Predictors of Malignancy in Patients with Cytologically Suspicious Thyroid Nodules

PubMed Central

Espiritu, Rachel P.; Bahn, Rebecca S.; Henry, Michael R.; Gharib, Hossein; Caraballo, Pedro J.; Morris, John C.

2011-01-01

Background Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology. Methods We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA. Results Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers. Conclusion In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown. PMID:22007937

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT

ClinicalTrials.gov

2018-06-22

Malignant Neoplasm of Breast; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

Comparison of Two Types of Double-J Ureteral Stents that Differ in Diameter and the Existence of Multiple Side Holes along the Straight Portion in Malignant Ureteral Strictures.

PubMed

Song, Myung Gyu; Seo, Tae-Seok; Lee, Chang Hee; Kim, Kyeong Ah; Kim, Jun Suk; Oh, Sang Cheul; Lee, Jae-Kwan

2015-06-01

This study was decided to evaluate the impact of diameter and the existences of multiple side holes along the straight portion of double-J ureteral stents (DJUS) on early dysfunction of stents placed for malignant ureteral strictures. Between April 2007 and December 2011, 141 DJUSs were placed via a percutaneous nephrostomy (PCN) tract in 110 consecutive patients with malignant ureteral strictures. 7F DJUSs with multiple side holes in the straight portion were placed in 58 ureters of 43 patients (Group 1). 8F DJUSs with three side holes in the proximal 2-cm of the straight portion were placed in 83 ureters of 67 patients (Group 2). The incidence of early DJUS dysfunction was compared between the two groups, and nephrostographic findings were evaluated in the cases of early dysfunction. Early dysfunction of the DJUS was noted in 14 of 58 patients (24.1 %) in Group 1, which was significantly higher (p = 0.001) than in Group 2 in which only 1 of 83 patients (1.2 %) had early dysfunction of the DJUS. Nephrostographic findings of early dysfunction included dilatation of the pelvicalyceal system, filling defects in the ureteral stent, and no passage of contrast media into the urinary bladder. In malignant ureteral strictures, multiple side holes in the straight portion of the 7-F DJUS seem to cause early dysfunction. The 8F DJUSs with three side holes in the proximal 2-cm of the straight portion may be superior at preventing early dysfunction.

Primary malignant melanoma of the gallbladder with multiple metastases: A case report.

PubMed

Wang, Jun-Ke; Su, Fei; Ma, Wen-Jie; Hu, Hai-Jie; Yang, Qin; Liu, Fei; Li, Quan-Sheng; Li, Fu-Yu

2017-11-01

Primary malignant melanoma of the gallbladder is an extremely rare tumor, with fewer than 40 cases reported in the literature worldwide. The majority of patients presented as a solitary lesion in the gallbladder. To our knowledge, only one case of primary malignant melanoma of the gallbladder with multiple metastases has been reported, which involved the stomach, duodenum, pancreas, jejunum and a mesenteric lymph node. We report a case of primary malignant melanoma of the gallbladder with metastases to the duodenal bulb, right adrenal and a celiac lymph node. Primary malignant melanoma of the gallbladder with multiple metastases. Gastrojejunostomy, cholecystectomy, and biopsy of the three metastatic lesions were performed. Histopathologic examination revealed melanin pigments were within the tumor cells of the four lesions, however, junctional activity was noted only in the gallbladder, supporting that the gallbladder was the primary site. No pigmented lesions were detected on the skin or eyes. The postoperative recovery was uneventful, and subsequently, chemotherapy with paclitaxel and carboplatin was administered. The patient survived for 16 months due to tumor. progression. The current case was unique due to the adrenal involvement. For patients with multiple metastases of malignant melanoma, gallbladder origin should be considered in the differential diagnosis from cutaneous origin.

Differentiation of benign and malignant hilar bile duct stenosis.

PubMed

Liu, Xiaolei; Yang, Zhiying; Tan, Haidong; Shao, Chen; Liu, Liguo; Si, Shuang; Xu, Li; Sun, Yongliang

2016-06-15

Failure to differentiate benign and malignant hilar bile duct stenosis may lead to inappropriate treatment. We retrospectively analyzed the methods for differentiation. A total of 53 patients with hilar bile duct stenosis were included, comprising 41 malignant cases (hilar cholangiocarcinoma) and 12 benign cases (six primary sclerosing cholangitis and six IgG4-associated sclerosing cholangitis). Data of clinical histories, laboratory tests, imaging studies, and liver pathologies were collected, and comparison was made between benign and malignant groups. Compared with malignant group, patients in the benign group were more likely to have multiorgan involvement of clinical histories (P < 0.001). There was no difference on bilirubin, liver enzyme, and serum tumor marker between the two groups, whereas serum IgG4 levels were higher in the benign group (P = 0.003). Patients in the benign group were more likely to have pancreatic changes (P < 0.001) and multiple-segmental bile duct stenosis (P < 0.001) on imaging. Compared with the malignant group, patients in the benign group were more likely to show severe periportal inflammation in noninvolved liver (P < 0.001), fibrosis around intrahepatic bile duct (P < 0.001), and more IgG4-positive plasma cells (P < 0.001) on liver pathology. Benign lesion should be considered for patients with history of multiorgan involvement, pancreas changes, or multiple-segmental bile duct stenosis on imaging. Liver biopsy could be helpful for differential diagnosis before surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Multiple Primary and Histology Coding Rules - SEER

Cancer.gov

Download the coding manual and training resources for cases diagnosed from 2007 to 2017. Sites included are lung, breast, colon, melanoma of the skin, head and neck, kidney, renal pelvis/ureter/bladder, benign brain, and malignant brain.

TAK228 With Carbo and Taxol in Advanced Malignancies

ClinicalTrials.gov

2018-03-12

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Multiple Myeloma, Version 2.2016

PubMed Central

Anderson, Kenneth C.; Alsina, Melissa; Atanackovic, Djordje; Biermann, J. Sybil; Chandler, Jason C.; Costello, Caitlin; Djulbegovic, Benjamin; Fung, Henry C.; Gasparetto, Cristina; Godby, Kelly; Hofmeister, Craig; Holmberg, Leona; Holstein, Sarah; Huff, Carol Ann; Kassim, Adetola; Krishnan, Amrita Y.; Kumar, Shaji K.; Liedtke, Michaela; Lunning, Matthew; Raje, Noopur; Singhal, Seema; Smith, Clayton; Somlo, George; Stockerl-Goldstein, Keith; Treon, Steven P.; Weber, Donna; Yahalom, Joachim; Shead, Dorothy A.; Kumar, Rashmi

2016-01-01

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Recent statistics from the American Cancer Society indicate that the incidence of MM is increasing. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) included in this issue address management of patients with solitary plasmacytoma and newly diagnosed MM. PMID:26553768

Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

PubMed

Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

2016-01-01

De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. To describe the overall pattern of de novo cancers in liver transplant recipients. Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

PubMed

Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

2016-10-01

Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation

PubMed Central

Arjunan, Ravi; Kumar, K V Veerendra; Premlatha, C S

2016-01-01

Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC. PMID:27891445

Insight into the number of pre-malignancies and malignancies of the skin in a hospital population in the Netherlands.

PubMed

van Rijsingen, Margit; Seubring, Inge; Maessen-Visch, Birgitte; Lavrijsen, Sjan; van Bergen, Bert; Groenewoud, Johannes; Gerritsen, Marie-Jeanne

2015-01-01

Skin cancer incidence is rising, placing a burden on healthcare systems worldwide. This problem may even be more extensive than expected, since registration of (pre)malignancies of the skin is poor. To provide insight into the numbers of (pre)malignancies in patients with actinic keratosis (AK) or basal cell carcinoma (BCC) in 2 university and 2 general hospitals. The types and numbers of previous tumours and of tumours during a two-year follow-up were collected from 574 patients. Mean time between the first diagnosed (pre)malignancy and time of inclusion was 6.6 years. Overall, 60% had multiple types of (pre)malignancies. In BCC patients, 61% had multiple BCCs, in patients with squamous cell carcinoma (SCC), 40% had multiple SCCs. The combination 'BCC and SCC' occurred in 10%, 'BCC and AK' in 47%, 'SCC and AK' in 14%. High numbers of patients with multiple (pre)malignancies were found in this patient population in university and general hospitals, which may well reflect the Dutch hospital population. We conclude that skin cancer patients are more extensively affected than was expected up till now. Consequently, the management of skin cancer may be in need of adaptation in near future and the question arises whether dermatologists have the capacity for providing care for all these patients.

Early Non Invasive Ventilation and Hematological Malignancies

ClinicalTrials.gov

2018-01-03

Hematological Malignancies; Chronic Hypoxemic Respiratory Failure; Blood And Marrow Transplantation; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Unclassified mixed germ cell-sex cord-stromal tumor with multiple malignant cellular elements in a young woman: a case report and review of the literature.

PubMed

Pang, Shujie; Zhang, Lin; Shi, Yiquan; Liu, Yixin

2014-01-01

Unclassified mixed germ cell-sex cord-stromal tumor composed of germ cells and sex cord derivatives is a rare neoplasm. Approximately 10% of such tumors have malignant germ cell components. We report the case of a 28 year-old female with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components. The germ cell portion contained multiple growth patterns with a malignant appearance, while the sex cord element consisted mainly of annular tubules. Within the malignant germ cell elements was a dysgerminoma that accounted for approximately 75% of the tumor volume. Other malignant germ cell elements included yolk sac tumor, embryonal carcinoma, and choriocarcinoma, which comprised about 15% of the tumor volume. The annular tubule structures comprised about 10% of the total tumor volume. To our knowledge, this is the first case reported in the literature of an unclassified mixed germ cell-sex cord-stromal tumor associated with embryonal carcinoma components. The patient had a 46XX karyotype, regular menstrual periods, and no evidence of gross abnormalities in the contralateral ovary. The patient remained clinically well and disease-free 2 years after surgery. In addition to a thorough case description, the literature concerning this entity is reviewed and discussed.

Update on non-acquired immunodeficiency syndrome-defining malignancies.

PubMed

Chiao, Elizabeth Y; Krown, Susan E

2003-09-01

Since the introduction of highly active antiretroviral therapy (HAART), the natural history of human immunodeficiency virus (HIV) infection has changed. Early in the acquired immunodeficiency syndrome (AIDS) epidemic, epidemiologic studies showed that HIV-infected patients were at higher risk for developing specific AIDS-defining malignancies. More recent studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. We review the most recent data regarding clinical presentation, pathology, and treatment outcomes for these non-AIDS-defining malignancies. Recent large cohort studies linking HIV/AIDS databases to cancer registries have shown that HIV-infected patients are also at higher risk of developing non-AIDS-defining malignancies. Besides anal cancer and Hodgkin disease, the cohort studies have identified other malignancies that appear to occur at a higher rate in the HIV-infected population as compared with the general population. These malignancies include lung cancer, skin cancer, germ cell tumors, leiomyosarcomas, cancers of the head and neck, conjunctival cancer, multiple myeloma, and leukemias. As the epidemiology of non-AIDS-defining malignancies continues to evolve, it is unclear whether the appropriate treatments and outcomes for these or other malignancies are changed for HIV-infected patients treated with HAART.

Differentiation of Benign and Malignant Head and Neck Lesions With Diffusion Tensor Imaging and DWI.

PubMed

Koontz, Nicholas A; Wiggins, Richard H

2017-05-01

The purpose of this study was to determine whether diffusion tensor imaging (DTI) can be used to differentiate between benign and malignant head and neck lesions. This retrospective study included patients with head and neck lesions who underwent clinical MRI at 1.5 or 3 T with DWI or DTI parameters. ROI analysis was performed, with lesion-to-medulla apparent diffusion coefficient (ADC) ratios generated. Sixty-five patients with head and neck lesions were included (71 benign, 40 malignant). Twenty-one patients had multiple lesions. Statistically significant differences (p < 0.001) were seen in the mean ADC values ± SD of malignant and benign lesions (0.55 × 10 -3 ± 0.14 × 10 -3 mm 2 /s vs 0.89 × 10 -3 ± 0.29 × 10 -3 mm 2 /s, respectively) and in the mean ADC ratios of malignant and benign lesions (0.88 ± 0.21 vs 1.40 ± 0.44, respectively) with DTI parameters. DTI and DWI parameters produced similar mean ADC ratio values for malignant (0.88 ± 0.21 and 0.92 ± 0.54, respectively) and benign lesions (1.40 ± 0.44 and 1.79 ± 0.52, respectively). ADC ratio thresholds for predicting malignancy for DTI (ADC ratio ≤ 1) and DWI (ADC ratio ≤ 0.94) were also similar. DTI is a useful predictor of malignancy for head and neck lesions, with ADC values of malignant lesions significantly lower than those of benign lesions. DTI ADC values were lower than DWI ADC values for all head and neck lesions in our study group, often below reported malignant DWI threshold values. Normalization of ADC values to an internal control resulted in similar ADC ratios on DWI and DTI.

The simultaneous occurrence of multiple myeloma and JAK2 positive myeloproliferative neoplasms - Report on two cases

PubMed Central

Badelita, S; Dobrea, C; Colita, A; Dogaru, M; Dragomir, M; Jardan, C; Coriu, D

2015-01-01

Multiple myeloma and JAK2 positive chronic myeloproliferative neoplasms are hematologic malignancies with a completely different cellular origin. Two cases of simultaneous occurrence of multiple myeloma, one with primary myelofibrosis and another one with essential thrombocythemia are reported in this article. In such cases, an accurate diagnosis requires a molecular testing, including gene sequencing and differential diagnosis of pancytosis associated with splenic amyloidosis. In general, in such cases, of two coexisting malignant hematologic diseases, the treatment of the most aggressive one is recommended. For our two cases, it was decided to start a Velcade based therapy. The main concern was the medullar toxicity, especially when a multiple myeloma was associated with a primary myelofibrosis. Abbreviations:JAK2 = Janus kinase 2 gene, PMF = primary myelofibrosis, MPNs = myeloproliferative neoplasms, ET = essential thrombocythemia, PV = polycythemia vera, MM = multiple myeloma, WBC = white blood cells, Hb = haemoglobin, Ht = haematocrit, Plt = platelets, BMB = bone marrow biopsy, CBC = blood cell count, CT = computerized tomography, LAP = leukocyte alkaline phosphatase, MGUS = monoclonal gammopathy of undetermined significance. PMID:25914740

The relationship between methylenetetrahydrofolate reductase polymorphism and hematological malignancy.

PubMed

Jiang, Ni; Zhu, Xishan; Zhang, Hongmei; Wang, Xiaoli; Zhou, Xinna; Gu, Jiezhun; Chen, Baoan; Ren, Jun

2014-01-01

Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for folate metabolism. Previous studies suggest a relationship between its single nucleotide polymorphisms (SNP) of C677T and A1298C with a variety of tumor susceptibility including hematological malignancy. SNP frequency distribution in different ethnic populations might lead to differences in disease susceptibility. There has been little research in Chinese people on the MTHFR SNP with the susceptibility of the hematological malignancy. Therefore, this study investigated the relationship between MTHFR SNPs and hematological malignancy in Jiangsu province in China. Gene microarray was used to detect MTHFR C677T and A1298C single nucleotide polymorphism loci on 157 healthy controls and 127 patients from Jiangsu province with hematological malignancies (30 with multiple myeloma, 28 with non-Hodgkin's lymphoma, 22 with acute lymphoblastic leukemia, 40 with acute myeloid leukemia, and seven with chronic myeloid leukemia). The allele frequency of 677T was 41.3% in patients and 33.1% in controls, showed significant difference (chi2 = 4.08, p = 0.043); 677TT genotype with a high susceptibility to hematological malignancy (OR 1.96, 95% CI 1.01 - 4.45, p = 0.041). In subgroup analyses, the genotypes 677TT and 1298CC were associated with significantly increased multiple myeloma risk (TT vs. CC: OR 8.92, 95% CI 1.06 - 75.24, p = 0.006; CC vs. AA: OR = 4.80, 95% CI 1.56 - 14.73, p = 0.044). No associations were found between polymorphisms and susceptibilities to acute lymphoblastic leukemia, acute myeloid leukemia, or non-Hodgkin's lymphoma. MTHFRC677T polymorphisms influence the risk of hematological malignancy among the population in Jiangsu province. Both MTHFR 677TT and MTHFR 1298CC genotypes increase susceptibility to myeloid leukemia.

Study to Evaluate the Safety and Tolerability of Avelumab in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies

ClinicalTrials.gov

2018-04-27

Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Neoplasms of Uncertain or Unknown Behavior

Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice.

PubMed

Wang, Jiapeng; Li, Zhaomin; He, Yongzheng; Pan, Feng; Chen, Shi; Rhodes, Steven; Nguyen, Lihn; Yuan, Jin; Jiang, Li; Yang, Xianlin; Weeks, Ophelia; Liu, Ziyue; Zhou, Jiehao; Ni, Hongyu; Cai, Chen-Leng; Xu, Mingjiang; Yang, Feng-Chun

2014-01-23

ASXL1 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis. De novo ASXL1 mutations cause Bohring-Opitz syndrome characterized by multiple congenital malformations. We show that Asxl1 deletion in mice led to developmental abnormalities including dwarfism, anophthalmia, and 80% embryonic lethality. Surviving Asxl1(-/-) mice lived for up to 42 days and developed features of myelodysplastic syndrome (MDS), including dysplastic neutrophils and multiple lineage cytopenia. Asxl1(-/-) mice had a reduced hematopoietic stem cell (HSC) pool, and Asxl1(-/-) HSCs exhibited decreased hematopoietic repopulating capacity, with skewed cell differentiation favoring granulocytic lineage. Asxl1(+/-) mice also developed mild MDS-like disease, which could progress to MDS/myeloproliferative neoplasm, demonstrating a haploinsufficient effect of Asxl1 in the pathogenesis of myeloid malignancies. Asxl1 loss led to an increased apoptosis and mitosis in Lineage(-)c-Kit(+) (Lin(-)c-Kit(+)) cells, consistent with human MDS. Furthermore, Asxl1(-/-) Lin(-)c-Kit(+) cells exhibited decreased global levels of H3K27me3 and H3K4me3 and altered expression of genes regulating apoptosis (Bcl2, Bcl2l12, Bcl2l13). Collectively, we report a novel ASXL1 murine model that recapitulates human myeloid malignancies, implying that Asxl1 functions as a tumor suppressor to maintain hematopoietic cell homeostasis. Future work is necessary to clarify the contribution of microenvironment to the hematopoietic phenotypes observed in the constitutional Asxl1(-/-) mice.

Comparison of Two Types of Double-J Ureteral Stents that Differ in Diameter and the Existence of Multiple Side Holes along the Straight Portion in Malignant Ureteral Strictures

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

Song, Myung Gyu, E-mail: acube808@naver.com; Seo, Tae-Seok, E-mail: g1q1papa@korea.ac.kr; Lee, Chang Hee, E-mail: chlee86@korea.ac.kr

PurposeThis study was decided to evaluate the impact of diameter and the existences of multiple side holes along the straight portion of double-J ureteral stents (DJUS) on early dysfunction of stents placed for malignant ureteral strictures.MethodsBetween April 2007 and December 2011, 141 DJUSs were placed via a percutaneous nephrostomy (PCN) tract in 110 consecutive patients with malignant ureteral strictures. 7F DJUSs with multiple side holes in the straight portion were placed in 58 ureters of 43 patients (Group 1). 8F DJUSs with three side holes in the proximal 2-cm of the straight portion were placed in 83 ureters of 67more » patients (Group 2). The incidence of early DJUS dysfunction was compared between the two groups, and nephrostographic findings were evaluated in the cases of early dysfunction.ResultsEarly dysfunction of the DJUS was noted in 14 of 58 patients (24.1 %) in Group 1, which was significantly higher (p = 0.001) than in Group 2 in which only 1 of 83 patients (1.2 %) had early dysfunction of the DJUS. Nephrostographic findings of early dysfunction included dilatation of the pelvicalyceal system, filling defects in the ureteral stent, and no passage of contrast media into the urinary bladder.ConclusionsIn malignant ureteral strictures, multiple side holes in the straight portion of the 7-F DJUS seem to cause early dysfunction. The 8F DJUSs with three side holes in the proximal 2-cm of the straight portion may be superior at preventing early dysfunction.« less

[A case of small-cell malignant melanoma in a pregnant patient].

PubMed

Calderón Garcidueñas, Anna Laura; Dragustinovis Valdez, Irma Yadira; Castelán Maldonado, Edmundo Erbey; Zavala, Pompa Angel

2005-01-01

Malignant melanoma (MM) is an aggressive neoplasm that may affect pregnant women. Malignant melanoma with small-cell morphology (MMSCM) is a rare variant of MM that can cause confusion in its diagnosis. To report a fatal case of MMSCM in a pregnant woman, highlighting immunohistochemistry (IHC) as a very useful tool in the final diagnosis. A 22-year-old pregnant female presented with a 5-cm cutaneous tumor in her right leg. The lesion was excised but the patient refused any further therapy. The natural outcome of this neoplasm occurred with local recurrence and multiple metastases to the lungs, liver, and kidneys. MM should be included in the differential diagnosis of small-cell cutaneous tumor, and IHC is mandatory for diagnosis confirmation. The recommended suggested screening includes, as a minimum, one sensitive marker (S-100 protein) and one specific (HMB45) marker for melanogenesis.

Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.

PubMed

Sekido, Yoshitaka

2018-03-22

Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF , NF2 , and BAP1 tumor-suppressor genes. Notably, activating oncogene mutations are very rare; thus, it is difficult to develop effective inhibitors to treat MM. The NF2 gene encodes merlin, a protein that regulates multiple cell-signaling cascades including the Hippo pathway. MMs also exhibit inactivation of Hippo pathway components including LATS1/2, strongly suggesting that merlin-Hippo pathway dysregulation plays a key role in the development and progression of MM. Furthermore, Hippo pathway inactivation has been shown to result in constitutive activation of the YAP1/TAZ transcriptional coactivators, thereby conferring malignant phenotypes to mesothelial cells. Critical YAP1/TAZ target genes, including prooncogenic CCDN1 and CTGF , have also been shown to enhance the malignant phenotypes of MM cells. Together, these data indicate the Hippo pathway as a therapeutic target for the treatment of MM, and support the development of new strategies to effectively target the activation status of YAP1/TAZ as a promising therapeutic modality for this formidable disease.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa

PubMed Central

Wood, William A.; Lee, Stephanie J.; Shea, Thomas C.; Naresh, Kikkeri N.; Kazembe, Peter N.; Casper, Corey; Hesseling, Peter B.; Mitsuyasu, Ronald T.

2012-01-01

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma–associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community. PMID:22461494

Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification or HER3/4 Mutation

ClinicalTrials.gov

2018-03-26

Malignant Neoplasm of Breast; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Neoplasms of Uncertain or Unknown Behavior

A review of urologic cancer patients with multiple primary malignancies.

PubMed

Mydlo, J H; Agins, J A; Donohoe, J; Grob, B M

2001-08-01

Much has been written on the treatment of solitary or multiple metastatic nodules that sometimes present in patients with urological malignancies. However, relatively little has been published regarding those patients with urological cancer who have another concomitant primary non-urologic tumor. We describe several cases of patients who presented with a urologic malignancy and a secondary non-urologic tumor. We also reviewed the literature using MEDLINE to gather information concerning this rare occurrence. We found that secondary malignancies, although not very common, are being increasingly reported. They are usually detected during the preoperative work-up of the primary tumor, usually by CT scan, ultrasound, or chest X-ray. Most authors suggest that treatment should be directed at the more aggressive lesion first, which would improve the overall status of the patient, and thus allow a better response from therapy for the secondary lesion. While patients with multiple primary malignancies are rare, the urologist should be alerted to this possibility when evaluating the patient for the initially presenting or detected tumor.

Cell of origin associated classification of B-cell malignancies by gene signatures of the normal B-cell hierarchy.

PubMed

Johnsen, Hans Erik; Bergkvist, Kim Steve; Schmitz, Alexander; Kjeldsen, Malene Krag; Hansen, Steen Møller; Gaihede, Michael; Nørgaard, Martin Agge; Bæch, John; Grønholdt, Marie-Louise; Jensen, Frank Svendsen; Johansen, Preben; Bødker, Julie Støve; Bøgsted, Martin; Dybkær, Karen

2014-06-01

Recent findings have suggested biological classification of B-cell malignancies as exemplified by the "activated B-cell-like" (ABC), the "germinal-center B-cell-like" (GCB) and primary mediastinal B-cell lymphoma (PMBL) subtypes of diffuse large B-cell lymphoma and "recurrent translocation and cyclin D" (TC) classification of multiple myeloma. Biological classification of B-cell derived cancers may be refined by a direct and systematic strategy where identification and characterization of normal B-cell differentiation subsets are used to define the cancer cell of origin phenotype. Here we propose a strategy combining multiparametric flow cytometry, global gene expression profiling and biostatistical modeling to generate B-cell subset specific gene signatures from sorted normal human immature, naive, germinal centrocytes and centroblasts, post-germinal memory B-cells, plasmablasts and plasma cells from available lymphoid tissues including lymph nodes, tonsils, thymus, peripheral blood and bone marrow. This strategy will provide an accurate image of the stage of differentiation, which prospectively can be used to classify any B-cell malignancy and eventually purify tumor cells. This report briefly describes the current models of the normal B-cell subset differentiation in multiple tissues and the pathogenesis of malignancies originating from the normal germinal B-cell hierarchy.

Novel Strategies for Immunotherapy in Multiple Myeloma: Previous Experience and Future Directions

PubMed Central

Danylesko, Ivetta; Beider, Katia; Shimoni, Avichai; Nagler, Arnon

2012-01-01

Multiple myeloma (MM) is a life-threatening haematological malignancy for which standard therapy is inadequate. Autologous stem cell transplantation is a relatively effective treatment, but residual malignant sites may cause relapse. Allogeneic transplantation may result in durable responses due to antitumour immunity mediated by donor lymphocytes. However, morbidity and mortality related to graft-versus-host disease remain a challenge. Recent advances in understanding the interaction between the immune system of the patient and the malignant cells are influencing the design of clinically more efficient study protocols for MM. Cellular immunotherapy using specific antigen-presenting cells (APCs), to overcome aspects of immune incompetence in MM patients, has received great attention, and numerous clinical trials have evaluated the potential for dendritic cell (DC) vaccines as a novel immunotherapeutic approach. This paper will summarize the data investigating aspects of immunity concerning MM, immunotherapy for patients with MM, and strategies, on the way, to target the plasma cell more selectively. We also include the MM antigens and their specific antibodies that are of potential use for MM humoral immunotherapy, because they have demonstrated the most promising preclinical results. PMID:22649466

Immunomodulatory drugs in multiple myeloma: mechanisms of action and clinical experience

PubMed Central

Holstein, Sarah A.; McCarthy, Philip L.

2017-01-01

Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs) which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting. The IMiDs have been reported to have a multitude of activities, including anti-angiogenic, cytotoxic, and immunomodulatory, however, the more recent discoveries that the IMiDs bind to cereblon and thus regulate the ubiquitination of key transcription factors including IKZF1 and IKZF3, have provided greater insight into their mechanism of action. Here the clinical efficacy of these agents in myeloma is reviewed as well as discussion of structure-function relationship, the molecular mechanisms of action, and the association of IMiDs with second primary malignancies and thrombosis. PMID:28205024

Multiple cutaneous malignancies in a patient of xeroderma pigmentosum.

PubMed

Grampurohit, Vandana U; Dinesh, U S; Rao, Ravikala

2011-01-01

Xeroderma pigmentosum is a genodermatosis characterized by photosensitivity and the development of cutaneous and internal malignancies at an early age. The basic defect underlying the clinical manifestations is a nucleotide excision repair defect, leading to defective repair of DNA damaged by ultraviolet radiation. These patients exhibit enhanced sensitivity to ionizing radiation. Patients with xeroderma pigmentosum who are younger than 20 years of age have a greater than 1000-fold increased risk of developing skin cancer. Early detection of these malignancies is necessary because they are fast growing, metastasize early and lead to death. Although, early detection and treatment of cutaneous malignancies will reduce the morbidity and mortality, genetic counseling remains the most important measure for preventing xeroderma pigmentosum. We report a case of xeroderma pigmentosum in an 18-year-old male presenting with multiple cutaneous malignancies: squamous cell carcinoma, malignant melanoma and pigmented basal cell carcinoma.

Pneumothorax caused by cystic and nodular lung metastases from a malignant uterine perivascular epithelioid cell tumor (PEComa).

PubMed

Okamoto, Shouichi; Komura, Moegi; Terao, Yasuhisa; Kurisaki-Arakawa, Aiko; Hayashi, Takuo; Saito, Tsuyoshi; Togo, Shinsaku; Shiokawa, Akira; Mitani, Keiko; Kobayashi, Etsuko; Kumasaka, Toshio; Takahashi, Kazuhisa; Seyama, Kuniaki

2017-01-01

Perivascular epithelioid cell tumors (PEComas) are mesenchymal neoplasms with immunoreactivity for both melanocytic and smooth muscle markers. PEComas occur at multiple sites, and malignant PEComas can undergo metastasis, recurrence and aggressive clinical courses. Although the lung is a common metastatic site of PEComas, they usually appear as multiple nodules but rarely become cystic or cavitary. Here, we describe a female patient whose lungs manifested multiple cystic, cavity-like and nodular metastases 3 years after the resection of uterine tumors tentatively diagnosed as epithelioid smooth muscle tumors with uncertain malignant potential. This patient's subsequent pneumothorax necessitated video-assisted thoracoscopic surgery, and examination of her resected lung specimens eventually led to correcting the diagnosis, i.e., to a PEComa harboring tuberous sclerosis complex 1 ( TSC1 ) loss-of-heterozygosity that originated in the uterus and then metastasized to the lungs. The administration of a gonadotropin-releasing hormone analogue later stabilized her clinical course. To the best of our knowledge, the present case is the first in the literature that associates PEComas with a TSC1 abnormality. Additionally, the pulmonary manifestations, including imaging appearance and pneumothorax, somewhat resembled those of lymphangioleiomyomatosis, a representative disease belonging to the PEComa family. Although PEComas are rare, clinicians, radiologists and pathologists should become aware of this disease entity, especially in the combined clinical setting of multiple cystic, cavity-like, nodular lesions on computed tomography of the chest and a past history of the tumor in the female reproductive system.

Reproductive disturbances in multiple neuroendocrine tumor syndromes.

PubMed

Lytras, Aristides; Tolis, George

2009-12-01

In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

B-Cell Hematologic Malignancy Vaccination Registry

ClinicalTrials.gov

2017-12-29

Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

A case of septic pulmonary embolism associated with renal abscess mimicking pulmonary metastases of renal malignancy.

PubMed

Jung, Jo Sung; Lee, Sang Mi; Kim, Han Jo; Jang, Si-Hyong; Lee, Jeong Won

2014-05-01

We report the case of a 46-year-old woman with acute febrile symptom who had multiple pulmonary nodules and a renal mass. She underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to find a hidden malignancy and the cause of her fever. FDG PET/CT images demonstrated a renal mass and multiple lung nodules with intense FDG uptake, which was suspicious of a renal malignancy with multiple pulmonary metastatic lesions. CT-guided biopsies of the pulmonary and renal lesions only showed chronic inflammatory infiltrates without evidence of malignancy. She was diagnosed with septic pulmonary embolism from a renal abscess. One month after antibiotic treatment, the follow-up chest and abdomen CT showed improvement of the lung and renal lesions. This is the first case demonstrating the FDG PET/CT finding of septic pulmonary embolism associated with renal abscess in the published literature.

Incidence and Clinical Features of Rare Cutaneous Malignancies in Olmsted County, Minnesota, 2000 to 2010.

PubMed

Tolkachjov, Stanislav N; Schmitt, Adam R; Muzic, John G; Weaver, Amy L; Baum, Christian L

2017-01-01

The incidence of rare cutaneous malignancies is unknown. Current estimates of rare cutaneous malignancy incidences are based on broad epidemiologic data or single institution experiences, not population-based data. To determine the incidence of several rare nonmelanoma skin cancers. The authors conducted a retrospective chart review of a population-based cohort between the years 2000 and 2010. Residents of Olmsted County, Minnesota, who were diagnosed with a biopsy-proven nonmelanoma skin cancer-excluding basal cell carcinoma and squamous cell carcinoma-were included in this study. The primary outcome was tumor incidence. Additionally, the authors extracted patient demographics, tumor characteristics, treatment modalities, and outcomes. The age-adjusted and sex-adjusted incidences per 100,000 persons of multiple rare cutaneous malignancies were: atypical fibroxanthoma (1.8), sebaceous carcinoma (0.8), dermatofibrosarcoma protuberans (0.4), microcystic adnexal carcinoma (0.7), eccrine carcinoma (0.4), eccrine porocarcinoma (0.2), and leiomyosarcoma (0.2). The authors report population-based incidences and clinical characteristics for these rare cutaneous malignancies. The immune status and smoking status of patients and the treatment and outcomes of these tumors are reported. Additional studies in a broader population are needed to further define the epidemiology and outcomes of these malignancies.

Liquid biopsy: a step forward towards precision medicine in urologic malignancies.

PubMed

Di Meo, Ashley; Bartlett, Jenni; Cheng, Yufeng; Pasic, Maria D; Yousef, George M

2017-04-14

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

Role of morphometry in the cytological differentiation of benign and malignant thyroid lesions

PubMed Central

Khatri, Pallavi; Choudhury, Monisha; Jain, Manjula; Thomas, Shaji

2017-01-01

Context: Thyroid nodules represent a common problem, with an estimated prevalence of 4–7%. Although fine needle aspiration cytology (FNAC) has been accepted as a first line diagnostic test, the rate of false negative reports of malignancy is still high. Nuclear morphometry is the measurement of nuclear parameters by image analysis. Image analysis can merge the advantages of morphologic interpretation with those of quantitative data. Aims: To evaluate the nuclear morphometric parameters in fine needle aspirates of thyroid lesions and to study its role in differentiating benign from malignant thyroid lesions. Material and Methods: The study included 19 benign and 16 malignant thyroid lesions. Image analysis was performed on Giemsa-stained FNAC slides by Nikon NIS-Elements Advanced Research software (Version 4.00). Nuclear morphometric parameters analyzed included nuclear size, shape, texture, and density parameters. Statistical Analysis: Normally distributed continuous variables were compared using the unpaired t-test for two groups and analysis of variance was used for three or more groups. Tukey or Tamhane's T2 multiple comparison test was used to assess the differences between the individual groups. Categorical variables were analyzed using the chi square test. Results and Conclusion: Five out of the six nuclear size parameters as well as all the texture and density parameters studied were significant in distinguishing between benign and malignant thyroid lesions (P < 0.05). Cut-off values were derived to differentiate between benign and malignant cases. PMID:28182069

Risk of Thyroid Cancer in Euthyroid Asymptomatic Patients with Thyroid Nodules with an Emphasis on Family History of Thyroid Cancer.

PubMed

Hwang, Shin Hye; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young

2016-01-01

To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors-such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels-were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041-0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.

Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers.

PubMed

Kruger, Thomas E; Miller, Andrew H; Godwin, Andrew K; Wang, Jinxi

2014-02-01

The mechanisms underlying malignant cell metastasis to secondary sites such as bone are complex and no doubt multifactorial. Members of the small integrin-binding ligand N-linked glycoproteins (SIBLINGs) family, particularly bone sialoprotein (BSP) and osteopontin (OPN), exhibit multiple activities known to promote malignant cell proliferation, detachment, invasion, and metastasis of several osteotropic cancers. The expression level of BSP and OPN is elevated in a variety of human cancers, particularly those that metastasize preferentially to the skeleton. Recent studies suggest that the "osteomimicry" of malignant cells is not only conferred by transmembrane receptors bound by BSP and OPN, but includes the "switch" in gene expression repertoire typically expressed in cells of skeletal lineage. Understanding the role of BSP and OPN in tumor progression, altered pathophysiology of bone microenvironment, and tumor metastasis to bone will likely result in development of better diagnostic approaches and therapeutic regimens for osteotropic malignant diseases. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies.

PubMed

Cao, Lei; Fan, Lei; Xu, Wei; Li, Jian-Yong

2015-01-01

Mouse double minute 4 (MDM4) as a member of MDM family, is an oncogene emerging as an imperative negative regulator of p53. Tumor suppressor protein p53 plays a crucial role in cell cycle arrest, apoptosis and homeostasis. It has been reported that frequent inactivation of p53 was observed in numerous human cancers including hematologic malignancies. MDM4, the newly discovered modulator of p53 protein, is frequently amplified in various solid tumors such as cutaneous melanoma, retinoblastoma and hematological malignances such as chronic lymphocytic leukemia, acute myeloid leukemia and mantle cell lymphoma. Multiple evidences implicate that over-expression of MDM4 is associated with tumor progression and poor prognosis which can be reversed by knockdown of MDM4 expression or restoration of p53 function, and support the rationale for the design of future MDM4-specific therapeutics. This article discusses and focuses on using MDM4 as a novel biomarker as well as a therapeutic target for hematologic malignancies.

Guided percutaneous fine-needle aspiration biopsy of the liver

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

Ho, C.S.; McLoughlin, M.J.; Tao, L.C.

1981-04-01

Forty patients with suspected malignant disease of the liver underwent percutaneous fine-needle aspiration biopsy with radioisotope scintigraphic and fluoroscopic guidance. The needle was aimed at focal defects identified on the liver scan and several passes were made. When the scan was diffusely abnormal, the liver was widely sampled with multiple passes. Thirty patients were eventually considered to have malignant disease and aspiration biopsy was positive in 28 (93%) of these patients, including 25 of 26 with liver metastases (96%). There were two false-positive results and one minor complication. In 24 patients, conventional wide-bore needle biopsy was also performed. In thismore » group, 16 patients had a final diagnosis of hepatic malignancy. Aspiration biopsies were positive in 14 of these (87%) and conventional needle biopsies were positive in four (25%). Guided percutaneous fine-needle aspiration biopsy is recommended for pathologic diagnosis of hepatic malignancy because of its simplicity, high yield, and reasonable safety.« less

Cancer of the head and neck region in solid organ transplant recipients.

PubMed

Rabinovics, Naomi; Mizrachi, Aviram; Hadar, Tuvia; Ad-El, Dean; Feinmesser, Raphael; Guttman, Dan; Shpitzer, Thomas; Bachar, Gideon

2014-02-01

Solid organ recipients are at an increased risk of developing various malignancies. We investigated the incidence, clinical features, and outcome of patients diagnosed with head and neck cancer after organ transplantation. A retrospective analysis was undertaken of patients who underwent solid organ transplantation (kidney, liver, lung, heart) treated at our institution from 1992 to 2010. Of 2817 organ recipients, 175 patients (6.1%) developed 391 head and neck malignancies. Cutaneous malignancies were the most common (93%): squamous cell carcinoma (SCC; 51%) and basal cell carcinoma (BCC; 42%). The average interval from transplantation to diagnosis of head and neck malignancy was 7.3 years, with liver recipients diagnosed earlier. Eighteen percent of patients presented with an aggressive pattern of head and neck cancer, including 24% of patients with cutaneous SCC. Organ transplantation recipients are at a higher risk to develop head and neck cancer with an aggressive behavior characterized by multiple recurrences and decreased survival. Copyright © 2013 Wiley Periodicals, Inc.

PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress

PubMed Central

Jiang, Lingyan; Luo, Xiuquan; Shi, Jingxue; Sun, Hong; Sun, Qing; Sheikh, M Saeed

2011-01-01

We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDRG1 may be linked to cell growth regulation. Yeast two-hybrid screening also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression. PMID:21193842

Spontaneous Epithelioid Hemangiosarcoma in a Rhesus Monkey (Macaca mulatta)

PubMed Central

Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

2014-01-01

Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey. PMID:25296017

Spontaneous epithelioid hemangiosarcoma in a rhesus monkey (Macaca mulatta).

PubMed

Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

2014-08-01

Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey.

The role of hypoxia-inducible factor-2 in digestive system cancers.

PubMed

Zhao, J; Du, F; Shen, G; Zheng, F; Xu, B

2015-01-15

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.

The role of hypoxia-inducible factor-2 in digestive system cancers

PubMed Central

Zhao, J; Du, F; Shen, G; Zheng, F; Xu, B

2015-01-01

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1α and HIF-2α, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2α in digestive system cancers. Indeed, HIF-2α has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2α a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies. PMID:25590810

NASA SMART Probe: Breast Cancer Application

NASA Technical Reports Server (NTRS)

Mah, Robert W.; Norvig, Peter (Technical Monitor)

2000-01-01

There is evidence in breast cancer and other malignancies that the physiologic environment within a tumor correlates with clinical outcome. We are developing a unique percutaneous Smart Probe to be used at the time of needle biopsy of the breast. The Smart Probe will simultaneously measure multiple physiologic parameters within a breast tumor. Direct and indirect measurements of tissue oxygen levels, blood flow, pH, and tissue fluid pressure will be analyzed in real-time. These parameters will be interpreted individually and collectively by innovative neural network techniques using advanced intelligent software. The goals are 1) develop a pecutaneous Smart Probe with multiple sensor modalities and applying advanced Information Technologies to provide real time diagnostic information of the tissue at tip of the probe, 2) test the percutaneous Smart Probe in women with benign and malignant breast masses who will be undergoing surgical biopsy, 3) correlate probe sensor data with benign and malignant status of breast masses, 4) determine whether the probe can detect physiologic differences within a breast tumor, and its margins, and in adjacent normal breast tissue, 5) correlate probe sensor data with known prognostic factors for breast caner, including tumor size, tumor grade, axillary lymph node metastases, estrogen receptor and progesterone receptor status.

Multiple myeloma: a clinical overview.

PubMed

Anderson, Kenneth C

2011-11-15

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, affecting slightly more men than women and twice as many African Americans as Caucasians. Older age is the primary risk factor for MM, but obesity also increases risk. MM is incurable, but treatment advances in the past decade have more than doubled the duration of survival. MM is a progressive plasma cell tumor in which an initially stable clone becomes malignant via a multistep process. Causative factors implicated in this process include radiation, environmental toxins, chronic antigen stimulation, and genetics. The malignant plasma cells interact with other hematopoietic and stromal cells within the bone marrow microenvironment to disrupt homeostasis among cells and within the extracellular matrix. These tumor-host interactions lead to MM cell proliferation and migration, angiogenesis, osteolysis, immunodeficiency, and anemia. As a result, patients often present with osteolytic bone lesions, recurrent infections, renal insufficiency, and fatigue. The Durie-Salmon and International Staging Systems are used to stage MM, with the latter providing prognostic information based on readily available laboratory data. However, a number of cytogenetic markers are emerging as prognostic indicators, introducing the possibility of more refined disease staging systems and tailored treatment strategies based on genetic profiles.

Dilatation by Soehendra stent retriever is feasible and effective in multiple deployment of metallic stents to malignant hilar biliary strictures.

PubMed

Kato, Hironari; Kawamoto, Hirofumi; Noma, Yasuhiro; Sonoyama, Takayuki; Tsutsumi, Koichiro; Fujii, Masakuni; Okada, Hiroyuki; Yamamoto, Kazuhide

2013-01-01

The endoscopic management of malignant hilar biliary strictures using multiple metallic stents (MS) is technically demanding, in the initial deployment of MS and the recovery from MS occlusion with deployment of multiple plastic stents (PS). We evaluated the outcomes of the application of a Soehendra stent retriever (SSR) as a dilator of intractable strictures. Fifty-nine patients with malignant hilar biliary strictures had multiple MS inserted using a partial stent-in-stent procedure. When we encountered intractable strictures, we adopted SSR to dilate the stricture and the interstice of the MS. We evaluated the success rate of MS or PS deployment after SSR application and procedural complications. Five of 59 patients (8%) were subjected to SSR application for the initial MS deployment. MS were successfully deployed in all of these patients (100%). MS occlusion was noted in 27 patients. We applied SSR to seven patients (26%) for the deployment of multiple PS after MS occlusion. In five patients (71%), successful PS deployment was achieved after the SSR application. No complications related to dilatation using SSR occurred in any patient. SSR proved to be a potent dilator of difficult strictures in the management of malignant hilar biliary strictures.

Bisphosphonates as potential adjuvants for patients with cancers of the digestive system.

PubMed

Ang, Celina; Doyle, Erin; Branch, Andrea

2016-01-21

Best known for their anti-resorptive activity in bone, bisphosphonates (BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor (HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

Large registry analysis to accurately define second malignancy rates and risks in a well-characterized cohort of 744 consecutive multiple myeloma patients followed-up for 25 years

PubMed Central

Engelhardt, Monika; Ihorst, Gabriele; Landgren, Ola; Pantic, Milena; Reinhardt, Heike; Waldschmidt, Johannes; May, Annette M.; Schumacher, Martin; Kleber, Martina; Wäsch, Ralph

2015-01-01

Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary malignancies have also gained attention since randomized data showed associations to newer drugs. We have conducted this large registry analysis in 744 consecutive patients and analyzed: 1) frequency and onset of additional malignancies; and 2) second primary malignancy- and myeloma-specific risks. We assessed the frequency of additional malignancies in terms of host-, myeloma- and treatment-specific characteristics. To compare these risks, we estimated cumulative incidence rates for second malignancies and myeloma with Fine and Gray regression models taking into account competing risks. Additional malignancies were found in 118 patients: prior or synchronous malignancies in 63% and subsequent in 37%. Cumulative incidence rates for second malignancies were increased in IgG-myeloma and decreased in bortezomib-treated patients (P<0.05). Cumulative incidence rates for myeloma death were increased with higher stage and age, but decreased in IgG-subtypes and due to anti-myeloma treatment (P<0.05). Cytogenetics in patients acquiring second primary malignancies were predominantly favorable, suggesting that indolent myeloma and long disease latency may allow the manifestation of additional malignancies. An assessment of the Surveillance, Epidemiology, and End Result Program of the National Cancer Institute and our data with long-term follow up of 25 years confirmed a prevalence of second malignancy of 10% at 25 years, whereas death from myeloma decreased from 90% to 83%, respectively. Our important findings widen our knowledge of second malignancies and show that they are of increasing relevance as the prognosis in myeloma improves and mortality rates decrease. PMID:26160877

Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

ClinicalTrials.gov

2017-10-25

Acute Myeloid Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Multiple Myeloma; Lymphocytic Leukemia; Myeloproliferative Disorder; Polycythemia Vera; Myelofibrosis; Aplastic Anemia

Mass screening of multiple abdominal solid organs using mobile helical computed tomography scanner--a preliminary report.

PubMed

Ishikawa, Susumu; Aoki, Jun; Ohwada, Susumu; Takahashi, Toru; Morishita, Yasuo; Ueda, Keisuke

2007-04-01

The possibility of a new screening procedure for multiple abdominal solid organs using a mobile helical computed tomography (CT) scanner was evaluated. A total of 4,543 residents, who were 40 years of age or older, received CT scanning without contrast medium. The mean age of participants was 64 years including 2,022 males and 2,521 females. A total of 2,105 abnormal findings were uniquely detected in 1,594 participants. Liver and kidney diseases including ureter occupied around 30% of total abnormal findings, respectively. Besides frequent cystic or calcified lesions, solid tumours were suspected in 56 lesions, which received further examination by specialized physicians. Five (9%) of them were confirmed as being malignant tumours including pancreatic cancer in two patients, and liver, lung and ovary cancers in one patient each, respectively. All five patients with each malignant lesion received curative operations. Small-sized abdominal aortic aneurysms and heart valve diseases were uniquely found in 22 and two patients, respectively. Qualitative diagnoses of solid tumours were difficult using CT findings without contrast medium. CT screening procedures require further investigation in aspect of the selection of examinees, CT scanning procedure, sensitivity and specificity, and cost-effectiveness.

Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum.

PubMed

Romaniuk, Wioletta; Kalita, Joanna; Ostrowska, Halina; Kloczko, Janusz

2018-03-05

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.

miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

PubMed

Luo, Chonglin; Tetteh, Paul W; Merz, Patrick R; Dickes, Elke; Abukiwan, Alia; Hotz-Wagenblatt, Agnes; Holland-Cunz, Stefan; Sinnberg, Tobias; Schittek, Birgit; Schadendorf, Dirk; Diederichs, Sven; Eichmüller, Stefan B

2013-03-01

MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

ClinicalTrials.gov

2017-03-22

Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

Malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers.

PubMed

Gluzman, Daniel; Imamura, Nobutaka; Sklyarenko, Lylia; Nadgornaya, Valentina; Zavelevich, Michael; Machilo, Vasily

2005-01-01

The question as to whether the incidence of leukemias and malignant lymphomas among the clean-up workers increased in 18 years after the catastrophe is still a point of much controversy. Precise diagnosis of the main forms of hematopoietic malignancies and comparison of these data with those in the general population will be helpful in estimating thr relative contribution of the radiation factor to the overall incidence of such pathologies. In all, 187 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues in Chernobyl clean-up workers were analyzed in Ukrainian Reference Laboratory in 1996-2003. A total of 1942 consecutive patients of general population, mainly the residents of Kyiv city and district, diagnosed in References Laboratory at the same period comprised the group of comparison. The morphology and cytochemistry of bone marrow and peripheral blood cells were studied. Immunocytochemical techniques (PAP, APAAP, ABC) and the panel of monoclonal antibodies to differentiation antigens of leukocytes were employed for immunophenotyping leukemic cells. Various types of malignant disease of hematopoietic and lymphoid tissues were registered in Chernobyl clean-up workers under study including myelodysplastic syndromes (nine patients), acute lymphoblastic leukemia (eight) and acute myeloblastic leukemia (31), chromic myeloid leukemia (17), multiple myeloma (17) and other forms of chromic myeloproliferative and lymphoproliferative disease including B-cell chromic lymphocytic leukemia (49 patients). The verified diagnosis of tumors of hematopoietic malignancies according to modern classification (EGIL, WHO) could be the prerequisite for further analytical epidemiology study of leukemias that may be related to the Chernobyl accident.

Pre-operative factors indicating risk of multiple operations versus a single operation in women undergoing surgery for screen detected breast cancer.

PubMed

O'Flynn, E A M; Currie, R J; Mohammed, K; Allen, S D; Michell, M J

2013-02-01

We aim to identify preoperative factors at diagnosis which could predict whether women undergoing wide local excision (WLE) would require further operations. 1593 screen-detected invasive and non-invasive breast cancers were reviewed. Age, presence of ductal carcinoma in situ (DCIS), invasive cancer size on mammography, mammographic sign, tumour type, grade and confidence of the radiologist in malignancy were compared. 83%(1315/1593) of women had a WLE. Of these, 70%(919/1315) had a single operation, and 30%(396/1315) multiple operations. These included repeat WLE to clear margins (60%(238/396)), mastectomy (34%(133/396)) and axillary dissection (6%(25/396)). The presence of mammographic microcalcification, lobular carcinoma and grade 2 malignancy on core biopsy were independent risk factors for multiple operations on multivariate analysis. Women with mammographic DCIS >30 mm were 3.4 times more likely to undergo repeat surgery than those with smaller foci. The multidisciplinary team should pay particular attention to these factors when planning surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Distinct organization of the candidate tumor suppressor gene RFP2 in human and mouse: multiple mRNA isoforms in both species- and human-specific antisense transcript RFP2OS.

PubMed

Baranova, Ancha; Hammarsund, Marianne; Ivanov, Dmitry; Skoblov, Mikhail; Sangfelt, Olle; Corcoran, Martin; Borodina, Tatiana; Makeeva, Natalia; Pestova, Anna; Tyazhelova, Tatiana; Nazarenko, Svetlana; Gorreta, Francesco; Alsheddi, Tariq; Schlauch, Karen; Nikitin, Eugene; Kapanadze, Bagrat; Shagin, Dmitry; Poltaraus, Andrey; Ivanovich Vorobiev, Andrey; Zabarovsky, Eugene; Lukianov, Sergey; Chandhoke, Vikas; Ibbotson, Rachel; Oscier, David; Einhorn, Stefan; Grander, Dan; Yankovsky, Nick

2003-12-04

In the present study, we describe the human and mouse RFP2 gene structure, multiple RFP2 mRNA isoforms in the two species that have different 5' UTRs and a human-specific antisense transcript RFP2OS. Since the human RFP2 5' UTR is not conserved in mouse, these findings might indicate a different regulation of RFP2 in the two species. The predicted human and mouse RFP2 proteins are shown to contain a tripartite RING finger-B-box-coiled-coil domain (RBCC), also known as a TRIM domain, and therefore belong to a subgroup of RING finger proteins that are often involved in developmental and tumorigenic processes. Because homozygous deletions of chromosomal region 13q14.3 are found in a number of malignancies, including chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), we suggest that RFP2 might be involved in tumor development. This study provides necessary information for evaluation of the role of RFP2 in malignant transformation and other biological processes.

MicroRNA and mRNA Features of Malignant Pleural Mesothelioma and Benign Asbestos-Related Pleural Effusion

PubMed Central

Ak, Guntulu; Tomaszek, Sandra C.; Kosari, Farhad; Metintas, Muzaffer; Jett, James R.; Metintas, Selma; Yildirim, Huseyin; Dundar, Emine; Dong, Jie; Aubry, Marie Christine; Wigle, Dennis A.; Thomas, Charles F.

2015-01-01

Introduction. We investigated the expression of microRNAs and mRNAs in pleural tissues from patients with either malignant pleural mesothelioma or benign asbestos-related pleural effusion. Methods. Fresh frozen tissues from a total of 18 malignant pleural mesothelioma and 6 benign asbestos-related pleural effusion patients were studied. Expression profiling of mRNA and microRNA was performed using standard protocols. Results. We discovered significant upregulation of multiple microRNAs in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Hsa-miR-484, hsa-miR-320, hsa-let-7a, and hsa-miR-125a-5p were able to discriminate malignant from benign disease. Dynamically regulated mRNAs were also identified. MET was the most highly overexpressed gene in malignant pleural mesothelioma compared to benign asbestos-related pleural effusion. Integrated analyses examining microRNA-mRNA interactions suggested multiple altered targets within the Notch signaling pathway. Conclusions. Specific microRNAs and mRNAs may have diagnostic utility in differentiating patients with malignant pleural mesothelioma from benign asbestos-related pleural effusion. These studies may be particularly helpful in patients who reside in a region with a high incidence of mesothelioma. PMID:25756049

The Promise of Chimeric Antigen Receptor Engineered T cells in the Treatment of Hematologic Malignancies

PubMed Central

Nagle, Sarah J.; Garfall, Alfred L.; Stadtmauer, Edward A.

2015-01-01

Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma (MM), acute myeloid leukemia (AML) and Hodgkin lymphoma (HL). At the same time, the design and production of CAR T cells is being advanced so that this therapy can be more widely utilized. Cytokine release syndrome (CRS) and neurotoxicity are common, but they are treatable and fully reversible. This review will review currently available data as well as future developments and challenges in the field. PMID:26841014

Multiple myeloma

MedlinePlus

Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies.

PubMed

Steuerman, Rachel; Shevah, Orit; Laron, Zvi

2011-04-01

To investigate whether congenital IGF1 deficiency confers protection against development of malignancies, by comparing the prevalence of malignancies in patients with congenital (secondary) deficiency of IGF1 with the prevalence of cancer in their family members. Only patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. In addition to our own patients, we performed a worldwide survey and collected data on a total of 538 patients, 752 of their first-degree family members, of which 274 were siblings and 131 were further family members. We found that none of the 230 LS patients developed cancer and that only 1 out of 116 patients with congenital IGHD, also suffering from xeroderma pigmentosum, had a malignancy. Out of 79 patients with GHRHR defects and out of 113 patients with congenital MPHD, we found three patients with cancer in each group. Among the first-degree family members (most heterozygotes) of LS, IGHD and MPHD, we found 30 cases of cancer and 1 suspected. In addition, 31 malignancies were reported among 131 further relatives. Our findings bear heavily on the relationship between GH/IGF1 and cancer. Homozygous patients with congenital IGF1 deficiency and insensitivity to GH such as LS seem protected from future cancer development, even if treated by IGF1. Patients with congenital IGHD also seem protected.

Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

PubMed

Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2012-09-19

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

Utility of positron emission tomography in schwannomatosis.

PubMed

Lieber, Bryan; Han, ByoungJun; Allen, Jeffrey; Fatterpekar, Girish; Agarwal, Nitin; Kazemi, Noojan; Zagzag, David

2016-08-01

Schwannomatosis is characterized by multiple non-intradermal schwannomas with patients often presenting with a painful mass in their extremities. In this syndrome malignant transformation of schwannomas is rare in spite of their large size at presentation. Non-invasive measures of assessing the biological behavior of plexiform neurofibromas in neurofibromatosis type 1 such as positron emission tomography (PET), CT scanning and MRI are well characterized but little information has been published on the use of PET imaging in schwannomatosis. We report a unique clinical presentation portraying the use of PET imaging in schwannomatosis. A 27-year-old woman presented with multiple, rapidly growing, large and painful schwannomas confirmed to be related to a constitutional mutation in the SMARCB1 complex. Whole body PET/MRI revealed numerous PET-avid tumors suggestive of malignant peripheral nerve sheath tumors. Surgery was performed on multiple tumors and none of them had histologic evidence of malignant transformation. Overall, PET imaging may not be a reliable predictor of malignant transformation in schwannomatosis, tempering enthusiasm for surgical interventions for tumors not producing significant clinical signs or symptoms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pleomorphic Malignant Mesothelioma in a Broiler Breeder Infected with Avian Leucosis Virus Subgroup J.

PubMed

Murakami, T; Sassa, Y

2018-04-01

Avian leucosis virus (ALV) is an oncogenic retrovirus that induces tumours including lymphoid leucosis and myeloid leucosis. Pleomorphic malignant mesothelioma and myelocytoma, which were thought to be induced by ALV subgroup J (ALV-J) infection, were identified in a 432-day-old broiler breeder. The bird showed no clinical signs; however, at necropsy examination there were multiple nodules in the alimentary tract. Microscopical analysis showed that these consisted of pleomorphic cells and myelocyte-like cells. Immunohistochemistry revealed that the pleomorphic cells were atypical and expressed cytokeratin, vimentin, c-kit, calretinin and ALV. The myelocyte-like cells were also positive for ALV. Retroviral type C particles were observed by electron microscopy. ALV-E and ALV-J nucleotide sequences were detected in DNA extracted from formalin-fixed and paraffin wax-embedded small intestinal tissue. Based on these results, the tumours were diagnosed as pleomorphic malignant mesothelioma and myelocytoma and were thought to have been induced by ALV-J infection. This is the first report of malignant mesothelioma associated with naturally acquired ALV-J infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical model to estimate the pretest probability of malignancy in patients with pulmonary focal Ground-glass Opacity.

