/100000, 5.92/100000), and glioblastoma (12.76/100000) in adults. Conclusions. The relative impact of malignant primary brain tumors is higher among children than any other age group; it emerges as the second most prevalent cancer among children. Complete prevalence estimates for primary malignant brain tumors fills a gap in overall cancer knowledge, which provides critical information toward public health and health care planning, including treatment, decision making, funding, and advocacy programs. PMID:28039365

Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model

PubMed Central

2013-01-01

Background Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations. Methods The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry. Results The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms. Conclusions Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing

Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model.

PubMed

Urueña, Claudia; Mancipe, Juan; Hernandez, John; Castañeda, Diana; Pombo, Luis; Gomez, Alejandra; Asea, Alexzander; Fiorentino, Susana

2013-04-03

Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations. The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry. The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms. Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing good potential for use as an adjuvant in

Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor

PubMed Central

Pandurengan, R. K.; Dumont, A. G.; Araujo, D. M.; Ludwig, J. A.; Ravi, V.; Patel, S.; Garber, J.; Benjamin, R. S.; Strom, S. S.; Trent, J. C.

2010-01-01

Background: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies. Patients and methods: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected. Results: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002). Conclusions: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated. PMID:20348145

[Evaluation of cardiac tumors by multidetector computed tomography and magnetic resonance imaging].

PubMed

Mercado-Guzman, Marcela P; Meléndez-Ramírez, Gabriela; Castillo-Castellon, Francisco; Kimura-Hayama, Eric

Cardiac tumors, are a rare pathology (0.002-0.3%) in all age groups, however, they have a clinic importance, due the affected organ. They are classified in primary (benign or malignant) and secondary (metastasis) types. Among primary type, mixoma, is the most common benign tumor, and sarcoma represents most of the malignant injuries. Cardiac metastasis are more frequent than primary tumors. Clinic effects of cardiac tumors are unspecific and vary according their location, size and agresivity. The use of Multidetector Computed Tomography (MDCT) and Magnetic Resonance Imaging (MRI) assist on the location, sizing, anatomical relationships and the compromise of adyacents structures, besides, MRI is useful for tissue characterization of the tumor. Due to the previous reasons, studies based on noninvasive cardiovascular imaging, have an important role on the characterization of these lesions and the differential diagnosis among them. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Survival According to BRAF-V600 Tumor Mutations – An Analysis of 437 Patients with Primary Melanoma

PubMed Central

Meckbach, Diana; Bauer, Jürgen; Pflugfelder, Annette; Meier, Friedegund; Busch, Christian; Eigentler, Thomas K.; Capper, David; von Deimling, Andreas; Mittelbronn, Michel; Perner, Sven; Ikenberg, Kristian; Hantschke, Markus; Büttner, Petra; Garbe, Claus; Weide, Benjamin

2014-01-01

The prognostic impact of BRAF-V600 tumor mutations in stage I/II melanoma patients has not yet been analyzed in detail. We investigated primary tumors of 437 patients diagnosed between 1989 and 2006 by Sanger sequencing. Mutations were detected in 38.7% of patients and were associated with age, histological subtype as well as mitotic rate. The mutational rate was 36.7% in patients with disease-free course and 51.7% in those with subsequent distant metastasis (p = 0.031). No difference in overall survival (p = 0.119) but a trend for worse distant-metastasis-free survival (p = 0.061) was observed in BRAF mutant compared to BRAF wild-type patients. Independent prognostic factors for overall survival were tumor thickness, mitotic rate and ulceration. An interesting significant prognostic impact was observed in patients with tumor thickness of 1 mm or less, with the mutation present in 6 of 7 patients dying from melanoma. In conclusion, no significant survival differences were found according to BRAF-V600 tumor mutations in patients with primary melanoma but an increasing impact of the mutational status was observed in the subgroup of patients with tumor thickness of 1 mm or less. A potential role of the mutational status as a prognostic factor especially in this subgroup needs to be investigated in larger studies. PMID:24475086

Cabozantinib Affects Osteosarcoma Growth Through A Direct Effect On Tumor Cells and Modifications In Bone Microenvironment.

PubMed

Fioramonti, M; Fausti, V; Pantano, F; Iuliani, M; Ribelli, G; Lotti, F; Pignochino, Y; Grignani, G; Santini, D; Tonini, G; Vincenzi, B

2018-03-08

Osteosarcoma (OS) is the most common primary malignant tumor of the bone. Due to its high heterogeneity and to survival signals from bone microenvironment, OS can resist to standard treatments, therefore novel therapies are needed. c-MET oncogene, a tyrosine-kinase receptor, plays a crucial role in OS initiation and progression. The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment. We tested different doses of CBZ in in vitro models of OS alone or in co-culture with bone cells in order to reproduce OS-tumor microenvironment interactions. CBZ is able to decrease proliferation and migration of OS cells, inhibiting ERK and AKT signaling pathways. Furthermore, CBZ leads to the inhibition of the proliferation of OS cells expressing receptor activator of nuclear factor κB (RANK), due to its effect on bone microenvironment, where it causes an overproduction of osteoprotegerin and a decrease of production of RANK ligand by osteoblasts. Overall, our data demonstrate that CBZ might represent a new potential treatment against OS, affecting both OS cells and their microenvironment. In this scenario, RANK expression in OS cells could represent a predictive factor of better response to CBZ treatment.

Penile sparing surgical approaches for primary penile tumors: preserving function and appearance

PubMed Central

Baumgarten, Adam S.; Fisher, John S.; Lawindy, Samuel M.; Pavlinec, Jonathan G.; Carrion, Rafael E.

2017-01-01

Penile cancer is a rare and potentially disfiguring disease. There are multiple treatment options for primary penile lesions. Penile sparing approaches offer an attractive option as they can provide several quality of life benefits without detrimental oncologic outcomes. With appropriate diagnostic evaluation and staging, penile sparing techniques provide proper cancer control with improved cosmetic and functional results. Regardless of the chosen treatment modality, a commitment to close follow-up remains a critical component of all treatment considerations. The goal of this review is to provide an overview of the multiple treatment strategies for primary penile tumors with a focus on penile sparing surgical approaches. PMID:29184777

Persistent hyperplastic primary vitreous with retinal tumor in tuberous sclerosis: report of a case including tumoral immunohistochemistry and cytogenetic analyses.

PubMed

Milot, J; Michaud, J; Lemieux, N; Allaire, G; Gagnon, M M

1999-03-01

The authors describe an ocular lesion combining the characteristics of persistent hyperplastic primary vitreous (PHPV) and a retinal tumor in an infant with tuberous sclerosis complex (TSC). Case report. Immunohistochemistry and cytogenetic studies were performed on TSC cells from an intraocular tumor in a 6-week-old infant. Histopathologic examination showed a thick fibrovascular membrane between the aspect of the lens and the astrocytic component of the mass. Glial fibrillary acidic protein (GFAP) showed a variable intracytoplasmic reaction in the astrocytic proliferation, involving approximately 50% of the cells. Tissue culture studies showed a fairly rapid proliferation of fusiform cells, consistent with bipolar astrocytic cells. Cytogenetic studies showed one abnormal clone consisting of three hyperdiploid cells with a loss of chromosome 9 and a gain of chromosomes 6 and 12. The atypical localization of the retinal tumor could be explained by the fact that it was trapped during its proliferation by the retinal detachment associated with the PHPV.

Assessment of left ventricular myocardial deformation by cardiac MRI strain imaging reveals myocardial dysfunction in patients with primary cardiac tumors.

PubMed

Chen, Jing; Yang, Zhi-Gang; Xu, Hua-Yan; Shi, Ke; Guo, Ying-Kun

2018-02-15

To assess left ventricular myocardial deformation in patients with primary cardiac tumors. MRI was retrospectively performed in 61 patients, including 31 patients with primary cardiac tumors and 30 matched normal controls. Left ventricular strain and function parameters were then assessed by MRI-tissue tracking. Differences between the tumor group and controls, left and right heart tumor groups, left ventricular wall tumor and non-left ventricular wall tumor groups, and tumors with and without LV enlargement groups were assessed. Finally, the correlations among tumor diameter, myocardial strain, and LV function were analyzed. Left ventricular myocardial strain was milder for tumor group than for normal group. Peak circumferential strain (PCS) and its diastolic strain rate, longitudinal strains (PLS) and its diastolic strain rates, and peak radial systolic and diastolic velocities of the right heart tumor group were lower than those of the left heart tumor group (all p<0.050), but the peak radial systolic strain rate of the former was higher than that of the latter (p=0.017). The corresponding strains were lower in the left ventricular wall tumor groups than in the non-left ventricular wall tumor group (p<0.050). Peak radial systolic velocities were generally higher for tumors with LV enlargement than for tumors without LV enlargement (p<0.050). Peak radial strain, PCS, and PLS showed important correlations with the left ventricular ejection fraction (all p<0.050). MRI-tissue tracking is capable of quantitatively assessing left ventricular myocardial strain to reveal sub-clinical abnormalities of myocardial contractile function. Copyright © 2017 Elsevier B.V. All rights reserved.

Up-front systemic chemotherapy is a feasible option compared to primary tumor resection followed by chemotherapy for colorectal cancer with unresectable synchronous metastases.

PubMed

Niitsu, Hiroaki; Hinoi, Takao; Shimomura, Manabu; Egi, Hiroyuki; Hattori, Minoru; Ishizaki, Yasuyo; Adachi, Tomohiro; Saito, Yasufumi; Miguchi, Masashi; Sawada, Hiroyuki; Kochi, Masatoshi; Mukai, Shoichiro; Ohdan, Hideki

2015-04-24

In stage IV colorectal cancer (CRC) with unresectable metastases, whether or not resection of the primary tumor should be indicated remains controversial. We aim to determine the impact of primary tumor resection on the survival of stage IV CRC patients with unresectable metastases. We retrospectively investigated 103 CRC patients with stage IV colorectal cancer with metastases, treated at Hiroshima University Hospital between 2007 and 2013. Of these, those who had resectable primary tumor but unresectable metastases and received any chemotherapy were included in the study. We analyzed the overall survival (OS) and short-term outcomes between the patients who received up-front systemic chemotherapy (USC group) and those who received primary tumor resection followed by chemotherapy (PTR group). Of the 57 included patients, 15 underwent USC and 42 PTR. The median survival times were 13.4 and 23.9 months in the USC and PTR groups, respectively (P = 0.093), but multivariate analysis for the overall survival showed no significant difference between the two groups (hazard ratio, 1.30; 95% confidence interval (CI), 0.60 to 2.73, P = 0.495). In the USC group, the disease control rate of primary tumor was observed in 12 patients (80.0%), but emergency laparotomy was required for 1 patient. Morbidity in the PTR group was observed in 18 cases (42.9%). The overall survival did not differ significantly between the USC and PTR groups. USC may help avoid unnecessary resection and consequently the high morbidity rate associated with primary tumor resection for stage IV CRC with unresectable metastases.

Simultaneous 11C-Methionine Positron Emission Tomography/Magnetic Resonance Imaging of Suspected Primary Brain Tumors

PubMed Central

Deuschl, Cornelius; Goericke, Sophia; Grueneisen, Johannes; Sawicki, Lino Morris; Goebel, Juliane; El Hindy, Nicolai; Wrede, Karsten; Binse, Ina; Poeppel, Thorsten; Quick, Harald; Forsting, Michael; Hense, Joerg; Umutlu, Lale; Schlamann, Marc

2016-01-01

Introduction The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone. Material and Methods Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging. Results Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone. Conclusions The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved. PMID:27907162

Pattern of metastasis outside tumor-bearing segments in primary lung cancer: rationale for segmentectomy.

PubMed

Sakairi, Yuichi; Yoshino, Ichiro; Yoshida, Shigetoshi; Suzuki, Hidemi; Tagawa, Tetsuzo; Iwata, Takekazu; Mizobuchi, Teruaki

2014-05-01

Patterns of intrapulmonary metastasis, particularly metastasis outside tumor-bearing segments, were investigated in lung cancer patients to address the rationale for segmentectomy. In a consecutive series of patients who underwent resection of two or more pulmonary segments for primary lung cancer, intrapulmonary spread patterns, such as segmental/intersegmental node metastasis and pulmonary parenchymal metastasis, were pathologically examined. Eligible 244 lesions included 167 adenocarcinomas, 66 squamous cell carcinomas, and 11 large cell carcinomas. Pathologic stages included 0 to IA (n=111), IB (n=56), IIA (n=31), IIB (n=20), IIIA (n=23), and IIIB to IV (n=3); and N1 (n=26) and N2 (n=22). Intrapulmonary spread was observed in 24 cases (9.8%). Of these, metastasis outside tumor-bearing segments was only observed in 4 cases (1.6%), and such cancer spread was more frequently seen in cases with extrapulmonary (hilar to mediastinal) nodal metastasis (7.9%) than in cases without extrapulmonary metastasis (0.5%; p=0.01). Metastasis outside tumor-bearing segments was not observed in 64 tumors with pure or mixed ground glass opacity features on computed tomography. Although tumor location (peripheral or central/intermediate) was not related to the incidence of metastasis outside tumor-bearing segments, intrapulmonary spread was observed in only 1 of 52 peripheral small (≤20 mm) tumors. Metastasis outside tumor-bearing segments is rarely observed in cases with tumors (1) without extrapulmonary nodal metastasis and (2) with ground glass opacity or peripheral small (≤20 mm) features. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection.

PubMed

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An; Wang, Li-Fu

2014-01-01

To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/ percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

Pain and Depressive Symptoms in Primary Care: Moderating Role of Positive and Negative Affect.

PubMed

Hirsch, Jameson K; Sirois, Fuschia M; Molnar, Danielle; Chang, Edward C

2016-07-01

Pain and its disruptive impact on daily life are common reasons that patients seek primary medical care. Pain contributes strongly to psychopathology, and pain and depressive symptoms are often comorbid in primary care patients. Not all those who experience pain develop depression, suggesting that the presence of individual-level characteristics, such as positive and negative affect, that may ameliorate or exacerbate this association. We assessed the potential moderating role of positive and negative affect on the pain-depression linkage. In a sample of 101 rural, primary care patients, we administered the Brief Pain Inventory, NEO Personality Inventory-Revised positive and negative affect subclusters, and the Center for Epidemiology Scale for Depression. In moderation models, covarying age, sex, and ethnicity, we found that positive affect, but not negative affect, was a significant moderator of the relation between pain intensity and severity and depressive symptoms. The association between pain and depressive symptoms is attenuated when greater levels of positive affects are present. Therapeutic bolstering of positive affect in primary care patients experiencing pain may reduce the risk for depressive symptoms.

Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

ClinicalTrials.gov

2016-10-20

Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor; Recurrent Ovarian Carcinoma; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Ovarian Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Ovarian Cancer

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

PubMed

Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena

Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy

PubMed Central

Phoenix, Kathryn N.; Vumbaca, Frank; Fox, Melissa M.; Evans, Rebecca

2010-01-01

Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events. PMID:20204498

Prognosis estimation under the light of metabolic tumor parameters on initial FDG-PET/CT in patients with primary extranodal lymphoma

PubMed Central

Okuyucu, Kursat; Ozaydın, Sukru; Alagoz, Engin; Ozgur, Gokhan; Oysul, Fahrettin Guven; Ozmen, Ozlem; Tuncel, Murat; Ozturk, Mustafa; Arslan, Nuri

2016-01-01

Abstract Background Non-Hodgkin’s lymphomas arising from the tissues other than primary lymphatic organs are named primary extranodal lymphoma. Most of the studies evaluated metabolic tumor parameters in different organs and histopathologic variants of this disease generally for treatment response. We aimed to evaluate the prognostic value of metabolic tumor parameters derived from initial FDG-PET/CT in patients with a medley of primary extranodal lymphoma in this study. Patients and methods There were 67 patients with primary extranodal lymphoma for whom FDG-PET/CT was requested for primary staging. Quantitative PET/CT parameters: maximum standardized uptake value (SUVmax), average standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were used to estimate disease-free survival and overall survival. Results SUVmean, MTV and TLG were found statistically significant after multivariate analysis. SUVmean remained significant after ROC curve analysis. Sensitivity and specificity were calculated as 88% and 64%, respectively, when the cut-off value of SUVmean was chosen as 5.15. After the investigation of primary presentation sites and histo-pathological variants according to recurrence, there is no difference amongst the variants. Primary site of extranodal lymphomas however, is statistically important (p = 0.014). Testis and central nervous system lymphomas have higher recurrence rate (62.5%, 73%, respectively). Conclusions High SUVmean, MTV and TLG values obtained from primary staging FDG-PET/CT are potential risk factors for both disease-free survival and overall survival in primary extranodal lymphoma. SUVmean is the most significant one amongst them for estimating recurrence/metastasis. PMID:27904443

A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis to the cervix uteri

PubMed Central

Gupta, Nupur; Mittal, Suneeta; Lal, Neena; Misra, Renu; Kumar, Lalit; Bhalla, Sunita

2007-01-01

Background Gastrointestinal stromal tumors are CD117 (C Kit) positive mesenchymal neoplasms, that may arise anywhere in the gastrointestinal tract. Their current therapy is imatinib mesylate before or after surgery. Case presentation We describe a case of 17-year-old female with metastasis to the cervix uteri of a primary mesenteric gastrointestinal tumor. Conclusion Surgery remains the mainstay of known curative treatment. The manifestations of GIST are not restricted to the typical locations within the bowel; may have very unusual metastatic sites or infiltrations per continuitatem. PMID:18045506

Primary CNS germ cell tumors in Japan and the United States: an analysis of 4 tumor registries

PubMed Central

McCarthy, Bridget J.; Shibui, Soichiro; Kayama, Takamasa; Miyaoka, Etsuo; Narita, Yoshitaka; Murakami, Michiko; Matsuda, Ayako; Matsuda, Tomohiro; Sobue, Tomotaka; Palis, Bryan E.; Dolecek, Therese A.; Kruchko, Carol; Engelhard, Herbert H.; Villano, J. Lee

2012-01-01

Intracranial germ cell tumors (GCTs) are relatively rare. Their incidence has been considered to be higher in East Asia than in the United States. This study estimates the incidence of CNS GCTs in Japan and the United States, investigates gender discrepancies in each country, and describes treatment outcomes. Data on primary CNS GCTs from 4 databases were utilized: population-based malignant incidence data from (1) the Japan Cancer Surveillance Research Group (2004–2006; 14 registries), malignant and nonmalignant incidence data from (2) the Surveillance, Epidemiology, and End Results Program (2004–2008; 17 registries), and hospital-based observed survival data from (3) the Brain Tumor Registry of Japan (1984–2000) and (4) the US National Cancer Data Base (1990–2003). Incidence rates per 100 000 for malignant GCTs were not statistically significantly different between Japan (males = 0.143, females = 0.046) and the United States (males = 0.118, females = 0.030). The malignant incidence-rate ratio was higher for pineal GCTs versus nonpineal (ie, the rest of the brain) GCTs in Japan (11.5:1 vs 1.9:1, respectively) and the United States (16.0:1 vs 1.7:1, respectively). In general, 5-year survival estimates were high: over 75% for all GCTs, and over 81% for germinomas, regardless of the type of treatment in either Japan or the United States. The incidence of primary GCTs is similar between Japan and the United States and has the same gender-based patterns by location. High rates of survival were observed in both countries. PMID:22869621

Performance of 177Lu-DOTATATE-based peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumor: a multiparametric response evaluation correlating with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics.

PubMed

Thapa, Pradeep; Ranade, Rohit; Ostwal, Vikas; Shrikhande, Shailesh V; Goel, Mahesh; Basu, Sandip

2016-10-01

To assess the performance of Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic gastroenteropancreatic neuroendocrine tumor (GEP-NET) and correlate it with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics. Fifty patients (M : F 33 : 17, age: 26-71 years) with histopathologically confirmed metastatic/inoperable NETs who had undergone at least three cycles of PRRT with Lu-DOTATATE were included in the analysis. As part of the pretreatment evaluation, they underwent either Tc-HYNIC TOC (n=40)/Ga-DOTATATE PET (n=10) or fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT). Response was assessed after three and five cycles PRRT on the basis of three parameters: (a) symptomatic and subjective scale, (b) biochemical tumor marker level, and (c) objective imaging (F-FDG/Ga DOTATATE PET/CT, Tc-HYNIC TOC, ceCT), and was categorized using predefined criteria (detailed in methods). Stable disease on imaging assessment with response on symptomatic or biochemical tumor marker scales or both were included in the responder group. The study population was broadly classified into (a) metastatic GEP-NET with known primary (n=43 i.e. 86%), which was further subclassified according to the site of primary and (b) those with unknown primary (n=7 i.e. 14%). Symptomatic response: 96% of patients showed a symptomatic response or improvement in health-related quality of life, irrespective of tumor proliferation index, dual tracer imaging characteristics, and response or progression of disease in the scan. Biochemical tumor marker response: 83% of scan responders showed a decrease, 10% showed a stable value, and 7% showed an increase in tumor marker levels. Among the scan nonresponders, 67% patients showed a corresponding increase in the tumor marker level, 22% patient showed a decrease, whereas 11% showed stable values. Scan response: 31 out of total 50 patients (62%) showed a partial scan response with either a

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

PubMed

Mete, Ozgur; Duan, Kai

2018-01-01

Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors.

PubMed

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm-56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm-68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n = 1; low density without

Diagnostic Value of Multidetector CT and Its Multiplanar Reformation, Volume Rendering and Virtual Bronchoscopy Postprocessing Techniques for Primary Trachea and Main Bronchus Tumors

PubMed Central

Luo, Mingyue; Duan, Chaijie; Qiu, Jianping; Li, Wenru; Zhu, Dongyun; Cai, Wenli

2015-01-01

Purpose To evaluate the diagnostic value of multidetector CT (MDCT) and its multiplanar reformation (MPR), volume rendering (VR) and virtual bronchoscopy (VB) postprocessing techniques for primary trachea and main bronchus tumors. Methods Detection results of 31 primary trachea and main bronchus tumors with MDCT and its MPR, VR and VB postprocessing techniques, were analyzed retrospectively with regard to tumor locations, tumor morphologies, extramural invasions of tumors, longitudinal involvements of tumors, morphologies and extents of luminal stenoses, distances between main bronchus tumors and trachea carinae, and internal features of tumors. The detection results were compared with that of surgery and pathology. Results Detection results with MDCT and its MPR, VR and VB were consistent with that of surgery and pathology, included tumor locations (tracheae, n = 19; right main bronchi, n = 6; left main bronchi, n = 6), tumor morphologies (endoluminal nodes with narrow bases, n = 2; endoluminal nodes with wide bases, n = 13; both intraluminal and extraluminal masses, n = 16), extramural invasions of tumors (brokethrough only serous membrane, n = 1; 4.0 mm—56.0 mm, n = 14; no clear border with right atelectasis, n = 1), longitudinal involvements of tumors (3.0 mm, n = 1; 5.0 mm—68.0 mm, n = 29; whole right main bronchus wall and trachea carina, n = 1), morphologies of luminal stenoses (irregular, n = 26; circular, n = 3; eccentric, n = 1; conical, n = 1) and extents (mild, n = 5; moderate, n = 7; severe, n = 19), distances between main bronchus tumors and trachea carinae (16.0 mm, n = 1; invaded trachea carina, n = 1; >20.0 mm, n = 10), and internal features of tumors (fairly homogeneous densities with rather obvious enhancements, n = 26; homogeneous density with obvious enhancement, n = 1; homogeneous density without obvious enhancement, n = 1; not enough homogeneous density with obvious enhancement, n = 1; punctate calcification with obvious enhancement, n

Breast cancer brain metastases show increased levels of genomic aberration based homologous recombination deficiency scores relative to their corresponding primary tumors.

PubMed

Diossy, M; Reiniger, L; Sztupinszki, Z; Krzystanek, M; Timms, K M; Neff, C; Solimeno, C; Pruss, D; Eklund, A C; Tóth, E; Kiss, O; Rusz, O; Cserni, G; Zombori, T; Székely, B; Tímár, J; Csabai, I; Szallasi, Z

2018-06-18

Based on its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Therefore, identification of tumor types with increased HRD is important for the optimal use of this class of therapeutic agents. HRD levels can be estimated using various mutational signatures from next generation sequencing data and we used this approach to determine whether breast cancer brain metastases show altered levels of HRD scores relative to their corresponding primary tumor. We used a previously published next generation sequencing dataset of twenty-one matched primary breast cancer/brain metastasis pairs to derive the various mutational signatures/HRD scores strongly associated with HRD. We also performed the myChoice HRD analysis on an independent cohort of seventeen breast cancer patients with matched primary/brain metastasis pairs. All of the mutational signatures indicative of HRD showed a significant increase in the brain metastases relative to their matched primary tumor in the previously published whole exome sequencing dataset. In the independent validation cohort the myChoice HRD assay showed an increased level in 87.5% of the brain metastases relative to the primary tumor, with 56% of brain metastases being HRD positive according to the myChoice criteria. The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment. This observation warrants further investigation to assess whether this increase is common to other metastatic sites as well, and whether clinical trials should adjust their strategy in the application of HRD measures for the prioritization of patients for PARP inhibitor therapy.

