Vinayak, Shaveta; Kurian, Allison W
Estrogen and progesterone receptor-negative breast cancer disproportionately affects young women and African Americans, has a poor prognosis, and lacks an effective chemoprevention agent. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as "statins," are appealing candidate agents for breast cancer chemoprevention because of their demonstrated safety after decades of widespread use. In preclinical studies, statins inhibit multiple cancer-associated pathways in both hormone receptor (HR)-negative and HR-positive cell lines. Epidemiologic studies of statins and breast cancer show inconsistent results, with some suggesting a reduction in HR-negative breast cancer incidence in lipophilic statin users. However, large meta-analyses show no association between statin use and overall risk of breast cancer, although most did not evaluate tumor HR status. Multiple phase 1 and 2 prevention studies of statins for breast cancer risk reduction are ongoing. If results are promising, they may justify a randomized trial of statins for breast cancer chemoprevention, with a focus on HR-negative disease.
Liu, Chao; Huang, Zhou; Wang, Qiusheng; Sun, Bing; Ding, Lijuan; Meng, Xiangying; Wu, Shikai
Purpose We aimed to investigate the relationship between pretreatment neutrophil-to-lymphocyte ratio (NLR)/platelet-to-lymphocyte ratio (PLR) and the estimation of hormone-receptor-negative (HR−) breast cancer patients’ survival in a Chinese cohort. Patients and methods Of 434 consecutive HR− nonmetastatic breast cancer patients treated between 2004 and 2010 in the Affiliated Hospital of Academy of Military Medical Sciences, 318 eligible cases with complete data were included in the present study. Kaplan–Meier analysis was performed to determine the overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox proportional hazards models were used to test the usefulness of NLR and PLR. Results Univariate analysis indicated that both elevated NLR and PLR (both P<0.001) were associated with poor OS. The utility of NLR remained in the multivariate analysis (P<0.001), but not PLR (P=0.104). The analysis results for DFS were almost the same as OS. Subgroup analysis revealed a significant association between increased NLR and PLR (P<0.001 and P=0.011) and poor survival in triple-negative breast cancer. However, for human epidermal growth factor receptor 2-positive breast cancer, only NLR was significantly associated with OS in the multivariate analysis (P=0.001). Conclusion The present study indicates that both increased NLR and PLR are associated with poor survival in HR−breast cancer patients. Meanwhile, NLR is independently correlated with OS and DFS, but PLR is not. PMID:27536129
Teoh, Zhi Hao; Archampong, David; Gate, Tim
A 41-year-old male-to-female (MtF) transgender patient presented with a symptomatic tender lump in the left breast. There was no family history of breast cancer. She had been receiving estrogen therapy for 14 years to maintain her secondary sexual characteristics. Triple assessment revealed a 13 mm triple-negative grade 3 invasive ductal carcinoma. The tumour was completely excised following a left wide local excision and sentinel lymph node biopsy. There was no regional lymph node involvement. She was referred to the oncologist for adjuvant chemotherapy and radiotherapy.
Briand, P.; Thorpe, S. M.; Daehnfeldt, J. L.
Administration of ovine prolactin alone supported growth of hormone-dependent GR mouse mammary tumours. Growth of hormone-independent tumours was not stimulated. Furthermore, administration of bromocriptine, a compound that inhibits release of prolactin from the pituitary gland, was shown to inhibit the growth of hormone-dependent tumours in animals receiving treatment with progesterone + oestrone. Administration of prolactin or bromocriptine to mice bearing tumours that grew independently of progesterone + oestrone treatment had no influence on tumour growth. We conclude that direct as well as indirect evidence has been found for the involvement of prolactin in the growth of transplanted, hormone-dependent GR mouse mammary tumours. PMID:577471
Gibelli, N; Zibera, C; Butti, G; Assietti, R; Sica, G; Scerrati, M; Iacopino, F; Roselli, R; Paoletti, P; Robustelli della Cuna, G
Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.
AWARD NUMBER: W81XWH-13-1-0400 TITLE: Targeting Epigenetics Therapy for Estrogen Receptor...2014 4. TITLE AND SUBTITLE Targeting Epigenetics Therapy for Estrogen Receptor-Negative Breast Cancers 5a. CONTRACT NUMBER 5b...estrogen- receptor positive breast cancer, estrogen receptor negative breast cancer, epigenetics , nuclear hormone receptor, estrogen Overall
de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark; Modlin, Irvin M
The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The pancreatic islet cells were first described in 1869 by Paul Langerhans. In 1924, Seale Harris was the first to describe endogenous hyperinsulinism/insulinoma. In 1942 William Becker and colleagues were the first to describe the glucagonoma syndrome. The first description of gastrinoma by Robert Zollinger and Edwin Ellison dates from 1955. The first description of the VIPoma syndrome by John Verner and Ashton Morrison dates from 1958. In 1977, the groups of Lars-Inge Larsson and Jens Rehfeld, and of Om Ganda reported the first cases of somatostatinoma. But only in 2013, Jens Rehfeld and colleagues described the CCK-oma syndrome. The most recently updated WHO classification for gastrointestinal neuroendocrine tumours dates from 2010.
Ansink, A C; Cross, P A; Scorer, P; de Barros Lopes, A; Monaghan, J M
AIM: To investigate the role of oestrogen and progesterone receptor status in uterine carcinosarcomas (mixed Müllerian tumours) to see whether the receptors were identifiable, and if so whether they were of significance clinically. METHODS: 11 cases of uterine carcinosarcoma were identified from clinical and pathology records. An immunohistochemical method was used to demonstrate oestrogen and progesterone hormone receptors on paraffin embedded material, with suitable tissue controls, staining being recorded. RESULTS: 10 of 11 cases showed staining for one or both hormone receptors in normal tissue adjacent to tumour. In four carcinosarcoma cases, staining for one or both receptors was shown within the epithelial component (appearing to correlate with the degree of epithelial differentiation); two of these cases had staining within sarcomatous areas. Two of the three patients still alive had epithelial hormone receptor positivity. CONCLUSIONS: Receptors for oestrogen and progesterone were found in four of 11 cases of uterine carcinosarcoma, using paraffin embedded material. There may be an association between hormone receptor positivity and clinical outcome. Images PMID:9215151
Levchuk, N I
Internucleosomal fragmentation of DNA that was isolated from the extratumour tissue of patients with hormonally active and inactive tumors, the tissues of hormonally active and inactive tumors, and also the hyperplastic adrenal tissue in patients with Itsenko-Cushing disease was studied in agarose gel using the method of electrophoresis. It has been established that the intensity of DNA fragmentation in hormonally inactive tumours did not differ from the tissue that was surrounding such tumours, and only a decrease in the mononucleosome level was revealed. The increased level of oligonucleosomas with the size of 200-800 p. o. owing to the high content of tri- and tetraoligonucleosomas was noted in the extratumour tissue of patients with hormonally active tumours, the hyperplastic tissue and in the tissue of aldosteromas, corticosteromas, and pheochromocytomas. Data obtained evidenced for the stimulating effect of the adrenal complex hormones and the adrenal meduliar layer on apoptotic processes both in the cells of extratumor adrenal tissue and in the tumor cells secreting hormonal abundance.