PubMed

Jiang, Long; Situ, Dongrong; Lin, Yongbin; Su, Xiaodong; Zheng, Yan; Zhang, Yigong; Long, Hao

2013-11-01

Effective strategies for managing patients with pulmonary focal Ground-glass Opacity (fGGO) depend on the pretest probability of malignancy. Estimating a clinical probability of malignancy in patients with fGGOs can facilitate the selection and interpretation of subsequent diagnostic tests. METHODS : Data from patients with pulmonary fGGO lesions, who were diagnosed at Sun Yat-sen University Cancer Center, was retrospectively collected. Multiple logistic regression analysis was used to identify independent clinical predictors for malignancy and to develop a clinical predictive model to estimate the pretest probability of malignancy in patients with fGGOs.  One hundred and sixty-five pulmonary fGGO nodules were detected in 128 patients. Independent predictors for malignant fGGOs included a history of other cancers (odds ratio [OR], 0.264; 95% confidence interval [CI], 0.072 to 0.970), pleural indentation (OR, 8.766; 95% CI, 3.033-25.390), vessel-convergence sign (OR, 23.626; 95% CI, 6.200 to 90.027) and air bronchogram (OR, 7.41; 95% CI, 2.037 to 26.961). Model accuracy was satisfactory (area under the curve of the receiver operating characteristic, 0.934; 95% CI, 0.894 to 0.975), and there was excellent agreement between the predicted probability and the observed frequency of malignant fGGOs. We have developed a predictive model, which could be used to generate pretest probabilities of malignant fGGOs, and the equation could be incorporated into a formal decision analysis. © 2013 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty Ltd.

[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.

Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies

PubMed Central

Zweidler-McKay, Patrick A.; He, Yiping; Xu, Lanwei; Rodriguez, Carlos G.; Karnell, Fredrick G.; Carpenter, Andrea C.; Aster, Jon C.; Allman, David; Pear, Warren S.

2005-01-01

Although Notch receptor expression on malignant B cells is widespread, the effect of Notch signaling in these cells is poorly understood. To investigate Notch signaling in B-cell malignancy, we assayed the effect of Notch activation in multiple murine and human B-cell tumors, representing both immature and mature subtypes. Expression of constitutively active, truncated forms of the 4 mammalian Notch receptors (ICN1-4) inhibited growth and induced apoptosis in both murine and human B-cell lines but not T-cell lines. Similar results were obtained in human precursor B-cell acute lymphoblastic leukemia lines when Notch activation was achieved by coculture with fibroblasts expressing the Notch ligands Jagged1 or Jagged2. All 4 truncated Notch receptors, as well as the Jagged ligands, induced Hes1 transcription. Retroviral expression of Hairy/Enhancer of Split-1 (Hes1) recapitulated the Notch effects, suggesting that Hes1 is an important mediator of Notch-induced growth arrest and apoptosis in B cells. Among the B-cell malignancies that were susceptible to Notch-mediated growth inhibition/apoptosis were mature B-cell and therapy-resistant B-cell malignancies, including Hodgkin, myeloma, and mixed-lineage leukemia (MLL)–translocated cell lines. These results suggest that therapies capable of activating Notch/Hes1 signaling may have therapeutic potential in a wide range of human B-cell malignancies. PMID:16118316

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma.

PubMed

Meier, Jeremy D; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D Gregory

2010-06-01

The objectives of this study were to 1) determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract, and 2) evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). Cross-sectional study. University-based medical center. Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700-picosecond pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared with the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than that of normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360 to approximately 660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7 +/- 0.06 ns [not significant] for normal and 1.3 +/- 0.06 ns for tumor, P = 0.0025) and the second-order Laguerre expansion coefficient (LEC-2) (i.e., at 460 nm: 0.135 +/- 0.001 for normal and 0.155 +/- 0.007 for tumor, P < 0.05). These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a noninvasive diagnostic technique for HNSCC. Copyright 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. Published by Mosby, Inc. All rights reserved.

Time-resolved laser-induced fluorescence spectroscopy as a diagnostic instrument in head and neck carcinoma

PubMed Central

Meier, Jeremy D.; Xie, Hongtao; Sun, Yang; Sun, Yinghua; Hatami, Nisa; Poirier, Brian; Marcu, Laura; Farwell, D. Gregory

2011-01-01

OBJECTIVE 1) Determine differences in lifetime fluorescence between normal and malignant tissue of the upper aerodigestive tract. 2) Evaluate the potential of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a diagnostic instrument for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN Cross-sectional study. SETTING University-based medical center. SUBJECTS AND METHODS Nine patients with suspected HNSCC were included. In the operating room, a nitrogen pulse laser (337 nm, 700 ps pulse width) was used to induce tissue autofluorescence of normal tissue and suspected malignant lesions. Spectral intensities and time-domain measurements were obtained and compared to the histopathology at each site. A total of 53 sites were measured. The fluorescence parameters that provided the most discrimination were determined. RESULTS Differences in spectral intensities allowed for discrimination between malignant and normal tissue. The spectral intensity of malignant tissue was lower than the normal tissue, and a shift of peak intensity to a longer wavelength was observed in the normalized spectrum of malignant tissue in the range of 360~660 nm. Multiple time-resolved fluorescence parameters provided the best diagnostic discrimination between normal tissue and carcinoma, including average lifetimes (i.e., at 390 nm: 1.7±0.06 ns for normal and 1.3±0.06 ns for tumor, P=0.0025), and the Laguerre coefficients, LEC-2 (i.e., at 460 nm: 0.135±0.001 for normal and 0.155±0.007 for tumor, P<0.05). CONCLUSION These findings highlight some of the differences in lifetime fluorescence between normal and malignant tissue. TR-LIFS has potential as a non-invasive diagnostic technique for HNSCC. PMID:20493355

Diagnostic criteria for constitutional mismatch repair deficiency syndrome: suggestions of the European consortium 'care for CMMRD' (C4CMMRD).

PubMed

Wimmer, Katharina; Kratz, Christian P; Vasen, Hans F A; Caron, Olivier; Colas, Chrystelle; Entz-Werle, Natacha; Gerdes, Anne-Marie; Goldberg, Yael; Ilencikova, Denisa; Muleris, Martine; Duval, Alex; Lavoine, Noémie; Ruiz-Ponte, Clara; Slavc, Irene; Burkhardt, Brigit; Brugieres, Laurence

2014-06-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain and intestinal tract tumours. Patients show a variety of non-malignant features that are indicative of CMMRD. However, currently no criteria that should entail diagnostic evaluation of CMMRD exist. We present a three-point scoring system for the suspected diagnosis CMMRD in a paediatric/young adult cancer patient. Tumours highly specific for CMMRD syndrome are assigned three points, malignancies overrepresented in CMMRD two points and all other malignancies one point. According to their specificity for CMMRD and their frequency in the general population, additional features are weighted with 1-2 points. They include multiple hyperpigmented and hypopigmented skin areas, brain malformations, pilomatricomas, a second childhood malignancy, a Lynch syndrome (LS)-associated tumour in a relative and parental consanguinity. According to the scoring system, CMMRD should be suspected in any cancer patient who reaches a minimum of three points by adding the points of the malignancy and the additional features. The diagnostic steps to confirm or refute the suspected diagnosis are outlined. We expect that application of the suggested strategy for CMMRD diagnosis will increase the number of patients being identified at the time when they develop their first tumour. This will allow adjustment of the treatment modalities, offering surveillance strategies for second malignancies and appropriate counselling of the entire family. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cutaneous sarcoidosis: a new subset in the spectrum of paraneoplastic dermatoses.

PubMed

El-Khalawany, M; Mosbeh, A; Aboeldahab, S; Ali, S

2018-05-20

Sarcoidosis is a well-described disease that can be associated with various malignancies; however, this correlation is still not fully clarified. To determine the clinical and histological features, demographic characteristics, and prognosis of patients diagnosed with paraneoplastic sarcoidosis (PS). This observational cohort prospective study included all patients diagnosed as cutaneous sarcoidosis. All patients were monitored for therapeutic response, prognosis, and any associated diseases or malignancies. Out of 94 patients with cutaneous sarcoidosis, we identified 12 patients (12.8%) with PS. There was a male (n = 8) preponderance (ratio 2 : 1),and the mean ± SD age of patients was 64.6 ± 13.21 years. The spectrum of paraneoplastic malignancies included six cases of Hodgkin lymphoma, five of multiple myeloma and one of non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma). The underlying malignancy was usually diagnosed within 4-25 months (mean ± SD 12.7 ± 6.85) from diagnosis of cutaneous sarcoidosis. The response to systemic steroid was relatively poor and patients on combination therapy showed frequent relapses. However, after treatment of the associated malignancy, seven patients (58.3%) showed complete resolution of the lesions and five (41.7%) showed moderate improvement. During follow-up, there was no relapse reported for either PS or malignancy. Our results suggest that sarcoidosis is a new subset in the spectrum of paraneoplastic syndrome. We propose that lymphoproliferative disorders should be considered in patients with cutaneous sarcoidosis who have a poor response to conventional therapy or whose skin biopsy shows a significant number of mitoses. © 2018 British Association of Dermatologists.

Modification of Hematopoietic Stem/Progenitor Cells with CD19-Specific Chimeric Antigen Receptors as a Novel Approach for Cancer Immunotherapy

PubMed Central

Ryan, Christine; Giannoni, Francesca; Hardee, Cinnamon L.; Tremcinska, Irena; Katebian, Behrod; Wherley, Jennifer; Sahaghian, Arineh; Tu, Andy; Grogan, Tristan; Elashoff, David; Cooper, Laurence J.N.; Hollis, Roger P.; Kohn, Donald B.

2013-01-01

Abstract Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells to specifically target B-lineage malignant cells in animal models and clinical trials, with efficient tumor cell lysis. However, in some cases, there has been insufficient persistence of effector cells, limiting clinical efficacy. We propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel approach to deliver the CD19-specific CAR, with potential for ensuring persistent production of effector cells of multiple lineages targeting B-lineage malignant cells. Assessments were performed using in vitro myeloid or natural killer (NK) cell differentiation of human HSPCs transduced with lentiviral vectors carrying first and second generations of CD19-specific CAR. Gene transfer did not impair hematopoietic differentiation and cell proliferation when transduced at 1–2 copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive cells, with second-generation CAR including CD28 domains being more efficient in NK cells. Our results provide evidence for the feasibility and efficacy of the modification of HSPC with CAR as a strategy for generating multiple lineages of effector cells for immunotherapy against B-lineage malignancies to augment graft-versus-leukemia activity. PMID:23978226

Metachronous T-Lymphoblastic Lymphoma and Burkitt Lymphoma in a Child With Constitutional Mismatch Repair Deficiency Syndrome.

PubMed

Alexander, Thomas B; McGee, Rose B; Kaye, Erica C; McCarville, Mary Beth; Choi, John K; Cavender, Cary P; Nichols, Kim E; Sandlund, John T

2016-08-01

Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with a high risk of developing early-onset malignancies of the blood, brain, and intestinal tract. We present the case of a patient with T-lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10 years later. This patient also exhibited numerous nonmalignant findings including café au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma, multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of malignant and nonmalignant neoplasms in this patient highlights the remarkable diversity, and early onset, of lesions seen in children with CMMRD. © 2016 Wiley Periodicals, Inc.

Transfer of interferon alfa into human breast milk.

PubMed

Kumar, A R; Hale, T W; Mock, R E

2000-08-01

Originally assumed to be antiviral substances, the efficacy of interferons in a number of pathologies, including malignancies, multiple sclerosis, and other immune syndromes, is increasingly recognized. This study provides data on the transfer of interferon alfa (2B) into human milk of a patient receiving massive intravenous doses for the treatment of malignant melanoma. Following an intravenous dose of 30 million IU, the amount of interferon transferred into human milk was only slightly elevated (1551 IU/mL) when compared to control milk (1249 IU/mL). These data suggest that even following enormous doses, interferon is probably too large in molecular weight to transfer into human milk in clinically relevant amounts.

Synchronous occurrence of prostate carcinoma and multiple myeloma: a case report.

PubMed

Sehgal, Tushar; Sharma, Sudha; Naseem, Shano; Varma, Neelam; Das, Ashim; Sharma, S C

2014-09-01

We describe a rare case of metastatic prostate cancer to bone marrow and synchronous multiple myeloma as the second malignant disease. Various diagnostic procedures, including cytomorphology and immunohistochemistry analyses together contributed to the detection of metastasis of prostate cancer and synchronous plasma cell proliferation in the bone marrow. The association between these two disorders is poorly understood however, some studies show that bone marrow microenvironment may play a crucial role. The need for further research in this regard is required to unfold this fascinating association.

Metastatic malignant pilomatrixoma, acanthomatous ameloblastoma, and liver tumor in a dog with polyphagia, polyuria, polydipsia, and weight loss.

PubMed

Barrot, Anne-Charlotte; Carioto, Lisa; Gains, Malcolm; Nadeau, Marie-Eve

2013-04-01

A 12-year-old, spayed female, Labrador dog was presented for evaluation of polyphagia, polyuria, polydipsia, weight loss of 2 months duration, and multiple cutaneous and subcutaneous masses. The dog was diagnosed with malignant pilomatrixoma with renal, lung, and lumbar metastases. This report describes an atypical presentation of malignant pilomatrixoma.

Metastatic malignant pilomatrixoma, acanthomatous ameloblastoma, and liver tumor in a dog with polyphagia, polyuria, polydipsia, and weight loss

PubMed Central

Barrot, Anne-Charlotte; Carioto, Lisa; Gains, Malcolm; Nadeau, Marie-Eve

2013-01-01

A 12-year-old, spayed female, Labrador dog was presented for evaluation of polyphagia, polyuria, polydipsia, weight loss of 2 months duration, and multiple cutaneous and subcutaneous masses. The dog was diagnosed with malignant pilomatrixoma with renal, lung, and lumbar metastases. This report describes an atypical presentation of malignant pilomatrixoma. PMID:24082168

Multiple cranial neuropathy: a common diagnostic problem.

PubMed

Garg, R K; Karak, B

1999-10-01

Syndrome of multiple cranial palsies is a common clinical problem routinely encountered in neurological practice. Anatomical patterns of cranial nerves involvement help in localizing the lesion. Various infections, malignant neoplasms and autoimmune vasculitis are common disorders leading to various syndromes of multiple cranial nerve palsies. A large number of diffuse neurological disorders (e.g. Gullian-Barre syndrome, myopathies) may also present with syndrome of multiple cranial nerve palsies. Despite extensive biochemical and radiological work-up the accurate diagnosis may not be established. Few such patients represent "idiopathic" variety of multiple cranial nerve involvement and show good response to corticosteroids. Widespread and sequential involvements of cranial nerves frequently suggest possibility of malignant infiltration of meninges, however, confirmation of diagnosis may not be possible before autopsy.

[Clinical significance of determination of serum B7-H4 in patients with malignant hematologic diseases].

PubMed

Wang, Xiao-Mei; Hu, Guo-Yan; Liu, Wei; Zheng, Shu-Hua; Lv, Jing; Wang, Hong-Mei; Xu, Jun-Fa

2010-09-01

To study the clinical significance of determination of serum B7-H4 in patients with malignant hematologic diseases. Serum B7-H4 levels were determined in 65 patients with leucemia, 34 patients with lymphoma, 12 patients with multiple myeloma as well as in 50 healthy controls. The serum B7-H4 levels in patients with lymphoma [(38.81+/-10.34) kappag/L] were significantly higher than healthy controls [(31.62+/-9.850) kappag/L] (P<0.01). But there are no significant difference of B7-H4 levels in serum among patients with leucemia, patients with multiple myeloma and healthy controls. These results suggest that the B7-H4 may correlated with lymphoma, but uncorrelated with leucemia and multiple myeloma. Measurement of serum B7-H4 level provide useful information for distinctive diagnosis of different kinds of malignant hematologic diseases.

A case of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection.

PubMed

Das, Joyutpal; Layton, Benjamin; Lamb, Harriet; Sinnott, Nicola; Leahy, Bernard C

2015-11-01

Serratia marcescens is a saprophytic gram-negative bacillus capable of causing a wide range of infections. A 57-year-old female was admitted to our hospital for four weeks with community acquired pneumonia. A chest x-ray, six weeks after discharge, demonstrated multiple, bilateral 'cannon ball'-like opacities and mediastinal lymphadenopathy which were highly suspicious of disseminated malignancy or tuberculosis. The only symptom that this patient had was a productive cough. She had multiple commodities, but no specific immunodeficiency disorder. Interestingly, her sputum and bronchial washing samples grew S. marcescens. The computed tomography-guided lung biopsy demonstrated necrotic granulomatous changes. There was no pathological evidence of tuberculosis or fungal infection, malignancy or vasculitis. There are only a handful of reported cases of Serratia granulomas. Thus, we are reporting a rare instance of pulmonary Serratia marcescens granuloma radiologically mimicking metastatic malignancy and tuberculosis infection. © The Author(s) 2015.

Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition

PubMed Central

McCoy, Erica L.; Iwanaga, Ritsuko; Jedlicka, Paul; Abbey, Nee-Shamo; Chodosh, Lewis A.; Heichman, Karen A.; Welm, Alana L.; Ford, Heide L.

2009-01-01

Six1 is a developmentally regulated homeoprotein with limited expression in most normal adult tissues and frequent misexpression in a variety of malignancies. Here we demonstrate, using a bitransgenic mouse model, that misexpression of human Six1 in adult mouse mammary gland epithelium induces tumors of multiple histological subtypes in a dose-dependent manner. The neoplastic lesions induced by Six1 had an in situ origin, showed diverse differentiation, and exhibited progression to aggressive malignant neoplasms, as is often observed in human carcinoma of the breast. Strikingly, the vast majority of Six1-induced tumors underwent an epithelial-mesenchymal transition (EMT) and expressed multiple targets of activated Wnt signaling, including cyclin D1. Interestingly, Six1 and cyclin D1 coexpression was found to frequently occur in human breast cancers and was strongly predictive of poor prognosis. We further show that Six1 promoted a stem/progenitor cell phenotype in the mouse mammary gland and in Six1-driven mammary tumors. Our data thus provide genetic evidence for a potent oncogenic role for Six1 in mammary epithelial neoplasia, including promotion of EMT and stem cell–like features. PMID:19726883

Laparoscopic approach to gastrointestinal malignancies: Toward the future with caution

PubMed Central

Bencini, Lapo; Bernini, Marco; Farsi, Marco

2014-01-01

After the rapid acceptance of laparoscopy to manage multiple benign diseases arising from gastrointestinal districts, some surgeons started to treat malignancies by the same way. However, if the limits of laparoscopy for benign diseases are mainly represented by technical issues, oncologic outcomes remain the foundation of any procedures to cure malignancies. Cancerous patients represent an important group with peculiar aspects including reduced survival expectancy, worsened quality of life due to surgery itself and adjuvant therapies, and challenging psychological impact. All these issues could, potentially, receive a better management with a laparoscopic surgical approach. In order to confirm such aspects, similarly to testing the newest weapons (surgical or pharmacologic) against cancer, long-term follow-up is always recommendable to assess the real benefits in terms of overall survival, cancer-free survival and quality of life. Furthermore, it seems of crucial importance that surgeons will be correctly trained in specific oncologic principles of surgical oncology as well as in modern miniinvasive technologies. Therefore, laparoscopic treatment of gastrointestinal malignancies requires more caution and deep analysis of published evidences, as compared to those achieved for inflammatory bowel diseases, gastroesophageal reflux disease or diverticular disease. This review tries to examine the evidence available to date for the use of laparoscopy and robotics in malignancies arising from the gastrointestinal district. PMID:24587655

Canine digital tumors: a veterinary cooperative oncology group retrospective study of 64 dogs.

PubMed

Henry, Carolyn J; Brewer, William G; Whitley, Elizabeth M; Tyler, Jeff W; Ogilvie, Gregory K; Norris, Alan; Fox, Leslie E; Morrison, Wallace B; Hammer, Alan; Vail, David M; Berg, John

2005-01-01

We compared clinical characteristics and outcomes for dogs with various digital tumors. Medical records and histology specimens of affected dogs from 9 veterinary institutions were reviewed. Risk factors examined included age, weight, sex, tumor site (hindlimb or forelimb), local tumor (T) stage, metastases, tumor type, and treatment modality. The Kaplan-Meier product limit method was used to determine the effect of postulated risk factors on local disease-free interval (LDFI), metastasis-free interval (MFI), and survival time (ST). Outcomes were thought to differ significantly between groups when P < or = .003. Sixty-four dogs were included. Squamous cell carcinoma (SCC) accounted for 33 (51.6%) of the tumors. Three dogs presented with or developed multiple digital SCC. Other diagnoses included malignant melanoma (MM) (n = 10; 15.6%), osteosarcoma (OSA) (n = 4; 6.3%), hemangiopericytoma (n = 3; 4.7%), benign soft tissue tumors (n = 5; 7.8%), and malignant soft tissue tumors (n = 9; 14%). Fourteen dogs with malignancies had black hair coats, including 5 of the 10 dogs with MM. Surgery was the most common treatment and, regardless of the procedure, had a positive impact on survival. None of the patient variables assessed, including age, sex, tumor type, site, and stage, had a significant impact on ST. Both LDFI and MFI were negatively affected by higher T stage, but not by type of malignancy. Although metastasis at diagnosis correlated with a shorter LDFI, it did not have a significant impact on ST. On the basis of these findings, early surgical intervention is advised for the treatment of dogs with digital tumors, regardless of tumor type or the presence of metastatic disease.

Novel BAFF-Receptor Antibody to Natively Folded Recombinant Protein Eliminates Drug-Resistant Human B-cell Malignancies In Vivo.

PubMed

Qin, Hong; Wei, Guowei; Sakamaki, Ippei; Dong, Zhenyuan; Cheng, Wesley A; Smith, D Lynne; Wen, Feng; Sun, Han; Kim, Kunhwa; Cha, Soungchul; Bover, Laura; Neelapu, Sattva S; Kwak, Larry W

2018-03-01

Purpose: mAbs such as anti-CD20 rituximab are proven therapies in B-cell malignancies, yet many patients develop resistance. Novel therapies against alternative targets are needed to circumvent resistance mechanisms. We sought to generate mAbs against human B-cell-activating factor receptor (BAFF-R/TNFRSF13C), which has not yet been targeted successfully for cancer therapy. Experimental Design: Novel mAbs were generated against BAFF-R, expressed as a natively folded cell surface immunogen on mouse fibroblast cells. Chimeric BAFF-R mAbs were developed and assessed for in vitro and in vivo monotherapy cytotoxicity. The chimeric mAbs were tested against human B-cell tumor lines, primary patient samples, and drug-resistant tumors. Results: Chimeric antibodies bound with high affinity to multiple human malignant B-cell lines and induced potent antibody-dependent cellular cytotoxicity (ADCC) against multiple subtypes of human lymphoma and leukemia, including primary tumors from patients who had relapsed after anti-CD20 therapy. Chimeric antibodies also induced ADCC against ibrutinib-resistant and rituximab-insensitive CD20-deficient variant lymphomas, respectively. Importantly, they demonstrated remarkable in vivo growth inhibition of drug-resistant tumor models in immunodeficient mice. Conclusions: Our method generated novel anti-BAFF-R antibody therapeutics with remarkable single-agent antitumor effects. We propose that these antibodies represent an effective new strategy for targeting and treating drug-resistant B-cell malignancies and warrant further development. Clin Cancer Res; 24(5); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Dietary Acrylamide Intake and the Risk of Lymphatic Malignancies: The Netherlands Cohort Study on Diet and Cancer

PubMed Central

Bongers, Mathilda L.; Hogervorst, Janneke G. F.; Schouten, Leo J.; Goldbohm, R. Alexandra; Schouten, Harry C.; van den Brandt, Piet A.

2012-01-01

Background Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. Methods The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n  = 5,000). Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs) were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles), for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. Results After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27) and 1.28 (95% CI: 1.03, 1.61) per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85). No associations were observed for women. Conclusion We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted. PMID:22723843

Familial solitary chondrosarcoma resulting from germline EXT2 mutation.

PubMed

Heddar, Abdelkader; Fermey, Pierre; Coutant, Sophie; Angot, Emilie; Sabourin, Jean-Christophe; Michelin, Paul; Parodi, Nathalie; Charbonnier, Françoise; Vezain, Myriam; Bougeard, Gaëlle; Baert-Desurmont, Stéphanie; Frébourg, Thierry; Tournier, Isabelle

2017-02-01

Germline mutations of EXT2, encoding Exostosin Glycosyltransferase 2, are associated with multiple osteochondromas (MO), an autosomal dominant disease characterized by the development of multiple peripheral cartilaginous benign tumors with a weak risk of malignant transformation. We report here a family with a remarkable clinical presentation characterized by the development of isolated chondrosarcomas, mostly located in ribs. Comparative analysis of exomes from two third-degree affected relatives led us to identify a single common disruptive variation, corresponding to a stop mutation (c.237G > A, p.Trp79*; (NM_000401.3); c.138G > A, p.Trp46*; (NM_207122.1)) within exon 2 of the EXT2 gene. Interestingly, no obvious sign of MO was detected in affected members by radiological examination. This report shows that germline mutations of EXT2 can result, not only in the development of multiple benign osteochondromas, but also in the development of isolated malignant cartilaginous tumors including central tumors, and that the presence of germline EXT2 mutation should be considered in patients suspected to have an inherited predisposition to chondrosarcoma, even in the absence of MO. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review.

PubMed

Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-02-01

Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor.

Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum

PubMed Central

Bae, Sung Hwan; Hwang, Jung Hwa; Da Nam, Bo; Kim, Hyun Jo; Kim, Ki-Up; Kim, Dong Won; Choi, In Ho

2016-01-01

Abstract Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID:26886614

Screening for adenoviruses in haematological neoplasia: High prevalence in mantle cell lymphoma.

PubMed

Kosulin, Karin; Rauch, Margit; Ambros, Peter F; Pötschger, Ulrike; Chott, Andreas; Jäger, Ulrich; Drach, Johannes; Nader, Alexander; Lion, Thomas

2014-02-01

Human adenoviruses possess oncogenic capacity which is well documented in mammalian animal models, but their possible implication in human malignancy has remained enigmatic. Following primary infection, adenoviruses can persist in a latent state in lymphocytes where the virus is apparently able to evade immune surveillance. In the present study, we have employed a broad-spectrum adenovirus polymerase chain reaction (PCR) assay to systematically screen more than 200 diagnostic specimens of different lymphoid malignancies including acute lymphocytic leukaemia (n=50), chronic lymphocytic leukaemia (n=50), various types of malignant lymphoma (n=100) and multiple myeloma (n=11) for the presence of adenoviral sequences. While most entities analysed revealed negative findings in virtually all specimens tested, adenoviral DNA was detected in 15/36 (42%) mantle cell lymphomas investigated. The most prevalent adenoviral species detected was C, and less commonly B. Adenovirus-positive findings in patients with mantle cell lymphoma were made at different sites including bone marrow (n=7), intestine (n=5), lymph nodes (n=2) and tonsillar tissue (n=1). The presence of adenoviral sequences identified by PCR was confirmed in individual cells by fluorescence in-situ hybridisation (FISH). The frequent observation of adenoviruses in mantle cell lymphoma is intriguings, and raises questions about their possible involvement in the pathogenesis of this lymphoid malignancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion

PubMed Central

Hall, Michael J; Innocent, Julie; Rybak, Christina; Veloski, Colleen; Scott, Walter J; Wu, Hong; Ridge, John A; Hoffman, John P; Borghaei, Hossein; Turaka, Aruna; Daly, Mary B

2015-01-01

Introduction Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. Case report A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo–oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). Discussion Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. Conclusion To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described. PMID:25733923

CT diagnosis and differentiation of benign and malignant varieties of solitary fibrous tumor of the pleura

PubMed Central

You, Xiaofang; Sun, Xiwen; Yang, Chunyan; Fang, Yong

2017-01-01

Abstract To investigate computed tomography (CT) characteristics of benign and malignant solitary fibrous tumors of the pleura (SFTPs). Preoperative CTs for 60 SFTP cases (49 benign and 11 malignant) with subsequently confirmed diagnoses were retrospectively analyzed. Tumor morphologies included mounded or mushroom umbrella-shape (19 cases, 31.7%), quasi-circular or oval-shape (30 cases, 50%), and growth resembling a casting mould (12 cases, 20%). Maximum tumor diameters were 1.1 to 18.9 cm (average: 6.4 ± 4.8 cm). Fifty-seven cases had clear boundaries, and 3 had partially coarse boundaries. Twenty-seven cases showed homogeneous density; 33, “geographic”-patterned inhomogeneous density; 6, calcifications; 12, intratumor blood vessels; and 3, thick nourishing peritumoral blood vessels. Pleural thickening (regular and irregular) was found adjacent to tumors in 4, compression of adjacent ribs with absorption and cortical sclerosis in 2, and location adjacent to ribs with bony destruction in 1. Four cases had a small amount of lung tissue enfolded along the boundary, 2 had multiple peritumoral pulmonary bullae, and 9 had small ipsilateral pleural effusions. Compared with benign and malignant SFTPs were larger (P < .001), had inhomogeneous density, and were more commonly associated with intratumor blood vessels and pleural effusions (P < .01). CT revealed characteristic patterns in SFTPs, including casting mould-like growth, rich blood supply, and “geographic”-patterned enhancement. In addition, larger tumor size, inhomogeneous intensities, abundant intratumor blood vessels, and pleural effusions were more common with malignancy. Lastly, multislice CT angiography can reveal feeding arteries and help guide surgical management. PMID:29245313

CT diagnosis and differentiation of benign and malignant varieties of solitary fibrous tumor of the pleura.

PubMed

You, Xiaofang; Sun, Xiwen; Yang, Chunyan; Fang, Yong

2017-12-01

To investigate computed tomography (CT) characteristics of benign and malignant solitary fibrous tumors of the pleura (SFTPs).Preoperative CTs for 60 SFTP cases (49 benign and 11 malignant) with subsequently confirmed diagnoses were retrospectively analyzed.Tumor morphologies included mounded or mushroom umbrella-shape (19 cases, 31.7%), quasi-circular or oval-shape (30 cases, 50%), and growth resembling a casting mould (12 cases, 20%). Maximum tumor diameters were 1.1 to 18.9 cm (average: 6.4 ± 4.8 cm). Fifty-seven cases had clear boundaries, and 3 had partially coarse boundaries. Twenty-seven cases showed homogeneous density; 33, "geographic"-patterned inhomogeneous density; 6, calcifications; 12, intratumor blood vessels; and 3, thick nourishing peritumoral blood vessels. Pleural thickening (regular and irregular) was found adjacent to tumors in 4, compression of adjacent ribs with absorption and cortical sclerosis in 2, and location adjacent to ribs with bony destruction in 1. Four cases had a small amount of lung tissue enfolded along the boundary, 2 had multiple peritumoral pulmonary bullae, and 9 had small ipsilateral pleural effusions. Compared with benign and malignant SFTPs were larger (P < .001), had inhomogeneous density, and were more commonly associated with intratumor blood vessels and pleural effusions (P < .01).CT revealed characteristic patterns in SFTPs, including casting mould-like growth, rich blood supply, and "geographic"-patterned enhancement. In addition, larger tumor size, inhomogeneous intensities, abundant intratumor blood vessels, and pleural effusions were more common with malignancy. Lastly, multislice CT angiography can reveal feeding arteries and help guide surgical management.

A preclinical model of CD38-pretargeted radioimmunotherapy for plasma cell malignancies.

PubMed

Green, Damian J; Orgun, Nural N; Jones, Jon C; Hylarides, Mark D; Pagel, John M; Hamlin, Donald K; Wilbur, D S; Lin, Yukang; Fisher, Darrell R; Kenoyer, Aimee L; Frayo, Shani L; Gopal, Ajay K; Orozco, Johnnie J; Gooley, Theodore A; Wood, Brent L; Bensinger, William I; Press, Oliver W

2014-02-15

The vast majority of patients with plasma cell neoplasms die of progressive disease despite high response rates to novel agents. Malignant plasma cells are very radiosensitive, but the potential role of radioimmunotherapy (RIT) in the management of plasmacytomas and multiple myeloma has undergone only limited evaluation. Furthermore, CD38 has not been explored as a RIT target despite its uniform high expression on malignant plasma cells. In this report, both conventional RIT (directly radiolabeled antibody) and streptavidin-biotin pretargeted RIT (PRIT) directed against the CD38 antigen were assessed as approaches to deliver radiation doses sufficient for multiple myeloma cell eradication. PRIT demonstrated biodistributions that were markedly superior to conventional RIT. Tumor-to-blood ratios as high as 638:1 were seen 24 hours after PRIT, whereas ratios never exceeded 1:1 with conventional RIT. (90)Yttrium absorbed dose estimates demonstrated excellent target-to-normal organ ratios (6:1 for the kidney, lung, liver; 10:1 for the whole body). Objective remissions were observed within 7 days in 100% of the mice treated with doses ranging from 800 to 1,200 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in treated mice compared with tumors that were 2,982% ± 2,834% of initial tumor volume in control animals) by day 23. Furthermore, 100% of animals bearing NCI-H929 multiple myeloma tumor xenografts treated with 800 μCi of anti-CD38 pretargeted (90)Y-DOTA-biotin achieved long-term myeloma-free survival (>70 days) compared with none (0%) of the control animals. ©2013 AACR.

Malignant Mesothelioma Mortality - United States, 1999-2015.

PubMed

Mazurek, Jacek M; Syamlal, Girija; Wood, John M; Hendricks, Scott A; Weston, Ainsley

2017-03-03

Malignant mesothelioma is a neoplasm associated with occupational and environmental inhalation exposure to asbestos* fibers and other elongate mineral particles (EMPs) (1-3). Patients have a median survival of approximately 1 year from the time of diagnosis (1). The latency period from first causative exposure to malignant mesothelioma development typically ranges from 20 to 40 years but can be as long as 71 years (2,3). Hazardous occupational exposures to asbestos fibers and other EMPs have occurred in a variety of industrial operations, including mining and milling, manufacturing, shipbuilding and repair, and construction (3). Current exposures to commercial asbestos in the United States occur predominantly during maintenance operations and remediation of older buildings containing asbestos (3,4). To update information on malignant mesothelioma mortality (5), CDC analyzed annual multiple cause-of-death records † for 1999-2015, the most recent years for which complete data are available. During 1999-2015, a total of 45,221 deaths with malignant mesothelioma mentioned on the death certificate as the underlying or contributing cause of death were reported in the United States, increasing from 2,479 deaths in 1999 to 2,597 in 2015 (in the same time period the age-adjusted death rates § decreased from 13.96 per million in 1999 to 10.93 in 2015). Malignant mesothelioma deaths increased for persons aged ≥85 years, both sexes, persons of white, black, and Asian or Pacific Islander race, and all ethnic groups. Despite regulatory actions and the decline in use of asbestos the annual number of malignant mesothelioma deaths remains substantial. The continuing occurrence of malignant mesothelioma deaths underscores the need for maintaining measures to prevent exposure to asbestos fibers and other causative EMPs and for ongoing surveillance to monitor temporal trends.

Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study.

PubMed

Pappone, Carlo; Vicedomini, Gabriele; Manguso, Francesco; Baldi, Mario; Pappone, Alessia; Petretta, Andrea; Vitale, Raffaele; Saviano, Massimo; Ciaccio, Cristiano; Giannelli, Luigi; Calovic, Zarko; Tavazzi, Luigi; Santinelli, Vincenzo

2012-02-07

The available amount of detailed long-term data in patients with Wolff-Parkinson-White syndrome is limited, and no prospective electrophysiological studies looking at predictors of malignant arrhythmia are available. Among 8575 symptomatic Wolff-Parkinson-White patients with atrioventricular reentrant tachycardia referred for electrophysiological test, 369 (mean age, 23±12.5 years) declined catheter ablation and were followed up. The primary end point of the study was to evaluate over a 5-year follow-up the predictors and characteristics of patients who develop malignant arrhythmias. After a mean follow-up of 42.1±10 months, malignant arrhythmias developed in 29 patients (mean age, 13.9±5.6 years; 26 male), resulting in presyncope/syncope (25 patients), hemodynamic collapse (3 patients), or cardiac arrest caused by ventricular fibrillation (1 patient). Of the remaining 340 patients, 168 (mean age, 34.2±9.0 years) remained asymptomatic up to 5 years, and 172 (mean age, 13.6±5.1 years) had benign recurrence, including sustained atrioventricular reentrant tachycardia (132 patients) or atrial fibrillation (40 patients). Compared with the group with no malignant arrhythmias, the group with malignant arrhythmias showed shorter accessory-pathway effective refractory period (P<0.001) and more often exhibited multiple accessory pathways (P<0.001), and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation was more frequently inducible (P<0.001). Multivariable analysis demonstrated that short accessory-pathway effective refractory period (P<0.001) and atrioventricular reentrant tachycardia triggering sustained pre-excited atrial fibrillation (P<0.001) were independent predictors of malignant arrhythmias. Symptomatic patients with Wolff-Parkinson-White syndrome generally have a good outcome, and predictors of malignant arrhythmias are similar to those reported for asymptomatic patients with ventricular pre-excitation.

Diagnosis and treatment of concurrent dermal malignant melanoma and melanocytomas in a pygmy hippopotamus (Choeropsis liberiensis).

PubMed

Saunders, Richard A; Killick, Rowena S; Barrows, Michelle G; Bowlt, Kelly A; Denk, Daniella

2017-10-01

Dermal melanocytic neoplasms are common in some even-toed ungulates (Artiodactyla), yet this entity has not been reported in the pygmy hippopotamus to date. Concurrent occurrence of multiple benign and malignant melanocytic neoplasms is unusual. Malignant transformation occurs in a small percentage of benign melanocytic tumours in people but this phenomenon has not been well documented in animals. To report the diagnosis and treatment of concurrent dermal melanocytomas and malignant melanomas in a pygmy hippopotamus. A 36-year-old intact male pygmy hippopotamus, part of a zoological collection, housed with a 10-year-old female of the same species, presented with multiple raised and pigmented skin masses. Initial impression smears of one ulcerated lesion were consistent with inflammation; subsequent histopathological findings from a skin biopsy revealed an underlying malignant melanoma. The animal was anaesthetised, ultrasonographic imaging of the local lymph nodes indicated no local involvement and all skin lesions were removed. Recovery from anaesthesia was unremarkable, skin healing was within normal limits for the species. There was no sign of recurrence 34 months post-surgery. A diagnosis of malignant melanomas and concurrent melanocytomas was made on histopathological evaluation. To the best of the authors' knowledge, this is the first reported case of melanocytic neoplasia in the pygmy hippopotamus. The occurrence of both benign and malignant melanocytic skin tumours should be considered in this species. © 2017 ESVD and ACVD.

Detection of genome-wide copy number variants in myeloid malignancies using next-generation sequencing.

PubMed

Shen, Wei; Paxton, Christian N; Szankasi, Philippe; Longhurst, Maria; Schumacher, Jonathan A; Frizzell, Kimberly A; Sorrells, Shelly M; Clayton, Adam L; Jattani, Rakhi P; Patel, Jay L; Toydemir, Reha; Kelley, Todd W; Xu, Xinjie

2018-04-01

Genetic abnormalities, including copy number variants (CNV), copy number neutral loss of heterozygosity (CN-LOH) and gene mutations, underlie the pathogenesis of myeloid malignancies and serve as important diagnostic, prognostic and/or therapeutic markers. Currently, multiple testing strategies are required for comprehensive genetic testing in myeloid malignancies. The aim of this proof-of-principle study was to investigate the feasibility of combining detection of genome-wide large CNVs, CN-LOH and targeted gene mutations into a single assay using next-generation sequencing (NGS). For genome-wide CNV detection, we designed a single nucleotide polymorphism (SNP) sequencing backbone with 22 762 SNP regions evenly distributed across the entire genome. For targeted mutation detection, 62 frequently mutated genes in myeloid malignancies were targeted. We combined this SNP sequencing backbone with a targeted mutation panel, and sequenced 9 healthy individuals and 16 patients with myeloid malignancies using NGS. We detected 52 somatic CNVs, 11 instances of CN-LOH and 39 oncogenic mutations in the 16 patients with myeloid malignancies, and none in the 9 healthy individuals. All CNVs and CN-LOH were confirmed by SNP microarray analysis. We describe a genome-wide SNP sequencing backbone which allows for sensitive detection of genome-wide CNVs and CN-LOH using NGS. This proof-of-principle study has demonstrated that this strategy can provide more comprehensive genetic profiling for patients with myeloid malignancies using a single assay. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neurofibromatosis.

PubMed

Korf, Bruce R

2013-01-01

The "neurofibromatoses" are a set of distinct genetic disorders that have in common the occurrence of tumors of the nerve sheath. They include NF1, NF2, and schwannomatosis. All are dominantly inherited with a high rate of new mutation and variable expression. NF1 includes effects on multiple systems of the body. The major NF1-associated tumor is the neurofibroma. In addition, clinical manifestations include bone dysplasia, learning disabilities, and an increased risk of malignancy. NF2 includes schwannomas of multiple cranial and spinal nerves, especially the vestibular nerve, as well as other tumors such as meningiomas and ependymomas. The schwannomatosis phenotype is limited to multiple schwannomas, and usually presents with pain. The genes that underlie each of the disorders are known: NF1 for neurofibromatosis type 1, NF2 for neurofibromatosis type 2, and INI1/SMARCB1 for schwannomatosis. Genetic testing is possible to identify mutations. Insights into pathogenesis are beginning to suggest new treatment strategies, and therapeutic trials with several new forms of treatment are underway. Copyright © 2013 Elsevier B.V. All rights reserved.

The NUP98 Gene as a Potential Modifier of NF2 Associated Tumors

DTIC Science & Technology

2017-06-01

limited to observation, surgical removal, and stereotactic radiation [ 1 ]. However, surgery may not be possible if the tumor is inaccessible or when...there are too many tumors. Radiation treatment may cause malignant transformation and/or growth acceleration of benign tumor cells. In addition...genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas

Asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma in an insulation worker.

PubMed Central

Fischbein, A; Luo, J C; Pinkston, G R

1991-01-01

Asbestos associated diseases consist of both benign and malignant conditions. A rare constellation of asbestosis, laryngeal carcinoma, and malignant peritoneal mesothelioma occurring in a patient with long term occupational exposure to airborne asbestos fibres is presented. The observation illustrates the powerful disease-causing potential of occupational exposure to asbestos. A brief discussion of multiple primary neoplasms associated with exposure to asbestos is also presented. Images PMID:2039746

[Multiple conjunctival malignant melanomas (author's transl)].

PubMed

Haddad, R

1979-04-01

5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.

Intercellular crosstalk in human malignant melanoma.

PubMed

Dvořánková, Barbora; Szabo, Pavol; Kodet, Ondřej; Strnad, Hynek; Kolář, Michal; Lacina, Lukáš; Krejčí, Eliška; Naňka, Ondřej; Šedo, Aleksi; Smetana, Karel

2017-05-01

Incidence of malignant melanoma is increasing globally. While the initial stages of tumors can be easily treated by a simple surgery, the therapy of advanced stages is rather limited. Melanoma cells spread rapidly through the body of a patient to form multiple metastases. Consequently, the survival rate is poor. Therefore, emphasis in melanoma research is given on early diagnosis and development of novel and more potent therapeutic options. The malignant melanoma is arising from melanocytes, cells protecting mitotically active keratinocytes against damage caused by UV light irradiation. The melanocytes originate in the neural crest and consequently migrate to the epidermis. The relationship between the melanoma cells, the melanocytes, and neural crest stem cells manifests when the melanoma cells are implanted to an early embryo: they use similar migratory routes as the normal neural crest cells. Moreover, malignant potential of these melanoma cells is overdriven in this experimental model, probably due to microenvironmental reprogramming. This observation demonstrates the crucial role of the microenvironment in melanoma biology. Indeed, malignant tumors in general represent complex ecosystems, where multiple cell types influence the growth of genetically mutated cancer cells. This concept is directly applicable to the malignant melanoma. Our review article focuses on possible strategies to modify the intercellular crosstalk in melanoma that can be employed for therapeutic purposes.

Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.

PubMed

Ripperger, Tim; Schlegelberger, Brigitte

2016-03-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of CMMRD patients develop hematological malignancies as primary (sometimes the only) malignancy or as secondary neoplasm. T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most frequent hematological malignancies. Besides malignant diseases, non-neoplastic features are frequently observed, e.g. café-au-lait spots sometimes resembling neurofibromatosis type I, hypopigmented skin lesions, numerous adenomatous polyps, multiple pilomatricomas, or impaired immunoglobulin class switch recombination. Within the present review, we summarize previously published CMMRD patients with at least one hematological malignancy, provide an overview of steps necessary to substantiate the diagnosis of CMMRD, and refer to the recent most relevant literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

SLC12A7 alters adrenocortical carcinoma cell adhesion properties to promote an aggressive invasive behavior.

PubMed

Brown, Taylor C; Murtha, Timothy D; Rubinstein, Jill C; Korah, Reju; Carling, Tobias

2018-06-08

Altered expression of Solute Carrier Family 12 Member 7 (SLC12A7) is implicated to promote malignant behavior in multiple cancer types through an incompletely understood mechanism. Recent studies have shown recurrent gene amplifications and overexpression of SLC12A7 in adrenocortical carcinoma (ACC). The potential mechanistic effect(s) of SLC12A7 amplifications in portending an aggressive behavior in ACC has not been previously studied and is investigated here using two established ACC cell lines, SW-13 and NCI-H295R. SW-13 cells, which express negligible amounts of SLC12A7, were enforced to express SLC12A7 constitutively, while RNAi gene silencing was performed in NCI-H295R cells, which have robust endogenous expression of SLC12A7. In vitro studies tested the outcomes of experimental alterations in SLC12A7 expression on malignant characteristics, including cell viability, growth, colony formation potential, motility, invasive capacity, adhesion and detachment kinetics, and cell membrane organization. Further, potential alterations in transcription regulation downstream to induced SLC12A7 overexpression was explored using targeted transcription factor expression arrays. Enforced SLC12A7 overexpression in SW-13 cells robustly promoted motility and invasive characteristics (p < 0.05) without significantly altering cell viability, growth, or colony formation potential. SLC12A7 overexpression also significantly increased rates of cellular attachment and detachment turnover (p < 0.05), potentially propelled by increased filopodia formation and/or Ezrin interaction. In contrast, RNAi gene silencing of SLC12A7 stymied cell attachment strength as well as migration and invasion capacity in NCI-H295R cells. Transcription factor expression analysis identified multiple signally pathways potentially affected by SLC12A7 overexpression, including osmotic stress, bone morphogenetic protein, and Hippo signaling pathways. Amplification of SLC12A7 observed in ACCs is shown here, in vitro, to exacerbate the malignant behavior of ACC cells by promoting invasive capacities, possibly mediated by alterations in multiple signaling pathways, including the osmotic stress pathway.

New targeted therapies for indolent B-cell malignancies in older patients.

PubMed

Krem, Maxwell M; Gopal, Ajay K

2015-01-01

Molecularly targeted agents have become an established component of the treatment of indolent B-cell malignancies (iNHL). iNHL disproportionately affects older adults, so treatments that have excellent tolerability and efficacy across multiple lines of therapy are in demand. The numbers and classes of targeted therapies for iNHL have proliferated rapidly in recent years; classes of agents that show promise for older patients with iNHL include anti-CD20 antibodies, phosphatidyl-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway inhibitors, immunomodulators, proteasome inhibitors, epigenetic modulators, and immunotherapies. Here, we review the proposed mechanisms of action, efficacy, and tolerability of novel agents for iNHL, with an emphasis on their applicability to older patients.

Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: A review

PubMed Central

Cháirez-Ramírez, MH; Moreno-Jiménez, MR; González-Laredo, RF; Gallegos-Infante, JA; Rocha-Guzmán, Nuria Elizabeth

2016-01-01

In recent times, a great deal of interest has been motivated on plant derived compounds known as nutraceuticals. These compounds exert important beneficial activities that improve people's health status when are consumed regularly, and now they appear as a viable option to explore their possible therapeutic effects against diseases like cancer. Particularly, lupane-type triterpenes have shown great ability to modulate multiple cancer-related signaling pathways and processes, including NF-κB, Wnt/β-catenin, PI3K/Akt, apoptosis, and many other routes related to proliferation or cell death, which are uncontrolled in malignant tumors. These investigations have promoted in vitro and in vivo studies, searching their mechanisms of action; although more research is still needed to prove its potential in human clinical trials. This review focuses on the ability of betulin, betulinic acid and lupeol to show benefits against the most common types of malignant tumors, which are considered a major global threat for public health. PMID:28337107

Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array.

PubMed

Serio, Gabriella; Pezzuto, Federica; Marzullo, Andrea; Scattone, Anna; Cavone, Domenica; Punzi, Alessandra; Fortarezza, Francesco; Gentile, Mattia; Buonadonna, Antonia Lucia; Barbareschi, Mattia; Vimercati, Luigi

2017-08-22

Malignant mesothelioma is a rare and aggressive tumor with limited therapeutic options. We report a case of a malignant peritoneal mesothelioma (MPM) epithelioid type, with environmental asbestos exposure, in a 36-year-old man, with a long survival (17 years). The patient received standard treatment which included cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Molecular analysis with comparative genomic hybridization (CGH)-array was performed on paraffin-embedded tumoral samples. Multiple chromosomal imbalances were detected. The gains were prevalent. Losses at 1q21, 2q11.1→q13, 8p23.1, 9p12→p11, 9q21.33→q33.1, 9q12→q21.33, and 17p12→p11.2 are observed. Chromosome band 3p21 ( BAP1 ), 9p21 ( CDKN2A ) and 22q12 ( NF2 ) are not affected. Conclusions: the defects observed in this case are uncommon in malignant peritoneal mesothelioma. Some chromosomal aberrations that appear to be random here, might actually be relevant events explaining the response to therapy, the long survival and, finally, may be considered useful prognostic factors in peritoneal malignant mesothelioma (PMM).

Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

PubMed Central

Ghosh, Sajal K.; Perrine, Susan P.; Faller, Douglas V.

2012-01-01

Epstein-Barr virus (EBV) is the causal agent in the etiology of Burkitt's lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin's and non-Hodgkin's lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies. PMID:22500168

Localized thin-section CT with radiomics feature extraction and machine learning to classify early-detected pulmonary nodules from lung cancer screening

NASA Astrophysics Data System (ADS)

Tu, Shu-Ju; Wang, Chih-Wei; Pan, Kuang-Tse; Wu, Yi-Cheng; Wu, Chen-Te

2018-03-01

Lung cancer screening aims to detect small pulmonary nodules and decrease the mortality rate of those affected. However, studies from large-scale clinical trials of lung cancer screening have shown that the false-positive rate is high and positive predictive value is low. To address these problems, a technical approach is greatly needed for accurate malignancy differentiation among these early-detected nodules. We studied the clinical feasibility of an additional protocol of localized thin-section CT for further assessment on recalled patients from lung cancer screening tests. Our approach of localized thin-section CT was integrated with radiomics features extraction and machine learning classification which was supervised by pathological diagnosis. Localized thin-section CT images of 122 nodules were retrospectively reviewed and 374 radiomics features were extracted. In this study, 48 nodules were benign and 74 malignant. There were nine patients with multiple nodules and four with synchronous multiple malignant nodules. Different machine learning classifiers with a stratified ten-fold cross-validation were used and repeated 100 times to evaluate classification accuracy. Of the image features extracted from the thin-section CT images, 238 (64%) were useful in differentiating between benign and malignant nodules. These useful features include CT density (p  =  0.002 518), sigma (p  =  0.002 781), uniformity (p  =  0.032 41), and entropy (p  =  0.006 685). The highest classification accuracy was 79% by the logistic classifier. The performance metrics of this logistic classification model was 0.80 for the positive predictive value, 0.36 for the false-positive rate, and 0.80 for the area under the receiver operating characteristic curve. Our approach of direct risk classification supervised by the pathological diagnosis with localized thin-section CT and radiomics feature extraction may support clinical physicians in determining truly malignant nodules and therefore reduce problems in lung cancer screening.

Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.

PubMed

Rasmussen, Thomas A; McMahon, James; Chang, J Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J; Van Der Weyden, Carrie; Prince, H Miles; Cameron, Paul U; Lewin, Sharon R

2017-08-24

To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4 T cells. Case report. Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4 T cells, in sorted malignant and nonmalignant CD4 T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. HIV-hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4 T cells, consistent with expansion of a noninfected CD4 T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4 T cells. Finally, alemtuzumab decreased HIV-DNA in CD4 T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4 T cells. Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4 T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.

Localized thin-section CT with radiomics feature extraction and machine learning to classify early-detected pulmonary nodules from lung cancer screening.

PubMed

Tu, Shu-Ju; Wang, Chih-Wei; Pan, Kuang-Tse; Wu, Yi-Cheng; Wu, Chen-Te

2018-03-14

Lung cancer screening aims to detect small pulmonary nodules and decrease the mortality rate of those affected. However, studies from large-scale clinical trials of lung cancer screening have shown that the false-positive rate is high and positive predictive value is low. To address these problems, a technical approach is greatly needed for accurate malignancy differentiation among these early-detected nodules. We studied the clinical feasibility of an additional protocol of localized thin-section CT for further assessment on recalled patients from lung cancer screening tests. Our approach of localized thin-section CT was integrated with radiomics features extraction and machine learning classification which was supervised by pathological diagnosis. Localized thin-section CT images of 122 nodules were retrospectively reviewed and 374 radiomics features were extracted. In this study, 48 nodules were benign and 74 malignant. There were nine patients with multiple nodules and four with synchronous multiple malignant nodules. Different machine learning classifiers with a stratified ten-fold cross-validation were used and repeated 100 times to evaluate classification accuracy. Of the image features extracted from the thin-section CT images, 238 (64%) were useful in differentiating between benign and malignant nodules. These useful features include CT density (p  =  0.002 518), sigma (p  =  0.002 781), uniformity (p  =  0.032 41), and entropy (p  =  0.006 685). The highest classification accuracy was 79% by the logistic classifier. The performance metrics of this logistic classification model was 0.80 for the positive predictive value, 0.36 for the false-positive rate, and 0.80 for the area under the receiver operating characteristic curve. Our approach of direct risk classification supervised by the pathological diagnosis with localized thin-section CT and radiomics feature extraction may support clinical physicians in determining truly malignant nodules and therefore reduce problems in lung cancer screening.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

PubMed

Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

2017-04-01

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

Laser micro-dissection and qPCR for identifying specific HPV types responsible for malignancy in penile lesions.

PubMed

Lebelo, Ramokone L; Thys, Sofie; Benoy, Ina; Depuydt, Christophe E; Bogers, John-Paul; Bida, Meshack N; Mphahlele, M Jeffrey

2015-10-01

The aim of the study was to identify specific human papillomavirus (HPV) type responsible for malignancy in penile tissue samples using laser micro-dissection and TaqMan quantitative real-time PCR (qPCR). The study was based on two pre-malignant and seven malignant penile tissue samples and laser micro-dissection was performed on all. Genotyping was performed on whole tissue sections and laser micro-dissection samples using qPCR. Two whole tissue section samples were HPV negative while seven were HPV positive. In four samples that were single HPV infections with whole tissue section PCR, identical HPV types were confirmed with laser micro-dissection PCR. Clearly confirming that the single HPV type detected is responsible for malignancy. In two samples that had multiple HPV infections with whole tissue section PCR, only one HPV type with the highest viral load was detected with laser micro-dissection PCR, suggesting that the HPV type with the highest viral load is most likely the cause of that particular lesion. HPV 11 and/or HPV 16 were the only types detected with laser micro-dissection PCR in these cases, compared to multiple HPV types (HPV 11, HPV 16, HPV 18, HPV 31, HPV 33, HPV 35, and HPV 39) initially detected with whole tissue section PCR. HPV 11 was associated with verrucous lesions while HPV 16 was associated with squamous cell carcinoma and PIN 3 lesions. This study confirms that laser micro-dissection and qPCR are essential tools in identifying the HPV types responsible for malignancy in penile lesions, particularly in samples with multiple infections. © 2015 Wiley Periodicals, Inc.

Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report from the Childhood Cancer Survivor Study

PubMed Central

Ellenberg, Leah; Liu, Qi; Gioia, Gerard; Yasui, Yutaka; Packer, Roger J.; Mertens, Ann; Donaldson, Sarah S.; Stovall, Marilyn; Kadan-Lottick, Nina; Armstrong, Gregory; Robison, Leslie L.; Zeltzer, Lonnie K.