R132H Mutation in IDH1 Gene is Associated with Increased Tumor HIF1-Alpha and Serum VEGF Levels in Primary Glioblastoma Multiforme.

PubMed

Yalaza, Cem; Ak, Handan; Cagli, Mehmet Sedat; Ozgiray, Erkin; Atay, Sevcan; Aydin, Hikmet Hakan

2017-05-01

Glioblastoma multiforme (GBM) is the most common form of primary brain tumors. Although mutations in isocitrate dehydrogenase-1 (IDH1) have been identified in a number of cancers, their role in tumor development has not been fully elucidated. In this study, we aimed to investigate the association between IDH1 mutations, tumor tissue HIF-1 alpha, and serum VEGF levels in patients with primary GBM for the first time. 32 patients (mean age, years: 58±14.0) diagnosed with primary glioblastoma multiforme were screened for IDH1 mutations (R132H, R132S, R132C and R132L) by direct sequencing. Serum VEGF and tumor tissue HIF1-alpha levels were measured by enzyme-linked immunosorbent assay. Associations between categoric variables were determined using chi-square tests. Differences between two groups were compared with t test for continuous variables. Six percent of patients were found to be heterozygous for R132H mutation. Tumor HIF1-alpha and serum VEGF levels were found to be significantly increased in IDH1 -mutated tumor tissues ( p <0.0001 and p =0.0454, respectively). Our results suggest that mutated IDH1 may contribute to carcinogenesis via induction of HIF-1 alpha pathway in primary GBM. © 2017 by the Association of Clinical Scientists, Inc.

Brown tumors of the anterior skull base as the initial manifestation of true normocalcemic primary hyperparathyroidism: report of three cases and review of the literature.

PubMed

Khalatbari, Mahmoud Reza; Hamidi, Mehrdokht; Moharamzad, Yashar; Setayesh, Ali; Amirjamshidi, Abbas

2013-01-01

Brown tumor is a bone lesion secondary to hyperparathyroidism of various etiologies. Skeletal involvement in primary hyperparathyroidism secondary to parathyroid adenoma is very uncommon and brown tumor has become extremely a rare clinical entity. Hyperparathyroidism is usually associated with high levels of serum calcium. Brown tumor as the only and initial symptom of normocalcemic primary hyperparathyroidism is extremely rare. Moreover, involvement of the skull base and the orbit is exceedingly rare. The authors would report three cases of brown tumor of the anterior skull base that were associated with true normocalcemic primary hyperparathyroidism. Clinical manifestations, neuroimaging findings, pathological findings, diagnosis and treatment of the patients are discussed and the relevant literature is reviewed.

[Metastasis revealing malignant peritoneum mesothelioma: About the difficulty to identify the primary tumors].

PubMed

Bretagne, Charles-Henri; Petitjean, Alain; Felix, Sophie; Bedgedjian, Isabelle; Algros, Marie-Paule; Delabrousse, Eric; Valmary-Degano, Séverine

2016-04-01

Peritoneal malignant mesothelioma is a rare and extremely aggressive tumor that is sometimes difficult to diagnose. We report two cases of metastatic malignant peritoneal mesothelioma. In one case, malignant metastatic cells were identified in cervical lymph nodes while in the other case, the cells were found in the liver. In both cases, metastases were identified before discovering the primary tumor. This led to the misdiagnosis of carcinoma of unknown origin. Nevertheless, the histological and immuno-histochemical patterns were typical of malignant mesothelioma. Regarding metastasis of unknown origin, a differentiation of epithelioid peritoneal malignant mesothelioma and adenocarcinoma proved to be difficult. Therefore, we discuss the diagnostic usefulness of immuno-histochemical mesothelioma markers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Benign notochordal cell tumors.

PubMed

Martínez Gamarra, C; Bernabéu Taboada, D; Pozo Kreilinger, J J; Tapia Viñé, M

Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Adult Antisocial Behavior and Affect Regulation among Primary Crack/Cocaine-Using Women

ERIC Educational Resources Information Center

Litt, Lisa Caren; Hien, Denise A.; Levin, Deborah

2003-01-01

The relationship between deficits in affect regulation and Adult Antisocial Behavior (ASB) in primary crack/cocaine-using women was explored in a sample of 80 inner-city women. Narrative early memories were coded for two components of affect regulation, Affect Tolerance and Affect Expression, using the Epigenetic Assessment Rating Scale (EARS;…

Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia.

PubMed

Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael

2017-10-01

The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

Happiness as a motivator: positive affect predicts primary control striving for career and educational goals.

PubMed

Haase, Claudia M; Poulin, Michael J; Heckhausen, Jutta

2012-08-01

What motivates individuals to invest time and effort and overcome obstacles (i.e., strive for primary control) when pursuing important goals? We propose that positive affect predicts primary control striving for career and educational goals, and we explore the mediating role of control beliefs. In Study 1, positive affect predicted primary control striving for career goals in a two-wave longitudinal study of a U.S. sample. In Study 2, positive affect predicted primary control striving for career and educational goals and objective career outcomes in a six-wave longitudinal study of a German sample. Control beliefs partially mediated the longitudinal associations with primary control striving. Thus, when individuals experience positive affect, they become more motivated to invest time and effort, and overcome obstacles when pursuing their goals, in part because they believe they have more control over attaining their goals.

Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

PubMed

van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

2018-05-01

Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

Brain Tumors

MedlinePlus

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice

PubMed Central

Panigrahy, Dipak; Edin, Matthew L.; Lee, Craig R.; Huang, Sui; Bielenberg, Diane R.; Butterfield, Catherine E.; Barnés, Carmen M.; Mammoto, Akiko; Mammoto, Tadanori; Luria, Ayala; Benny, Ofra; Chaponis, Deviney M.; Dudley, Andrew C.; Greene, Emily R.; Vergilio, Jo-Anne; Pietramaggiori, Giorgio; Scherer-Pietramaggiori, Sandra S.; Short, Sarah M.; Seth, Meetu; Lih, Fred B.; Tomer, Kenneth B.; Yang, Jun; Schwendener, Reto A.; Hammock, Bruce D.; Falck, John R.; Manthati, Vijaya L.; Ingber, Donald E.; Kaipainen, Arja; D’Amore, Patricia A.; Kieran, Mark W.; Zeldin, Darryl C.

2011-01-01

Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer. PMID:22182838

Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice.

PubMed

Panigrahy, Dipak; Edin, Matthew L; Lee, Craig R; Huang, Sui; Bielenberg, Diane R; Butterfield, Catherine E; Barnés, Carmen M; Mammoto, Akiko; Mammoto, Tadanori; Luria, Ayala; Benny, Ofra; Chaponis, Deviney M; Dudley, Andrew C; Greene, Emily R; Vergilio, Jo-Anne; Pietramaggiori, Giorgio; Scherer-Pietramaggiori, Sandra S; Short, Sarah M; Seth, Meetu; Lih, Fred B; Tomer, Kenneth B; Yang, Jun; Schwendener, Reto A; Hammock, Bruce D; Falck, John R; Manthati, Vijaya L; Ingber, Donald E; Kaipainen, Arja; D'Amore, Patricia A; Kieran, Mark W; Zeldin, Darryl C

2012-01-01

Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.

The inhibition of 45A ncRNA expression reduces tumor formation, affecting tumor nodules compactness and metastatic potential in neuroblastoma cells

PubMed Central

Russo, Debora; Poggi, Alessandro; Villa, Federico; Brizzolara, Antonella; Canale, Claudio; Mescola, Andrea; Daga, Antonio; Russo, Claudio; Nizzari, Mario; Florio, Tullio; Menichini, Paola; Pagano, Aldo

2017-01-01

We recently reported the in vitro over-expression of 45A, a RNA polymerase III-transcribed non-coding (nc)RNA, that perturbs the intracellular content of FE65L1 affecting cell proliferation rate, short-term response to genotoxic stress, substrate adhesion capacity and, ultimately, increasing the tumorigenic potential of human neuroblastoma cells. In this work, to deeply explore the mechanism by which 45A ncRNA contributes to cancer development, we targeted in vitro and in vivo 45A levels by the stable overexpression of antisense 45A RNA. 45A downregulation leads to deep modifications of cytoskeleton organization, adhesion and migration of neuroblastoma cells. These effects are correlated with alterations in the expression of several genes including GTSE1 (G2 and S phase-expressed-1), a crucial regulator of tumor cell migration and metastatic potential. Interestingly, the downregulation of 45A ncRNA strongly affects the in vivo tumorigenic potential of SKNBE2 neuroblastoma cells, increasing tumor nodule compactness and reducing GTSE1 protein expression in a subcutaneous neuroblastoma mouse model. Moreover, intracardiac injection of neuroblastoma cells showed that downregulation of 45A ncRNA also influences tumor metastatic ability. In conclusion, our data highlight a key role of 45A ncRNA in cancer development and suggest that its modulation might represent a possible novel anticancer therapeutic approach. PMID:28029658

The inhibition of 45A ncRNA expression reduces tumor formation, affecting tumor nodules compactness and metastatic potential in neuroblastoma cells.

PubMed

Penna, Ilaria; Gigoni, Arianna; Costa, Delfina; Vella, Serena; Russo, Debora; Poggi, Alessandro; Villa, Federico; Brizzolara, Antonella; Canale, Claudio; Mescola, Andrea; Daga, Antonio; Russo, Claudio; Nizzari, Mario; Florio, Tullio; Menichini, Paola; Pagano, Aldo

2017-01-31

We recently reported the in vitro over-expression of 45A, a RNA polymerase III-transcribed non-coding (nc)RNA, that perturbs the intracellular content of FE65L1 affecting cell proliferation rate, short-term response to genotoxic stress, substrate adhesion capacity and, ultimately, increasing the tumorigenic potential of human neuroblastoma cells. In this work, to deeply explore the mechanism by which 45A ncRNA contributes to cancer development, we targeted in vitro and in vivo 45A levels by the stable overexpression of antisense 45A RNA.45A downregulation leads to deep modifications of cytoskeleton organization, adhesion and migration of neuroblastoma cells. These effects are correlated with alterations in the expression of several genes including GTSE1 (G2 and S phase-expressed-1), a crucial regulator of tumor cell migration and metastatic potential. Interestingly, the downregulation of 45A ncRNA strongly affects the in vivo tumorigenic potential of SKNBE2 neuroblastoma cells, increasing tumor nodule compactness and reducing GTSE1 protein expression in a subcutaneous neuroblastoma mouse model. Moreover, intracardiac injection of neuroblastoma cells showed that downregulation of 45A ncRNA also influences tumor metastatic ability. In conclusion, our data highlight a key role of 45A ncRNA in cancer development and suggest that its modulation might represent a possible novel anticancer therapeutic approach.

Diagnostic value of 3.0T (1)H MRS with choline-containing compounds ratio (∆CCC) in primary malignant hepatic tumors.

PubMed

Zhang, Li; Zhao, Xinming; Ouyang, Han; Wang, Shuang; Zhou, Chunwu

2016-08-22

The purpose of this study was to investigate the diagnostic value of 3.0-T (1)H magnetic resonance spectroscopy ((1)H MRS) in primary malignant hepatic tumors and to compare the effects of (1)H MRS on the diagnostic accuracy of liver-occupying lesions between junior and experienced radiologists. This study included 50 healthy volunteers and 40 consecutive patients (50 lesions). Informed consent was obtained from each subject. Images were obtained on clinical whole-body 3.0-T MR system. Point -Resolved Spectroscopy was used to obtain the spectroscopy image. All conventional images were reviewed blindly by junior radiologist and experienced radiologist, respectively. The choline-containing compounds peak area (CCC-A) was measured with SAGE software, and the choline-containing compound ratio (∆CCC) was calculated. The efficacy of CCC-A and ∆CCC in the diagnosis of primary malignant hepatic tumors was determined by plotting receiver operating characteristic (ROC) curves. We also compared the effects of MRS on the diagnostic accuracy of liver-occupying lesions with junior and experienced radiologist. A significant increase in mean CCC-A was observed in malignant tumors compared with benign tumors. The ROC curve showed ∆CCC had a high discriminatory ability in diagnosing primary malignant hepatic tumors with a sensitivity and specificity of 94.3 and 93.3 %, respectively. The ∆CCC area under the curve (AUC) was 0.97 that was larger than that of both junior and experienced radiologist, while the significantly statistical difference was only obtained between ∆CCC and junior radiologist (P = 0.01). (1)H MRS with ∆CCC demonstrates good efficacy in diagnosing primary malignant hepatic tumors. The technique improves the accuracy of diagnosing liver-occupying lesions, particularly for junior radiologists.

Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis.

PubMed

Kamran, Sophia C; Clark, Jeffrey W; Zheng, Hui; Borger, Darrell R; Blaszkowsky, Lawrence S; Allen, Jill N; Kwak, Eunice L; Wo, Jennifer Y; Parikh, Aparna R; Nipp, Ryan D; Murphy, Janet E; Goyal, Lipika; Zhu, Andrew X; Iafrate, A John; Corcoran, Ryan B; Ryan, David P; Hong, Theodore S

2018-05-17

Recent reports demonstrate inferior outcomes associated with primary right-sided vs left-sided colorectal tumors in patients with metastatic colorectal cancer (mCRC). We sought to describe our experience with mCRC patients on whom we have molecular data to determine whether primary tumor sidedness was an independent prognostic marker for overall survival (OS). mCRC patients with documented primary tumor sidedness who received mutational profiling between 2009 and 2014 were identified (n = 367, median follow-up 30.4 months). Mutational profiling for >150 mutations across commonly mutated cancer genes including RAS, PIK3CA, BRAF, and PTEN as well as treatment data, including receipt of a biologic agent, were collected. Univariable/multivariable models were used to analyze relationships between collected data and OS. Among 367 patients, sidedness breakdown was as follows: 234 left (64%), 133 right (36%). 56% were male, with a median age at diagnosis of 57 (range 24-89). A total of 143 patients had RAS mutations. Five-year OS was 41%, median OS was 54 months (range 1-149). Five-year OS for left- vs right-sided tumors was 46% vs 24% (P < .0001). On univariable analysis, among both RAS wildtype and mutant tumors, left-sided tumors continued to have improved OS vs right-sided tumors (HR: 0.49, 95% CI: 0.34-0.69 RAS wildtype; HR: 0.61, 95% CI: 0.40-0.95 RAS mutant). Left-sidedness was an important prognostic factor for OS among RAS wildtype patients despite treatment with or without a biologic agent (P < .05). Left-sidedness remained significant for improved OS on multivariable analysis (P < .0001). Left-sided primary tumor remained most important prognostic factor for OS, even when adjusting for mutational status and receipt of biologic agent. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

PubMed

Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

2014-08-01

Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita

2007-09-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less

Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt.

PubMed

Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica; Bajetto, Adirano; Corsaro, Alessandro; Parodi, Alessia; Sirito, Rodolfo; Massollo, Michela; Marini, Cecilia; Zona, Gianluigi; Fenoglio, Daniela; Sambuceti, Gianmario; Filaci, Gilberto; Daga, Antonio; Barbieri, Federica; Florio, Tullio

2013-01-01

Cancer stem cell theory postulates that a small population of tumor-initiating cells is responsible for the development, progression and recurrence of several malignancies, including glioblastoma. In this perspective, tumor-initiating cells represent the most relevant target to obtain effective cancer treatment. Metformin, a first-line drug for type II diabetes, was reported to possess anticancer properties affecting the survival of cancer stem cells in breast cancer models. We report that metformin treatment reduced the proliferation rate of tumor-initiating cell-enriched cultures isolated from four human glioblastomas. Metformin also impairs tumor-initiating cell spherogenesis, indicating a direct effect on self-renewal mechanisms. Interestingly, analyzing by FACS the antiproliferative effects of metformin on CD133-expressing subpopulation, a component of glioblastoma cancer stem cells, a higher reduction of proliferation was observed as compared with CD133-negative cells, suggesting a certain degree of cancer stem cell selectivity in its effects. In fact, glioblastoma cell differentiation strongly reduced sensitivity to metformin treatment. Metformin effects in tumor-initiating cell-enriched cultures were associated with a powerful inhibition of Akt-dependent cell survival pathway, while this pathway was not affected in differentiated cells. The specificity of metformin antiproliferative effects toward glioblastoma tumor-initiating cells was confirmed by the lack of significant inhibition of normal human stem cells (umbilical cord-derived mesenchymal stem cells) in vitro proliferation after metformin exposure. Altogether, these data clearly suggest that metformin exerts antiproliferative activity on glioblastoma cells, showing a higher specificity toward tumor-initiating cells, and that the inhibition of Akt pathway may represent a possible intracellular target of this effect.

Primary perivascular epithelioid cell tumor in the rectum: a case report and review of the literature.

PubMed

Im, Soyoung; Yoo, Changyoung; Jung, Ji-Han; Choi, Hyun Joo; Yoo, Jinyoung; Kang, Chang Suk

2013-04-01

Perivascular epithelioid cell tumor (PEComa) is a rare collection of tumors arising in a wide array of anatomic locations. It is characterized by the presence of a peculiar population of myomelanocytic marker-positive perivascular epithelioid cells, and is commonly detected in the uterus. The colorectal area is an uncommon site for primary PEComa. In this study, we describe a 17-year-old patient presenting with a rectal polyp. Histologically, the tumor consisted of sheets of round to polygonal epithelioid cells with clear and granular cytoplasm, and a prominent capillary network. Some of the tumor cells were positive for Fontana-Masson staining. Immunohistochemically, the tumor cells were positive for HMB-45, and were negative for cytokeratin, vimentin, S-100 protein, actin, desmin, EMA, CD34, and c-kit. After finding melanosomes or premelanosomes at the ultrastructural level, the diagnosis of PEComa was made. Although PEComa arising within the intestinal tract is unusual and clinically unexpected, PEComa should be considered in the differential diagnosis of rectal polypoid lesions. Copyright © 2013 Elsevier GmbH. All rights reserved.

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PubMed

Stuart, Lauren N; Tipton, Russell G; DeWall, Michael R; Parker, Douglas C; Stelton, Christina D; Morrison, Annie O; Coleman, Landon W; Fosko, Scott W; Vidal, Claudia I; Yadira Hurley, Maria; Deeken, Amy H; Gardner, Jerad M

2017-08-01

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A primary tumor of mixed histological type is a novel poor prognostic factor for patients undergoing resection of liver metastasis from gastric cancer.

PubMed

Ikari, Naoki; Taniguchi, Kiyoaki; Serizawa, Akiko; Yamada, Takuji; Yamamoto, Masakazu; Furukawa, Toru

2017-05-01

Surgical resection can be an option for the treatment of metastatic liver tumors originating from gastric cancer; however, its prognostic impact is controversial. The aim of this study was to identify prognostic factors in patients with surgical resection of liver metastasis from gastric cancer. We retrospectively analyzed the clinicopathological features of 38 consecutive patients undergoing hepatectomy for metastatic tumors from gastric cancer in our institution between 1990 and 2014. The median overall survival of the patients was 28 months. The 5-year survival rate was 33.9%. Primary tumors of a mixed histological type, and residual tumors during the course of treatment were identified as significant independent poor prognostic factors. Histological evaluation of primary tumors may aid to identify patients suitable for undergoing surgical resection of liver metastasis from gastric cancer. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

The challenge of diagnosing a malignancy metastatic to the ovary: clinicopathological characteristics vary and morphology can be different from that of the corresponding primary tumor.

PubMed

Lobo, João; Machado, Bianca; Vieira, Renata; Bartosch, Carla

2017-01-01

An accurate diagnosis of metastases to the ovary is essential for adequate patient management. The aim of this retrospective study was to characterize clinicopathological features of metastatic malignancies that presented as an ovarian mass and compare them with their corresponding primary tumors. We reviewed clinical files and histological material of 120 patients with metastases to the ovary, diagnosed in our center between 2000 and 2014. Metastases were diagnosed before (18 %), synchronously (33 %), or after (49 %) the primary tumor was identified; 25 % were single, 40 % were unilateral; 47 % were ≥13 cm. Most originated from the gastrointestinal tract (73 %), followed by breast (13 %), and female reproductive organs (10 %). Gross features varied with primary tumor site. Metastases from gastrointestinal malignancies were significantly larger and frequently showed necrosis. Metastases to the appendix were cystic (94 %), and almost all metastases to the stomach (96 %) and breast (87 %) were solid. The predominant histological pattern was discordant in 44 % cases, mostly due to cystic changes in ovarian metastases which were observed across several histological types. Other metastases showed a predominant histological pattern which was present only focally in the primary tumor. Metastases showed significantly more edema, necrosis, and hemorrhage, but less lymphovascular invasion and inflammatory infiltrate than the corresponding primary tumors. Metastases to the ovary present highly variable clinicopathological features which frequently differ from those of the corresponding primary tumor. A metastasis should always be considered in the differential diagnosis of an ovarian mass. All clinical, imaging, macroscopic, and histological aspects must be taken into account to establish a correct diagnosis which is essential for adequate treatment.

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol

Complete prevalence proportions illustrate the burden of disease in a population. Here, this study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y).

Complete prevalence of malignant primary brain tumors registry data in the United States compared with other common cancers, 2010

DOE PAGES

Zhang, Adah S.; Ostrom, Quinn T.; Kruchko, Carol; ...

2016-12-29

Complete prevalence proportions illustrate the burden of disease in a population. Here, this study estimates the 2010 complete prevalence of malignant primary brain tumors overall and by Central Brain Tumor Registry of the United States (CBTRUS) histology groups, and compares the brain tumor prevalence estimates to the complete prevalence of other common cancers as determined by the Surveillance, Epidemiology, and End Results Program (SEER) by age at prevalence (2010): children (0–14 y), adolescent and young adult (AYA) (15–39 y), and adult (40+ y).

Ewing's Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue.

PubMed

Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C

2016-04-30

The molecular mechanism responsible for Ewing's Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis.

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

PubMed Central

Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

2017-01-01

The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

Surgical management of patients with primary brain tumors.

PubMed

Bohan, Eileen; Glass-Macenka, Deanna

2004-11-01

To provide an overview of the diagnostic work-up, intraoperative technologies, postoperative treatment options, and investigational new therapies in patients with malignant brain tumors. Published textbooks and articles and other reference materials. Recent improvements in diagnostic and surgical equipment have influenced outcomes and overall quality of life for patients with central nervous system tumors. The ability to more accurately target and more safely remove brain tumors has enhanced the postoperative period and decreased hospital stays. However, malignant neoplasms continue to be refractory to current treatments, necessitating innovative surgical approaches at the time of initial diagnosis and at tumor recurrence. Nurses with an understanding of current diagnostic and surgical treatment modalities for brain tumors are able to provide accurate patient education and comprehensive care, enhancing the overall hospital and outpatient experience.

Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis

PubMed Central

Goldstein, Robert H; Reagan, Michaela R; Anderson, Kristen; Kaplan, David L; Rosenblatt, Michael

2010-01-01

American women have a nearly 25% lifetime risk of developing breast cancer, with 20–40% of these patients developing life-threatening metastases. Over 70% of patients presenting with metastases have skeletal involvement, which signals progression to an incurable stage. Tumor-stroma cell interactions are only superficially understood, specifically regarding the ability of stromal cells to affect metastasis. In vivo models show that exogenously supplied hBMSCs (human bone-marrow derived stem cells) migrate to breast cancer tumors, but no reports have shown endogenous hBMSC migration from the bone to primary tumors. Here we present a model of in vivo hBMSC migration from a physiologic human bone environment to human breast tumors. Further, hBMSCs alter tumor growth and bone metastasis frequency. hBMSCs may home to certain breast tumors based on tumor-derived TGF-β1. Moreover, at the primary tumor IL-17B/IL-17BR signaling may mediate interactions between hBMSCs and breast cancer cells (BCCs). PMID:21159629

Circulating tumor cell levels are elevated in colorectal cancer patients with high tumor burden in the liver.