Sernbo, Sandra; Borrebaeck, Carl A K; Uhlén, Mathias; Jirström, Karin; Ek, Sara
T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.
Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta
Summary A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Learning points: Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly. Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion
Smets, Eva M L; Dijkstra-Lagemaat, Josien E; Blankenstein, Marinus A
Introduction of preanalytical automation in our laboratory required the use of plastic blood collection tubes. Because of possible interference caused by adsorption of components to the plastic wall and because there is virtually no literature on this subject, we investigated the influence of collection of serum in plastic tubes on the results of nearly all our immunoassays for hormones and tumour markers. Blood from healthy volunteers was collected simultaneously in glass and plastic tubes, or sera prepared from blood collected in glass tubes were brought into the plastic tubes under investigation. Hormone and tumour marker levels were measured in the pairs thus obtained. Results were analysed using paired t-tests or Wilcoxon signed rank tests. We found small but statistically significant differences (p<0.05) between glass and plastic for free triiodothyronine, progesterone, prolactin, prostate-specific antigen and pregnancy-associated plasma protein-A. Non-significant trends (0.05
Evans, Angharad; Jamieson, Stephen M F; Liu, Dong-Xu; Wilson, William R; Perry, Jo K
Human GH expression is associated with poor survival outcomes for endometrial cancer patients, enhanced oncogenicity of endometrial cancer cells and reduced sensitivity to ionising radiation in vitro, suggesting that GH is a potential target for anticancer therapy. However, whether GH receptor inhibition sensitises to radiotherapy in vivo has not been tested. In the current study, we evaluated whether the GH receptor antagonist, pegvisomant (Pfizer), sensitises to radiotherapy in vivo in an endometrial tumour xenograft model. Subcutaneous administration of pegvisomant (20 or 100 mg/kg/day, s.c.) reduced serum IGF1 levels by 23% and 68%, respectively, compared to vehicle treated controls. RL95-2 xenografts grown in immunodeficient NIH-III mice were treated with vehicle or pegvisomant (100 mg/kg/day), with or without fractionated gamma radiation (10 × 2.5 Gy over 5 days). When combined with radiation, pegvisomant significantly increased the median time tumours took to reach 3× the pre-radiation treatment volume (49 days versus 72 days; p = 0.001). Immunohistochemistry studies demonstrated that 100 mg/kg pegvisomant every second day was sufficient to abrogate MAP Kinase signalling throughout the tumour. In addition, treatment with pegvisomant increased hypoxic regions in irradiated tumours, as determined by immunohistochemical detection of pimonidazole adducts, and decreased the area of CD31 labelling in unirradiated tumours, suggesting an anti-vascular effect. Pegvisomant did not affect intratumoral staining for HIF1α, VEGF-A, CD11b, or phospho-EGFR. Our results suggest that blockade of the human GH receptor may improve the response of GH and/or IGF1-responsive endometrial tumours to radiation.
Gajulapalli, Vijaya Narasihma Reddy; Malisetty, Vijaya Lakshmi; Chitta, Suresh Kumar; Manavathi, Bramanandam
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of oestrogen receptor α (ERα) expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable. To answer that, two important approaches are considered: (1) understanding the cellular origin of heterogeneity and ER negativity in breast cancers and (2) characterization of molecular regulators of endocrine resistance. Breast tumours are heterogeneous in nature, having distinct molecular, cellular, histological and clinical behaviour. Recent advancements in perception of the heterogeneity of breast cancer revealed that the origin of a particular mammary tumour phenotype depends on the interactions between the cell of origin and driver genetic hits. On the other hand, histone deacetylases (HDACs), DNA methyltransferases (DNMTs), miRNAs and ubiquitin ligases emerged as vital molecular regulators of ER negativity in breast cancers. Restoring response to endocrine therapy through re-expression of ERα by modulating the expression of these molecular regulators is therefore considered as a relevant concept that can be implemented in treating ER-negative breast cancers. In this review, we will thoroughly discuss the underlying mechanisms for the loss of ERα expression and provide the future prospects for implementing the strategies to negate ER negativity in breast cancers. PMID:27884978
... affect many different processes, including Growth and development Metabolism - how your body gets energy from the foods you eat Sexual function Reproduction Mood Endocrine glands, which are special groups of cells, make hormones. The major endocrine glands are the ...