2009-01-01

Background Among survivors of childhood cancer, those with Central Nervous System (CNS) malignancies have been found to be at greatest risk for neuropsychological dysfunction in the first few years following diagnosis and treatment. This study follows survivors to adulthood to assess the long term impact of childhood CNS malignancy and its treatment on neurocognitive functioning. Participants & Methods As part of the Childhood Cancer Survivor Study (CCSS), 802 survivors of childhood CNS malignancy, 5937 survivors of non-CNS malignancy and 382 siblings without cancer completed a 25 item Neurocognitive Questionnaire (CCSS-NCQ) at least 16 years post cancer diagnosis assessing task efficiency, emotional regulation, organizational skills and memory. Neurocognitive functioning in survivors of CNS malignancy was compared to that of non-CNS malignancy survivors and a sibling cohort. Within the group of CNS malignancy survivors, multiple linear regression was used to assess the contribution of demographic, illness and treatment variables to reported neurocognitive functioning and the relationship of reported neurocognitive functioning to educational, employment and income status. Results Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all factors assessed by the CCSS-NCQ than non-CNS cancer survivors or siblings (p<.01), with mean T scores of CNS malignancy survivors substantially more impaired that those of the sibling cohort (p<.001), with a large effect size for Task Efficiency (1.16) and a medium effect size for Memory (.68). Within the CNS malignancy group, medical complications, including hearing deficits, paralysis and cerebrovascular incidents resulted in a greater likelihood of reported deficits on all of the CCSS-NCQ factors, with generally small effect sizes (.22-.50). Total brain irradiation predicted greater impairment on Task Efficiency and Memory (Effect sizes: .65 and .63, respectively), as did partial brain irradiation, with smaller effect sizes (.49 and .43, respectively). Ventriculoperitoneal (VP) shunt placement was associated with small deficits on the same scales (Effect sizes: Task Efficiency .26, Memory .32). Female gender predicted a greater likelihood of impaired scores on 2 scales, with small effect sizes (Task Efficiency .38, Emotional Regulation .45), while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor with a moderate effect size (.64). CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p<.01), less household income (p<.001) and less full time employment (p<.001). Conclusions Survivors of childhood CNS malignancy are at significant risk for impairment in neurocognitive functioning in adulthood, particularly if they have received cranial radiation, had a VP shunt placed, suffered a cerebrovascular incident or are left with hearing or motor impairments. Reported neurocognitive impairment adversely affected important adult outcomes, including education, employment, income and marital status. PMID:19899829

Fingolimod in relapsing multiple sclerosis: An integrated analysis of safety findings.

PubMed

Kappos, Ludwig; Cohen, Jeffrey; Collins, William; de Vera, Ana; Zhang-Auberson, Lixin; Ritter, Shannon; von Rosenstiel, Philipp; Francis, Gordon

2014-07-01

Fingolimod 0.5mg once daily is the first approved oral therapy for relapsing multiple sclerosis (MS). To report integrated long-term safety data from phase 2/3 fingolimod studies. Descriptive safety data are reported from the FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study, a 24-month, randomized, double-blind study comparing fingolimod 0.5mg and 1.25mg with placebo, and an All Studies group (patients who received fingolimod 0.5mg (n=1640) or 1.25-0.5mg (n=1776) in phase 2/3 studies and associated extensions). Relevant post-marketing experience, up to December 2011, is included. The incidence of adverse events (AEs) and serious AEs (SAEs) was similar with fingolimod and placebo in FREEDOMS. In the All Studies group, fingolimod 0.5mg was associated with transient, rarely symptomatic (0.5%), bradycardia and second-degree atrioventricular block on treatment initiation, minor blood pressure increases, frequent (9%) but generally asymptomatic liver enzyme elevations, and macular oedema (0.4%). The incidences of infections (including serious and herpes infections), malignancies, SAEs and treatment discontinuations due to AEs were similar with fingolimod 0.5mg and placebo. The safety profile of fingolimod has been well characterized in this large combined trial population. Although infrequent SAEs can occur, there is no increased risk of infections, malignancies or serious cardiovascular events versus placebo. Copyright © 2014. Published by Elsevier B.V.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

PubMed Central

Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

2012-01-01

We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present. PMID:24213321

Comb-push ultrasound shear elastography of breast masses: initial results show promise.

PubMed

Denis, Max; Mehrmohammadi, Mohammad; Song, Pengfei; Meixner, Duane D; Fazzio, Robert T; Pruthi, Sandhya; Whaley, Dana H; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

2015-01-01

To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young's modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses.

Predicting ovarian malignancy: application of artificial neural networks to transvaginal and color Doppler flow US.

PubMed

Biagiotti, R; Desii, C; Vanzi, E; Gacci, G

1999-02-01

To compare the performance of artificial neural networks (ANNs) with that of multiple logistic regression (MLR) models for predicting ovarian malignancy in patients with adnexal masses by using transvaginal B-mode and color Doppler flow ultrasonography (US). A total of 226 adnexal masses were examined before surgery: Fifty-one were malignant and 175 were benign. The data were divided into training and testing subsets by using a "leave n out method." The training subsets were used to compute the optimum MLR equations and to train the ANNs. The cross-validation subsets were used to estimate the performance of each of the two models in predicting ovarian malignancy. At testing, three-layer back-propagation networks, based on the same input variables selected by using MLR (i.e., women's ages, papillary projections, random echogenicity, peak systolic velocity, and resistance index), had a significantly higher sensitivity than did MLR (96% vs 84%; McNemar test, p = .04). The Brier scores for ANNs were significantly lower than those calculated for MLR (Student t test for paired samples, P = .004). ANNs might have potential for categorizing adnexal masses as either malignant or benign on the basis of multiple variables related to demographic and US features.

A simple and robust classification tree for differentiation between benign and malignant lesions in MR-mammography.

PubMed

Baltzer, Pascal A T; Dietzel, Matthias; Kaiser, Werner A

2013-08-01

In the face of multiple available diagnostic criteria in MR-mammography (MRM), a practical algorithm for lesion classification is needed. Such an algorithm should be as simple as possible and include only important independent lesion features to differentiate benign from malignant lesions. This investigation aimed to develop a simple classification tree for differential diagnosis in MRM. A total of 1,084 lesions in standardised MRM with subsequent histological verification (648 malignant, 436 benign) were investigated. Seventeen lesion criteria were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. A classification tree incorporating 5 lesion descriptors with a depth of 3 ramifications (1, root sign; 2, delayed enhancement pattern; 3, border, internal enhancement and oedema) was calculated. Of all 1,084 lesions, 262 (40.4 %) and 106 (24.3 %) could be classified as malignant and benign with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 88.4 %. The classification algorithm reduced the number of categorical descriptors from 17 to 5 (29.4 %), resulting in a high classification accuracy. More than one third of all lesions could be classified with accuracy above 95 %. • A practical algorithm has been developed to classify lesions found in MR-mammography. • A simple decision tree consisting of five criteria reaches high accuracy of 88.4 %. • Unique to this approach, each classification is associated with a diagnostic certainty. • Diagnostic certainty of greater than 95 % is achieved in 34 % of all cases.

Retrograde pyelography predicts retrograde ureteral stenting failure and reduces unnecessary stenting trials in patients with advanced non-urological malignant ureteral obstruction

PubMed Central

Kim, Sung Han; Park, Boram; Joo, Jungnam; Joung, Jae Young; Seo, Ho Kyung; Chung, Jinsoo; Lee, Kang Hyun

2017-01-01

Objective To evaluate predictive factors for retrograde ureteral stent failure in patients with non-urological malignant ureteral obstruction. Materials and methods Between 2005 and 2014, medical records of 284 malignant ureteral obstruction patients with 712 retrograde ureteral stent trials including 63 (22.2%) having bilateral malignant ureteral obstruction were retrospectively reviewed. Retrograde ureteral stent failure was defined as the inability to place ureteral stents by cystoscopy, recurrent stent obstruction within one month, or non-relief of azotemia within one week from the prior retrograde ureteral stent. The clinicopathological parameters and first retrograde pyelographic findings were analyzed to investigate the predictive factors for retrograde ureteral stent failure and conversion to percutaneous nephrostomy in multivariate analysis with a statistical significance of p < 0.05. Results Retrograde ureteral stent failure was detected in 14.1% of patients. The mean number of retrograde ureteral stent placements and indwelling duration of the ureteral stents were 2.5 ± 2.6 times and 8.6 ± 4.0 months, respectively. Multivariate analyses identified several specific RGP findings as significant predictive factors for retrograde ureteral stent failure (p < 0.05). The significant retrograde pyelographic findings included grade 4 hydronephrosis (hazard ratio 4.10, 95% confidence interval 1.39–12.09), irreversible ureteral kinking (hazard ratio 2.72, confidence interval 1.03–7.18), presence of bladder invasion (hazard ratio 4.78, confidence interval 1.81–12.63), and multiple lesions of ureteral stricture (hazard ratio 3.46, confidence interval 1.35–8.83) (p < 0.05). Conclusion Retrograde pyelography might prevent unnecessary and ineffective retrograde ureteral stent trials in patients with advanced non-urological malignant ureteral obstruction. PMID:28931043

Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

ClinicalTrials.gov

2016-02-18

Breast Cancer; Hypercalcemia of Malignancy; Colon Cancer; Endocrine Cancer; Head and Neck Cancer; Kidney Cancer; Lung Cancer; Lymphoma; Metastatic Cancer; Multiple Myeloma; Parathyroid Neoplasms; Renal Cancer; Thyroid Cancer; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Non-Small Cell Lung Cancer

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study.

PubMed

Cook, S; Vermersch, P; Comi, G; Giovannoni, G; Rammohan, K; Rieckmann, P; Sørensen, P Soelberg; Hamlett, A; Miret, M; Weiner, J; Viglietta, V; Musch, B; Greenberg, S J

2011-05-01

Cladribine is a synthetic deoxyadenosine analogue in development as an oral multiple sclerosis (MS) therapy. To report in detail the safety findings from the 96-week, phase III, double-blind CLARITY study, which evaluated treatment with cladribine tablets in relapsing-remitting MS. A total of 1,326 patients were randomized 1:1:1 to two short-course regimens of cladribine tablets (3.5 or 5.25 mg/kg cumulative dose over 96 weeks) or placebo. Safety assessments included monitoring for adverse events (AEs), routine physical and neurologic examinations and frequent laboratory parameter assessments. Of the randomized patients, 88.6% completed treatment with cladribine tablets versus 86.3% with placebo. Lymphopenia was the most commonly reported AE in patients treated with cladribine tablets and was anticipated based on the mechanism of action. The incidence of infections was 48.3% with cladribine tablets and 42.5% with placebo, with 99.1% and 99.0% rated mild-to-moderate by investigators. Herpes zoster infections developed in 20 (2.3%) cladribine-treated patients; all cases were dermatomal. There were no herpes zoster infections in the placebo group. Nine (1.0%) patients experienced events related to uterine leiomyomas in the cladribine tablets groups versus one (0.2%) with placebo. Three isolated cases of malignancy were reported in cladribine-treated patients during the study; a fourth was reported during post-study surveillance. A pre-malignant cervical carcinoma in situ was also reported. The incidence of malignancies during the study did not exceed the expected rate in a population standardized for country, gender and age. The safety and tolerability profile observed in the CLARITY study together with the reported efficacy support the potential for cladribine tablets as an MS therapy.

Long Non-Coding RNAs in Multiple Myeloma

PubMed Central

Ronchetti, Domenica; Taiana, Elisa; Vinci, Cristina; Neri, Antonino

2018-01-01

Multiple myeloma (MM) is an incurable disease caused by the malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Although a large fraction of the genome is actively transcribed, most of the transcripts do not serve as templates for proteins and are referred to as non-coding RNAs (ncRNAs), broadly divided into short and long transcripts on the basis of a 200-nucleotide threshold. Short ncRNAs, especially microRNAs, have crucial roles in virtually all types of cancer, including MM, and have gained importance in cancer diagnosis and prognosis, predicting the response to therapy and, notably, as innovative therapeutic targets. Long ncRNAs (lncRNAs) are a very heterogeneous group, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis, and invasion. LncRNAs are aberrantly expressed in various types of cancers, including hematological malignancies, showing either oncogenic or tumor suppressive functions. However, the mechanisms of the related disease-causing events are not yet revealed in most cases. Besides emerging as key players in cancer initiation and progression, lncRNAs own many interesting features as biomarkers with diagnostic and prognostic importance and, possibly, for their utility in therapeutic terms as druggable molecules. This review focuses on the role of lncRNAs in the pathogenesis of MM and summarizes the recent literature. PMID:29389884

Targeted therapy of multiple myeloma.

PubMed

Dolloff, Nathan G; Talamo, Giampaolo

2013-01-01

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

A Rare Case of Multiple Myeloma with Biclonal Gammopathy.

PubMed

Banerjee, Abhik; Pimpalgaonkar, Kshama; Christy, Alap Lukiyas

2016-12-01

Multiple myeloma is a debilitating malignancy arising from plasma cells. These malignant plasma cells called myeloma cells proliferate and infiltrate the bone marrow. The disease is characterized by the presence of a monoclonal protein in plasma and/or the urine. In this report, we present a case of biclonal multiple myeloma which showed two M bands on serum protein electrophoresis. The patient had elevated serum IgA and IgG levels. To reveal the nature of M bands or clonality, serum Immunofixation study was performed which revealed IgA with Lambda and IgG with Kappa light chains. Such pattern is very rare if we consider the various immunofixation patterns observed in different gammopathies.

A Rare Case of Multiple Myeloma with Biclonal Gammopathy

PubMed Central

Banerjee, Abhik; Christy, Alap Lukiyas

2016-01-01

Multiple myeloma is a debilitating malignancy arising from plasma cells. These malignant plasma cells called myeloma cells proliferate and infiltrate the bone marrow. The disease is characterized by the presence of a monoclonal protein in plasma and/or the urine. In this report, we present a case of biclonal multiple myeloma which showed two M bands on serum protein electrophoresis. The patient had elevated serum IgA and IgG levels. To reveal the nature of M bands or clonality, serum Immunofixation study was performed which revealed IgA with Lambda and IgG with Kappa light chains. Such pattern is very rare if we consider the various immunofixation patterns observed in different gammopathies. PMID:28208846

Disseminated Pleural Siliconoma Mimicking Malignant Pleural Mesothelioma.

PubMed

Tanaka, Toshiki; Tao, Hiroyuki; Hayashi, Tatsuro; Yoshiyama, Koichi; Furukawa, Masashi; Yoshida, Kumiko; Okabe, Kazunori

2015-12-01

A 48-year-old woman with a 3-month history of back pain was admitted for further examination of multiple left pleural nodules. She had undergone bilateral breast augmentation with silicone implants 10 years previously. Nine years after the operation, both ruptured implants were removed, and autologous fat was injected. Computed tomography revealed multiple pleural nodules suggestive of malignant pleural mesothelioma. Thoracoscopic exploration revealed multiple pleural nodules with massive pleural adhesions. The nodules were filled with viscous liquid and were histologically determined to be siliconomas. Disseminated pleural siliconoma should be recognized as a late adverse event of silicone breast implantation. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Study of MGUS, Smoldering Myeloma, Early MDS and CLL to Assess Molecular Events of Progression and Clinical Outcome

ClinicalTrials.gov

2017-08-25

Monoclonal Gammopathy of Undetermined Significance (MGUS); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic-Myeloproliferative Diseases; Hematological Malignancies; B-cell Malignancy, Low-grade; Myelodysplastic Syndrome With Low-grade Lesions; IgG Monoclonal Gammopathy of Uncertain Significance; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia

Venetoclax: A First-in-Class Oral BCL-2 Inhibitor for the Management of Lymphoid Malignancies.

PubMed

King, Amber C; Peterson, Tim J; Horvat, Troy Z; Rodriguez, Mabel; Tang, Laura A

2017-05-01

To review the pharmacology, efficacy, and safety of venetoclax for treatment of lymphoid malignancies. A literature search was performed of PubMed and MEDLINE databases (2005 to September 2016), abstracts from the American Society of Hematology and the American Society of Clinical Oncology, and ongoing studies from clinicaltrials.gov. Searches were performed utilizing the following key terms: venetoclax, ABT-199, GDC-199, obatoclax, GX15-070, BCL-2 inhibitor, navitoclax, ABT-263, and Venclexta. Studies of pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of venetoclax in lymphoid malignancies were identified. Recently, treatment of B-cell lymphoproliferative disorders has shifted from conventional cytotoxic chemotherapy to novel small-molecule inhibitors. The advent of recently Food and Drug Administration-approved oral agents ibrutinib and idelalisib has shifted the paradigm of chronic lymphocytic leukemia (CLL) treatment; however, complete remission is uncommon, and the outcome for patients progressing on these treatments remains poor. Attention has been focused on a novel target, the B-cell lymphoma-2 protein (BCL-2), which serves an essential role in regulation of apoptosis. Venetoclax has demonstrated efficacy in multiple subtypes of lymphoid malignancies, including patients with relapsed/refractory CLL harboring deletion 17p, with an overall response rate of nearly 80%. Venetoclax is generally well tolerated, with the significant adverse effect being tumor lysis syndrome, for which there are formal management recommendations. Venetoclax has demonstrated promising results in relapsed/refractory lymphoid malignancies, with an acceptable adverse effect profile. As the role of BCL-2 inhibition in various malignancies becomes further elucidated, venetoclax may offer benefit to a myriad other patient populations.

High frequency of telomeric association in a family with multiple congenital neoplasia.

PubMed

Dhaliwal, M K; Satya-Prakash, K L; Davis, P C; Pathak, S

1994-01-01

Chromosomal analysis of the peripheral blood cultures of a married couple whose second pregnancy gave birth to twin daughters with multiple congenital malignancies revealed normal karyotypes of 46,XX and 46,XY, respectively. However, in the father's blood, 23.3% of metaphases showed telomere-telomere associations involving single-single and double-double chromatids. Such associations were not observed in the metaphases of the mother. We speculate from these observations that the father's genotype may somehow be responsible for the congenital malignancies in their twin daughters.

Novel Medical Strategies Combating Nonmelanoma Skin Cancer

PubMed Central

Bhandari, Prasan R; Pai, Varadraj V

2014-01-01

The incidence of nonmelanoma skin cancer (NMSC) continues to rise, partly because of aging, the frequency of early childhood sunburns, and sporadic extreme recreational sun exposure. A nonsurgical approach to selected cutaneous malignancy could possibly reduce the cost as well as morbidity of surgical treatment for NMSC. There has been growing interest in isolating compounds that could suppress or reverse the biochemical changes necessary for cutaneous malignancies to progress by pharmacologic intervention. By targeting diverse pathways recognized as important in the pathogenesis of nonmelanoma skin cancers, a combination approach with multiple agents or addition of chemopreventative agents to topical sunscreens may offer the potential for novel and synergistic therapies in treating nonmelanoma skin cancer. This preliminary information will expand to include more therapeutic options for NMSC in the future. PMID:25484380

Prevalence of monoclonal gammopathy of undetermined significance in Asia: a viewpoint from nagasaki atomic bomb survivors.

PubMed

Iwanaga, Masako; Tomonaga, Masao

2014-02-01

Exposure to ionizing radiation is a known environmental risk factor for a variety of cancers including hematological malignancies, such as leukemia, myelodysplastic syndromes, and multiple myeloma. Therefore, for Hiroshima and Nagasaki atomic bomb survivors (surviving victims who were exposed to ionizing radiation emitted from the nuclear weapons), several cancer-screening tests have been provided annually, with government support, to detect the early stage of malignancies. An M-protein screening test has been used to detect multiple myeloma at an early stage among atomic bomb survivors. In the screening process, a number of patients with monoclonal gammopathy of undetermined significance (MGUS), in addition to multiple myeloma, have been identified. In 2009 and 2011, we reported the age- and sex-specific prevalence of MGUS between 1988 and 2004 and the possible role of radiation exposure in the development of MGUS using the screening data of more than 1000 patients with MGUS among approximately 52,000 Nagasaki atomic bomb survivors. The findings included: (1) a significant lower overall prevalence (2.1%) than that observed in Caucasian or African-origin populations; (2) a significantly higher prevalence in men than in women; (3) an age-related increase in the prevalence; (4) a significantly higher prevalence in people exposed to higher radiation doses only among those exposed at age 20 years or younger; and (5) a lower frequency of immunoglobulin M MGUS in Japanese patients than in patients in Western countries. The large study of MGUS among Nagasaki atomic bomb survivors has provided important findings for the etiology of MGUS, including a possible role of radiation exposure on the cause of MGUS and an ethnicity-related difference in the characteristics of MGUS. Copyright © 2014 Elsevier Inc. All rights reserved.

Castleman's Disease: An Interesting Cause of Hematuria.

PubMed

Tolofari, Sotonye Karl; Chow, Wai-Man; Hussain, Basharat

2015-03-01

Castleman's disease is a rare benign lymphoproliferative disorder, characterized by benign growths of the lymph node tissue. It is associated with a number of malignancies, including Kaposi sarcoma, non-Hodgkin's and Hodgkins lymphoma, and POEMS syndrome. This report describes the case of a 38 year old gentleman, presenting with painless hematuria. Initial investigations, including flexible cystoscopy were unremarkable. However, subsequent imaging including CT Urogram and MR pelvis revealed multiple prevesical lesions. Histology obtained from excision biopsy revealed histological features consistent with Castleman's disease. In this report we discuss the nature, presentation and treatment modalities of this rare condition.

Non-epithelial malignancies and metastatic tumours of the breast

PubMed Central

O'Donnell, Mark E; McCavert, Mark; Carson, Jim; Mullan, Fred J; Whiteside, Michael W; Garstin, W Ian

2009-01-01

Introduction Non-epithelial breast malignancies include primary lymphomas, sarcomas, haematological malignancies, melanomas as well as secondary metastases to the breast. They account for less than 1% of all breast tumours. The demographics and clinical features are similar to epithelial breast cancers but the prognosis and management options are often very different. Most reported series are small with limited follow-up. The main aim of this study was to review our experience for these malignancies and to compare this with the published literature. Methods A 14-year retrospective review of all breast resection specimens was completed in the Antrim Area Hospital Cancer Unit. Clinical records of patients diagnosed with non-epithelial breast malignancies were then reviewed for data regarding patient demographics, clinical presentation, pre-operative investigations, operative findings and outcome. Pathology reports were examined carefully for tumour type, location and for evidence of lymphovascular spread. This data was compared with the available literature. Results Nineteen (F = 16) patients were found to have non-epithelial breast malignancies between April 1994 and August 2007. Mean age was 61.6 years (range 25–86). 17 patients (89.5%) presented with a palpable lump, mastalgia or skin change, while 2 (10.5%) patients' tumours were detected through screening. The histological types of non-epithelial malignancies were as follows: lymphoma (n = 8; M = 1 and F = 7, mean age: 68.5 range 52–86), sarcoma (n = 5; M = 1 and F = 4, mean age 56.4 range 29–69), malignant melanoma (n = 3; M = 1 and F = 2, mean age 54.3 range 25–70), multiple myeloma (n = 1; F, 71), metastatic renal cell carcinoma (n = 1; F, 63) and metastatic carcinoid tumour (n = 1; F, 52). The mean follow-up was 1541 days (32–4589 days). Nine patients were alive at the end of follow-up. Only 1 of 11 deaths was not directly related to the malignancy. The average time from surgery to death was 798.5 days (range 32–3248 days). Conclusion Non-epithelial breast malignancies are rare cancers with significant mortality rates. Correct diagnosis and avoidance of inappropriate therapies requires a comprehensive triple assessment and a multidisciplinary management approach. PMID:19568446

Diagnosis and management of malignant pleural effusions: state of the art in 2017

PubMed Central

Lee, Hans J.

2017-01-01

Malignant pleural effusion (MPE) is a known complication of both thoracic and extra thoracic malignancies. The presence of MPE regardless of the primary site translates into advanced stage disease. Diagnosis and management of MPE with the goals of palliation and improving quality of life poses a challenge for chest physicians. Recently, multiple studies have made attempts to answer questions regarding optimal management in various clinical scenarios. We will review the current evidence and available options for the management of MPE. PMID:29214068

Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

PubMed

Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

2015-09-01

Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies.

PubMed

Chang, Ellen T; Boffetta, Paolo; Adami, Hans-Olov; Mandel, Jack S

2015-04-01

Establishing a causal relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and risk of specific lymphoid cancers, including non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM), would be useful for risk assessment. This article systematically and critically reviews epidemiologic studies of the association between exposure to TCDD or TCDD-contaminated herbicides and risk of lymphoid malignancies. These include studies of military, industrial, accidental environmental, and general environmental exposure to Agent Orange or TCDD. Collectively, the epidemiologic evidence from industrial cohorts suggests a positive association with NHL mortality, but results are not consistent across other studies, a clear exposure-response gradient is not evident, and data are insufficient to conclude that the association is causal. Furthermore, available studies provide little information on NHL incidence or specific NHL subtypes. Epidemiologic studies do not show an association of TCDD exposure with HL, whereas the indication of a positive association with MM in a limited number of studies, but not others, remains to be confirmed in additional research. Exposure classification error and small numbers are important limitations of the available epidemiologic studies. Overall, a causal effect of TCDD on NHL, HL, MM, or subtypes of these lymphoid malignancies has not been established. Copyright © 2015 Elsevier Inc. All rights reserved.

Nutritionally Variant Streptococci Bacteremia in Cancer Patients: A Retrospective Study, 1999–2014

PubMed Central

Yacoub, Abraham T.; Krishnan, Jayasree; Acevedo, Ileana M.; Halliday, Joseph; Greene, John N.

2015-01-01

Background Nutritionally variant Streptococci (NVS), Abiotrophia and Granulicatella are implicated in causing endocarditis and blood stream infections more frequently than other sites of infection. Neutropenia and mucositis are the most common predisposing factors for infection with other pathogens in cancer patients. In this study, we investigated the clinical characteristics of NVS bacteremia in cancer patients and identified risk factors and outcomes associated with these infections. Materials and Methods We retrospectively reviewed all cases of NVS bacteremia occurring from June 1999 to April 2014 at H. Lee Moffitt Cancer Center and Research Institute. The computerized epidemiology report provided by the microbiology laboratory identified thirteen cancer patients with NVS bacteremia. We collected data regarding baseline demographics and clinical characteristics such as age, sex, underlying malignancy, neutropenic status, duration of neutropenia, treatment, and outcome. Results Thirteen patients were identified with positive NVS blood stream infection. Ten patients (77%) had hematologic malignancies, including chronic lymphocytic leukemia (CLL)(1), multiple myeloma (MM)(1), acute myelogenous leukemia (AML)(4), and non-Hodgkin’s lymphoma (NHL)(4). The non-hematologic malignancies included esophageal cancer(2) and bladder cancer (1). Conclusion NVS should be considered as a possible agent of bacteremia in cancer patients with neutropenia and a breach in oral, gastrointestinal and genitourinary mucosa (gingivitis/mucositis). PMID:25960858

Pleural effusion in 11:14 translocation q1 multiple myeloma in the setting of proteasome inhibitor presents therapeutic complexity.

PubMed

Ghannam, Malik; Bryan, Maria; Kuross, Erik; Berry, Brent

2018-01-01

Primary malignant pleural effusion has been reported in about 134 cases of multiple myeloma (MM). Associated pleural effusions in cases of MM portend a poor prognosis and identifying them is highly relevant. Reported is the case of a man diagnosed with MM who developed primary myelomatous pleural effusion in the setting of multiple relapses and subsequent mortality within 2 months of the pleural effusion diagnosis. A 61-year-old African American man was diagnosed with MM in 2011. He received induction therapy of lenalidomide and dexamethasone and an autologous stem cell transplant in 2012. Over the next 5 years, the patient went through alternating periods of remission and relapse that were treated with two rounds of thoracic spine radiation therapy and chemotherapeutic agents. In September 2017, the patient presented with worsening dyspnea and was found to have pleural effusion. Fluid analysis showed plasma cell dyscrasia. Fluid drainage was performed, then the patient was discharged after 1 week which was followed by rapid re-accumulation of fluid and rehospitalization about 10 days after discharge. The patient passed away a few weeks after the second admission. Pleural effusion carries a differential diagnosis which may include malignancy but is commonly thought to be less specific to multiple myeloma but should still remain in the differential diagnosis. To our knowledge, this is the first case of myelomatous pleural effusion (MPE) that was reported after multiple relapses of MM. MPE is a very rare complication of MM, and its presence is a strong indicator of imminent mortality and need for comfort care in case of multiple relapses. End-stage pleural effusion in MM in the setting of proteasome inhibitor adds more therapeutic and diagnostic challenges.

Reliability of Frozen Section Examination in a Large Cohort of Testicular Masses: What Did We Learn?

PubMed

Matei, Deliu Victor; Vartolomei, Mihai Dorin; Renne, Giuseppe; Tringali, Valeria Maria Lucia; Russo, Andrea; Bianchi, Roberto; Cozzi, Gabriele; Bottero, Danilo; Musi, Gennaro; Mazzarol, Giovanni; Ferro, Matteo; de Cobelli, Ottavio

2017-08-01

Frozen section examination (FSE) for testicular masses is gaining popularity because of the possibility of performing testis-sparing surgery (TSS) on the basis of the FSE results. The aim of our study was to investigate the reliability of FSE in the diagnosis of testicular masses. From 1999 to 2016, 144 of 692 patients who underwent surgery in our tertiary center for testicular masses had FSE. The indications for FSE were: masses < 1 cm, nonpalpable, multiple, or with unusual presentation. Mean follow-up for patients was 25.5 months. The algorithm of surgery determined by FSE was: orchiectomy if malignant or nonconclusive pathology; TSS if benign or nontumor pathology. FSE data were analyzed retrospectively. Specificity and sensitivity of the method was calculated for benign, malignant, seminoma, and nonseminoma tumors. Intraoperative FSE was conducted on 21% of candidates for surgery on testicular masses. The sensitivity and specificity of FSE were 93% and 98%, respectively, for malignant tumors, and 90% and 99%, respectively, for benign tumors. The κ agreement coefficient between FSE and final histopathology was statistically significant (0.76). TSS was performed in 57 (40%) patients, including 6 of 23 monorchid patients. FSE correlates well with final histopathological diagnosis of testicular masses. Thus, it reliably identifies patients who might benefit from TSS. FSE should be considered always in small, nonpalpable, multiple, or uncommonly presenting masses in solitary testis or both testes. Copyright © 2017 Elsevier Inc. All rights reserved.

Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry.

PubMed

Alomari, Ahmed K; Glusac, Earl J; Choi, Jennifer; Hui, Pei; Seeley, Erin H; Caprioli, Richard M; Watsky, Kalman L; Urban, Jennifer; Lazova, Rossitza

2015-10-01

A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration. Following induction of labor, the patient underwent re-excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies.

PubMed

Qiu, Jianguo; Chen, Shuting; Wu, Hong

2014-05-01

Hepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). Data from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed. A total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively. HRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data. Copyright © 2014 Elsevier Inc. All rights reserved.

Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies

ClinicalTrials.gov

2018-03-26

Acute Lymphoblastic Leukemia; Burkitt Lymphoma; Natural Killer Cell Malignancies; Chronic Myelogenous Leukemia; Myelodysplastic Syndromes; Large-cell Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone B-Cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Leukemia; Hodgkin Lymphoma; Multiple Myeloma; Acute Myelogenous Leukemia; Biphenotypic Leukemia; Undifferentiated Leukemia

The role of Epstein–Barr virus in epithelial malignancies

PubMed Central

Tsao, Sai-Wah; Tsang, Chi Man; To, Ka-Fai; Lo, Kwok-Wai

2015-01-01

The close association of Epstein–Barr virus (EBV) infection with non-keratinizing nasopharyngeal carcinomas and a subset of gastric carcinomas suggests that EBV infection is a crucial event in these cancers. The difficulties encountered in infecting and transforming primary epithelial cells in experimental systems suggest that the role of EBV in epithelial malignancies is complex and multifactorial in nature. Genetic alterations in the premalignant epithelium may support the establishment of latent EBV infection, which is believed to be an initiation event. Oncogenic properties have been reported in multiple EBV latent genes. The BamH1 A rightwards transcripts (BARTs) and the BART-encoded microRNAs (miR-BARTs) are highly expressed in EBV-associated epithelial malignancies and may induce malignant transformation. However, enhanced proliferation may not be the crucial function of EBV infection in epithelial malignancies, at least in the early stages of cancer development. EBV-encoded gene products may confer anti-apoptotic properties and promote the survival of infected premalignant epithelial cells harbouring genetic alterations. Multiple EBV-encoded microRNAs have been reported to have immune evasion functions. Genetic alterations in host cells, as well as inflammatory stroma, could modulate the expression of EBV genes and alter the growth properties of infected premalignant epithelial cells, encouraging their selection during carcinogenesis. PMID:25251730

Change descriptors for determining nodule malignancy in national lung screening trial CT screening images

NASA Astrophysics Data System (ADS)

Geiger, Benjamin; Hawkins, Samuel; Hall, Lawrence O.; Goldgof, Dmitry B.; Balagurunathan, Yoganand; Gatenby, Robert A.; Gillies, Robert J.

2016-03-01

Pulmonary nodules are effectively diagnosed in CT scans, but determining their malignancy has been a challenge. The rate of change of the volume of a pulmonary nodule is known to be a prognostic factor for cancer development. In this study, we propose that other changes in imaging characteristics are similarly informative. We examined the combination of image features across multiple CT scans, taken from the National Lung Screening Trial, with individual scans of the same patient separated by approximately one year. By subtracting the values of existing features in multiple scans for the same patient, we were able to improve the ability of existing classification algorithms to determine whether a nodule will become malignant. We trained each classifier on 83 nodules determined to be malignant by biopsy and 172 nodules determined to be benign by their clinical stability through two years of no change; classifiers were tested on 77 malignant and 144 benign nodules, using a set of features that in a test-retest experiment were shown to be stable. An accuracy of 83.71% and AUC of 0.814 were achieved with the Random Forests classifier on a subset of features determined to be stable via test-retest reproducibility analysis, further reduced with the Correlation-based Feature Selection algorithm.

[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.

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.

Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses.

PubMed

Saret, Cayla J; Winn, Aaron N; Shah, Gunjan; Parsons, Susan K; Lin, Pei-Jung; Cohen, Joshua T; Neumann, Peter J

2015-03-19

We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money. © 2015 by The American Society of Hematology.

Raman spectroscopic analysis identifies testicular microlithiasis as intratubular hydroxyapatite.

PubMed

De Jong, B W D; De Gouveia Brazao, C A; Stoop, H; Wolffenbuttel, K P; Oosterhuis, J W; Puppels, G J; Weber, R F A; Looijenga, L H J; Kok, D J

2004-01-01

As diagnosed by ultrasonography, testicular microlithiasis is associated with various benign and malignant conditions. The molecular constitution of these microliths is largely unknown. Raman spectroscopy provides detailed in situ information about the molecular composition of tissues and to our knowledge it has not been applied to gonadal microliths. We analyzed the molecular composition of gonadal microlithiasis and its surrounding region using Raman spectroscopy in malignant and benign conditions. Multiple microliths from 6 independent samples diagnosed with gonadal microlithiasis by ultrasound and histologically confirmed were investigated by Raman spectroscopy. The samples included 4 testicular parenchyma samples adjacent to a germ cell tumor (4 seminomas), a gonadoblastoma of a dysgenetic gonad and testicular biopsy of a subfertile male without malignancy. Raman spectroscopic mapping demonstrated that testicular microliths were located within the seminiferous tubule. Glycogen surrounded all microliths in the samples associated with germ cell neoplasm but not in the benign case. The molecular composition of the 26 microliths in all 6 conditions was pure hydroxyapatite. Microliths in the testis are located in the seminiferous tubules and composed of hydroxyapatite. In cases of germ cell neoplasm they co-localize with glycogen deposits.

Head and neck cancer in transplant recipients.

PubMed

Deeb, Robert; Sharma, Saurabh; Mahan, Meredith; Al-Khudari, Samer; Hall, Francis; Yoshida, Atsushi; Schweitzer, Vanessa

2012-07-01

The development of malignancy in organ transplant patients is a well-known complication of long-term immunosuppressive therapy. We sought to characterize our institution's 20-year experience with head and neck cancer after solid organ transplantation. Retrospective review. Patients who underwent a solid organ transplant with subsequent development of a head and neck malignancy, including cutaneous and noncutaneous (upper aerodigestive tract and salivary gland) cancers, from January 1990 through December 2011 were identified. Patients were stratified according to cancer type, location, stage, and survival and compared to a nontransplant cohort in our institution's tumor registry. Of 95 patients identified, 17 had noncutaneous and 78 had cutaneous head and neck malignancies post-transplant. Among the noncutaneous group, no statistically significant differences occurred in age, gender, stage, or 5-year survival status when compared to the nontransplant tumor registry cohort. However, significantly fewer transplant patients were alive at 1 year. Among the cutaneous group, >50% had multiple malignancies. The total incidence of head and neck cancer following organ transplantation was 2.6%. Although the development of head and neck cancer is a rare side effect of immunosuppression, it still warrants attention. These patients have been found to be less likely to survive >1 year when compared to their nontransplant counterparts. Patients who develop head and neck malignancies following organ transplantation require aggressive screening, treatment, and follow-up, as this diagnosis may portend a poor prognosis. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Comb-Push Ultrasound Shear Elastography of Breast Masses: Initial Results Show Promise

PubMed Central

Song, Pengfei; Fazzio, Robert T.; Pruthi, Sandhya; Whaley, Dana H.; Chen, Shigao; Fatemi, Mostafa

2015-01-01

Purpose or Objective To evaluate the performance of Comb-push Ultrasound Shear Elastography (CUSE) for classification of breast masses. Materials and Methods CUSE is an ultrasound-based quantitative two-dimensional shear wave elasticity imaging technique, which utilizes multiple laterally distributed acoustic radiation force (ARF) beams to simultaneously excite the tissue and induce shear waves. Female patients who were categorized as having suspicious breast masses underwent CUSE evaluations prior to biopsy. An elasticity estimate within the breast mass was obtained from the CUSE shear wave speed map. Elasticity estimates of various types of benign and malignant masses were compared with biopsy results. Results Fifty-four female patients with suspicious breast masses from our ongoing study are presented. Our cohort included 31 malignant and 23 benign breast masses. Our results indicate that the mean shear wave speed was significantly higher in malignant masses (6 ± 1.58 m/s) in comparison to benign masses (3.65 ± 1.36 m/s). Therefore, the stiffness of the mass quantified by the Young’s modulus is significantly higher in malignant masses. According to the receiver operating characteristic curve (ROC), the optimal cut-off value of 83 kPa yields 87.10% sensitivity, 82.61% specificity, and 0.88 for the area under the curve (AUC). Conclusion CUSE has the potential for clinical utility as a quantitative diagnostic imaging tool adjunct to B-mode ultrasound for differentiation of malignant and benign breast masses. PMID:25774978

Reduced-intensity conditioning for the treatment of malignant and life-threatening non-malignant disorders.

PubMed

Slavin, Shimon; Aker, Mehmet; Shapira, Michael Y; Resnick, Igor; Bitan, Menachem; Or, Reuven

2003-01-01

Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an important therapeutic tool for the treatment of an otherwise incurable broad spectrum of malignant and non-malignant diseases. Until recently, BMT was used primarily to replace a malignant, genetically abnormal or deficient immunohematopoietic compartment and therefore, highly toxic myeloablative regimens were considered mandatory for more effective eradication of all undesirable host-derived hematopoietic cells, including stem cells and their progeny. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells can be mediated by donor lymphocytes in the process of adoptive allogeneic cell therapy following BMT. Thus, eradication of all malignant cells, especially in patients with CML and, to a lesser extent, in patients with other hematologic malignancies can be accomplished despite complete resistance of puch tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft-versus-malignancy effects might be used as a tool for eradication of otherwise resistant tumor cells of host origin. We speculated that the therapeutic benefit of BMT may be improved by using safer conditioning for engraftment of donor stem cells induce host-versus-graft unresponsiveness to enable engraftment of donor lymphocytes for subsequent induction of graft-versus-malignancy effects, or even graft-versus-autoimmunity and graft-versus-genetically abnormal cells. In other words, focusing on more selective and smarter rather than stronger modalities. Effective BMT procedures may be accomplished without lethal conditioning of the host, using a new, well-tolerated and user-friendly non-myeloablative regimen, thus eliminating or minimizing immediate and late procedure-related toxicity and mortality. It appears that initial induction of graft tolerance, mediated by engraftment of donor stem cells, leads to durable engraftment of immunocompetent donor lymphocytes, which may be necessary for induction of effective biologic warfare against host-type immunohematopoietic cells. Consequently, stem-cell therapy following induction of transplantation tolerance by selective elimination of alloreactive donor lymphocytes may represent the treatment of choice for a wide range of otherwise incurable diseases, including cancer (hematologic malignancies and certain metastatic solid tumors), genetic disorders (hemoglobinopathies and enzyme deficiency disorders), diseases caused by self-reactive lymphocytes (autoimmune diseases such as multiple sclerosis, rheumatoid arthritis) to mention just a few. Using reduced intensity conditioning, non-myeloablative stem cell transplantation (NST) can be accomplished with no major procedure-related toxicity or mortality. Thus, NST offers the feasibility of safe stem cell transplantation and cell-mediated procedures for a large and constantly growing spectrum of clinical indications for all patients in need without lower or upper age limit. Future strategies currently under investigation include developing new approaches for control of alloreactivity of host-versus-graft and graft-versus host reactivity reactions and developing better approaches for maximizing the capacity of donor lymphocytes to eliminate cancer cells more selectively, while avoiding or minimizing GVHD for safer and more effective treatment of patients in need of BMT.

Facial resurfacing with a monoblock full-thickness skin graft after multiple malignant melanomas excision in xeroderma pigmentosum.

PubMed

Ozmen, Selahattin; Uygur, Safak; Eryilmaz, Tolga; Ak, Betul

2012-09-01

Xeroderma pigmentosum is an autosomal recessive disease, characterized by vulnerability of the skin to solar radiation. Increase in sunlight-induced cancer is a direct consequence of an increase in mutated cells of the skin of patients with xeroderma pigmentosum. There is no specific technique for facial resurfacing in patients with xeroderma pigmentosum. In this article, a patient with xeroderma pigmentosum with multiple malignant melanomas on her face and radical excision of total facial skin followed by facial resurfacing with monoblock full-thickness skin graft from the abdomen is presented.

Prevention and treatment of relapse after stem cell transplantation in lymphoid malignancies.

PubMed

Sureda, Anna; Dreger, Peter; Bishop, Michael R; Kroger, Nicolaus; Porter, David L

2018-05-24

Relapse is now the major cause of treatment failure after allogeneic HSCT (alloHSCT). Many novel strategies to address this critical issue are now being developed and tested. At the 3rd International Workshop on Biology, Prevention, and Treatment of Relapse held in Hamburg, Germany in November 2016, international experts presented and discussed recent developments in the field. Some approaches may be applicable to a wide range of patients after transplant, whereas some may be very disease-specific. We present a report from the session dedicated to issues related to prevention and treatment of relapse of lymphoid malignancies after alloHSCT. This session included detailed reviews as well as forward-looking commentaries that focused on Hodgkin lymphoma, chronic lymphocytic leukemia and mantle cell lymphoma, diffuse large cell and follicular lymphoma, and multiple myeloma.

Diagnostic value of alarm symptoms for upper GI malignancy in patients referred to GI clinic: A 7 years cross sectional study.

PubMed

Emami, Mohammad Hasan; Ataie-Khorasgani, Masoud; Jafari-Pozve, Nasim

2017-01-01

Early upper gastrointestinal (UGI) cancer detection had led to organ-preserving endoscopic therapy. Endoscopy is a suitable method of early diagnosis of UGI malignancies. In Iran, exclusion of malignancy is the most important indication for endoscopy. This study is designed to see whether using alarm symptoms can predict the risk of cancer in patients. A total of 3414 patients referred to a tertiary gastrointestinal (GI) clinic in Isfahan, Iran, from 2009 to 2016 with dyspepsia, gastroesophageal reflux disease (GERD), and alarm symptoms, such as weight loss, dysphagia, GI bleeding, vomiting, positive familial history for cancer, and anorexia. Each patient had been underwent UGI endoscopy and patient data, including histology results, had been collected in the computer. We used logistic regression models to estimate the diagnostic accuracy of each alarm symptoms. A total of 3414 patients with alarm symptoms entered in this study, of whom 72 (2.1%) had an UGI malignancy. According to the logistic regression model, dysphagia ( P < 0.001) and weight loss ( P < 0.001) were found to be significant positive predictive factors for malignancy. Furthermore, males were in a significantly higher risk of developing UGI malignancy. Through receiver operating characteristic curve and the area under the curve (AUC) with adequate overall calibration and model fit measures, dysphagia and weight loss as a related cancer predictor had a high diagnostic accuracy (accuracy = 0. 72, AUC = 0. 881). Using a combination of age, alarm symptoms will lead to high positive predictive value for cancer. We recommend to do an early endoscopy for any patient with UGI symptoms and to take multiple biopsies from any rudeness or suspicious lesion, especially for male gender older than 50, dysphagia, or weight loss.

Indeterminate lung nodules in cancer patients: pretest probability of malignancy and the role of 18F-FDG PET/CT.

PubMed

Evangelista, Laura; Panunzio, Annalori; Polverosi, Roberta; Pomerri, Fabio; Rubello, Domenico

2014-03-01

The purpose of this study was to determine likelihood of malignancy for indeterminate lung nodules identified on CT comparing two standardized models with (18)F-FDG PET/CT. Fifty-nine cancer patients with indeterminate lung nodules (solid tumors; diameter, ≥5 mm) on CT had FDG PET/CT for lesion characterization. Mayo Clinic and Veterans Affairs Cooperative Study models of likelihood of malignancy were applied to solitary pulmonary nodules. High probability of malignancy was assigned a priori for multiple nodules. Low (<5%), intermediate (5-60%), and high (>60%) pretest malignancy probabilities were analyzed separately. Patients were reclassified with PET/CT. Histopathology or 2-year imaging follow-up established diagnosis. Outcome-based reclassification differences were defined as net reclassification improvement. A null hypothesis of asymptotic test was applied. Thirty-one patients had histology-proven malignancy. PET/CT was true-positive in 24 and true-negative in 25 cases. Negative predictive value was 78% and positive predictive value was 89%. On the basis of the Mayo Clinic model (n=31), 18 patients had low, 12 had intermediate, and one had high pretest likelihood; on the basis of the Veterans Affairs model (n=26), 5 patients had low, 20 had intermediate, and one had high pretest likelihood. Because of multiple lung nodules, 28 patients were classified as having high malignancy risk. PET/CT showed 32 negative and 27 positive scans. Net reclassification improvements respectively were 0.95 and 1.6 for Mayo Clinic and Veterans Affairs models (both p<0.0001). Fourteen of 31 (45.2%) and 12 of 26 (46.2%) patients with low and intermediate pretest likelihood, respectively, had positive findings on PET/CT for the Mayo Clinic and Veterans Affairs models, respectively. Of 15 patients with high pretest likelihood and negative findings on PET/CT, 13 (86.7%) did not have lung malignancy. PET/CT improves stratification of cancer patients with indeterminate pulmonary nodules. A substantial number of patients considered at low and intermediate pretest likelihood of malignancy with histology-proven lung malignancy showed abnormal PET/CT findings.

Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

PubMed Central

Liu, Lin-Na; Xu, Hui-Xiong; Lu, Ming-De; Xie, Xiao-Yan; Wang, Wen-Ping; Hu, Bing; Yan, Kun; Ding, Hong; Tang, Shao-Shan; Qian, Lin-Xue; Luo, Bao-Ming; Wen, Yan-Ling

2012-01-01

Objective To assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases. Methods This study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed. Results Among the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS. Conclusion CEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy. PMID:23118996

Mucosal Malignant Melanoma of Nasal Cavity Recurring a Year After Radiotherapy.

PubMed

Çomunoğlu, Cem; Kuzey, Gamze Mocan; Inançli, Mete; Baba, Füsun; Özkayalar, Hanife

2017-01-01

Sinonasal mucosal malignant melanoma is a rare entity. In this report we present a nasal mucosal malignant melanoma case with its histopathological and clinical features. An 88-year-old female patient presented with epistaxis a month ago. Examination revealed a polypoid mass lesion of right nasal cavity originating from the middle concha. Her medical history revealed that she had been found to have a mass lesion in the right nasal cavity 15 months ago. She then underwent a punch biopsy from that lesion. A definitive histopathological diagnosis was not made but it was declared that the lesion had been a malignant epithelial tumor. The patient then had radiotherapy and the lesion showed complete regression. One year after completion of radiotherapy, the lesion recurred. Her last PET-CT showed multiple metastatic foci. Endoscopic excisional biopsy was performed for her recurrent lesion. Fragmented tumoral tissues were measured as 3,6x3x0,5 cm. Macroscopically the tumor was brownish in color. Histopathologically the tumor consisted of spindled and epitheloid cells. Immunohistochemically the tumor cells displayed positivity for S-100, HMB-45 and Melan-A. Findings were consistent with malignant melanoma. Mucosal malignant melanomas have a poor prognosis despite chemotherapy and radiotherapy. Five-year survival for sinonasal melanoma is reported to be lower than 35%. Sinonasal melanomas show a high recurrence rate. The immunohistochemical markers showing high specificity for malignant melanoma such as S-100, HMB-45 and Melan-A are used in order to reach a correct diagnosis. In our case the tumor showed recurrence and multiple metastases 1 year after completion of radiotherapy. For this recurrent tumor, chemotherapy and radiotherapy have been planned.

Utility of Diffusion Weighted Magnetic Resonance Imaging with Multiple B Values in Evaluation of Pancreatic Malignant and Benign Lesions and Pancreatitis.

PubMed

Karadeli, Elif; Erbay, Gurcan; Parlakgumus, Alper; Koc, Zafer

2018-02-01

To determine the feasibility of diffusion-weighted imaging in evaluation of pancreatic lesions and in differentiation of benign from malignant lesions. Descriptive study. Baskent University Adana Teaching and Research Center, Adana, Turkey, between September 2013 and May 2015. Forty-three lesions [pancreas adenocarcinoma (n=25)], pancreatitis (n=10), benign lesion (n=8)] were utilized with diffusion-weighted magnetic resonance imaging with multiple b-values. Different ADC maps of diffusion weighted images by using b-values were acquired. The median ADC at all b values for malignant lesions was significantly different from that for benign lesions (p<0.001). When ADCs at all b values were compared between benign lesions/normal parenchyma and malignant lesions/normal parenchyma, there was a significant statistical difference in all b values between benign and malignant lesions except at b 50 and b 200 (p<0.05). The lesion/normal parenchyma ADC ratio for b 600 value (AUC=0.804) was more effective than the lesion ADC for b 600 value (AUC=0.766) in differentiation of benign and malignant lesions. The specificity and sensitivity of the lesion/normal parenchyma ADC ratio were higher than those of ADC values of lesions. When the ADC was compared between benign lesions and pancreatitis, a significant difference was found at all b values (p<0.001). There was not a statistically significant difference between the ADC for pancreatitis and that for malignant lesions at any b value combinations (p>0.05). Diffusion-weighted magnetic resonance images can be helpful in differentiation of pancreatic carcinoma and benign lesions. Lesion ADC / normal parenchyma ADC ratios are more important than lesion ADC values in assessment of pancreatic lesions.

Multiple sclerosis therapeutic pipeline: opportunities and challenges.

PubMed

Krieger, Stephen

2011-01-01

The year 2010 marked the beginning of the era of oral medications for the treatment of multiple sclerosis, with the approval of dalfampridine to improve walking and fingolimod as the first oral disease-modifying agent. This review provides an overview of these and other emerging therapies, with an emphasis on the opportunities for new treatment paradigms they have the potential to offer, followed by a discussion of the challenges they will pose in the new era of multiple sclerosis management. Therapeutics in late-stage development for MS include non-selective immunosupressants, targeted immune-modulators, and monoclonal antibodies. Oral agents including cladribine, teriflunomide, laquinimod, and dimethyl fumarate, as well as monoclonal antibodies alemtuzumab, daclizumab, and rituximab are considered. Potential side effects and adverse event monitoring, including opportunistic infections, emergent malignancies, and other systemic consequences of immunosuppression are discussed in a unified section. Challenges of optimally staging, sequencing, and combining treatments in the expanding multiple sclerosis armamentarium are discussed. This review emphasizes the multifactorial decision making that these new therapeutics will warrant in terms of patient selection and personalization/individualization of therapy, and the increasingly interdisciplinary approach that will be necessitated by the new generation of agents. © 2011 Mount Sinai School of Medicine.

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells.

DTIC Science & Technology

1997-08-01

enzyme) into the multiple cloning site (MCS). This template will not only replicate inside a mammalian cell (utilizing the E-B virus origin), and...Maniatis, T. Commonly used techniques in molecular cloning . In: Molecular cloning : REFERENCES a laboratory manual, 2nd edition. Cold Spring Harbor...A vatit"Y Of DNA synthesis and the typt of DNA replica~tion Products " celular prca including DNA rsplicatlon. DNA repsair. R~NA formed in experiments

Left atrial extension of hepatoblastoma via left superior pulmonary vein.

PubMed

Atalay, Atakan; Gocen, Uğur; Yaliniz, Hafize

2014-10-01

Hepatoblastoma is the most common malignant liver tumour in early childhood. The metastatic extension of hepatoblastoma into the left atrium via the pulmonary vein is rare. Reported lesions almost always involve a right-sided approach. Here we report the case of a 3-year-old girl with a recurrent hepatoblastoma at multiple sites, including the left atrium, brain, and lung. The patient was treated surgically for the prevention of further embolic complications and cardiac failure.

Multiple chimeric antigen receptors successfully target chondroitin sulfate proteoglycan 4 in several different cancer histologies and cancer stem cells

PubMed Central

2014-01-01

Background The development of immunotherapy has led to significant progress in the treatment of metastatic cancer, including the development of genetic engineering technologies that redirect lymphocytes to recognize and target a wide variety of tumor antigens. Chimeric antigen receptors (CARs) are hybrid proteins combining antibody recognition domains linked to T cell signaling elements. Clinical trials of CAR-transduced peripheral blood lymphocytes (PBL) have induced remission of both solid organ and hematologic malignancies. Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target antigen that is overexpressed in multiple cancer histologies including melanoma, triple-negative breast cancer, glioblastoma, mesothelioma and sarcoma. Methods CSPG4 expression in cancer cell lines was assayed using flow cytometry (FACS) and reverse-transcription PCR (RT-PCR). Immunohistochemistry was utilized to assay resected melanomas and normal human tissues (n = 30) for CSPG4 expression and a reverse-phase protein array comprising 94 normal tissue samples was also interrogated for CSPG4 expression. CARs were successfully constructed from multiple murine antibodies (225.28S, TP41.2, 149.53) using second generation (CD28.CD3ζ) signaling domains. CAR sequences were cloned into a gamma-retroviral vector with subsequent successful production of retroviral supernatant and PBL transduction. CAR efficacy was assayed by cytokine release and cytolysis following coculture with target cell lines. Additionally, glioblastoma stem cells were generated from resected human tumors, and CSPG4 expression was determined by RT-PCR and FACS. Results Immunohistochemistry demonstrated prominent CSPG4 expression in melanoma tumors, but failed to demonstrate expression in any of the 30 normal human tissues studied. Two of 94 normal tissue protein lysates were positive by protein array. CAR constructs demonstrated cytokine secretion and cytolytic function after co-culture with tumor cell lines from multiple different histologies, including melanoma, breast cancer, mesothelioma, glioblastoma and osteosarcoma. Furthermore, we report for the first time that CSPG4 is expressed on glioblastoma cancer stem cells (GSC) and demonstrate that anti-CSPG4 CAR-transduced T cells recognize and kill these GSC. Conclusions The functionality of multiple different CARs, with the widespread expression of CSPG4 on multiple malignancies, suggests that CSPG4 may be an attractive candidate tumor antigen for CAR-based immunotherapies using appropriate technology to limit possible off-tumor toxicity. PMID:25197555

Over-expression of tetraspanin 8 in malignant glioma regulates tumor cell progression

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

Pan, Si-Jian; Wu, Yue-Bing; Cai, Shang

Tumor cell invasion and proliferation remain the overwhelming causes of death for malignant glioma patients. To establish effective therapeutic methods, new targets implied in these processes have to be identified. Tetraspanin 8 (Tspn8) forms complexes with a large variety of trans-membrane and/or cytosolic proteins to regulate several important cellular functions. In the current study, we found that Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. Tspn8 expression in malignant glioma cells (U251MG and U87MG lines) is important for cell proliferation and migration. siRNA-mediated knockdown of Tspn8 markedly reduced in vitromore » proliferation and migration of U251MG and U87MG cells. Meanwhile, Tspn8 silencing also increased the sensitivity of temozolomide (TMZ), and significantly increased U251MG or U87MG cell death and apoptosis by TMZ were achieved with Tspn8 knockdown. We observed that Tspn8 formed a complex with activated focal adhesion kinase (FAK) in both human malignant glioma tissues and in above glioma cells. This complexation appeared required for FAK activation, since Tspn8 knockdown inhibited FAK activation in U251MG and U87MG cells. These results provide evidence that Tspn8 contributes to the pathogenesis of glioblastoma probably by promoting proliferation, migration and TMZ-resistance of glioma cells. Therefore, targeting Tspn8 may provide a potential therapeutic intervention for malignant glioma. - Highlights: • Tspn8 is over-expressed in multiple clinical malignant glioma tissues. • Tspn8 expression is correlated with the grade of malignant gliomas. • Tspn8 knockdown suppresses U251MG/U87MG proliferation and in vitro migration. • Tspn8 knockdown significantly increases TMZ sensitivity in U251MG/U87MG cells. • Tspn8 forms a complex with FAK, required for FAK activation.« less

Estimation of Fractal Dimension in Differential Diagnosis of Pigmented Skin Lesions

NASA Astrophysics Data System (ADS)

Aralica, Gorana; Milošević, Danko; Konjevoda, Paško; Seiwerth, Sven; Štambuk, Nikola

Medical differential diagnosis is a method of identifying the presence of a particular entity (disease) within a set of multiple possible alternatives. The significant problem in dermatology and pathology is the differential diagnosis of malignant melanoma and other pigmented skin lesions, especially of dysplastic nevi. Malignant melanoma is the most malignant skin neoplasma, with increasing incidence in various parts of the world. It is hoped that the methods of quantitative pathology, i.e. morphometry, can help objectification of the diagnostic process, since early discovery of melanoma results in 10-year survival rate of 90%. The aim of the study was to use fractal dimension calculated from the perimeter-area relation of the cell nuclei as a tool for the differential diagnosis of pigmented skin lesions. We analyzed hemalaun-eosin stained pathohistological slides of pigmented skin lesions: intradermal naevi (n = 45), dysplastic naevi (n = 47), and malignant melanoma (n = 50). It was found that fractal dimension of malignant melanoma cell nuclei differs significantly from the intradermal and dysplastic naevi (p ≤ 0. 001, Steel-Dwass Multiple Comparison Test). Additionaly, ROC analysis confirmed the value of fractal dimension based evaluation. It is suggested that the estimation of fractal dimension from the perimeter-area relation of the cell nuclei may be a potentially useful morphometric parameter in the medical differential diagnosis of pigmented skin lesions.