PubMed

Kaifi, Jussuf T; Kunkel, Miriam; Dicker, David T; Joude, Jamal; Allen, Joshua E; Das, Avisnata; Zhu, Junjia; Yang, Zhaohai; Sarwani, Nabeel E; Li, Guangfu; Staveley-O'Carroll, Kevin F; El-Deiry, Wafik S

2015-01-01

Metastatic spread is the most common cause of cancer-related death in colorectal cancer (CRC) patients, with the liver being the mostly affected organ. Circulating tumor cells (CTCs) are a prognostic marker in stage IV CRC. We hypothesized that tumor burden in the liver correlates with CTC quantity. Blood (7.5 ml) was prospectively collected from 24 patients with novel stage IV CRC diagnosis. Baseline EpCAM+ CTCs were analyzed with the FDA-approved CellSearch® system. Clinicopathological data were collected, and hepatic tumor burden was determined by radiographic liver volumetry with contrast-enhanced CT scans. CRC primary tumors were immunohistochemically stained for EpCAM expression with BerEP4 monoclonal antibody. Statistical analyses were performed using 2-sample T-test, non-parametric Wilcoxon Rank-Sum test, and Fisher's exact test. CTCs were detected n 17 (71%) of 24 patients. The overall mean CTC number as determined by EpCAM-based CellSearch® detection was 6.3 (SEM 2.9). High baseline CTC numbers (≥3) correlated significantly with a high tumor/liver ratio (≥30%), and with high serum CEA levels, as determined by two-sample T-test on log-transformed data and by Fisher's Exact test on categorical data analysis (P < 0.05). The CRC primary tumors were consistently expressing EpCAM by immunostaining. High tumor burden in the liver and high baseline serum CEA levels are associated with high number of baseline CTCs in stage IV CRC patients. Future studies should further investigate the biological role and expression patterns of single CTCs in cancer patients to further improve personalized treatment strategies.

[Secondary tumors of the gastrointestinal tract].

PubMed

Langner, C

2012-02-01

Metastatic involvement of the gastrointestinal tract is rare and may cause considerable difficulties with respect to differential diagnosis. The gastrointestinal tract may either be affected by direct invasion, intraperitoneal dissemination or hematogenous cancer spread, the latter most often originating from malignant melanoma, breast and lung carcinomas. Metastatic deposits primarily develop within the submucosa. Secondary involvement of the mucosa typically leads to centrally depressed and/or ulcerated (volcano-like) nodular lesions. In histology, lack of a mucosal in situ component favors diagnosis of metastasis, whereas presence of an adenomatous precursor lesion is regarded to be characteristic of primary tumors. This concept, however, has recently been challenged by demonstrating metastatic cancer growth along intact basement membranes within the mucosal layer, i.e. mucosal colonization. The histopathological, immunohistochemical and clinical features of secondary gastrointestinal tumors are discussed in detail, focusing on criteria for differential diagnosis. The prognosis of affected patients is generally poor.

Adrenal Gland Tumors: Statistics

MedlinePlus

... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

Role of Caspase-9 Gene Ex5+32 G>A (rs1052576) Variant in Susceptibility to Primary Brain Tumors.

PubMed

Ozdogan, Selcuk; Kafadar, Ali; Yilmaz, Seda Gulec; Timirci-Kahraman, Ozlem; Gormus, Uzay; Isbir, Turgay

2017-09-01

This study is the first to evaluate the relationship of caspase-9 (CASP-9) gene polymorphism with the risk for primary brain tumor development. The study group included 43 glioma and 27 meningioma patients and 76 healthy individuals. CASP-9 gene Ex5+32 G>A (rs1052576) polymorphism was analyzed by real-time polymerase chain reaction (RT-PCR). Individuals with the CASP-9 GG genotype had significantly decreased risk of developing a glioma brain tumor (p=0.024). Additionally, the GA genotype was significantly lower in patients with glioma than the control group (p=0.019). A significantly decreased risk of developing glioma was found in the A allele carrier group (p=0.024). However, there was no statistically significant relationship between CASP-9 polymorphism and brain meningioma (p=0.493). CASP-9 (rs1052576) mutant A allele seems to be a protective factor for glioma brain tumor. Future studies with a larger sample size will clarify the possible roles of CASP-9 gene in the etiology and progression of primary brain tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Biliary intraductal papillary neoplasm with metachronous multiple tumors - true multicentric tumors or intrabiliary dissemination: A case report and review of the literature.

PubMed

Yokode, Masataka; Yamashita, Yukimasa; Zen, Yoh

2017-03-01

Intraductal papillary neoplasms of the bile duct (IPNBs) are recognized as a distinct type of biliary tumor. We herein discuss the possible mechanisms underlying the development of multiple tumors in patients with IPNBs through a case presentation and literature review. A 64-year-old woman initially underwent extended right hepatectomy for IPNB in the right hepatic duct. Although the surgical margin of the common bile duct was tumor-free, recurrence was detected in the intrapancreatic bile duct 26 months later. Both tumors had similar histopathological characteristics (intestinal-type IPNB with high-grade dysplasia, but no invasive cancer). A literature review identified 9 additional cases of multiple IPNBs. Unlike conventional IPNBs, which typically affect the intrahepatic or hilar bile duct, 80% of recurrent multiple tumors developed in the extrahepatic bile duct. Although multicentric tumors have been suggested in such cases, the intrabiliary dissemination of tumor cells appears to be more likely, as the majority of recurrent tumors develop in more distal parts of the bile duct compared with the primary tumor.

Alternative site of implantation affects tumor malignancy and metastatic potential in mice: its comparison to the flank model.

PubMed

Speroni, Lucia; Bustuoabad, Victoria de Los Angeles; Gasparri, Julieta; Chiaramoni, Nadia Silvia; Taira, María Cristina; Ruggiero, Raúl Alejandro; Alonso, Silvia Del Valle

2009-02-01

MC-C fibrosarcoma and B16F0 melanoma tumors were implanted intradermally in the dorsal region of the foot of mice. Tumor progression was compared to standard implantation in the flank. Although foot tumors only reached 13% (MC-C) and 25% (B16F0) of the mean volume of flank tumors, a more malignant phenotype in terms of histology and survival rate was observed in this type of tumors. Moreover, lung metastases were only detected in hosts bearing foot tumors, in contrast to MC-C and B16F0 populations with tumors growing in the flank. In addition, cellular influx and local immune reaction were higher in the dorsal region of the foot. According to our results, the dermis of the flank allows excessive tumor growth due to its low reactivity. Thus, differences in innate and adaptive immune effectors between the evaluated tumor microenvironments would account for the differences in tumor malignancy. Due to its striking differences with the standard flank inoculation, the tumor implantation model herein introduced could be a valuable tool to study the metastatic potential of different cell lines and the microenvironment components affecting tumor growth.

Emergent Behaviors from a Cellular Automaton Model for Invasive Tumor Growth in Heterogeneous Microenvironments

PubMed Central

Jiao, Yang; Torquato, Salvatore

2011-01-01

Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of the extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA model predicts a rich spectrum of growth dynamics and emergent behaviors of invasive tumors. Besides robustly reproducing the salient features of dendritic invasive growth, such as least-resistance paths of cells and intrabranch homotype attraction, we also predict nontrivial coupling between the growth dynamics of the primary tumor mass and the invasive cells. In addition, we show that the properties of the host microenvironment can significantly affect tumor morphology and growth dynamics, emphasizing the importance of understanding the tumor-host interaction. The capability of our CA model suggests that sophisticated in silico tools could eventually be utilized in clinical situations to predict neoplastic progression and propose individualized optimal treatment strategies. PMID:22215996

Thermal Dose Fractionation Affects Tumor Physiologic Response

PubMed Central

Thrall, Donald E; Maccarini, Paolo; Stauffer, Paul; MacFall, James; Hauck, Marlene; Snyder, Stacey; Case, Beth; Linder, Keith; Lan, Lan; McCall, Linda; Dewhirst, Mark W.

2013-01-01

Purpose It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this, we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in 1 versus 3–4 fractions per week, over 5 weeks. Materials and Methods Canine sarcomas were randomized to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumor response was based on changes in tumor volume, oxygenation, water diffusion quantified using MRI, and a panel of histologic and immunohistochemical endpoints. Results There was a greater reduction in tumor volume and water diffusion at the end of therapy In tumors receiving 1 hyperthermia fraction per week. There was a weak but significant association between improved tumor oxygenation 24 hours after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF 1α and CA IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA IX. There were no significant changes in interstitial fluid pressure, VEGF, wVf, apoptosis or necrosis as a function of treatment group or temperature. Conclusions We did not identify an advantage to a 3–4/week hyperthermia prescription and response data pointed to a 1/week prescription being superior. PMID:22804741

Quality of life, primary traumatisation, and positive and negative affects in primary school students in the Gaza Strip.

PubMed

Veronese, Guido; Pepe, Alessandro; Almurnak, Feda; Jaradah, Alaa; Hamdouna, Husam

2018-02-21

Many researchers have reported that exposure to war and ongoing political violence increases mental health problems in children. Results of studies have also shown a high prevalence (58-80%) of post-traumatic stress disorder in war-affected children living in the occupied Palestinian territory. The aim of this study was to estimate the direct and indirect effects of perceived life satisfaction on the consequences of children's exposure to trauma and the balance of positive and negative affect. Palestinian children were recruited from primary schools in four refugee camps in the Gaza Strip (Bureij, Gaza Beach Camp, Jabalia, Rafah). All children had been involved in or witnessed one or more episodes of violence involving other people in the 2 months prior to the study (the 2012 Gaza War). We used the Multidimensional Students Life Satisfaction Scale (peers, self, living environment, school, family), the Positive and Negative Affect Scale for Children, and the revised Children Impact of Events scale (intrusion and avoidance symptoms) to test (through structural equation modelling) the moderation effect of life satisfaction on war trauma via positive emotions. 1276 Palestinian children were enrolled in this study. The model tested with structural equation modelling was robust. Children's life satisfaction influenced both the intrusion (β=-0·48; p=0.003) and avoidance (β=-11; p=0·021) effects of primary traumatisation. The consequences of primary traumatisation by intrusion (β=0·34; p=0·008) and avoidance (β=0·27; p=0.011) contributed to increasing negative affect. Finally, perceived life satisfaction had direct effects on affective experience, specifically increasing positive affect and diminishing negative affect. Perceived quality of life in children has a role in controlling war-related traumas. Life satisfaction contributes both directly and indirectly to change affectivity. When children perceive themselves to be highly satisfied with their home and

Long-term effectiveness and safety of stereotactic gamma knife surgery as a primary sole treatment in the management of glomus jagulare tumor.

PubMed

Hafez, Raef F A; Morgan, Magad S; Fahmy, Osama M; Hassan, Hamdy T

2018-05-01

This study aims to report and confirm long-term effectiveness and safety of stereotactic Gamma Knife Surgery as a primary sole treatment in the management of 40 glomus jagulare tumors patients. Retrospective analysis of clinical and radiological outcomes of 40 GJTs consecutive patients treated with GKS as primary sole treatment at International Medical Center (IMC), Cairo-Egypt from the beginning of 2005 till the end of 2014,with mean follow-up period of 84 months (range 36-156 months), mean tumor volume was 6.5 cc, and mean peripheral radiation dose of 15 Gy, to mean isodose curve of 38%. The most common neurological deficit at initial evaluation was bulbar symptoms in 24 patients, followed by pulsatile tinnitus in 22, deterioration of hearing in 20 patients. The overall clinical control achieved in 92.5% of patients, while actuarial tumor size control rate post- GKS was 97.5% at 3 years, 97% at 5 years and 92% at 10 years of follow-up period. Gamma knife surgery could be used effectively and safely as a primary sole treatment tool in the management of glomus jugulare tumors. Copyright © 2018 Elsevier B.V. All rights reserved.

Plerixafor Improves Primary Tumor Response and Reduces Metastases in Cervical Cancer Treated with Radio-Chemotherapy.

PubMed

Chaudary, Naz; Pintilie, Melania; Jelveh, Salomeh; Lindsay, Patricia; Hill, Richard P; Milosevic, Michael

2017-03-01

Purpose: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer. Experimental Design: CXCR4 expression was measured in 115 patients with cervical cancer. Two primary orthotopic cervical cancer xenografts (OCICx) with different levels of CXCR4 expression were treated with RT (30 Gy: 15 daily fractions) and weekly cisplatin (4 mg/kg), with or without the CXCR4 inhibitor Plerixafor (5 mg/kg/day). The endpoints were tumor growth delay and lymph node metastases. Acute intestinal toxicity was assessed using a crypt cell assay. Results: There was a fivefold variation in CXCR4 mRNA expression in the patient samples, and good correlation between the expression in patients and in the xenografts. The combination of RTCT and Plerixafor produced substantial tumor growth delay and reduced lymph node metastases compared with RTCT alone in both of the xenograft models. There was a trend toward reduced acute intestinal toxicity with the addition of Plerixafor to RTCT. There were no changes in normal organ morphology to suggest increased late toxicity. Conclusions: This study demonstrates that the addition of Plerixafor to standard RTCT improves primary tumor response and reduces metastases in cervical cancer with no increase in toxicity. This combination warrants further investigation in phase I/II clinical trials. Clin Cancer Res; 23(5); 1242-9. ©2016 AACR . ©2016 American Association for Cancer Research.

Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

PubMed

Gao, Yuping; Jiang, Jiyao; Liu, Qiang

2014-01-01

Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

PubMed Central

Langbecker, Danette; Janda, Monika

2014-01-01

Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model

PubMed Central

Bethge, Anja; Schumacher, Udo

2017-01-01

Background Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities. Methods The biological data gained during these experiments were fed into our previously developed computer model “Cancer and Treatment Simulation Tool” (CaTSiT) to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model. Results According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels’ geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor’s therapeutic susceptibility and its metastatic spreading behavior. Conclusion Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry

Primary Intracranial Germinomas: Retrospective Analysis of Five Cases.

PubMed

Abdallah, Anas; Asilturk, Murad; Uysal, Mustafa Levent; Emel, Erhan; Abdallah, Betul Guler; Bilgic, Bilge; Gundogdu, Gokcen

2018-01-01

Primary intracranial germinomas (PIGs) are rare malignant brain tumors that represent approximately 0.2% to 1.7% of all primary intracranial tumors. PIGs have infrequent, but there is a possibility of spinal cord metastases. In this study, clinical outcomes of five consecutive PIGs have been presented. Medical records were retrospectively reviewed in 1,849 cases of intracranial tumors who underwent surgery between the years 2005 and 2015 and cases confirmed as germinoma histopathologically were included in this study. Five cases of PIGs were detected in two female (40%) and 3 male (60%) patients. The mean age was 15.2±5.6 (8-23) years. The mean follow-up period was 52.3±56.4 (9-135) months. The most common complaint was headache (60%), followed by nausea±vomiting (40%). Four cases (80%) affected the suprasellar region while the fifth patient"s tumor was localized in the pineal region. The duration between the initial symptom and time of surgical intervention ranged between 15 days and 2 months. Twelve months after the first operation, one patient presented with drop seeding metastasis. Four-year survival (with exception of the case that died as a early surgical complication) was 100%. Gross total resection (GTR) was achieved in one patient. Surgical mortality rate was 20%. PIGs" morbidity rate was 60%. PIG is a mostly malignant tumor that generally affects the pediatric age group. They are radiosensitive tumors. Subtotal or near-total resection using stereotactic guide or direct surgery to confirm the histopathological diagnosis followed by chemotherapy and whole brain or in some cases craniospinal radiotherapy rather than GTR is therefore the treatment of choice.

Prognostic value of lymphovascular invasion of the primary tumor in hypopharyngeal carcinoma after total laryngopharyngectomy.

PubMed

Saito, Yuki; Omura, Go; Yasuhara, Kazuo; Rikitake, Ryoko; Akashi, Ken; Fukuoka, Osamu; Yoshida, Masafumi; Ando, Mizuo; Asakage, Takahiro; Yamasoba, Tatsuya

2017-08-01

We aimed to determinate the prognostic value of lymphovascular invasion in the specimens resected during total laryngopharyngectomy for hypopharyngeal carcinoma. Patients who underwent total laryngopharyngectomy at our institution between 2004 and 2014 were included in this study and retrospectively analyzed. We then discriminated for vascular invasion and lymphatic invasion of the primary tumor in all cases. We reviewed 135 records (120 men and 15 women; age range, 36-84 years). Tumors with lymphatic invasion tended to be associated with more metastatic lymph nodes and extracapsular spread (ECS) of metastatic lymph nodes. Tumors with vascular invasion tended to be associated with nonpyriform sinus locations. In a multivariate analysis, nonpyriform sinus locations, >3 metastatic lymph nodes, and vascular invasion remained significant prognostic factors for overall survival (OS); in recursive partitioning analysis, ECS and vascular invasion remained important categorical variables for OS. Vascular invasion is a strong prognostic biomarker for advanced hypopharyngeal carcinoma. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1535-1543, 2017. © 2017 Wiley Periodicals, Inc.

Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer.

PubMed

Li, Qingguo; Wang, Changjian; Li, Yaqi; Li, Xinxiang; Xu, Ye; Cai, Guoxiang; Lian, Peng; Cai, Sanjun

2017-07-18

Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042), NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was significantly more favorable than that of patients at stage N2 (P = 0.038). In conclusion, primary tumor LN status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.

Primary cutaneous perivascular epithelioid cell tumor: a clinicopathological and molecular reappraisal.

PubMed

Charli-Joseph, Yann; Saggini, Andrea; Vemula, Swapna; Weier, Jingly; Mirza, Sonia; LeBoit, Philip E

2014-12-01

Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm of uncertain histogenesis with a mixed myomelanocytic immunophenotype, rarely arising in the skin (primary cutaneous PEComa [pcPEComa]). We analyzed the clinicopathological features of 8 pcPEComas, assayed for DNA copy number changes and for initiating mutations common in melanocytic neoplasms. pcPEComas were evaluated using immunohistochemistry, comparative genomic hybridization, and DNA sequencing. pcPEComas were erythematous nodules, mostly in the lower extremities of women (5/8), composed of large pale-staining epithelioid cells. The patient's age range was 26 to 67 (mean 46) years. The percentages of tumors staining positively were as follows: micro-ophthalmia-associated transcription factor, NKI/C3, bcl-1, E-cadherin, and cathepsin K (100%); HMB-45, 4E-binding protein 1, and CD68 (88%); smooth muscle actin and muscle-specific actin (40%); S100 (38%); calponin (20%); desmin (13%); and melan-A, SOX10, and keratin (0%). No chromosomal copy number changes or initiating mutations were identified. Small sample size is a limitation. pcPEComas have a different molecular signature than extracutaneous tumors and are unrelated to tuberous sclerosis. However, the common expression of 4E-binding protein 1 points to a role of the mTOR pathway in their pathogenesis. Because pcPEComas are diagnostically challenging, we propose that micro-ophthalmia-associated transcription factor, NKIC3, smooth muscle actin, desmin, bcl-1, cathepsin K, and 4E-binding protein 1 can be used when evaluating a possible pcPEComa. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Sensitivity of endometrial cancer cells from primary human tumor samples to new potential anticancer peptide lactaptin.

PubMed

Koval, Olga A; Sakaeva, Galiya R; Fomin, Alexander S; Nushtaeva, Anna A; Semenov, Dmitry V; Kuligina, Elena V; Gulyaeva, Ludmila F; Gerasimov, Alexey V; Richter, Vladimir A

2015-01-01

Endometrial carcinoma is the most common gynecologic malignancy which is associated with a poor prognosis when diagnosed at an advanced stage; therefore, the discovery of efficacious new drugs is required to reinforce conventional chemotherapy. Short-term cultures of primary cells from endometrial tumors could be used for testing new anticancer therapeutics as well as for the development of personalized cancer therapy strategy. Here, the antitumor effect of a recombinant analogue of lactaptin (RL2), a new potential anticancer molecule, was examined against primary human endometrial cancer cells. Primary cell cultures of malignant and normal human endometrium were performed by enzymatic digestion of endometrial tissue from biopsy material. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the messenger ribonucleic acid (mRNA) state of estrogen (ERs) and progesterone (PRs) hormone receptors and aromatase (Cyp 19) in cell cultures. Dynamic monitoring of cell adhesion and proliferation was made using the iCELLigence system (ASEA Biosciences). The sensitivity of cell cultures to conventional anticancer drugs and the lactaptin analog was estimated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry, and the iCELLligence system. Established short-term primary cultures of endometrial cancer cells were ERα/ERβ/PR-positive and sensitive for RL2. The IC 50 values of doxorubicin and cisplatin were determined for all of the primary cultures designed. KE normal cells displaying low Cyp19 mRNA levels and high ERβ and PR mRNA levels were more resistant to RL2 treatment as well as to cisplatin and doxorubicin. Our results indicate that the recombinant analog of lactaptin, RL2, exerts cytotoxic effects against primary hormone-dependent endometrial tumor cells in vitro with features of apoptosis.

Prognostic Impact of Radiation Therapy to the Primary Tumor in Patients With Non-small Cell Lung Cancer and Oligometastasis at Diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez Guerra, Jose Luis; Department of Radiation Oncology, Instituto Madrileno de Oncologia/Grupo IMO, Madrid; Gomez, Daniel, E-mail: dgomez@mdanderson.org

2012-09-01

Purpose: We investigated prognostic factors associated with survival in patients with non-small cell lung cancer (NSCLC) and oligometastatic disease at diagnosis, particularly the influence of local treatment to the primary site on prognosis. Methods and Materials: From January 2000 through June 2011, 78 consecutive patients with oligometastatic NSCLC (<5 metastases) at diagnosis underwent definitive chemoradiation therapy ({>=}45 Gy) to the primary site. Forty-four of these patients also received definitive local treatment for the oligometastases. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: Univariate Cox proportional hazard analysis revealed bettermore » overall survival (OS) for those patients who received at least 63 Gy of radiation to the primary site (P=.002), received definitive local treatment for oligometastasis (P=.041), had a Karnofsky performance status (KPS) score >80 (P=.007), had a gross tumor volume {<=}124 cm{sup 3} (P=.002), had adenocarcinoma histology (P=.002), or had no history of respiratory disease (P=.016). On multivariate analysis, radiation dose, performance status, and tumor volume retained significance (P=.004, P=.006, and P<.001, respectively). The radiation dose also maintained significance when patients with and without brain metastases were analyzed separately. Conclusions: Tumor volume, KPS, and receipt of at least 63 Gy to the primary tumor are associated with improved OS in patients with oligometastatic NSCLC at diagnosis. Our results suggest that a subset of such patients may benefit from definitive local therapy.« less

Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

PubMed

Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

2009-09-01

For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model

PubMed Central

d'Angelo, Michele; Cristiano, Loredana; Galzio, Renato; Destouches, Damien; Florio, Tiziana Marilena; Dhez, Anne Chloé; Astarita, Carlo; Cinque, Benedetta; Fidoamore, Alessia; Rosati, Floriana; Cifone, Maria Grazia; Ippoliti, Rodolfo; Giordano, Antonio; Courty, José; Cimini, Annamaria

2015-01-01

Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma. PMID:26540346

Subclonal diversification of primary breast cancer revealed by multiregion sequencing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yates, Lucy R.; Gerstung, Moritz; Knappskog, Stian

Sequencing cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and latemore » in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.« less

Subclonal diversification of primary breast cancer revealed by multiregion sequencing

DOE PAGES

Yates, Lucy R.; Gerstung, Moritz; Knappskog, Stian; ...

2015-06-22

Sequencing cancer genomes may enable tailoring of therapeutics to the underlying biological abnormalities driving a particular patient's tumor. However, sequencing-based strategies rely heavily on representative sampling of tumors. To understand the subclonal structure of primary breast cancer, we applied whole-genome and targeted sequencing to multiple samples from each of 50 patients' tumors (303 samples in total). The extent of subclonal diversification varied among cases and followed spatial patterns. No strict temporal order was evident, with point mutations and rearrangements affecting the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumors and latemore » in others. In 13 out of 50 cancers, potentially targetable mutations were subclonal. Landmarks of disease progression, such as resistance to chemotherapy and the acquisition of invasive or metastatic potential, arose within detectable subclones of antecedent lesions. These findings highlight the importance of including analyses of subclonal structure and tumor evolution in clinical trials of primary breast cancer.« less

Gene silencing in primary and metastatic tumors by small interfering RNA delivery in mice: quantitative analysis using melanoma cells expressing firefly and sea pansy luciferases.

PubMed

Takahashi, Yuki; Nishikawa, Makiya; Kobayashi, Naoki; Takakura, Yoshinobu

2005-07-20

Silencing of oncogenes or other genes contributing to tumor malignancy or progression by RNA interference (RNAi) offers a promising approach to treating tumor patients. To achieve RNAi-based tumor therapy, a small interfering RNA (siRNA) or siRNA-expressing vector needs to be delivered to tumor cells, but little information about its in vivo delivery has been reported. In this study, we examined whether the expression of the target gene in tumor cells can be suppressed by the delivery of RNAi effectors to primary and metastatic tumor cells. To quantitatively evaluate the RNAi effects in tumor cells, mouse melanoma B16-BL6 cells were stably transfected with both firefly (a model target gene) and sea pansy (an internal standard gene) luciferase genes to obtain B16-BL6/dual Luc cells. The target gene expression in subcutaneous primary tumors of B16-BL6/dual Luc cells was significantly suppressed by direct injection of the RNAi effectors followed by electroporation. The expression in metastatic hepatic tumors was also significantly reduced by an intravenous injection of either RNAi effector by the hydrodynamics-based procedure. These results indicate that the both RNAi effectors have a potential to silence target gene in tumor cells in vivo when successfully delivered to tumor cells.

Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer

DTIC Science & Technology

2004-07-01

by quantitative RT-QPCR. Further analysis of epithelium from matched spine metastases revealed some genes that were up-regulated further at the...9-fold in matched bone metastases. The expression in spine metastases was verified by in situ hybridisation whilst the expression of stefin Al in...growth in the mammary gland of Balb/c mice. Fresh resected tissue (normal fat pad, primary tumor tissue or the metastatic sites spine , femur and lung) was

Angiopoietin-1 deficiency increases tumor metastasis in mice.

PubMed

Michael, Iacovos P; Orebrand, Martina; Lima, Marta; Pereira, Beatriz; Volpert, Olga; Quaggin, Susan E; Jeansson, Marie

2017-08-11

Angipoietin-1 activation of the tyrosine kinase receptor Tek expressed mainly on endothelial cells leads to survival and stabilization of endothelial cells. Studies have shown that Angiopoietin-1 counteracts permeability induced by a number of stimuli. Here, we test the hypothesis that loss of Angiopoietin-1/Tek signaling in the vasculature would increase metastasis. Angiopoietin-1 was deleted in mice just before birth using floxed Angiopoietin-1 and Tek mice crossed to doxycycline-inducible bitransgenic ROSA-rtTA/tetO-Cre mice. By crossing Angiopoietin-1 knockout mice to the MMTV-PyMT autochthonous mouse breast cancer model, we investigated primary tumor growth and metastasis to the lung. Furthermore, we utilized B16F10 melanoma cells subcutaneous and experimental lung metastasis models in Angiopoietin-1 and Tek knockout mice. We found that primary tumor growth in MMTV-PyMT mice was unaffected, while metastasis to the lung was significantly increased in Angiopoietin-1 knockout MMTV-PyMT mice. In addition, angiopoietin-1 deficient mice exhibited a significant increase in lung metastasis of B16F10 melanoma cells, compared to wild type mice 3 weeks after injection. Additional experiments showed that this was likely an early event due to increased attachment or extravasation of tumor cells, since seeding of tumor cells was significantly increased 4 and 24 h post tail vein injection. Finally, using inducible Tek knockout mice, we showed a significant increase in tumor cell seeding to the lung, suggesting that Angiopoietin-1/Tek signaling is important for vascular integrity to limit metastasis. This study show that loss of the Angiopoietin-1/Tek vascular growth factor system leads to increased metastasis without affecting primary tumor growth.

Fibrosarcoma of the jaws: two cases of primary tumors with intraosseous growth.

PubMed

Angiero, Francesca; Rizzuti, Tommaso; Crippa, Rolando; Stefani, Michele

2007-01-01

Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that rarely affects the oral cavity. Two cases of primary FS of the jaws with intraosseous growth (2 men, aged 53 and 71 years) are described. Microscopically, in one case the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, with significant mitotic activity and nuclear pleomorphism; the second case was characterized by low cellularity comprising spindle-shaped cells, deposited in a variably fibrous and myxoid stroma. On immunohistochemistry, cells in both cases were strongly immunoreactive for MIB-1 and vimentin, focally positive for CD68, and negative for S-100 protein, pancytokeratin, HMB45, CD34, desmin, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). Based on clinical, histological and immunohistochemical findings, the final diagnosis was FS in the first case, myxofibrosarcoma in the second. Treatment was radical surgery with mandibular reconstruction. After two years, the first patient displayed multiple metastases and died during the third year after the initial diagnosis; the second patient was still alive and doing well five years after treatment. We discuss the differential diagnosis versus other forms of sarcoma, examining the morphological appearance that is frequently very similar, the immunohistochemical expression of MIB-1, vimentin, S-100, CD-34, CD68, EMA, as well as conventional clinicopathological features that may help to distinguish FS from other sarcomas.

Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs).

PubMed

Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

2017-12-19

KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC 50 : 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC 50 : 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan ™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs.

Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs)

PubMed Central

Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

2017-01-01

KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC50: 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC50: 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs. PMID:29340041

Stereotactic body radiotherapy for primary and metastatic liver tumors - the Mayo Clinic experience.

PubMed

Merrell, Kenneth W; Johnson, Jedediah E; Mou, Benjamin; Barney, Brandon M; Nelson, Kathryn E; Mayo, Charles S; Haddock, Michael G; Hallemeier, Christopher L; Olivier, Kenneth R

2016-01-01

To better understand the efficacy of liver SBRT we reviewed our prospectively collected institutional SBRT database. Between May 2008 and March 2013, 80 patients with 104 liver lesions received SBRT. The Kaplan-Meier method estimated local control (LC), overall survival (OS). Cox proportional hazards regression models identified factors associated with LC and OS. The median follow-up for living patients was 38.6 months. Patients had primary (n=17) or metastatic (n=63) tumors. The median tumor size was 2.7 cm (range, 0.6-14.0). The 1 and 4 year rates of LC were 89.4% and 88%, respectively. Colorectal (CRC) metastasis was associated with lower rates of LC (p=0.013). OS at 1 and 4 years was 78% and 25%, respectively. Patients with CRC metastases had higher rates of OS (p=0.03). The occurrence of severe acute and late toxicity was 3.8% and 6.3%, respectively. SBRT should be studied in prospective clinical trials compared with other liver-directed treatment modalities.

Implementing a Primary Healthcare Framework: The Importance of Nursing Leadership in Developing and Maintaining a Brain Tumor Support Group.

PubMed

Nichols, Linda J; Wright, Kylie M

2015-08-01

Although brain tumor support groups have been available internationally for many years, Liverpool Hospital in Australia has not traditionally provided this service. As a leadership initiative, the development of a brain tumor support group that incorporates a primary healthcare framework is a sustainable approach that showcases the role of nursing leaders in changing attitudes and improving outcomes. The purpose of this review of the literature and reflection of clinical experience is to explore nursing leadership within brain tumor-specific support groups. This article will showcase a nurse-led group that incorporated a coordinated approach to delivering patient-centered care. The initiation of activities and interventions that reflected the five tenets of primary health care resulted in improved outcomes for individuals and their family caregivers throughout the trajectory of their illness. Vital to the success of this project was moving from a standalone leader to building collective and collaborative leadership more conducive to facilitating change. The support group successfully demonstrated that individuals and family caregivers may see ongoing and long-term improvements during and following treatment.

RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development.

PubMed

Elchuri, Sailaja V; Rajasekaran, Swetha; Miles, Wayne O

2018-01-01

Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1). Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area's to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

Individual differences in Affective Neuroscience Personality Scale (ANPS) primary emotional traits and depressive tendencies.

PubMed

Montag, Christian; Widenhorn-Müller, Katharina; Panksepp, Jaak; Kiefer, Markus

2017-02-01

The present study investigated individual differences in the Affective Neuroscience Personality Scales (ANPS), representing measures of primary emotional systems, and depressive tendencies in two independent samples. In order to be able to find support for a continuum model with respect to the relation of strength in the cross-species "affective neuroscience" taxonomy of primary emotional systems, we investigated ANPS measured personality traits in a psychologically mostly healthy population (n=614 participants) as well as a sample of clinically depressed people (n=55 depressed patients). In both normal and depressed samples robust associations appeared between higher FEAR and SADNESS scores and depressive tendencies. A similar - albeit weaker - association was observed with lower SEEKING system scores and higher depressive tendencies, an effect again seen in both samples. The study is of cross-sectional nature and therefore only associations between primary emotional systems and depressive tendencies were evaluated. These results show that similar associations between ANPS monitored primary emotional systems and tendencies toward depression can be observed in both healthy and depressed participants. This lends support for a continuum of affective changes accompanying depression, potentially reflecting differences in specific brain emotional system activities in both affectively normal as well as clinically depressed individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

Surgical management of primary bone tumors of the spine: validation of an approach to enhance cure and reduce local recurrence.

PubMed

Fisher, Charles G; Saravanja, Davor D; Dvorak, Marcel F; Rampersaud, Y Raja; Clarkson, Paul W; Hurlbert, John; Fox, Richard; Zhang, Hongbin; Lewis, Stephen; Riaz, Salman; Ferguson, Peter C; Boyd, Michael C

2011-05-01

Multicenter ambispective cohort analysis. The purpose of this study is to determine whether applying Enneking's principles to surgical management of primary bone tumors of the spine significant decreases local recurrence and/or mortality. Oncologic management of primary tumors of spine has historically been inconsistent, controversial, and open to individual interpretation. A multicenter ambispective cohort analysis from 4 tertiary care spine referral centers was done. Patients were analyzed in 2 cohorts, "Enneking Appropriate" (EA), surgical margin as recommended by Enneking, and "Enneking Inappropriate" (EI), surgical margin not recommended by Enneking. Benign tumors were not included in mortality analysis. Two cohorts represented an analytic dataset with 147 patients, 86 male, average age 46 years (range: 10-83). Median follow-up was 4 (2-7) years in the EA and 6 (5.5-15.5) years in the EI. Seventy-one patients suffered at least 1 local recurrence during the study, 57 of 77 in the EI group and 14 of 70 in the EA group. EI surgical approach caused higher risk of first local recurrence (P < 0.0001). There were 48 deaths in total; 29 in the EI group and 19 in the EA. There was a strong correlation between the first local recurrence and mortality with an odds ratio of 4.69, (P < 0.0001). EI surgical approach resulted in a higher risk of mortality with a hazard ratio of 3.10, (P = 0.0485) compared to EA approach. Surgery results in a significant reduction in local recurrence when primary bone tumors of the spine are resected with EA margins. Local recurrence has a high concordance with mortality in resection of these tumors. A significant decrease in mortality occurs when EA surgery is used.

How sequestration cuts affect primary care physicians and graduate medical education.

PubMed

Chauhan, Bindiya; Coffin, Janis

2013-01-01

On April 1, 2013, sequestration cuts went into effect impacting Medicare physician payments, graduate medical education, and many other healthcare agencies. The cuts range from 2% to 5%, affecting various departments and organizations. There is already a shortage of primary care physicians in general, not including rural or underserved areas, with limited grants for advanced training. The sequestration cuts negatively impact the future of many primary care physicians and hinder the care many Americans will receive over time.

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.

PubMed

Contractor, Tanupriya; Kobayashi, Shinta; da Silva, Edaise; Clausen, Richard; Chan, Chang; Vosburgh, Evan; Tang, Laura H; Levine, Arnold J; Harris, Chris R

2016-05-24

In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors.

Large mass affecting retroperitoneal great vessels: a rare presentation of a cancer of unknown primary with diagnostic dilemma and challenged surgical intervention.

PubMed

Stakia, Paraskevi; Lagos, Panagiotis; Gourgiotis, Stavros; Tzilalis, Vasilios D; Aloizos, Stavros; Salemis, Nikolaos S

2009-01-01

Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study.

PubMed

Thomas, Nancy E; Busam, Klaus J; From, Lynn; Kricker, Anne; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Groben, Pamela A; Hao, Honglin; Orlow, Irene; Reiner, Anne S; Luo, Li; Paine, Susan; Ollila, David W; Wilcox, Homer; Begg, Colin B; Berwick, Marianne

2013-11-20

Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.

Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study

PubMed Central

Thomas, Nancy E.; Busam, Klaus J.; From, Lynn; Kricker, Anne; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Groben, Pamela A.; Hao, Honglin; Orlow, Irene; Reiner, Anne S.; Luo, Li; Paine, Susan; Ollila, David W.; Wilcox, Homer; Begg, Colin B.; Berwick, Marianne

2013-01-01

Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions. PMID:24127443

DCB - Tumor Metastasis Research

Cancer.gov

Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

Outcome of primary childhood central nervous system tumors: results from a single center in Iran.

PubMed

Rafsanjani, Kh Arjmandi; Bahoush, Gr; Nikpoor, F; Vossough, P

2012-10-01

Childhood primary central nervous system (CNS) malignancies are one of the most important concerns in pediatric oncology. In this historical cohort, 82 patients treated in Ali-Asghar Children's Hospital between 1996 and 2005 were evaluated for age, gender, type of treatment, tumor pathology, and survival. The records of 38 female (46.3%) and 44 male (53.7%) patients were included. The mean age was 6.8 ± 3.39 years (6 months to 14 years); the frequency of medulloblastoma was significantly more than others (p = 0.012). Complete resection, radiotherapy, and chemotherapy were done in 47.5, 82.9, and 97.56%, respectively. Estimated 5 years overall and event-free survivals (EFSs) were approximately 68.5 and 35%, respectively. The patients with complete resected tumors had significantly better outcome (p = 0.013). Also, low-grade versus high-grade astrocytoma was significantly a better outcome (p = 0.01). The poor EFS with consideration of high number of progressive disease among our patients (50% unresectable tumor) suggests that children in Iran with CNS tumors had high quality of care but availability of advanced treatment protocol and sharing of cooperative trial study is essential for survival improvement. In addition to use more advanced methods and equipments of radiotherapy and chemotherapeutic drugs, we should seriously consider development of better surgical techniques to increase the rate of complete resection of malignant CNS tumors. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Clinical results of primary malignant musculoskeletal tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen.

PubMed

Paholpak, Permsak; Sirichativapee, Winai; Wisanuyotin, Taweechok; Kosuwon, Weerachai; Jeeravipoolvarn, Polasak

2015-06-01

To evaluate the clinical results of primary malignant musculoskeletal tumors treated with wide resection and recycling autograft reconstruction using liquid nitrogen. We reviewed 12 patients who had a primary malignant bone and soft tissue tumor treated by wide resection and recycling autograft reconstruction using liquid nitrogen between March 2006 and March 2013. The results were judged by recurrence, functional status and complications. Functional status was assessed according to the Musculoskeletal Tumor Society Score (MSTSS). Clinical failure was defined as need for reoperation in order to change the type of reconstruction or to amputate, and the presence of local recurrence. The most common tumor was osteosarcoma (eight cases) followed by Ewing's sarcoma (two cases). The tibia was the most frequently involved skeletal site (six cases) followed by the femur (three cases). The median follow-up period was 32 months. In 12 patients, 7 were still alive without recurrence. There were 3 clinical failures: 1 local recurrence and 2 graft complications at 28, 51 and 20 months after reconstruction, respectively. The main complication was infection (three cases). All osteotomy sites were radiographic unions, and the union time was 8.2 ± 2.7 months. The mean ± SD MSTSS score was 79% ± 11%; excellent functional results were achieved in seven patients. Recycling autograft reconstruction using liquid nitrogen had favorable clinical outcomes in terms of functional status and local recurrence. This reconstruction method, therefore, represents a reasonable alternative for limb salvage surgery. © 2014 Wiley Publishing Asia Pty Ltd.

Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.

PubMed

Thakur, Archana; Bollig, Aliccia; Wu, Jiusheng; Liao, Dezhong J

2008-01-24

Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials. Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples. We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.

[Immunohistochemical hormonal mismatch and human epidermal growth factor type 2 [HER2] phenotype of brain metastases in breast cancer carcinoma compared to primary tumors].

PubMed

Joubert, C; Boissonneau, S; Fina, F; Figarella-Branger, D; Ouafik, L; Fuentes, S; Dufour, H; Gonçalves, A; Charaffe-Jauffret, E; Metellus, P

2016-06-01

Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer. This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records. Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test). the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John

2012-04-01

Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, andmore » size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.« less

Multiple primary tumors: Colorectal carcinoma and non-Hodgkin's lymphoma.

PubMed

Pantoja Pachajoa, Diana A; Bruno, Marco Antonio; Alvarez, Fernando A; Viscido, Germán; Mandojana, Facundo; Doniquian, Alejandro

2018-05-30

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, whereas lymphoma is the sixth leading cause of cancer death, 90% of which corresponds to non-Hodgkin's lymphoma (NHL). The association of these two primary tumors, a solid tumor with an hematological malignancy, is very uncommon. We report the case of a 47-year-old man who presented with abdominal pain, a right upper quadrant mass and 12 kg of weight loss in 9 months. The computed tomography (CT) showed a large intra-abdominal mass and a wall thickening at the rectosigmoid junction. A colonoscopic biopsy confirmed a colorectal adenocarcinoma and a laparoscopic biopsy of the intraabdominal mass confirmed a diffuse large B-cell NHL. After multidisciplinary discussion it was decided to treat first the NHL with 3 cycles of R-CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone). The patient experienced a good response with a 70% decrease in the intraabdominal mass and a negative PET/CT. Four months after diagnosis an anterior rectal resection was performed. The patient recovered uneventfully and was discharged 5 days after surgery. The patient finally died 20 months after surgery due to disease progression. The association of CRC and NHL is an extremely rare scenario that represents a great multidisciplinary challenge with respect to treatment due to the scarce literature found on this topic. When CRC and NHL are present, all the different disease patterns must be considered in a multidisciplinary and patient-oriented fashion, in order to decide the best therapeutic strategy for each individual. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

PubMed

Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

2018-06-01

In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

LAG-3 in Non-Small-cell Lung Cancer: Expression in Primary Tumors and Metastatic Lymph Nodes Is Associated With Improved Survival.

PubMed

Hald, Sigurd M; Rakaee, Mehrdad; Martinez, Inigo; Richardsen, Elin; Al-Saad, Samer; Paulsen, Erna-Elise; Blix, Egil Støre; Kilvaer, Thomas; Andersen, Sigve; Busund, Lill-Tove; Bremnes, Roy M; Donnem, Tom

2018-05-01

Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non-small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3 + tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification. Primary tumor tissue from 553 stage I-IIIB NSCLC patients and 143 corresponding metastatic lymph nodes were collected. The expression of LAG-3 was evaluated by immunohistochemistry on tissue microarrays. On univariate analysis, LAG-3 + TILs in the intraepithelial and stromal compartments of primary tumors and in the intraepithelial and extraepithelial compartments of metastatic lymph nodes were associated with improved disease-specific survival (DSS). On multivariate analysis, stromal LAG-3 + TILs were a significant independent predictor of improved DSS (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.43-0.82; P = .002). Stromal LAG-3 + TILs did not have prognostic impact across all pathologic stages. In the metastatic lymph nodes, intraepithelial (HR, 0.61; 95% CI, 0.38-0.99; P = .049) and extraepithelial (HR, 0.54; 95% CI, 0.29-0.70; P < .001) LAG-3 + TILs were independently associated with favorable DSS. LAG-3 + TILs are an independent positive prognostic factor in stage I-IIIB NSCLC. LAG-3 in metastatic lymph nodes is a candidate marker for an immunoscore in NSCLC. Copyright © 2017 Elsevier Inc. All rights reserved.

Prognostic factors of primary gastrointestinal stromal tumors: a cohort study based on high-volume centers.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2018-02-01

We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Of the included patients, 1,375 (53.5%) were male, and the patient age range was 18 to 95 (median, 58) years. The tumors were mostly found in the stomach (64.5%), small intestine (25.1%) and colorectal region (5.1%). At the time of diagnosis, the median tumor size was 4.0 (range: 0.1-55.0) cm, and the median mitotic index per 50 high power fields (HPFs) was 3 (range: 0-254). Of the 2,168 resected patients, 2,009 (92.7%) received curative resection. According to the modified National Institutes of Health (NIH) classification, 21.9%, 28.9%, 14.1% and 35.1% were very low-, low-, intermediate- and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1 (DOG-1), 8.0% for S-100, 31.0% for smooth muscle actin (SMA) and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib (P<0.001), whereas intermediate-risk patients did not (P=0.954). Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Characteristics of time-activity curves obtained from dynamic 11C-methionine PET in common primary brain tumors.

PubMed

Nomura, Yuichi; Asano, Yoshitaka; Shinoda, Jun; Yano, Hirohito; Ikegame, Yuka; Kawasaki, Tomohiro; Nakayama, Noriyuki; Maruyama, Takashi; Muragaki, Yoshihiro; Iwama, Toru

2018-07-01

The aim of this study was to assess whether dynamic PET with 11 C-methionine (MET) (MET-PET) is useful in the diagnosis of brain tumors. One hundred sixty patients with brain tumors (139 gliomas, 9 meningiomas, 4 hemangioblastomas and 8 primary central nervous system lymphomas [PCNSL]) underwent dynamic MET-PET with a 3-dimensional acquisition mode, and the maximum tumor MET-standardized uptake value (MET-SUV) was measured consecutively to construct a time-activity curve (TAC). Furthermore, receiver operating characteristic (ROC) curves were generated from the time-to-peak (TTP) and the slope of the curve in the late phase (SLOPE). The TAC patterns of MET-SUVs (MET-TACs) could be divided into four characteristic types when MET dynamics were analyzed by dividing the MET-TAC into three phases. MET-SUVs were significantly higher in early and late phases in glioblastoma compared to anaplastic astrocytoma, diffuse astrocytoma and the normal frontal cortex (P < 0.05). The SLOPE in the late phase was significantly lower in tumors that included an oligodendroglial component compared to astrocytic tumors (P < 0.001). When we set the cutoff of the SLOPE in the late phase to - 0.04 h -1 for the differentiation of tumors that included an oligodendroglial component from astrocytic tumors, the diagnostic accuracy was 74.2% sensitivity and 64.9% specificity. The area under the ROC curve was 0.731. The results of this study show that quantification of the MET-TAC for each brain tumor identified by a dynamic MET-PET study could be helpful in the non-invasive discrimination of brain tumor subtypes, in particular gliomas.

FSensitive detection of mono- and polyclonal ESR1 mutations in primary tumors, metastatic lesions and cell free DNA of breast cancer patients

PubMed Central

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C.; Hartmaier, Ryan J.; Watters, Rebecca J.; Jonnalagadda, Amruth R.; Trejo Bittar, Humberto E.; Berg, Aaron; Hamilton, Ronald L.; Kurland, Brenda F.; Weiss, Kurt R.; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N.; Brufsky, Adam M.; Ambros, Tadeu F.; Stern, Andrew M.; Puhalla, Shannon L.; Lee, Adrian V.; Oesterreich, Steffi

2015-01-01

Purpose Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell free DNA (cfDNA). Patients and Methods Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n=43), bone (n=12) and brain metastases (n=38), and cfDNA (n=29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. Results ESR1 mutations were detected for D538G (n=13), Y537S (n=3) and Y537C (n=1), and not for K303R, S463P or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3 to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n=5), mutations were detected in both (n=3) or in cfDNA only (n=2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. Conclusions ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1 mutant clones are enriched by endocrine therapy. Further studies should address if sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. PMID:26500237

Predictive Value of Primary Tumor Site for Loco-regional Recurrence in Early Breast Cancer Patients with One to Three Positive Axillary Lymphadenophy.

PubMed

Niu, Shaoqing; Wen, Ge; Ren, Yufeng; Li, Yiyang; Feng, Lingling; Wang, Chengtao; Huang, Xiaobo; Wen, Bixiu; Zhang, Yujing

2017-01-01

Introduction: It remains controversial on high risks for early breast cancer patients with one to three axillary nodes after mastectomy who is predisposition to locoregional recurrence. The present study is to investigate the relationship between primary tumor site and loco-regional recurrence (LRR) and explore the predictive value of clinicopathological characteristics in LRR for early breast cancer patients with one to three positive axillary lymph nodes after mastectomy. Methods: We reviewed the clinical data of 656 consecutively diagnosed patients with pT 1-2 N 1 M 0 breast cancer who were treated in Sun Yat-sen University Cancer Center with radical operation without postoperative radiotherapy between March 1998 and December 2010. The primary tumor sites included outer quadrant in 455 patients (69.36%), inner quadrant in 156 patients (23.78%)and central quadrant in 45 patients (6.86%). LRR and LRR-free survival (LRFS) in combination with clinical and pathological features were analyzed to screen out patients with higher risk of LRR. Results: The median follow-up time was 64.9 months. The 5-, 10-year LRR for the cohort was 8.6% and 12.9%, respectively; the 5-, 10-year LRFS was 86.2% and 76.4%, respectively. Multivariate analyses showed that age of ≤35 years, inner quadrant tumor and non-luminal subtype were independent risk factors for LRR and LRFS. Patients with primary tumor in inner quadrant showed higher LRR and poorer LRFS when risk factors are ≥2 than those with tumors in other sites. Conclusions: Inner quadrant tumor was an independent predictor for LRR and LRFS in patients with early breast cancer and one to three positive axillary lymph nodes, which would be more accurate in combination with other prognostic indexes including patients' age, pathological T stage, Ki67 status, molecular subtypes.