Czarnywojtek, Agata; Bączyk, Maciej; Ziemnicka, Katarzyna; Fischbach, Jakub; Wrotkowska, Elżbieta; Ruchała, Marek
Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377
Background Oocytes mature in ovarian follicles surrounded by granulosa cells. During follicle growth, granulosa cells replicate and secrete hormones, particularly steroids close to ovulation. However, most follicles cease growing and undergo atresia or regression instead of ovulating. To investigate the effects of stimulatory (follicle-stimulating hormone; FSH) and inhibitory (tumour necrosis factor alpha; TNFα) factors on the granulosa cell transcriptome, bovine ovaries were obtained from a local abattoir and pools of granulosa cells were cultured in vitro for six days under defined serum-free conditions with treatments present on days 3–6. Initially dose–response experiments (n = 4) were performed to determine the optimal concentrations of FSH (0.33 ng/ml) and TNFα (10 ng/ml) to be used for the microarray experiments. For array experiments cells were cultured under control conditions, with FSH, with TNFα, or with FSH plus TNFα (n = 4 per group) and RNA was harvested for microarray analyses. Results Statistical analysis showed primary clustering of the arrays into two groups, control/FSH and TNFα/TNFα plus FSH. The effect of TNFα on gene expression dominated that of FSH, with substantially more genes differentially regulated, and the pathways and genes regulated by TNFα being similar to those of FSH plus TNFα treatment. TNFα treatment reduced the endocrine activity of granulosa cells with reductions in expression of FST, INHA, INBA and AMH. The top-ranked canonical pathways and GO biological terms for the TNFα treatments included antigen presentation, inflammatory response and other pathways indicative of innate immune function and fibrosis. The two most significant networks also reflect this, containing molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor β signalling, and these were up regulated. Upstream regulator analyses also predicted TNF, interferons γ and
Huang, Qi; Nai, Yong-Jun; Jiang, Zhi-Wei; Li, Jie-Shou
Changes in the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis, especially acquired GH resistance, develop in many severe illnesses, including cachexia. To study changes in the GH-IGF-I axis in patients with cancer cachexia, biochemical markers and body composition parameters were measured in eighty-eight gastric cancer patients, thirty colorectal cancer patients (subclassified according to the presence or absence of cachexia) and twenty-four healthy control subjects. Fifty-nine patients were defined as cachectic, based on the percentage of weight loss compared with their previous normal weight. The remaining fifty-nine patients were defined as non-cachectic. Measurements were repeated in twenty-seven patients (sixteen with gastric cancer and eleven with colorectal cancer) 3 months after radical operation. Compared with the controls, the cachectic gastric cancer patients had high GH levels (1.36 v. 0.32 ng/ml; P=0.001), a trend towards high IGF-I levels (223.74 v. 195.15 ng/ml; P=0.128 compared with non-cachectic patients) and a low log IGF-I/GH ratio (2.55 and 2.66 v. 3.00; P=0.002), along with a decreased BMI; the cachectic colorectal cancer patients showed the biochemical characteristics of acquired GH resistance: high GH (0.71 v. 0.32 ng/ml; P=0.016), a trend towards decreased IGF-I levels (164.18 v. 183.24 ng/ml; P=0.127) and a low log IGF-I/GH ratio (2.54 v. 2.99; P=0.005), with increased IGF-I levels following radical surgery (200.49 v. 141.91 ng/ml; P=0.046). These findings suggest that normal GH reaction and sensitivity occur in gastric cancer patients, controlled by nutritional status, whereas acquired GH resistance develops in cachectic colorectal cancer patients, which may be caused by tumour itself.
Garcia, Marcel; Derocq, Danielle; Freiss, Gilles; Rochefort, Henri
Breast cancers containing estrogen receptors are responsive to antiestrogen treatment and have a better prognosis than estrogen receptor-negative tumors. The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated tumors. We transfected the human estrogen receptor into the estrogen receptor-negative metastatic breast cancer cell line MDA-MB-231 in an attempt to restore their sensitivity to antiestrogens. Two stable sublines of MDA-MB-231 cells (HC1 and HE5) expressing functional estrogen receptors were studied for their ability to grow and invade in vitro and to metastasize in athymic nude mice. The number and size of lung metastases developed by these two sublines in ovariectomized nude mice was not markedly altered by tamoxifen but was inhibited 3-fold by estradiol. Estradiol also significantly inhibited in vitro cell proliferation of these sublines and their invasiveness in Matrigel, a reconstituted basement membrane, whereas the antiestrogens 4-hydroxytamoxifen and ICI 164,384 reversed these effects. These results show that estradiol inhibits the metastatic ability of estrogen receptornegative breast cancer cells following transfection with the estrogen receptor, whereas estrogen receptor-positive breast cancers are stimulated by estrogen, indicating that factors other than the estrogen receptor are involved in progression toward hormone independence. Reactivation or transfer of the estrogen receptor gene can therefore be considered as therapeutic approaches to hormone-independent cancers
Tumours induce the growth of host blood vessels to support their proliferation. This process of angiogenesis is evoked by specific chemical signals. Recognition of these angiogenic factors has led to experimental methods for cancer diagnosis and for inhibiting malignant growth by specifically blocking neovascularisation. The clinical potential of these techniques is discussed. PMID:2413796
Lecavalier, D.R.; Main, J.H.P.
The authors of this article review briefly the anatomy of the oral soft tissues and describe the more common benign and malignant tumours of the mouth, giving emphasis to their clinical features. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8 PMID:21253197
Martos-Moreno, G A; Pozo-Román, J; Argente, J
This special article aims to summarise the current knowledge regarding the two groups of tumours with their origin in the adrenal gland: 1) adrenocortical tumours, derived from the cortex of the adrenal gland and 2) phaeochromocytomas and paragangliomas, neuroendocrine tumours derived from nodes of neural crest derived cells symmetrically distributed at both sides of the entire spine (paragangliomas [PG]). These PGs can be functioning tumors that secrete catecholamines, which confers their typical dark colour after staining with chromium salts (chromaffin tumors). Among these, the term phaeochromocytoma (PC) is restricted to those PGs derived from the chromaffin cells in the adrenal medulla (intra-adrenal PGs), whereas the term PG is used for those sympathetic or parasympathetic ones in an extra-adrenal location. We analyse the state of the art of their pathogenic and genetic bases, as well as their clinical signs and symptoms, the tests currently available for performing their diagnosis (biochemical, hormonal, imaging and molecular studies) and management (surgery, pre- and post-surgical medical treatment), considering the current and developing strategies in chemo- and radiotherapy.
Dawood, S.; Broglio, K.; Esteva, F. J.; Yang, W.; Kau, S.-W.; Islam, R.; Albarracin, C.; Yu, T. K.; Green, M.; Hortobagyi, G. N.; Gonzalez-Angulo, A. M.