Inflammatory pathways in cervical cancer - the UCT contribution.

PubMed

Sales, Kurt Jason; Katz, Arieh Anthony

2012-03-23

Cervical cancer is the leading gynaecological malignancy in Southern Africa. The main causal factor for development of the disease is infection of the cervix with human papillomavirus. It is a multi-step disease with several contributing co-factors including multiple sexual partners, a compromised immune system and cervical inflammation caused by infections with Chlamydia trachomatis or Neisseria gonorrhoeae. Inflammation involves extensive tissue remodelling events which are orchestrated by complex networks of cytokines, chemokines and bio-active lipids working across multiple cellular compartments to maintain tissue homeostasis. Many pathological disorders or diseases, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways. In this review we highlight our findings pertaining to activation of inflammatory pathways in cervical cancers, addressing their potential role in pathological changes of the cervix and the significance of these findings for intervention strategies.

Endoscopic fluorescent diagnostics and PDT of early malignancies of lung and esophagus

NASA Astrophysics Data System (ADS)

Sokolov, Victor V.; Chissov, Valery I.; Trakhtenberg, A. K.; Mamontov, A. S.; Frank, George A.; Filonenko, E. V.; Telegina, L. V.; Gladunov, V. K.; Belous, T. A.; Aristarkhova, E. I.; Zharkova, Natalia N.; Smirnov, V. V.; Kozlov, Dmitrij N.

1996-01-01

In this paper the results of fluorescence diagnostics and photodynamic therapy of early stage malignancies of lung (17 patients) and esophagus (8 patients) are presented. 13 patients had multiple primary tumors. As photosensitizers the new drugs Photoheme and Photosense were used. Complete remission was obtained in 92%. The patients are followed up without relapses to 2,5 years.

Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients

PubMed Central

Fucikova, Jitka; Truxova, Iva; Hensler, Michal; Becht, Etienne; Kasikova, Lenka; Moserova, Irena; Vosahlikova, Sarka; Klouckova, Jana; Church, Sarah E.; Cremer, Isabelle; Kepp, Oliver; Kroemer, Guido; Galluzzi, Lorenzo; Salek, Cyril

2016-01-01

Cancer cell death can be perceived as immunogenic by the host only when malignant cells emit immunostimulatory signals (so-called “damage-associated molecular patterns,” DAMPs), as they die in the context of failing adaptive responses to stress. Accumulating preclinical and clinical evidence indicates that the capacity of immunogenic cell death to (re-)activate an anticancer immune response is key to the success of various chemo- and radiotherapeutic regimens. Malignant blasts from patients with acute myeloid leukemia (AML) exposed multiple DAMPs, including calreticulin (CRT), heat-shock protein 70 (HSP70), and HSP90 on their plasma membrane irrespective of treatment. In these patients, high levels of surface-exposed CRT correlated with an increased proportion of natural killer cells and effector memory CD4+ and CD8+ T cells in the periphery. Moreover, CRT exposure on the plasma membrane of malignant blasts positively correlated with the frequency of circulating T cells specific for leukemia-associated antigens, indicating that ecto-CRT favors the initiation of anticancer immunity in patients with AML. Finally, although the levels of ecto-HSP70, ecto-HSP90, and ecto-CRT were all associated with improved relapse-free survival, only CRT exposure significantly correlated with superior overall survival. Thus, CRT exposure represents a novel powerful prognostic biomarker for patients with AML, reflecting the activation of a clinically relevant AML-specific immune response. PMID:27802968

Musculoskeletal Imaging Findings of Hematologic Malignancies.

PubMed

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review

PubMed Central

Berger, Garrett K.; McBride, Ali; Lawson, Stephanie; Royball, Kelsey; Yun, Seongseok; Gee, Kevin; Riaz, Irbaz Bin; Saleh, Ahlam A.; Puvvada, Soham; Anwer, Faiz

2016-01-01

Background Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. Objective Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. Data sources We searched various databases including PubMed (1946–2015), EMBASE (1947–2015), and Cochrane Central Register of Controlled Trials (1898–2015). Eligibility criteria Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. Included studies A total of 28 articles met these criteria and are summarized in this manuscript. Conclusion Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies. PMID:28010897

Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules: A systematic review and meta-analysis.

PubMed

Hu, Xiangdong; Liu, Yujiang; Qian, Linxue

2017-10-01

Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules.

Diagnostic potential of real-time elastography (RTE) and shear wave elastography (SWE) to differentiate benign and malignant thyroid nodules

PubMed Central

Hu, Xiangdong; Liu, Yujiang; Qian, Linxue

2017-01-01

Abstract Background: Real-time elastography (RTE) and shear wave elastography (SWE) are noninvasive and easily available imaging techniques that measure the tissue strain, and it has been reported that the sensitivity and the specificity of elastography were better in differentiating between benign and malignant thyroid nodules than conventional technologies. Methods: Relevant articles were searched in multiple databases; the comparison of elasticity index (EI) was conducted with the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC curve of RTE and SWE were performed with STATA 10.0 software. In addition, sensitivity analysis and bias analysis of the studies were conducted to examine the quality of articles; and to estimate possible publication bias, funnel plot was used and the Egger test was conducted. Results: Finally 22 articles which eventually satisfied the inclusion criteria were included in this study. After eliminating the inefficient, benign and malignant nodules were 2106 and 613, respectively. The meta-analysis suggested that the difference of EI between benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly comparable, whereas the difference of specificities between these 2 methods was statistically significant. In addition, statistically significant difference of AUC between RTE and SWE was observed between RTE and SWE (P < .01). Conclusion: The specificity of RTE was statistically higher than that of SWE; which suggests that compared with SWE, RTE may be more accurate on differentiating benign and malignant thyroid nodules. PMID:29068996

Investigational Antibody-Drug Conjugates for Treatment of B-lineage Malignancies.

PubMed

Herrera, Alex F; Molina, Arturo

2018-05-10

Antibody-drug conjugates (ADCs) are tripartite molecules consisting of a monoclonal antibody, a covalent linker, and a cytotoxic payload. ADC development has aimed to target the specificity inherent in antigen-antibody interactions to deliver potent cytotoxins preferentially to tumor cells and maximize antitumor activity and simultaneously minimize off-target toxicity. The earliest ADCs provided disappointing results in the clinic; however, the lessons learned regarding the need for human or humanized antibodies, more stable linkers, and greater potency payloads led to improved ADCs. Three ADCs, gemtuzumab ozogamicin, brentuximab vedotin (BV), and inotuzumab ozogamicin, have been approved for hematologic malignancies. Site-specific conjugation methods have now resulted in a new generation of more uniform, molecularly defined ADCs. These are expected to display improved in vivo properties and have recently entered the clinic. We reviewed investigational ADCs currently in clinical testing for the treatment of B-cell lineage malignancies, including leukemias, lymphomas, and multiple myeloma. The rationales for antigen targeting, data reported to date, current trial status, and preclinical results for several newer ADCs expected to enter first-in-human studies are presented. Owing to the large number of ongoing and reported BV clinical studies, only the studies of BV for diffuse large B-cell lymphoma and those combining BV with checkpoint inhibitors in B-lineage malignancies have been reviewed. With > 40 ongoing clinical trials and 7 investigational ADCs already having advanced to phase II studies, the role of ADCs in the armamentarium for the treatment of B-lineage malignancies continues to be elucidated. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple cutaneous melanomas associated with gastric and brain metastases*

PubMed Central

Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

2016-01-01

The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909

Multimodal imaging of bilateral diffuse uveal melanocytic proliferation associated with an iris mass lesion.

PubMed

Naysan, Jonathan; Pang, Claudine E; Klein, Robert W; Freund, K Bailey

2016-01-01

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare, paraneoplastic syndrome characterized by bilateral painless visual loss and proliferation of choroidal melanocytes in association with an underlying systemic malignancy. We report a case of bilateral diffuse uveal melanocytic proliferation associated with an underlying gynecological malignancy that also features the infrequent finding of an iris mass lesion, using multimodal imaging including ultra-widefield imaging, spectral domain and swept-source optical coherence tomography. A 59-year-old white female with a prior history of gynecological malignancy in remission presented with progressive bilateral visual loss over several weeks. The patient was noted to have a focal iris mass lesion in her right eye. Ultra-widefield color fundus photography showed a characteristic bilateral 'giraffe pattern' of pigmentary changes extending into the periphery as well as multiple discrete deeply pigmented lesions. Ultra-widefield autofluorescence was useful for visualizing the full extent of involvement. Indocyanine green angiography helped to demarcate the discrete pigmented choroidal lesions. Swept-source OCT clearly delineated the alternating zones of retinal pigment epithelium (RPE) thickening and RPE loss, as well as the prominent choroidal infiltration and thickening. BDUMP is an important diagnosis to consider in the presence of multiple discrete melanocytic choroidal lesions, diffuse choroidal thickening, characteristic RPE changes, iris mass lesions and exudative retinal detachment. Ultra-widefield imaging may demonstrate more extensive lesions than that detected on clinical examination or standard field imaging. Imaging with SS-OCT shows choroidal and RPE characteristics that correlate well with known histopathology of this entity.

Multiple myeloma presenting as CEA-producing rectal cancer.

PubMed

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-03-31

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

Gorlin-Goltz syndrome: A rare case report.

PubMed

Pol, Chetan A; Ghige, Suvarna K; Kalaskar, Ritesh R; Gosavi, Suchitra R

2013-10-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts (OKCs) and musculoskeletal malformations. A rare case of this syndrome observed in a 13-year-old male patient is presented in which multiple OKCs were causing disfigurement of the lower jaw as well as displacement and malocclusion of the teeth. Early diagnosis and treatment of this syndrome is important to reduce the severity of complications including cutaneous and cerebral malignancy and oromaxillofacial deformation and destruction due to jaw cysts.

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma

PubMed Central

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P. Leif; Camaschella, Clara; Campanella, Alessandro

2015-01-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. PMID:25715406

Erythroblast apoptosis and microenvironmental iron restriction trigger anemia in the VK*MYC model of multiple myeloma.

PubMed

Bordini, Jessica; Bertilaccio, Maria Teresa Sabrina; Ponzoni, Maurilio; Fermo, Isabella; Chesi, Marta; Bergsagel, P Leif; Camaschella, Clara; Campanella, Alessandro

2015-06-01

Multiple myeloma is a malignant disorder characterized by bone marrow proliferation of plasma cells and by overproduction of monoclonal immunoglobulin detectable in the sera (M-spike). Anemia is a common complication of multiple myeloma, but the underlying pathophysiological mechanisms have not been completely elucidated. We aimed to identify the different determinants of anemia using the Vk*MYC mouse, which spontaneously develops an indolent bone marrow localized disease with aging. Affected Vk*MYC mice develop a mild normochromic normocytic anemia. We excluded the possibility that anemia results from defective erythropoietin production, inflammation or increased hepcidin expression. Mature erythroid precursors are reduced in Vk*MYC bone marrow compared with wild-type. Malignant plasma cells express the apoptogenic receptor Fas ligand and, accordingly, active caspase 8 is detected in maturing erythroblasts. Systemic iron homeostasis is not compromised in Vk*MYC animals, but high expression of the iron importer CD71 by bone marrow plasma cells and iron accumulation in bone marrow macrophages suggest that iron competition takes place in the local multiple myeloma microenvironment, which might contribute to anemia. In conclusion, the mild anemia of the Vk*MYC model is mainly related to the local effect of the bone marrow malignant clone in the absence of an overt inflammatory status. We suggest that this reproduces the initial events triggering anemia in patients. Copyright© Ferrata Storti Foundation.

[Anorectal Malignant Melanoma Is a Very Rare Disease and Has a Poor Prognosis].

PubMed

Yoshida, Yuta; Noura, Shingo; Matsumura, Tae; Hirota, Masaki; Shuto, Takashi; Muratsu, Arisa; Yasuyama, Harunobu; Takata, Akihiro; Koga, Chikato; Kameda, Chizu; Murakami, Masahiro; Kawabata, Ryohei; Shimizu, Junzo; Miwa, Hideaki; Hasegawa, Junichi

2017-11-01

We performed abdomino-perineal-resection(APR)on 2 cases of anorectal malignant melanoma. The first case was a 70- year-old woman suffering from bloody stool. Colonoscopy showed a black tumor in the rectum. Biopsy revealed a malignant melanoma. A CT scan showed multiple lung metastases and liver metastasis. She underwent surgery for the purpose of bleeding control, but died shortly thereafter because her liver and lung metastases had worsened. The second case was a 43- years-old man suffering from bloody stool. He had a black type 3 tumor in the rectum. A biopsy revealed malignant melanoma. A CT scan showed lateral lymph node swelling. He underwent APR with right side-lateral dissection. An established treatment for anorectal malignant melanoma has not been agreed upon and it is controversial. We experienced 2 cases that underwent surgery and we report them along with relevant information from the literature.

STAT3 inhibition as a therapeutic strategy for leukemia.

PubMed

Kanna, Rubashruti; Choudhary, Gaurav; Ramachandra, Nandini; Steidl, Ulrich; Verma, Amit; Shastri, Aditi

2017-11-22

Leukemia is characterized by selective overgrowth of malignant hematopoietic stem cells (HSC's) that interfere with HSC differentiation. Cytoreductive chemotherapy can kill rapidly dividing cancerous cells but cannot eradicate the malignant HSC pool leading to relapses. Leukemic stem cells have several dysregulated pathways and the Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) pathway are prominent among them. STAT3 is an important transcription factor that regulates cell growth, proliferation, and inhibits apoptosis. High STAT3 expression in leukemia has been associated with an increased risk for relapse and decreased overall survival. Multiple strategies for interfering with STAT3 activity in leukemic cells include inhibition of STAT3 phosphorylation, interfering with STAT3 interactions, preventing nuclear transfer, inhibiting transcription and causing interference in STAT: DNA binding. A better understanding of key interactions and upstream mediators of STAT3 activity will help facilitate the development of effective cancer therapies and may result in durable remissions.

Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.

PubMed

Andreasson, P; Johansson, B; Billström, R; Garwicz, S; Mitelman, F; Höglund, M

1998-03-01

Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.

Correlation of sociodemographic and clinical parameters with depression and distress in patients with hematologic malignancies.

PubMed

Shreders, Amanda J; Niazi, Shehzad K; Hodge, David O; Chimato, Nicolette T; Kureti, Megha; Kirla, Navya; Agrawal, Ankit; Swaika, Abhisek; Gustetic, Elaine; Foster, Renee; Nelson, Kimberly A; Jani, Prachi; Chanan-Khan, Asher A; Ailawadhi, Sikander

2018-03-01

A quarter of cancer patients struggle with distress or depression during their illness. Multiple organizations including the National Comprehensive Cancer Network recommend universal screening for distress and depression. Herein, we describe a universal screening program in patients with hematologic malignancies and factors associated with distress and depression. Between December 2013 and February 2015, patients with hematologic malignancies took the Patient Health Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their first outpatient parenteral chemotherapy. Patient demographic information as well as information regarding visit burden and baseline use of psychiatric medications were recorded. A PHQ-9 score of ≥ 9 and a DT score ≥ 4 suggested a high risk of major depression and distress. Intergroup comparisons of categorical and continuous variables were performed via chi-square and Wilcoxon rank-sum tests. Multivariate models were constructed using the stepwise selection technique using all potential variables. Two hundred forty-six patients with a median age at diagnosis 65 years (range 18-94 years) were included. In the multivariate analysis, a PHQ-9 score ≥ 9 was associated with living alone (P = 0.007), positive PHQ-2 (P = 0.003), and high Charlson comorbidity index (CCI; P = 0.02), while a DT score ≥ 4 was associated with being married (P = 0.03) and female (P = 0.03). There was no other association with high scores on either questionnaire. Patients with hematologic malignancies often have prolonged treatment and surveillance. We identified subpopulations within this group who may be at high risk of developing distress and depression and who should be aggressively screened even when universal screening programs are not available.

Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real-time near-infrared fluorescence guidance.

PubMed

Boogerd, Leonora S F; Handgraaf, Henricus J M; Lam, Hwai-Ding; Huurman, Volkert A L; Farina-Sarasqueta, Arantza; Frangioni, John V; van de Velde, Cornelis J H; Braat, Andries E; Vahrmeijer, Alexander L

2017-02-01

Tumor recurrence after radical resection of hepatic tumors is not uncommon, suggesting that malignant lesions are missed during surgery. Intraoperative navigation using fluorescence guidance is an innovative technique enabling real-time identification of (sub)capsular liver tumors. The objective of the current study was to compare fluorescence imaging (FI) and conventional imaging modalities for laparoscopic detection of both primary and metastatic tumors in the liver. Patients undergoing laparoscopic resection of a malignant hepatic tumor were eligible for inclusion. Patients received standard of care, including preoperative CT and/or MRI. In addition, 10 mg indocyanine green was intravenously administered 1 day prior to surgery. After introduction of the laparoscope, inspection, FI, and laparoscopic ultrasonography (LUS) were performed. Histopathological examination of resected suspect tissue was considered the gold standard. Twenty-two patients suspected of having hepatocellular carcinoma (n = 4), cholangiocarcinoma (n = 2) or liver metastases from colorectal carcinoma (n = 12), uveal melanoma (n = 2), and breast cancer (n = 2) were included. Two patients were excluded because their surgery was unexpectedly postponed several days. Twenty-six malignancies were resected in the remaining 20 patients. Sensitivity for various modalities was 80 % (CT), 84 % (MRI), 62 % (inspection), 86 % (LUS), and 92 % (FI), respectively. Three metastases (12 %) were identified solely by FI. All 26 malignancies could be detected by combining LUS and FI (100 % sensitivity). This study demonstrates added value of FI during laparoscopic resections of several hepatic tumors. Although larger series will be needed to confirm long-term patient outcome, the technology already aids the surgeon by providing real-time fluorescence guidance.

Arsenic-induced malignant transformation of human keratinocytes: Involvement of Nrf2

PubMed Central

Pi, Jingbo; Diwan, Bhalchandra A.; Sun, Yang; Liu, Jie; Qu, Wei; He, Yuying; Styblo, Miroslav; Waalkes, Michael P.

2009-01-01

Arsenic is a well-known human skin carcinogen but the underlying mechanisms of carcinogenesis are unclear. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism, and emerging data suggest that constitutive activation of Nrf2 contributes to malignant phenotype. In the present study when an immortalized, non-tumorigenic human keratinocyte cell line (HaCaT) was continuously exposed to environmentally relevant level of inorganic arsenite (100 nM) for 28 weeks, malignant transformation occurred as evidenced by the formation of highly aggressive squamous cell carcinoma after inoculation into nude mice. To investigate the mechanisms involved, a broad array of biomarkers for transformation were assessed in these arsenic-transformed cells (termed As-TM). In addition to increased secretion of matrix metalloproteinase-9 (MMP-9), a set of markers for squamous differentiation and skin keratinization, including keratin-1, keratin-10, involucrin, and loricrin, were significantly elevated in As-TM cells. Furthermore, As-TM cells showed increased intracellular glutathione, elevated expression of Nrf2 and its target genes, as well as generalized apoptotic resistance. In contrast to increased basal Nrf2 activity in As-TM cells, a diminished Nrf2-mediated antioxidant response induced by acute exposure to high dose of arsenite or tert-butyl hydroxyquinone occurred. The findings that multiple biomarkers for malignant transformation observed in As-TM cells, including MMP-9 and cytokeratins, are potentially regulated by Nrf2 suggest constitutive Nrf2 activation may be involved in arsenic carcinogenesis of skin. The weakened Nrf2 activation in response to oxidative stressors observed in As-TM cells, coupled with acquired apoptotic resistance, would potentially have increased the likelihood of transmittable oxidative DNA damage and fixation of mutational/DNA damage events. PMID:18572023

Multiple myeloma presenting as CEA-producing rectal cancer

PubMed Central

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-01-01

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas. PMID:21139949

Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome.

PubMed

Chao, Angel; Lai, Chyong-Huey; Lee, Yun-Shien; Ueng, Shir-Hwa; Lin, Chiao-Yun; Wang, Tzu-Hao

2015-01-15

Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively. A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation. Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.

Therapeutic Antibodies for Myeloid Neoplasms—Current Developments and Future Directions

PubMed Central

Schürch, Christian M.

2018-01-01

Therapeutic monoclonal antibodies (mAbs) such as antibody–drug conjugates, ligand–receptor antagonists, immune checkpoint inhibitors and bispecific T cell engagers have shown impressive efficacy in the treatment of multiple human cancers. Numerous therapeutic mAbs that have been developed for myeloid neoplasms, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are currently investigated in clinical trials. Because AML and MDS originate from malignantly transformed hematopoietic stem/progenitor cells—the so-called leukemic stem cells (LSCs) that are highly resistant to most standard drugs—these malignancies frequently relapse and have a high disease-specific mortality. Therefore, combining standard chemotherapy with antileukemic mAbs that specifically target malignant blasts and particularly LSCs or utilizing mAbs that reinforce antileukemic host immunity holds great promise for improving patient outcomes. This review provides an overview of therapeutic mAbs for AML and MDS. Antibody targets, the molecular mechanisms of action, the efficacy in preclinical leukemia models, and the results of clinical trials are discussed. New developments and future studies of therapeutic mAbs in myeloid neoplasms will advance our understanding of the immunobiology of these diseases and enhance current therapeutic strategies. PMID:29868474

Ovulation and extra-ovarian origin of ovarian cancer

PubMed Central

Yang-Hartwich, Yang; Gurrea-Soteras, Marta; Sumi, Natalia; Joo, Won Duk; Holmberg, Jennie C.; Craveiro, Vinicius; Alvero, Ayesha B.; Mor, Gil

2014-01-01

The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies. PMID:25135607

Targeting the TAM Receptors in Leukemia.

PubMed

Huey, Madeline G; Minson, Katherine A; Earp, H Shelton; DeRyckere, Deborah; Graham, Douglas K

2016-11-08

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

Comparison of peritumoral stromal tissue stiffness obtained by shear wave elastography between benign and malignant breast lesions.

PubMed

Park, Hye Sun; Shin, Hee Jung; Shin, Ki Chang; Cha, Joo Hee; Chae, Eun Young; Choi, Woo Jung; Kim, Hak Hee

2018-01-01

Background Aggressive breast cancers produce abnormal peritumoral stiff areas, which can differ between benign and malignant lesions and between different subtypes of breast cancer. Purpose To compare the tissue stiffness of the inner tumor, tumor border, and peritumoral stroma (PS) between benign and malignant breast masses by shear wave elastography (SWE). Material and Methods We enrolled 133 consecutive patients who underwent preoperative SWE. Using OsiriX commercial software, we generated multiple 2-mm regions of interest (ROIs) in a linear arrangement on the inner tumor, tumor border, and PS. We obtained the mean elasticity value (E mean ) of each ROI, and compared the E mean between benign and malignant tumors. Odds ratios (ORs) for prediction of malignancy were calculated. Subgroup analyses were performed among tumor subtypes. Results There were 85 malignant and 48 benign masses. The E mean of the tumor border and PS were significantly different between benign and malignant masses ( P < 0.05 for all). ORs for malignancy were 1.06, 1.08, 1.05, and 1.04 for stiffness of the tumor border, proximal PS, middle PS, and distal PS, respectively ( P < 0.05 for all). Malignant masses with a stiff rim were significantly larger than malignant masses without a stiff rim, and were more commonly associated with the luminal B and triple negative subtypes. Conclusion Stiffness of the tumor border and PS obtained by SWE were significantly different between benign and malignant masses. Malignant masses with a stiff rim were larger in size and associated with more aggressive pathologic subtypes.

Anthropometric characteristics and risk of multiple myeloma.

PubMed

Blair, Cindy K; Cerhan, James R; Folsom, Aaron R; Ross, Julie A

2005-09-01

Few studies have examined obesity and risk for multiple myeloma, and the results are inconsistent. Laboratory evidence suggests mechanisms through which obesity could influence carcinogenesis of this hematopoietic malignancy. We examined the association between anthropometric characteristics and incident multiple myeloma in a prospective, population-based sample of 37,083 postmenopausal women. In 1986, the women completed a mailed questionnaire that included self-report of height and weight, and friend measurement of waist and hip circumferences. During 16 years of follow up, 95 cases of multiple myeloma were identified through linkage to the Iowa Cancer Registry. In an age-adjusted model, women in the highest category of several anthropometric measurements compared with the lowest category were at increased risk of developing multiple myeloma. For body mass index (kg/m), the rate ratio (95% confidence interval) was 1.5 (0.92-2.6); for weight, 1.9 (1.1-3.4); for waist circumference, 2.0 (1.1-3.5); and for hip circumference, 1.8 (1.0-3.0). Greater adiposity may increase the risk of multiple myeloma.

Bryostatin and Vincristine in B-Cell Malignancies

ClinicalTrials.gov

2013-01-10

Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Multiple Myeloma

Pathogenesis of renal failure in multiple myeloma: any role of contrast media?

PubMed

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function.

Pathogenesis of Renal Failure in Multiple Myeloma: Any Role of Contrast Media?

PubMed Central

Mussap, Michele; Merlini, Giampaolo

2014-01-01

The spectrum of kidney disease-associated monoclonal immunoglobulin and plasma cell malignancies is remarkably broad and encompasses nearly all nephropathologic entities. Multiple myeloma with kidney impairment at presentation is a medical emergency since the recovery of kidney function is associated with survival benefits. In most cases, kidney impairment may be the first clinical manifestation of malignant plasma cell dyscrasias like multiple myeloma and light chain amyloidosis. Multiple myeloma per se cannot be considered a main risk factor for developing acute kidney injury following intravascular administration of iodinated contrast media. The risk is increased by comorbidities such as chronic kidney disease, diabetes, hypercalcemia, dehydration, and use of nephrotoxic drugs. Before the administration of contrast media, the current recommended laboratory tests for assessing kidney function are serum creatinine measurement and the estimation of glomerular filtration rate by using the CKD-EPI equation. The assessment of Bence Jones proteinuria is unnecessary for evaluating the risk of kidney failure in patients with multiple myeloma, since this test cannot be considered a surrogate biomarker of kidney function. PMID:24877060

Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

PubMed

Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

2009-02-15

Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in combination with conventional and novel therapies to potentially improve patient outcome in multiple myeloma and other malignancies.

Two is better than one: advances in pathogen-boosted immunotherapy and adoptive T-cell therapy.

PubMed

Xin, Gang; Schauder, David M; Zander, Ryan; Cui, Weiguo

2017-09-01

The recent tremendous successes in clinical trials take cancer immunotherapy into a new era and have attracted major attention from both academia and industry. Among the variety of immunotherapy strategies developed to boost patients' own immune systems to fight against malignant cells, the pathogen-based and adoptive cell transfer therapies have shown the most promise for treating multiple types of cancer. Pathogen-based therapies could either break the immune tolerance to enhance the effectiveness of cancer vaccines or directly infect and kill cancer cells. Adoptive cell transfer can induce a strong durable antitumor response, with recent advances including engineering dual specificity into T cells to recognize multiple antigens and improving the metabolic fitness of transferred cells. In this review, we focus on the recent prospects in these two areas and summarize some ongoing studies that represent potential advancements for anticancer immunotherapy, including testing combinations of these two strategies.

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 neoplasms, single primaries, and patient survival

PubMed Central

Amer, Magid H

2014-01-01

Background Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. Methods This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Results Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991). Conclusion Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition. PMID:24623992

Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome?

PubMed

Katodritou, E; Gastari, V; Verrou, E; Hadjiaggelidou, C; Varthaliti, M; Georgiadou, S; Laschos, K; Xirou, P; Yiannaki, E; Constantinou, N; Markala, D; Zervas, K

2009-08-01

Extramedullary relapse constitutes an uncommon manifestation of multiple myeloma (MM), characterized by highly malignant histology, special biological features, resistance to treatment and poor outcome. Its incidence has been increased during the last years, probably due to the introduction of novel strategies in the management of MM, including intensified treatment and immunomodulatory drugs. Here we report nine cases of extramedullary relapse of MM, presented in unusual locations, seven of which had previously been treated with thalidomide-containing regimens (TCR). Our aim was to explore the morphological, immunophenotypical, molecular and laboratory characteristics accompanying EMP-relapse and seek possible correlations with treatment and clinical outcome.

Paraganglioma with intracranial metastasis: a case report and review of the literature.

PubMed

Cai, Peihao; Mahta, Ali; Kim, Ryan Y; Kesari, Santosh

2012-10-01

Paragangliomas are rare neuroendocrine tumors of neural crest origin. They are mostly benign, however; malignant tumors with aggressive behavior and distant metastasis can also occur. Intracranial involvement is extremely rare and has been sporadically reported in the literature. Here we report a case who presented with progressive neurologic deficits due to multiple intracranial lesions found to be metastasis from an occult retroperitoneal malignant paraganglioma.

Genomic profiles of low-grade murine gliomas evolve during progression to glioblastoma. | Office of Cancer Genomics

Cancer.gov

Background: Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear.Methods: We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease.

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

Endocrine causes of calcium disorders.

PubMed

Greco, Deborah S

2012-11-01

Endocrine diseases that may cause hypercalcemia and hypocalcemia include hyperparathyroidism, hypoparathyroidism, thyroid disorders, hyperadrenocorticism, hypoadrenocorticism, and less commonly pheochromocytoma and multiple endocrine neoplasias. The differential diagnosis of hypercalcemia may include malignancy (lymphoma, anal sac carcinoma, and squamous cell carcinoma), hyperparathyroidism, vitamin D intoxication, chronic renal disease, hypoadrenocorticism, granulomatous disorders, osteolysis, or spurious causes. Hypocalcemia may be caused by puerperal tetany, pancreatitis, intestinal malabsorption, ethlyene glycol intoxication, acute renal failure, hypopararthyroidism, hypovitaminosis D, hypomagnesemia, and low albumin. This article focuses on the endocrine causes of calcium imbalance and provides diagnostic and therapeutic guidelines for identifying the cause of hypercalcemia and hypocalcemia in veterinary patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Quantum Dots for Molecular Pathology

PubMed Central

True, Lawrence D.; Gao, Xiaohu

2007-01-01

Assessing malignant tumors for expression of multiple biomarkers provides data that are critical for patient management. Quantum dot-conjugated probes to specific biomarkers are powerful tools that can be applied in a multiplex manner to single tissue sections of biopsies to measure expression levels of multiple biomarkers. PMID:17251330

Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness

PubMed Central

Emdad, Luni; Janjic, Aleksandar; Alzubi, Mohammad A.; Hu, Bin; Santhekadur, Prasanna K.; Menezes, Mitchell E.; Shen, Xue-Ning; Das, Swadesh K.; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

Background Malignant glioma is an aggressive cancer requiring new therapeutic targets. MicroRNAs (miRNAs) regulate gene expression post transcriptionally and are implicated in cancer development and progression. Deregulated expressions of several miRNAs, specifically hsa-miR-184, correlate with glioma development. Methods Bioinformatic approaches were used to identify potential miR-184-regulated target genes involved in malignant glioma progression. This strategy identified a multifunctional nuclease, SND1, known to be overexpressed in multiple cancers, including breast, colon, and hepatocellular carcinoma, as a putative direct miR-184 target gene. SND1 levels were evaluated in patient tumor samples and human-derived cell lines. We analyzed invasion and signaling in vitro through SND1 gain-of-function and loss-of-function. An orthotopic xenograft model with primary glioma cells demonstrated a role of miR-184/SND1 in glioma pathogenesis in vivo. Results SND1 is highly expressed in human glioma tissue and inversely correlated with miR-184 expression. Transfection of glioma cells with a miR-184 mimic inhibited invasion, suppressed colony formation, and reduced anchorage-independent growth in soft agar. Similar phenotypes were evident when SND1 was knocked down with siRNA. Additionally, knockdown (KD) of SND1 induced senescence and improved the chemoresistant properties of malignant glioma cells. In an orthotopic xenograft model, KD of SND1 or transfection with a miR-184 mimic induced a less invasive tumor phenotype and significantly improved survival of tumor bearing mice. Conclusions Our study is the first to show a novel regulatory role of SND1, a direct target of miR-184, in glioma progression, suggesting that the miR-184/SND1 axis may be a useful diagnostic and therapeutic tool for malignant glioma. PMID:25216670

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

Late radiation responses in man: Current evaluation from results from Hiroshima and Nagasaki

NASA Astrophysics Data System (ADS)

Schull, William J.

Among the late effects of exposure to the atomic bombings of Hiroshima and Nagasaki, none looms larger than radiation related malignancies. Indeed, the late effects of A-bomb radiation on mortality appear to be limited to an increase in malignant tumors. At present, it can be shown that cancers of the breast, colon, esophagus, lungs, stomach, thyroid, and urinary tract as well as leukemia and multiple myeloma increase in frequency with an increase in exposure. No significant relationship to radiation can as yet be established for malignant lymphoma, nor cancers of the rectum, pancreas or uterus. Radiation induced malignancies other than leukemia seem to develop proportionally to the natural cancer rate for the attained age. For specific age-at-death intervals, both relative and absolute risks tend to be higher for those of younger age at the time of bombing. Other late effects include radiation-related lenticular opacities, disturbances of growth among those survivors still growing at the time of exposure, and mental retardation and small head sizes among the in utero exposed. Chromosomal abnormalities too are more frequently encountered in the peripheral leucocytes of survivors, and this increase is functionally related to their exposure. Some uncertainty continues to surround both the quantity and quality of the radiation released by these two nuclear devices, particularly the Hiroshima bomb. A recent reassessment suggests that the gamma radiation estimates which have been used in the past may be too low at some distances and the neutron radiation estimates too high at all distances; moreover, the energies of the neutrons released now appear ``softer'' than previously conjectured. These uncertainties not sufficiently large, however, to compromise the reality of the increased frequency of malignancy, but make estimates of the dose response, particularly in terms of gamma and neutron exposures, tentative.

Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

PubMed

Bonanad, S; De la Rubia, J; Gironella, M; Pérez Persona, E; González, B; Fernández Lago, C; Arnan, M; Zudaire, M; Hernández Rivas, J A; Soler, A; Marrero, C; Olivier, C; Altés, A; Valcárcel, D; Hernández, M T; Oiartzabal, I; Fernández Ordoño, R; Arnao, M; Esquerra, A; Sarrá, J; González-Barca, E; González, J; Calvo, X; Nomdedeu, M; García Guiñón, A; Ramírez Payer, A; Casado, A; López, S; Durán, M; Marcos, M; Cruz-Jentoft, A J

2015-09-01

The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.

Initial genome sequencing and analysis of multiple myeloma

PubMed Central

Chapman, Michael A.; Lawrence, Michael S.; Keats, Jonathan J.; Cibulskis, Kristian; Sougnez, Carrie; Schinzel, Anna C.; Harview, Christina L.; Brunet, Jean-Philippe; Ahmann, Gregory J.; Adli, Mazhar; Anderson, Kenneth C.; Ardlie, Kristin G.; Auclair, Daniel; Baker, Angela; Bergsagel, P. Leif; Bernstein, Bradley E.; Drier, Yotam; Fonseca, Rafael; Gabriel, Stacey B.; Hofmeister, Craig C.; Jagannath, Sundar; Jakubowiak, Andrzej J.; Krishnan, Amrita; Levy, Joan; Liefeld, Ted; Lonial, Sagar; Mahan, Scott; Mfuko, Bunmi; Monti, Stefano; Perkins, Louise M.; Onofrio, Robb; Pugh, Trevor J.; Vincent Rajkumar, S.; Ramos, Alex H.; Siegel, David S.; Sivachenko, Andrey; Trudel, Suzanne; Vij, Ravi; Voet, Douglas; Winckler, Wendy; Zimmerman, Todd; Carpten, John; Trent, Jeff; Hahn, William C.; Garraway, Levi A.; Meyerson, Matthew; Lander, Eric S.; Getz, Gad; Golub, Todd R.

2013-01-01

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumor genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the dataset. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signaling was suggested by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge. PMID:21430775

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

PubMed

Dunphy, Cherie H; Galambos, Csaba; Polski, Jacek M; Evans, H Lance; Gardner, Laura J; Grosso, Leonard E; Montone, Kathleen T

2002-03-01

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction.

PubMed

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-06-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)-associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy.

Prolapsing Gastric Polyp Causing Intermittent Gastric Outlet Obstruction

PubMed Central

Kosai, Nik Ritza; Gendeh, Hardip Singh; Norfaezan, Abdul Rashid; Razman, Jamin; Sutton, Paul Anthony; Das, Srijit

2015-01-01

Gastric polyps are often an incidental finding on upper gastrointestinal endoscopy, with an incidence up to 5%. The majority of gastric polyps are asymptomatic, occurring secondary to inflammation. Prior reviews discussed Helicobacter pylori (H pylori)–associated singular gastric polyposis; however, we present a rare and unusual case of recurrent multiple benign gastric polyposis post H pylori eradication resulting in intermittent gastric outlet obstruction. A 70-year-old independent male, Chinese in ethnicity, with a background of diabetes mellitus, hypertension, and a simple renal cyst presented with a combination of melena, anemia, and intermittent vomiting of partially digested food after meals. Initial gastroscopy was positive for H pylori; thus he was treated with H pylori eradication and proton pump inhibitors. Serial gastroscopy demonstrated multiple sessile gastric antral polyps, the largest measuring 4 cm. Histopathologic examination confirmed a benign hyperplastic lesion. Computed tomography identified a pyloric mass with absent surrounding infiltration or metastasis. A distal gastrectomy was performed, whereby multiple small pyloric polyps were found, the largest prolapsing into the pyloric opening, thus explaining the intermittent nature of gastric outlet obstruction. Such polyps often develop from gastric ulcers and, if left untreated, may undergo neoplasia to form malignant cells. A distal gastrectomy was an effective choice of treatment, taking into account the polyp size, quantity, and potential for malignancy as opposed to an endoscopic approach, which may not guarantee a complete removal of safer margins and depth. Therefore, surgical excision is favorable for multiple large gastric polyps with risk of malignancy. PMID:25578789

Cks1 Is Required for Tumor Cell Proliferation but Not Sufficient to Induce Hematopoietic Malignancies

PubMed Central

Kratzat, Susanne; Nikolova, Viktoriya; Miething, Cornelius; Hoellein, Alexander; Schoeffmann, Stephanie; Gorka, Oliver; Pietschmann, Elke; Illert, Anna-Lena; Ruland, Jürgen; Peschel, Christian; Nilsson, Jonas; Duyster, Justus; Keller, Ulrich

2012-01-01

The Cks1 component of the SCFSkp2 complex is necessary for p27Kip1 ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27Kip1 levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma. Surprisingly, loss of Skp2 in the same mouse model also resulted in elevated p27Kip1 levels but exhibited no impact on tumor onset. This raises the possibility that Cks1 could have other oncogenic activities than suppressing p27Kip1. To challenge this notion we have targeted overexpression of Cks1 to B cells using a conditional retroviral bone marrow transduction-transplantation system. Despite potent ectopic overexpression, Cks1 was unable to promote B cell hyperproliferation or B cell malignancies, indicating that Cks1 is not oncogenic when overexpressed in B cells. Since Skp2 overexpression can drive T-cell tumorigenesis or other cancers we also widened the quest for oncogenic activity of Cks1 by ubiquitously expressing Cks1 in hematopoetic progenitors. At variance with c-Myc overexpression, which caused acute myeloid leukemia, Cks1 overexpression did not induce myeloproliferation or leukemia. Therefore, despite being associated with a poor prognosis in various malignancies, sole Cks1 expression is insufficient to induce lymphoma or a myeloproliferative disease in vivo. PMID:22624029

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers.

PubMed

Ma, Xuefei; Zhang, Wei; Zhang, Rong; Li, Jingming; Li, Shufen; Ma, Yunlin; Jin, Wen; Wang, Kankan

2018-05-26

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

Melatonin as a multifunctional anti-cancer molecule: Implications in gastric cancer.

PubMed

Asghari, Mohammad Hossein; Moloudizargari, Milad; Ghobadi, Emad; Fallah, Marjan; Abdollahi, Mohammad

2017-09-15

Gastric cancer (GC) is a predominant malignancy with a high mortality rate affecting a large population worldwide. The etiology of GC is multifactorial spanning from various genetic determinants to different environmental causes. Current tretaments of GC are not efficient enough and require improvements to minimize the adverse effects. Melatonin, a naturally occurring compound with known potent inhibitory effects on cancer cells is one of the major candidates which can be recruited herein. Here we reviewed the articles conducted on the therapeutic effects of melatonin in gastric cancer in various models. The results are classified according to different aspects of cancer pathogenesis and the molecular mechanisms by which melatonin exerts its effects. Melatonin could be used to combat GC exploiting its effects on multiple aspects of its pathogenesis, including formation of cancer cells, tumor growth and angiogenesis, differentiation and metastasis as well as enhancing the anti-tumor immunity. Melatonin is a pleiotropic anti-cancer molecule that affects malignant cells via multiple mechanisms. It has been shown to benefit cancer patients indirectly by reducing side effects of current therapies which have been discussed in this review. This field of research is still underdeveloped and may serve as an interesting subject for further studies aiming at the molecular mechanisms of melatonin and novel treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

Atypical Clinical Behavior of p16-Confirmed HPV-Related Oropharyngeal Squamous Cell Carcinoma Treated With Radical Radiotherapy

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

Huang Shaohui; Perez-Ordonez, Bayardo; Liu Feifei

Purpose: To report atypical clinical behavior observed in human papillomavirus (HPV)-related oropharyngeal carcinoma (OPC) treated with radiotherapy. Methods and Materials: A retrospective cohort study was conducted for all newly diagnosed OPC cases treated with radiotherapy on July 1, 2003 to April 30, 2009. HPV positivity was determined by p16 immunostaining in tumors. The incidence of additional malignancies and the pattern of distant metastases (DMs) were compared between the HPV-positive (HPV+) and HPV-negative (HPV-) cohorts. Results: HPV status was evaluated in 318 of 613 consecutive OPC cases (52%), showing 236 HPV+ and 82 HPV- patients. Compared with HPV-, HPV+ cases weremore » less likely to have additional malignancies (prior: 11% vs. 20%, p = 0.038; synchronous: 1% vs. 9%, p = 0.001; metachronous: 6% vs. 16%, p = 0.003). Whereas the majority (10 of 12) of HPV- additional head-and-neck (HN) mucosal malignancies were in the oral cavity, there was none (0 of 7) in the HPV+ cohort (p < 0.001). HPV+ synchronous HN second primaries (SPs) were in the supraglottis, post-cricoid, and nasopharynx; metachronous HN SPs were in the glottis, supraglottis, and ethmoid plus glottis/post-cricoid region. All SPs that could be tested were HPV+. There was no difference in DM rate (10% vs. 15%, p = 0.272), but HPV+ DMs were more likely to involve multiple organs (46% vs. 0%, p = 0.005) and unusual sites. Conclusions: This study reports atypical clinical behavior seen in HPV+ OPC, including multicentric lesions in HN mucosa and DM to multiple organs and unusual sites. The frequency of these events is low, but they may have clinical implications. The routine assessment of HPV status for all OPC is warranted.« less

A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy

PubMed Central

Williams, Brent A.; Law, Arjun Datt; Routy, Bertrand; denHollander, Neal; Gupta, Vikas; Wang, Xing-Hua; Chaboureau, Amélie; Viswanathan, Sowmya; Keating, Armand

2017-01-01

Background Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. Materials and Methods We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT). The objectives were to determine safety, feasibility and evidence of activity. Patients were treated at one of three dose levels (1 × 109 cells/m2, 3 × 109 cells/m2 and 5 × 109 cells/m2), given on day 1, 3 and 5 for a planned total of six monthly cycles. Results Twelve patients with lymphoma or multiple myeloma who relapsed after AHCT for relapsed/refractory disease were enrolled in this trial. The treatment was well tolerated, with minor toxicities restricted to acute infusional events, including fever, chills, nausea and fatigue. Two patients achieved a complete response (Hodgkin lymphoma and multiple myeloma), two patients had minor responses and one had clinical improvement on the trial. Conclusions Irradiated NK-92 cells can be administered at very high doses with minimal toxicity in patients with refractory blood cancers, who had relapsed after AHCT. We conclude that high dose NK-92 therapy is safe, shows some evidence of efficacy in patients with refractory blood cancers and warrants further clinical investigation. PMID:29179517

Malignant fat-forming solitary fibrous tumor (so-called "lipomatous hemangiopericytoma"): clinicopathologic analysis of 14 cases.

PubMed

Lee, Jen-Chieh; Fletcher, Christopher D M

2011-08-01

Fat-forming solitary fibrous tumor is a rare variant of solitary fibrous tumor (SFT). Generally regarded as benign, very few fat-forming SFTs with malignant histologic features have been reported. Here, we report 14 histologically malignant fat-forming SFTs to better characterize this subset. Seven patients were female and 7 were male, with ages ranging 20 to 93 years (median, 57 y). Five tumors were located in the lower limb, 3 in the trunk, 3 in abdominopelvic locations, 2 in the head and neck region, and 1 in the upper limb. The tumor size ranged from 3.4 to 20 cm (median, 8.6 cm). Histologically, all exhibited at least focal hypercellularity; 12 tumors had mitoses >4/10 high-power fields (range, 2 to 37; median, 8), 12 showed at least moderate atypia, and 8 showed necrosis. It should be noted that 7 tumors contained only mature adipose tissue, whereas 5 contained multivacuolated lipoblasts and 2 had areas resembling atypical lipomatous tumor (ALT). Immunohistochemically, CD34 and CD99 were positive in most cases (11 of 14 and 8 of 10, respectively); MDM2 and CDK4 were both negative in all 4 cases tested (including both tumors with ALT-like areas). Follow-up data from 10 cases (median duration, 47.5 mo; range, 5 to 76) showed 2 patients with multiple metastases (both to lung and bones, and 1 each to breast and to soft tissue), both of whom died of disease. In conclusion, fat-forming SFTs exhibiting malignant histologic features have potential for aggressive behavior. The presence of lipoblasts and/or ALT-like areas, although described in some "benign" examples of fat-forming SFT, seems much more common in the malignant subset and may prompt a careful search for morphologic evidence of malignancy in any case of fat-forming SFT.

Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90

PubMed Central

2011-01-01

Background Multiple myeloma (MM) is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma. PMID:21871133

Describing care coordination of gynecologic oncology in western healthcare settings: a rapid review.

PubMed

Grant, Sean; Motala, Aneesa; Chrystal, Joya G; Shanman, Roberta; Zuchowski, Jessica; Zephyrin, Laurie; Cordasco, Kristina M

2018-05-23

Caring for women with gynecologic malignancies requires multidisciplinary communication and coordination across multiple providers. This article discusses a rapid review of the literature on characteristics of care coordination for gynecologic malignancies. Five electronic databases (from inception through March 2015) were searched for empirical studies on coordinated care models for female adults with gynecologic malignancies. A single reviewer extracted and synthesized information on how care was coordinated, how care teams made decisions, who performed what tasks, how care teams communicated information to coordinate care, and potential impact of the characteristic on delivering coordinated care. From 26 included studies, predominant characteristics of coordinated care were identified: multidisciplinary teams, patient navigators, scheduled follow-ups, survivorship care plans, and colocated services. Decision-making was best documented for studies that utilized teams that had periodic scheduled meetings with set agendas and consistent procedures. Providers' roles in coordinating care were numerous, reflecting professional backgrounds: oncologists had most authority in making treatment decisions; radiologists and pathologists shared vital biomedical information; and nurses coordinated care and communicated with patients. Communication tools and strategies across studies included having shared medical records, integrated treatment plans, and telephone-based or teleconferencing communication. There was limited information available on the impact of characteristics and accompanying strategies or tools. Several characteristics of care coordination models for gynecologic cancers have been published in the literature. Further investigation is needed to understand the relative effectiveness of these ways to coordinate care.

Cladribine tablets: in relapsing-remitting multiple sclerosis.

PubMed

Muir, Victoria J; Plosker, Greg L

2011-03-01

Cladribine, an immunosuppressant that selectively reduces peripheral lymphocyte levels, has potential as an oral therapy for relapsing-remitting multiple sclerosis. An oral (tablet) formulation is being investigated in clinical trials. In the large, well designed, phase III CLARITY trial, short-course treatment with oral cladribine (cumulative dose of 3.5 or 5.25 mg/kg) resulted in a significantly greater reduction in annualized relapse rates at 96 weeks compared with placebo in patients with relapsing-remitting multiple sclerosis. Improvements in the annualized relapse rate with oral cladribine were independent of key baseline patient characteristics which included age, sex, previous treatment with disease-modifying drugs and the number of relapses in the previous 12 months. In addition, a significantly higher proportion of patients were relapse-free at 96 weeks and there were significant reductions in the risk of 3-month sustained progression of disability in cladribine recipients compared with placebo recipients. The mean numbers of brain lesions on magnetic resonance imaging were also significantly reduced with cladribine compared with placebo in the CLARITY trial. Lymphocytopenia, herpes zoster infections and neoplasms (including malignancies) were more common in cladribine than placebo recipients.

Malignancy in Noonan syndrome and related disorders.

PubMed

Smpokou, P; Zand, D J; Rosenbaum, K N; Summar, M L

2015-12-01

Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen-activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dual malignancy in a thyroid; papillary thyroid carcinoma and small lymphocytic lymphoma; a report of a case with a cyto-histologic correlation.

PubMed

Ahmed, Omar I; Salih, Ziyan T

2017-09-01

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Simultaneous involvement of the thyroid gland by multiple malignancies, is a rare occurrence. Similarly, primary thyroid lymphomas are also rare. We are reporting a rare case of a dual thyroid malignancy; PTC with secondary thyroid involvement by chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diagnosed on cytology and confirmed with flow cytometry, histology and immunohistochemistry. Imaging showed two hypermetabolic nodules, one in left parotid gland, and the other in the thyroid isthmus. Cytology smears showed features of PTC along with an atypical lymphocytic infiltrate, which co-expressed CD5, CD19, and CD23 on flowcytometry analysis. Subsequent thyroidectomy showed the atypical lymphocytic infiltrate involving the PTC papillae themselves. The diagnosis of dual malignancies on thyroid FNA is extremely rare and often unexpected, but is possible using appropriate ancillary studies. © 2017 Wiley Periodicals, Inc.

Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

ClinicalTrials.gov

2011-12-07

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition; Small Intestine Cancer

Gorlin-Goltz syndrome: A rare case report

PubMed Central

Pol, Chetan A; Ghige, Suvarna K; Kalaskar, Ritesh R; Gosavi, Suchitra R

2013-01-01

Gorlin-Goltz syndrome is an uncommon autosomal dominant inherited disorder characterized by numerous basal cell carcinomas, odontogenic keratocysts (OKCs) and musculoskeletal malformations. A rare case of this syndrome observed in a 13-year-old male patient is presented in which multiple OKCs were causing disfigurement of the lower jaw as well as displacement and malocclusion of the teeth. Early diagnosis and treatment of this syndrome is important to reduce the severity of complications including cutaneous and cerebral malignancy and oromaxillofacial deformation and destruction due to jaw cysts. PMID:24403808

Adenoid cystic carcinoma: An unusual presentation.

PubMed

Pushpanjali, M; Sujata, D Naga; Subramanyam, S Bala; Jyothsna, M

2014-05-01

The adenoid cystic carcinoma is a relatively rare epithelial tumor of the major and minor salivary glands, accounting for about 1% of all malignant tumor of the oral and maxillofacial regions. Peak incidence occurs between the 5(th) and 6(th) decades of life. The clinical and pathological findings typical of this tumor include slow growth, peri-neural invasion, multiple local recurrences and distant metastasis. Herein, we report a case of adenoid cystic carcinoma of oropharynx with unusual clinical presentation. The diagnosis of this case and importance of cytology in diagnosing such cases is discussed.

Adenoid cystic carcinoma: An unusual presentation

PubMed Central

Pushpanjali, M; Sujata, D Naga; Subramanyam, S Bala; Jyothsna, M

2014-01-01

The adenoid cystic carcinoma is a relatively rare epithelial tumor of the major and minor salivary glands, accounting for about 1% of all malignant tumor of the oral and maxillofacial regions. Peak incidence occurs between the 5th and 6th decades of life. The clinical and pathological findings typical of this tumor include slow growth, peri-neural invasion, multiple local recurrences and distant metastasis. Herein, we report a case of adenoid cystic carcinoma of oropharynx with unusual clinical presentation. The diagnosis of this case and importance of cytology in diagnosing such cases is discussed. PMID:25328314

The pathogenesis of constipation.

PubMed

Sykes, Nigel P

2006-05-01

The pathogenesis of the constipation that is commonly experienced by cancer patients, especially those with advanced disease, is the result of multiple influences on the control of intestinal motility and fluid handling. These factors include the direct effects of malignancy on gut structure, paraneoplastic neural impairment, biochemical disturbance, and adverse effects of cancer treatments. In addition, the debility and reduced oral intake associated with cancer also contribute, as, perhaps, might the older age of many cancer patients. A detailed understanding of the mechanisms of constipation, especially in association with illness, is lacking, and most treatments remain nonspecific.

Myxoid malignant fibrous histiocytoma presenting as a midline nasal mass.

PubMed

DeRosa, Jaimie; Smit, Jeffrey R

2012-04-01

Myxoid malignant fibrous histiocytoma is a rare type of pediatric non-rhabdomyosarcoma soft-tissue sarcoma. The case of a 5-year-old girl is presented, highlighting the potential for multiple pitfalls and aberrant differential diagnoses that need to be identified for successful treatment of pediatric myxofibrosarcomas. An awareness of these tumors and a call for standardized postsurgical treatment protocols is necessary in order to successfully treat children with this disease.

Novel genomic findings in multiple myeloma identified through routine diagnostic sequencing.

PubMed

Ryland, Georgina L; Jones, Kate; Chin, Melody; Markham, John; Aydogan, Elle; Kankanige, Yamuna; Caruso, Marisa; Guinto, Jerick; Dickinson, Michael; Prince, H Miles; Yong, Kwee; Blombery, Piers

2018-05-14

Multiple myeloma is a genomically complex haematological malignancy with many genomic alterations recognised as important in diagnosis, prognosis and therapeutic decision making. Here, we provide a summary of genomic findings identified through routine diagnostic next-generation sequencing at our centre. A cohort of 86 patients with multiple myeloma underwent diagnostic sequencing using a custom hybridisation-based panel targeting 104 genes. Sequence variants, genome-wide copy number changes and structural rearrangements were detected using an inhouse-developed bioinformatics pipeline. At least one mutation was found in 69 (80%) patients. Frequently mutated genes included TP53 (36%), KRAS (22.1%), NRAS (15.1%), FAM46C/DIS3 (8.1%) and TET2/FGFR3 (5.8%), including multiple mutations not previously described in myeloma. Importantly we observed TP53 mutations in the absence of a 17 p deletion in 8% of the cohort, highlighting the need for sequencing-based assessment in addition to cytogenetics to identify these high-risk patients. Multiple novel copy number changes and immunoglobulin heavy chain translocations are also discussed. Our results demonstrate that many clinically relevant genomic findings remain in multiple myeloma which have not yet been identified through large-scale sequencing efforts, and provide important mechanistic insights into plasma cell pathobiology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Germline mutations in candidate predisposition genes in individuals with cutaneous melanoma and at least two independent additional primary cancers.

PubMed

Pritchard, Antonia L; Johansson, Peter A; Nathan, Vaishnavi; Howlie, Madeleine; Symmons, Judith; Palmer, Jane M; Hayward, Nicholas K

2018-01-01

While a number of autosomal dominant and autosomal recessive cancer syndromes have an associated spectrum of cancers, the prevalence and variety of cancer predisposition mutations in patients with multiple primary cancers have not been extensively investigated. An understanding of the variants predisposing to more than one cancer type could improve patient care, including screening and genetic counselling, as well as advancing the understanding of tumour development. A cohort of 57 patients ascertained due to their cutaneous melanoma (CM) diagnosis and with a history of two or more additional non-cutaneous independent primary cancer types were recruited for this study. Patient blood samples were assessed by whole exome or whole genome sequencing. We focussed on variants in 525 pre-selected genes, including 65 autosomal dominant and 31 autosomal recessive cancer predisposition genes, 116 genes involved in the DNA repair pathway, and 313 commonly somatically mutated in cancer. The same genes were analysed in exome sequence data from 1358 control individuals collected as part of non-cancer studies (UK10K). The identified variants were classified for pathogenicity using online databases, literature and in silico prediction tools. No known pathogenic autosomal dominant or previously described compound heterozygous mutations in autosomal recessive genes were observed in the multiple cancer cohort. Variants typically found somatically in haematological malignancies (in JAK1, JAK2, SF3B1, SRSF2, TET2 and TYK2) were present in lymphocyte DNA of patients with multiple primary cancers, all of whom had a history of haematological malignancy and cutaneous melanoma, as well as colorectal cancer and/or prostate cancer. Other potentially pathogenic variants were discovered in BUB1B, POLE2, ROS1 and DNMT3A. Compared to controls, multiple cancer cases had significantly more likely damaging mutations (nonsense, frameshift ins/del) in tumour suppressor and tyrosine kinase genes and higher overall burden of mutations in all cancer genes. We identified several pathogenic variants that likely predispose to at least one of the tumours in patients with multiple cancers. We additionally present evidence that there may be a higher burden of variants of unknown significance in 'cancer genes' in patients with multiple cancer types. Further screens of this nature need to be carried out to build evidence to show if the cancers observed in these patients form part of a cancer spectrum associated with single germline variants in these genes, whether multiple layers of susceptibility exist (oligogenic or polygenic), or if the occurrence of multiple different cancers is due to random chance.

Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma.