NK cell heparanase controls tumor invasion and immune surveillance

PubMed Central

Putz, Eva M.; Mayfosh, Alyce J.; Barkauskas, Deborah S.; Nakamura, Kyohei; Town, Liam; Goodall, Katharine J.; Yee, Dean Y.; Poon, Ivan K.H.; Baschuk, Nikola; Souza-Fonseca-Guimaraes, Fernando; Hulett, Mark D.; Smyth, Mark J.

2017-01-01

NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Hpsefl/fl NKp46-iCre mice were also more susceptible to tumor growth than were their littermate controls when challenged with the established mouse lymphoma cell line RMA-S-RAE-1β, which overexpresses the NK cell group 2D (NKG2D) ligand RAE-1β, or when inoculated with metastatic melanoma, prostate carcinoma, or mammary carcinoma cell lines. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase. Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. Our data suggest that heparanase plays a critical role in NK cell invasion into tumors and thereby tumor progression and metastases. This should be considered when systemically treating cancer patients with heparanase inhibitors, since the potential adverse effect on NK cell infiltration might limit the antitumor activity of the inhibitors. PMID:28581441

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma

PubMed Central

Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-01-01

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides “killing” PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors. PMID:28146424

Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.

PubMed

Cao, Yueyu; Qiao, Jing; Lin, Zhen; Zabaleta, Jovanny; Dai, Lu; Qin, Zhiqiang

2017-02-28

Primary effusion lymphoma (PEL) is a rare and highly aggressive B-cell malignancy with Kaposi's sarcoma-associated herpesvirus (KSHV) infection, while lack of effective therapies. Our recent data indicated that targeting the sphingolipid metabolism by either sphingosine kinase inhibitor or exogenous ceramide species induces PEL cell apoptosis and suppresses tumor progression in vivo. However, the underlying mechanisms for these exogenous ceramides "killing" PEL cells remain largely unknown. Based on the microarray analysis, we found that exogenous dhC16-Cer treatment affected the expression of many cellular genes with important functions within PEL cells such as regulation of cell cycle, cell survival/proliferation, and apoptosis/anti-apoptosis. Interestingly, we found that a subset of tumor suppressor genes (TSGs) was up-regulated from dhC16-Cer treated PEL cells. One of these elevated TSGs, Thrombospondin-1 (THBS1) was required for dhC16-Cer induced PEL cell cycle arrest. Moreover, dhC16-Cer up-regulation of THBS1 was through the suppression of multiple KSHV microRNAs expression. Our data demonstrate that exogenous ceramides display anti-cancer activities for PEL through regulation of both host and oncogenic virus factors.

Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors.

PubMed

Carlsson, J; Shen, L; Xiang, J; Xu, J; Wei, Q

2013-01-01

The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extra-cellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGFR-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression. In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR- and HER2-targeted therapy are briefly discussed in the

Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis

PubMed Central

Fan, Zheng; Sehm, Tina; Rauh, Manfred; Buchfelder, Michael

2014-01-01

Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA), a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc −; SLC7a11) and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G) resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage. PMID:24714627

Raman spectroscopic imaging as complementary tool for histopathologic assessment of brain tumors

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Bergner, Norbert; Romeike, Bernd; Reichart, Rupert; Kalff, Rolf; Geiger, Kathrin; Kirsch, Matthias; Schackert, Gabriele; Popp, Jürgen

2012-02-01

Raman spectroscopy enables label-free assessment of brain tissues and tumors based on their biochemical composition. Combination of the Raman spectra with the lateral information allows grading of tumors, determining the primary tumor of brain metastases and delineating tumor margins - even during surgery after coupling with fiber optic probes. This contribution presents exemplary Raman spectra and images collected from low grade and high grade regions of astrocytic gliomas and brain metastases. A region of interest in dried tissue sections encompassed slightly increased cell density. Spectral unmixing by vertex component analysis (VCA) and N-FINDR resolved cell nuclei in score plots and revealed the spectral contributions of nucleic acids, cholesterol, cholesterol ester and proteins in endmember signatures. The results correlated with the histopathological analysis after staining the specimens by hematoxylin and eosin. For a region of interest in non-dried, buffer immersed tissue sections image processing was not affected by drying artifacts such as denaturation of biomolecules and crystallization of cholesterol. Consequently, the results correspond better to in vivo situations. Raman spectroscopic imaging of a brain metastases from renal cell carcinoma showed an endmember with spectral contributions of glycogen which can be considered as a marker for this primary tumor.

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites.

PubMed

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-26

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan(®) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)(®) microarrays from Agilent(®) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.

Cavernous sinus involvement is not a risk factor for the primary tumor site treatment outcome of Sinonasal adenoid cystic carcinoma.

PubMed

Lee, Yi-Chan; Lee, Ta-Jen; Tsang, Ngan-Ming; Huang, Yenlin; Hsu, Cheng-Lung; Hsin, Li-Jen; Lee, Yi-Hsuan; Chang, Kai-Ping

2018-02-05

Sinonasal adenoid cystic carcinoma is a rare malignancy of the head and neck. Cavernous sinus invasion from sinonasal adenoid cystic carcinoma and its related management have rarely been investigated. This study evaluated the relationship between treatment outcome and cavernous sinus involvement in addition to other parameters. A retrospective case series study was conducted at a tertiary referral center. The medical records of 47 patients diagnosed with primary sinonasal adenoid cystic carcinoma between 1984 and 2015 were retrospectively reviewed. The survival impact of the primary treatment modalities and the anatomic sites of tumor involvement were analyzed. Cavernous sinus invasion was observed in 8 patients (17%), of whom 7 had ACC tumors originating from the maxillary sinus. The results of univariate analysis revealed that tumor stage, primary surgery, and the absence of skull-base and infratemporal fossa invasion were associated with better overall survival (P = 0.033, P = 0.012, P = 0.011, and P = 0.040, respectively) and better disease-free survival (P = 0.019, P = 0.001, P = 0.017, and P = 0.029, respectively). Multivariate analysis identified primary surgery as the only independent prognostic factor for disease-free survival (P = 0.026). Cavernous sinus invasion by sinonasal adenoid cystic carcinoma was not associated with worse overall survival or disease-free survival (P = 0.200 and P = 0.198, respectively). Because maxillary adenoid cystic carcinoma is associated with a higher rate of cavernous sinus invasion, such cases warrant caution during preoperative planning. Primary surgery as the initial therapy provides better locoregional control and survival for patients with sinonasal adenoid cystic carcinoma. Cavernous sinus invasion did not significantly impact survival; thus, it should not be regarded as a contraindication for curative treatment.

Cilengitide in Treating Children With Refractory Primary Brain Tumors

ClinicalTrials.gov

2013-09-27

Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

The impact of surgical resection of the primary tumor on the development of synchronous colorectal liver metastasis: a systematic review.

PubMed

Pinson, H; Cosyns, S; Ceelen, Wim P

2018-05-22

In recent years different therapeutic strategies for synchronously liver metastasized colorectal cancer were described. Apart from the classical staged surgical approach, simultaneous and liver-first strategies are now commonly used. One theoretical drawback of the classical approach is, however, the stimulatory effect on liver metastases growth that may result from resection of the primary tumour. This systematic review, therefore, aims to investigate the current insights on the stimulatory effects of colorectal surgery on the growth of synchronous colorectal liver metastases in humans. The systematic review was conducted according to the PRISMA statement. A literature search was performed using PubMed and Embase. Articles investigating the effects of colorectal surgery on synchronous colorectal liver metastases were included. Primary endpoints were metastatic tumor volume, metabolic and proliferative activity and tumour vascularization. Four articles meeting the selection criteria were found involving 200 patients. These studies investigate the effects of resection of the primary tumour on synchronous liver metastases using histological and radiological techniques. These papers support a possible stimulatory effect of resection of the primary tumor. Some limited evidence supports the hypothesis that colorectal surgery might stimulate the growth and development of synchronous colorectal liver metastases.

Extraneural metastases of primary central nervous system tumors identified by fine needle aspiration: a retrospective analysis.

PubMed

Vandenbussche, Christopher J; Ho, Cheng-Ying; Nugent, Summer L; Ali, Syed Z

2014-01-01

Extraneural metastasis (EM) of primary central nervous system (PCNS) neoplasms is rare and signifies a poor clinical outcome. Due to its infrequent occurrence, relatively few reports on the cytomorphology of these neoplasms have been published. We describe a series of 19 cases from 16 patients at a single, large tertiary care center. A retrospective analysis of 19 cases of metastases from PCNS neoplasms identified on fine needle aspiration (FNA) in 8 male and 8 female patients aged 14-72 years (mean age 39.6) from 1989 to 2013 was conducted to further characterize the cytomorphologic features identified at metastatic sites. Six different PCNS neoplasms were identified: meningioma, glioblastoma, hemangiopericytoma (HPC), oligodendroglioma, medulloblastoma, and retinoblastoma. The mean latency period between the diagnoses of the primary and first metastatic tumors was 7.4 years (range 0-15). The most common PCNS malignancy responsible for EM was HPC. The most common metastatic sites were the lung (31%) and soft tissue/bone (31%). EM of PCNS tumors is extremely rare. FNA allows for quick, safe and accurate diagnosis. Cytomorphologic features are characteristic, and in conjunction with the clinical history and immunohistochemistry, an accurate diagnosis was obtained in 100% of the cases.

Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon.

PubMed

Xu, Bin; Scognamiglio, Theresa; Cohen, Perry R; Prasad, Manju L; Hasanovic, Adnan; Tuttle, Robert Michael; Katabi, Nora; Ghossein, Ronald A

2017-07-01

Metastatic papillary thyroid carcinoma (PTC) without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon.We retrieved 7 of such cases and described in detail the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was PTC (n=5), poorly differentiated thyroid carcinoma in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma in association with a PTC tall cell variant (n=1). Fibrosis was present in the thyroid of 5 patients. All patients with PTC were alive without evidence of recurrence. The 76-year-old patient with poorly differentiated thyroid carcinoma did not recur and died of unknown causes. Finally, the patient with anaplastic thyroid carcinoma was alive with distant metastasis at last follow-up. The median follow-up for this cohort was 2.2years (range, 0.8-17). BRAF V600E was detected in 4 of 6 cases by immunohistochemistry. In conclusion, metastatic nodal disease without identifiable thyroid primary is a rare but real phenomenon of unknown mechanisms. Although most tumors are low grade and well differentiated, aggressive behavior due to poorly differentiated or anaplastic carcinoma can happen. Most cases are BRAF V600E -positive thyroid tumors. A papillary carcinoma phenotype is found in all reported cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Solid Tumor Second Primary Neoplasms: Who is at Risk, What Can We Do?

PubMed Central

Oeffinger, Kevin C.; Baxi, Shrujal S.; Friedman, Danielle Novetsky; Moskowitz, Chaya S.

2014-01-01

Eighteen percent of incident malignancies in the U.S. are a second (or subsequent) cancer. Second primary neoplasms (SPN), particularly solid tumors, are a major cause of mortality and serious morbidity among cancer survivors successfully cured of their first cancer. Multiple etiologies may lead to a cancer survivor subsequently being diagnosed with an SPN, including radiotherapy for the first cancer, unhealthy lifestyle behaviors, germline and somatic mutations, aging, or an interaction between any of these factors. In this article, we discuss these factors and synthesize this information for use in clinical practice, including preventive strategies and screening recommendations for SPNs. PMID:24331190

Primary tuberculosis of the eustachian tube causing otitis media with effusion.

PubMed

Oh, Se-Joon; Yi, Keun-Ik; Lee, Chang-Hoon; Cho, Kyu-Sup

2015-01-01

Eustachian tube (ET) dysfunction may cause pathological changes in the middle ear, including recurrent acute otitis media and otitis media with effusion (OME). Mechanical obstruction of the ET may be caused by primary tumor-like lesions arising from ET or secondary ET infiltration due to nasopharyngeal and parapharyngeal space tumor. Tuberculosis is known to affect almost every organ in the body, and it should be a concern of each and every medical practitioner. However, tuberculosis of the ET has not been reported in the literature previously. This article reports primary tuberculosis arising in the ET that presented as aural fullness and hearing disturbance in a patient with OME. Copyright © 2015 Elsevier Inc. All rights reserved.

Deriving Therapies for Children with Primary CNS Tumors Using Pharmacokinetic Modeling and Simulation of Cerebral Microdialysis Data

PubMed Central

Jacus, M.O.; Throm, S.L.; Turner, D.C.; Patel, Y.T.; Freeman, B.B.; Morfouace, M.; Boulos, N.; Stewart, C. F.

2014-01-01

The treatment of children with primary central nervous system (CNS) tumors continues to be a challenge despite recent advances in technology and diagnostics. In this overview, we describe our approach for identifying and evaluating active anticancer drugs through a process that enables rational translation from the lab to the clinic. The preclinical approach we discuss uses tumor subgroup-specific models of pediatric CNS tumors, cerebral microdialysis sampling of tumor extracellular fluid (tECF), and pharmacokinetic modeling and simulation to overcome challenges that currently hinder researchers in this field. This approach involves performing extensive systemic (plasma) and target site (CNS tumor) pharmacokinetic studies. Pharmacokinetic modeling and simulation of the data derived from these studies are then used to inform future decisions regarding drug administration, including dosage and schedule. Here, we also present how our approach was used to examine two FDA approved drugs, simvastatin and pemetrexed, as candidates for new therapies for pediatric CNS tumors. We determined that due to unfavorable pharmacokinetic characteristics and insufficient concentrations in tumor tissue in a mouse model of ependymoma, simvastatin would not be efficacious in further preclinical trials. In contrast to simvastatin, pemetrexed was advanced to preclinical efficacy studies after our studies determined that plasma exposures were similar to those in humans treated at similar tolerable dosages and adequate unbound concentrations were found in tumor tissue of medulloblastoma-bearing mice. Generally speaking, the high clinical failure rates for CNS drug candidates can be partially explained by the fact that therapies are often moved into clinical trials without extensive and rational preclinical studies to optimize the transition. Our approach addresses this limitation by using pharmacokinetic and pharmacodynamic modeling of data generated from appropriate in vivo models to

Relative value of physical examination, mammography, and breast sonography in evaluating the size of the primary tumor and regional lymph node metastases in women receiving neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Herrada, J; Iyer, R B; Atkinson, E N; Sneige, N; Buzdar, A U; Hortobagyi, G N

1997-09-01

The purpose of this study was to correlate physical examination and sonographic and mammographic measurements of breast tumors and regional lymph nodes with pathological findings and to evaluate the effect of neoadjuvant chemotherapy on clinical Tumor-Node-Metastasis stage by noninvasive methods. This was a retrospective analysis of 100 patients with locally advanced breast cancer registered and treated in prospective trials of neoadjuvant chemotherapy. All patients received four cycles of a doxorubicin-containing regimen and had noninvasive evaluation of the primary tumor and regional lymph nodes before and after neoadjuvant chemotherapy by physical examination, sonography, and mammography and underwent breast surgery and axillary dissection within 5 weeks after completion of neoadjuvant chemotherapy. The correlations between clinical and pathological measurements were determined by Spearman rank correlation analysis. A proportional odds model was used to examine predictive values. Eighty-three patients had both a clinically detectable primary tumor and lymph node metastases. Sixty-four patients had a decrease in Tumor-Node-Metastasis stage after chemotherapy. For 54% of patients, there was concordance in clinical response between the primary tumor and lymph node compartment; for the rest, results were discordant. Physical examination correlated best with pathological findings in the measurement of the primary tumor (P = 0.0003), whereas sonography was the most accurate predictor of size for axillary lymph nodes (P = 0.0005). The combination of physical examination and mammography worked best for assessment of the primary tumor (P = 0.003), whereas combining physical examination with sonography gave optimal evaluation of regional lymph nodes (P = 0.0001). In conclusion, physical examination is the best noninvasive predictor of the real size of locally advanced primary breast cancer, whereas sonography correlates better with the real dimensions of axillary lymph

Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

PubMed

Sorensen, Eric P; Fanucci, Kristina A; Saraiya, Ami; Volf, Eva; Au, Shiu-chung; Argobi, Yahya; Mansfield, Ryan; Gottlieb, Alice B

2015-08-01

Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With RAS and BRAF Mutational Status.

PubMed

Taieb, Julien; Kourie, Hampig Raphael; Emile, Jean-François; Le Malicot, Karine; Balogoun, Ralyath; Tabernero, Josep; Mini, Enrico; Folprecht, Gunnar; Van Laethem, Jean-Luc; Mulot, Claire; Bouché, Olivier; Aparicio, Thomas; Michel, Pierre; Thaler, Josef; Bridgewater, John; Van Cutsem, Eric; Perkins, Géraldine; Lepage, Come; Salazar, Ramon; Laurent-Puig, Pierre

2017-11-22

We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy. To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab. This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure. The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status. Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046

Renin-secreting tumors.

PubMed

Roswell, R H

1990-02-01

Hypertension resulting from a renin-secreting tumor was first reported in 1967 by Robertson et al. Kihara and coworkers subsequently coined the term juxtaglomerular cell tumor for a similar tumor in a young woman with hyperreninemic hypertension. Since the description of these first two cases, it has become clear that renin-secreting tumors of both renal and nonrenal origin can cause surgically curable hypertension. Primary reninism has been suggested as a more appropriate term for the clinical syndrome associated with renin-secreting tumors, both renal and extrarenal, whether benign or malignant.

Effect of intra-tumoral magnetic nanoparticle hyperthermia and viral nanoparticle immunogenicity on primary and metastatic cancer

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Mazur, Courtney M.; Osterberg, Bjorn; Song, Ailin; Gladstone, David J.; Steinmetz, Nicole F.; Veliz, Frank A.; Bursey, Alicea A.; Wagner, Robert J.; Fiering, Steven N.

2017-02-01

Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia. Based on the prior experience of our research group including; cancer-based heat therapy, magnetic nanoparticle (mNP) hyperthermia, radiation biology, cancer immunology and Cowpea Mosaic Virus that has been engineered to over express antigenic proteins without RNA or DNA (eCPMV/VLP). This research was designed to determine if and how the intra-tumoral delivery of mNP hyperthermia and VLP can work together to improve local and systemic tumor treatment efficacy. Using the C3H mouse/MTG-B mammary adenocarcinoma cell model and the C57-B6 mouse/B-16-F10 melanoma cancer cell model, our data suggests the appropriate combination of intra-tumoral mNP heat (e.g. 43°C /30-60 minutes) and VLP (100 μg/200 mm3 tumor) not only result in significant primary tumor regression but the creation a systemic immune reaction that has the potential to retard secondary tumor growth (abscopal effect) and resist tumor rechallenge. Molecular data from these experiments suggest treatment based cell damage and immune signals such as Heat Shock Protein (HSP) 70/90, calreticulin, MTA1 and CD47 are potential targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of hyperthermia cancer treatment

Local Control After Stereotactic Body Radiation Therapy for Liver Tumors.

PubMed

Ohri, Nitin; Tomé, Wolfgang A; Méndez Romero, Alejandra; Miften, Moyed; Ten Haken, Randall K; Dawson, Laura A; Grimm, Jimm; Yorke, Ellen; Jackson, Andrew

2018-01-06

To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy 10 vs >100 Gy 10 ). Comparisons were made using log-rank testing. Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy 10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy 10 (3-year local control 65%, P < .001). Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy 10 are utilized. Copyright © 2018

Conditional survival of all primary brain tumor patients by age, behavior, and histology.

PubMed

Porter, Kimberly R; McCarthy, Bridget J; Berbaum, Michael L; Davis, Faith G

2011-01-01

Survival statistics commonly reflect survival from the time of diagnosis but do not take into account survival already achieved after a diagnosis. The objective of this study was to provide conditional survival estimates for brain tumor patients as a more accurate measure of survival for those who have already survived for a specified amount of time after diagnosis. Data on primary malignant and nonmalignant brain tumor cases diagnosed from 1985-2005 from selected SEER state cancer registries were obtained. Relative survival up to 15 years postdiagnosis and varying relative conditional survival rates were computed using the life-table method. The overall 1-year relative survival estimate derived from time of diagnosis was 67.8% compared to the 6-month relative conditional survival rate of 85.7% for 6-month survivors (the probability of surviving to 1 year given survival to 6 months). The 10-year overall relative survival rate was 49.5% from time of diagnosis compared to the 8-year relative conditional survival rate of 79.2% for 2-year survivors. Conditional survival estimates and standard survival estimates varied by histology, behavior, and age at diagnosis. The 5-year relative survival estimate derived from time of diagnosis for glioblastoma was 3.6% compared to the 3-year relative conditional survival rate of 36.4% for 2-year survivors. For most nonmalignant tumors, the difference between relative survival and the corresponding conditional survival estimates were minimal. Older age groups had greater numeric gains in survival but lower conditional survival estimates than other age groups. Similar findings were seen for other conditional survival intervals. Conditional survival is a useful disease surveillance measure for clinicians and brain tumor survivors to provide them with better 'real-time' estimates and hope. Copyright © 2011 S. Karger AG, Basel.

Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness.

PubMed

Galaup, Ariane; Cazes, Aurelie; Le Jan, Sebastien; Philippe, Josette; Connault, Elisabeth; Le Coz, Emmanuelle; Mekid, Halima; Mir, Lluis M; Opolon, Paule; Corvol, Pierre; Monnot, Catherine; Germain, Stephane

2006-12-05

Angiopoietin-like 4 (ANGPTL4), a secreted protein of the angiopoietin-like family, is induced by hypoxia in both tumor and endothelial cells as well as in hypoxic perinecrotic areas of numerous cancers. Here, we investigated whether ANGPTL4 might affect tumor growth as well as metastasis. Metastatic 3LL cells were therefore xenografted into control mice and mice in which ANGPTL4 was expressed by using in vivo DNA electrotransfer. Whereas primary tumors grew at a similar rate in both groups, 3LL cells metastasized less efficiently to the lungs of mice that expressed ANGPTL4. Fewer 3LL emboli were observed in primary tumors, suggesting that intravasation of 3LL cells was inhibited by ANGPTL4. Furthermore, melanoma B16F0 cells injected into the retro-orbital sinus also metastasized less efficiently in mice expressing ANGPTL4. Although B16F0 cells were observed in lung vessels, they rarely invaded the parenchyma, suggesting that ANGPTL4 affects extravasation. In addition, recombinant B16F0 cells that overexpress ANGPTL4 were generated, showing a lower capacity for in vitro migration, invasion, and adhesion than control cells. Expression of ANGPTL4 induced reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. Together, these results show that ANGPTL4, through its action on both vascular and tumor compartments, prevents the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness.

Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness

PubMed Central

Galaup, Ariane; Cazes, Aurelie; Le Jan, Sebastien; Philippe, Josette; Connault, Elisabeth; Le Coz, Emmanuelle; Mekid, Halima; Mir, Lluis M.; Opolon, Paule; Corvol, Pierre; Monnot, Catherine; Germain, Stephane

2006-01-01

Angiopoietin-like 4 (ANGPTL4), a secreted protein of the angiopoietin-like family, is induced by hypoxia in both tumor and endothelial cells as well as in hypoxic perinecrotic areas of numerous cancers. Here, we investigated whether ANGPTL4 might affect tumor growth as well as metastasis. Metastatic 3LL cells were therefore xenografted into control mice and mice in which ANGPTL4 was expressed by using in vivo DNA electrotransfer. Whereas primary tumors grew at a similar rate in both groups, 3LL cells metastasized less efficiently to the lungs of mice that expressed ANGPTL4. Fewer 3LL emboli were observed in primary tumors, suggesting that intravasation of 3LL cells was inhibited by ANGPTL4. Furthermore, melanoma B16F0 cells injected into the retro-orbital sinus also metastasized less efficiently in mice expressing ANGPTL4. Although B16F0 cells were observed in lung vessels, they rarely invaded the parenchyma, suggesting that ANGPTL4 affects extravasation. In addition, recombinant B16F0 cells that overexpress ANGPTL4 were generated, showing a lower capacity for in vitro migration, invasion, and adhesion than control cells. Expression of ANGPTL4 induced reorganization of the actin cytoskeleton through inhibition of actin stress fiber formation and vinculin localization at focal contacts. Together, these results show that ANGPTL4, through its action on both vascular and tumor compartments, prevents the metastatic process by inhibiting vascular activity as well as tumor cell motility and invasiveness. PMID:17130448

Energy Metabolism Rewiring Precedes UVB-Induced Primary Skin Tumor Formation.