Background: The purpose of this study was to determine the incidence of and survival following brain metastases among women with triple receptor-negative breast cancer. Patients and methods: In all, 679 patients with nonmetastatic triple receptor-negative breast cancer diagnosed from 1980 to 2006 were identified. Cumulative incidence of brain metastases was computed. Cox proportional hazards models were fitted to explore factors that predict for development of brain metastases. Survival was computed using the Kaplan–Meier product limit method. Results: Median follow-up was 26.9 months. In all, 42 (6.2%) patients developed brain metastases with a cumulative incidence at 2 and 5 years of 5.6% [95% confidence interval (CI) 3.8% to 7.9%] and 9.6% (95% CI 6.8% to 13%), respectively. A total of 24 (3.5%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 2 and 5 years of 2.0% (95% CI 2.6% to 6.0%) and 4.9% (95% CI 3.2% to 7.0%), respectively. In the multivariable model, no specific factor was observed to be significantly associated with time to brain metastases. Median survival for all patients who developed brain metastases and those who developed brain metastases as the first site of recurrence was 2.9 months (95% CI 2.0–7.6 months) and 5.8 months (95% CI 1.7–11.0 months), respectively. Conclusion: In this single-institutional study, patients with nonmetastatic triple receptor-negative breast tumors have a high early incidence of brain metastases associated with poor survival and maybe an ideal cohort to target brain metastases preventive strategies. PMID:19150943
Dugué, B; Leppänen, E A; Teppo, A M; Fyhrquist, F; Gräsbeck, R
The study was undertaken to determine whether psychological stress influences immunobiological functions and is an important preanalytical factor to be considered in connection with blood specimen collection. Two kinds of stress were applied, the Stroop colour conflict test and the thrill of a novice about to make the first jump with a parachute. In both test situations, the level of the stress indicators cortisol or anti-diuretic hormone rose significantly. The concentrations of the cytokines studied did not change significantly. However, in the parachute test significant positive correlations were found, e.g. between the changes of cortisol and C-reactive protein and between anti-diuretic hormone and interleukin-1 beta. This suggests that there is an interaction between the endocrine and the immune systems in the response to a psychological stress.
Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer
Jiang, Donghai; Huang, Yuan; Han, Ning; Xu, Mingjie; Xu, Liang; Zhou, Lin; Wang, Shu; Fan, Weimin
Drug resistance frequently results in poor prognosis and high 5-year recurrence rate in estrogen receptor-negative (ER-) breast cancer patients. Herein, we examined the reversal effects of fulvestrant on multidrug resistance (MDR) in ER- breast cancer cells. Co-administration of fulvestrant significantly sensitized ER- MDR tumors to paclitaxel both in vitro and in vivo. Further analyses indicated that fulvestrant did not affect P-gp expression, but could inhibit P-gp function and subsequently reverse P-gp mediated drug resistance in ER- breast cancer cells. These results showed that combination of fulvestrant and chemotherapeutic agents might provide an effective treatment for ER- MDR breast cancers.
Guilbert, A; Gautier, M; Dhennin-Duthille, I; Rybarczyk, P; Sahni, J; Sevestre, H; Scharenberg, A M; Ouadid-Ahidouch, H
Oestrogen receptor negative (ER(-)) invasive ductal carcinoma (IDC) represents a significant clinical challenge and therefore prompts the discovery of novel biomarkers. Transient receptor potential melastatin 7 (TRPM7), a channel protein that also contains a regulatory kinase domain, is overexpressed in IDC and regulates migration. However, the molecular mechanism remains poorly defined. Here, we examined whether TRPM7 regulates migration by its channel function or by its kinase domain. A Magnesium Inhibited Cation current was recorded in two ER(-) highly metastatic breast cancer cell lines. Down-regulation of TRPM7 neither affected Ca(2+)-, nor Mg(2+)-homoeostasis but significantly reduced cell migration via a Ca(2+)-independent pathway. Notably, the overexpression of the truncated kinase domain form of TRPM7 decreased cell migration, while the overexpression of the wild-type form strongly increased it. Concomitantly, TRPM7 silencing reduced the myosin IIA heavy chain phosphorylation. Furthermore, we found higher TRPM7 expression in ER(-) IDC tissues and lymph nodes than in the non-invasive tumoural samples. In conclusion, TRPM7 plays a critical role in breast cancer cell migration through its kinase domain, and our data support the consideration of using TRPM7 as a novel biomarker and a potential therapeutic target in the treatment of human ER(-) IDC.
Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression. PMID:21521500
Levchuk, N I; Pushkar'ov, V M; Kovzun, O I; Mykosha, O S; Hula, N M; Tron'ko, M D
The effect of different concentrations of N-stearoylethanolamine (NSE 18:0) on fragmentation of DNA in the tumoural and extratumour tissues of the adrenal glands in vitro was studied. In this work the following types of tissue were investigated: extratumoural tissue from patients with hormonally active tumours, benign tumour tissue (hormonally active and hormonally inactive), tissue of malignant tumours and hyperplasic tissue of the adrenal glands (Itsenko-Cushing disease). It has been established that the NSE increases the intensity of DNA fragmentation only in the tissue of hormonally inactive tumours. Benign hormonally active tumours, malignant tumours and hyperplastic tissue of the adrenal glands were resistant to the NSE. The possible mechanisms of resistance to the drug are discussed.
Misra, Sunayana; Bihari, Chhagan
Desmoplastic nested spindle cell tumour of liver (DNSTL), nested stromal-epithelial tumour (NSET) and calcifying nested stromal-epithelial tumour (CNSET) are recently described entities with similar morphology, immunohistochemistry and molecular genetics. These are rare entities with only three large case series described till date. These tumours commonly present in the paediatric age group. NSETs, in addition have been described to be associated with ectopic adrenocorticotropic hormone (ACTH) production and Cushingoid features. It is important to discuss this rare group of tumours with a low malignant potential as the most common radiological differential diagnosis is hepatoblastoma, which has a relatively poorer prognosis. Thus, a pathologist needs to keep this entity in mind, so as to offer a correct histological diagnosis.
Pócsik, E; González-Cabello, R; Benedek, K; Perl, A; Láng, I; Gergely, P
Con A-induced cytotoxic activity of human lymphocyte subpopulations obtained by cell fractionation procedures was studied in a test system using human epipharynx carcinoma cells (HEp 2) as targets. Only T lymphocytes were cytotoxic, non-T cells exerted no cytotoxic activity, but enhanced the adherence of the tumour cells. Tnon-G lymphocytes (Fc-receptor negative T cells) were more active than TG cells (Fc-receptor-positive T cells) in mediating the Con A-induced cytotoxic reaction.