PubMed

Drent, Esther; Groen, Richard W J; Noort, Willy A; Themeli, Maria; Lammerts van Bueren, Jeroen J; Parren, Paul W H I; Kuball, Jürgen; Sebestyen, Zsolt; Yuan, Huipin; de Bruijn, Joost; van de Donk, Niels W C J; Martens, Anton C M; Lokhorst, Henk M; Mutis, Tuna

2016-05-01

Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody sequences to generate second-generation retroviral CD38-chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite becoming CD38-negative during culture. CD38-chimeric antigen receptor-transduced T cells also displayed significant anti-tumor effects in a xenotransplant model, in which multiple myeloma tumors were grown in a human bone marrow-like microenvironment. CD38-chimeric antigen receptor-transduced T cells also appeared to lyse the CD38(+) fractions of CD34(+) hematopoietic progenitor cells, monocytes, natural killer cells, and to a lesser extent T and B cells but did not inhibit the outgrowth of progenitor cells into various myeloid lineages and, furthermore, were effectively controllable with a caspase-9-based suicide gene. These results signify the potential importance of CD38-chimeric antigen receptor-transduced T cells as therapeutic tools for CD38(+) malignancies and warrant further efforts to diminish the undesired effects of this immunotherapy using appropriate strategies. Copyright© Ferrata Storti Foundation.

[Rapidly progressive pulmonary malignant perivascular epithelioid cell tumor: a case report and literature review].

PubMed

Shi, X Y; Long, F; Liang, B; Su, L L; Li, H C; Jiang, S J

2016-10-12

Objective: To analyze the pathogenesis, clinical features, diagnosis and differential diagnosis of primary perivascular epithelioid cell tumor(PEComa). Methods: The clinical features, auxiliary examinations and diagnosis of a case with rapidly progressive pulmonary malignant PEComa were reported and the related literatures were reviewed.The literature review was carried out respectively in Wanfang Data, CNKI and PubMed from Jan. 1975 to Jul. 2015 with "pulmonary malignant perivascular epithelioid cell tumor" and "PEComa" being the search terms. Results: A 50 year-old female patient was admitted to the hospital on September 4, 2014 because of cough and dyspnea for 60 days, hemoptysis for 40 days and fever for 7 days.Chest CT scan showed diffuse small nodules with infiltrative border and multiple pure and mixed ground-glass opacity. Transbronchial lung biopsy (TBLB) was performed and the pathological study confirmed the diagnosis of primary pulmonary malignant PEComa. The patient declined further specific therapy, but followed by rapidly progressive respiratory failure, and died two weeks after the diagnosis. A total of 8 literatures were retrieved from Wanfang Data, CNKI and PubMed and all of them were case reports.There were 3 male and 5 female patients, aging from 50 to 79 years.Radiographically, the previously reported cases presented as round and well-circumscribed masses with or without multiple nodules in both lungs. The symptoms had no specificity. Conclusions: Pulmonary malignant PEComa is a rare disease.It is easily misdiagnosed because of non-specific clinical and imaging manifestations.The final diagnosis depends on pathological biopsy.TBLB is an effective diagnostic method.

Malignant testicular tumour incidence and mortality trends

PubMed Central

Wojtyła-Buciora, Paulina; Więckowska, Barbara; Krzywinska-Wiewiorowska, Małgorzata; Gromadecka-Sutkiewicz, Małgorzata

2016-01-01

Aim of the study In Poland testicular tumours are the most frequent cancer among men aged 20–44 years. Testicular tumour incidence since the 1980s and 1990s has been diversified geographically, with an increased risk of mortality in Wielkopolska Province, which was highlighted at the turn of the 1980s and 1990s. The aim of the study was the comparative analysis of the tendencies in incidence and death rates due to malignant testicular tumours observed among men in Poland and in Wielkopolska Province. Material and methods Data from the National Cancer Registry were used for calculations. The incidence/mortality rates among men due to malignant testicular cancer as well as the tendencies in incidence/death ratio observed in Poland and Wielkopolska were established based on regression equation. The analysis was deepened by adopting the multiple linear regression model. A p-value < 0.05 was arbitrarily adopted as the criterion of statistical significance, and for multiple comparisons it was modified according to the Bonferroni adjustment to a value of p < 0.0028. Calculations were performed with the use of PQStat v1.4.8 package. Results The incidence of malignant testicular neoplasms observed among men in Poland and in Wielkopolska Province indicated a significant rising tendency. The multiple linear regression model confirmed that the year variable is a strong incidence forecast factor only within the territory of Poland. A corresponding analysis of mortality rates among men in Poland and in Wielkopolska Province did not show any statistically significant correlations. Conclusions Late diagnosis of Polish patients calls for undertaking appropriate educational activities that would facilitate earlier reporting of the patients, thus increasing their chances for recovery. Introducing preventive examinations in the regions of increased risk of testicular tumour may allow earlier diagnosis. PMID:27095941

Proposed Nomogram Predicting the Individual Risk of Malignancy in the Patients With Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.

PubMed

Jang, Jin-Young; Park, Taesung; Lee, Selyeong; Kim, Yongkang; Lee, Seung Yeoun; Kim, Sun-Whe; Kim, Song-Cheol; Song, Ki-Byung; Yamamoto, Masakazu; Hatori, Takashi; Hirono, Seiko; Satoi, Sohei; Fujii, Tsutomu; Hirano, Satoshi; Hashimoto, Yasushi; Shimizu, Yashuhiro; Choi, Dong Wook; Choi, Seong Ho; Heo, Jin Seok; Motoi, Fuyuhiko; Matsumoto, Ippei; Lee, Woo Jung; Kang, Chang Moo; Han, Ho-Seong; Yoon, Yoo-Seok; Sho, Masayuki; Nagano, Hiroaki; Honda, Goro; Kim, Sang Geol; Yu, Hee Chul; Chung, Jun Chul; Nagakawa, Yuichi; Seo, Hyung Il; Yamaue, Hiroki

2017-12-01

This study evaluated individual risks of malignancy and proposed a nomogram for predicting malignancy of branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) using the large database for IPMN. Although consensus guidelines list several malignancy predicting factors in patients with BD-IPMN, those variables have different predictability and individual quantitative prediction of malignancy risk is limited. Clinicopathological factors predictive of malignancy were retrospectively analyzed in 2525 patients with biopsy proven BD-IPMN at 22 tertiary hospitals in Korea and Japan. The patients with main duct dilatation >10 mm and inaccurate information were excluded. The study cohort consisted of 2258 patients. Malignant IPMNs were defined as those with high grade dysplasia and associated invasive carcinoma. Of 2258 patients, 986 (43.7%) had low, 443 (19.6%) had intermediate, 398 (17.6%) had high grade dysplasia, and 431 (19.1%) had invasive carcinoma. To construct and validate the nomogram, patients were randomly allocated into training and validation sets, with fixed ratios of benign and malignant lesions. Multiple logistic regression analysis resulted in five variables (cyst size, duct dilatation, mural nodule, serum CA19-9, and CEA) being selected to construct the nomogram. In the validation set, this nomogram showed excellent discrimination power through a 1000 times bootstrapped calibration test. A nomogram predicting malignancy in patients with BD-IPMN was constructed using a logistic regression model. This nomogram may be useful in identifying patients at risk of malignancy and for selecting optimal treatment methods. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Common Head and Neck Cases in Our Consultation Referrals: Diagnostic Dilemmas in Inverted Papilloma

PubMed Central

2009-01-01

Papillomas of the nose and paranasal sinuses comprise three morphologically distinct variants—everted papilloma, inverted papilloma and cylindric cell papilloma in descending order of frequency. Recurrence of everted papilloma is unusual and malignant change does not occur. However, inverted papilloma is associated with multiple recurrences and malignant change. The histology of low grade squamous cell carcinoma of the nose may mimic that of inverted papilloma and low grade squamous cell carcinoma may coexist with inverted papilloma and be present in the same biopsy material. There is a high index of suspicion of concomitant malignancy in the presence of severe atypia or hyperkeratosis. Columnar cell papillomas are also associated with an increased risk of malignancy but the rarity of these lesions makes accurate assessment of malignant potential difficult. The most common diagnostic dilemma for pathologists referring cases for second opinion is the recognition of low grade malignancy versus benign inverted papilloma at presentation and in lesions which recur. Recent studies have addressed the requirement for histological parameters to predict the clinical course of these lesions and new molecular markers are being applied to tissue diagnosis. The early recognition and treatment of malignancy associated with inverted papilloma is key to decreased morbidity and improved patient survival and forms the basis of this discussion. PMID:20596982

Protein kinase inhibitors against malignant lymphoma

PubMed Central

D’Cruz, Osmond J; Uckun, Fatih M

2013-01-01

Introduction Tyrosine kinases (TKs) are intimately involved in multiple signal transduction pathways regulating survival, activation, proliferation and differentiation of lymphoid cells. Deregulation or overexpression of specific oncogenic TKs is implicated in maintaining the malignant phenotype in B-lineage lymphoid malignancies. Several novel targeted TK inhibitors (TKIs) have recently emerged as active in the treatment of relapsed or refractory B-cell lymphomas that inhibit critical signaling pathways, promote apoptotic mechanisms or modulate the tumor microenvironment. Areas covered In this review, the authors summarize the clinical outcomes of newer TKIs in various B-cell lymphomas from published and ongoing clinical studies and abstracts from major cancer and hematology conferences. Expert opinion Multiple clinical trials have demonstrated that robust antitumor activity can be obtained with TKIs directed toward specific oncogenic TKs that are genetically deregulated in various subtypes of B-cell lymphomas. Clinical success of targeting TKIs is dependent upon on identifying reliable molecular and clinical markers associated with select cohorts of patients. Further understanding of the signaling pathways should stimulate the identification of novel molecular targets and expand the development of new therapeutic options and individualized therapies. PMID:23496343

Sphingolipid Signaling and Hematopoietic Malignancies: To the Rheostat and Beyond

PubMed Central

Loh, Kenneth C.; Baldwin, Dianna; Saba, Julie D.

2011-01-01

Sphingosine-1-phosphate (S1P) is a bioactive lipid with diverse functions including the promotion of cell survival, proliferation, and migration, as well as the regulation of angiogenesis, inflammation, immunity, vascular permeability and nuclear mechanisms that control gene transcription. S1P is derived from metabolism of ceramide, which itself has diverse and generally growth-inhibitory effects through its impact on downstream targets involved in regulation of apoptosis, senescence and cell cycle progression. Regulation of ceramide, S1P and the biochemical steps that modulate the balance and interconversion of these two lipids are major determinants of cell fate, a concept referred to as the “sphingolipid rheostat.” There is abundant evidence that the sphingolipid rheostat plays a role in the origination, progression and drug resistance patterns of hematopoietic malignancies. The pathway has also been exploited to circumvent the problem of chemotherapy resistance in leukemia and lymphoma. Given the broad effects of sphingolipids, targeting multiple steps in the metabolic pathway may provide possible therapeutic avenues. However, new observations have revealed that sphingolipid signaling effects are more complex than previously recognized, requiring a revision of the sphingolipid rheostat model. Here, we summarize recent insights regarding the sphingolipid metabolic pathway and its role in hematopoietic malignancies. PMID:21707493

Giant melanocytic nevus with malignant melanoma: a rare disorder in a black African child.

PubMed

Katibi, Oludolapo Sherifat; Ogunbiyi, Adebola; Brown, Biobele Jotham; Adeyemi, Oyedeji Oladele

2014-10-01

Giant congenital melanocytic nevus (GCMN) is rare in babies of African descent. Unfortunately, it has an increased potential for malignant transformation. A 3-year-old female child presented with a 6-month history of multiple nodules on an existing giant congenital melanocytic nevus and swelling in the right axilla of four weeks duration. Skin biopsy of the nodular skin lesions was in keeping with a metastatic malignant melanoma (Clark stage 4). She completed a full course of chemotherapy but subsequently died four months after presentation. Patients with large GCMN should be counseled and followed up appropriately to improve and prolong life. © 2014 The International Society of Dermatology.

Epithelioid Malignant Peripheral Nerve Sheath Tumor Arising in a Schwannoma, in a Patient with “Neuroblastoma-like” Schwannomatosis and a Novel Germline SMARCB1 mutation

PubMed Central

Carter, Jodi M.; O'Hara, Carolyn; Dundas, George; Gilchrist, Dawna; Collins, Mark S.; Eaton, Katherine; Judkins, Alexander R.; Biegel, Jaclyn A.; Folpe, Andrew L.

2011-01-01

Epithelioid malignant peripheral nerve sheath tumors arising in pre-existing schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but one of which showed “neuroblastoma-like” histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and three of her children, two of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain. PMID:22082606

Cholangiocarcinoma…Or Not?

PubMed Central

Kenny, Patrick; Kerns, Tamie

2013-01-01

Introduction Cholangiocarcinoma includes all tumors originating in the epithelium of the bile duct and is the ninth most common gastrointestinal tract cancer. Metastatic disease may also rarely be present in the common bile duct. We present a case of metastatic malignant melanoma presenting as obstructive hepatitis and initially was thought to be and was almost treated as cholangiocarcinoma prior to adequate tissue sampling. Case Report A 76-year-old man presented with nausea, vomiting, and painless jaundice. He had a mixed hepatocellular pattern with transaminases and alkaline phosphatase greater than 1000 and total bilirubin of 12. A three-phase liver CT showed an enhancing mass within a dilated common bile duct and extension of the mass into the right and left intrahepatic bile ducts. He subsequently underwent ERCP with bile duct brushings and stent placement. Bile duct brushings showed benign reactive ductal epithelial cells. An endoscopic ultrasound with fine needle aspiration of the bile duct mass was performed. Pathology was negative for CK7, CK20, and positive for S100, Pan-melanoma, and negative for BRAF. No suspicious skin lesions were seen on close inspection by a dermatologist. However, two years prior the patient was diagnosed with cutaneous malignant melanoma in situ that was surgically resected. Thus, it was felt that this case represented metastatic melanoma to the bile duct. Due to significant comorbidities the patient was determined to be a poor surgical candidate. He has completed first line therapy for unresectable multiple melanoma with four rounds of ipilimumab. Discussion Pathologic diagnosis of cholangiocarcinoma is often difficult to obtain from ERCP secondary to paucicellularity of these tumors and with no imaging modality that is specific for cholangiocarcinma. The hepatobiliary tract is a possible, though relatively rare, location for metastatic focus of malignant melanoma and should be considered in a patient with a history of melanoma and no tissue diagnosis after ERCP. There are multiple case reports of metastatic melanoma to the ampula of Vater causing obstructive hepatitis, but only 10 reports of disease found in the common bile duct. This case highlights the importance of obtaining tissue from suspected malignant lesions using various forms of endoscopy to ensure proper treatment and prolonged survival.

Biomarkers in Tumorigenesis Using Cancer Cell Lines: A Systematic Review

PubMed Central

K, Lizbeth Raju; Augustine, Dominic; Rao, Roopa S; SV, Sowmya; Haragannavar, Vanishri C; Nambiar, Shwetha; Prasad, Kavitha; Awan, Kamran Habib; Patil, Shankargouda

2017-01-01

Cancer is a leading cause of death worldwide. Despite many research advancements in the field, the genetic changes regulating the transformation of normal oral cells into malignant cells have not been fully elucidated. Several studies have evaluated carcinogenesis at the molecular level. Cancer cell lines are commonly used in biomedical research because they provide an unlimited source of cells and represent various stages of initiation and progression of carcinogenesis in vitro. Aims: The objective of the study was to review original research articles using cancer cell lines as a tool to understand carcinogenesis and to identify the genes involved in tumor development. Additionally, we also examined the application of the genes as predictive biomarkers. Methods and Materials: Several databases, including PubMed, Google Scholar, Ebsco, and Science Direct, were searched from 1985 to December 2016 using various combinations of the following key words: “mouth neoplasm”, “cell lines”, and “tumorigenesis”. Original experimental studies published in English were included. We excluded letters to the editor, historic reviews, and unpublished data from the analysis. Results: There were 17 studies (in vitro) included in the analysis. There were 14 genes and 4 miRNAs involved in malignant transformation of oral keratinocytes into cancer cells. The most commonly studied genes were p53, cyclin D1, and hTERT. Conclusion: Additional reviews and studies are needed to identify a panel of genes specific to various potentially malignant disorders and to aid in the early detection of oral squamous cell carcinoma (OSCC) because tumorigenesis involves the mutation of multiple genes. Furthermore, improving advanced cost-effective diagnostic methods may benefit the public health sector. PMID:28950674

The Bethesda system for reporting thyroid cytopathology: An experience of 1,382 cases in a community practice setting with the implication for risk of neoplasm and risk of malignancy.

PubMed

Wu, Howard Her-Juing; Rose, Crystal; Elsheikh, Tarik M

2012-05-01

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has provided a set of uniform diagnostic terminology including benign (B), atypia of undetermined significance (AUS), follicular neoplasm (FN), suspicious for malignancy (SM), malignancy (M), and nondiagnostic (ND) for the interpretation of thyroid fine-needle aspiration (FNA). We applied this terminology on our 1,382 thyroid aspirates in a community practice setting, which included 539 cases of B (39%), 376 cases of AUS (27.2%), 116 cases of FN (8.4%), 37 cases of malignant (2.7%), 36 cases of SM (2.6%), and 278 cases of ND (20.1%). Two hundred twenty-one cases (16%) of thyroid FNA had corresponding follow-up thyroidectomies. Each diagnostic category represented a unique association with risk of malignancy and risk of neoplasm. Based on histologic follow-up, the risk of neoplasm (including benign and malignant neoplasm) was B 14%, AUS 44%, FN 67%, SM 77%, and M 100% and the risk of malignancy was B 3%, AUS 6%, FN 22%, SM 56%, and M 100%. The classification and follow-up recommendation of TBSRTC are appropriate for each category. Both B and AUS are low-risk lesions with low probability of malignancy. FN predicts a higher rate for neoplasm but an intermediate rate for malignancy while SM carries a high risk for malignancy. Copyright © 2011 Wiley-Liss, Inc.

OSTEOCHONDROMA OF THE PROXIMAL HUMERUS WITH FRICTIONAL BURSITIS AND SECONDARY SYNOVIAL OSTEOCHONDROMATOSIS.

PubMed

De Groote, J; Geerts, B; Mermuys, K; Verstraete, K

2015-01-01

We report a case of multiple hereditary exostosis in a 33-year old patient with clinical symptoms of pain and impression of a growing mass of the left shoulder alerting potential risk of malignant transformation of an osteochondroma. Imaging studies illustrated perilesional bursitis surrounding an osteochondroma of the proximal humerus. Malignant transformation was excluded with MRI. Fragments of the osteochondroma were dislocated in the inflammatory synovial bursa illustrating a case of secondary synovial osteochondromatosis.

Percutaneous biliary drainage using open cell stents for malignant biliary hilar obstruction.

PubMed

Ahn, Sun Jun; Bae, Jae Ik; Han, Tae Sun; Won, Je Hwan; Kim, Ji Dae; Kwack, Kyu-Sung; Lee, Jae Hee; Kim, Young Chul

2012-01-01

To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n = 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

PubMed

Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

2012-08-29

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Venetoclax: First Global Approval.

PubMed

Deeks, Emma D

2016-06-01

Venetoclax (Venclexta™) is an oral selective inhibitor of the prosurvival protein BCL-2 and therefore restores the apoptotic ability of malignant cells. The drug arose from research by Abbott Laboratories (now AbbVie) during a collaboration with Genentech and is being co-developed by AbbVie and Genentech/Roche primarily for the treatment of haematological malignancies. Venetoclax is approved in the USA for use as monotherapy in patients with chronic lymphocytic leukaemia (CLL) with the 17p deletion (as detected by an approved FDA test) who have received at least one prior therapy, and is awaiting approval for similar indications in the EU and Canada. Venetoclax is also in phase I-III development as combination therapy for CLL, phase I/II development as monotherapy and/or combination therapy for non-Hodgkin lymphomas (including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma) and acute myeloid leukaemia, and phase I development for multiple myeloma, systemic lupus erythematosus and breast cancer. This article summarizes the milestones in the development of venetoclax leading to this first approval for CLL.

[Hematopoietic stem cell transplantation. Indications, foundations and perspective].

PubMed

Buchholz, S; Ganser, A

2009-05-01

The hematopoietic stem cell transplantation (HSCT) has become a standard therapy for many inherited and acquired disorders of the bone marrow and immune system. Autologous HSCT is mainly done as part of the primary therapy in multiple myeloma and as part of relapse therapy in malignant lymphoma. In contrast, allogeneic HSCT is predominantly performed in patients with acute leukemias. The selection process for allogeneic HSCT takes disease-specific as well as patient-specific factors into account. Risk factors which can predict for poor response to chemotherapy can now be identified in acute myeloid as well as lymphoid leukemia, based on phenotype, cytogenetics, molecular genetics and response to therapy. In these patients allogeneic HSCT can improve overall survival from 0-20% to 30-60%. New conditioning protocols have now raised the upper age limit for transplantation to 70 years. In elderly patients the selection of patients based on absence of comorbidities becomes especially important. The increasing number of long-term survivors requires knowledge of organ-specific late toxicities including secondary malignancies.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

Arsenic Trioxide – An Old Drug Rediscovered

PubMed Central

Emadi, Ashkan; Gore, Steven D.

2010-01-01

Over the last 17 years, clinical trials conducted worldwide have demonstrated the efficacy of arsenic trioxide (As2O3) in the treatment of relapsed acute promyelocytic leukemia (APL). Currently, the role of As2O3 in front-line therapy is under investigation. Recent trials in the US have demonstrated that the addition of As2O3 to standard treatment regimens improves survival outcomes in patients with APL and may allow a reduction in cytotoxic chemotherapy exposure. As2O3 has also shown efficacy in other malignancies, particularly multiple myeloma and myelodysplastic syndromes. Therapeutic doses of As2O3 are well tolerated, with no evidence of long-term toxicity. Adverse events include APL differentiation syndrome, electrocardiographic abnormalities, and mild elevations in liver enzymes. This review highlights trials investigating the role of As2O3 in induction and consolidation for newly diagnosed APL, as well as its role in other hematologic malignancies. The chemistry, mechanisms of action, and clinical side effects of As2O3 are also discussed. PMID:20471733

Multiple sclerosis - etiology and diagnostic potential.

PubMed

Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

2017-06-30

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

Rational combination strategies to enhance venetoclax activity and overcome resistance in hematologic malignancies.

PubMed

Grant, Steven

2018-06-01

Venetoclax (ABT-199) is a Bcl-2-specific BH3-mimetic that has shown significant promise in certain subtypes of CLL as well as in several other hematologic malignancies. As in the case of essentially all targeted agents, intrinsic or acquired resistance to this agent generally occurs, prompting the search for new strategies capable of circumventing this problem. A logical approach to this challenge involves rational combination strategies designed to disable preexisting or induced compensatory survival pathways. Many of these strategies involve downregulation of Mcl-1, a pro-survival Bcl-2 family member that is not targeted by venetoclax, and which often confers resistance to this agent. Given encouraging clinical results involving venetoclax in both lymphoid and myeloid malignancies, it is likely that such combination approaches will be incorporated into the therapeutic armamentarium for multiple hematologic malignancies in the near future.

Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

ClinicalTrials.gov

2018-06-25

Advanced Malignant Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Cervical Carcinoma; Colon Carcinoma; Colorectal Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Glioma; Head and Neck Carcinoma; Kidney Carcinoma; Liver and Intrahepatic Bile Duct Carcinoma; Lung Carcinoma; Lymphoma; Malignant Uterine Neoplasm; Melanoma; Ovarian Carcinoma; Pancreatic Carcinoma; Plasma Cell Myeloma; Prostate Carcinoma; Rectal Carcinoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Colon Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Glioma; Recurrent Head and Neck Carcinoma; Recurrent Liver Carcinoma; Recurrent Lung Carcinoma; Recurrent Lymphoma; Recurrent Malignant Solid Neoplasm; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Carcinoma; Recurrent Plasma Cell Myeloma; Recurrent Prostate Carcinoma; Recurrent Rectal Carcinoma; Recurrent Skin Carcinoma; Recurrent Thyroid Gland Carcinoma; Recurrent Uterine Corpus Carcinoma; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Plasma Cell Myeloma; Skin Carcinoma; Thyroid Gland Carcinoma; Uterine Corpus Cancer

Predicting the impact of combined therapies on myeloma cell growth using a hybrid multi-scale agent-based model.

PubMed

Ji, Zhiwei; Su, Jing; Wu, Dan; Peng, Huiming; Zhao, Weiling; Nlong Zhao, Brian; Zhou, Xiaobo

2017-01-31

Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth. We constructed a hybrid multi-scale agent-based model (HABM) that combines an ODE system and Agent-based model (ABM). The ODEs was used for modeling the dynamic changes of intracellular signal transductions and ABM for modeling the cell-cell interactions between stromal cells, tumor, and immune components in the BM. This model simulated myeloma growth in the bone marrow microenvironment and revealed the important role of immune system in this process. The predicted outcomes were consistent with the experimental observations from previous studies. Moreover, we applied this model to predict the treatment effects of three key therapeutic drugs used for MM, and found that the combination of these three drugs potentially suppress the growth of myeloma cells and reactivate the immune response. In summary, the proposed model may serve as a novel computational platform for simulating the formation of MM and evaluating the treatment response of MM to multiple drugs.

Quadruple cancer including Bowen's disease after arsenic injections 40 years earlier: report of a case.

PubMed

Murata, K; Iwazawa, T; Takayama, T; Yamashita, K; Okagawa, K

1994-01-01

This report describes the successful treatment of quadruple cancer including Bowen's disease in a 71-year-old man who had been given injections of salvarsan, an arsenic compound, for syphilis more than 40 years earlier. Resection of a skin lesion on his chest subsequently confirmed a diagnosis of Bowen's disease, 3 years after which he was operated on for concurrent gastric cancer and sigmoid colon cancer. A fourth cancer was discovered on his left vocal cord 2 weeks after this operation; it was resected 2 years later. A discussion of multiple malignant neoplasms and the possible relationship between arsenic and cancer is presented following this case report.

Malignant insulinoma with hepatic and pulmonary metastases associated with primary hyperparathyroidism. Case report and review of the literature

PubMed Central

A., Albu; A., Zirnea; O., Georgescu; D., Terzea; D., Jinga; S., Fica

2008-01-01

Malignant insulinomas are rare tumors (10% of insulinomas) that often present as multicentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30mg/dl) associated with increased insulin level (16μU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71,2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma. PMID:20108468

Single vs. combination immunotherapeutic strategies for glioma

PubMed Central

Chandran, Mayuri; Candolfi, Marianela; Shah, Diana; Mineharu, Yohei; Yadav, Vivek; Koschmann, Carl; Asad, Antonela S.; Lowenstein, Pedro R.; Castro, Maria G.

2017-01-01

Introduction Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific featuresmay substantially improve upon existing treatments. Areas covered Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review we discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While we describe a limited number of combination immunotherapies which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration. PMID:28286975

Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

PubMed

Silverberg, J I; Ratner, D

2015-07-01

Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P < 0.0001). Smokers with a history of NMSC or melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P < 0.0001). History of NMSC was associated with higher odds of malignancies of the bladder, brain, breast, colon, oesophagus, kidney, lung, lymphoma, melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P < 0.0001), with even higher rates of increase in those with history of NMSC or melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

Computer-aided classification of mammographic masses using the deep learning technology: a preliminary study

NASA Astrophysics Data System (ADS)

Qiu, Yuchen; Yan, Shiju; Tan, Maxine; Cheng, Samuel; Liu, Hong; Zheng, Bin

2016-03-01

Although mammography is the only clinically acceptable imaging modality used in the population-based breast cancer screening, its efficacy is quite controversy. One of the major challenges is how to help radiologists more accurately classify between benign and malignant lesions. The purpose of this study is to investigate a new mammographic mass classification scheme based on a deep learning method. In this study, we used an image dataset involving 560 regions of interest (ROIs) extracted from digital mammograms, which includes 280 malignant and 280 benign mass ROIs, respectively. An eight layer deep learning network was applied, which employs three pairs of convolution-max-pooling layers for automatic feature extraction and a multiple layer perception (MLP) classifier for feature categorization. In order to improve robustness of selected features, each convolution layer is connected with a max-pooling layer. A number of 20, 10, and 5 feature maps were utilized for the 1st, 2nd and 3rd convolution layer, respectively. The convolution networks are followed by a MLP classifier, which generates a classification score to predict likelihood of a ROI depicting a malignant mass. Among 560 ROIs, 420 ROIs were used as a training dataset and the remaining 140 ROIs were used as a validation dataset. The result shows that the new deep learning based classifier yielded an area under the receiver operation characteristic curve (AUC) of 0.810+/-0.036. This study demonstrated the potential superiority of using a deep learning based classifier to distinguish malignant and benign breast masses without segmenting the lesions and extracting the pre-defined image features.

Organ differences in the impact of p27(kip1) deficiency on carcinogenesis induced by N-methyl-N-nitrosourea.

PubMed

Ogawa, Kumiko; Murasaki, Toshiya; Sugiura, Satoshi; Nakanishi, Makoto; Shirai, Tomoyuki

2013-06-01

To evaluate the impact of p27 on carcinogenesis in various organs, N-methyl-N-nitrosourea (MNU), a direct-acting alkylating agent, was given to p27 knock-out mice. Groups of 20-40 male and female mice with null, hetero- or wild-type p27 alleles were given drinking water containing 240 ppm MNU or distilled water every other week for five cycles. The incidence and multiplicity of the induced proliferative lesions were then histologically evaluated at weeks 14 and 20. MNU treatment induced various lesions including squamous hyperplasia and squamous cell carcinoma in the forestomach, atypical hyperplasia and adenocarcinomas in the fundic and pyloric glands, adenomas and adenocarcinomas in the duodenum, malignant lymphomas in the thymus, liver, kidney and spleen and alveolar hyperplasia, adenomas, adenocarcinomas and malignant lymphomas in the lung. Although the incidences of the lesions in the forestomach, fundic and pyloric glands did not differ among the p27 genotypes, those of alveolar hyperplasia of the lung and malignant lymphoma of the thymus were significantly increased in p27-null males as compared with both wild- and hetero-type animals. Moreover, in both p27(+/+) and p27(+/-) cases, the rates for p27-positive cells were obviously increased in proliferative lesions of the pyloric gland and the lung. However, an increased rate of p27-positive cells was not observed in malignant lymphoma of the thymus. These findings suggest that p27 does not control the cell cycle equally in all organs affected by MNU-induced carcinogenesis. Copyright © 2011 John Wiley & Sons, Ltd.

Adrenal Gland Cancer

MedlinePlus

... either benign or malignant. Benign tumors aren't cancer. Malignant ones are. Most adrenal gland tumors are ... and may not require treatment. Malignant adrenal gland cancers are uncommon. Types of tumors include Adrenocortical carcinoma - ...

Risk of malignant transformation in patients with monoclonal gammopathy of undetermined significance.

PubMed

Pasqualetti, P; Casale, R

1997-01-01

The acturial probability of malignant transformation was analyzed in a series of 263 patients with monoclonal gammopathy of undetermined significance (MGUS) over a 15-year period and followed from 5 to 20 years. At a median follow-up of 11.5 years, 157 patients (59.7%) had died of causes unrelated to MGUS, 47 (17.9%) were still alive and presented no increase in monoclonal component, 11 (4.1%) presented an increase in monoclonal component without evidence of malignant immunoproliferative disease, and 48 (18.3%) had developed a malignant transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia, three of malignant lymphoma, two of amyloidosis, one of chronic lymphocytic leukemia, and one of plasma cell leukemia. The cumulative incidence of malignant transformation was 18.3%; and the actuarial risk of malignant transformation was 6.1, 15.4, and 31.3% at 5, 10 and 20 years, respectively. The multivariate regression analysis according to Cox's proportional hazard model selected among 22 different variables established at initial diagnosis of MGUS only age as the factor significantly (P < 0.011) and negatively (b = -1.104) related to the risk of developing a malignant immunoproliferative disease. Therefore, patients with MGUS present an increased risk of developing a malignant lymphoproliferative or plasma cell proliferative disease, and MGUS could be considered a pre-neoplastic condition. Since no clinical or laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up periodically and over an indefinite period.

Malignant Mesothelioma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Malignant mesothelioma treatment may include surgery, radiation therapy, and chemotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent malignant mesothelioma in this summary for clinicians.

Comprehensive molecular profiling of 718 Multiple Myelomas reveals significant differences in mutation frequencies between African and European descent cases

PubMed Central

Christofferson, Austin; Aldrich, Jessica; Jewell, Scott; Kittles, Rick A.; Derome, Mary; Craig, David Wesley; Carpten, John D.

2017-01-01

Multiple Myeloma (MM) is a plasma cell malignancy with significantly greater incidence and mortality rates among African Americans (AA) compared to Caucasians (CA). The overall goal of this study is to elucidate differences in molecular alterations in MM as a function of self-reported race and genetic ancestry. Our study utilized somatic whole exome, RNA-sequencing, and correlated clinical data from 718 MM patients from the Multiple Myeloma Research Foundation CoMMpass study Interim Analysis 9. Somatic mutational analyses based upon self-reported race corrected for ancestry revealed significant differences in mutation frequency between groups. Of interest, BCL7A, BRWD3, and AUTS2 demonstrate significantly higher mutation frequencies among AA cases. These genes are all involved in translocations in B-cell malignancies. Moreover, we detected a significant difference in mutation frequency of TP53 and IRF4 with frequencies higher among CA cases. Our study provides rationale for interrogating diverse tumor cohorts to best understand tumor genomics across populations. PMID:29166413

Patients with urologic cancer and other nonurologic malignancies: analysis of a sample and review of the literature.

PubMed

Mydlo, J H; Gerstein, M

2001-12-01

To describe our experience with patients with urologic cancers who also have malignancies of nonurologic origin, before, after, or simultaneously, to review the literature, and to suggest treatment options. We reviewed our institutions' tumor registry from 1995 to 2000 to discover how many patients had a urologic malignancy and another nonurologic cancer (antecedent, subsequent, or synchronous). We reviewed Medline from 1966 to 2000 and also questioned several urologists at major centers in the United States concerning this clinical dilemma. We encountered 18 patients during a 6-year period with a urologic cancer and another primary malignancy. Thirteen patients had their second cancer detected during the workup of their primary urologic tumor. Two patients developed a second tumor within 1 year of treatment of the primary urologic tumor. Another patient was referred with two primaries already diagnosed, and another had renal carcinoma detected during her colon cancer workup. We found that multiple tumors, although very rare, are usually detected during the preoperative workup of the primary tumor, usually by physical examination and improved radiologic imaging, or during the follow-up examinations. Most reports suggest that treatment should be performed simultaneously, especially if the lesions are relatively small and require a single incision, and the patient's medical condition allows longer anesthesia exposure. If these prerequisites are not met, most investigators agree that treatment should be directed at the more aggressive lesion first, which may improve the condition and/or survival, and thus, if a second operation is warranted, it will be possible. Although patients with multiple malignancies are rare, the urologist and/or other specialist should be alerted to this possibility when evaluating patients for the initially presenting symptoms and/or detected tumor, as well as during the follow-up evaluations.

Primary Germ Cell Tumor of Testes with Extensive Lymph Nodal and Splenic Metastases Masquerading Lymphoma on 18-F-FDG PET/CT

PubMed Central

Tripathy, Sarthak; Mukherjee, Anirban; Bal, Chandrasekhar; Tripathi, Madhavi; Mallick, Saumyaranjan; Shamim, Shamim Ahmed

2017-01-01

Germ cell tumors (GCT) account for the 95% of the malignancies associated with testes. They are the most common solid malignancies affecting the males in the age group of 15–35 years. It is known to be bilateral in 3% of cases. We herein present FDG PET-CT findings of a case with biopsy proven GCT with multiple lymph nodal and splenic metastases mimicking lymphomatous neoplasm. PMID:28533651

An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

PubMed

Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

2015-07-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

Circadian and seasonal variation of malignant arrhythmias in a pediatric and congenital heart disease population.

PubMed

Stephenson, Elizabeth A; Collins, Kathryn K; Dubin, Anne M; Epstein, Michael R; Hamilton, Robert M; Kertesz, Naomi J; Alexander, Mark E; Cecchin, Frank; Triedman, John K; Walsh, Edward P; Berul, Charles I

2002-10-01

Recent studies in adult populations have revealed seasonal variation in the frequency of acute cardiovascular events, including life-threatening arrhythmias, demonstrating increased events during winter and early spring. Trends in the time of day that arrhythmias occur also were noted. We sought to establish whether pediatric and young adult congenital heart disease implantable cardioverter defibrillator (ICD) recipients have circadian or seasonal variability in shock frequency, similar to adult populations. Data from ICD patients at six pediatric centers in North America were analyzed to assess the timing of life-threatening arrhythmias. The populations consisted of children and adults with congenital heart disease and ICDs placed for malignant arrhythmias. Data were considered in 46 patients who received appropriate therapy (total 139 episodes) for ventricular tachycardia or ventricular fibrillation. Multiple variables were analyzed, including time of day, day of week, and month of year. In contrast to previously studied adult patients, fewer events occurred in the early morning (7.5%), with the most therapies occurring between 6 P.M. and midnight (35%). An increased frequency of therapies was observed in the fall and winter (September-January), representing 60% of all appropriate shocks. Unlike adult populations, Mondays did not have an increased frequency of malignant arrhythmias. Pediatric and adult congenital heart disease populations have moderate seasonal and 24-hour variation in ICD event rate, with some distinctly different peaks than those seen in typical adult ICD populations. These findings suggest circadian variation in arrhythmia vulnerability that may differ from conventional occupational, physical, or emotional stressors. (J Cardiovasc Electrophysiol, Vol. 13, pp.

CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.

PubMed

Nishibaba, Rie; Higashi, Yuko; Su, Juan; Furukawa, Tatsuhiko; Kawai, Kazuhiro; Kanekura, Takuro

2012-01-01

CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK. © 2011 Japanese Dermatological Association.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

PubMed

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC scores for any S1PR (cytoplasmic or nuclear) between benign and malignant changes. This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

PubMed Central

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M.; Zhou, Xinchun

2014-01-01

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC score of any S1PR (cytoplasmic or nuclear) between benign and malignant changes. Conclusion This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. PMID:25084322

Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-06-05

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic; Leukemia, Lymphoblastic, Acute; Lymphocytic Leukemia, Chronic; Myelodysplastic Syndromes; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma

PubMed Central

Murray, Megan Y; Zaitseva, Lyubov; Auger, Martin J; Craig, Jenny IO; MacEwan, David J; Rushworth, Stuart A; Bowles, Kristian M

2015-01-01

Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10–15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ). We identified enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5 μM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously bortezomib-resistant MM cells to further bortezomib therapy at a physiologically relevant concentration (5 nM). Further analysis of pro-survival signaling revealed a role for the NF-κB p65 subunit in MM bortezomib-resistance, thus a combination of BTK and NF-κB p65 inhibition, either pharmacologically or via further lenti-viral miRNA NF-κB p65 interference, also restored sensitivity to bortezomib, significantly reducing cell viability (37.5 ± 6 .9 %, ANOVA P ≤ 0 .001). Accordingly, we propose the clinical evaluation of a bortezomib/ibrutinib combination therapy, including in patients resistant to single-agent bortezomib. PMID:25565020

Ibrutinib inhibits BTK-driven NF-κB p65 activity to overcome bortezomib-resistance in multiple myeloma.

PubMed

Murray, Megan Y; Zaitseva, Lyubov; Auger, Martin J; Craig, Jenny Io; MacEwan, David J; Rushworth, Stuart A; Bowles, Kristian M

2015-01-01

Multiple Myeloma (MM) is a haematologic malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. Over the last 10-15 y the introduction of the proteasome-inhibitor bortezomib has improved MM prognosis, however relapse due to bortezomib-resistance is inevitable and the disease, at present, remains incurable. To model bortezomib-resistant MM we generated bortezomib-resistant MM cell lines (n = 4 ) and utilised primary malignant plasma cells from patients relapsing after bortezomib treatment (n = 6 ). We identified enhanced Bruton's tyrosine kinase (BTK) activity in bortezomib-resistant MM cells and found that inhibition of BTK, either pharmacologically with ibrutinib (0.5 μM) or via lenti-viral miRNA-targeted BTK interference, re-sensitized previously bortezomib-resistant MM cells to further bortezomib therapy at a physiologically relevant concentration (5 nM). Further analysis of pro-survival signaling revealed a role for the NF-κB p65 subunit in MM bortezomib-resistance, thus a combination of BTK and NF-κB p65 inhibition, either pharmacologically or via further lenti-viral miRNA NF-κB p65 interference, also restored sensitivity to bortezomib, significantly reducing cell viability (37.5 ± 6 .9 %, ANOVA P ≤ 0 .001). Accordingly, we propose the clinical evaluation of a bortezomib/ibrutinib combination therapy, including in patients resistant to single-agent bortezomib.

Proof of Concept: A review on how network and systems biology approaches aid in the discovery of potent anticancer drug combinations

PubMed Central

Azmi, Asfar S.; Wang, Zhiwei; Philip, Philip A.; Mohammad, Ramzi M.; Sarkar, Fazlul H.

2010-01-01

Cancer therapies that target key molecules have not fulfilled expected promises for most common malignancies. Major challenges include the incomplete understanding and validation of these targets in patients, the multiplicity and complexity of genetic and epigenetic changes in the majority of cancers, and the redundancies and cross-talk found in key signaling pathways. Collectively, the uses of single-pathway targeted approaches are not effective therapies for human malignances. To overcome these barriers, it is important to understand the molecular cross-talk among key signaling pathways and how they may be altered by targeted agents. This requires innovative approaches such as understanding the global physiological environment of target proteins and the effects of modifying them without losing key molecular details. Such strategies will aid the design of novel therapeutics and their combinations against multifaceted diseases where efficacious combination therapies will focus on altering multiple pathways rather than single proteins. Integrated network modeling and systems biology has emerged as a powerful tool benefiting our understanding of drug mechanism of action in real time. This mini-review highlights the significance of the network and systems biology-based strategy and presents a “proof-of-concept” recently validated in our laboratory using the example of a combination treatment of oxaliplatin and the MDM2 inhibitor MI-219 in genetically complex and incurable pancreatic adenocarcinoma. PMID:21041384

Concurrent BRAF and PTEN mutations in melanoma of unknown origin presenting as a breast mass

PubMed Central

Agosto-Arroyo, Emmanuel; Rosa, Marilin; Chau, Alec; Khazai, Laila

2017-01-01

Background: Metastases represent a small percentage of the malignancies affecting the breast, and only 5% of melanomas originate from non-cutaneous sites. Multiple genetic aberrations have been associated with the development of melanocytic lesions, including BRAF V600E mutation. Mutations in PTEN gene have also been related to the pathogenesis of multiple malignancies. Purpose/Method: This is the case of a 28-year-old female who presented with a tender, palpable mass in the upper outer quadrant of the right breast. Ultrasound showed a 1-cm solid mass, initially diagnosed as invasive ductal carcinoma on biopsy. During pre-operative workup, a second mass was identified and biopsied. Immunohistochemical stains performed on the second mass biopsy demonstrated that the neoplastic cells were positive for cytokeratin AE1/3, pan-melanoma, tyrosinase, and SOX-10 and negative for CK7, CAM5.2, and GATA-3. Subsequent workup showed widespread metastatic disease involving the liver, lungs, bones, and brain. The brain metastasis tested positive for BRAF p.V600E and PTEN p.R130Efs*4 mutations. Thorough skin and eye examination did not reveal a primary melanoma. Conclusion: Only few reports have been published of melanoma presenting as a breast mass. This is an interesting case due to the clinical presentation, diagnostic challenges, and genetic mutations profile. PMID:28607685

Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.

PubMed

Valent, Peter; Akin, Cem; Arock, Michel; Bock, Christoph; George, Tracy I; Galli, Stephen J; Gotlib, Jason; Haferlach, Torsten; Hoermann, Gregor; Hermine, Olivier; Jäger, Ulrich; Kenner, Lukas; Kreipe, Hans; Majeti, Ravindra; Metcalfe, Dean D; Orfao, Alberto; Reiter, Andreas; Sperr, Wolfgang R; Staber, Philipp B; Sotlar, Karl; Schiffer, Charles; Superti-Furga, Giulio; Horny, Hans-Peter

2017-12-01

Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The Diagnostic and Prognostic Value of Hematological and Chemical Abnormalities in Soft Tissue Sarcoma: A Comparative Study in Patients with Benign and Malignant Soft Tissue Tumors.

PubMed

Ariizumi, Takashi; Kawashima, Hiroyuki; Ogose, Akira; Sasaki, Taro; Hotta, Tetsuo; Hatano, Hiroshi; Morita, Tetsuro; Endo, Naoto

2018-01-01

The value of routine blood tests in malignant soft tissue tumors remains uncertain. To determine if these tests can be used for screening, the routine pretreatment blood test findings were retrospectively investigated in 359 patients with benign and malignant soft tissue tumors. Additionally, the prognostic potential of pretreatment blood abnormalities was evaluated in patients with soft tissue sarcomas. We compared clinical factors and blood tests findings between patients with benign and malignant soft tissue tumors using univariate and multivariate analysis. Subsequently, patients with malignant tumors were divided into two groups based on blood test reference values, and the prognostic significance of each parameter was evaluated. In the univariate analysis, age, tumor size, and tumor depth were significant clinical diagnostic factors. Significant increases in the granulocyte count, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), and γ-glutamyl transpeptidase (γ-GTP) levels were found in patients with malignant soft tissue tumors. Multiple logistic regression showed that tumor size and ESR were independent factors that predicted malignant soft tissue tumors. The Kaplan-Meier survival analysis revealed that granulocyte counts, γ-GTP levels, and CRP levels correlated significantly with overall survival. Thus, pretreatment routine blood tests are useful diagnostic and prognostic markers for diagnosing soft tissue sarcoma. © 2018 by the Association of Clinical Scientists, Inc.

Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary

PubMed Central

Dosi, Rupal; Ambaliya, Annirudh; Joshi, Harshal; Patell, Rushad

2014-01-01

Serotonin syndrome and neuroleptic malignant syndrome are two drug toxidromes that have often overlapping and confusing clinical pictures. We report a case of a young man who presented with alteration of mental status, autonomic instability and neuromuscular hyperexcitability following ingestion of multiple psychiatric and antiepileptic medications. The patient satisfied criteria for serotonin syndrome and neuroleptic malignant syndrome, and based on the characteristic clinical features, laboratory findings and clinical course it was concluded that the patient had both toxidromes. The patient was managed with cyproheptadine and supportive measures, and recovered over the course of 3 weeks. A brief review of literature highlighting the diagnostic clues as well as the importance of recognising and distinguishing the often missed and confounding diagnoses follows. PMID:24957740

Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Undergoing Single Umbilical Cord Blood Transplant

ClinicalTrials.gov

2017-08-31

Single Umbilical Cord Blood Transplantation; Non-myeloablative Conditioning; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Multiple Myeloma; Chronic Lymphocytic Leukemia

Periocular Skin Cancer in Solid Organ Transplant Recipients.

PubMed

Perry, Julian D; Polito, Sara C; Chundury, Rao V; Singh, Arun D; Fritz, Michael A; Vidimos, Allison T; Gastman, Brian R; Koyfman, Shlomo A

2016-01-01

To determine the proportion of solid organ transplant recipients developing periocular nonmelanoma skin cancer and to describe the morbidity of these cancers in transplant recipients. Cohort study. Consecutive patients undergoing solid organ transplantation at the Cleveland Clinic between 1990 and 2008. The charts of all patients receiving a solid organ transplant from 1990-2008 evaluated in the dermatology department for a subsequent biopsy-proven head and neck malignancy through April 2015 were reviewed. Patients with a periocular region nonmelanoma skin cancer (NMSC) or a nonperiocular NMSC causing a complication requiring eyelid surgery were included. Charts were reviewed for demographic data; transplant date, type, and source; immunosuppressive agents received at diagnosis; and type of NMSC, number of nonperiocular NMSCs, ophthalmologic findings, and periocular sequelae after the repair. Primary outcome measures included the type, location, final defect size, tumor-node-metastasis classification, presence of perineural invasion, and reconstruction technique(s) used for each periocular NMSC. Secondary outcome measures included the type and treatment of ocular sequelae due to nonperiocular facial NMSC. A total of 3489 patients underwent solid organ transplantation between 1990 and 2008. Of these, 420 patients were evaluated in the dermatology clinic for biopsy-proven NMSC of the head and neck during the study period, and 11 patients (15 malignancies) met inclusion criteria. Nine patients developed 12 periocular malignancies and 3 patients required eyelid surgery for facial malignancies outside the periocular zone. All 11 patients developed a squamous cell carcinoma (14 malignancies), and 1 patient (1 malignancy) also developed a periocular basal cell carcinoma. There was orbital invasion in 4 cases and paranasal and/or cavernous sinus invasion in 3 cases. Two patients underwent exenteration. Seven cases required reconstruction with a free flap or graft. Periocular sequelae included lower eyelid ectropion (6 malignancies), dry eye and/or exposure symptoms (8 malignancies), unilateral vision loss (3 malignancies), and facial nerve paresis (5 malignancies). Squamous cell carcinoma affecting the periocular region represents a risk of solid organ transplantation and may produce significant ocular morbidity, including the need for major eyelid reconstruction, globe loss, and disfiguring surgery. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Trial watch

PubMed Central

Vacchelli, Erika; Galluzzi, Lorenzo; Fridman, Wolf Hervé; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Kroemer, Guido

2012-01-01

The long-established notion that apoptosis would be immunologically silent, and hence it would go unnoticed by the immune system, if not tolerogenic, and hence it would actively suppress immune responses, has recently been revisited. In some instances, indeed, cancer cells undergo apoptosis while emitting a spatiotemporally-defined combination of signals that renders them capable of eliciting a long-term protective antitumor immune response. Importantly, only a few anticancer agents can stimulate such an immunogenic cell death. These include cyclophosphamide, doxorubicin and oxaliplatin, which are currently approved by FDA for the treatment of multiple hematologic and solid malignancies, as well as mitoxantrone, which is being used in cancer therapy and against multiple sclerosis. In this Trial Watch, we will review and discuss the progress of recent (initiated after January 2008) clinical trials evaluating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone. PMID:22720239

Machine learning aided diagnosis of hepatic malignancies through in vivo dielectric measurements with microwaves.

PubMed

Yilmaz, Tuba; Kılıç, Mahmut Alp; Erdoğan, Melike; Çayören, Mehmet; Tunaoğlu, Doruk; Kurtoğlu, İsmail; Yaslan, Yusuf; Çayören, Hüseyin; Arkan, Akif Enes; Teksöz, Serkan; Cancan, Gülden; Kepil, Nuray; Erdamar, Sibel; Özcan, Murat; Akduman, İbrahim; Kalkan, Tunaya

2016-06-20

In the past decade, extensive research on dielectric properties of biological tissues led to characterization of dielectric property discrepancy between the malignant and healthy tissues. Such discrepancy enabled the development of microwave therapeutic and diagnostic technologies. Traditionally, dielectric property measurements of biological tissues is performed with the well-known contact probe (open-ended coaxial probe) technique. However, the technique suffers from limited accuracy and low loss resolution for permittivity and conductivity measurements, respectively. Therefore, despite the inherent dielectric property discrepancy, a rigorous measurement routine with open-ended coaxial probes is required for accurate differentiation of malignant and healthy tissues. In this paper, we propose to eliminate the need for multiple measurements with open-ended coaxial probe for malignant and healthy tissue differentiation by applying support vector machine (SVM) classification algorithm to the dielectric measurement data. To do so, first, in vivo malignant and healthy rat liver tissue dielectric property measurements are collected with open-ended coaxial probe technique between 500 MHz to 6 GHz. Cole-Cole functions are fitted to the measured dielectric properties and measurement data is verified with the literature. Malign tissue classification is realized by applying SVM to the open-ended coaxial probe measurements where as high as 99.2% accuracy (F1 Score) is obtained.

[Cost-effectiveness trial of self-expandable metal stents and plastic biliary stents in malignant biliary obstruction].

PubMed

Daróczi, Tímea; Bor, Renáta; Fábián, Anna; Szabó, Ella; Farkas, Klaudia; Bálint, Anita; Czakó, László; Rutka, Mariann; Szűcs, Mónika; Milassin, Ágnes; Molnár, Tamás; Szepes, Zoltán

2016-02-14

Self-expandable metal and plastic stents can be applied in the palliative endoscopic treatment of patients with unresectable malignant biliary obstruction. The use of metal stentsis recommended if the patient's life expectancy is more than four months. To compare the therapeutic efficacy and cost-effectiveness of metal and plastic stents in the treatment of malignant biliary obstruction. The authors retrospectively enrolled patients who received metal (37 patients) or plastic stent (37 patients). The complication rate, stent patency and cumulative cost of treatment were assessed in the two groups. The complication rate of metal stents was lower (37.84% vs. 56.76%), but the stent patency was higher compared with plastic stents (19.11 vs. 8.29 weeks; p = 0.0041). In the plastic stent group the frequency of hospitalization of patients in context with stent complications (1.18 vs. 2.32; p = 0.05) and the necessity of reintervention for stent dysfunction (17 vs. 27; p = 0.033) were substantially higher. In this group multiple stent implantation raised the stent patency from 7.68 to 10.75 weeks. There was no difference in the total cost of treatment of malignant biliary obstruction between the two groups (p = 0.848). Considering the cost of treatment and the burden of patients the authors recommend self-expandable metal sten timplantation if the life expectancy of patients is more than two months. In short survival cases multiple plastic stent implantation is recommended.

Cellular Mechanisms of Multiple Myeloma Bone Disease

PubMed Central

Oranger, Angela; Carbone, Claudia; Izzo, Maddalena; Grano, Maria

2013-01-01

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and decreased osteoblast differentiation. A dysregulated production of numerous cytokines that can contribute to the uncoupling of bone cell activity is well documented in the bone marrow microenvironment of MM patients. These molecules are produced not only by malignant plasma cells, that directly contribute to MM bone disease, but also by bone, immune, and stromal cells interacting with each other in the bone microenvironment. This review focuses on the current knowledge of MM bone disease biology, with particular regard on the role of bone and immune cells in producing cytokines critical for malignant plasma cell proliferation as well as in osteolysis development. Therefore, the understanding of MM pathogenesis could be useful to the discovery of novel agents that will be able to both restore bone remodelling and reduce tumor burden. PMID:23818912

[Supportive care for malignant ascites in palliative phase: Place of paracentesis and diuretics].

PubMed

Gamblin, Vincent; Da Silva, Arlette; Villet, Stéphanie; El Hajbi, Farid

2015-11-01

Malignant ascites, occurring in advanced stages of cancer, is linked with poor prognosis and can cause invalidating symptoms. Physiopathological mechanisms of ascites formation are complex and have yet to be fully elucidated. In most cases, ascites is due to peritoneal carcinomatosis in which vascular permeability is enhanced by VEGF production while lymphatic drainage decreases. Ascites can also be secondary to portal hypertension, for example in case of multiple liver metastases, or due to lymphatic obstruction. While paracentesis and diuretics are commonly used, their efficiency has never been compared in a randomized controlled study. Paracentesis brings immediate but temporary relief in over 90% of cases, and implies multiple hospitalizations. Literature reports ascites control by aldosterone alone or in association with furosemide. But, available data is controversial, and there is no predictive factor to identify patients that respond to diuretic treatment. The indication of diuretic treatment is left to the appreciation of physicians. Existing recommendations are old, and practices influenced by results obtained in non-neoplastic ascites. Additional evidences are required before guidelines can be established for the palliative management of malignant ascites. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Multiple malignant extragastrointestinal stromal tumors of the greater omentum and results of immunohistochemistry and mutation analysis: A case report

PubMed Central

Kim, Jong-Han; Boo, Yoon-Jung; Jung, Cheol-Woong; Park, Sung-Soo; Kim, Seung-Joo; Mok, Young-Jae; Kim, Sang-Dae; Chae, Yang-Suk; Kim, Chong-Suk

2007-01-01

To report an extragastrointestinal stromal tumor (EGIST) that occurs outside the gastrointestinal tract and shows unique clinicopathologic and immunohistochemical features. In our case, we experienced multiple soft tissue tumors that originate primarily in the greater omentum, and in immunohistochemical analysis, the tumors showed features that correspond to malignant EGIST. Two large omental masses measured 15 cm x 10 cm and 5 cm × 4 cm sized and several small ovoid fragments were attached to small intestine, mesentery and peritoneum. On histologic findings, the masses were separated from small bowel serosa and had high mitotic count (115/50 HPFs). In the results of immunohistochemical stains, the tumor showed CD117 (c-kit) positive reactivity and high Ki-67 labeling index. On mutation analysis, the c-kit gene mutation was found in the juxtamembrane domain (exon 11) and it was heterozygote. Platelet-derived growth factor receptor (PDGFR) gene mutation was also found in the juxtamemembrane (exon 12) and it was polymorphism. From above findings, we proposed that there may be several mutational pathways to malignant EGIST, so further investigations could be needed to approach this unfavorable disease entity. PMID:17659683

The Population Benefit of Radiotherapy for Malignant Brain Tumors: Local Control and Survival Estimates for Guideline-Based Use.

PubMed

Hanna, Timothy Paul; Delaney, Geoffrey Paul; Barton, Michael Bernard

2016-09-01

To estimate the population benefit of radiotherapy (RT) for primary malignant brain tumors if evidence-based guidelines were routinely followed. This study investigated 5-year local control (LC) and 2- and 5-year overall survival (OS) benefits. RT benefit was the absolute proportional benefit of RT alone over no RT for radical indications, and over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemotherapy and RT over RT alone. Decision tree models were adapted to define the incidence of each indication. Citation databases were systematically queried for the highest level of evidence defining indication benefits. Meta-analysis was performed if there were multiple sources of the same evidence level, and deterministic and probabilistic sensitivity analysis was also performed. Among all patients with malignant brain tumors, 82% had indications for curative- or adjuvant-intent RT. The magnitude of benefit was based on level I or II evidence in 44% of all patients. A total of 25 relevant studies were used to quantify indication benefits. All RT benefit included in the model was irreplaceable. For malignant brain tumors, the estimated population benefit for RT alone was 9% for 5-year LC (95% CI, 7%-10%), 9% for 2-year OS (95% CI, 8%-11%), and 5% for 5-year OS (95% CI, 4%-5%). The incremental benefit of CRT was 1% for 5-year LC (95% CI, 0%-2%), 7% for 2-year OS (95% CI, 4%-11%), and 3% for 5-year OS (95% CI, 1%-5%). The model was robust in sensitivity analysis. When optimally used, RT provides an important benefit for many patients with malignant brain tumors. The model provided a robust means for estimating the magnitude of this benefit. Copyright © 2016 by the National Comprehensive Cancer Network.