PubMed

Hosseini, Mohsen; Dousset, Léa; Mahfouf, Walid; Serrano-Sanchez, Martin; Redonnet-Vernhet, Isabelle; Mesli, Samir; Kasraian, Zeinab; Obre, Emilie; Bonneu, Marc; Claverol, Stephane; Vlaski, Marija; Ivanovic, Zoran; Rachidi, Walid; Douki, Thierry; Taieb, Alain; Bouzier-Sore, Anne-Karine; Rossignol, Rodrigue; Rezvani, Hamid Reza

2018-06-19

Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Chromosomal instability affects the tumorigenicity of glioblastoma tumor-initiating cells

PubMed Central

Godek, Kristina M.; Venere, Monica; Wu, Quilian; Mills, Kevin D.; Hickey, William F.; Rich, Jeremy N.; Compton, Duane A.

2016-01-01

Tumors are dynamic organs that evolve during disease progression with genetic, epigenetic, and environmental differences among tumor cells serving as the foundation for selection and evolution in tumors. Tumor-initiating cells (TICs) that are responsible for tumorigenesis are a source of functional cellular heterogeneity while chromosomal instability (CIN) is a source of karyotypic genetic diversity. However, the extent that CIN contributes to TIC genetic diversity and its relationship to TIC function remains unclear. Here we demonstrate that glioblastoma TICs display chromosomal instability with lagging chromosomes at anaphase and extensive non-clonal chromosome copy number variations. Elevating the basal chromosome mis-segregation rate in TICs both decreases proliferation and the stem-like phenotype of TICs in vitro. Consequently tumor formation is abolished in an orthotopic mouse model. These results demonstrate that TICs generate genetic heterogeneity within tumors but that TIC function is impaired if the rate of genetic change is elevated above a tolerable threshold. PMID:27001151

Presence of S100A8/Gr1-Positive Myeloid-Derived Suppressor Cells in Primary Tumors and Visceral Organs Invaded by Breast Carcinoma Cells.

PubMed

Tanriover, Gamze; Eyinc, Mehmet Berk; Aliyev, Elnur; Dilmac, Sayra; Erin, Nuray

2018-04-26

Increased S100A8/A9 expression in Gr1-positive cells has been shown in myeloid-derived suppressor cells and may play a role in the formation of a metastatic milieu. We aimed to determine S100A8/A9 expression alone and with coexpression of Gr1 (a myeloid marker) in primary tumor and visceral tissues invaded by metastatic breast carcinoma. Female BALB/c mice were injected with 4TLM, 4THM, and 67NR orthotopically. Confluent cells (75%-80%) were used. Primary tumor, lung, liver, and spleen tissue samples were removed 26 days after injection. Peripheral blood smears and metastasis assay were performed, as was immunohistochemistry and staining. S100A8/A9 immunoreactivity alone or coexpressed with Gr1 was found in primary tumors formed by 4TLM and 4THM cells, which was markedly higher than in primary tumors formed by nonmetastatic 67NR cells. Similarly, liver and lung tissues obtained from mice injected with 4TLM or 4THM cells were invaded by S100A8/A9-positive and Gr1-positive cells. Double-positive cells were markedly fewer in liver and lung tissues of animals injected with 67NR cells. S100A8/A9-positive cells were mostly localized in red pulp of spleens. We observed an increased number of neutrophils in the peripheral blood of mice injected with metastatic breast carcinoma cells. Tumor-derived factors may increase S100A8/A9-positive cells locally and systemically, and S100A8/A9-positive cells may provide an appropriate milieu for the formation of metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Sensitive Detection of Mono- and Polyclonal ESR1 Mutations in Primary Tumors, Metastatic Lesions, and Cell-Free DNA of Breast Cancer Patients.

PubMed

Wang, Peilu; Bahreini, Amir; Gyanchandani, Rekha; Lucas, Peter C; Hartmaier, Ryan J; Watters, Rebecca J; Jonnalagadda, Amruth R; Trejo Bittar, Humberto E; Berg, Aaron; Hamilton, Ronald L; Kurland, Brenda F; Weiss, Kurt R; Mathew, Aju; Leone, Jose Pablo; Davidson, Nancy E; Nikiforova, Marina N; Brufsky, Adam M; Ambros, Tadeu F; Stern, Andrew M; Puhalla, Shannon L; Lee, Adrian V; Oesterreich, Steffi

2016-03-01

Given the clinical relevance of ESR1 mutations as potential drivers of resistance to endocrine therapy, this study used sensitive detection methods to determine the frequency of ESR1 mutations in primary and metastatic breast cancer, and in cell-free DNA (cfDNA). Six ESR1 mutations (K303R, S463P, Y537C, Y537N, Y537S, D538G) were assessed by digital droplet PCR (ddPCR), with lower limits of detection of 0.05% to 0.16%, in primary tumors (n = 43), bone (n = 12) and brain metastases (n = 38), and cfDNA (n = 29). Correlations between ESR1 mutations in metastatic lesions and single (1 patient) or serial blood draws (4 patients) were assessed. ESR1 mutations were detected for D538G (n = 13), Y537S (n = 3), and Y537C (n = 1), and not for K303R, S463P, or Y537N. Mutation rates were 7.0% (3/43 primary tumors), 9.1% (1/11 bone metastases), 12.5% (3/24 brain metastases), and 24.1% (7/29 cfDNA). Two patients showed polyclonal disease with more than one ESR1 mutation. Mutation allele frequencies were 0.07% to 0.2% in primary tumors, 1.4% in bone metastases, 34.3% to 44.9% in brain metastases, and 0.2% to 13.7% in cfDNA. In cases with both cfDNA and metastatic samples (n = 5), mutations were detected in both (n = 3) or in cfDNA only (n = 2). Treatment was associated with changes in ESR1 mutation detection and allele frequency. ESR1 mutations were detected at very low allele frequencies in some primary breast cancers, and at high allele frequency in metastases, suggesting that in some tumors rare ESR1-mutant clones are enriched by endocrine therapy. Further studies should address whether sensitive detection of ESR1 mutations in primary breast cancer and in serial blood draws may be predictive for development of resistant disease. See related commentary by Gu and Fuqua, p. 1034. ©2015 American Association for Cancer Research.

Exposure to 3G mobile phone signals does not affect the biological features of brain tumor cells.

PubMed

Liu, Yu-xiao; Li, Guo-qing; Fu, Xiang-ping; Xue, Jing-hui; Ji, Shou-ping; Zhang, Zhi-wen; Zhang, Yi; Li, An-ming

2015-08-08

The increase in mobile phone use has generated concerns about possible risks to human health, especially the development of brain tumors. Whether tumor patients should continue to use mobile telephones has remained unclear because of a paucity of information. Herein, we investigated whether electromagnetic fields from mobile phones could alter the biological features of human tumor cells and act as a tumor-promoting agent. Human glioblastoma cell lines, U251-MG and U87-MG, were exposed to 1950-MHz time division-synchronous code division multiple access (TD-SCDMA) at a specific absorption rate (maximum SAR = 5.0 W/kg) for 12, 24, and 48 h. Cell morphologies and ultra-structures were observed by microscopy and the rates of apoptosis and cell cycle progression were monitored by flow cytometry. Additionally, cell growth was determined using the CKK-8 assay, and the expression levels of tumor and apoptosis-related genes and proteins were analyzed by real-time PCR and western blotting, respectively. Tumor formation and invasiveness were measured using a tumorigenicity assay in vivo and migration assays in vitro. No significant differences in either biological features or tumor formation ability were observed between unexposed and exposed glioblastoma cells. Our data showed that exposure to 1950-MHz TD-SCDMA electromagnetic fields for up to 48 h did not act as a cytotoxic or tumor-promoting agent to affect the proliferation or gene expression profile of glioblastoma cells. Our findings implied that exposing brain tumor cells in vitro for up to 48 h to 1950-MHz continuous TD-SCDMA electromagnetic fields did not elicit a general cell stress response.

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors.

PubMed

Felsberg, Jörg; Hentschel, Bettina; Kaulich, Kerstin; Gramatzki, Dorothee; Zacher, Angela; Malzkorn, Bastian; Kamp, Marcel; Sabel, Michael; Simon, Matthias; Westphal, Manfred; Schackert, Gabriele; Tonn, Jörg C; Pietsch, Torsten; von Deimling, Andreas; Loeffler, Markus; Reifenberger, Guido; Weller, Michael

2017-11-15

Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR -amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies. Experimental Design: EGFR -amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR -amplified tumors and 33 patients with EGFR -nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium. Results: Sixty of 106 EGFR -amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR -amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR- nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR -amplified tumors, but were not linked to survival. Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR -amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. Clin Cancer Res; 23(22); 6846-55. ©2017 AACR . ©2017 American Association for Cancer Research.

The Influence of Frontal Lobe Tumors and Surgical Treatment on Advanced Cognitive Functions.

PubMed

Fang, Shengyu; Wang, Yinyan; Jiang, Tao

2016-07-01

Brain cognitive functions affect patient quality of life. The frontal lobe plays a crucial role in advanced cognitive functions, including executive function, meta-cognition, decision-making, memory, emotion, and language. Therefore, frontal tumors can lead to serious cognitive impairments. Currently, neurosurgical treatment is the primary method to treat brain tumors; however, the effects of the surgical treatments are difficult to predict or control. The treatment may both resolve the effects of the tumor to improve cognitive function or cause permanent disabilities resulting from damage to healthy functional brain tissue. Previous studies have focused on the influence of frontal lesions and surgical treatments on patient cognitive function. Here, we review cognitive impairment caused by frontal lobe brain tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

PubMed Central

Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

2006-01-01

Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

[Metastatic tumors in the ovary, difficulties of histologic diagnosis].

PubMed

Tamás, Judit; Vereczkey, Ildikó; Tóth, Erika

2015-09-01

The ovary is a common site of metastases. Secondary tumors account for 3-40% of all ovarian malignancies. Most ovarian metastases arise from the colon, although tumors of the breast, stomach and endometrium are also common places of origin. Clinical and histological features of metastatic tumors frequently mimic primary ovarian malignancies, causing serious diagnostic problems for the surgical pathologist. However, differentiation between primary ovarian cancer and ovarian metastasis is important in order to prevent inappropriate management and suboptimal treatment. The distinction between primary and secondary ovarian malignancies is especially difficult in cases when the metastasis is diagnosed before the primary tumor. Frozen section is widely used in the intra-operative assessment of patients with ovarian tumors but it can be very difficult to distinguish certain types of primary ovarian tumors and metastases from other sites. We examined 152 cases of secondary ovarian neoplasm diagnosed at the National Institute of Oncology, Hungary from 2000 to 2014. Colorectal cancer was the most common primary tumor (58 cases), followed by breast (33 cases), endometrium (30 cases) and stomach cancer (13 cases). The differential diagnosis proved the most difficult in cases when endometrioid and mucinous tumors were present in the ovaries. Metastases of colorectal and gastric adenocarcinomas may simulate benign or borderline cystadenomas too. In these cases the knowledge of the patient's history and immunohistochemical stains were helpful. In our study we discuss the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasms and the limits of the intraoperative frozen sections.

Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 mice.

PubMed

Taylor, Peter; Noriega, Raquel; Farah, Carla; Abad, María-Jesús; Arsenak, Miriam; Apitz, Rafael

2006-08-08

Ajoene is an organosulphur compound derived from garlic with important effects on several membrane-associated processes such as platelet aggregation, as well as being cytotoxic for tumor cell lines in vitro. In the present study, we investigated the effect of ajoene on different cell types in vitro, as well as its inhibitory effects on both primary tumors and metastasis in a mouse model. We found ajoene to inhibit tumor cell growth in vitro, but also to inhibit strongly metastasis to lung in the B16/BL6 melanoma tumor model in C57BL/6 mice. As far as we are aware, this is the first report of the anti-metastatic effect of ajoene. Ajoene also inhibited tumor-endothelial cell adhesion, as well as the in vivo TNF-alpha response to lipopolysaccharide. Possible mechanisms of its antitumoral activity are discussed in the light of these results.

Fertility Sparing Strategies in Patients Affected by Placental Site Trophoblastic Tumor.

PubMed

Chiofalo, Benito; Palmara, Vittorio; Laganà, Antonio Simone; Triolo, Onofrio; Vitale, Salvatore Giovanni; Conway, Francesca; Santoro, Giuseppe

2017-08-24

Placental site trophoblastic tumor (PSTT) is the least common and the most ambiguous gestational trophoblastic tumor. Presentation of PSTT may occur in the course of gestation or from 1 week to 14 years after a normal or an abnormal pregnancy (mole, ectopic pregnancy, abortion). The indicators of aggressive behavior for this tumor are not well established. Due to the rarity of this disease that usually affects women of childbearing potential, we aimed to review the current literature, to identify risk factors and the best conservative therapeutic choices among the cases described. We performed a systematic literature search of articles in English language, published from 1996 to 2017 and indexed in PubMed and Scopus. Based on selective inclusion/exclusion criteria, we considered eight papers eligible for the review. Five were case reports and three were retrospective studies. We extracted and organized data into three different categories depending on the main treatment used. A total of 12 cases were treated with laparotomy; in 5 cases, the treatment was not curative. Therefore, a total abdominal hysterectomy was needed. Five cases were treated successfully with a minimally invasive approach, 2 with uterine evacuation, 2 with hysteroscopic resection, and 1 with a combined hysteroscopic/laparoscopic resection. Only 1 case treated with exclusive chemotherapy proved curative for the patient. Preservation of fertility in PSTT patients of childbearing age should be considered and as showed by the abovementioned studies, is a possible and safe therapeutic choice. Laparotomy for local uterine resection with the modified Strassman approach could be offered in patients at clinical stage 1 that are very motivated to retain fertility, extensively informing the patient of the risks and benefits related to this choice.

Oral pathogens change proliferation properties of oral tumor cells by affecting gene expression of human defensins.

PubMed

Hoppe, T; Kraus, D; Novak, N; Probstmeier, R; Frentzen, M; Wenghoefer, M; Jepsen, S; Winter, J

2016-10-01

The impact of oral pathogens onto the generation and variability of oral tumors has only recently been investigated. To get further insights, oral cancer cells were treated with pathogens and additionally, as a result of this bacterial cellular infection, with human defensins, which are as anti-microbial peptide members of the innate immune system. After cell stimulation, proliferation behavior, expression analysis of oncogenic relevant defensin genes, and effects on EGFR signaling were investigated. The expression of oncogenic relevant anti-microbial peptides was analyzed with real-time PCR and immunohistochemistry. Cell culture experiments were performed to examine cellular impacts caused by stimulation, i.e., altered gene expression, proliferation rate, and EGF receptor-dependent signaling. Incubation of oral tumor cells with an oral pathogen (Porphyromonas gingivalis) and human α-defensins led to an increase in cell proliferation. In contrast, another oral bacterium used, Aggregatibacter actinomycetemcomitans, enhanced cell death. The bacteria and anti-microbial peptides exhibited diverse effects on the transcript levels of oncogenic relevant defensin genes and epidermal growth factor receptor signaling. These two oral pathogens exhibited opposite primary effects on the proliferation behavior of oral tumor cells. Nevertheless, both microbe species led to similar secondary impacts on the proliferation rate by modifying expression levels of oncogenic relevant α-defensin genes. In this respect, oral pathogens exerted multiplying effects on tumor cell proliferation. Additionally, human defensins were shown to differently influence epidermal growth factor receptor signaling, supporting the hypothesis that these anti-microbial peptides serve as ligands of EGFR, thus modifying the proliferation behavior of oral tumor cells.

Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells.

PubMed

Faget, Julien; Biota, Cathy; Bachelot, Thomas; Gobert, Michael; Treilleux, Isabelle; Goutagny, Nadège; Durand, Isabelle; Léon-Goddard, Sophie; Blay, Jean Yves; Caux, Christophe; Ménétrier-Caux, Christine

2011-10-01

In breast carcinomas, patient survival seems to be negatively affected by the recruitment of regulatory T cells (T(reg)) within lymphoid aggregates by CCL22. However, the mechanisms underpinning this process, which may be of broader significance in solid tumors, have yet to be described. In this study, we determined how CCL22 production is controlled in tumor cells. In human breast carcinoma cell lines, CCL22 was secreted at low basal levels that were strongly increased in response to inflammatory signals [TNF-α, IFN-γ, and interleukin (IL)-1β], contrasting with CCL17. Primary breast tumors and CD45(+) infiltrating immune cells appeared to cooperate in driving CCL22 secretion, as shown clearly in cocultures of breast tumor cell lines and peripheral blood mononuclear cells (PBMC) or their supernatants. We determined that monocyte-derived IL-1β and TNF-α are key players as monocyte depletion or neutralization of these cytokines attenuated secretion of CCL22. However, when purified monocytes were used, exogenous human IFN-γ was also required to generate this response suggesting a role for IFN-γ-producing cells within PBMCs. In this setting, we found that human IFN-γ could be replaced by the addition of (i) IL-2 or K562-activated natural killer (NK) cells or (ii) resting NK cells in the presence of anti-MHC class I antibody. Taken together, our results show a dialogue between NK and tumor cells leading to IFN-γ secretion, which in turn associates with monocyte-derived IL-1β and TNF-α to drive production of CCL22 by tumor cells and subsequent recruitment of T(reg). As one validation of this conclusion in primary breast tumors, we showed that NK cells and macrophages tend to colocalize within tumors. In summary, our findings suggest that at early times during tumorigenesis, the detection of tumor cells by innate effectors (monocytes and NK cells) imposes a selection for CCL22 secretion that recruits T(reg) to evade this early antitumor immune response.

Molecular and clinical evidence for an ARMC5 tumor syndrome: concurrent inactivating germline and somatic mutations are associated with both primary macronodular adrenal hyperplasia and meningioma.

PubMed

Elbelt, Ulf; Trovato, Alessia; Kloth, Michael; Gentz, Enno; Finke, Reinhard; Spranger, Joachim; Galas, David; Weber, Susanne; Wolf, Cristina; König, Katharina; Arlt, Wiebke; Büttner, Reinhard; May, Patrick; Allolio, Bruno; Schneider, Jochen G

2015-01-01

Primary macronodular adrenal hyperplasia (PMAH) is a rare cause of Cushing's syndrome, which may present in the context of different familial multitumor syndromes. Heterozygous inactivating germline mutations of armadillo repeat containing 5 (ARMC5) have very recently been described as cause for sporadic PMAH. Whether this genetic condition also causes familial PMAH in association with other neoplasias is unclear. The aim of the present study was to delineate the molecular cause in a large family with PMAH and other neoplasias. Whole-genome sequencing and comprehensive clinical and biochemical phenotyping was performed in members of a PMAH affected family. Nodules derived from adrenal surgery and pancreatic and meningeal tumor tissue were analyzed for accompanying somatic mutations in the identified target genes. PMAH presenting either as overt or subclinical Cushing's syndrome was accompanied by a heterozygous germline mutation in ARMC5 (p.A110fs*9) located on chromosome 16. Analysis of tumor tissue showed different somatic ARMC5 mutations in adrenal nodules supporting a second hit hypothesis with inactivation of a tumor suppressor gene. A damaging somatic ARMC5 mutation was also found in a concomitant meningioma (p.R502fs) but not in a pancreatic tumor, suggesting biallelic inactivation of ARMC5 as causal also for the intracranial meningioma. Our analysis further confirms inherited inactivating ARMC5 mutations as a cause of familial PMAH and suggests an additional role for the development of concomitant intracranial meningiomas.

Supporting mental health in South African HIV-affected communities: primary health care professionals’ understandings and responses

PubMed Central

Burgess, Rochelle Ann

2015-01-01

How do practitioners respond to the mental distress of HIV-affected women and communities? And do their understandings of patients’ distress matter? The World Health Organization (WHO) along with advocates from the Movement for Global Mental Health (MGMH) champion a primary mental health care model to address burgeoning mental health needs in resource-poor HIV-affected settings. Whilst a minority of studies have begun to explore interventions to target this group of women, there is a dearth of studies that explore the broader contexts that will likely shape service outcomes, such as health sector dynamics and competing definitions of mental ill-health. This study reports on an in-depth case study of primary mental health services in a rural HIV-affected community in Northern KwaZulu-Natal. Health professionals identified as the frontline staff working within the primary mental health care model (n = 14) were interviewed. Grounded thematic analysis of interview data highlighted that practitioners employed a critical and socially anchored framework for understanding their patients’ needs. Poverty, gender and family relationships were identified as intersecting factors driving HIV-affected patients’ mental distress. In a divergence from existing evidence, practitioner efforts to act on their understandings of patient needs prioritized social responses over biomedical ones. To achieve this whilst working within a primary mental health care model, practitioners employed a series of modifications to services to increase their ability to target the sociostructural realities facing HIV-affected women with mental health issues. This article suggests that beyond attention to the crucial issues of funding and human resources that face primary mental health care, attention must also be paid to promoting the development of policies that provide practitioners with increased and more consistent opportunities to address the complex social realities that frame the mental

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites

PubMed Central

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-01

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan® Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)® microarrays from Agilent® was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort. PMID:26821018

Hippocampus-sparing radiotherapy using volumetric modulated arc therapy (VMAT) to the primary brain tumor: the result of dosimetric study and neurocognitive function assessment.

PubMed

Kim, Kyung Su; Wee, Chan Woo; Seok, Jin-Yong; Hong, Joo Wan; Chung, Jin-Beom; Eom, Keun-Yong; Kim, Jae-Sung; Kim, Chae-Yong; Park, Young Ho; Kim, Yu Jung; Kim, In Ah

2018-02-20

We hypothesized that hippocampal-sparing radiotherapy via volumetric modulated arc therapy (VMAT) could preserve the neurocognitive function (NCF) of patients with primary brain tumors treated with radiotherapy. We reviewed data from patients with primary brain tumors who underwent hippocampal-sparing brain radiotherapy via VMAT between February 2014 and December 2015. The optimization criteria for the contralateral hippocampus was a maximum dose (D max ) of less than 17 Gy. For NCF evaluations, the Seoul Verbal Learning Test for total recall, delayed recall, and recognition (SVLT-TR, DR, and Recognition) was performed at baseline and at seven months after radiotherapy. A total of 26 patients underwent NCF testing seven months after radiotherapy. Their median age was 49.5 years (range 26-77 years), and 14 (53.8%) had grade III/IV tumors. The median D max to the contralateral hippocampus was 16.4 Gy (range 3.5-63.4). The median mean dose to the contralateral hippocampus, expressed as equivalent to a 2-Gy dose (EQD 2/2 ), was 7.4 Gy 2 (0.7-13.1). The mean relative changes in SVLT-TR, SVLT-DR, and SVLT-Recognition at seven months compared to the baseline were - 7.7% (95% confidence interval [CI], - 19.6% to 4.2%), - 9.2% (95% CI, - 25.4% to 7.0%), and - 3.4% (- 12.7% to 5.8%), respectively. Two patients (7.7%) showed deteriorated NCF in the SVLT-TR and SVLT-DR, and three (11.5%) in the SVLT-Recognition. The mean dose of the left hippocampus and bilateral hippocampi were significantly higher in patients showing deterioration of the SVLT-TR and SVLT-Recognition than in those without deterioration. The contralateral hippocampus could be effectively spared in patients with primary brain tumor via VMAT to preserve the verbal memory function. Further investigation is needed to identify those patients who will most benefit from hippocampal-sparing radiotherapy of the primary brain tumor.

Dose-response study for the highly aggressive and metastatic primary F3II mammary carcinoma under direct current.

PubMed

González, Maraelys M; Morales, Dasha F; Cabrales, Luis E B; Pérez, Daniel J; Montijano, Juan I; Castañeda, Antonio R S; González, Victoriano G S; Posada, Oscar O; Martínez, Janet A; Delgado, Arlem G; Martínez, Karina G; Mon, Mayrel L; Monzón, Kalet L; Ciria, Héctor M C; Beatón, Emilia O; Brooks, Soraida C A; González, Tamara R; Jarque, Manuel V; Mateus, Miguel A Ó; Rodríguez, Jorge L G; Calzado, Enaide M

2018-06-05

Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Primary (de novo) dedifferentiated liposarcoma in the extremities: a multi-institution Tohoku Musculoskeletal Tumor Society study of 18 cases in northern Japan.