Accumulation of the advanced glycation end product carboxymethyl lysine in breast cancer is positively associated with estrogen receptor expression and unfavorable prognosis in estrogen receptor-negative cases.
Nass, Norbert; Ignatov, Atanas; Andreas, Ludwig; Weißenborn, Christine; Kalinski, Thomas; Sel, Saadettin
Advanced glycation end products (AGEs) accumulate as a result of high concentrations of reactive aldehydes, oxidative stress, and insufficient degradation of glycated proteins. AGEs are therefore accepted biomarkers for aging, diabetes, and several degenerative diseases. Due to the Warburg effect and increased oxidative stress, cancer cells frequently accumulate significant amounts of AGEs. As the accumulation of AGEs may reflect the metabolic state and receptor signaling, we evaluated the potential prognostic and predictive value of this biomarker. We used immunohistochemistry to determine the AGE Nε-carboxymethyl lysine (CML) in 213 mammary carcinoma samples and Western blotting to detect AGEs in cell cultures. Whereas no significant correlation between hormone receptor status and CML was observed in cell lines, CML accumulation in tumors was positively correlated with the presence of estrogen receptor alpha, the postmenopausal state, and age. A negative correlation was found for grade III carcinomas and triple-negative cases. In a retrospective Kaplan-Meier survival analysis, there was a statistical trend that high CML accumulation correlated with a more favorable prognosis (relapse-free survival, RFS) under tamoxifen treatment (p = 0.1). In estrogen receptor-negative cases, the high CML content was significantly correlated with an unfavorable outcome (RFS) of chemotherapy (p = 0.046). CML is a therefore a potentially predictive marker for the treatment of breast cancer patients with tamoxifen or chemotherapy.
Sokołowski, Grzegorz; Bałdys-Waligórska, Agata; Trofimiuk, Małgorzata; Adamek, Dariusz; Hubalewska-Dydejczyk, Alicja; Gołkowski, Filip
Summary Background Microvessel density in angiogenesis is regarded as a prognostic factor of tumour invasiveness, independent of cell proliferation. In recent studies of pituitary tumours, correlation between the expression of cyclooxygenase-2 (COX-2) and micro-vascularization density and microvessel surface density has been established. We studied the expression of COX-2 in different types of pituitary adenomas to determine the usefulness of COX-2 expression as a prognostic factor of tumour progression or recurrence in patients with hypophyseal tumours. Material/Methods We retrospectively studied a group of 60 patients of mean age 46.7±17.6 (range, 18 to 85) years who underwent pituitary tumour surgery. Expression of COX-2, as determined by immunohistochemistry, was analyzed in relation to histopathology features of tumour, clinical symptoms, MR imaging and post-operative recurrence/progression of disease. Results COX-2 was expressed in adenomas of 87% of patients, with a median index value of 57.5% [IQR=60.5]. Highest COX-2 expression was observed in hormonally inactive adenomas and gonadotropinomas and lowest in prolactinomas. We found no differences in COX-2 expression with respect to patient age, gender, tumour size, degree of tumour invasiveness, or whether tumours were immunopositive or immunonegative for pituitary hormones, nor have we found any relation between COX-2 expression and recurrence or progression of tumour size. Conclusions COX-2 does not appear to be a predictive factor for recurrence or progression of tumour size. Nevertheless, due to the observed relatively high expression of COX-2 in pituitary adenomas, further studies with COX-2 inhibitors are justified in these tumours. PMID:22460097
Chowhan, A K; Reddy, M K; Javvadi, V; Kannan, T
We report an unusual case of extrarenal teratoid Wilms' tumour in a 15-month-old male child. The tumour was retroperitoneal in location and consisted of triphasic Wilms' tumour elements, along with the presence of heterologous components. The heterologous teratoid elements were composed of predominantly glandular epithelium with the presence of focal skeletal muscle, adipose and neuroglial tissues. Although extrarenal Wilms' tumours have been documented in the literature, only a few cases have been noted to date. We present the relevant clinical, radiological, histomorphological, histochemical and immunohistochemical features of this rare tumour, and discuss the various theories of its histogenesis.
Fahlenkamp, D; Reinke, P; Kirchner, S; Schnorr, D; Lindeke, A; Loening, S A
In 1243 patients after renal transplantation, 39 malignant tumours were detected in 37 patients. The average latency period between transplantation and tumour disease was 72 months. Tumours included 8 malignant lymphomas, 7 dermatomas and 24 visceral tumours. The patients who developed a tumour had received fewer blood transfusions before transplantation than a tumour-free control group of 60 patients with renal transplants. Rejection crises occurred in a significantly smaller number of tumour patients compared with the control group.
Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...
Zulkarnaen, Mohammad; Tang, Ing Ping; Wong, Siong Lung
We present a case of a papillary tumour at the cerebellopontine angle in a 41-year-old man. He presented with left-sided facial and ear pain associated with dizziness, nystagmus and hearing loss. CT scan of the temporal bone showed a destructive tumour at the left cerebellopontine angle. Surgical excision was performed and the diagnosis of the endolymphatic sac tumour was made. Endolymphatic tumour is a low grade adenocarcinoma that originates from the endolymphatic sac. The definitive diagnosis requires a combination of clinical features, radiological finding and pathological correlation.
Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos
The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068
Font, Joan; López-Cano, Marc; Notartomaso, Serena; Scarselli, Pamela; Di Pietro, Paola; Bresolí-Obach, Roger; Battaglia, Giuseppe; Malhaire, Fanny; Rovira, Xavier; Catena, Juanlo; Giraldo, Jesús; Pin, Jean-Philippe; Fernández-Dueñas, Víctor; Goudet, Cyril; Nonell, Santi; Nicoletti, Ferdinando; Llebaria, Amadeu; Ciruela, Francisco
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders.
Alexander, Hamish; Tannenburg, Anthony; Walker, David G; Coyne, Terry
Dysembryoplastic neuroepithelial tumour (DNET) is a benign tumour characterised by cortical location and presentation with drug resistant partial seizures in children. Recently the potential for malignant transformation has been reported, however progression without malignant transformation remains rare. We report a case of clinical and radiologic progression of a DNET in a girl 10 years after initial biopsy.