Hereditary Melanoma: Update on Syndromes and Management - Genetics of familial atypical multiple mole melanoma syndrome

PubMed Central

Soura, E.; Eliades, P.; Shannon, K.; Stratigos, A.; Tsao, H.

2015-01-01

Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis. PMID:26892650

Connections between constitutional mismatch repair deficiency syndrome and neurofibromatosis type 1.

PubMed

Wimmer, K; Rosenbaum, T; Messiaen, L

2017-04-01

Constitutional mismatch repair (MMR) deficiency (CMMRD) is a rare childhood cancer susceptibility syndrome resulting from biallelic germline loss-of-function mutations in one of the MMR genes. Individuals with CMMRD have high risk to develop a broad spectrum of malignancies and frequently display features reminiscent of neurofibromatosis type 1 (NF1). Evaluation of the clinical findings of genetically proven CMMRD patients shows that not only multiple café-au-lait macules but also any of the diagnostic features of NF1 may be present in a CMMRD patient. This phenotypic overlap may lead to misdiagnosis of CMMRD patients as having NF1, which impedes adequate management of the patients and their families. The spectrum of CMMRD-associated childhood malignancies includes high-grade glioma, acute myeloid leukaemia or rhabdomyosarcoma, also reported as associated with NF1. Reported associations between NF1 and these malignancies are to a large extent based on studies that neither proved the presence of an NF1 germline mutation nor ruled-out CMMRD in the affected. Hence, these associations are challenged by our current knowledge of the phenotypic overlap between NF1 and CMMRD and should be re-evaluated in future studies. Recent advances in the diagnostics of CMMRD should render it possible to definitely state or refute this diagnosis in these individuals. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens.

PubMed

Jiang, Zhong; Li, Cuizhen; Fischer, Andrew; Dresser, Karen; Woda, Bruce A

2005-02-01

We assessed the usefulness of immunohistochemical analysis with a 3-antibody cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63) and a double-chromogen reaction for detection of limited prostate cancer in 138 needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma and 56 benign prostates. When carcinoma was present, red cytoplasmic granular staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63) and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78 (95%) expressed AMACR; all malignant glands were negative for basal cell staining. All benign glands adjacent to malignant glands were recognized easily by basal cell marker positivity and little or no AMACR expression. No benign glands were simultaneously positive for AMACR and negative for basal cell markers (specificity, 100%). There were no differences in intensity and numbers of positive glands with double-chromogen staining compared with using 1-color staining. Our results indicate that immunohistochemistry with a 3-antibody cocktail and double chromogen is a simple and easy assay that can be used as a routine test, which overcomes the problems of studying small lesions in prostate needle biopsies with multiple immunohistochemical stains.

Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

PubMed

Bhatt, Shruti; Sarosiek, Kristopher A; Lossos, Izidore S

2017-01-01

Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4 + /CD8 + T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

A user’s guide to cannabinoid therapies in oncology

PubMed Central

Maida, V.; Daeninck, P.J.

2016-01-01

“Cannabinoid” is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously. Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors. Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options. Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities. Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants. The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia. Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy. The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy. PMID:28050136

Ultrasound-Based Risk Stratification for Malignancy in Thyroid Nodules: A Four-Tier Categorization System.

PubMed

Seo, Hyobin; Na, Dong Gyu; Kim, Ji-Hoon; Kim, Kyung Won; Yoon, Ji Won

2015-07-01

The purpose of this study was to stratify the malignancy risk of US features, with an emphasis on nodule echogenicity. A total of 1,058 nodules of 824 consecutive patients (236 malignant and 822 benign) were included in this study. Malignancy risk of each nodule was analyzed according to US features, with an emphasis on nodule echogenecity, and was stratified into 4-tier categories. In multivariate analysis, isoechogenicity, indistinct margin, non-solid internal content, and parallel orientation were predictive of benign nodules (P < 0.002), while hypoechogenicity, marked hypoechogenicity, spiculated/microlobulated margin, solid content, nonparallel orientation (taller than wide), microcalcification, and macrocalcification were predictive of malignancy (P ≤ 0.037). Although the presence of US features associated with malignancy was significantly predictive of malignancy in hypoechoic and markedly hypoechoic nodules (P ≤ 0.004), it was not associated with malignancy in isoechoic or hyperechoic nodules. Thyroid nodules could be stratified into four categories according to the malignancy risk: benign (risk 0%), probably benign (risk ≤ 5%), indeterminate (risk > 5 and < 50%), and suspicion of malignancy (risk > 50%). The US-based four-tier categorization system will be useful for predicting the risk of malignancy and decisions regarding FNA for thyroid nodules. • No US feature was predictive of malignancy in isoechoic nodules. • Isoechoic nodules without calcification can be included in the probably benign category. • We suggest a four-tier categorization stratified primarily by nodule echogenecity. • The four-tier categorization of thyroid nodules will be useful for FNA decisions.

Gene Expression Profiling of Benign and Malignant Pheochromocytoma

PubMed Central

BROUWERS, FREDERIEKE M.; ELKAHLOUN, ABDEL G.; MUNSON, PETER J.; EISENHOFER, GRAEME; BARB, JENNIFER; LINEHAN, W. MARSTON; LENDERS, JACQUES W.M.; DE KRIJGER, RONALD; MANNELLI, MASSIMO; UDELSMAN, ROBERT; OCAL, IDRIS T.; SHULKIN, BARRY L.; BORNSTEIN, STEFAN R.; BREZA, JAN; KSINANTOVA, LUCIA; PACAK, KAREL

2016-01-01

There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes pre-disposing to the tumor. Correcting for the confounding influence of nora-drenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype–phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers. PMID:17102123

Small Nodules Localization on CT Images of Lungs

NASA Astrophysics Data System (ADS)

Snezhko, E. V.; Kharuzhyk, S. A.; Tuzikov, A. V.; Kovalev, V. A.

2017-05-01

According to the World Health Organization (WHO) lung cancer remains the leading cause of death of men among all malignant tumors [1, 2]. One of the reasons of such a statistics is the fact that the lung cancer is hardly diagnosed on the yearly stages when it is almost asymptomatic. The purpose of this paper is to present a Computer-Aided Diagnosis (CAD) software developed for assistance of early detection of nodules in CT lung images including solitary pulmonary nodules (SPN) as well as multiple nodules. The efficiency of nodule localization was intended to be as high as the level of the best practice. The software developed supports several functions including lungs segmentation, selection of nodule candidates and nodule candidates filtering.

Occurrence of Multiple Subsequent Neoplasms in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PubMed Central

Armstrong, Gregory T.; Liu, Wei; Leisenring, Wendy; Yasui, Yutaka; Hammond, Sue; Bhatia, Smita; Neglia, Joseph P.; Stovall, Marilyn; Srivastava, Deokumar; Robison, Leslie L.

2011-01-01

Purpose Childhood cancer survivors experience an increased incidence of subsequent neoplasms (SNs). Those surviving the first SN (SN1) remain at risk to develop multiple SNs. Because SNs are a common cause of late morbidity and mortality, characterization of rates of multiple SNs is needed. Patients and Methods In a total of 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, analyses were carried out among 1,382 survivors with an SN1. Cumulative incidence of second subsequent neoplasm (SN2), either malignant or benign, was calculated. Results A total of 1,382 survivors (9.6%) developed SN1, of whom 386 (27.9%) developed SN2. Of those with SN2, 153 (39.6%) developed more than two SNs. Cumulative incidence of SN2 was 46.9% (95% CI, 41.6% to 52.2%) at 20 years after SN1. The cumulative incidence of SN2 among radiation-exposed survivors was 41.3% (95% CI, 37.2% to 45.4%) at 15 years compared with 25.7% (95% CI, 16.5% to 34.9%) for those not treated with radiation. Radiation-exposed survivors who developed an SN1 of nonmelanoma skin cancer (NMSC) had a cumulative incidence of subsequent malignant neoplasm (SMN; ie, malignancies excluding NMSC) of 20.3% (95% CI, 13.0% to 27.6%) at 15 years compared with only 10.7% (95% CI, 7.2% to 14.2%) for those who were exposed to radiation and whose SN1 was an invasive SMN (excluding NMSC). Conclusion Multiple SNs are common among aging survivors of childhood cancer. SN1 of NMSC identifies a population at high risk for invasive SMN. Survivors not exposed to radiation who develop multiple SNs represent a population of interest for studying genetic susceptibility to neoplasia. PMID:21709189

Targeted PET imaging strategy to differentiate malignant from inflamed lymph nodes in diffuse large B-cell lymphoma

PubMed Central

Salloum, Darin; Carney, Brandon; Brand, Christian; Kossatz, Susanne; Sadique, Ahmad; Lewis, Jason S.; Weber, Wolfgang A.; Wendel, Hans-Guido; Reiner, Thomas

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL. PMID:28827325

[The Value of High Frequency Color Doppler Ultrasonography in the Diagnosis of Solid Skin Tumorsa-a Preliminary Study].

PubMed

Zhong, Lin; Tang, Yuan-Jiao; Yang, Yu-Jia; Qiu, Li

2017-01-01

To explore the value of high frequency color doppler ultrasonography in differentiating benign and malignant skin solid tumors. Clinical and ultrasonic data of cutaneous solid tumors confirmed by pathology in our hospital were collected. The differences in clinical and sonographic features between benign and malignant tumors were statistically analyzed. A total of 512 patients, involving 527 cases of skin solid tumors, were enrolled in this study. The ultrasonic detected 99.43% of the cases, with 99.02% accuracy in locating the lesions. The benign and malignant tumors showed differences in patient age, location, multiple occurance, location and depth, surface skin condition, tumor size, echo, morphology, uniformity, calcification, blood flow status, tumor rear area and peripheral echo, and pathological requests ( P <0.05). High frequency ultrasound has excellent detection rate of skin tumors, which can locate invasion depth of skin accurately. Benign and malignant skin tumors show differences in a number of clinical and ultrasound features.

Microenvironmental regulation of the progression of oral potentially malignant disorders towards malignancy

PubMed Central

Ai, Ruixue; Tao, Yan; Hao, Yilong; Jiang, Lu; Dan, Hongxia; Ji, Ning; Zeng, Xin; Zhou, Yu; Chen, Qianming

2017-01-01

Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies. PMID:29113419

Biosimilar G-CSF Based Mobilization of Peripheral Blood Hematopoietic Stem Cells for Autologous and Allogeneic Stem Cell Transplantation

PubMed Central

Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

2014-01-01

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen®) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF. PMID:24505236

Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

PubMed

Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

2014-01-01

The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

PubMed

Karmali, Reem; Dalovisio, Andrew; Borgia, Jeffrey A; Venugopal, Parameswaran; Kim, Brian W; Grant-Szymanski, Kelly; Hari, Parameswaran; Lazarus, Hillard

2015-03-01

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fully-human Heavy-chain-only Anti-B-cell Maturation Antigen (BCMA) Chimeric Antigen Receptors (CARs) | NCI Technology Transfer Center | TTC

Cancer.gov

Chimeric Antigen Receptor T cell (CAR-T) therapies that specifically target B-cell maturation antigen (BCMA) are strong therapeutic candidates for patients with plasma cell malignancy diseases such as, multiple myeloma (MM), as well as for patients with Hodgkin’s lymphoma. BCMA is a cell surface protein preferentially expressed on a subset of B cells and mature plasma cells, but not on other cells in the body. The limited expression of BCMA on B and plasma cells makes BCMA an attractive therapeutic target for B cell and plasma cell malignancy diseases. The 12 anti-BCMA CARs described are fully human CARS and have the potential to treat patients with various plasma cell and B cell malignancy diseases.

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies.

PubMed

Ponti, Giovanni; Martorana, Davide; Pellacani, Giovanni; Ruini, Cristel; Loschi, Pietro; Baccarani, Alessio; De Santis, Giorgio; Pollio, Annamaria; Neri, Tauro Maria; Mandel, Victor Desmond; Maiorana, Antonio; Maccio, Livia; Maccaferri, Monia; Tomasi, Aldo

2014-06-01

Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

NASA Astrophysics Data System (ADS)

Raju, G. J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G. A. V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P. V. B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

2006-06-01

Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors.

Time Lapse to Colorectal Cancer: Telomere Dynamics Define the Malignant Potential of Polyps.

PubMed

Druliner, Brooke R; Ruan, Xiaoyang; Johnson, Ruth; Grill, Diane; O'Brien, Daniel; Lai, Tsung-Po; Rashtak, Shahrooz; Felmlee-Devine, Donna; Washechek-Aletto, Jill; Malykh, Andrei; Smyrk, Thomas; Oberg, Ann; Liu, Hongfang; Shay, Jerry W; Ahlquist, David A; Boardman, Lisa A

2016-09-01

Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients. The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04-1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01. Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.

The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke.

PubMed

Jasim, Sina; Alahdab, Fares; Ahmed, Ahmed T; Tamhane, Shrikant U; Sharma, Anu; Donegan, Diane; Nippoldt, Todd B; Murad, M Hassan

2017-05-01

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995-2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53-1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70-1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51-2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus

PubMed Central

Kubo, Shuji; Kawasaki, Yoshiko; Yamaoka, Norie; Tagawa, Masatoshi; Kasahara, Noriyuki; Terada, Nobuyuki; Okamura, Haruki

2010-01-01

Background Malignant mesothelioma is a highly aggressive tumor with poor prognosis. Conventional therapies for mesothelioma are generally non-curative, and new treatment paradigms are urgently needed. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma. Methods We analyzed Mdk expression by quantitative RT-PCR in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. Based on these data, we constructed a replication-selective oncolytic adenovirus, designated AdMdk-E1-iresTK, which contains an Mdk promoter-driven adenoviral E1 gene and HSV-thymidine kinase (TK) suicide gene, and CMV promoter-driven green fluorescent protein (GFP) marker gene. Selectivity of viral replication and cytolysis were characterized in normal vs. mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo. Results Mdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk-E1-iresTK was seen to efficiently replicate, produce viral progeny, and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk-E1-iresTK mediated efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk-E1-iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk-E1-iresTK-derived signals, which vanished after tumor eradication. Conclusions These data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with upregulated Mdk expression, including malignant mesothelioma. PMID:20635326

Xeroderma pigmentosum complementation group F: Report of a case and review of Japanese patients.

PubMed

Tofuku, Yukari; Nobeyama, Yoshimasa; Kamide, Ryoichi; Moriwaki, Shinichi; Nakagawa, Hidemi

2015-09-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by extraordinary sensitivity to sunlight, resulting in cutaneous malignant tumors. Among XP, XP-F presents relatively uniquely in Japanese. To clarify the characteristics of this group, we describe a case of XP-F and review Japanese cases previously reported. A 50-year-old Japanese woman was referred to us with multiple, variously sized, light- or dark-brown macules on the face and sunlight-exposed extremities. She had experienced bulla formation with approximately 10 min of sunlight exposure during her elementary school years. Her parents had been first cousins, and her mother and sister had photosensitivity. She showed no neurological or developmental abnormalities. Ultraviolet (UV) irradiation testing revealed normal levels for minimal erythema dose with UV-A and UV-B. Sensitivity to UV-C and DNA repair ability in the patient's fibroblasts were indicated between that in normal individuals and that in an XP-A patient. Complementation assay revealed that transfection of the XPF gene led most efficient DNA repair compared with the other XP genes. Therefore, the patient was diagnosed with XP-F. Twenty-three cases of Japanese patients (six males, 17 females) with XP-F have been reported, including the present case. Our review suggested a relatively high prevalence of 50% (11/22) for cutaneous malignant tumors. A significant difference was evident in the mean age at first medical consultation between patients with cutaneous malignant tumors (53.6 years) and patients without such tumors (30.8 years). This suggests that cutaneous malignant tumors could occur in the age range of 30-50 years in XP-F patients. © 2015 Japanese Dermatological Association.

Evaluation of patients with gastric polyps.

PubMed

Olmez, Sehmus; Sayar, Suleyman; Saritas, Bunyamin; Savas, Ayla Yildiz; Avcioglu, Ufuk; Tenlik, Ilyas; Ozaslan, Ersan; Koseoglu, Hasan Tankut; Altiparmak, Emin

2018-01-01

The incidence of gastric polyps (GPs) greatly differs according to study populations and was found to be 0.33%-6.7% in various studies. The majority of GPs are composed of hyperplastic polyps (HPs), fundic gland polyps (FGPs), and adenomatous polyps (APs). Although APs have a high risk of malignant potential, sporadic FGPs have no malignant potential. Conversely, HPs have a low risk of malignant potential. It is not sufficient to perform a biopsy to identify the polyp type and the presence of dysplasia; thus, some polyps may require multiple biopsies or total excision. This retrospective study included patients with GPs or polypoid lesions found on esophagogastroscopy with polyp or malignant histology on biopsy at Ankara Numune Training and Research Hospital Endoscopy Unit between 2005 and 2011. In a series of 56.300 upper endoscopies, 192 patients (0.34%) were found to have GPs. Among the patients, 51 (26.6%) were men and 151 (73.4%) were women. The average age of the patients was 61.9±13.3 (14-90) years. The frequency of HPs, APs, and FGPs were 88%, 2.6%, and 1.6%, respectively. The size of the polyps was ≤1 cm in 137 (70%) patients. One polyp was determined in 141 (73.4%) patients. The most common localizations of polyps were the antrum and corpus. Endoscopic snare polypectomy was performed in 64 patients. One bleeding episode was observed, which required endoscopic treatment after ESP. In our study, the GP frequency was low (0.34%), whereas the frequency of HP maybe high due to the high frequency of Helicobacter pylori (HPy) infection in our country. The frequency of FGP is probably low due to the high frequency of HPy infection and the short-term use of proton-pump inhibitors.

Epidemiological Profile and Treatment Outcomes in Young Adults (19-29 Years of Age) Treated for Cancer in a Tertiary Hospital in São Paulo, Brazil.

PubMed

de Jesus, Victor Hugo Fonseca; Ribeiro, Taynan Nunes; Chinen, Ludmilla T Domingos; Alves, Vanessa; Curado, Maria Paula; Fanelli, Marcello Ferretti

2017-06-01

Worldwide, the incidence of cancer in young adults (20-39 years) is increasing, and represents an important cause of mortality in this age group. A retrospective study was undertaken to provide information that may lead to improved treatment outcomes. Epidemiological, clinicopathological, treatment, and survival information were retrieved from the electronic database registry of a tertiary referral hospital in São Paulo, Brazil for patients 19-29 years of age diagnosed with cancer between January 2007 and December 2012. There were 960 patients with a median age at diagnosis of 26 years; female patients comprised 59.2%. A previous diagnosis of malignancy was present in 2.3%; 0.4% had malignant tumors that were radiation-associated; regular alcohol use was present in 10.4%; 9% of patients reported tobacco use; a family history of cancer was present in 41.7%. Malignant tumors included carcinomas (45.7%), germ cell and trophoblastic neoplasms (12.3%), and lymphomas (12.1%). Median follow-up was 47.7 months (range: 0.62-100.9 months) during which time 111 patients (13.5%) died. Carcinomas (n = 43, 38.7%), soft tissue sarcomas (n = 18, 16.2%), and leukemias (n = 10, 9.0%) were the most common causes of death. This study has shown that carcinomas represent the most common malignancy in adolescents and young adults referred to a tertiary cancer center in Brazil and are the most common cause of mortality. Because clinical outcome may be affected by multiple factors in this patient population, further global studies are needed to characterize this population and improve clinical care.

Effect of Combined 68Ga-PSMAHBED-CC Uptake Pattern and Multiparametric MRI Derived With Simultaneous PET/MRI in the Diagnosis of Primary Prostate Cancer: Initial Experience.

PubMed

Taneja, Sangeeta; Jena, Amarnath; Taneja, Rajesh; Singh, Aru; Ahuja, Aashim

2018-06-01

The purpose of this study is to assess whether temporal changes in 68 Ga-prostate-specific membrane antigen (PSMA)-HBED-CC uptake and multiparametric MRI parameters derived using PET/MRI can aid in characterization of benign and malignant prostate lesions. Thirty-five men with 29 malignant and six benign prostate lesions undergoing complete clinical workup including histologic analysis were enrolled for this retrospective study. All had undergone simultaneous whole-body 68 Ga-PSMAHBED-CC PET/MRI. Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) assessment was made using a 5-point scale showing the likelihood of cancer with the combination of multiparametric MRI findings. Gallium-68-PSMA uptake was recorded at two time points: early (7 minutes) and delayed (54 minutes), adopting a copy-and-paste function of the ROI defined on MR images. ROC curve analysis was performed to test the diagnostic accuracy of early versus delayed PSMA uptake (measured as maximum standardized uptake value [SUV]). A multiple-ROI analysis was done to obtain ROCs for combined PET SUV and multiparametric MRI datasets. Spearman analysis was performed to assess the correlations. There was a significant difference between early and delayed PSMA uptake in malignant prostatic lesions (p < 0.01), which was able to characterize prostate lesions with an AUC of 0.83 and 0.94. Combined ROC analysis of PI-RADSv2 category derived from multiparametric MRI and differential PSMA uptake in characterizing prostatic lesions improved the AUC to 0.99. Dual-phase PSMA uptake improves accuracy of classifying malignant versus benign prostate lesions and complements multiparametric MRI in the diagnosis of prostate cancer.

The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

PubMed

Hu, Min; Hu, Haoyu; Cai, Wei; Mo, Zhikang; Xiang, Nan; Yang, Jian; Fang, Chihua

2018-05-01

Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was <40%, right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals.

PubMed

Hossain, Mohammad Sorowar; Iqbal, Mohd S; Khan, Mohiuddin Ahmed; Rabbani, Mohammad Golam; Khatun, Hazera; Munira, Sirajam; Miah, M Morshed Zaman; Kabir, Amin Lutful; Islam, Naima; Dipta, Tashmim Farhana; Rahman, Farzana; Mottalib, Abdul; Afrose, Salma; Ara, Tasneem; Biswas, Akhil Ranjan; Rahman, Mizanur; Abedin, Akm Mustafa; Rahman, Mahbubur; Yunus, A B M; Niessen, Louis W; Sultana, Tanvira Afroze

2014-06-14

The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the "French American British" classification system. A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n=3468) and 30.8% females (n=1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin's lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country.

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals

PubMed Central

2014-01-01

Background The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. Methods This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the “French American British” classification system. Results A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n = 3468) and 30.8% females (n = 1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin’s lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. Conclusions For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country. PMID:24929433

Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia)

PubMed Central

Golombick, Terry; Diamond, Terrence H.; Manoharan, Arumugam; Ramakrishna, Rajeev

2016-01-01

Hypothesis. Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design. Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods. Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results. Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion. Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies. PMID:27154182

Malignant Mesothelioma Treatment (PDQ®)—Patient Version

Cancer.gov

Treatment for malignant mesothelioma may include surgery, radiation therapy, and chemotherapy, as well as targeted therapy. The type of treatment you receive depends on where the cancer is found and at what stage. Find out about treatment options for malignant mesothelioma.

Analysis of Trends and Factors in Breast Multiple Primary Malignant Neoplasms

PubMed Central

Motuzyuk, Igor; Sydorchuk, Oleg; Kovtun, Natalia; Palian, Zinaida; Kostiuchenko, Yevhenii

2018-01-01

Background: The study aims to evaluate the current state and tendencies in multiple primary breast cancer incidence, behavior, and treatment in Ukraine. Methods: A total of 2032 patients who received special treatment at the Department of Breast Tumors and Reconstructive Surgery of the National Cancer Institute from 2008 to 2015 were included in the study. Among them, there were 195 patients with multiple primary malignant neoplasms: 54.9% patients with synchronous cancer and 45.1% patients with metachronous cancer. The average age of patients was 46.6 years, and the percentage of postmenopausal women was 63.1%. Among patients with synchronous cancer, there were 56.1% patients with only breast localizations and 43.9% with combination of breast and other localizations, and among patients with metachronous cancer, there were 46.6% patients with only breast localizations and 53.4% with combination of breast and other localizations. All the patients were evaluated in terms of aggressiveness of the disease, survival rates, as well as risk factors and treatment options. Results: A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chernobyl accident under the age of 30 years (P < .01). The clinical course of disease in patients with synchronous cancer is worse and prognostically unfavorable compared with metachronous cancer (P < .01). The course of the disease in patients who underwent mastectomy is worse compared with patients who underwent breast-conserving surgery (P < .01). Plastic and reconstructive surgery in patients with synchronous cancer was proven to be reasonable in terms of increase in survival (P < .01). Conclusions: The patients with multiple primary breast cancer should have attentive management and treatment. Multidisciplinary team should concern all the risk factors and provide the most sufficient option of management. This is crucial to continue research in this oncological area. PMID:29531473

Intrapleural cisplatin for management of malignant pleural effusion in a patient with plasma cell leucaemia.

PubMed

Agarwal, Abhishek; Klair, Jagpal; Patolia, Setu; Meena, Nikhil K

2015-06-29

Plasma cell leucaemia (PCL) is a rare aggressive form of multiple myeloma. It occasionally involves the pleura, causing malignant pleural effusion (MPE). MPE presents a management dilemma for physicians, given the different treatment options available with varying efficacy and side effects. We report a case of a 64-year-old man with MPE due to PCL, successfully managed with intrapleural cisplatin and a tunnelled pleural catheter. We believe this to be the first report of management of PCL-associated MPE with intrapleural cisplatin. 2015 BMJ Publishing Group Ltd.

Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models. | Office of Cancer Genomics

Cancer.gov

T- and NK-cell lymphomas (TCL) are a heterogenous group of lymphoid malignancies with poor prognosis. In contrast to B-cell and myeloid malignancies, there are few preclinical models of TCLs, which has hampered the development of effective therapeutics. Here we establish and characterize preclinical models of TCL. We identify multiple vulnerabilities that are targetable with currently available agents (e.g., inhibitors of JAK2 or IKZF1) and demonstrate proof-of-principle for biomarker-driven therapies using patient-derived xenografts (PDXs).

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

PubMed

Bhutani, Manoop S; Saftoiu, Adrian; Chaya, Charles; Gupta, Parantap; Markowitz, Avi B; Willis, Maurice; Kessel, Ivan; Sharma, Gulshan; Zwischenberger, Joseph B

2009-06-01

Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. Tertiary Care university hospital. An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

Pilot Study of Umbilical Cord Blood Transplantation in Adult Patient With Advanced Hematopoietic Malignancies

ClinicalTrials.gov

2013-08-13

Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Lymphoma, Large-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, T-Cell, Peripheral; T-NK Cell Lymphoma; Hodgkin Disease

Metastatic rhabdomyosarcoma to the breast.

PubMed

Sheen-Chen, Shyr-Ming; Eng, Hock-Liew; Ko, Sheung-Fat

2005-01-01

Secondary malignancy metastatic to the breast is uncommon, with an incidence of 0.5% to 3% of patients with extramammary malignancy. Although rhabdomyosarcoma is a common aggressive primary malignancy in the pediatric age group, metastatic deposits to the breast rarely occur and are mainly seen in adolescent girls. Here, we report an intriguing, rare adult case with metastasis to the breast from nasal rhabdomyosarcoma. A 31-year-old woman with the complaint of right neck mass noted recently came to this hospital for help. She had a history of nasal malignancy treated with radiotherapy in another hospital three months previously. Physical examination revealed multiple neck masses at bilateral neck areas. Bilateral neck dissection was performed and rhabdomyosarcoma, metastatic to lymph node, was the final diagnosis. One year after operation, the patient felt a large lump in her left breast. Surgical excision was performed and histological analysis was consistent with rhabdomyoblastic origin. Secondary malignancy metastatic to the breast is uncommon, yet this entity does exist. In view of the therapeutic implication, a metastatic breast lesion should not be mistaken as the primary breast carcinoma. Only with the awareness of such a possibility can prompt diagnosis and optimal treatment be achieved.

Curcumin and its Derivatives: Their Application in Neuropharmacology and Neuroscience in the 21st Century

PubMed Central

Lee, Wing-Hin; Loo, Ching-Yee; Bebawy, Mary; Luk, Frederick; Mason, Rebecca S; Rohanizadeh, Ramin

2013-01-01

Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Since the second half of the last century, this traditional medicine has attracted the attention of scientists from multiple disciplines to elucidate its pharmacological properties. Of significant interest is curcumin’s role to treat neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) and malignancy. These diseases all share an inflammatory basis, involving increased cellular reactive oxygen species (ROS) accumulation and oxidative damage to lipids, nucleic acids and proteins. The therapeutic benefits of curcumin for these neurodegenerative diseases appear multifactorial via regulation of transcription factors, cytokines and enzymes associated with (Nuclear factor kappa beta) NFκB activity. This review describes the historical use of curcumin in medicine, its chemistry, stability and biological activities, including curcumin's anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory properties. The review further discusses the pharmacology of curcumin and provides new perspectives on its therapeutic potential and limitations. Especially, the review focuses in detail on the effectiveness of curcumin and its mechanism of actions in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and brain malignancies. PMID:24381528

Histone deacetylases (HDAC) in physiological and pathological bone remodelling.

PubMed

Cantley, M D; Zannettino, A C W; Bartold, P M; Fairlie, D P; Haynes, D R

2017-02-01

Histone deacetylases (HDACs) 2 play important roles in the epigenetic regulation of gene expression in cells and are emerging therapeutic targets for treating a wide range of diseases. HDAC inhibitors (HDACi) 3 that act on multiple HDAC enzymes have been used clinically to treat a number of solid and hematological malignancies. HDACi are also currently being studied for their efficacy in non-malignant diseases, including pathologic bone loss, but this has necessitated a better understanding of the roles of individual HDAC enzymes, particularly the eleven zinc-containing isozymes. Selective isozyme-specific inhibitors currently being developed against class I HDACs (1, 2, 3 and 8) and class II HDACs (4, 5, 6, 7, 9 and 10) will be valuable tools for elucidating the roles played by individual HDACs in different physiological and pathological settings. Isozyme-specific HDACi promise to have greater efficacy and reduced side effects, as required for treating chronic disease over extended periods of time. This article reviews the current understanding of roles for individual HDAC isozymes and effects of HDACi on bone cells, (osteoblasts, osteoclasts and osteocytes), in relation to bone remodelling in conditions characterised by pathological bone loss, including periodontitis, rheumatoid arthritis and myeloma bone disease. Copyright © 2016 Elsevier Inc. All rights reserved.

A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies.

PubMed

Gilbert, J; Baker, S D; Bowling, M K; Grochow, L; Figg, W D; Zabelina, Y; Donehower, R C; Carducci, M A

2001-08-01

Phenylbutyrate (PB) is an aromatic fatty acid with multiple mechanisms of action including histone deacetylase inhibition. Preclinically, PB demonstrates both cytotoxic and differentiating effects at a concentration of 0.5 mM. We conducted a Phase I trial of p.o. PB patients with refractory solid tumor malignancies to evaluate toxicity, pharmacokinetic parameters, and feasibility of p.o. administration. Twenty-eight patients with refractory solid tumor malignancies were enrolled on this dose-escalation to maximally tolerated dose trial. Five dose levels of PB were studied: 9 g/day (n = 4), 18 g/day (n = 4), 27 g/day (n = 4), 36 g/day (n = 12), and 45 g/day (n = 4). Pharmacokinetic studies were performed and included an p.o. bioavailability determination. Compliance data were also collected. The recommended Phase II dose is 27 g/day. Overall the drug was well tolerated with the most common toxicities being grade 1-2 dyspepsia and fatigue. Nonoverlapping dose-limiting toxicities of nausea/vomiting and hypocalcemia were seen at 36 g/day. The p.o. bioavailability of PB was 78% for all dose levels, and the biologically active concentration of 0.5 mM was achieved at all dose levels. Compliance was excellent with 93.5% of all possible doses taken. No partial remission or complete remission was seen, but 7 patients had stable disease for more than 6 months while on the drug. PB (p.o.) is well tolerated and achieves the concentration in vivo that has been shown to have biological activity in vitro. PB may have a role as a cytostatic agent and should be additionally explored in combination with cytotoxics and other novel drugs.

ID2 collaborates with ID3 to suppress iNKT and innate-like tumors1

PubMed Central

Li, Jia; Roy, Sumedha; Kim, Young-Mi; Li, Shibo; Zhang, Baojun; Love, Cassandra; Reddy, Anupama; Rajagopalan, Deepthi; Dave, Sandeep; Diehl, Anna Mae; Zhuang, Yuan

2017-01-01

Inhibitor of DNA binding (ID) proteins, including ID1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins has been associated with a broad spectrum of tumors, recent studies have identified that ID3 plays a tumor suppressor role in the development of Burkitt’s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. Here, we report rapid lymphoma development in Id2/Id3 double knockout (L-DKO) mice caused by unchecked expansion of either invariant Natural Killer T (iNKT) cells, or a unique subset of innate-like, CD1d-independent T cells. These populations started expansion in neonatal mice and, upon malignant transformation, caused fatality at age between 3–11 months. The malignant cells also gave rise to lymphomas upon transfer to Rag-deficient and wild-type hosts, reaffirming their inherent tumorigenic potential. Microarray analysis revealed a significantly modified program in these neonatal iNKT cells that ultimately led to their malignant transformation. The lymphoma cells demonstrated chromosome instability, along with upregulation of several different signaling pathways, including the cytokine-cytokine receptor interaction pathway, which can promote their expansion and migration. Dysregulation of genes with reported driver mutations and the NF-kB pathway were found to be shared between L-DKO lymphomas and human NKT tumors. Our work identifies a distinct premalignant state and multiple tumoriogenic pathways caused by loss function of ID2 and ID3. Thus, conditional deletion of Id2 and Id3 in developing T cells establishes a unique animal model for iNKT and relevant innate-like lymphomas. PMID:28258199

Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer.

PubMed

Subramaniam, Deepa; He, Aiwu Ruth; Hwang, Jimmy; Deeken, John; Pishvaian, Michael; Hartley, Marion L; Marshall, John L

2015-01-01

Overactivation of the ErbB protein family, which is comprised of 4 receptor tyrosine kinase members (ErbB1/epidermal growth factor receptor [EGFR]/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4), can drive the development and progression of a wide variety of malignancies, including colorectal, head and neck, and certain non-small cell lung cancers (NSCLCs). As a result, agents that target a specific member of the ErbB family have been developed for the treatment of cancer. These agents include the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib; the EGFR-targeting monoclonal antibodies cetuximab and panitumumab; and the HER2-targeting monoclonal antibody trastuzumab. Lapatinib is a dual TKI that targets both EGFR and HER2. In addition, TKIs that inhibit multiple members of the ErbB family and also bind their targets irreversibly are under evaluation for the treatment of cancer. Three such compounds have progressed into clinical studies: the EGFR, HER2, and HER4 inhibitors afatinib, dacomitinib, and neratinib. Phase I studies of these agents have shown clinical activity in NSCLC, breast cancer, and other malignancies. Currently, afatinib is approved for EGFR mutation-positive NSCLC and is in development for squamous NSCLC, and dacomitinib is in phase III of clinical development for NSCLC, neratinib is in phase III of clinical development for the treatment of breast cancer, and afatinib is also in phase III development in head and neck cancer. Final results from clinical trials may lead to the potential approval of these agents in a variety of solid tumor malignancies.

Risk Factors for De Novo Malignancies in Women After Kidney Transplantation: A Multicenter Transversal Study.

PubMed

Helmy, Samir; Marschalek, Julian; Bader, Yvonne; Koch, Marianne; Schmidt, Alice; Kanzler, Marina; Gyoeri, Georg; Polterauer, Stephan; Reinthaller, Alexander; Grimm, Christoph

2016-06-01

Transplantation results in a 5-time elevated risk for a variety of malignancies (Kaposi sarcoma, skin, liver, lung, gastrointestinal cancer). A patient's risk for malignancies could be of particular interest for the follow-up programs of patients and risk adaption after kidney transplantation. The aim of this study was to identify independent risk factors for de novo malignancies in women after renal transplantation. This is a multicenter transversal study, conducted at the Medical University of Vienna and Hospital Rudolfstiftung, Vienna, Austria. We included female kidney graft recipients who were transplanted between 1980 and 2012 and followed-up at our institutions (N = 280). Clinical data of patients were extracted from hospital charts and electronic patient files. Patients were interviewed using a standardized questionnaire regarding their medical history, history of transplantation, and malignant diseases. Detailed information about present and past immunosuppressive regimens, rejection episodes and therapies, renal graft function, and information about primary disease was obtained. Diagnostic work-up and/or surgical exploration was performed if any presence of malignancy was suspected during routine follow-up. Histological specimens were obtained from all patients. the presence of de novo malignancy after kidney transplantation. Two hundred sixty-two women were included for statistical analysis. Median (interquartile range) follow-up period after transplantation was 101.1 (27.3-190.7) months. Thirty-two patients (12.2%) developed a malignancy: dermatologic malignancies (5.7%), breast cancer (3.4%), cervical cancer (0.8%), lung cancer (0.4%), gastrointestinal malignancies (1.5%), vulvar cancer (0.4%), and unclassified malignancies (1.9%). Median (interquartile range) time to malignancy after transplantation was 185.9 (92.0-257.6) months. Cumulative cancer rates were 4.9% (1 year), 14.4% (3 years), 16.4% (5 years), and 21.8% (10 years). Second transplantations were identified as independent risk factor for development of malignancy after transplantation. Long-term risk of developing a malignancy after kidney transplantation is high, which might justify a follow-up of more than 10 years.

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

PubMed Central

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-01-01

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples. PMID:29312638

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies.

PubMed

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-12-12

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples.

Fecal Molecular Markers for Colorectal Cancer Screening

PubMed Central

Kanthan, Rani; Senger, Jenna-Lynn; Kanthan, Selliah Chandra

2012-01-01

Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer. PMID:22969796

The Potential Role of Aerobic Exercise to Modulate Cardiotoxicity of Molecularly Targeted Cancer Therapeutics

PubMed Central

Lakoski, Susan; Mackey, John R.; Douglas, Pamela S.; Haykowsky, Mark J.; Jones, Lee W.

2013-01-01

Molecularly targeted therapeutics (MTT) are the future of cancer systemic therapy. They have already moved from palliative therapy for advanced solid malignancies into the setting of curative-intent treatment for early-stage disease. Cardiotoxicity is a frequent and potentially serious adverse complication of some targeted therapies, leading to a broad range of potentially life-threatening complications, therapy discontinuation, and poor quality of life. Low-cost pleiotropic interventions are therefore urgently required to effectively prevent and/or treat MTT-induced cardiotoxicity. Aerobic exercise therapy has the unique capacity to modulate, without toxicity, multiple gene expression pathways in several organ systems, including a plethora of cardiac-specific molecular and cell-signaling pathways implicated in MTT-induced cardiac toxicity. In this review, we examine the molecular signaling of antiangiogenic and HER2-directed therapies that may underpin cardiac toxicity and the hypothesized molecular mechanisms underlying the cardioprotective properties of aerobic exercise. It is hoped that this knowledge can be used to maximize the benefits of small molecule inhibitors, while minimizing cardiac damage in patients with solid malignancies. PMID:23335619

Malignant otitis externa in a healthy non-diabetic patient.

PubMed

Liu, Xiao-Long; Peng, Hong; Mo, Ting-Ting; Liang, Yong

2016-08-01

A healthy 60-year-old male was initially treated for external otitis, and subsequently received multiple surgeries including abscess drainage, temporal bone debridement, canaloplasty of the external auditory meatus, and fistula excision and was treated with numerous antibiotics at another hospital over a 1-year period. He was seen at our hospital on February 14, 2014 with a complaint of a non-healing wound behind the left ear and drainage of purulent fluid. He had no history of diabetes mellitus or compromised immune function. Computed tomography (CT) and magnetic resonance imaging (MRI) studies at our hospital showed osteomyelitis involving the left temporal, occipital, and sphenoid bones, the mandible, and an epidural abscess. Routine blood testing and tests of immune function were normal, and no evidence of other infectious processes was found. He was diagnosed with malignant otitis externa (MOE). Bone debridement and incision and drainage of the epidural abscess were performed, and vancomycin was administered because culture results revealed Corynebacterium jeikeium, Corynebacterium xerosis, and Enterococcus faecalis. MOE should be considered in healthy patients with external otitis who fail initial treatment.

Recent advances in targeting protein arginine methyltransferase enzymes in cancer therapy.

PubMed

Smith, Emily; Zhou, Wei; Shindiapina, Polina; Sif, Said; Li, Chenglong; Baiocchi, Robert A

2018-05-21

Exploration in the field of epigenetics has revealed the diverse roles of the protein arginine methyltransferase (PRMT) family of proteins in multiple disease states. These findings have led to the development of specific inhibitors and discovery of several new classes of drugs with potential to treat both benign and malignant conditions. Areas covered: We provide an overview on the role of PRMT enzymes in healthy and malignant cells, highlighting the role of arginine methylation in specific pathways relevant to cancer pathogenesis. Additionally, we describe structure and catalytic activity of PRMT and discuss the mechanisms of action of novel small molecule inhibitors of specific members of the arginine methyltransferase family. Expert opinion: As the field of PRMT biology advances, it's becoming clear that this class of enzymes is highly relevant to maintaining normal physiologic processes as well and disease pathogenesis. We discuss the potential impact of PRMT inhibitors as a broad class of drugs, including the pleiotropic effects, off target effects the need for more detailed PRMT-centric interactomes, and finally, the potential for targeting this class of enzymes in clinical development of experimental therapeutics for cancer.

History, genetics, and strategies for cancer prevention in Lynch syndrome.

PubMed

Kastrinos, Fay; Stoffel, Elena M

2014-05-01

Colorectal cancer (CRC) is the most common gastrointestinal malignancy and the third cause of cancer death in men and women in the United States. The majority of CRC cases diagnosed annually are due to sporadic events, but up to 6% are attributed to known monogenic disorders that confer a markedly increased risk for the development of CRC and multiple extracolonic malignancies. Lynch syndrome is the most common inherited CRC syndrome and is associated with mutations in DNA mismatch repair genes, mainly MLH1 and MSH2 but also MSH6, PMS2, and EPCAM. Although the risk of CRC and endometrial cancer may approach near 75% and 50%, respectively, in gene mutation carriers, the identification of these individuals and at-risk family members through predictive genetic testing provides opportunities for cancer prevention including specialized cancer screening, intensified surveillance, and/or prophylactic surgeries. This article will provide a review of the major advances in risk assessment, molecular genetics, DNA mutational analyses, and cancer prevention and management made since Lynch syndrome was first described 100 years ago. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases.

PubMed

Jakobiec, F A; Rini, F J; Fraunfelder, F T; Brownstein, S

1988-08-01

Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the conjunctival sac in six patients. No metastases were encountered among patients with strictly limbal nodules and among five patients with invasive nodules composed of spindle cells in part or in toto. Therapeutic success in this spectrum of melanocytic proliferations is closely correlated with the clinical extent of the disease when initiating definitive therapy.

Unexpected visitor on FDG PET/CT--brown adipose tissue (BAT) in mesentery in a case of retroperitoneal extra-adrenal pheochromocytoma: is the BAT activation secondary to catecholamine-secreting pheochromocytoma?

PubMed

Joshi, Prathamesh Vijay; Lele, Vikram Ramchandra

2012-05-01

Fused positron emission tomography-computed tomography (PET/CT) technology has enabled the determination that nonmalignant fluorodeoxyglucose (FDG) uptake is observed in brown adipose tissue (BAT). FDG uptake in BAT is a known potential source of false-positive interpretations for PET. The typical locations of BAT include neck, supraclavicular area, mediastinum, and paravertebral intercostal spaces. Examples of atypical locations for BAT include posterior neck, left paratracheal area, axillae, perirenal area, and retrocrural area. We report PET/CT findings in a young male patient with malignant retroperitoneal extra-adrenal pheochromocytoma, who demonstrated FDG uptake in BAT at multiple locations including mesenteric BAT. We also propose catecholamine-secreting pheochromocytoma as a possible cause of BAT activation in our case.

Malignant transformation of actinic cheilitis: A systematic review of observational studies.

PubMed

Dancyger, Alex; Heard, Victoria; Huang, Baikai; Suley, Cameron; Tang, Dorothy; Ariyawardana, Anura

2018-06-04

The aim of the present systematic review was to determine the malignant transformation rate of actinic cheilitis (AC). A comprehensive literature search was conducted using Medline/PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, OvidSP, and Google Scholar. The inclusion criteria comprised of observational human studies involving the malignant transformation of AC and publications in English. Studies included in this review were clinical follow-up, cohort, retrospective, or prospective investigations. The search yielded 1126 articles, and after exclusion, 34 full-text articles were eligible for full-text analysis. Only one article met the inclusion criteria. Based on the included article, it was determined that the malignant transformation rate of AC to squamous cell carcinoma (SCC) was 3.07%. Excluded articles focused on the clinicopathological characteristics and treatment efficacies of AC, and no malignant transformation rate was assessed. There is a need for more clinical studies on the malignant transformation of AC, as lip cancer is a public health concern. High-risk populations, including those living in tropical regions, have excessive exposure to UV radiation, and have older aged males, fair-skinned people, and smokers should be identified to prevent AC and its malignant change. Health practitioners should facilitate early intervention to prevent the progression of AC to SCC of the lip. © 2018 John Wiley & Sons Australia, Ltd.

Metabolic Features of Multiple Myeloma.

PubMed

El Arfani, Chaima; De Veirman, Kim; Maes, Ken; De Bruyne, Elke; Menu, Eline

2018-04-14

Cancer is known for its cellular changes contributing to tumour growth and cell proliferation. As part of these changes, metabolic rearrangements are identified in several cancers, including multiple myeloma (MM), which is a condition whereby malignant plasma cells accumulate in the bone marrow (BM). These metabolic changes consist of generation, inhibition and accumulation of metabolites and metabolic shifts in MM cells. Changes in the BM micro-environment could be the reason for such adjustments. Enhancement of glycolysis and glutaminolysis is found in MM cells compared to healthy cells. Metabolites and enzymes can be upregulated or downregulated and play a crucial role in drug resistance. Therefore, this review will focus on changes in glucose and glutamine metabolism linked with the emergence of drug resistance. Moreover, metabolites do not only affect other metabolic components to benefit cancer development; they also interfere with transcription factors involved in proliferation and apoptotic regulation.

Cystic fibrosis transmembrane conductance regulator-emerging regulator of cancer.

PubMed

Zhang, Jieting; Wang, Yan; Jiang, Xiaohua; Chan, Hsiao Chang

2018-05-01

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial-mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.

Antimicrobial Solution or Saline Solution in Maintaining Catheter Patency and Preventing Catheter-Related Blood Infections in Patients With Malignancies

ClinicalTrials.gov

2013-02-13

Chronic Myeloproliferative Disorders; Infection; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

[Multiple recurrent eccrine porocarcinoma with inguinal metastasis. A case report].

PubMed

Acosta-Arencibia, Aida; Abrante-Expósito, Begoña; Ramos-Gordillo, Matilde

2016-01-01

Eccrine porocarcinoma, first described in 1963, is a rare malignant lesion arising from the eccrine sweat glands. It is usually a primary tumour, or even more common, a malignant degeneration of an eccrine poroma. It usually affects older persons and is located most commonly on the lower extremities. About 20% of eccrine porocarcinoma will recur after treatment. The treatment is wide local excision of the primary lesion. This uncommon skin tumour has a locally aggressive behaviour and a high recurrence rate. An 82 year-old man presenting with multiple recurrent eccrine porocarcinoma with inguinal metastasis. The treatment was a radical excision and inguinal lymphadenectomy. There were no postoperative complications, but there was local recurrence after six months. Early diagnosis and wide excision is the best way to achieve a good prognosis, due to the aggressiveness of this tumour. Copyright © 2015. Published by Masson Doyma México S.A.

Long-term outcomes in patients with early stage nodular lymphocyte-predominant Hodgkin's lymphoma treated with radiotherapy.

PubMed

Solanki, Abhishek A; LeMieux, Melissa Horoschak; Chiu, Brian C-H; Mahmood, Usama; Hasan, Yasmin; Koshy, Matthew

2013-01-01

Radiation therapy (RT) is commonly used as definitive treatment for early-stage nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). We evaluated the cause-specific survival (CSS), overall survival (OS), and second malignancy (SM) rates in patients with early-stage NLPHL treated with RT. Patients with stage I-II NLPHL between 1988 and 2009 who underwent RT were selected from the Surveillance, Epidemiology and End Results database. Univariate analysis (UVA) for CSS and Os was performed using the Kaplan-Meier method and included age, gender, involved site, year of diagnosis, presence of B-symptoms, and extranodal involvement (ENI). Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling and included the above clinical variables. SM were classified as RT-related or non-RT-related. Freedom from SM and freedom from RT-related SM were determined using the Kaplan-Meier method. The study cohort included 469 patients. Median age was 37 years. The most common involved sites were the head and neck (36%), axilla/arm (26%), and multiple lymph node regions (18%). Sixty-eight percent had stage I disease, 70% were male, 4% had ENI, and 7% had B-symptoms. Median follow-up was 6 years. Ten-year CSS and Os were 98% and 88%, respectively. On UVA, none of the covariates was associated with CSS. Increasing age (p<0.01) and female gender (p<0.01) were associated with worse Os. On MVA, older age (p<0.01), female gender (p=0.04), multiple regions of involvement (p=0.03), stage I disease (p=0.02), and presence of B-symptoms (p=0.02) were associated with worse Os. Ten-year freedom from SM and freedom from RT-related SM were 89% and 99%, respectively. This is the largest series to evaluate the outcomes of stage I-II NLPHL patients treated with RT and found that this patient population has an excellent long-term prognosis and a low rate of RT-related second malignancies.

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

PubMed

Karp, J E; Humphrey, R L; Burke, P J

1981-03-01

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

A 12-year experience at a tertiary hospital on patients with multiple primary malignant neoplasms.

PubMed

Papaconstantinou, Ioannis; Mantzos, Dionysios S; Asimakoula, Konstantina; Michalaki, Vasiliki; Kondi-Pafiti, Agathi

2015-01-01

The incidence of multiple primary malignant neoplasms (MPMN) has dramatically increased. The purpose of this retrospective study was to present the 12-year experience at a University Hospital in patients with MPMN and to investigate the role of genetic factors in their pathogenesis. The medical records of 7516 cancer patients, treated in our Institution from 2000 to 2012, were reviewed. Diagnosis of MPMN was based on the Warren and Gates' criteria. Among 7516 patients, 39 (0.5%) (10 men, mean age 70.0±6.98 years, and 29 women, mean age 64.7±8.24 years) presented with MPMN. Eighty-two percent of them developed 2 primary malignant neoplasms (PMNs), whereas 3 PMNs were developed in 7 patients. Breast cancer was the most common cancer type diagnosed among female patients (59%); 14 and 3 had 2 and 3 PMNs, respectively. Eight had a family history of breast cancer while in 3 genetic testing revealed mutations in BRCA1 and BRCA2 genes. The second most common type of malignancy was colorectal cancer (24%); 5 developed 2 PMNs, whereas 2 developed 3 PMNs. Five patients had a family history of colorectal cancer. Colon cancer was the most frequent neoplasm among male patients (50%; 3 developed 2 and 2 3 PMNs. In 2 patients the family history was positive for colorectal cancer. Although many factors may contribute to MPMN development, positive family history and inherent mutations significantly predispose to MPMN appearance. Thus, management of MPMN patients should be based on a detailed family history and genetic testing.

THE ECSTACY OF GOLD Patent Expirations for Trastuzumab, Bevacizumab, Rituximab, and Cetuximab.

PubMed

Serna-Gallegos, Tasha R; LaFargue, Christopher J; Tewari, Krishnansu S

2017-11-22

Fully humanized monoclonal antibodies have revolutionized the treatment of many solid tumors, including breast, lung, colorectal, and ovarian cancer. Among the most widely used monoclonal antibodies in clinical oncology are cetuximab, trastuzumab, rituximab, and bevacizumab. This article will review these four notable monoclonal antibodies, their role in clinical oncology, and the drug patents that are nearing expiration. They are used in both first and second line treatment regimens for multiple common malignancies. With recent patent expirations, pharmaceutical companies involved in biosimilar manufacture are looking to establish ownership over these financial monopolies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Legionnaire's Disease and Immunosuppressive Drugs.

PubMed

Htwe, Tin Han; Khardori, Nancy M

2017-03-01

Immunosuppressive agents predispose patients to legionnaire's disease. Patients receiving tumor necrosis factor antagonists are generally not severely immunocompromised by the underlying disease. In patients with malignancy receiving immunosuppressive therapies, it is difficult to balance the underlying disease versus the therapy used. Transplant recipients are often on multiple drugs, including immunosuppressants. It seems that immunosuppressive drugs add to the risk for legionella infection. The index of suspicion should be high for legionella infection early during a compatible clinical syndrome. The control of Legionella species and prevention of transmission should be the foremost goal in protecting susceptible populations from Legionnaire's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Malignant gastric lymphoma with spontaneous perforation.

PubMed

Shimada, Satoko; Gen, Tokichi; Okamoto, Hiroyuki

2013-01-17

Malignant gastric lymphoma, accounting only for 1% of primary gastric carcinoma, is usually a diffuse large B-cell lymphoma. Toyota et al reported that 37% of gastric perforations involved malignancy, generally gastric carcinoma. Fukuda et al found that less than 5% of malignant gastric lymphomas perforate. While it is relatively well known that perforations often take place during chemotherapy, they are rare in patients not receiving chemotherapy. To our knowledge, spontaneous perforation is rare in gastric malignant lymphoma, having been reported in the Japanese literature only 26 times, including this case, in the last 25 years.

Malignant transformation of a residual cerebellopontine angle epidermoid cyst.

PubMed

Pikis, Stylianos; Margolin, Emil

2016-11-01

Malignant transformation is a rare but devastating complication following partial resection of an intracranial epidermoid cyst (EC). Time to malignant transformation is highly variable and optimal management is unclear. A literature search from 1965 to January 2016 identified manuscripts discussing clinical presentation, management, and outcome of malignant transformation of a remnant intracranial EC. One male patient diagnosed with malignant transformation of a remnant intracranial EC in our institution was also included in the study. There were 21 patients with malignant transformation of a remnant intracranial EC, including the current patient. Mean age was 51.4years (range 36 to 77) and there was a female predominance (12 women, 9 men, ratio 1.33:1). The mean time interval from partial resection of a benign intracranial EC to malignant transformation was 7.74years (range from 3months to 33years). Surgical resection of the tumor alone was the treatment of choice in 10 patients with one of them requiring a second operation and radiotherapy 2months following the first operation. Adjuvant treatment modalities were employed in 11 patients and included radiotherapy (n=4), stereotactic radiosurgery (SRS) (n=3), chemotherapy (n=1), chemotherapy combined with SRS (n=1) and with radiotherapy (n=1) and radiotherapy combined with SRS and followed by a second tumor resection (n=1). Follow-up period ranged from 1 day to 5years and 11/19 patients (57.8%) were reported dead on follow-up. Prospective studies are required to define the optimal management of malignant transformation of remnant intracranial EC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Unsuspected Active Ulcerative Colitis in a Patient With Dermatomyositis: A Rare Association Detected on 18F-FDG PET/CT During the Search for an Occult Malignancy.

PubMed

Rayamajhi, Sampanna Jung; Gorla, Arun Kumar Reddy; Basher, Rajender Kumar; Sood, Ashwani; Mittal, Bhagwant Rai

2017-01-01

Dermatomyositis is an inflammatory myopathy with the characteristic features of skin rash and myopathy. We here present a known case of dermatomyositis evaluated with 18 F-FDG PET/CT for the presence of any occult malignancy. The scan was negative for the presence of any malignancy. However, it revealed multiple intensely FDG avid colonic strictures that were later proven on colonoscopic biopsy to be ulcerative colitis. Also, a well-known association of bilateral sacroilitis was simultaneously demonstrated on the scan. The present case demonstrates that 18 F-FDG PET/CT imaging can serve as a one-stop shop imaging modality in dermatomyositis by facilitating detection of occult primary if any and by providing insight into other rare systemic associations.

Unsuspected Active Ulcerative Colitis in a Patient With Dermatomyositis: A Rare Association Detected on 18F-FDG PET/CT During the Search for an Occult Malignancy

PubMed Central

Rayamajhi, Sampanna Jung; Gorla, Arun Kumar Reddy; Basher, Rajender Kumar; Sood, Ashwani; Mittal, Bhagwant Rai

2017-01-01

Dermatomyositis is an inflammatory myopathy with the characteristic features of skin rash and myopathy. We here present a known case of dermatomyositis evaluated with 18F-FDG PET/CT for the presence of any occult malignancy. The scan was negative for the presence of any malignancy. However, it revealed multiple intensely FDG avid colonic strictures that were later proven on colonoscopic biopsy to be ulcerative colitis. Also, a well-known association of bilateral sacroilitis was simultaneously demonstrated on the scan. The present case demonstrates that 18F-FDG PET/CT imaging can serve as a one-stop shop imaging modality in dermatomyositis by facilitating detection of occult primary if any and by providing insight into other rare systemic associations. PMID:28533643

Leiomyosarcoma of the broad ligament: a case report with CT and MRI images.

PubMed

Makihara, N; Maeda, T; Ebina, Y; Kitajima, K; Kawakami, F; Hara, S; Yamada, H

2014-01-01

Primary leiomyosarcoma of the broad ligament is a very rare and highly malignant gynecological tumor. The authors report a 61-year-old postmenopausal woman with signs and symptoms of malignant ovarian tumor. Preoperative magnetic resonance imaging (MRI) was interpreted as being suspicious for malignant tumors, such as an ovarian cancer or a leiomyosarcoma of the broad ligament, so laparotomy was performed. Macroscopically, the tumor was revealed with a 18 x 13.7 x 9.5 cm degenerated, multiple cystic part and solid whitish part arising from broad ligament which on histopathology proved to be leiomyosarcoma. To the best of the authors' knowledge, primary leiomyosarcoma of the broad ligament has been documented in 21 reports or so, and no imaging findings are available. Here the authors present the MRI findings of primary leiomyosarcoma of the broad ligament.