PubMed

Okada, Kyoji; Hasegawa, Tadashi; Kawai, Akira; Ogose, Akira; Nishida, Jun; Yanagisawa, Michiro; Morita, Tetsuro; Tajino, Takahiro; Tsuchiya, Takashi

2011-09-01

Dedifferentiated liposarcomas usually occur in the retroperitoneal space and relatively rarely in the extremities. We identified 18 patients with primary dedifferentiated liposarcoma in the extremities from the files of Tohoku Musculoskeletal Tumor Society and analyzed demographics, histologic findings, treatments and prognostic factors. The average follow-up period was 58 months. The subjects were 12 men and 6 women with a mean age of 65 years. All tumors were in the thigh. Nine patients noticed a rapid enlargement of the long-standing tumor. Histologic subtypes of the dedifferentiated area were undifferentiated pleomorphic sarcoma (n = 12), osteosarcoma (n = 2), rhabdomyosarcoma (n = 2), leiomyosarcoma (n = 1) and malignant peripheral nerve sheath tumor (n = 1). In the patient with rhabdomyosarcoma-like dedifferentiated area, extensive necrosis was observed after the preoperative chemotherapy. One patient who underwent marginal excision developed a local recurrence, but inadequate surgical margin was not associated with a risk of local recurrence. Three patients had lung metastasis at initial presentation, and four other patients developed lung metastases during the follow-up period. The overall survival rate was 61.1% at 5 years. On univariate analyses, large size of the dedifferentiated area (>8 cm), high MIB-1-labeling index (>30%) for the dedifferentiated area and lung metastasis at initial presentation were significantly associated with poor prognosis. Primary dedifferentiated liposarcoma in the extremities predominantly occurred in the thigh and a rapid enlargement of long-standing tumors was a characteristic symptom. Although the local behavior of these tumors was less aggressive than that of retroperitoneal dedifferentiated liposarcomas, they had a relatively high metastatic potential.

Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

PubMed Central

Man, Yan-gao; Stojadinovic, Alexander; Mason, Jeffrey; Avital, Itzhak; Bilchik, Anton; Bruecher, Bjoern; Protic, Mladjan; Nissan, Aviram; Izadjoo, Mina; Zhang, Xichen; Jewett, Anahid

2013-01-01

It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness. PMID:23386907

Chromosomal Instability Affects the Tumorigenicity of Glioblastoma Tumor-Initiating Cells.

PubMed

Godek, Kristina M; Venere, Monica; Wu, Quilian; Mills, Kevin D; Hickey, William F; Rich, Jeremy N; Compton, Duane A

2016-05-01

Tumors are dynamic organs that evolve during disease progression with genetic, epigenetic, and environmental differences among tumor cells serving as the foundation for selection and evolution in tumors. Tumor-initiating cells (TIC) that are responsible for tumorigenesis are a source of functional cellular heterogeneity, whereas chromosomal instability (CIN) is a source of karyotypic genetic diversity. However, the extent that CIN contributes to TIC genetic diversity and its relationship to TIC function remains unclear. Here, we demonstrate that glioblastoma TICs display CIN with lagging chromosomes at anaphase and extensive nonclonal chromosome copy-number variations. Elevating the basal chromosome missegregation rate in TICs decreases both proliferation and the stem-like phenotype of TICs in vitro Consequently, tumor formation is abolished in an orthotopic mouse model. These results demonstrate that TICs generate genetic heterogeneity within tumors, but that TIC function is impaired if the rate of genetic change is elevated above a tolerable threshold. Genetic heterogeneity among TICs may produce advantageous karyotypes that lead to therapy resistance and relapse; however, we found that TICs have an upper tolerable limit for CIN. Thus, increasing the chromosome missegregation rate offers a new therapeutic strategy to eliminate TICs from tumors. Cancer Discov; 6(5); 532-45. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 461. ©2016 American Association for Cancer Research.

Percutaneous Radiofrequency Ablation of Lung Tumors in Contact with the Aorta: Dangerous and Difficult but Efficient: A Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, Loukas, E-mail: loutharad@yahoo.co; Mylona, Sofia; Giannoulakos, Nikolaos

Percutaneous imaging-guided tumor ablation is a widely accepted method for the treatment of primary and secondary lung tumors. Although it is generally feasible and effective for local tumor control, some conditions may affect its feasibility and effectiveness. Herein the authors report their experience with two patients with lung malignancies contiguous to the aorta who were successfully treated with radiofrequency ablation, even though it initially appeared highly risky due to the possible fatal complications.

Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer.

PubMed

Moretto, Roberto; Cremolini, Chiara; Rossini, Daniele; Pietrantonio, Filippo; Battaglin, Francesca; Mennitto, Alessia; Bergamo, Francesca; Loupakis, Fotios; Marmorino, Federica; Berenato, Rosa; Marsico, Valentina Angela; Caporale, Marta; Antoniotti, Carlotta; Masi, Gianluca; Salvatore, Lisa; Borelli, Beatrice; Fontanini, Gabriella; Lonardi, Sara; De Braud, Filippo; Falcone, Alfredo

2016-08-01

Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09-7.53; p < .0001). Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs. Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right-sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices. ©AlphaMed Press.

Magnetic resonance guided focused ultrasound surgery (MRgFUS) of bone metastases: From primary pain palliation to local tumor control

NASA Astrophysics Data System (ADS)

Napoli, A.; Leonardi, A.; Andrani, F.; Boni, F.; Anzidei, M.; Catalano, C.

2017-03-01

Purpose: To evaluate the clinical performance of MRgFUS in primary pain palliation of painful bone metastases and in local tumor control. Materials and Methods: We enrolled 26 consecutive patients (female/male 12/14; age: 64.7±7.5yrs) with painful bone metastases. Before and 3 months after MRgFUS treatment pain severity and pain interference scores were assessed according to Brief Pain Inventory-Quality of Life (BPI-QoL) criteria and patients underwent both CT and MRI. Local tumor control was evaluated according to lesion size, density and perfusion at CT, dynamic contrast enhancement at MRI (Discovery 750HD, GE; Gd-Bopta, Bracco) and metabolic activity at PET or scintigraphy. Patients were classified as responders or non-responders. Results: No treatment-related adverse events were recorded during the study. As statistically significant difference between baseline and follow-up values for both pain severity and pain interference scores was observed (p<0.05). Increased bone density was observed in 9/26 (34.6%) patients. Non-Perfused Volume values ranged between 20% and 92%. There was no difference in NPV values between responders and non-responders (46.7±24.2% [25 - 90 %] vs. 45±24.9% [20 - 93 %]; p=0.7). In 6 patients (5 prostate and 1 breast primary cancer) there was nearly absence of metabolic activity after treatment (mean SUV=1.2). Conclusion: MRgFUS can be safely and effectively used as the primary treatment for pain palliation in patients with painful bone metastases; moreover our experience demonstrated also a potential role for the MRgFUS in local tumor control.

Collision tumor of primary laryngeal mucosal melanoma and invasive squamous cell carcinoma with IL-17A and CD70 gene over-expression.

PubMed

Sirikanjanapong, Sasis; Lanson, Biana; Amin, Milan; Martiniuk, Frank; Kamino, Hideko; Wang, Beverly Y

2010-12-01

The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorγT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt-PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes.

Stereotactic body radiotherapy for primary and metastatic liver tumors — the Mayo Clinic experience

PubMed Central

Merrell, Kenneth W.; Johnson, Jedediah E.; Mou, Benjamin; Barney, Brandon M.; Nelson, Kathryn E.; Mayo, Charles S.; Haddock, Michael G.; Hallemeier, Christopher L.

2016-01-01

Introduction To better understand the efficacy of liver SBRT we reviewed our prospectively collected institutional SBRT database. Methods Between May 2008 and March 2013, 80 patients with 104 liver lesions received SBRT. The Kaplan-Meier method estimated local control (LC), overall survival (OS). Cox proportional hazards regression models identified factors associated with LC and OS. Results The median follow-up for living patients was 38.6 months. Patients had primary (n=17) or metastatic (n=63) tumors. The median tumor size was 2.7 cm (range, 0.6-14.0). The 1 and 4 year rates of LC were 89.4% and 88%, respectively. Colorectal (CRC) metastasis was associated with lower rates of LC (p=0.013). OS at 1 and 4 years was 78% and 25%, respectively. Patients with CRC metastases had higher rates of OS (p=0.03). The occurrence of severe acute and late toxicity was 3.8% and 6.3%, respectively. Conclusions SBRT should be studied in prospective clinical trials compared with other liver-directed treatment modalities. PMID:29296438

Imaging Primary Mouse Sarcomas After Radiation Therapy Using Cathepsin-Activatable Fluorescent Imaging Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuneo, Kyle C.; Mito, Jeffrey K.; Javid, Melodi P.

2013-05-01

Purpose: Cathepsin-activated fluorescent probes can detect tumors in mice and in canine patients. We previously showed that these probes can detect microscopic residual sarcoma in the tumor bed of mice during gross total resection. Many patients with soft tissue sarcoma (STS) and other tumors undergo radiation therapy (RT) before surgery. This study assesses the effect of RT on the ability of cathepsin-activated probes to differentiate between normal and cancerous tissue. Methods and Materials: A genetically engineered mouse model of STS was used to generate primary hind limb sarcomas that were treated with hypofractionated RT. Mice were injected intravenously with cathepsin-activatedmore » fluorescent probes, and various tissues, including the tumor, were imaged using a hand-held imaging device. Resected tumor and normal muscle samples were harvested to assess cathepsin expression by Western blot. Uptake of activated probe was analyzed by flow cytometry and confocal microscopy. Parallel in vitro studies using mouse sarcoma cells were performed. Results: RT of primary STS in mice and mouse sarcoma cell lines caused no change in probe activation or cathepsin protease expression. Increasing radiation dose resulted in an upward trend in probe activation. Flow cytometry and immunofluorescence showed that a substantial proportion of probe-labeled cells were CD11b-positive tumor-associated immune cells. Conclusions: In this primary murine model of STS, RT did not affect the ability of cathepsin-activated probes to differentiate between tumor and normal muscle. Cathepsin-activated probes labeled tumor cells and tumor-associated macrophages. Our results suggest that it would be feasible to include patients who have received preoperative RT in clinical studies evaluating cathepsin-activated imaging probes.« less

Oncogenic transformation induced by cell-free nucleic acids circulating in plasma (genometastasis) remains after the surgical resection of the primary tumor: a pilot study.

PubMed

García-Olmo, Damián; García-Olmo, Dolores C; Domínguez-Berzosa, Carolina; Guadalajara, Hector; Vega, Luz; García-Arranz, Mariano

2012-06-01

The oncogenic transformation by cell-free nucleic acids circulating in plasma has been named as genometastasis. The feasibility of this phenomenon has been demonstrated and now it is necessary to value the impact of this phenomenon and to determine what conditions could promote or inhibit it. The goal of this study was to examine the transforming ability of plasma from colorectal cancer patients in a long-term follow-up after the surgical excision of the primary tumor, and to try correlate it with the clinical picture of patients. Blood samples were taken from eight patients with K-ras-mutated colorectal tumors, who were under surgical primary tumor resection at least 2 years before. Plasma was isolated by two centrifugations and added to cultures of NIH-3T3 cells and human adipose-derived stem cells (hASCs). In two cases, plasma was separated from cells by a membrane with 0.4-μm pores. The presence of mutated and non-mutated human K-ras sequences was tested by real-time PCR in cultured cells. After 30 days, cells were subcutaneously injected into athymic nude mice in order to test their ability to generate tumors. In four of the eight patients analyzed after surgery, tumor DNA was detected in plasma. Plasmas from three of them were able to oncogenically transform NIH-3T3 cells in culture and, when those cells were injected in mice, carcinomas were generated. After a 2-year follow-up, metastases were found in two of the three patients whose plasmas were able to transform cells, and in two of the four in whom plasma tumor DNA was not detected. Thus, after a mean follow-up of 29.5 months, only four of 13 patients (30.8%) were alive and disease-free. Primary tumor resection does not assure a complete clean of blood of circulating oncogenes, in spite of a disease-free clinical picture. Moreover, in some cases plasma kept their oncogenic capabilities. The value of these findings as prognosis factor remains unclear and needs further investigations.

Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaake, Eva E.; Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam; Rossi, Maddalena M.G.

2014-11-15

Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancermore » during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced

Primary epidural malignant hemangiopericytoma of thoracic spinal column causing cord compression: case report.

PubMed

Mohammadianpanah, Mohammad; Torabinejad, Simin; Bagheri, Mohammad Hadi; Omidvari, Shapour; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-09-02

Hemangiopericytoma is an uncommon mesenchymal neoplasm that rarely affects the spinal canal. Primary malignant hemangiopericytoma of the spinal column is extremely rare. We report on a case of primary epidural malignant hemangiopericytoma of the thoracic spinal column that invaded vertebral bone and caused spinal cord compression in a 21-year-old man. The patient presented with progressive back pain over a four-month period that progressed to paraparesis, bilateral leg paresthesia and urinary incontinence. The surgical intervention involved laminectomy and subtotal resection of the tumor, with posterior vertebral fixation. Postoperative involved-field radiotherapy was administered. A marked neurological improvement was subsequently observed. We describe the clinical, radiological, and histological features of this tumor and review the literature.

Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.

PubMed

Goldoni, Silvia; Iozzo, Renato V

2008-12-01

Decorin, the prototype member of the small leucine-rich proteoglycans, resides in the tumor microenvironment and affects the biology of various types of cancer by downregulating the activity of several receptors involved in cell growth and survival. Decorin binds to and modulates the signaling of the epidermal growth factor receptor and other members of the ErbB family of receptor tyrosine kinases. It exerts its antitumor activity by a dual mechanism: via inhibition of these key receptors through their physical downregulation coupled with attenuation of their signaling, and by binding to and sequestering TGFbeta. Decorin also modulates the insulin-like growth factor receptor and the low-density lipoprotein receptor-related protein 1, which indirectly affects the TGFbeta receptor pathway. When expressed in tumor xenograft-bearing mice or injected systemically, decorin inhibits both primary tumor growth and metastatic spreading. In this review, we summarize the latest reports on decorin and related molecules that are relevant to cancer and bring forward the idea of decorin as an anticancer therapeutic and possible prognostic marker for patients affected by various types of tumors. We also discuss the role of lumican and LRIG1, a novel cell growth inhibitor homologous to decorin. (c) 2008 Wiley-Liss, Inc.

Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma

PubMed Central

Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

2017-01-01

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations. PMID:29151905

Role of host microenvironment in angiogenesis and microvascular functions in human breast cancer xenografts: mammary fat pad versus cranial tumors.

PubMed

Monsky, Wayne L; Mouta Carreira, Carla; Tsuzuki, Yoshikazu; Gohongi, Takeshi; Fukumura, Dai; Jain, Rakesh K

2002-04-01

The host microenvironment differs between primary and metastatic sites, affecting gene expression and various physiological functions. Here we show the differences in the physiological parameters between orthotopic primary and metastatic breast tumor xenografts using intravital microscopy and reveal the relationship between angiogenic gene expression and microvascular functions in vivo. ZR75-1, a human estrogen-dependent mammary carcinoma, was implanted into the mammary fat pad (primary site) of ovariectomized SCID female mice carrying estrogen pellets. The same tumor line was also grown in the cranial window (metastasis site). When tumors reached the diameter of 2.5 mm, angiogenesis, hemodynamics, and vascular permeability were measured by intravital microscopy, and expression of angiogenic growth factors was determined by quantitative reverse transcription-PCR. ZR75-1 tumors grown in the mammary fat pad had higher microvascular permeability but lower vascular density than the same tumors grown in the cranial window (2.5- and 0.7-fold, respectively). There was no significant difference in RBC velocity, vessel diameter, blood flow rate, and shear rate between two sites. The levels of vascular endothelial growth factor (VEGF), its receptors VEGFR1 and VEGFR2, and angiopoietin-1 mRNA tended to be higher in the mammary fat pad tumors than in the cranial tumors (1.5-, 1.5-, 3-, and 2-fold, respectively). The primary breast cancer exhibited higher vascular permeability, but the cranial tumor showed more angiogenesis, suggesting that the cranial environment is leakage resistant but proangiogenic. Collectively, host microenvironment is an important determinant of tumor gene expression and microvascular functions, and, thus, orthotopic breast tumor models should be useful for obtaining clinically relevant information.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma

PubMed Central

Ni, Haifeng; Jiang, Bo; Zhou, Zhen; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-01-01

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation-specific PCR, semi-quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3-methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC. PMID:28656302

Primary Pulmonary Ewing's Sarcoma/Primitive Neuroectodermal Tumor in a 67-year-old Man

PubMed Central

Lee, Yoon Young; Kim, Do Hoon; Lee, Ji Hye; Choi, Jong Sang; In, Kwang Ho; Oh, Yu Whan; Cho, Kyung Hwan

2007-01-01

Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy. PMID:17923745

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

PubMed

Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

2016-02-01

To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

"A novel in vivo model for the study of human breast cancer metastasis using primary breast tumor-initiating cells from patient biopsies"

PubMed Central

2012-01-01

Background The study of breast cancer metastasis depends on the use of established breast cancer cell lines that do not accurately represent the heterogeneity and complexity of human breast tumors. A tumor model was developed using primary breast tumor-initiating cells isolated from patient core biopsies that would more accurately reflect human breast cancer metastasis. Methods Tumorspheres were isolated under serum-free culture conditions from core biopsies collected from five patients with clinical diagnosis of invasive ductal carcinoma (IDC). Isolated tumorspheres were transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. Tumors and metastatic lesions were analyzed by hematoxylin and eosin (H+E) staining and immunohistochemistry (IHC). Results Tumorspheres were successfully isolated from all patient core biopsies, independent of the estrogen receptor α (ERα)/progesterone receptor (PR)/Her2/neu status or tumor grade. Each tumorsphere was estimated to contain 50-100 cells. Transplantation of 50 tumorspheres (1-5 × 103 cells) in combination with Matrigel into the mammary fat pad of NUDE mice resulted in small, palpable tumors that were sustained up to 12 months post-injection. Tumors were serially transplanted three times by re-isolation of tumorspheres from the tumors and injection into the mammary fat pad of NUDE mice. At 3 months post-injection, micrometastases to the lung, liver, kidneys, brain and femur were detected by measuring content of human chromosome 17. Visible macrometastases were detected in the lung, liver and kidneys by 6 months post-injection. Primary tumors variably expressed cytokeratins, Her2/neu, cytoplasmic E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. In lung and liver metastases, variable redistribution of E-cadherin and β catenin to the membrane of tumor cells was observed. ERα was re-expressed in lung metastatic cells in two of five samples. Conclusions

M-HIFU Inhibits Tumor Growth, Suppresses STAT3 Activity and Enhances Tumor Specific Immunity in a Transplant Tumor Model of Prostate Cancer

PubMed Central

Huang, Xiaoyi; Yuan, Fang; Liang, Meihua; Lo, Hui-Wen; Shinohara, Mari L.; Robertson, Cary; Zhong, Pei

2012-01-01

Objective In this study, we explored the use of mechanical high intensity focused ultrasound (M-HIFU) as a neo-adjuvant therapy prior to surgical resection of the primary tumor. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in M-HIFU elicited anti-tumor immune response using a transplant tumor model of prostate cancer. Methods RM-9, a mouse prostate cancer cell line with constitutively activated STAT3, was inoculated subcutaneously in C57BL/6J mice. The tumor-bearing mice (with a maximum tumor diameter of 5∼6 mm) were treated by M-HIFU or sham exposure two days before surgical resection of the primary tumor. Following recovery, if no tumor recurrence was observed in 30 days, tumor rechallenge was performed. The growth of the rechallenged tumor, survival rate and anti-tumor immune response of the animal were evaluated. Results No tumor recurrence and distant metastasis were observed in both treatment groups employing M-HIFU + surgery and surgery alone. However, compared to surgery alone, M-HIFU combined with surgery were found to significantly inhibit the growth of rechallenged tumors, down-regulate intra-tumoral STAT3 activities, increase cytotoxic T cells in spleens and tumor draining lymph nodes (TDLNs), and improve the host survival. Furthermore, M-HIFU combined with surgery was found to significantly decrease the level of immunosuppression with concomitantly increased number and activities of dendritic cells, compared to surgery alone. Conclusion Our results demonstrate that M-HIFU can inhibit STAT3 activities, and when combined synergistically with surgery, may provide a novel and promising strategy for the treatment of prostate cancers. PMID:22911830

[Epidemiology of lung tumors].

PubMed

Ott, S; Geiser, T

2012-07-01

Approximately one out of 500 chest radiographs shows the incidental finding of a solitary pulmonary nodule and almost one half of these pulmonary lesions are caused by a tumor. Unfortunately, only 2% to 5% of all lung tumors are of benign origin, e. g. lipoma, fibroma, hamartoma, and chondroma, and the majority are malignant neoplasms, most commonly primary lung cancer followed by metastases of extrapulmonary primary carcinomas. Thus, a careful diagnostic work up of solitary pulmonary nodules, including histological diagnosis, is mandatory for an adequate management and treatment of patients with pulmonary lesions. Despite all recent improvements of treatment modalities, lung cancer continues to be a major cause of morbidity and mortality among malignant diseases worldwide. The prognosis of affected patients is still very poor and a 5-years survival rate of only 14% makes lung cancer the number one cause of death due to cancer in Switzerland. Active and passive tobacco smoking are by far the best known risk factor for the development of lung cancer, but there are severe other probably less known factors that may increase the individual risk for malignant neoplasms of the lung. These risk factors include e. g. exposure to natural ionic radiation, consisting of terrestrial radiation and indoor radiation caused by radon gas, exposure to respirable dust and Diesel engine emissions, asbestos, and polycyclic aromatic hydrocarbons. In the majority of cases, the latency between exposure and development of cancer is years to decades and the person concerned was occupationally exposed. Therefore, a detailed evaluation of a patient's medical and occupational history is needed. Due to its poor prognosis, prevention and early diagnosis of lung cancer is crucial to improve our patients' outcome. Good knowledge of epidemiology and aetiology of pulmonary tumors is the key to preventive measures and identification of individuals at increased risk for lung cancer. An overview will

Brain Tumors: The Influence of Tumor Type and Routine MR Imaging Characteristics at BOLD Functional MR Imaging in the Primary Motor Gyrus

PubMed Central

Fraga de Abreu, Vitor Hugo; Peck, Kyung K.; Petrovich-Brennan, Nicole M.; Woo, Kaitlin M.

2016-01-01

Purpose To evaluate the effects of histologic features and anatomic magnetic resonance (MR) imaging characteristics of brain tumors on the functional MR imaging signal in the primary motor cortex (PMC), as false-negative blood oxygen level–dependent (BOLD) functional MR imaging activation can limit the accurate localization of eloquent cortices. Materials and Methods Institutional review board approval was obtained, and informed consent was waived for this HIPAA-compliant retrospective study. It comprised 63 patients referred between 2006 and 2014 for preoperative functional MR imaging localization of the Rolandic cortex. The patients had glioblastoma multiforme (GBM) (n = 20), metastasis (n = 21), or meningioma (n = 22). The volumes of functional MR imaging activation were measured during performance of a bilateral hand motor task. Ratios of functional MR imaging activation were normalized to PMC volume. Statistical analysis was performed for the following: (a) differences between hemispheres within each histologic tumor type (paired Wilcoxon test), (b) differences across tumor types (Kruskal-Wallis and Fisher tests), (c) pairwise tests between tumor types (Mann-Whitney U test), (d) relationships between fast fluid-attenuated inversion recovery (FLAIR) data and enhancement volume with activation (Spearman rank correlation coefficient), and (e) differences in activation volumes by tumor location (Mann-Whitney U test). Results A significant interhemispheric difference was found between the activation volumes in GBMs (mean, 511.43 voxels ± 307.73 [standard deviation] and 330.78 voxels ± 278.95; P < .01) but not in metastases (504.68 voxels ± 220.98 and 460.22 voxels ± 276.83; P = .15) or meningiomas (424.07 voxels ± 247.58 and 415.18 voxels ± 222.36; P = .85). GBMs showed significantly lower activation ratios (median, 0.49; range, 0.04–1.15) than metastases (median, 0.79; range, 0.28–1.66; P = .043) and meningiomas (median, 0.91; range, 0.52–2.05; P

A new ODE tumor growth modeling based on tumor population dynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

2015-10-22

In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

Concurrent primary carcinoid tumor arising within mature teratoma and clear cell renal cell carcinoma in the horseshoe kidney: report of a rare case and review of the literature.

PubMed

Sun, Ke; You, Qihan; Zhao, Ming; Yao, Hongtian; Xiang, Hua; Wang, Lijun

2013-01-01

Primary carcinoid tumor arising in a mature teratoma of the horseshoe kidney is exceptionally rare and only 4 such cases have been reported in the world literature to date. The simultaneous occurrence of different subtypes of renal cell carcinoma (RCC) or RCC coexistence with non-RCC neoplasms from the same kidney is unusual and infrequently reported. Herein we report a case of primary carcinoid tumor arising within mature teratoma, concurrent with a clear cell RCC in the horseshoe kidney of a 37-year-old man. Histologically, both the carcinoid tumor and clear cell RCC demonstrated the characteristic morphology in their classic forms. In addition to the carcinoid tumor, the mature teratoma consisted of variably sized, large cystic spaces lined by cytologically bland mucinous columnar epithelium, pseudostratified columnar epithelium, ciliated epithelium and mature smooth muscle fibers were also identified within the cystic wall. Furthermore, foci of round, small nodules composed of mature prostatic acinus were noted in the teratoma which was confirmed by exhibiting strong immunoreactivity for prostate specific antigen. The present case serves to expand the histologic component that may be encountered in the mature terotoma of the kidney and further broadens the spectrum of primary tumors occurring in the horseshoe kidney.