Diez-Itza, I.; Merino, A. M.; Tolivia, J.; Vizoso, F.; Sánchez, L. M.; López-Otín, C.
We have examined by immunohistochemistry the ability of breast carcinomas to produce pepsinogen C, an aspartyl proteinase usually involved in the digestion of proteins in the stomach. A total of 113 out of 245 breast tumours (46%) were positive for pepsinogen C immunostaining. There was a significant association between pepsinogen C and oestrogen receptors with proteinase levels higher (HSCORE) in oestrogen receptor positive tumours than in oestrogen receptor negative. There was also a significant association between pepsinogen C and histological grade, pepsinogen C levels being higher in well and moderately differentiated breast carcinomas than in poorly differentiated tumours. On the basis of these results, we suggest that pepsinogen C may be useful as a marker of good prognosis in breast cancer. Images Figure 2 Figure 1 PMID:8353054
Massoud, A; Powell, M; Williams, R; Hindmarsh, P; Brook, C
Accepted 29 January 1997 OBJECTIVES—Transsphenoidal surgery (TSS) is the preferred method for the excision of pituitary microadenomas in adults. This study was carried out to establish the long term efficacy and safety of TSS in children. STUDY DESIGN—A 14 year retrospective analysis was carried out on 23 children (16 boys and seven girls), all less than 18 years of age, who had undergone TSS at our centre. RESULTS—Twenty nine transsphenoidal surgical procedures were carried out. The most common diagnosis was an adrenocorticotrophic hormone (ACTH) secreting adenoma (14 (61%) patients). The median length of follow up was 8.0 years (range 0.3-14.0 years). Eighteen (78%) patients were cured after the first procedure. No death was related to the operation. The most common postoperative complication was diabetes insipidus, which was transient in most patients. Other complications were headaches in two patients and cerebrospinal fluid leaks in two patients. De novo endocrine deficiencies after TSS in children were as follows: three (14%) patients developed panhypopituitarism, eight (73%) developed growth hormone insufficiency, three (14%) developed secondary hypothyroidism, and four (21%) developed gonadotrophin deficiency. Permanent ACTH deficiency occurred in five (24%) patients, though all patients received postoperative glucocorticoid treatment until dynamic pituitary tests were performed three months after TSS. CONCLUSIONS—TSS in children is a safe and effective treatment for pituitary tumours, provided it is performed by surgeons with considerable experience and expertise. Surgical complications are minimal. Postoperative endocrine deficit is considerable, but is only permanent in a small proportion of patients. • Transsphenoidal surgery is a safe and effective treatment for pituitary tumours in children • Transsphenoidal surgery should be performed by surgeons with considerable experience and expertise • Surgical complications of
Starting with Paul Langerhans, who first described pancreatic islets in 1869, this article reviews the various protagonists who, in the last century and a half, have contributed to the discovery of the main hormones originating in the pancreas, the analytical methods for their measurement, the imaging techniques for identifying tumoural location, and the various pancreatic neoplasms.
Dalmau, Elsa; Armengol-Alonso, Alejandra; Muñoz, Montserrat; Seguí-Palmer, Miguel Ángel
The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer.
Blankenstein, Thomas; Coulie, Pierre G.; Gilboa, Eli; Jaffee, Elizabeth M.
Many standard and targeted therapies, as well as radiotherapy, have been shown to induce an anti-tumour immune response, and immunotherapies rely on modulating the host immune system to induce an anti-tumour immune response. However, the immune response to such therapies is often reliant on the immunogenicity of a tumour. Tumour immunogenicity varies greatly between cancers of the same type in different individuals and between different types of cancer. So, what do we know about tumour immunogenicity and how might we therapeutically improve tumour immunogenicity? We asked four leading cancer immunologists around the world for their opinions on this important issue. PMID:22378190
Ha, Ngoc-Han; Long, Jirong; Cai, Qiuyin; Shu, Xiao Ou
Breast cancer mortality is primarily due to metastasis rather than primary tumors, yet relatively little is understood regarding the etiology of metastatic breast cancer. Previously, using a mouse genetics approach, we demonstrated that inherited germline polymorphisms contribute to metastatic disease, and that these single nucleotide polymorphisms (SNPs) could be used to predict outcome in breast cancer patients. In this study, a backcross between a highly metastatic (FVB/NJ) and low metastatic (MOLF/EiJ) mouse strain identified Arntl2, a gene encoding a circadian rhythm transcription factor, as a metastasis susceptibility gene associated with progression, specifically in estrogen receptor-negative breast cancer patients. Integrated whole genome sequence analysis with DNase hypersensitivity sites reveals SNPs in the predicted promoter of Arntl2. Using CRISPR/Cas9-mediated substitution of the MOLF promoter, we demonstrate that the SNPs regulate Arntl2 transcription and affect metastatic burden. Finally, analysis of SNPs associated with ARNTL2 expression in human breast cancer patients revealed reproducible associations of ARNTL2 expression quantitative trait loci (eQTL) SNPs with disease-free survival, consistent with the mouse studies. PMID:27656887
Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Marchand, Loïc Le; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
Shalet, S M; Beardwell, C G; Morris-Jones, P H; Pearson, D
Pituitary-function tests have been done in twenty-seven patients at various times after treatment in childhood for intracranial tumours not directly involving the hypothalamic-pituitary region. Impaired growth hormone (G.H.) responses to hypoglycaemia and 'Bovril' were found in ten children. There seeems to be progressive impairment in G.H. production with time after treatment. During the first 3 months after neurosurgery no child was found to be G.H. deficient, but the peak G.H. response of this group seemed to be blunted when compared with a control group of children who had been treated for abdominal tumours. The rest of anterior-pituitary function in G.H.-deficient children seems quite normal except for a significantly greater basal thyroid-stimulating hormone (T.S.H.) level and T;S.H. response after thyrotrophin-releasing hormone. Two girls have developed secondary amenorrhoea, and one is G.H. deficient.
Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.
The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786
Biswas, Debajit K.; Dai, Sun-Chun; Cruz, Antonio; Weiser, Barbara; Graner, Edgard; Pardee, Arthur B.