Lymphoscintigraphy mapping of truncal malignant melanoma: A study of 212 patients at the Christie NHS Foundation Trust.

PubMed

El Muntasar, Ahmed; Oudit, Deems

2017-01-01

Malignant melanoma (MM) on the trunk, because of its anatomical location, has multiple potential lymphatic basins to which to drain. The aim of this study is to map the location of the sentinel lymph node (SLN) on the basis of the anatomical location of the primary malignant melanoma on the trunk. Patients diagnosed with MM on the trunk who had undergone a SLN biopsy from January 2006 to March 2015 were identified in the Christie NHS Foundation Trust through a computer database search. The anterior and posterior surfaces of the trunk were divided into four sections each. A total of 212 patients were evaluated. MM was more common on the posterior trunk, accounting for 73% of cases, and 57% of melanomas were on the right side of the trunk. The axillary basins were involved in drainage in 91.5% of all truncal melanomas. Drainage was to a single lymphatic basin in 68.3% of cases. The incidence of drainage to multiple lymphatic basins was not uniform for the anterior and posterior surfaces of the trunks. One-third of MM on the posterior surface of the trunk will drain to multiple basins. Around 50% of the melanomas of the upper back drain to a contralateral basin. Independent of the location of the MM, the axillary basins were the most common location of drainage, with a total of 91% of the cohort. Therefore, the location of the SLN could be predicted, depending on the location of the MM on the trunk. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Benefits and limitations of multimodality imaging in the diagnosis of a primary cardiac lymphoma.

PubMed

Nijjar, Prabhjot Singh; Masri, Sofia Carolina; Tamene, Ashenafi; Kassahun, Helina; Liao, Kenneth; Valeti, Uma

2014-12-01

Primary cardiac tumors are far rarer than tumors metastatic to the heart. Angiosarcoma is the primary cardiac neoplasm most frequently detected; lymphomas constitute only 1% of primary cardiac tumors. We present the case of a 55-year-old woman with a recently diagnosed intracardiac mass who was referred to our institution for consideration of urgent orthotopic heart transplantation. Initial images suggested an angiosarcoma; however, a biopsy specimen of the mass was diagnostic for diffuse large B-cell lymphoma. The patient underwent chemotherapy rather than surgery, and she was asymptomatic 34 months later. We use our patient's case to discuss the benefits and limitations of multiple imaging methods in the evaluation of cardiac masses. Certain features revealed by computed tomography, cardiac magnetic resonance, and positron emission tomography can suggest a diagnosis of angiosarcoma rather than lymphoma. Cardiac magnetic resonance and positron emission tomography enable reliable distinction between benign and malignant tumors; however, the characteristics of different malignant tumors can overlap. Despite the great usefulness of multiple imaging methods for timely diagnosis, defining the extent of spread and the hemodynamic impact, and monitoring responses to treatment, we think that biopsy analysis is still warranted in order to obtain a correct histologic diagnosis in cases of suspected malignant cardiac tumors.

Multiple lymphomatous polyposis.

PubMed

Kadayifçi, A; Benekli, M; Savaş, M C; Arslan, S; Uzunalimoğlu, B; Barişta, I; Güllü, I H; Tekuzman, G

1997-04-01

Multiple lymphomatous polyposis (MLP) is a distinctive and particularly rare clinical type of malignant gastrointestinal lymphoma, which is classified as B-cell centrocytic non-Hodgkin's lymphoma. this rare entity has been recently reclassified as mantle cell lymphoma. We herein report three additional cases of MLP involving various segments of the gastrointestinal tract. MLP has an aggressive biologic behavior and a relatively poor prognosis and must be treated accordingly as a high-grade lymphoma with systemic chemotherapy.

Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

ClinicalTrials.gov

2012-11-07

Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Follicular Lymphoma; Multiple Myeloma; NHL; Myeloproliferative Diseases; Chronic Myeloid Leukemia; Renal Cell Carcinoma; Aplastic Anemia

Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)

ClinicalTrials.gov

2017-12-04

Hematologic Cancer; Relapse Leukemia; Relapsed Adult ALL; Relapsed Adult AML; Relapsed CLL; Relapsed Non Hodgkin Lymphoma; Relapsed Hodgkin's Lymphoma; Relapsed Myelodysplastic Syndromes; Relapsed Multiple Myeloma

Cadmium-induced malignant transformation of rat liver cells: Potential key role and regulatory mechanism of altered apolipoprotein E expression in enhanced invasiveness.

PubMed

Suzuki, Masayo; Takeda, Shuso; Teraoka-Nishitani, Noriko; Yamagata, Akane; Tanaka, Takahiro; Sasaki, Marika; Yasuda, Natsuki; Oda, Makiko; Okano, Tatsuji; Yamahira, Kazuhiro; Nakamura, Yuta; Kobayashi, Takanobu; Kino, Katsuhito; Miyazawa, Hiroshi; Waalkes, Michael P; Takiguchi, Masufumi

2017-05-01

Cadmium is a transition metal that is classified as human carcinogen by the International Agency for Research on Cancer (IARC) with multiple target sites. Many studies using various model systems provide evidence of cadmium-induced malignancy formation in vivo or malignant cell transformation in vitro. Nonetheless, further studies are needed to completely understand the mechanisms of cadmium carcinogenicity. Our prior studies have utilized a rat liver epithelial cell line (TRL 1215) as a model for cadmium-induced malignant transformation. In the present study, we focused on the molecular mechanisms of this malignant transformation, especially with regard to hyper-invasiveness stimulated by cadmium transformation. By performing a series of biochemical analyses on cadmium transformed cells, it was determined that cadmium had significantly down-regulated the expression of apolipoprotein E (ApoE). ApoE was recently established as a suppressor of cell invasion. A key factor in the suppression of ApoE by cadmium appeared to be that the metal evoked a 5-aza-2'-deoxycytidine-sensitive hypermethylation of the regulatory region of ApoE, coupled with interference of the action of liver X receptor α (LXRα), a transcriptional regulator for ApoE. Furthermore, the expression of LXRα itself was suppressed by cadmium-mediated epigenetic modification. Re-expression of ApoE clearly abrogated the cell invasion stimulated by cadmium-induced malignant transformation. Together, the current results suggest that the cadmium-mediated enhanced cell invasion is linked to down-regulation of ApoE during malignant transformation these liver cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Coffee consumption and the risk of malignant melanoma in the Norwegian Women and Cancer (NOWAC) Study.

PubMed

Lukic, Marko; Jareid, Mie; Weiderpass, Elisabete; Braaten, Tonje

2016-07-29

Coffee contains biologically-active substances that suppress carcinogenesis in vivo, and coffee consumption has been associated with a lower risk of malignant melanoma. We studied the impact of total coffee consumption and of different brewing methods on the incidence of malignant melanoma in a prospective cohort of Norwegian women. We had baseline information on total coffee consumption and consumption of filtered, instant, and boiled coffee from self-administered questionnaires for 104,080 women in the Norwegian Women and Cancer (NOWAC) Study. We also had follow-up information collected 6-8 years after baseline. Multiple imputation was used to deal with missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for malignant melanoma by consumption category of total, filtered, instant, and boiled coffee. During 1.7 million person-years of follow-up, 762 cases of malignant melanoma were diagnosed. Compared to light consumers of filtered coffee (≤1 cup/day), we found a statistically significant inverse association with low-moderate consumption (>1-3 cups/day, HR = 0.80; 95 % confidence interval [CI] 0.66-0.98) and high-moderate consumption of filtered coffee (>3-5 cups/day, HR = 0.77; 95 % CI 0.61-0.97) and melanoma risk (p trend = 0.02). We did not find a statistically significant association between total, instant, or boiled coffee consumption and the risk of malignant melanoma in any of the consumption categories. The data from the NOWAC Study indicate that a moderate intake of filtered coffee could reduce the risk of malignant melanoma.

Apparent diffusion coefficient of vertebral haemangiomas allows differentiation from malignant focal deposits in whole-body diffusion-weighted MRI.

PubMed

Winfield, Jessica M; Poillucci, Gabriele; Blackledge, Matthew D; Collins, David J; Shah, Vallari; Tunariu, Nina; Kaiser, Martin F; Messiou, Christina

2018-04-01

The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits. This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded. The ADC of haemangiomas (72 ROIs, median ADC 1,085×10 -6 mm 2 s -1 , interquartile range 927-1,295×10 -6 mm 2 s -1 ) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10 -6 mm 2 s -1 , interquartile range 583-781×10 -6 mm 2 s -1 ) with a p-value < 10 -6 . Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10 -6 mm 2 s -1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %. ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion. • Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases. • ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits. • High ADCs of haemangiomas allows them to be distinguished from active disease.

Arsenic compounds as anticancer agents.

PubMed

Wang, Z Y

2001-08-01

In this paper the use of arsenic compounds as anticancer agents in clinical trials and in in vitro investigations is reviewed, including the experience at our institute. Treatment of newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL) with arsenic trioxide (As2O3) has been found to result in complete remission (CR) rates of 85-93% when given by intravenous infusion for 2-3 h at a dose of 10 mg/day diluted in 5% glucose saline solution. Patients exhibit a response in 28-42 days. CR rates after administration of Composite Indigo Naturalis tablets containing arsenic sulfide and of pure tetraarsenic tetrasulfide reached 98% and 84.9%, respectively. At higher concentrations (1-2 microM), arsenic induced apoptosis, while at lower concentrations (0.1-0.5 microM), it triggered cell differentiation in vitro. As2O3-induced apoptosis has been observed in many cancer cell lines, including esophageal carcinoma, gastric cancer, neuroblastoma, lymphoid malignancies, and multiple myeloma. Its effectiveness was confirmed in the treatment of multiple myeloma. Arsenic compounds are effective agents in the treatment of APL and their activity against other types of cancer requires further investigation.

Metabolic Reprogramming in Glioma

PubMed Central

Strickland, Marie; Stoll, Elizabeth A.

2017-01-01

Many cancers have long been thought to primarily metabolize glucose for energy production—a phenomenon known as the Warburg Effect, after the classic studies of Otto Warburg in the early twentieth century. Yet cancer cells also utilize other substrates, such as amino acids and fatty acids, to produce raw materials for cellular maintenance and energetic currency to accomplish cellular tasks. The contribution of these substrates is increasingly appreciated in the context of glioma, the most common form of malignant brain tumor. Multiple catabolic pathways are used for energy production within glioma cells, and are linked in many ways to anabolic pathways supporting cellular function. For example: glycolysis both supports energy production and provides carbon skeletons for the synthesis of nucleic acids; meanwhile fatty acids are used both as energetic substrates and as raw materials for lipid membranes. Furthermore, bio-energetic pathways are connected to pro-oncogenic signaling within glioma cells. For example: AMPK signaling links catabolism with cell cycle progression; mTOR signaling contributes to metabolic flexibility and cancer cell survival; the electron transport chain produces ATP and reactive oxygen species (ROS) which act as signaling molecules; Hypoxia Inducible Factors (HIFs) mediate interactions with cells and vasculature within the tumor environment. Mutations in the tumor suppressor p53, and the tricarboxylic acid cycle enzymes Isocitrate Dehydrogenase 1 and 2 have been implicated in oncogenic signaling as well as establishing metabolic phenotypes in genetically-defined subsets of malignant glioma. These pathways critically contribute to tumor biology. The aim of this review is two-fold. Firstly, we present the current state of knowledge regarding the metabolic strategies employed by malignant glioma cells, including aerobic glycolysis; the pentose phosphate pathway; one-carbon metabolism; the tricarboxylic acid cycle, which is central to amino acid metabolism; oxidative phosphorylation; and fatty acid metabolism, which significantly contributes to energy production in glioma cells. Secondly, we highlight processes (including the Randle Effect, AMPK signaling, mTOR activation, etc.) which are understood to link bio-energetic pathways with oncogenic signals, thereby allowing the glioma cell to achieve a pro-malignant state. PMID:28491867

Thromboembolic complications following aminocaproic acid use in patients with hematologic malignancies.

PubMed

Juhl, Rebecca C; Roddy, Julianna V F; Wang, Tzu-Fei; Li, Junan; Elefritz, Jessica L

2018-02-09

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.

The Making of a Skull Base Team and the Value of Multidisciplinary Approach in the Management of Sinonasal and Ventral Skull Base Malignancies.

PubMed

Snyderman, Carl H; Wang, Eric W; Fernandez-Miranda, Juan C; Gardner, Paul A

2017-04-01

The management of sinonasal and ventral skull base malignancies is best performed by a team. Although the composition of the team may vary, it is important to have multidisciplinary representation. There are multiple obstacles, both individual and institutional, that must be overcome to develop a highly functioning team. Adequate training is an important part of team-building and can be fostered with surgical telementoring. A quality improvement program should be incorporated into the activities of a skull base team. Copyright © 2016 Elsevier Inc. All rights reserved.

Refeeding Syndrome in Oncology: Report of Four Cases.

PubMed

Windpessl, Martin; Mayrbaeurl, Beate; Baldinger, Christian; Tiefenthaller, Gernot; Prischl, Friedrich C; Wallner, Manfred; Thaler, Josef

2017-02-01

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality.

Refeeding Syndrome in Oncology: Report of Four Cases

PubMed Central

Windpessl, Martin; Mayrbaeurl, Beate; Baldinger, Christian; Tiefenthaller, Gernot; Prischl, Friedrich C.; Wallner, Manfred; Thaler, Josef

2017-01-01

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality. PMID:28983382

[A case of malignant lymphoma successfully diagnosed using Sasada transbronchial angled biopsy forceps].

PubMed

Komori, Chika; Sasada, Shinji; Okamoto, Norio; Kawahara, Kunimitsu; Uehara, Nobuko; Shimada, Kazutaka; Kuhara, Hanako; Terada, Haruko; Tsujino, Kazuyuki; Matsunashi, Tatsuro; Minami, Toshiyuki; Suzuki, Hidekazu; Kobayashi, Masashi; Hirashima, Tomonori; Matsui, Kaoru; Kawase, Ichiro; Kusunoki, Yoko

2009-01-01

A 68-year-old man was referred to our hospital due to general fatigue, fever and weight loss. His chest radiograph showed a nodule (2.8 cm) in the right middle lobe. Computed tomography and positron emission tomography showed multiple metastases to the bone, liver and lymph nodes. The lung nodule was not accessible by standard transbronchial forceps. However, biopsy specimens obtained using Sasada Transbronchial Angled Biopsy Forceps (STAF) pathologically confirmed the diagnosis of malignant lymphoma. We report the case, and discuss the utility of STAF for lung lesions that are difficult to access with standard forceps.

Jumping translocations in hematological malignancies: a cytogenetic study of five cases.

PubMed

Manola, Kalliopi N; Georgakakos, Vasileios N; Stavropoulou, Chryssa; Spyridonidis, Alexandros; Angelopoulou, Maria K; Vlachadami, Ioanna; Katsigiannis, Andreas; Roussou, Paraskevi; Pantelias, Gabriel E; Sambani, Constantina

2008-12-01

Jumping translocations (JT) are rare cytogenetic aberrations in hematological malignancies that include unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to two or more different recipient chromosomes in different cell lines. We report five cases associated with different hematologic disorders and JT to contribute to the investigation of the origin, pathogenesis, and clinical significance of JT. These cases involve JT of 1q in a case of acute myeloblastic leukemia (AML)-M1, a case of Burkitt lymphoma, and a case of BCR/ABL-positive acute lymphoblastic leukemia, as well as a JT of 13q in a case of AML-M5, and a JT of 11q segment in a case of undifferentiated leukemia. To our knowledge, with regard to hematologic malignancies, this study presents the first case of JT associated with AML-M1, the first case of JT involving 13q as a donor chromosome, and the first report of JT involving a segment of 11q containing two copies of the MLL gene, jumping on to two recipient chromosomes in each cell line and resulting in six copies of the MLL gene. Our investigation suggests that JT may not contribute to the pathogenesis but rather to the progression of the disease, and it demonstrates that chromosome band 1q10 as a breakpoint of the donor chromosome 1q is also implicated in AML, not only in multiple myeloma as it has been known until now.

Diagnosis and treatment of a dermal malignant melanoma in an African lion (Panthera leo).

PubMed

Steeil, James C; Schumacher, Juergen; Baine, Katherine; Ramsay, Edward C; Sura, Patricia; Hodshon, Rebecca; Donnell, Robert L; Lee, Nathan D

2013-09-01

A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.

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

Mutational analysis of PI3K/AKT and RAS/RAF pathway activation in malignant salivary gland tumours with a new mutation of PIK3CA.

PubMed

Shalmon, B; Drendel, M; Wolf, M; Hirshberg, A; Cohen, Y

2016-06-01

The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The relationship of silicone breast implants and cancer at other sites.

PubMed

Brinton, Louise A

2007-12-01

Although most attention regarding the effects of silicone breast implants on cancer risk has focused on breast cancer, there have also been concerns regarding effects on other cancers. This includes malignancies that could occur as a result of foreign-body carcinogenesis (sarcomas) or immune alterations (hematopoietic malignancies), or cancers suggested as possibly elevated on the basis of previous epidemiologic studies (cancers of the cervix, vulva, lung, and brain). Searches of the English language literature on the topic of silicone breast implants and cancer risk were conducted and reviewed to determine relationships that might have etiologic relevance. Epidemiologic studies provide no support for an increased risk of either sarcoma or multiple myeloma among breast implant recipients, disputing clinical and laboratory findings suggesting such a link. Although a number of epidemiologic studies have demonstrated elevated risks of cervical, vulvar, and lung cancers among breast implant patients, it is likely that these excesses relate more to lifestyle characteristics (e.g., cigarette smoking, sexual behavior) than to the effects of the implants. Brain cancer excesses, suggested in one study, have not been confirmed in either an update of the mortality experience in this study or on the basis of other investigations. At present, there is no convincing evidence that breast implants alter the risk of nonbreast malignancies. Breast implant patients should continue to be monitored for longer term risks and to assess whether cancer risk is influenced by various patient and implant characteristics.

Bcl-2 antisense therapy in B-cell malignancies.

PubMed

Chanan-Khan, Asher

2005-07-01

Bcl-2 is an apoptosis regulating protein, overexpression of which is associated with chemotherapy resistant disease, aggressive clinical course, and poor survival in patients with B-cell lymphoproliferative disorders. Overexpression of Bcl-2 protein results in an aberrant intrinsic apoptotic pathway that confers a protective effect on malignant cells against a death signal (e.g., chemotherapy or radiotherapy). Downregulation of this oncoprotein, thus, represents a possible new way to target clinically aggressive disease. Preclinical studies have shown that this oncoprotein can be effectively decreased by Bcl-2 antisense in malignant lymphoid cells and can reverse chemotherapy resistance, as well as enhance the anti-apoptotic potential of both chemotherapeutic and biologic agents. Ongoing clinical trials are exploring the role of Bcl-2 downregulation with oblimersen (Bcl-2 antisense) in patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia and multiple myeloma. Early results from these studies are promising and support the proof of the principle. As these studies are completed and mature data emerges, the role of Bcl-2 antisense therapy in the treatment of B-cell malignancies will become clearer.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

Synchronous quintuple primary gastrointestinal tract malignancies: Case report

PubMed Central

Kim, Soo-Hong; Park, Byung-Soo; Kim, Hyun Sung; Kim, Jae Hun

2017-01-01

Multiple primary malignancy is defined as two or more malignancies detected in an individual person. In particular, synchronous quintuple primary malignancy is extremely rare. A 52-year-old male with anal pain and intermittent blood-tinged stool was diagnosed with malignancies in the stomach, jejunum, ascending colon, transverse colon and rectum. He underwent a subtotal gastrectomy, segmental resection of the jejunum and total protocolectomy with end ileostomy. The postoperative pathologic findings were moderate differentiated gastric adenocarcinoma (pT1bN0M0, pStageIA), combined adenocarcinoma and neuroendocrine carcinoma of the jejunum (pT3N0M0, pStageIIA), three mucinous adenocarcinoma of the ascending colon (pT3N0M0, pStageIIA), transverse colon (pT1N0M0, pStageI) and rectum (pT3N1aM0, pStageIIIB). The tumors did not lack MLH-1 and MSH-2 expression, as the markers (bat26, D5S346, bat25, D2S123) suggest MSI-H presence. Adjuvant chemoradiotherapy was started according to regimen, FOLFOX 4 for advanced rectal cancer. Six years post-operation, the patient is currently attending regular follow-ups without recurrence or metastasis. PMID:28104993

Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers.

PubMed

Shimizu, Yasuhiro; Yamaue, Hiroki; Maguchi, Hiroyuki; Yamao, Kenji; Hirono, Seiko; Osanai, Manabu; Hijioka, Susumu; Hosoda, Waki; Nakamura, Yasushi; Shinohara, Toshiya; Yanagisawa, Akio

2013-07-01

The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Does human papilloma virus play a role in sinonasal inverted papilloma?

PubMed

Govindaraj, Satish; Wang, Hailun

2014-02-01

Inverted papillomas are a benign sinonasal tumor with a propensity for recurrence and malignant transformation. Although many investigations have been made into the nature of this disease, its etiology and causes for malignant transformation have yet to be fully elucidated. It is the authors' objective to present a review on management of the disease and evaluate the present relationship between human papilloma virus (HPV) and inverted papilloma. A causal relationship between HPV and the pathogenesis and progression of inverted papilloma has been posited since the 1980s. Although widely varied HPV detection rates have been reported, recent studies have noted a substantial increase in both recurrence and malignant transformation in HPV-infected inverted papillomas. However, exact cellular mechanisms by which infection leads to subsequent recurrence and development of carcinoma have yet to be elucidated. Evidence exists suggesting that HPV infection plays a role in the progression of inverted papilloma and confers an increased risk for recurrence and malignant transformation. PCR is the preferred detection method, and fresh or frozen specimens are the ideal source of tissue for evaluation. Although multiple studies have detected an association between HPV and inverted papilloma (both recurrent and malignant transformation), further studies are necessary to elucidate the underlying molecular pathways before an association can be changed to causation.

Methotrexate Is a JAK/STAT Pathway Inhibitor

PubMed Central

Thomas, Sally; Fisher, Katherine H.; Snowden, John A.; Danson, Sarah J.; Brown, Stephen; Zeidler, Martin P.

2015-01-01

Background The JAK/STAT pathway transduces signals from multiple cytokines and controls haematopoiesis, immunity and inflammation. In addition, pathological activation is seen in multiple malignancies including the myeloproliferative neoplasms (MPNs). Given this, drug development efforts have targeted the pathway with JAK inhibitors such as ruxolitinib. Although effective, high costs and side effects have limited its adoption. Thus, a need for effective low cost treatments remains. Methods & Findings We used the low-complexity Drosophila melanogaster pathway to screen for small molecules that modulate JAK/STAT signalling. This screen identified methotrexate and the closely related aminopterin as potent suppressors of STAT activation. We show that methotrexate suppresses human JAK/STAT signalling without affecting other phosphorylation-dependent pathways. Furthermore, methotrexate significantly reduces STAT5 phosphorylation in cells expressing JAK2 V617F, a mutation associated with most human MPNs. Methotrexate acts independently of dihydrofolate reductase (DHFR) and is comparable to the JAK1/2 inhibitor ruxolitinib. However, cells treated with methotrexate still retain their ability to respond to physiological levels of the ligand erythropoietin. Conclusions Aminopterin and methotrexate represent the first chemotherapy agents developed and act as competitive inhibitors of DHFR. Methotrexate is also widely used at low doses to treat inflammatory and immune-mediated conditions including rheumatoid arthritis. In this low-dose regime, folate supplements are given to mitigate side effects by bypassing the biochemical requirement for DHFR. Although independent of DHFR, the mechanism-of-action underlying the low-dose effects of methotrexate is unknown. Given that multiple pro-inflammatory cytokines signal through the pathway, we suggest that suppression of the JAK/STAT pathway is likely to be the principal anti-inflammatory and immunosuppressive mechanism-of-action of low-dose methotrexate. In addition, we suggest that patients with JAK/STAT-associated haematological malignancies may benefit from low-dose methotrexate treatments. While the JAK1/2 inhibitor ruxolitinib is effective, a £43,200 annual cost precludes widespread adoption. With an annual methotrexate cost of around £32, our findings represent an important development with significant future potential. PMID:26131691

Undifferentiated carcinoma of parotid gland.

PubMed Central

López, J I; Alfaro, J; Ballestin, C

1991-01-01

Two cases of undifferentiated carcinomas of the major salivary glands were studied using immunohistochemical techniques. Results showed that this entity was a high grade malignant neoplasm arising from the excretory duct. Despite the undifferentiated appearance multiple immunophenotypes were evident in both cases. PMID:2045506

Cause-Specific Mortality Due to Malignant and Non-Malignant Disease in Korean Foundry Workers

PubMed Central

Yoon, Jin-Ha; Ahn, Yeon-Soon

2014-01-01

Background Foundry work is associated with serious occupational hazards. Although several studies have investigated the health risks associated with foundry work, the results of these studies have been inconsistent with the exception of an increased lung cancer risk. The current study evaluated the mortality of Korean foundry workers due to malignant and non-malignant diseases. Methods This study is part of an ongoing investigation of Korean foundry workers. To date, we have observed more than 150,000 person-years in male foundry production workers. In the current study, we stratified mortality ratios by the following job categories: melting-pouring, molding-coremaking, fettling, and uncategorized production work. We calculated standard mortality ratios (SMR) of foundry workers compare to general Korean men and relative risk (RR) of mortality of foundry production workers reference to non-production worker, respectively. Results Korean foundry production workers had a significantly higher risk of mortality due to malignant disease, including stomach (RR: 3.96; 95% CI: 1.41–11.06) and lung cancer (RR: 2.08; 95% CI: 1.01–4.30), compared with non-production workers. High mortality ratios were also observed for non-malignant diseases, including diseases of the circulatory (RR: 1.92; 95% CI: 1.18–3.14), respiratory (RR: 1.71; 95% CI: 1.52–21.42 for uncategorized production worker), and digestive (RR: 2.27; 95% CI: 1.22–4.24) systems, as well as for injuries (RR: 2.36; 95% CI: 1.52–3.66) including suicide (RR: 3.64; 95% CI: 1.32–10.01). Conclusion This study suggests that foundry production work significantly increases the risk of mortality due to some kinds of malignant and non-malignant diseases compared with non-production work. PMID:24505454

Tenure Eligible/Tenure Track Investigator | Center for Cancer Research

Cancer.gov

The HIV and AIDS Malignancy Branch (HAMB), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), is a national leader in research in the cancers associated with HIV/AIDS, in the development of therapies for HIV infection, and in oncogenic viruses.  We are seeking a tenure-eligible or tenure-track investigator in the field of HIV–related malignancies or viral oncogenesis.  It is anticipated that the investigator will establish an independent translational research program targeted to the study of the treatment, pathogenesis, and/or prevention of viral-induced or other HIV-associated tumors. The program can be primarily clinical, laboratory-based, or a combination of the two, and can also include animal model studies.  There is the potential to interface with a strong existing clinical research program. Potential areas of focus may include, but are not limited to, therapies for HIV malignancies, including novel immunologic approaches; viral oncogenesis; pathogenesis of HIV-associated malignancies; and virus host interactions, including immunologic interactions. 

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions

PubMed Central

Basourakos, Spyridon P.; Li, Likun; Aparicio, Ana M.; Corn, Paul G.; Kim, Jeri; Thompson, Timothy C.

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a “molecular landscape,” i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with ”BRCAness”, i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent–induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. PMID:27978798

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

PubMed

Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

PubMed Central

Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

2013-01-01

Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas. PMID:24202450

Role of stents and laser therapy in biliary strictures

NASA Astrophysics Data System (ADS)

Chennupati, Raja S.; Trowers, Eugene A.

2001-05-01

The most frequent primary cancers causing malignant obstructive jaundice were pancreatic cancer (57%), hilar biliary cancer (19% including metastatic disease), nonhilar biliary cancer (14%) and papillary cancer (10%). Endoscopic stenting has widely replaced palliative surgery for malignant biliary obstruction because of its lower risk and cost. Self-expandable metal stents are the preferred mode of palliation for hilar malignancies. Plastic stents have a major role in benign biliary strictures. Major complications and disadvantages associated with metallic stents include high cost, cholangitis. malposition, migration, unextractability, and breakage of the stents, pancreatitis and stent dysfunction. Dysfunction due to tumor ingrowth can be relieved by thermal methods (argon plasma coagulator therapy). We present a concise review of the efficacy of metallic stents for palliation of malignant strictures.

Sequential multiple-assignment randomized trial design of neurobehavioral treatment for patients with metastatic malignant melanoma undergoing high-dose interferon-alpha therapy.

PubMed

Auyeung, S Freda; Long, Qi; Royster, Erica Bruce; Murthy, Smitha; McNutt, Marcia D; Lawson, David; Miller, Andrew; Manatunga, Amita; Musselman, Dominique L

2009-10-01

Interferon-alpha therapy, which is used to treat metastatic malignant melanoma, can cause patients to develop two distinct neurobehavioral symptom complexes: a mood syndrome and a neurovegetative syndrome. Interferon-alpha effects on serotonin metabolism appear to contribute to the mood and anxiety syndrome, while the neurovegetative syndrome appears to be related to interferon-alpha effects on dopamine. Our goal is to propose a design for utilizing a sequential, multiple assignment, randomized trial design for patients with malignant melanoma to test the relative efficacy of drugs that target serotonin versus dopamine metabolism during 4 weeks of intravenous, then 8 weeks of subcutaneous, interferon-alpha therapy. Patients will be offered participation in a double-blinded, randomized, controlled, 14-week trial involving two treatment phases. During the first month of intravenous interferon-alpha therapy, we will test the hypotheses that escitalopram will be more effective in reducing depressed mood, anxiety, and irritability, whereas methylphenidate will be more effective in diminishing interferon-alpha-induced neurovegetative symptoms, such as fatigue and psychomotor slowing. During the next 8 weeks of subcutaneous interferon therapy, participants whose symptoms do not improve significantly will be randomized to the alternate agent alone versus escitalopram and methylphenidate together. We present a prototype for a single-center, sequential, multiple assignment, randomized trial, which seeks to determine the efficacy of sequenced and targeted treatment for the two distinct symptom complexes suffered by patients treated with interferon-alpha. Because we cannot completely control for external factors, a relevant question is whether or not 'short-term' neuropsychiatric interventions can increase the number of interferon-alpha doses tolerated and improve long-term survival. This sequential, multiple assignment, randomized trial proposes a framework for developing optimal treatment strategies; however, additional studies are needed to determine the best strategy for treating or preventing neurobehavioral symptoms induced by the immunotherapy interferon-alpha.

Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

ClinicalTrials.gov

2013-03-26

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Myelodysplastic Syndromes; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Disseminated Neuroblastoma; Malignant Neoplasm; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Mixed Germ Cell Tumor; Ovarian Monodermal and Highly Specialized Teratoma; Ovarian Polyembryoma; Ovarian Yolk Sac Tumor; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Seminoma; Testicular Choriocarcinoma and Teratoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Seminoma; Testicular Embryonal Carcinoma and Teratoma; Testicular Embryonal Carcinoma and Teratoma With Seminoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma and Yolk Sac Tumor With Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor; Testicular Yolk Sac Tumor and Teratoma; Testicular Yolk Sac Tumor and Teratoma With Seminoma

Familial association of specific histologic types of ovarian malignancy with other malignancies.

PubMed

Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

2004-04-01

Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

Neural Stem Cells: Implications for the Conventional Radiotherapy of Central Nervous System Malignancies

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

Barani, Igor J.; Benedict, Stanley H.; Lin, Peck-Sun

Advances in basic neuroscience related to neural stem cells and their malignant counterparts are challenging traditional models of central nervous system tumorigenesis and intrinsic brain repair. Neurogenesis persists into adulthood predominantly in two neurogenic centers: subventricular zone and subgranular zone. Subventricular zone is situated adjacent to lateral ventricles and subgranular zone is confined to the dentate gyrus of the hippocampus. Neural stem cells not only self-renew and differentiate along multiple lineages in these regions, but also contribute to intrinsic brain plasticity and repair. Ionizing radiation can depopulate these exquisitely sensitive regions directly or impair in situ neurogenesis by indirect, dose-dependentmore » and inflammation-mediated mechanisms, even at doses <2 Gy. This review discusses the fundamental neural stem cell concepts within the framework of cumulative clinical experience with the treatment of central nervous system malignancies using conventional radiotherapy.« less

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types

PubMed Central

Ekeowa-Anderson, A. L.; Harwood, C. A.; Perrett, C. M.; Sahota, A.; Annan, H.; Ran, H.; Leigh, I. M.; Gibbon, K. L.

2008-01-01

Summary Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple α and β papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited. PMID:17362236

Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies

ClinicalTrials.gov

2018-05-09

Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin's Lymphoma; Non-Hodgkin Lymphoma; Hodgkin Disease; Hodgkins Disease; Hodgkin's Disease; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

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

Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promotermore » activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation. • Luteolin inhibited chronic Cr(VI)-induced inflammation. • Luteolin inhibited chronic Cr(VI)-induced angiogenesis.« less

Secondary malignancy following radiotherapy for thyroid eye disease.

PubMed

Gillis, Christopher C; Chang, Eun Hae; Al-Kharazi, Khalid; Pickles, Tom

2016-01-01

To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience. Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy. The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies. The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575). Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3-1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.

Economic burden of non-malignant blood disorders across Europe: a population-based cost study.

PubMed

Luengo-Fernandez, Ramon; Burns, Richeal; Leal, Jose

2016-08-01

Blood disorders comprise a wide range of diseases including anaemia, malignant blood disorders, and haemorrhagic disorders. Although they are a common cause of disease, no systematic cost-of-illness studies have been done to assess the economic effect of non-malignant blood disorders in Europe. We aimed to assess the economic burden of non-malignant blood disorders across the 28 countries of the European Union (EU), Iceland, Norway, and Switzerland. Non-malignant blood disorder-related costs (WHO International Classification of Diseases, 10th revision [ICD] D50-89) were estimated for 28 EU countries, Iceland, Norway, and Switzerland for 2012. Country-specific costs were estimated with aggregate data on morbidity, mortality, and health-care resource use obtained from international and national sources. Health-care costs were estimated from expenditure on primary care, outpatient care, emergency care, hospital inpatient care, and drugs. Costs of informal care and productivity losses due to morbidity and early death were also included. To these costs we added those due to malignant blood disorders (ICD-10 C81-96 and D47) as estimated in a Burns and colleagues' companion Article to obtain the total costs of blood disorders. Non-malignant disorders of the blood cost the 31 European countries €11 billion in 2012. Health-care costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for less than €1 billion (6%). Averaged across the European population studied, non-malignant disorders of the blood represented an annual health-care cost of €159 per ten citizens. Combining malignant and non-malignant blood disorders, the total cost of blood disorders was €23 billion in 2012. Our study highlights the economic burden that non-malignant blood disorders place on European health-care systems and societies. Our study also shows that blood disorder costs were evenly distributed between malignant and non-malignant blood disorders. Our results should be of use to decision makers and research-funding authorities charged with allocating health-care resources and research funds. European Hematology Association. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison and Optimization of 3.0 T Breast Images Quality of Diffusion-Weighted Imaging with Multiple B-Values.

PubMed

Han, Xiaowei; Li, Junfeng; Wang, Xiaoyi

2017-04-01

Breast 3.0 T magnetic resonance diffusion-weighted imaging (MR-DWI) of benign and malignant lesions were obtained to measure and calculate the signal-to-noise ratio (SNR), signal intensity ratio (SIR), and contrast-to-noise ratio (CNR) of lesions at different b-values. The variation patterns of SNR and SIR were analyzed with different b-values and the images of DWI were compared at four different b-values with higher image quality. The effect of SIR on the differential diagnostic efficiency of benign and malignant lesions was compared using receiver operating characteristic curves to provide a reference for selecting the optimal b-value. A total of 96 qualified patients with 112 lesions and 14 patients with their contralateral 14 normal breasts were included in this study. The single-shot echo planar imaging sequence was used to perform the DWI and a total of 13 b-values were used: 0, 50, 100, 200, 400, 600, 800, 1000, 1200, 1500, 1800, 2000, and 2500 s/mm 2 . On DWI, the suitable regions of interest were selected. The SNRs of normal breasts (SNR normal ), SNR lesions , SIR, and CNR of benign and malignant lesions were measured on DWI with different b-values and calculated. The variation patterns of SNR, SIR, and CNR values on DWI for normal breasts, benign lesions, and malignant lesions with different b-values were analyzed by using Pearson correlation analysis. The SNR and SIR of benign and malignant lesions with the same b-values were compared using t-tests. The diagnostic efficiencies of SIR with different b-values for benign and malignant lesions were evaluated using receiver operating characteristic curves. Breast DWI had higher CNR for b-values ranging from 600 to 1200 s/mm 2 . It had the best CNR at b = 1000 s/mm 2 for the benign lesions and at b = 1200 s/mm 2 for the malignant lesions. The signal intensity and SNR values of normal breasts decreased with increasing b-values, with a negative correlation (r = -0.945, P < 0.01). The mean SNR values of benign and malignant lesions were negatively correlated (r = -0.982 and -0.947, respectively, and P < 0.01), gradually decreasing with increasing b-values. The mean SIR value of benign lesions gradually decreased with increasing b-values, a negative correlation (r = -0.991, P < 0.01). The mean SIR values of malignant lesions gradually increased with increasing b-values between 0 and 1200 s/mm 2 , and gradually decreased with increasing b-values ≥ 1500 s/mm 2 . For b-values of 600, 800, 1000, and 1200 s/mm 2 , the sensitivity and specificity of SIR in identifying benign and malignant lesions gradually increased with increasing b-values, peaking at 1200 s/mm 2 . Breast DWI had higher image quality for b-values ranging from 600 to 1200 s/mm 2 , and was best for b-values ranging from 1000 to 1200 s/mm 2 . The SIR had the highest diagnostic efficiency in differentiating benign and malignant lesions for a b-value of 1200 s/mm 2 . Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Potential Anticancer Properties of Osthol: A Comprehensive Mechanistic Review

PubMed Central

Shokoohinia, Yalda; Jafari, Fataneh; Mohammadi, Zeynab; Bazvandi, Leili; Hosseinzadeh, Leila; Chow, Nicholas; Bhattacharyya, Piyali; Farzaei, Mohammad Hosein; Farooqi, Ammad Ahmad; Nabavi, Seyed Mohammad; Bishayee, Anupam

2018-01-01

Cancer is caused by uncontrolled cell proliferation which has the potential to occur in different tissues and spread into surrounding and distant tissues. Despite the current advances in the field of anticancer agents, rapidly developing resistance against different chemotherapeutic drugs and significantly higher off-target effects cause millions of deaths every year. Osthol is a natural coumarin isolated from Apiaceaous plants which has demonstrated several pharmacological effects, such as antineoplastic, anti-inflammatory and antioxidant properties. We have attempted to summarize up-to-date information related to pharmacological effects and molecular mechanisms of osthol as a lead compound in managing malignancies. Electronic databases, including PubMed, Cochrane library, ScienceDirect and Scopus were searched for in vitro, in vivo and clinical studies on anticancer effects of osthol. Osthol exerts remarkable anticancer properties by suppressing cancer cell growth and induction of apoptosis. Osthol’s protective and therapeutic effects have been observed in different cancers, including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia, lung adenocarcinoma, glioma, hepatocellular, glioblastoma, renal and invasive mammary carcinoma. A large body of evidence demonstrates that osthol regulates apoptosis, proliferation and invasion in different types of malignant cells which are mediated by multiple signal transduction cascades. In this review, we set spotlights on various pathways which are targeted by osthol in different cancers to inhibit cancer development and progression. PMID:29301373

Changing presentation of cutaneous malignant melanoma.

PubMed

Klit, Anders; Lassen, Cecilie Brandt; Olsen, Caroline Holkmann; Lock-Andersen, Jørgen

2015-10-01

The incidence of cutaneous malignant melanoma is rapidly increasing in Denmark like in other Northern and Western European countries. Our objective was to investigate the characteristics of current patients suffering from cutaneous malignant melanoma. We evaluated patient and tumour characteristics in a cross-sectional study based on data from the Danish Melanoma Register. We included all patients diagnosed with cutaneous malignant melanoma in Healthcare Region Zealand in 2012 and 2013. We identified 520 patients with invasive cutaneous malignant melanoma. More females than males suffered from cutaneous malignant melanoma. Furthermore, females were younger than males, and the anatomical distribution of malignant melanoma varied between the genders. Outcome of sentinel lymph node biopsy was associated with tumour thickness. When comparing findings in our study with earlier Danish studies, we see a trend towards an increase in age at diagnosis. Furthermore, tumour thickness is decreasing and the topical distribution of cutaneous malignant melanoma in females changes towards a male pattern. none. The study has been approved by the Danish National Data Protection Agency.

Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

PubMed Central

Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

2016-01-01

The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

Clear cell hidradenocarcinoma of the breast: a very rare breast skin tumor.

PubMed

Mezzabotta, Maurizio; Declich, Paolo; Cardarelli, Mery; Bellone, Stefano; Pacilli, Paolo; Riggio, Eliana; Pallino, Antonio

2012-01-01

Hidradenocarcinoma is an uncommon malignant intradermal tumor of sweat gland origin with a predilection for the face and extremities. It is encountered equally in males and females, usually in the second half of life. These tumors tend to be locally aggressive. In our case, the tumor was located relatively superficially but without any apparent connection to the overlying skin. The typical disease course includes local and sometimes multiple recurrences, and some patients develop regional lymph node and distant metastases. These type of tumors in the parenchyma of the breast are extremely rare. We report a case of hidradenocarcinoma in a 77-year-old woman who presented with a palpable inflammatory nodule in the right breast.

Café-au-lait macules and pediatric malignancy caused by biallelic mutations in the DNA mismatch repair (MMR) gene PMS2.

PubMed

Jackson, Carl-Christian; Holter, Spring; Pollett, Aaron; Clendenning, Mark; Chou, Shirley; Senter, Leigha; Ramphal, Raveena; Gallinger, Steven; Boycott, Kym

2008-06-01

A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum. (c) 2007 Wiley-Liss, Inc.

Defining disease with laser precision: laser capture microdissection in gastroenterology.

PubMed

Blatt, Richard; Srinivasan, Shanthi

2008-08-01

Laser capture microdissection (LCM) is an efficient and precise method for obtaining pure cell populations or specific cells of interest from a given tissue sample. LCM has been applied to animal and human gastroenterology research in analyzing the protein, DNA, and RNA from all organs of the gastrointestinal system. There are numerous potential applications for this technology in gastroenterology research, including malignancies of the esophagus, stomach, colon, biliary tract, and liver. This technology can also be used to study gastrointestinal infections, inflammatory bowel disease, pancreatitis, motility, malabsorption, and radiation enteropathy. LCM has multiple advantages when compared with conventional methods of microdissection, and this technology can be exploited to identify precursors to disease, diagnostic biomarkers, and therapeutic interventions.

Malignancy in solitary thyroid nodule: A clinicoradiopathological evaluation.

PubMed

Jena, Amitabh; Patnayak, Rashmi; Prakash, Jaya; Sachan, Alok; Suresh, V; Lakshmi, Amarchala Yadagiri

2015-01-01

Thyroid nodules are common. They can be either benign or malignant. Solitary thyroid nodules (STN) have a high likelihood of being malignant. They should be characterized properly for optimum management. In this study, we have analyzed our departmental data over a period of 5 years. All the patients who presented to the outpatient department with a clinically detected STN were included in the study group. Our approach was individualized. Preoperative ultrasonography (USG) and fine-needle aspiration cytology were planned in all these patients. Hemi thyroidectomy and total thyroidectomy with and without neck dissection were performed wherever appropriate. There were 162 cases of clinically detected STN. USG findings were available in 146 cases. Postoperative histopathology was reported as malignant in 58 cases. Malignant STN was more likely in males. Ultrasonographically detected solid STN were more prone for malignancy as compared to multinodular goiter (P = 0.000) Presence of micro calcification and cervical lymphadenopathy were more commonly noted in malignant thyroid swellings. Solitary thyroid nodules do have a high likelihood of harboring a malignancy. Solid echogenicity, micro calcification and cervical lymphadenopathy on USG were seen more frequently in malignant nodules.

The diagnostic performance of shear wave elastography for malignant cervical lymph nodes: A systematic review and meta-analysis.

PubMed

Suh, Chong Hyun; Choi, Young Jun; Baek, Jung Hwan; Lee, Jeong Hyun

2017-01-01

To evaluate the diagnostic performance of shear wave elastography for malignant cervical lymph nodes. We searched the Ovid-MEDLINE and EMBASE databases for published studies regarding the use of shear wave elastography for diagnosing malignant cervical lymph nodes. The diagnostic performance of shear wave elastography was assessed using bivariate modelling and hierarchical summary receiver operating characteristic modelling. Meta-regression analysis and subgroup analysis according to acoustic radiation force impulse imaging (ARFI) and Supersonic shear imaging (SSI) were also performed. Eight eligible studies which included a total sample size of 481 patients with 647 cervical lymph nodes, were included. Shear wave elastography showed a summary sensitivity of 81 % (95 % CI: 72-88 %) and specificity of 85 % (95 % CI: 70-93 %). The results of meta-regression analysis revealed that the prevalence of malignant lymph nodes was a significant factor affecting study heterogeneity (p < .01). According to the subgroup analysis, the summary estimates of the sensitivity and specificity did not differ between ARFI and SSI (p = .93). Shear wave elastography is an acceptable imaging modality for diagnosing malignant cervical lymph nodes. We believe that both ARFI and SSI may have a complementary role for diagnosing malignant cervical lymph nodes. • Shear wave elastography is acceptable modality for diagnosing malignant cervical lymph nodes. • Shear wave elastography demonstrated summary sensitivity of 81 % and specificity of 85 %. • ARFI and SSI have complementary roles for diagnosing malignant cervical lymph nodes.

Skin rash in the intensive care unit: Stevens-Johnson syndrome, toxic epidermal necrolysis, or a rare manifestation of a hidden cutaneous malignancy: A case report.

PubMed

Al-Saffar, Farah; Ibrahim, Saif; Patel, Pujan; Jacob, Rafik; Palacio, Carlos; Cury, James

2016-03-01

Skin rashes are infrequently encountered in the intensive care units, either as a result or as a cause of admission. The entities of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of desquamating skin diseases that have multiple etiologies, the most common being drug-related reactions; very rarely, the cause may be cutaneous malignancies. We herein present a unique case of a 54-year-old male patient with psoriasis treated with methotrexate, who presented with a cellulitis-like clinical picture, then developed a severe progressive systemic inflammatory response syndrome, and progressed clinically to SJS, then TEN even after discontinuing the antibiotics and methotrexate. A skin biopsy demonstrated an aggressive and rapidly-progressing T-cell lymphoma. The present case highlights the necessity of skin biopsy when encountering SJS and TEN in the ICU in order to identify potentially treatable/controllable causes. Although it appeared reasonable to correlate TEN solely to medications, the skin biopsies clearly demonstrated an aggressive T-cell skin lymphoma. In a patient with a better general condition it may have been helpful to treat this malignancy. TEN is a life-threatening condition and skin biopsy is the cornerstone of diagnosis, despite the presence of multiple risk factors and the typical physical findings of a drug-induced reaction.

Detection of monoclonal immunoglobulin heavy chain gene rearrangement (FR3) in Thai malignant lymphoma by High Resolution Melting curve analysis.

PubMed

Kummalue, Tanawan; Chuphrom, Anchalee; Sukpanichanant, Sanya; Pongpruttipan, Tawatchai; Sukpanichanant, Sathien

2010-05-19

Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Detection of antigen receptor gene rearrangement including T cell receptor (TCR) and immunoglobulin heavy chain (IgH) by polymerase chain reaction followed by heteroduplex has currently become standard whereas fluorescent fragment analysis (GeneScan) has been used for confirmation test. In this study, three techniques had been compared: thermocycler polymerase chain reaction (PCR) followed by heteroduplex and polyacrylamide gel electrophoresis, GeneScan analysis, and real time PCR with High Resolution Melting curve analysis (HRM). The comparison was carried out with DNA extracted from paraffin embedded tissues diagnosed as B- cell non-Hodgkin lymphoma. Specific PCR primers sequences for IgH gene variable region 3, including fluorescence labeled IgH primers were used and results were compared with HRM. In conclusion, the detection IgH gene rearrangement by HRM in the LightCycler System showed potential for distinguishing monoclonality from polyclonality in B-cell non-Hodgkin lymphoma. Malignant lymphoma, especially non-Hodgkin lymphoma, is one of the most common hematologic malignancies in Thailand. The incidence rate as reported by Ministry of Public Health is 3.1 per 100,000 population in female whereas the rate in male is 4.5 per 100,000 population 1. At Siriraj Hospital, the new cases diagnosed as malignant lymphoma were 214.6 cases/year 2. The diagnosis of malignant lymphoma is often problematic, especially in early stages of the disease. Therefore, detection of antigen receptor gene rearrangement including T cell receptor (TCR) and immunoglobulin heavy chain (IgH) by polymerase chain reaction (PCR) assay has recently become a standard laboratory test for discrimination of reactive from malignant clonal lymphoproliferation 34. Analyzing DNA extracted from formalin-fixed, paraffin-embedded tissues by multiplex PCR techniques is more rapid, accurate and highly sensitive. Measuring the size of the amplicon from PCR analysis could be used to diagnose malignant lymphoma with monoclonal pattern showing specific and distinct bands detected on acrylamide gel electrophoresis. However, this technique has some limitations and some patients might require a further confirmation test such as GeneScan or fragment analysis 56.GeneScan technique or fragment analysis reflects size and peak of DNA by using capillary gel electrophoresis. This technique is highly sensitive and can detect 0.5-1% of clonal lymphoid cells. It measures the amplicons by using various fluorescently labeled primers at forward or reverse sides and a specific size standard. Using a Genetic Analyzer machine and GeneMapper software (Applied Bioscience, USA), the monoclonal pattern revealed one single, sharp and high peak at the specific size corresponding to acrylamide gel pattern, whereas the polyclonal pattern showed multiple and small peak condensed at the same size standard. This technique is the most sensitive and accurate technique; however, it usually requires high technical experience and is also of high cost 7. Therefore, rapid and more cost effective technique are being sought.LightCycler PCR performs the diagnostic detection of amplicon via melting curve analysis within 2 hours with the use of a specific dye 89. This dye consists of two types: one known as SYBR-Green I which is non specific and the other named as High Resolution Melting analysis (HRM) which is highly sensitive, more accurate and stable. Several reports demonstrated that this new instrument combined with DNA intercalating dyes can be used to discriminate sequence changes in PCR amplicon without manual handling of PCR product 1011. Therefore, current investigations using melting curve analysis are being developed 1213.In this study, three different techniques were compared to evaluate the suitability of LightCycler PCR with HRM as the clonal diagnostic tool for IgH gene rearrangement in B-cell non-Hogdkin lymphoma, i.e. thermocycler PCR followed by heteroduplex analysis and PAGE, GeneScan analysis and LightCycler PCR with HRM.

Contrast-enhanced spectral mammography: Impact of the qualitative morphology descriptors on the diagnosis of breast lesions.

PubMed

Mohamed Kamal, Rasha; Hussien Helal, Maha; Wessam, Rasha; Mahmoud Mansour, Sahar; Godda, Iman; Alieldin, Nelly

2015-06-01

To analyze the morphology and enhancement characteristics of breast lesions on contrast-enhanced spectral mammography (CESM) and to assess their impact on the differentiation between benign and malignant lesions. This ethics committee approved study included 168 consecutive patients with 211 breast lesions over 18 months. Lesions classified as non-enhancing and enhancing and then the latter group was subdivided into mass and non-mass. Mass lesions descriptors included: shape, margins, pattern and degree of internal enhancement. Non-mass lesions descriptors included: distribution, pattern and degree of internal enhancement. The impact of each descriptor on diagnosis individually assessed using Chi test and the validity compared in both benign and malignant lesions. The overall performance of CESM were also calculated. The study included 102 benign (48.3%) and 109 malignant (51.7%) lesions. Enhancement was encountered in 145/211 (68.7%) lesions. They further classified into enhancing mass (99/145, 68.3%) and non-mass lesions (46/145, 31.7%). Contrast uptake was significantly more frequent in malignant breast lesions (p value ≤ 0.001). Irregular mass lesions with intense and heterogeneous enhancement patterns correlated with a malignant pathology (p value ≤ 0.001). CESM showed an overall sensitivity of 88.99% and specificity of 83.33%. The positive and negative likelihood ratios were 5.34 and 0.13 respectively. The assessment of the morphology and enhancement characteristics of breast lesions on CESM enhances the performance of digital mammography in the differentiation between benign and malignant breast lesions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Malignant nerve-sheath neoplasms in neurofibromatosis: distinction from benign tumors by using imaging techniques

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

Levine, E.; Huntrakoon, M.; Wetzel, L.H.

Malignant peripheral nerve-sheath neoplasms frequently complicate neurofibromatosis causing pain, enlarging masses, or neurologic deficits. However, similar findings sometimes also occur with benign nerve neoplasms. Our study was done retrospectively to determine if imaging techniques can differentiate malignant from benign nerve tumors in neurofibromatosis. Eight patients with symptomatic neoplasms (three benign, five malignant) were studied by CT in eight, MR in six, and /sup 67/Ga-citrate scintigraphy in seven. Uptake of /sup 67/Ga occurred in all five malignant lesions but not in two benign neoplasms studied. On CT or MR, all eight lesions, including three benign neoplasms, showed inhomogeneities. Of five lesionsmore » with irregular, infiltrative margins on CT or MR, four were malignant and one was benign. Of three lesions with smooth margins, one was malignant and two were benign. One malignant neoplasm caused irregular bone destruction. Accordingly, CT and MR could not generally distinguish malignant from benign lesions with certainty. However, both CT and MR provided structural delineation to help surgical planning for both types of lesion. /sup 67/Ga scintigraphy appears promising as a screening technique to identify lesions with malignant degeneration in patients with neurofibromatosis. Any area of abnormal radiogallium uptake suggests malignancy warranting further evaluation by CT or MR. Biopsy of any questionable lesion is essential.« less

Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component.

PubMed

Cuadra-Urteaga, José Luis; Font, Albert; Tapia, Gustavo; Areal, Juan; Taron, Miquel

2016-01-01

Carcinosarcomas (CS) are biphasic tumors with malignant epithelial and mesenchymal elements. The sarcomatoid elements of CS can include chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, leiomyosarcoma, fibrosarcoma, or liposarcoma. CS of the upper urinary tract are extremely rare but are associated with a poor prognosis. We report a case of a 44-year-old man with a localized right renal pelvis mass treated with a right nephroureterectomy. The pathological examination showed a high-grade urothelial carcinoma of the renal pelvis, stage III (pT3aNxM0). A few days later, he developed lower back pain, hematuria, cough with hemoptoic sputum and progressive dyspnea. Radiological explorations showed multiple bilateral lung nodules and a retroperitoneal mass. A CT-guided biopsy of the retroperitoneal mass revealed a high-grade angiosarcoma. A review of the nephrectomy specimen showed a microscopic focus of angiosarcoma in the urothelial carcinoma. Therefore, the initial diagnosis was changed to CS of the renal pelvis with an angiosarcoma component. The patient developed progressive respiratory failure and died 8 weeks after surgery. An autopsy revealed a large retroperitoneal mass with metastatic nodules to the abdominal wall, diaphragm, small intestine, liver, spleen, and lung. All lesions were angiosarcoma, with no evidence of urothelial carcinoma. This is the first case reported of a patient with CS of the upper urinary tract with an angiosarcoma component with a very aggressive course that caused the immediate appearance of multiple angiosarcoma metastases. We also describe the clinical and molecular characteristics of CS, which will help to contribute to a better understanding of this type of tumor.

Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component

PubMed Central

Cuadra-Urteaga, José Luis; Font, Albert; Tapia, Gustavo; Areal, Juan; Taron, Miquel

2016-01-01

ABSTRACT Carcinosarcomas (CS) are biphasic tumors with malignant epithelial and mesenchymal elements. The sarcomatoid elements of CS can include chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, leiomyosarcoma, fibrosarcoma, or liposarcoma. CS of the upper urinary tract are extremely rare but are associated with a poor prognosis. We report a case of a 44-year-old man with a localized right renal pelvis mass treated with a right nephroureterectomy. The pathological examination showed a high-grade urothelial carcinoma of the renal pelvis, stage III (pT3aNxM0). A few days later, he developed lower back pain, hematuria, cough with hemoptoic sputum and progressive dyspnea. Radiological explorations showed multiple bilateral lung nodules and a retroperitoneal mass. A CT-guided biopsy of the retroperitoneal mass revealed a high-grade angiosarcoma. A review of the nephrectomy specimen showed a microscopic focus of angiosarcoma in the urothelial carcinoma. Therefore, the initial diagnosis was changed to CS of the renal pelvis with an angiosarcoma component. The patient developed progressive respiratory failure and died 8 weeks after surgery. An autopsy revealed a large retroperitoneal mass with metastatic nodules to the abdominal wall, diaphragm, small intestine, liver, spleen, and lung. All lesions were angiosarcoma, with no evidence of urothelial carcinoma. This is the first case reported of a patient with CS of the upper urinary tract with an angiosarcoma component with a very aggressive course that caused the immediate appearance of multiple angiosarcoma metastases. We also describe the clinical and molecular characteristics of CS, which will help to contribute to a better understanding of this type of tumor. PMID:26891233

Differentiation of benign from malignant cervical lymph nodes in patients with head and neck cancer using PET/CT imaging.