Clinicopathologic features and surgical management of primary umbilical melanoma: a case series.

PubMed

Di Monta, Gianluca; Caracò, Corrado; Marone, Ugo; Grimaldi, Antonio Maria; Anniciello, Anna Maria; Di Marzo, Massimiliano; Simeone, Ester; Mori, Stefano

2015-04-15

Primary umbilical melanoma is an uncommon tumor that is poorly described in the medical literature. The umbilical region is a particular anatomic site owing to the presence of embryonal remnants, which can be a potential metastatic pathway, as well as the braided lymphatic network drainage. Hence, primary malignant neoplasms affecting the umbilicus require a different and more radical surgical approach compared with other melanomas. In this report, we describe a series of three patients of Caucasian ethnicity who presented with primary umbilical melanoma at the National Cancer Institute of Naples, Italy. All patients underwent wide excision of the tumor including the underlying peritoneum. No surgical complications, either immediate or delayed, were observed in any of the patients. Sentinel lymph node biopsy was negative in two cases. Two of the patients developed metastatic disease and died after systemic medical therapy. The other patient is currently in follow-up, and remains disease-free after 21 months. The umbilicus has vascular and embryological connections with the underlying peritoneum, so that early visceral involvement is more likely to occur with primary umbilical melanomas. As such, tumor resection including the underlying peritoneum is required to avoid local relapse, whilst sentinel lymph node biopsy appears to be of poor diagnostic value.

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature

PubMed Central

KALAMPOKAS, EMMANOUIL; KALAMPOKAS, THEODOROS; DAMASKOS, CHRISTOS

2017-01-01

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. PMID:28064232

Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

ClinicalTrials.gov

2013-05-01

Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model

NASA Astrophysics Data System (ADS)

Acquaviva, Joseph T.; Hasanjee, Aamr M.; Bahavar, Cody F.; Zhou, Fefian; Liu, Hong; Howard, Eric W.; Bullen, Liz C.; Silvy, Ricardo P.; Chen, Wei R.

2015-03-01

Laser immunotherapy (LIT) is being developed as a treatment modality for metastatic cancer which can destroy primary tumors and induce effective systemic anti-tumor responses by using a targeted treatment approach in conjunction with the use of a novel immunoadjuvant, glycated chitosan (GC). In this study, Non-invasive Laser Immunotherapy (NLIT) was used as the primary treatment mode. We incorporated single-walled carbon nanotubes (SWNTs) into the treatment regimen to boost the tumor-killing effect of LIT. SWNTs and GC were conjugated to create a completely novel, immunologically modified carbon nanotube (SWNT-GC). To determine the efficacy of different laser irradiation durations, 5 minutes or 10 minutes, a series of experiments were performed. Rats were inoculated with DMBA-4 cancer cells, a highly aggressive metastatic cancer cell line. Half of the treatment group of rats receiving laser irradiation for 10 minutes survived without primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 minutes had no survivors. Thus, Laser+SWNT-GC treatment with 10 minutes of laser irradiation proved to be effective at reducing tumor size and inducing long-term anti-tumor immunity.

Colorectal breast carcinoma metastasis diagnosed as an obstructive colonic primary tumor. A case report and review of the literature.

PubMed

Théraux, J; Bretagnol, F; Guedj, N; Cazals-Hatem, D; Panis, Y

2009-12-01

Common sites of colorectal breast carcinoma metastasis are bones, lungs, the central nervous system and the liver. Metastases in the gastrointestinal (GI) tract are rare and especially involve the stomach rather than the colon. Clinical or radiological features usually cannot differentiate them from a primary colorectal tumor, resulting in inappropriate treatment. In some cases, this lesion suggests multifocal spread of breast cancer with peritoneal carcinomatosis. Colorectal breast cancer metastasis is a rare finding and there is no consensus on the management of these lesions. The present case report describes a 69-year-old female with metastatic breast cancer presenting as an obstructive tumor of the transverse colon.

Effect of reducing acid etching time on bond strength to noncarious and caries-affected primary and permanent dentin.

PubMed

Scheffel, Débora Lopes Salles; Ricci, Hérica Adad; de Souza Costa, Carlos Alberto; Pashley, David Henry; Hebling, Josimeri

2013-01-01

The purpose was to evaluate the effect of acid etching time on the bond strength of a simplified etch-and-rinse adhesive system to noncarious and caries-affected dentin of primary and permanent teeth. Twenty-four extracted primary and permanent teeth were divided into three groups, according to the acid etching time. Four teeth from each group were exposed to a microbiological caries-inducing protocol. After caries removal, noncarious and caries-affected dentin surfaces were etched with 37 percent phosphoric acid for five, 10, or 15 seconds prior to the application of Prime & Bond NT adhesive. Crowns were restored with resin composite and prepared for microtensile testing. Data were submitted to Kruskal-Wallis and Mann-Whitney tests (α=0.05). Higher bond strengths were obtained for noncarious dentin vs. caries-affected dentin for both primary and permanent teeth. Reducing the acid etching time from 15 to five seconds did not affect the bond strength to caries-affected or noncarious dentin in primary teeth. For permanent teeth, lower bond strength values were observed when the noncarious dentin was etched for five seconds, while no difference was seen between 10 and 15 seconds. For Prime & Bond NT, the etching of dentin for five seconds could be recommended for primary teeth, while 10 seconds would be the minimum time for permanent teeth.

Detailed longitudinal sampling of glioma stem cells in situ reveals Chr7 gain and Chr10 loss as repeated events in primary tumor formation and recurrence.

PubMed

Baysan, Mehmet; Woolard, Kevin; Cam, Margaret C; Zhang, Wei; Song, Hua; Kotliarova, Svetlana; Balamatsias, Demosthenes; Linkous, Amanda; Ahn, Susie; Walling, Jennifer; Belova, Galina I; Fine, Howard A

2017-11-15

Intratumoral heterogeneity at the genetic, epigenetic, transcriptomic, and morphologic levels is a commonly observed phenomenon in many aggressive cancer types. Clonal evolution during tumor formation and in response to therapeutic intervention can be predicted utilizing reverse engineering approaches on detailed genomic snapshots of heterogeneous patient tumor samples. In this study, we developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, and from multiple sections of distant tumor locations of the deceased patient's brain following tumor recurrence. Our analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor and chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. Moreover, chromosome 7 gain and chromosome 10 loss produced similar alterations in mRNA expression profiles in primary and recurrent tumors despite possessing other highly heterogeneous and divergent genomic alterations between the tumors. We identified ETV1 and CDK6 as putative candidate genes, and NFKB (complex), IL1B, IL6, Akt and VEGF as potential signaling regulators, as potentially central downstream effectors of chr7 gain and chr10 loss. Finally, the differences caused by the transcriptomic shift following gain of chromosome 7 and loss of chromosome 10 were consistent with those generally seen in GBM samples compared to normal brain in large-scale patient-tumor data sets. © 2017 UICC.

HER2-specific T cells target primary glioblastoma stem cells and induce regression of autologous experimental tumors.

PubMed

Ahmed, Nabil; Salsman, Vita S; Kew, Yvonne; Shaffer, Donald; Powell, Suzanne; Zhang, Yi J; Grossman, Robert G; Heslop, Helen E; Gottschalk, Stephen

2010-01-15

Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and is currently incurable. Immunotherapies have the potential to target GBM stem cells, which are resistant to conventional therapies. Human epidermal growth factor receptor 2 (HER2) is a validated immunotherapy target, and we determined if HER2-specific T cells can be generated from GBM patients that will target autologous HER2-positive GBMs and their CD133-positive stem cell compartment. HER2-specific T cells from 10 consecutive GBM patients were generated by transduction with a retroviral vector encoding a HER2-specific chimeric antigen receptor. The effector function of HER2-specific T cells against autologous GBM cells, including CD133-positive stem cells, was evaluated in vitro and in an orthotopic murine xenograft model. Stimulation of HER2-specific T cells with HER2-positive autologous GBM cells resulted in T-cell proliferation and secretion of IFN-gamma and interleukin-2 in a HER2-dependent manner. Patients' HER2-specific T cells killed CD133-positive and CD133-negative cells derived from primary HER2-positive GBMs, whereas HER2-negative tumor cells were not killed. Injection of HER2-specific T cells induced sustained regression of autologous GBM xenografts established in the brain of severe combined immunodeficient mice. Gene transfer allows the reliable generation of HER2-specific T cells from GBM patients, which have potent antitumor activity against autologous HER2-positive tumors including their putative stem cells. Hence, the adoptive transfer of HER2-redirected T cells may be a promising immunotherapeutic approach for GBM.

Elevated VEGF-D Modulates Tumor Inflammation and Reduces the Growth of Carcinogen-Induced Skin Tumors.

PubMed

Honkanen, Hanne-Kaisa; Izzi, Valerio; Petäistö, Tiina; Holopainen, Tanja; Harjunen, Vanessa; Pihlajaniemi, Taina; Alitalo, Kari; Heljasvaara, Ritva

2016-07-01

Vascular endothelial growth factor D (VEGF-D) promotes the lymph node metastasis of cancer by inducing the growth of lymphatic vasculature, but its specific roles in tumorigenesis have not been elucidated. We monitored the effects of VEGF-D in cutaneous squamous cell carcinoma (cSCC) by subjecting transgenic mice overexpressing VEGF-D in the skin (K14-mVEGF-D) and VEGF-D knockout mice to a chemical skin carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate treatments. In K14-mVEGF-D mice, tumor lymphangiogenesis was significantly increased and the frequency of lymph node metastasis was elevated in comparison with controls. Most notably, the papillomas regressed more often in K14-mVEGF-D mice than in littermate controls, resulting in a delay in tumor incidence and a remarkable reduction in the total tumor number. Skin tumor growth and metastasis were not obviously affected in the absence of VEGF-D; however, the knockout mice showed a trend for reduced lymphangiogenesis in skin tumors and in the untreated skin. Interestingly, K14-mVEGF-D mice showed an altered immune response in skin tumors. This consisted of the reduced accumulation of macrophages, mast cells, and CD4(+) T-cells and an increase of cytotoxic CD8(+) T-cells. Cytokine profiling by flow cytometry and quantitative real time PCR revealed that elevated VEGF-D expression results in an attenuated Th2 response and promotes M1/Th1 and Th17 polarization in the early stage of skin carcinogenesis, leading to an anti-tumoral immune environment and the regression of primary tumors. Our data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGF-D-induced tumor lymphatics provide a route for metastasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Primary cement spacers: a cost-effective, durable limb salvage option for knee tumors.

PubMed

Puri, Ajay; Gulia, Ashish; Pruthi, Manish; Koushik, S

2012-08-01

Of a total of 818 limb sparing resections in the lower limb requiring reconstruction between December 2002 and April 2010 at our centre, primary cement spacers were used in 15 cases. In three cases they were used as joint sparing intercalary reconstructions and in 12 cases knee arthrodesis was done. Implants used to provide stability to the construct included stacked intramedullary Kuntscher nails in four, an interlocking nail in one, plates in two and a combination of nail with plate in eight. Mean length of bone resected was 18 cm. Mean follow-up was 26 months (10-87 months). There were no local recurrences and none of the spacers needed revision for mechanical failure. The Musculoskeletal Tumor Society score for patients ranged from 20 to 29 with a mean of 24 (80%). Patients with intercalary resection had better functional scores than those with arthrodesis. The construct was successfully revised to a vascularised fibula arthrodesis or prosthesis with good eventual function in three cases. Cement spacers are a suitable cost-effective, durable reconstruction modality in selected patients with good functional outcomes. They are an option to amputation in patients with financial constraints and those that present with large volume or infected fungating tumors. Copyright © 2011 Elsevier B.V. All rights reserved.

Interactive effect of negative affectivity and anxiety sensitivity in terms of mental health among Latinos in primary care.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Bakhshaie, Jafar; Garza, Monica; Ochoa-Perez, Melissa; Medvedeva, Angela; Bogiaizian, Daniel; Robles, Zuzuky; Manning, Kara; Schmidt, Norman B

2016-09-30

From a public health perspective, primary care medical settings represent a strategic location to address mental health disapirty among Latinos. Yet, there is little empirical work that addresses affective vulnerability processes for mental health problems in such settings. To help address this gap in knowledge, the present investigation examined an interactive model of negative affectivity (tendency to experience negative mood states) and anxiety sensitivity (fear of the negative consequences of aversive sensations) among a Latino sample in primary care in terms of a relatively wide range of anxiety/depression indices. Participants included 390 Latino adults (Mage=38.7, SD=11.3; 86.9% female; 95.6% reported Spanish as first language) from a primary care health clinic. Primary dependent measures included depressive, suicidal, social anxiety, and anxious arousal symptoms, number of mood and anxiety disorders, and disability. Consistent with prediction, the interaction between negative affectivity and anxiety sensitivity was significantly related to suicidal, social anxiety, and anxious arousal symptoms, as well as number of mood/anxiety diagnoses and disability among the primary care Latino sample. The form of the interactions indicated a synergistic effect, such that the greatest levels of each outcome were found among those with high negative affectivity and high anxiety sensitivity. There was a trending interaction for depressive symptoms. Overall, these data provide novel empirical evidence suggesting that there is a clinically-relevant interplay between anxiety sensitivity and negative affectivity in regard to the expression of anxiety and depressive symptoms among a Latino primary care sample. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knybel, Lukas; VŠB-Technical University of Ostrava, Ostrava; Cvek, Jakub, E-mail: Jakub.cvek@fno.cz

Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, andmore » sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in

Adult Central Nervous System Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Most primary brain tumors are astrocytomas, glioblastomas, and meningiomas. Most primary spinal tumors are schwannomas, meningiomas, and ependymomas. Metastatic brain tumors have spread to the brain from other parts of the body. Get detailed information about CNS tumors and treatment in this summary for clinicians.

Soft-tissue reactions following irradiation of primary brain and pituitary tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baglan, R.J.; Marks, J.E.

1981-04-01

One hundred and ninety-nine patients who received radiation therapy for a primary brain or pituitary tumor were studied for radiation-induced soft-tissue reactions of the cranium, scalp, ears and jaw. The frequency of these reactions was studied as a function of: the radiation dose 5 mm below the skin surface, dose distribution, field size and fraction size. Forty percent of patients had complete and permanent epilation, while 21% had some other soft-tissue complication, including: scalp swelling-6%, external otitis-6%, otitis media-5%, ear swelling-4%, etc. The frequency of soft-tissue reactions correlates directly with the radiation dose at 5 mm below the skin surface.more » Patients treated with small portals (<70 cm/sup 2/) had few soft-tissue reactions. The dose to superficial tissues, and hence the frequency of soft-tissue reactions can be reduced by: (1) using high-energy megavoltage beams; (2) using equal loading of beams; and (3) possibly avoiding the use of electron beams.« less

Attitudinal Variables Affecting Education Reforms and Quality of Primary Education in Uganda

ERIC Educational Resources Information Center

Nyenje, Aida; Nkata, James

2016-01-01

This paper establishes the extent to which attitudinal variables affect the education reforms and subsequently the quality of primary education in Uganda. The paper is based on the views of a wide spectrum of different education stakeholders including: policy analysts, Members of Parliament (MPs), education officers, Headteachers, teaching staff,…

The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.

PubMed

Hernández-Ruiz, Eugenia; Toll, Agustí; García-Diez, Irene; Andrades, Evelyn; Ferrandiz-Pulido, Carla; Masferrer, Emili; Yébenes, Mireia; Jaka, Ane; Gimeno, Javier; Gimeno, Ramón; García-Patos, Vicenç; Pujol, Ramón M; Hernández-Muñoz, Inmaculada

2018-03-08

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCCs) when compared with non-metastasizing cSCCs (non-MSCCs). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NF-κB signaling pathway. Accordingly, non-MSCCs display higher levels of membranous pS176-inhibitor of NF-kB kinase, and their stroma is enriched in neutrophils and eosinophils when compared with MSCCs. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb-depleted cSCC cells. Altogether, these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high-risk cSCCs could benefit from clinical therapies addressed to harness the immune response.

Primary Fibro Sarcoma of the Heart

PubMed Central

Kabashi, Serbeze; Hoxha, Naim; Gashi, Shkelzen; Ahmegjekaj, Ilir; Bejta, Ilir; Sadiku, Muharrem; Ymeri, Halit; Kabashi, Antigona; Bicaj, Xhavit; Mucaj, Sefedin

2013-01-01

Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography. PMID:24167396

Primary fibro sarcoma of the heart.

PubMed

Kabashi, Serbeze; Hoxha, Naim; Gashi, Shkelzen; Ahmegjekaj, Ilir; Bejta, Ilir; Sadiku, Muharrem; Ymeri, Halit; Kabashi, Antigona; Bicaj, Xhavit; Mucaj, Sefedin

2013-01-01

Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography.

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

PubMed

Gallo, O; Sardi, I; Pepe, G; Franchi, A; Attanasio, M; Giusti, B; Bocciolini, C; Abbate, R

1999-07-19

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Multiple Head and Neck Tumors Frequently Originate from a Single Preneoplastic Lesion

PubMed Central

Tabor, Maarten P.; Brakenhoff, Ruud H.; Ruijter-Schippers, Henrique J.; van der Wal, Jacqueline E.; Snow, Gordon B.; Leemans, C. René; Braakhuis, Boudewijn J. M.

2002-01-01

The development of second primary tumors has a negative impact on the prognosis of head and neck squamous cell carcinoma. Previously, we detected genetically altered and tumor-related mucosal lesions in the resection margins in 25% of unselected head and neck squamous cell carcinoma patients (Tabor MP, Brakenhoff RH, van Houten VMM, Kummer JA, Snel MHJ, Snijders PJF, Snow GB, Leemans CR, Braakhuis BJM: Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res 2001, 7: 1523–1532). The aim of this study was to determine whether first and second primary tumors are clonally related and originate from a single genetically altered field. From 10 patients we analyzed the first tumor of the oral cavity or oropharynx, the >3-cm remote second primary tumor, and the mucosa from the tumor-free margins from both resection specimens. We compared TP53 mutations and loss of heterozygosity profiles using 19 microsatellite markers at chromosomes 3p, 9p, 13q, and 17p. In all patients, genetically altered mucosal lesions were detected in at least one resection margin from both first and second primary tumor. Evidence for a common clonal origin of the first tumor, second primary tumor, and the intervening mucosa was found for at least 6 of 10 patients. Our results indicate that a proportion of multiple primary tumors have developed within a single preneoplastic field. Based on different etiology and clinical consequences, we propose that independent second primary tumors should be distinguished from second field tumors, that arise from the same genetically altered field the first tumor has developed from. PMID:12213734

Ovarian Germ Cell Tumors Treatment

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Measuring the apparent diffusion coefficient in primary rectal tumors: is there a benefit in performing histogram analyses?

PubMed

van Heeswijk, Miriam M; Lambregts, Doenja M J; Maas, Monique; Lahaye, Max J; Ayas, Z; Slenter, Jos M G M; Beets, Geerard L; Bakers, Frans C H; Beets-Tan, Regina G H

2017-06-01

The apparent diffusion coefficient (ADC) is a potential prognostic imaging marker in rectal cancer. Typically, mean ADC values are used, derived from precise manual whole-volume tumor delineations by experts. The aim was first to explore whether non-precise circular delineation combined with histogram analysis can be a less cumbersome alternative to acquire similar ADC measurements and second to explore whether histogram analyses provide additional prognostic information. Thirty-seven patients who underwent a primary staging MRI including diffusion-weighted imaging (DWI; b0, 25, 50, 100, 500, 1000; 1.5 T) were included. Volumes-of-interest (VOIs) were drawn on b1000-DWI: (a) precise delineation, manually tracing tumor boundaries (2 expert readers), and (b) non-precise delineation, drawing circular VOIs with a wide margin around the tumor (2 non-experts). Mean ADC and histogram metrics (mean, min, max, median, SD, skewness, kurtosis, 5th-95th percentiles) were derived from the VOIs and delineation time was recorded. Measurements were compared between the two methods and correlated with prognostic outcome parameters. Median delineation time reduced from 47-165 s (precise) to 21-43 s (non-precise). The 45th percentile of the non-precise delineation showed the best correlation with the mean ADC from the precise delineation as the reference standard (ICC 0.71-0.75). None of the mean ADC or histogram parameters showed significant prognostic value; only the total tumor volume (VOI) was significantly larger in patients with positive clinical N stage and mesorectal fascia involvement. When performing non-precise tumor delineation, histogram analysis (in specific 45th ADC percentile) may be used as an alternative to obtain similar ADC values as with precise whole tumor delineation. Histogram analyses are not beneficial to obtain additional prognostic information.

Clinical outcomes from maximum-safe resection of primary and metastatic brain tumors using awake craniotomy.

PubMed

Groshev, Anastasia; Padalia, Devang; Patel, Sephalie; Garcia-Getting, Rosemarie; Sahebjam, Solmaz; Forsyth, Peter A; Vrionis, Frank D; Etame, Arnold B

2017-06-01

To retrospectively analyze outcomes in patients undergoing awake craniotomies for tumor resection at our institution in terms of extent of resection, functional preservation and length of hospital stay. All cases of adults undergoing awake-craniotomy from September 2012-February 2015 were retrospectively reviewed based on an IRB approved protocol. Information regarding patient age, sex, cancer type, procedure type, location, hospital stay, extent of resection, and postoperative complications was extracted. 76 patient charts were analyzed. Resected cancer types included metastasis to the brain (41%), glioblastoma (34%), WHO grade III anaplastic astrocytoma (18%), WHO grade II glioma (4%), WHO grade I glioma (1%), and meningioma (1%). Over a half of procedures were performed in the frontal lobes, followed by temporal, and occipital locations. The most common indication was for motor cortex and primary somatosensory area lesions followed by speech. Extent of resection was gross total for 59% patients, near-gross total for 34%, and subtotal for 7%. Average hospital stay for the cohort was 1.7days with 75% of patients staying at the hospital for only 24h or less post surgery. In the postoperative period, 67% of patients experienced improvement in neurological status, 21% of patients experienced no change, 7% experienced transient neurological deficits, which resolved within two months post op, 1% experienced transient speech deficit, and 3% experienced permanent weakness. In a consecutive series of 76 patients undergoing maximum-safe resection for primary and metastatic brain tumors, awake-craniotomy was associated with a short hospital stay and low postoperative complications rate. Copyright © 2017 Elsevier B.V. All rights reserved.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

PubMed

Ni, Haifeng; Jiang, Bo; Zhou, Zhen; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-09-01

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3‑methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.

The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study.

PubMed

Schovanek, Jan; Martucci, Victoria; Wesley, Robert; Fojo, Tito; Del Rivero, Jaydira; Huynh, Thanh; Adams, Karen; Kebebew, Electron; Frysak, Zdenek; Stratakis, Constantine A; Pacak, Karel

2014-07-21

Succinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes. These tumors are often larger, extra-adrenal, and contain lower catecholamine concentrations than other hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic behavior and outcome (survival). One hundred six patients with SDHB mutation-related PHEO/PGL were included in this retrospective study. The recorded largest diameters, locations, and patient ages at initial diagnosis of SDHB-related primary tumors were analyzed in the context of time to metastasis and patient survival. First, the development of metastatic disease in patients with primary tumors ≥4.5 cm was significantly earlier than in patients with smaller tumors (P = 0.003). Second, patients with primary tumors larger than 5.5 cm also had worse overall survival than patients with smaller tumors (P = 0.008). Third, age at initial diagnosis was found to be an independent predictor of patient survival (PHEOs: P = 0.041; PGLs: P < 0.001). Fourth, we did not observe a significant difference in survival based on the specific SDHB mutations or patient sex. Receiver operating characteristic curves established 4.5 cm as the best value to dichotomize the primary SDHB-related PHEO/PGL in order to evaluate the development of metastatic disease and 5.5 cm as the best value for survival prediction. Subsequently, the size of the primary tumor was found as an age-independent predictor of patient survival and metastases development in PGL. In both PHEO and PGL, age at diagnosis was found to be a size-independent predictor of patient survival. No significant difference was found in metastases development or patient survival between males and females or among specific SDHB mutations. This data further extends and supports previous

Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules

PubMed Central

Gentile, Luciana B.; Nagamine, Marcia K.; Biondi, Luiz R.; Sanches, Daniel S.; Toyota, Fábio; Giovani, Tatiane M.; de Jesus, Isis P.; da Fonseca, Ivone I. M.; Queiroz-Hazarbassanov, Nicolle; Diaz, Bruno L.; Salles Gomes, Cristina de O. Massoco

2017-01-01

There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development. PMID:28945747