The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor (EGF)-stimulated estrogen receptor negative (ER−) breast cancer cells in vivo and role of nuclear factor kappa B (NF-κB) on tumorogenesis have been investigated. This was studied in an animal model by implanting ER− mouse mammary epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of tumors and caused extensive necrotic degeneration and regression of the tumors without causing any microscopically detectable damage to the vital organs liver and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit (dnIkkβ) of the inhibitory kappa B (IκB) kinase (dnIkk) that selectively blocked activation of NF-κB caused loss of tumorigenic potential of CSMLO cells. Stable expression of dnIkkβ also blocked phorbol 12-myristate 13-acetate (PMA)-induced activation of NF-κB and overexpression of cyclin D1, concomitantly with the loss or reduced tumorigenic potential of these cells. Thus, results from in vivo and in vitro experiments strongly suggest the involvement of NF-κB in ER− mammary epithelial cell-mediated tumorigenesis. We propose that blocking NF-κB activation not only inhibits cell proliferation, but also antagonizes the antiapoptotic role of this transcription factor in ER− breast cancer cells. Thus, NF-κB is a potential target for therapy of EGFR family receptor-overexpressing ER− breast cancers. PMID:11517301
Sasidharan, Balukrishna; Manipadam, Marie Therese; Paul, M J; Backianathan, Selvamani
Introduction Phyllodes Tumour (PT) of the breast is a relatively rare breast neoplasm (<1%) with diverse range of pathology and biological behaviour. Aim To describe the clinical course of PT and to define the role of Radiotherapy (RT) in PT of the breast. Materials and Methods Retrospective analysis of hospital data of patients with PT presented from 2005 to 2014 was done. Descriptive statistics was used to analyze the results. Simple description of data was done in this study. Age and duration of symptoms were expressed in median and range. Percentages, tables and general discussions were used to understand the meaning of the data analyzed. Results Out of the 98 patients, 92 were eligible for analysis. The median age of presentation was 43 years. A total of 64/92 patients were premenopausal. There was no side predilection for this tumour but 57/92 patients presented as an upper outer quadrant lump. Fifty percent of the patients presented as giant (10 cm) PT. The median duration of symptoms was 12 months (range: 1-168 months). A 60% of patients had Benign (B), 23% had Borderline (BL) and 17% had malignant (M) tumours. The surgical treatment for benign histology included Lumpectomy (L) for 15%, Wide Local Excision (WLE) for 48%, and Simple Mastectomy (SM) for 37%. All BL and M tumours were treated with WLE or SM. There was no recurrence in B and BL group when the margin was ≥1 cm. All non-metastatic M tumours received adjuvant RT irrespective of their margin status. Total 3/16 patients with M developed local recurrence. Total 6/16 M patients had distant metastases (lung or bone). Our median duration of follow up was 20 months (range: 1-120 months). Conclusion Surgical resection with adequate margins (>1 cm) gave excellent local control in B and BL tumours. For patients with BL PT, local radiotherapy is useful, if margins are close or positive even after the best surgical resection. There is a trend towards improved local control with adjuvant radiotherapy for
Carter, Simon R.; Spooner, David; Sneath, Rodney S.
In 1993 we became aware of a worrying increase in apparent errors in the histopathological diagnosis of musculoskeletal tumours in our Unit. As a result all cases seen over the past 8 years were reviewed by an independent panel. Of the 1996 cases reviewed there was an error in 87. In 54 cases (2.7%) this had led to some significant change in the active management of the patient. The main areas where errors arose were in those very cases where clinical and radiological features were not helpful in confirming or refuting the diagnosis. The incidence of errors rose with the passage of time, possibly related to a deterioration in the pathologist’s health. The error rate in diagnosing bone tumours in previously published series ranges from 9 to 40%. To ensure as accurate a rate of diagnosis as possible multidisciplinary working and regular audit are essential. PMID:18521309
Nielsen, Svend W.; Mackey, L. J.; Misdorp, W.
The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. ImagesFig. 5,6Fig. 7Fig. 8Fig. 1,2Fig. 3,4Fig. 16,17,18,19Fig. 9,10Fig. 11Fig. 12Fig. 13Fig. 14,15 PMID:1086154
Dawood, Shaheenah; Lei, Xiudong; Litton, Jennifer K.; Buchholz, Thomas A.; Hortobagyi, Gabriel N.; Gonzalez-Angulo, Ana M.
Background The aim of this retrospective study was to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC). Methods 2448 patients with stage I–III TNBC diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases. Results At a median follow up of 39 months 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% CI 2.9%–4.5%) and 5.4% (95% CI 4.4%–6.5%), respectively. Among patients with stage I, II and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1% and 8%, respectively (p<0.0001). 5-year cumulative incidence was 2.8%, 4.6% and 9.6% among patients with stage I, II and III disease, respectively (p<0.0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (HR = 3.51; 95% CI 1.85 – 6.67; p = .0001) compared to patients with stage I disease. Those with stage II disease had a non significant increased risk of developing brain metastases as a first site of recurrence (HR = 1.61; 95% CI 0.92 – 2.81; p = .10) compared to patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range 5.7 to 9.4 months). Conclusion Patients with non metastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort to
van Gils, A. P.; van der Mey, A. G.; Hoogma, R. P.; Sandkuijl, L. A.; Maaswinkel-Mooy, P. D.; Falke, T. H.; Pauwels, E. K.
Paragangliomas of the head and neck (glomus tumours) can occur in a hereditary pattern and may be hormonally active as well as being associated with paragangliomas elsewhere. A number of these tumours may be present without symptoms. To detect the presence of subclinical paragangliomas we screened 83 members of a family at risk of developing hereditary paragangliomas using whole body MRI and urinary catecholamine testing. In eight previously diagnosed members, eight known glomus tumours of which one functioning, and two unknown glomus tumours and one unknown pheochromocytoma were present. Six unsuspected members showed ten glomus tumours and one pheochromocytoma. It has been suggested that the manifestation of hereditary glomus tumours is determined by the sex of the transmitting parent. There were no tumours in the descendants of female gene carriers. Comparing the likelihood of inheritance with genomic imprinting versus inheritance without genomic imprinting we found an odds ratio of 23375 in favour of genomic imprinting. PMID:1616861
den Exter, Paul L; Hornstra, Bonne J; Vree, Robbert
A 40-year-old woman presented at the breast outpatient clinic with a giant tumour of her left breast. The size, rapid growth and radiological characteristics of the lesion led us to suspect a phyllodes tumour. A histological examination of a needle biopsy confirmed this diagnosis. An additional CT scan revealed no signs of metastases. We performed a mastectomy during which a tumour measuring 48 x 33 x 25 cm was resected. Histological examination revealed a borderline phyllodes tumour. Phyllodes tumours are rare fibroepithelial neoplasms of the breast and pre-operatively these are often difficult to differentiate from fibroadenomas. Phyllodes tumours have a variable clinical course with the ability to metastasize and a propensity to recur locally. Complete excision with wide margins is essential to prevent local recurrence. In our case, the surgical margins were limited and our patient was therefore treated with postoperative radiation therapy.