PubMed

Payabvash, Seyedmehdi; Meric, Kaan; Cayci, Zuzan

2016-01-01

To differentiate malignant from benign cervical lymph nodes in patients with head/neck cancer. In this retrospective study, 39 patients with primary head/neck cancer who underwent Positron Emission Tomography (PET)/Computerized Tomography (CT) and image-guided lymph node biopsy were included. Overall, 23 (59%) patients had biopsy-proven malignant cervical lymphadenopathy. Malignant lymph nodes had higher maximum standardized uptake (SUV-max) value (P<.001) and short-axis diameter (P=.015) compared to benign nodes. An SUV-max of ≥2.5 was 100% sensitive, and an SUV-max ≥5.5 was 100% specific for malignant lymphadenopathy. The PET/CT SUV-max value can help with differentiation of malignant cervical lymph nodes in patients with head/neck cancer. Published by Elsevier Inc.

Shorter Course Tacro After NMA, Related Donor PBSCT With High-dose Posttransplant Cy for Hard-to-Engraft Malignancies

ClinicalTrials.gov

2018-03-13

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Chronic Myeloid Leukemia; Chronic Myeloproliferative Disorders; Multiple Myeloma; Plasma Cell Neoplasm; Plasma Cell Dyscrasia; Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Plasma Cell Leukemia

Study of CB-103 in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies

ClinicalTrials.gov

2018-01-30

Advanced or Metastatic Solid Tumours; Breast Cancer; Colorectal Cancer; Gastric Cancer; Cholangiocellular Carcinoma; Ovarian Cancer; Cervical Cancer; Prostate Cancer; Melanoma; Sarcoma; NSCLC; Desmoid Tumour; Adenoid Cystic Carcinoma; Glioblastoma Multiforme; Hodgkin Lymphoma; Non-hodgkin Lymphoma; Multiple Myeloma

Multiple strategies of oxygen supply in Drosophila malignancies identify tracheogenesis as a novel cancer hallmark.

PubMed

Grifoni, Daniela; Sollazzo, Manuela; Fontana, Elisabetta; Froldi, Francesca; Pession, Annalisa

2015-03-12

Angiogenesis is the term used to describe all the alterations in blood vessel growth induced by a tumour mass following hypoxic stress. The occurrence of multiple strategies of vessel recruitment favours drug resistance, greatly complicating the treatment of certain tumours. In Drosophila, oxygen is conveyed to the internal organs by the tracheal system, a closed tubular network whose role in cancer growth is so far unexplored. We found that, as observed in human cancers, Drosophila malignant cells suffer from oxygen shortage, release pro-tracheogenic factors, co-opt nearby vessels and get incorporated into the tracheal walls. We also found that the parallelisms observed in cellular behaviours are supported by genetic and molecular conservation. Finally, we identified a molecular circuitry associated with the differentiation of cancer cells into tracheal cells. In summary, our findings identify tracheogenesis as a novel cancer hallmark in Drosophila, further expanding the power of the fly model in cancer research.

Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012.

PubMed

Blake, Mary Kay; Carr, Brittany J; Mauldin, Glenna E

2016-02-01

Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing.

Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007–2012

PubMed Central

Blake, Mary Kay; Carr, Brittany J.; Mauldin, Glenna E.

2016-01-01

Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L-asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L-asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing. PMID:26834270

Variant hairy cell leukemia following papillary urothelial neoplasm of bladder.

PubMed

Beyan, Cengiz; Kaptan, Kürsat

2014-03-01

A 65 years old man was admitted with multiple lymphadenopathy, weight loss, night sweats and fatigue for 2 months. He had been treated for bladder cancer 2 years ago. Leukocyte count was 37.9 x10(9)/l. Peripheral blood smear had 91% lymphocytes. Lymphocytes had large nuclei with prominent nucleoli, heterogeneous appearance, and large cytoplasm with hairy projections. Flow cytometric immunophenotyping revealed CD20, CD22, CD24, CD45 and HLA-DR positivity. Atypical lymphocytes were stained with tartrate resistant acid phosphatase. Increased metabolic activity was detected in multiple lymph nodes, bone marrow and extremely enlarged spleen with positron emission tomography-computed tomography. Excisional biopsy of the left axillary lymph node revealed infiltration with diffuse B-cell leukemia/lymphoma. Immunohistochemistry showed CD20 positive atypical cells with weak expression of CD11c. The patient was diagnosed as a case of variant hairy cell leukemia and cladribine was administered. A probable second primary malignancy should be kept in mind in cases with a defined malignancy in the presence of unusual symptoms.

Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

PubMed

Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

1984-06-01

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

Use of chloro-aluminum sulfonated phthalocyanine as a photosensitizer in the treatment of malignant tumors in dogs and cats

NASA Astrophysics Data System (ADS)

Peavy, George M.; Klein, Mary K.; Newman, H. C.; Roberts, Walter G.; Berns, Michael W.

1991-05-01

Chloro-aluminum sulfonated phthalocyanine (CASPc) has been proposed as a photosensitizing agent for photodynamic therapy (PDT) of neoplasia. This paper reviews the results of PDT treatment using CASPc as a photosensitizing agent in the treatment of 15 cats representing 23 sites of facial, solar induced squamous cell carcinoma, 4 dogs with hemangiopericytomas, 3 dogs with fibrosarcomas, and 1 dog with multiple cutaneous mast cell tumors. The results of this study to date suggest that CASPc is a good photosensitizing agent for the treatment of some forms of spontaneously occurring malignant neoplasia and should be more thoroughly evaluated for this purpose.

Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond

PubMed Central

Hall, MJ; Obeid, EI; Schwartz, SC; Mantia-Smaldone, G; Forman, AD; Daly, MB

2016-01-01

Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multigene panel tests is critical for providers on the front-line of women’s health. PMID:26812021

Zebrafish as a model to assess cancer heterogeneity, progression and relapse

PubMed Central

Blackburn, Jessica S.; Langenau, David M.

2014-01-01

Clonal evolution is the process by which genetic and epigenetic diversity is created within malignant tumor cells. This process culminates in a heterogeneous tumor, consisting of multiple subpopulations of cancer cells that often do not contain the same underlying mutations. Continuous selective pressure permits outgrowth of clones that harbor lesions that are capable of enhancing disease progression, including those that contribute to therapy resistance, metastasis and relapse. Clonal evolution and the resulting intratumoral heterogeneity pose a substantial challenge to biomarker identification, personalized cancer therapies and the discovery of underlying driver mutations in cancer. The purpose of this Review is to highlight the unique strengths of zebrafish cancer models in assessing the roles that intratumoral heterogeneity and clonal evolution play in cancer, including transgenesis, imaging technologies, high-throughput cell transplantation approaches and in vivo single-cell functional assays. PMID:24973745

Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression.

PubMed

Bacigalupo, María L; Carabias, Pablo; Troncoso, María F

2017-08-07

Gastrointestinal cancer is a group of tumors that affect multiple sites of the digestive system, including the stomach, liver, colon and pancreas. These cancers are very aggressive and rapidly metastasize, thus identifying effective targets is crucial for treatment. Galectin-1 (Gal-1) belongs to a family of glycan-binding proteins, or lectins, with the ability to cross-link specific glycoconjugates. A variety of biological activities have been attributed to Gal-1 at different steps of tumor progression. Herein, we summarize the current literature regarding the roles of Gal-1 in gastrointestinal malignancies. Accumulating evidence shows that Gal-1 is drastically up-regulated in human gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic ductal adenocarcinoma tissues, both in tumor epithelial and tumor-associated stromal cells. Moreover, Gal-1 makes a crucial contribution to the pathogenesis of gastrointestinal malignancies, favoring tumor development, aggressiveness, metastasis, immunosuppression and angiogenesis. We also highlight that alterations in Gal-1-specific glycoepitopes may be relevant for gastrointestinal cancer progression. Despite the findings obtained so far, further functional studies are still required. Elucidating the precise molecular mechanisms modulated by Gal-1 underlying gastrointestinal tumor progression, might lead to the development of novel Gal-1-based diagnostic methods and/or therapies.

Combination of methylated-DNA precipitation and methylation-sensitive restriction enzymes (COMPARE-MS) for the rapid, sensitive and quantitative detection of DNA methylation.

PubMed

Yegnasubramanian, Srinivasan; Lin, Xiaohui; Haffner, Michael C; DeMarzo, Angelo M; Nelson, William G

2006-02-09

Hypermethylation of CpG island (CGI) sequences is a nearly universal somatic genome alteration in cancer. Rapid and sensitive detection of DNA hypermethylation would aid in cancer diagnosis and risk stratification. We present a novel technique, called COMPARE-MS, that can rapidly and quantitatively detect CGI hypermethylation with high sensitivity and specificity in hundreds of samples simultaneously. To quantitate CGI hypermethylation, COMPARE-MS uses real-time PCR of DNA that was first digested by methylation-sensitive restriction enzymes and then precipitated by methyl-binding domain polypeptides immobilized on a magnetic solid matrix. We show that COMPARE-MS could detect five genome equivalents of methylated CGIs in a 1000- to 10,000-fold excess of unmethylated DNA. COMPARE-MS was used to rapidly quantitate hypermethylation at multiple CGIs in >155 prostate tissues, including benign and malignant prostate specimens, and prostate cell lines. This analysis showed that GSTP1, MDR1 and PTGS2 CGI hypermethylation as determined by COMPARE-MS could differentiate between malignant and benign prostate with sensitivities >95% and specificities approaching 100%. This novel technology could significantly improve our ability to detect CGI hypermethylation.

Adult bile duct strictures: differentiating benign biliary stenosis from cholangiocarcinoma.

PubMed

Nguyen Canh, Hiep; Harada, Kenichi

2016-12-01

Biliary epithelial cells preferentially respond to various insults under chronic pathological conditions leading to reactively atypical changes, hyperplasia, or the development of biliary neoplasms (such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and cholangiocarcinoma). Moreover, benign biliary strictures can be caused by a variety of disorders (such as IgG4-related sclerosing cholangitis, eosinophilic cholangitis, and follicular cholangitis) and often mimic malignancies, despite their benign nature. In addition, primary sclerosing cholangitis is a well-characterized precursor lesion of cholangiocarcinoma and many other chronic inflammatory disorders increase the risk of malignancies. Because of these factors and the changes in biliary epithelial cells, biliary strictures frequently pose a diagnostic challenge. Although the ability to differentiate neoplastic from non-neoplastic biliary strictures has markedly progressed with the advance in radiological modalities, brush cytology and bile duct biopsy examination remains effective. However, no single modality is adequate to diagnose benign biliary strictures because of the low sensitivity. Therefore, understanding the underlying causes by compiling the entire clinical, laboratory, and imaging data; considering the under-recognized causes; and collaborating between experts in various fields including cytopathologists with multiple approaches is necessary to achieve an accurate diagnosis.

Malignant external otitis: long-term (months) antimicrobial therapy

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

Strauss, M.; Aber, R.C.; Conner, G.H.

1982-04-01

Since Chandler's initial report in 1968 on malignant external otitis (MEO), this entity has been recognized in its earlier stages with increasing frequency. As a result of this, the availability of new antimicrobial agents, and the judicious use of surgery, there has been an improvement in the results of therapy. There remains, however, a subgroup of patients who continue to experience a significant mortality from this infection. A review and selected discussion of our experience with MEO from 1976 to 1979 is presented. Six patients have been diagnosed and successfully treated for MEO. They presented with problems ranging from severemore » otalgia to multiple cranial neuropathy. For the most part, therapy consisted of the now standard aminoglycoside and carbenicillin combination. Two of the patients were in the high mortality risk group. One of these patients developed an osteomyelitis which extended across the skull base resulting in bilateral cranial neuropathies. His therapy included surgery as well as long-term (months) outpatient treatment with tobramycin and carbenicillin with an excellent result. The second patient was treated similarly. The efficacy of this approach is discussed as well as the usefulness of radionuclide bone scanning in assessing the course and therapy of patients with MEO.« less

The key role of extracellular vesicles in the metastatic process.

PubMed

Zhao, Hongyun; Achreja, Abhinav; Iessi, Elisabetta; Logozzi, Mariantonia; Mizzoni, Davide; Di Raimo, Rossella; Nagrath, Deepak; Fais, Stefano

2018-01-01

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Gaining ground on a cure through synergy: combining checkpoint inhibitors with cancer vaccines.

PubMed

Vreeland, T J; Clifton, G T; Herbert, G S; Hale, D F; Jackson, D O; Berry, J S; Peoples, G E

2016-12-01

The approval of multiple checkpoint inhibitors (CPIs) for the treatment of advanced malignancies has sparked an explosion of research in the field of cancer immunotherapy. Despite the success of these medications, a large number of patients with advanced malignancy do not benefit from therapy. Early research indicates that a therapeutic combination of cancer vaccines with checkpoint inhibitors may lead to synergistic effects and higher response rates than monotherapy. Areas covered: This paper summarizes the previously completed and ongoing research on this exciting combination, including the use of the tumor lysate, particle-loaded dendritic cell (TLPLDC) vaccine combined with checkpoint inhibitors in advanced melanoma. Expert commentary: Increasing experience with CPIs has led to improved understanding of which patients may benefit and it is increasingly clear that the presence of a pre-existing immune response to the tumor, along with tumor-infiltrating lymphocytes, is key to the success of CPIs. One exciting possibility for the future is the addition of a cancer vaccine to CPI therapy, eliciting these crucial T cells, which can then be augmented and protected by the CPI. A number of current and future studies are addressing this very exciting combination therapy.

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas.

PubMed

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-05-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas

PubMed Central

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-01-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance. PMID:24518818

Is Kidney Transplantation a Better State of CKD? Impact on Diagnosis and Management.

PubMed

Parajuli, Sandesh; Clark, Dana F; Djamali, Arjang

2016-09-01

Patients with CKD are at increased risk for cardiovascular events, hospitalizations, and mortality. Kidney transplantation (KTx) is the preferred treatment for end-stage kidney disease. Although comorbidities including anemia and bone and mineral disease improve or are even halted after KTx, kidney transplant recipients carry higher cardiovascular mortality risk than the general population, as well as an increased risk of infections, malignancies, fractures, and obesity. When comparing CKD with CKD after transplantation (CKD-T), the rate of decline of estimated glomerular filtration rate (eGFR) is significantly lower in CKD-T. Higher rate of decline of eGFR has been associated with increased risk of mortality. However, due to the significant increased risk of mortality due to cardiovascular events, infections, and malignancies, many kidney transplant recipients may not benefit of decline in the rate of eGFR. Patients with CKD-T are a unique subset of patients with multiple traditional and transplant-specific risk factors. Proper management and appropriate preventive health measures may improve long-term patient and allograft survival in patients with CKD-T. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Precision Medicine in Gastrointestinal Pathology.

PubMed

Wang, David H; Park, Jason Y

2016-05-01

-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

The development of a malignant tumor is due to a desperate asexual self-cloning process in which cancer stem cells develop the ability to mimic the genetic program of germline cells

PubMed Central

Vinnitsky, Vladimir

2014-01-01

To date there is no explanation why the development of almost all types of solid tumors occurs sharing a similar scenario: (1) creation of a cancer stem cell (CSC), (2) CSC multiplication and formation of a multicellular tumor spheroid (TS), (3) vascularization of the TS and its transformation into a vascularized primary tumor, (4) metastatic spreading of CSCs, (5) formation of a metastatic TSs and its transformation into metastatic tumors, and (6) potentially endless repetition of this cycle of events. The above gaps in our knowledge are related to the biology of cancer and specifically to tumorigenesis, which covers the process from the creation of a CSC to the formation of a malignant tumor and the development of metastases. My Oncogerminative Theory of Tumorigenesis considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. In the initial step in that process, gene mutations combined with epigenetic dysregulation cause somatic cells to be reprogrammed into CSCs, which are immortal pseudo-germline cells. Mimicking the behavior of fertilized germline cells, the CSC achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor. In this view, the development of a malignant tumor from a CSC is a phenomenon of developmental biology, which we named a desperate asexual self-cloning event. The theory explains seven core characteristics of malignant tumors: (1) CSC immortality, (2) multistep development of a malignant tumor from a single CSC, (3) heterogeneity of malignant tumor cell populations, (4) metastatic spread of CSCs, (5) invasive growth, (6) malignant progression, and (7) selective immune tolerance toward cancer cells. The Oncogerminative Theory of Tumorigenesis suggests new avenues for discovery of revolutionary therapies to treat, prevent, and eradicate cancer. PMID:28232878

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2007-10-01

in NF1 and NF2 Patients. Persons with NF1 are predisposed to benign neurofibromas, optic nerve gliomas, and to specific malignant neoplasms ...anatomic location. The malignant neoplasms seen in NF1 patients include astrocytoma, malignant peripheral nerve sheath tumor (MPNST), pheochromocytoma, and...hematopoietic cells results in a progressive myeloproliferative disorder. Blood 2004; 103: 4243-4250. Reilly KM, Tuskan RG, Christy E, Loisel DA

Risk of metastatic ovarian involvement in nongynecologic malignancies.

PubMed

Kim, Kidong; Cho, Soo Youn; Park, Sang-Il; Kang, Hye Jin; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Ryu, Sang-Young; Lee, Eui-Don

2012-01-01

The objectives were to evaluate the risk of malignant adnexal tumors in women with nongynecologic malignancies and to identify variables associated with the risk of malignant adnexal tumors. The eligibility criteria included the diagnosis of a nongynecologic malignancy and adnexal tumors, which were resected or subjected to biopsy at our institute between 1999 and 2010. The risk of malignant adnexal tumors was assessed by dividing the number of patients with metastatic tumors to the adnexa or primary adnexal cancers by the total number of patients. The association of clinicopathologic variables with the risk of malignant adnexal tumors was evaluated using the Fisher exact test and binary logistic regression analysis. In patients with metastatic tumors to the adnexa, the association of clinicopathologic variables with overall survival after adnexal surgery was examined using the log-rank test. In 166 patients with adnexal tumors, 41 benign tumors, 113 metastatic tumors to the adnexa, and 12 primary adnexal cancers were diagnosed. Age older than 46 years, a tumor type associated with a high risk for malignant adnexal tumors, and bilateral tumors significantly increased the risk of malignant adnexal tumors. The overall survival of the patients with stomach cancer was significantly worse than the patients with colorectal or breast cancers. One hundred twenty-five of the 166 patients with nongynecologic malignancies who had adnexal tumors managed surgically were shown to have malignant tumors, and most of the tumors were metastatic from primary sites. The risk of malignant adnexal tumors was associated with age, nongynecologic malignancy, and bilaterality.

Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

PubMed Central

Smith, Louise J.; Husain, Ehab A.

2012-01-01

Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV. PMID:24765446

Anaplastic transformation of an atypical intraventricular meningioma with metastases to the liver: case report.

PubMed

Garcia-Conde, M; Roldan-Delgado, H; Martel-Barth-Hansen, D; Manzano-Sanz, C

2009-12-01

Malignant intraventricular meningiomas are very rare. To the best of our knowledge, only eleven cases have been reported thus far. Seven of them developed cerebrospinal fluid (CSF) metastases. We present herein the first case of a malignant intraventricular meningioma with extraneural metastases. We report a 44 year-old-man with a history of progressive headache and disorientation. Magnetic resonance imaging (MRI) revealed a 5-cm homogeneously-enhancing mass in the right trigone. The lesion was totally resected via a parietooccipital transcortical approach. Histological examination demonstrated an atypical meningioma. Thereafter, the tumor recurred twice. At first recurrence, the tumor was completely removed again and external radiotherapy was administered. At surgery at second recurrence, the tumor was more aggressive, invading the brain parenchyma. Histological examination showed anaplastic meningioma. The patient was readmitted to hospital with fever and pain in right hypochondrium. Abdominal ultrasound examination disclosed multiple hypoechoic liver lesions. Biopsy was consistent with liver metastases of a malignant meningioma. The patient died of acute liver failure seven months after initial diagnosis. Malignant intraventricular meningiomas are prone to recur and develop metastases, mainly through the CSF. Nevertheless, our case shows that extraneural metastases are also possible. Therefore, when systemic deterioration occurs in a patient with a malignant intraventricular meningioma, metastases to extraneural organs such as the liver must be ruled out.

Risk of malignancy in ankylosing spondylitis: a systematic review and meta-analysis.

PubMed

Deng, Chuiwen; Li, Wenli; Fei, Yunyun; Li, Yongzhe; Zhang, Fengchun

2016-08-18

Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis &rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03-1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

Efficient Cancer Detection Using Multiple Neural Networks.

PubMed

Shell, John; Gregory, William D

2017-01-01

The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings.

Efficient Cancer Detection Using Multiple Neural Networks

PubMed Central

Gregory, William D.

2017-01-01

The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings. PMID:29282435

Inhibition of monomethylarsonous acid (MMA(III))-induced cell malignant transformation through restoring dysregulated histone acetylation.

PubMed

Ge, Yichen; Gong, Zhihong; Olson, James R; Xu, Peilin; Buck, Michael J; Ren, Xuefeng

2013-10-04

Inorganic arsenic (iAs) and its high toxic metabolite, monomethylarsonous acid (MMA(III)), are able to induce malignant transformation of human cells. Chronic exposure to these chemicals is associated with an increased risk of developing multiple cancers in human. However, the mechanisms contributing to iAs/MMA(III)-induced cell malignant transformation and carcinogenesis are not fully elucidated. We recently showed that iAs/MMA(III) exposure to human cells led to a decreased level of histone acetylation globally, which was associated with an increased sensitivity to arsenic cytotoxicity. In the current study, it demonstrated that prolonged exposure to low-level MMA(III) in human urothelial cells significantly increased the expression and activity of histone deacetylases (HDACs) with an associated reduction of histone acetylation levels both globally and lysine specifically. Administration of the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), at 4 weeks after the initial MMA(III) treatment inhibited the MMA(III)-mediated up-regulation of the expression and activities of HDACs, leading to increase histone acetylation and prevention of MMA(III)-induced malignant transformation. These new findings suggest that histone acetylation dysregulation may be a key mechanism in MMA(III)-induced malignant transformation and carcinogenesis, and that HDAC inhibitors could be targeted to prevent or treat iAs-related cancers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Update on Breast Cancer Detection Using Comb-push Ultrasound Shear Elastography

PubMed Central

Denis, Max; Bayat, Mahdi; Mehrmohammadi, Mohammad; Gregory, Adriana; Song, Pengfei; Whaley, Dana H.; Pruthi, Sandhya; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

2015-01-01

In this work, tissue stiffness estimates are used to differentiate between benign and malignant breast masses in a group of pre-biopsy patients. The rationale being that breast masses are often stiffer than healthy tissue; furthermore, malignant masses are stiffer than benign masses. The comb-push ultrasound shear elastography (CUSE) method is used to noninvasively assess a tissue’s mechanical properties. CUSE utilizes a simultaneous multiple laterally spaced radiation force (ARF) excitations and detection sequence to reconstruct the region of interest (ROI) shear wave speed map, from which a tissue stiffness property is quantified by Young’s modulus. In this study, the tissue stiffness of 73 breast masses is interrogated. The mean shear wave speeds for malignant masses (3.42 ± 1.32 m/s) were higher than benign breast masses (6.04 ± 1.25 m/s). These speed values correspond to higher stiffness in malignant breast masses (114.9 ± 40.6 kPa) than benign masses (39.4 ± 28.1 kPa and p < 0.001), when tissue elasticity is quantified by Young’s modulus. A Young’s modulus > 83 kPa is established as a cut-off value for differentiating between malignant and benign suspicious breast masses, with receiver operating characteristic curve (ROC) of 89.19% sensitivity, 88.69% specificity, and 0.911 for the area under the curve (AUC). PMID:26688871

Update on Breast Cancer Detection Using Comb-Push Ultrasound Shear Elastography.

PubMed

Denis, Max; Bayat, Mahdi; Mehrmohammadi, Mohammad; Gregory, Adriana; Song, Pengfei; Whaley, Dana H; Pruthi, Sandhya; Chen, Shigao; Fatemi, Mostafa; Alizad, Azra

2015-09-01

In this work, tissue stiffness estimates are used to differentiate between benign and malignant breast masses in a group of pre-biopsy patients. The rationale is that breast masses are often stiffer than healthy tissue; furthermore, malignant masses are stiffer than benign masses. The comb-push ultrasound shear elastography (CUSE) method is used to noninvasively assess a tissue's mechanical properties. CUSE utilizes a sequence of simultaneous multiple laterally spaced acoustic radiation force (ARF) excitations and detection to reconstruct the region of interest (ROI) shear wave speed map, from which a tissue stiffness property can be quantified. In this study, the tissue stiffnesses of 73 breast masses were interrogated. The mean shear wave speeds for benign masses (3.42 ± 1.32 m/s) were lower than malignant breast masses (6.04 ± 1.25 m/s). These speed values correspond to higher stiffness in malignant breast masses (114.9 ± 40.6 kPa) than benign masses (39.4 ± 28.1 kPa and p <; 0.001), when tissue elasticity is quantified by Young's modulus. A Young's modulus >83 kPa is established as a cut-off value for differentiating between malignant and benign suspicious breast masses, with a receiver operating characteristic curve (ROC) of 89.19% sensitivity, 88.69% specificity, and 0.911 for the area under the curve (AUC).

Regulatory Control of Breast Tumor Cell Poly (ADP-Ribose) Polymerase

DTIC Science & Technology

2002-08-01

DNA replication complex (designated the DNA synthesome) from a variety of non-malignant and malignant tumor cells including breast cancer cells. We have shown that poly(ADP-ribose) polymerase PARP is among the components of the DNA synthesome. The transformation of a non-malignant human breast cell to a malignant state was accompanied by a significant alteration in the 2-D PAGE profile of specific protein components of the DNA synthesome (such as PCNA) together with a 6-8 decrease in the replication fidelity of the DNA

A new fully covered metal stent for the treatment of benign and malignant dysphagia: a prospective follow-up study.

PubMed

Hirdes, Meike M C; Siersema, Peter D; Vleggaar, Frank P

2012-04-01

Fully covered self-expandable metal stents (FCSEMSs) are increasingly being used for malignant and benign strictures. Particularly in the latter, FCSEMSs are known for their high migration rates. A new FCSEMS with a dog-bone shape and internal covering was developed to reduce migration risk. To evaluate recurrent dysphagia and safety of the new FC stent in benign and malignant esophageal disorders. Prospective follow-up study. Tertiary referral center. Between November 2009 and February 2011, 48 consecutive patients (mean age 61 years, range 28-81 years) underwent FC stent placement for malignant (n = 33) or benign (n = 15) dysphagia. FC stent placement. Recurrent dysphagia and complications. Indications for FC stent placement included esophageal cancer (n = 28), extrinsic malignant compression (n = 4), recurrent malignancy after esophagectomy (n = 1), and refractory benign esophageal stricture (n = 15). In malignant strictures, recurrent dysphagia occurred in 5 patients (15%) because of stent migration (n = 3), tissue overgrowth (n = 1), and acute edema (n = 1). In benign strictures, stents were prematurely removed in 9 (60%) patients because of stent migration (n = 5), tissue overgrowth (n = 3), and pain (n = 1). Recurrent dysphagia occurred in all patients after stent removal. Major complications occurred in 10 patients (30%) with malignant strictures and in 3 patients (20%) with benign strictures and included severe pain and/or vomiting (n = 8), fistula formation (n = 2), bleeding (n = 2), and aspiration pneumonia (n = 1). Nonrandomized study design. Although the new FC stent effectively treats malignant dysphagia, it is associated with substantial major complications. In patients with refractory benign esophageal strictures, recurrent dysphagia occurs rapidly after removal of the new FC stent. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Hashimoto thyroiditis: Part 2, sonographic analysis of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis.

PubMed

Anderson, Lauren; Middleton, William D; Teefey, Sharlene A; Reading, Carl C; Langer, Jill E; Desser, Terry; Szabunio, Margaret M; Mandel, Susan J; Hildebolt, Charles F; Cronan, John J

2010-07-01

The purpose of this article is to compare sonographic features of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis. As part of an ongoing multiinstitutional study, patients who underwent ultrasound and fine-needle aspiration of one or more thyroid nodules were analyzed for a variety of predetermined sonographic features. Patients with a sonographic appearance consistent with diffuse Hashimoto thyroiditis and with coexisting nodules that could be confirmed to be benign or malignant by fine-needle aspiration or surgical pathologic analysis were included in the study. Among nodules within diffuse Hashimoto thyroiditis, 84% (69/82) were benign (35 nodular Hashimoto thyroiditis, 32 nodular hyperplasia, and two follicular adenoma), and 16% (13/82) were malignant (12 papillary carcinoma and one lymphoma). Malignant nodules were more likely to be solid and hypoechoic (62% vs 19%). All types of calcifications were more prevalent among malignant nodules, including microcalcifications (39% vs 0%), nonspecific tiny bright reflectors (39% vs 6%), macrocalcifications (15% vs 3%), and eggshell (15% vs 2%). Benign nodules were more likely to be hyperechoic (46% vs 9%), to have a halo (39% vs 15%), and to lack calcifications (88% vs 23%). Benign nodules more often had ill-defined margins (36% vs 8%). Sonographic features of benign and malignant nodules within diffuse Hashimoto thyroiditis are generally similar to the features typical of benign and malignant nodules in the general population. If calcifications of any type are added to the list of malignant sonographic features, the decision to biopsy a nodule in patients with diffuse Hashimoto thyroiditis can be based on recommendations that have been published previously.

Combined value of Virtual Touch tissue quantification and conventional sonographic features for differentiating benign and malignant thyroid nodules smaller than 10 mm.

PubMed

Zhang, Huiping; Shi, Qiusheng; Gu, Jiying; Jiang, Luying; Bai, Min; Liu, Long; Wu, Ying; Du, Lianfang

2014-02-01

This study aimed to investigate the value of sonographic features including Virtual Touch tissue quantification (VTQ; Siemens Medical Solutions, Mountain View, CA) for differentiating benign and malignant thyroid nodules smaller than 10 mm. Seventy-one thyroid nodules smaller than 10 mm with pathologic diagnoses were included in this study. The conventional sonographic features and quantitative elasticity features (VTQ) were observed and compared between benign and malignant nodules. There were 39 benign and 32 malignant nodules according to histopathologic examination. When compared with benign nodules, malignant nodules were more frequently taller than wide, poorly defined, and markedly hypoechoic (P < .05). Color Doppler sonographic features were not significantly different between benign and malignant nodules. The VTQ value for malignant nodules (mean ± SD 3.260 ± 0.725 m/s) was significantly higher than that of benign ones (2.108 ± 0.455 m/s; P < .001). The cutoff point for the differential diagnosis was 2.910 m/s, with sensitivity, specificity, a positive predictive value, a negative predictive value, and diagnostic accuracy of 71.9%, 100%, 100%, 81.2%, and 87.3% respectively. Logistic regression analysis showed that a taller-than-wide shape, a poorly defined boundary, marked hypoechogenicity, and a VTQ value greater than 2.910 m/s were independent risk factors for malignancy, with odds ratios of 69.366, 41.864, 5.945, and 64.991. The combination of VTQ with a taller-than-wide shape had the highest sensitivity and specificity of 90.6% and 97.4%. The shape, margin, echogenicity, and VTQ value are useful sonographic criteria for differentiating benign and malignant thyroid nodules smaller than 10 mm. When VTQ was combined with B-mode sonographic features, the sensitivity was improved significantly.

Predictor of Severe Gastroduodenal Toxicity After Stereotactic Body Radiotherapy for Abdominopelvic Malignancies

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

Bae, Sun Hyun; Kim, Mi-Sook, E-mail: mskim@kcch.re.kr; Cho, Chul Koo

2012-11-15

Purpose: To identify the predictors for the development of severe gastroduodenal toxicity (GDT) in patients treated with stereotactic body radiotherapy (SBRT) using 3 fractionations for abdominopelvic malignancies. Methods and Materials: From 2001 to 2011, 202 patients with abdominopelvic malignancies were treated with curative-intent SBRT. Among these patients, we retrospectively reviewed the clinical records of 40 patients with the eligibility criteria as follows: 3 fractionations, follow-up period {>=}1 year, absence of previous radiation therapy (RT) history or combination of external-beam RT and the presence of gastroduodenum (GD) that received a dose higher than 20% of prescribed dose. The median SBRT dosemore » was 45 Gy (range, 33-60 Gy) with 3 fractions. We analyzed the clinical and dosimetric parameters, including multiple dose-volume histogram endpoints: V{sub 20} (volume of GD that received 20 Gy), V{sub 25}, V{sub 30}, V{sub 35}, and D{sub max} (the maximum point dose). The grade of GDT was defined by the National Cancer Institute Common Toxicity Criteria version 4.0, and GDT {>=}grade 3 was defined as severe GDT. Results: The median time to the development of severe GDT was 6 months (range, 3-12 months). Severe GDT was found in 6 patients (15%). D{sub max} was the best dosimetric predictor for severe GDT. D{sub max} of 35 Gy and 38 Gy were respectively associated with a 5% and 10% probability of the development of severe GDT. A history of ulcer before SBRT was the best clinical predictor on univariate analysis (P=.0001). Conclusions: We suggest that D{sub max} is a valuable predictor of severe GDT after SBRT using 3 fractionations for abdominopelvic malignancies. A history of ulcer before SBRT should be carefully considered as a clinical predictor, especially in patients who receive a high dose to GD.« less

Isolation and identification of human metabolites from a novel anti-tumor candidate drug 5-chlorogenic acid injection by HPLC-HRMS/MSn and HPLC-SPE-NMR.

PubMed

Ren, Tiankun; Wang, Yanan; Wang, Caihong; Zhang, Mengtian; Huang, Wang; Jiang, Jiandong; Li, Wenbin; Zhang, Jinlan

2017-12-01

A novel anti-tumor candidate drug, 5-chlorogenic acid (5-CQA) injection, was used for the treatment of malignant glioma in clinical trial (phase I) in China. The isolation and identification of the metabolites of 5-CQA injection in humans were investigated in the present study. Urine and feces samples obtained after intramuscular administration of 5-CQA injection to healthy adults have been analyzed by high-performance liquid chromatography coupled with high-resolution mass and multiple-stage mass spectrometry (HPLC-HRMS/MS n ). No metabolite was detected in human feces; however, in human urine, a total of six metabolites were identified including isomerized 5-CQA (P1 and P2), hydrolyzed 5-CQA (M1and M2), and methylated 5-CQA (M3 and M4). Among them, M3 and M4 were the main metabolites and target analytes for human mass balance study. Additionally, the structure of M3 and M4 was characterized by high-performance liquid chromatography-solid phase extraction-nuclear magnetic resonance (HPLC-SPE-NMR), and the results demonstrated that the methoxy group of M3 and M4 was exclusively attributed to C-3' and C-4', respectively. Due to the unavailability of commercial reference, the pure products of M3 and M4 were synthesized by 5-CQA methylation and followed by isolation and purification. Moreover, the potential activity of M3 and M4 on malignant glioma was predicted using a reverse molecular docking analysis on eight malignant glioma-related pathways. The results showed that M3 and M4 had various interactions against malignant glioma-related targets. Our study provides an insight into the metabolism of 5-CQA injection in humans and supports the clinical human mass balance study. Graphical abstract ᅟ.

The occasional role of low-risk human papillomaviruses 6, 11, 42, 44, and 70 in anogenital carcinoma defined by laser capture microdissection/PCR methodology: results from a global study.

PubMed

Guimerà, Núria; Lloveras, Belén; Lindeman, Jan; Alemany, Laia; van de Sandt, Miekel; Alejo, Maria; Hernandez-Suarez, Gustavo; Bravo, Ignacio G; Molijn, Anco; Jenkins, David; Cubilla, Antonio; Muñoz, Nubia; de Sanjose, Silvia; Bosch, Francesc Xavier; Quint, Wim

2013-09-01

Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of <2% of anogenital malignancies of 2 distinct clinicopathologic patterns related to the genetic structure of the HPV types 6/11 and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly all carcinomas associated with HPV6/11 globally showed verruco-papillary, well-differentiated, squamous, or transitional histology without p16 expression.

Brain cancer and pesticide relationship in orchard farmers of Kashmir.

PubMed

Bhat, Abdul Rashid; Wani, Muhammed Afzal; Kirmani, A R

2010-09-01

The increasing trend in the incidence of primary malignant brain tumors in orchard farmers and their families in Kashmir. To determine the relationship between the patients of primary malignant brain tumors and their occupation. Retrospectively, case files along with death certificates of 432 patients of primary malignant brain tumors and 457 controls (non-tumor neurologic diseases), admitted for treatment simultaneously over a period of 4 years from January 2005 to December 2008, to the Neurosurgery, Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Kashmir, were studied. Follow-up and family interaction was established. Analysis revealed that 90.04% (389 out of 432) patients were orchard farm workers, orchard residents and orchard playing children exposed to the high levels of multiple types of neurotoxic and carcinogenic (chlorpyriphos, dimethoate, mancozeb and captan) chemicals for more than 10 years [relative risk (RR) = 10.6; odds ratio (OR) = >10; 95% confidence interval (CI) = >25-40]. The 9.96% (43 out of 432) patients were not exposed to pesticides. On the other hand, only 19 patients out of 457 controls had recorded history of pesticide exposure and 438 were unrelated to pesticides. Out of 389 patients, 71.7% (279 out of 389) were males and 28.3% (110 out of 389), including six members of three families, were females (one male child). All orchard-related 389 patients had high-grade tumors as compared to the non-pesticide tumors. Mortality in pesticide-exposed tumors was 12%. The higher or upper-normal levels of serum cholinesterase (AChE) were observed in 54.7% (213 out of 389) patients and decreased levels were found in only 45.3% (176 out of 389) orchard-related patients (RR = 19.4; OR = >5; 95% CI = >1-10). Although serum AChE levels were a routine investigation in malignant brain tumors, this was not a routine in other neurological conditions (hospitalized controls). The familial gliomas have shown an emerging trend in the orchard residents of valley of Kashmir.

Diagnosis of human malignancies using laser-induced breakdown spectroscopy in combination with chemometric methods

NASA Astrophysics Data System (ADS)

Chen, Xue; Li, Xiaohui; Yu, Xin; Chen, Deying; Liu, Aichun

2018-01-01

Diagnosis of malignancies is a challenging clinical issue. In this work, we present quick and robust diagnosis and discrimination of lymphoma and multiple myeloma (MM) using laser-induced breakdown spectroscopy (LIBS) conducted on human serum samples, in combination with chemometric methods. The serum samples collected from lymphoma and MM cancer patients and healthy controls were deposited on filter papers and ablated with a pulsed 1064 nm Nd:YAG laser. 24 atomic lines of Ca, Na, K, H, O, and N were selected for malignancy diagnosis. Principal component analysis (PCA), linear discriminant analysis (LDA), quadratic discriminant analysis (QDA), and k nearest neighbors (kNN) classification were applied to build the malignancy diagnosis and discrimination models. The performances of the models were evaluated using 10-fold cross validation. The discrimination accuracy, confusion matrix and receiver operating characteristic (ROC) curves were obtained. The values of area under the ROC curve (AUC), sensitivity and specificity at the cut-points were determined. The kNN model exhibits the best performances with overall discrimination accuracy of 96.0%. Distinct discrimination between malignancies and healthy controls has been achieved with AUC, sensitivity and specificity for healthy controls all approaching 1. For lymphoma, the best discrimination performance values are AUC = 0.990, sensitivity = 0.970 and specificity = 0.956. For MM, the corresponding values are AUC = 0.986, sensitivity = 0.892 and specificity = 0.994. The results show that the serum-LIBS technique can serve as a quick, less invasive and robust method for diagnosis and discrimination of human malignancies.

[Non-Hodgkin's malignant lymphoma with cervicofacial expression. Modulation of the radiotherapy-chemotherapy combination according to the cytological class].

PubMed

Bolla, M; Sotto, J J; Sotto, M F; Junien Lavillauroy, C; Bryon, J P; Vrousos, C; Holland, D

1984-01-01

An analysis was conducted in March 1983, after a mean follow up of 40 months, of cases of cervicofacial stages I and II non-Hodgkins malignant lymphoma in 3 children and 41 adults (mean age: 51 years, range: 6-90 years) treated between 1969 and March 1981. According to the Working Formulation malignancy was low in 4 cases, intermediate in 24 and high in 13; 3 cases could not ne classified retrospectively. Cytologic classification showed 13 of class 1 of low malignancy, 7 of class 2 of high malignancy with leukemic potential, and 16 of class 3 of high malignancy with a course leading to tumor formation. The cavum was involved in 10 cases, the tonsils in 9, the parotids in 1, the uvula in 1, isolated cervical adenopathies in 14, multiple unilateral adenopathies in 3 and bilateral cervical adenopathies in 5 cases. Therapy varied according to the series: in the first series (1969-1975) the 23 cases were treated by radiotherapy alone (40-55 Gy). In the second series (1976-1981) of 21 cases, chemotherapy was given as a function of the cytologic class: prophylactic chemotherapy for 6 months after radiation for classes 1 and 2, initial chemotherapy for 6 weeks, cerebral radiation and methotrexate intrathecally, and maintenance chemotherapy for 3 months in class 3. The failure rate for radiated zones was identical in the 2 series (less than 10%). Adjusted 5-year survival rate was 60% for series 1 against 70% for series 2 (p = 0.9), and adjusted remission rate was 43% against 64% (p = 0.8).

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

Primary Malignant Melanoma of Pleura: A Case Report and Literature Review.

PubMed

Agarwal, Poojan; Nambiyar, Kaniyyapan; Manju Kaushal; Bhardwaj, Minakshi

2016-07-01

Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648-652. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A web platform for the network analysis of high-throughput data in melanoma and its use to investigate mechanisms of resistance to anti-PD1 immunotherapy.

PubMed

Dreyer, Florian S; Cantone, Martina; Eberhardt, Martin; Jaitly, Tanushree; Walter, Lisa; Wittmann, Jürgen; Gupta, Shailendra K; Khan, Faiz M; Wolkenhauer, Olaf; Pützer, Brigitte M; Jäck, Hans-Martin; Heinzerling, Lucie; Vera, Julio

2018-06-01

Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex molecular relationships behind the emergence of malignancy, but full exploitation of this massive amount of data requires bioinformatics tools that rely on network-based analyses. In this report we present the Virtual Melanoma Cell, an online tool developed to facilitate the mining and interpretation of high-throughput data on melanoma by biomedical researches. The platform is based on a comprehensive, manually generated and expert-validated regulatory map composed of signaling pathways important in malignant melanoma. The Virtual Melanoma Cell is a tool designed to accept, visualize and analyze user-generated datasets. It is available at: https://www.vcells.net/melanoma. To illustrate the utilization of the web platform and the regulatory map, we have analyzed a large publicly available dataset accounting for anti-PD1 immunotherapy treatment of malignant melanoma patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Recent advances in the use of therapeutic cancer vaccines in genitourinary malignancies.

PubMed

Surolia, Ira; Gulley, James; Madan, Ravi A

2014-12-01

Despite a recent increase in US FDA-approved treatments, genitourinary malignancies remain a source of significant morbidity and mortality. One focus of research is the use of therapeutic cancer vaccines in these diseases, and a significant body of clinical trial experience now exists for refining vaccine strategies to enhance antitumor efficacy and develop immune-based combination regimens. In recent years, clinical data from multiple trials in genitourinary malignancies have enhanced our understanding of the potential for immunotherapy in these cancers. There are also emerging clinical strategies that combine cancer vaccines with chemotherapy, radiation, androgen-deprivation therapy and immune checkpoint inhibitors. This review is based on a search of relevant literature for data presented over the past 5 years from clinical trials of cancer vaccines in prostate, bladder and renal carcinomas. In the coming years, clinical trials informed by decades of preclinical data and emerging clinical data will help to define the role of immunotherapy in genitourinary malignancies. Combination strategies that capitalize on the immune properties of standard treatments will bring greater clinical benefits, and immune-based combinations will likely be moved to the neoadjuvant setting, where they may have optimal clinical impact.

Drugs Approved for Malignant Mesothelioma

Cancer.gov

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for malignant mesothelioma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

ClinicalTrials.gov

2018-04-30

Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

Hair follicle nevus in a distribution following Blaskho's lines.

PubMed

Germain, Marguerite; Smith, Kathleen J

2002-05-01

We present a case of a rare follicular hamartoma, a hair follicle nevus. Although most previous reports have been solitary lesions, the case we are reporting had multiple papules and nodules following Blaskho's lines. There have been no reports of malignancies arising in these hamartomas.

OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation.

PubMed

Cui, Yan; Ying, Ying; van Hasselt, Andrew; Ng, Ka Man; Yu, Jun; Zhang, Qian; Jin, Jie; Liu, Dingxie; Rhim, Johng S; Rha, Sun Young; Loyo, Myriam; Chan, Anthony T C; Srivastava, Gopesh; Tsao, George S W; Sellar, Grant C; Sung, Joseph J Y; Sidransky, David; Tao, Qian

2008-08-20

Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing. Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies.

Management of hepatocellular adenoma: Solitary-uncomplicated, multiple and ruptured tumors

PubMed Central

Toso, Christian; Majno, Pietro; Andres, Axel; Rubbia-Brandt, Laura; Berney, Thierry; Buhler, Léo; Morel, Philippe; Mentha, Gilles

2005-01-01

AIM: While hepatocellular adenomas (HAs) have often been studied as a unique entity, we aimed to better define current management of the various forms of HAs. METHODS: Twenty-five consecutive patients operated for solitary-uncomplicated (9), multiple (6), and ruptured (10) HAs were reviewed according to management strategies and outcomes. RESULTS: All solitary-uncomplicated HAs (ranged 2.2-14 cm in size) were removed. Out of 25 HAs, 2 (8%) included foci of carcinoma. In the multiple HA group, previously undiagnosed tumors were identified during surgery in 5/6 cases. In three cases with multiple spread HA, several lesions had to be left unresected. They remained unmodified after 4-, 6-, and 6-year radiological follow-up. Patients with ruptured HA (ranged 1.7-10 cm in size) were initially managed with hemodynamic support and angiography, allowing the embolization of actively bleeding tumors in two patients. All ruptured tumors were subsequently removed 5.5 d (range 4-70 d) after admission. CONCLUSION: Tumors suspected of HA, regardless of the size, should be resected, because of high chances of rupture causing bleeding, and/or containing malignant foci. Although it is desirable to remove all lesions of multiple HA, this may not be possible in some patients, for whom long-term radiological follow-up is advised. Ruptured HA can be managed by hemodynamic support and angiography, allowing scheduled surgery. PMID:16237767

1H-MRS evaluation of breast lesions by using total choline signal-to-noise ratio as an indicator of malignancy: a meta-analysis.

PubMed

Wang, Xin; Wang, Xiang Jiang; Song, Hui Sheng; Chen, Long Hua

2015-05-01

The aim of this study was to evaluate the diagnostic performance of the use of total choline signal-to-noise ratio (tCho SNR) criteria in MRS studies for benign/malignant discrimination of focal breast lesions. We conducted (1) a meta-analysis based on 10 studies including 480 malignant breast lesions and 312 benign breast lesions and (2) a subgroup meta-analysis of tCho SNR ≥ 2 as cutoff for malignancy based on 7 studies including 371 malignant breast lesions and 239 benign breast lesions. (1) The pooled sensitivity and specificity of proton MRS with tCho SNR were 0.74 (95 % CI 0.69-0.77) and 0.76 (95 % CI 0.71-0.81), respectively. The PLR and NLR were 3.67 (95 % CI 2.30-5.83) and 0.25 (95 % CI 0.14-0.42), respectively. From the fitted SROC, the AUC and Q* index were 0.89 and 0.82. Publication bias was present (t = 2.46, P = 0.039). (2) Meta-regression analysis suggested that neither threshold effect nor evaluated covariates including strength of field, pulse sequence, TR and TE were sources of heterogeneity (all P value >0.05). (3) Subgroup meta-analysis: The pooled sensitivity and specificity were 0.79 and 0.72, respectively. The PLR and NLR were 3.49 and 0.20, respectively. The AUC and Q* index were 0.92 and 0.85. The use of tCho SNR criteria in MRS studies was helpful for differentiation between malignant and benign breast lesions. However, pooled diagnostic measures might be overestimated due to publication bias. A tCho SNR ≥ 2 as cutoff for malignancy resulted in higher diagnostic accuracy.

The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: an institutional experience.

PubMed

Rossi, Esther Diana; Bizzarro, Tommaso; Schmitt, Fernando; Longatto-Filho, Adhemar

2015-04-01

Fine-needle aspiration cytology (FNAC) of serous membrane effusions may fulfil a challenging role in the diagnostic analysis of both primary and metastatic disease. From this perspective, liquid-based cytology (LBC) represents a feasible and reliable method for empowering the performance of ancillary techniques (ie, immunocytochemistry and molecular testing) with high diagnostic accuracy. In total, 3171 LBC pleural and pericardic effusions were appraised between January 2000 and December 2013. They were classified as negative for malignancy (NM), suspicious for malignancy (SM), or positive for malignancy (PM). The cytologic diagnoses included 2721 NM effusions (2505 pleural and 216 pericardic), 104 SM effusions (93 pleural and 11 pericardic), and 346 PM effusions (321 pleural and 25 pericardic). The malignant pleural series included 76 unknown malignancies (36 SM and 40 PM effusions), 174 metastatic lesions (85 SM and 89 PM effusions), 14 lymphomas (3 SM and 11 PM effusions), 16 mesotheliomas (5 SM and 11 SM effusions), and 3 myelomas (all SM effusions). The malignant pericardic category included 20 unknown malignancies (5 SM and 15 PM effusions), 15 metastatic lesions (1 SM and 14 PM effusions), and 1 lymphoma (1 PM effusion). There were 411 conclusive immunocytochemical analyses and 47 molecular analyses, and the authors documented 88% sensitivity, 100% specificity, 98% diagnostic accuracy, 98% negative predictive value, and 100% positive predictive value for FNAC. FNAC represents a primary diagnostic tool for effusions and a reliable approach with which to determine the correct follow-up. Furthermore, LBC is useful for ancillary techniques, such as immunocytochemistry and molecular analysis, with feasible diagnostic and predictive utility. © 2015 American Cancer Society.

Classification of malignant and benign liver tumors using a radiomics approach

NASA Astrophysics Data System (ADS)

Starmans, Martijn P. A.; Miclea, Razvan L.; van der Voort, Sebastian R.; Niessen, Wiro J.; Thomeer, Maarten G.; Klein, Stefan

2018-03-01

Correct diagnosis of the liver tumor phenotype is crucial for treatment planning, especially the distinction between malignant and benign lesions. Clinical practice includes manual scoring of the tumors on Magnetic Resonance (MR) images by a radiologist. As this is challenging and subjective, it is often followed by a biopsy. In this study, we propose a radiomics approach as an objective and non-invasive alternative for distinguishing between malignant and benign phenotypes. T2-weighted (T2w) MR sequences of 119 patients from multiple centers were collected. We developed an efficient semi-automatic segmentation method, which was used by a radiologist to delineate the tumors. Within these regions, features quantifying tumor shape, intensity, texture, heterogeneity and orientation were extracted. Patient characteristics and semantic features were added for a total of 424 features. Classification was performed using Support Vector Machines (SVMs). The performance was evaluated using internal random-split cross-validation. On the training set within each iteration, feature selection and hyperparameter optimization were performed. To this end, another cross validation was performed by splitting the training sets in training and validation parts. The optimal settings were evaluated on the independent test sets. Manual scoring by a radiologist was also performed. The radiomics approach resulted in 95% confidence intervals of the AUC of [0.75, 0.92], specificity [0.76, 0.96] and sensitivity [0.52, 0.82]. These approach the performance of the radiologist, which were an AUC of 0.93, specificity 0.70 and sensitivity 0.93. Hence, radiomics has the potential to predict the liver tumor benignity in an objective and non-invasive manner.

Cancerous leptomeningitis and familial congenital hypopituitarism.

PubMed

Vujovic, S; Vujosevic, S; Kavaric, S; Sopta, J; Ivovic, M; Saveanu, A; Brue, T; Korbonits, M; Popovic, V

2016-05-01

People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

Genetically engineered mouse models shed new light on the pathogenesis of neurofibromatosis type I-related neoplasms of the peripheral nervous system.

PubMed

Brossier, Nicole M; Carroll, Steven L

2012-05-01

Neurofibromatosis type 1 (NF1), the most common genetic disorder affecting the human nervous system, is characterized by the development of multiple benign Schwann cell tumors in skin and large peripheral nerves. These neoplasms, which are termed dermal and plexiform neurofibromas respectively, have distinct clinical courses; of particular note, plexiform, but not dermal, neurofibromas often undergo malignant progression to form malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy occurring in NF1 patients. In recent years, a number of genetically engineered mouse models have been created to investigate the molecular mechanisms driving the pathogenesis of these tumors. These models have been designed to address key questions including: (1) whether NF1 loss in the Schwann cell lineage is essential for tumorigenesis; (2) what cell type(s) in the Schwann cell lineage gives rise to dermal neurofibromas, plexiform neurofibromas and MPNSTs; (3) how the tumor microenvironment contributes to neoplasia; (4) what additional mutations contribute to neurofibroma-MPNST progression; (5) what role different neurofibromin-regulated Ras proteins play in this process and (6) how dysregulated growth factor signaling facilitates PNS tumorigenesis. In this review, we summarize the major findings from each of these models and their limitations as well as how discrepancies between these models may be reconciled. We also discuss how information gleaned from these models can be synthesized to into a comprehensive model of tumor formation in peripheral nervous system and consider several of the major questions that remain unanswered about this process. Copyright © 2011 Elsevier Inc. All rights reserved.

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

PubMed Central

van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.

2014-01-01

Background and objectives Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated. Design, setting, participants, & measurements Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose–response relationship between cyclophosphamide and cancer. Results Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6–9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively. Conclusion Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival. PMID:24855280

The effect of IDH1 mutation on the structural connectome in malignant astrocytoma.

PubMed

Kesler, Shelli R; Noll, Kyle; Cahill, Daniel P; Rao, Ganesh; Wefel, Jeffrey S

2017-02-01

Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p < 0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p = 0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p < 0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing.

Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness.

PubMed

Xie, Ying; Wehrkamp, Cody J; Li, Jing; Wang, Yan; Wang, Yazhe; Mott, Justin L; Oupický, David

2016-03-07

Cholangiocarcinoma is the second most common primary liver malignancy with extremely poor prognosis due to early invasion and widespread metastasis. The invasion and metastasis are regulated by multiple factors including CXCR4 chemokine receptor and multiple microRNAs. The goal of this study was to test the hypothesis that inhibition of CXCR4 combined with the action of miR-200c mimic will cooperatively enhance the inhibition of the invasion of human cholangiocarcinoma cells. The results show that CXCR4-inhibition polycation PCX can effectively deliver miR-200c mimic and that the combination treatment consisting of PCX and miR-200c results in cooperative antimigration activity, most likely by coupling the CXCR4 axis blockade with epithelial-to-mesenchymal transition inhibition in the cholangiocarcinoma cells. The ability of the combined PCX/miR-200c treatment to obstruct two migratory pathways represents a promising antimetastatic strategy in cholangiocarcinoma.

Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation.

PubMed

Amodio, Nicola; D'Aquila, Patrizia; Passarino, Giuseppe; Tassone, Pierfrancesco; Bellizzi, Dina

2017-01-01

Multiple Myeloma (MM) is a clonal late B-cell disorder accounting for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent studies on the molecular pathogenesis and biology of MM have highlighted a complex epigenomic landscape contributing to MM onset, prognosis and high individual variability. Areas covered: We describe here the current knowledge on epigenetic events characterizing MM initiation and progression, focusing on the role of DNA and histone methylation and on the most promising epi-therapeutic approaches targeting the methylation pathway. Expert opinion: Data published so far indicate that alterations of the epigenetic framework, which include aberrant global or gene/non-coding RNA specific methylation profiles, feature prominently in the pathobiology of MM. Indeed, the aberrant expression of components of the epigenetic machinery as well as the reversibility of the epigenetic marks make this pathway druggable, providing the basis for the design of epigenetic therapies against this still fatal malignancy.

Multiple primary malignancies of the liver and the colon: a complex diagnostic and decisional process with a final unanswered question.

PubMed

Portolani, Nazario; Baiocchi, Gianluca; Baronchelli, Carla; Gheza, Federico; Giulini, Stefano Maria

2014-03-29

We herein present the case of a 78-year-old man with an incidental finding of a solid hepatic mass without symptoms and only a laparotomic cholecystectomy for acute cholecystitis in the past surgical history. A colonoscopy, a magnetic resonance imaging scan, a positron emission tomography scan, and a computed tomography scan completed the preoperative workup: a neoplastic lesion 4.3×3 cm in size was diagnosed at segments IV and V, associated with a neoplastic involvement of the splenic flexure without signs of colonic occlusion. After colonic resection, a frozen section on a granulomatous-like tissue at gastric border suggested a diagnosis of an adenocarcinoma of bilio-pancreatic type, changing the surgical strategy to include gastric resection and hepatic pedicle node dissection. The discussion turns around the idea that a final diagnosis of colon cancer with regional nodal involvement (pT3N1) and metastatic gallbladder cancer with multiple peritoneal seedings cannot be excluded.

[Pay attention to the application of the international intraocular retinoblastoma classification and sequential multiple modality treatment].

PubMed

Fan, X Q

2017-08-11

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. It may seriously affect vision, and even threaten the life. The early diagnosis rate of RB in China remains low, and the majority of patients are at late phase with high rates of enucleation and mortality. The International Intraocular Retinoblastoma Classification and TNM staging system are guidances for therapeutic choices and bases for prognosis evaluation. Based on the sequential multi-method treatment modality, chemotherapy combined with local therapy is the mainstream in dealing with RB, which may maximize the results of eye saving and even vision retaining. New therapeutic techniques including supra-selective ophthalmic artery interventional chemotherapy and intravitreal chemotherapy can further improve the efficacy of treatment, especially the eye salvage rate. The overall level of RB treatment should be improved by promoting the international staging, new therapeutic techniques, and the sequential multiple modality treatment. (Chin J Ophthalmol, 2017, 53: 561 - 565) .

Cancer stem cells and differentiation therapy.

PubMed

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

Bioengineering Strategies for Designing Targeted Cancer Therapies

PubMed Central

Wen, Xuejun

2014-01-01

The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509