Al-Futaisi, Abdullah; Saif, Al-Yaarubi; Al-Zakwani, Ibrahim; Al-Qassabi, Salim; Al-Riyami, Shaden; Wali, Yasser
Objective: From a recently instituted web-based pituitary tumour registry at Sultan Qaboos University Hospital, Oman, this study explores the results of comprehensive clinical evaluation, hormonal levels, radiological evidence of pituitary mass lesion using magnetic resonance (MRI) and the different treatment modalities. Methods: All patients who were diagnosed with pituitary mass tumours in our tertiary care endocrinology clinic between January 1998 and February 2006 were registered in the Oman pituitary tumour registry. Two physicians performed hospital chart review and data entry. Results: A total of 160 entries were made into the pituitary tumour registry. The overall mean age of the cohort was 32 ±12 years (age range 8–73 years). The majority of registrations were female (n=114; 71%). There were 81 patients with non-functioning adenomas (50.6%), 59 with prolactinoma (36.9%) eight with acromegaly (5%), seven with craniopharyngioma (4.4%), four with Cushing’s disease (2.5%) and one with sarcoidosis (0.6%). Sub-group analyses were done only for the subjects with the 3 most prevalent pituitary tumours (non-functioning adenomas, prolactinomas, and acromegaly). The most prevalent symptoms are amenorrhea-galactorrhea (n=55; 37%), headache (n=31; 21%) and fatigue (n=23; 16%). The most common treatment modality was medical (n=58; 39%), followed by observation (n=56; 38%), surgery (n=31; 21%) and surgery plus medical (n=3; 2%). None of the patients in this registry are recorded to have died. Conclusion: To our knowledge, this is the first pituitary tumour registry in the Arabian Gulf countries using a web-based programme. This tumour registry will enable us to characterize clinical and the epidemiological features of pituitary tumours in the Sultanate of Oman. PMID:21654941
Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.
Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice.
Milotti, E.; Vyshemirsky, V.; Sega, M.; Stella, S.; Chignola, R.
Tumour metabolism is an outstanding topic of cancer research, as it determines the growth rate and the global activity of tumours. Recently, by combining the diffusion of oxygen, nutrients, and metabolites in the extracellular environment, and the internal motions that mix live and dead cells, we derived a growth law of solid tumours which is linked to parameters at the cellular level1. Here we use this growth law to obtain a metabolic scaling law for solid tumours, which is obeyed by tumours of different histotypes both in vitro and in vivo, and we display its relation with the fractal dimension of the distribution of live cells in the tumour mass. The scaling behaviour is related to measurable parameters, with potential applications in the clinical practice. PMID:23727729
... estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...
Goel, Hira Lal; Mercurio, Arthur M
The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.
Price, S J; Gillard, J H
Invasion of tumour cells into the normal brain is one of the major reasons of treatment failure for gliomas. Although there is a good understanding of the molecular and cellular processes that occur during this invasion, it is not possible to detect the extent of the tumour with conventional imaging. However, there is an understanding that the degree of invasion differs with individual tumours, and yet they are all treated the same. Newer imaging techniques that probe the pathological changes within tumours may be suitable biomarkers for invasion. Imaging methods are now available that can detect subtle changes in white matter organisation (diffusion tensor imaging), tumour metabolism and cellular proliferation (using MR spectroscopy and positron emission tomography) occurring in regions of tumour that cannot be detected by conventional imaging. The role of such biomarkers of invasion should allow better delineation of tumour margins, which should improve treatment planning (especially surgery and radiotherapy) and provide information on the invasiveness of an individual tumour to help select the most appropriate therapy and help stratify patients for clinical trials.
Rivera-Arkoncel, Maria Luisa Cecilia; Pacquing-Songco, Debby; Lantion-Ang, Frances Lina
Androgen secreting tumours are the least commonly encountered androgen excess disorders, having a prevalence of 0.2%. Androblastomas of the ovary comprise less than 0.5% of all ovarian tumours. Pure Leydig cell tumours are very rare and almost always show secretion of male sex hormones. A 41-year-old multipara Filipino woman presented with a 2-year history of amenorrhoea and virilisation characterised by hirsutism, androgenic alopecia, masculine habitus and clitoromegaly. Diagnostic evaluation showed markedly elevated serum testosterone and normal dehydroepiandrosterone sulfate. Normal ovaries were seen on initial transvaginal ultrasound. A low dose dexamethasone suppression test suggested an ovarian source. A left adrenal nodule was seen on CT scan. Doppler transvaginal ultrasound revealed a solid lobulated structure in the right ovary. The patient underwent surgery and histopathology showed a Leydig cell tumour, hilar type. Serum testosterone levels normalised 3 days after surgery. Specific clinical and biochemical investigation of androgen secreting neoplasms is very important for correct diagnosis of these rare tumours. PMID:22802276
Ilhan, Tolgay Tuyan; Gül, Ayhan; Ugurluoglu, Ceyhan; Çelik, Çetin
Uterine Tumour Resembling Ovarian Sex-Cord Tumours (UTROSCTs) are an extremely rare type of uterine body tumours arising from the endometrial stroma. Epidemiology, aetiology, pathogenesis, management and natural history of UTROSCTs are still a question of debate, as there is little available data in the literature. Although rare, the possibility of UTROSCTs should be kept in mind, when a patient presents with abnormal bleeding and an enlarged uterus. UTROSCTs appear dirty white/cream-coloured, gelatinous, well-circumscribed mass with smooth surface on macroscopic examination. We present a rare case of endometrial stromal tumour with sex-cord-like differentiation which was successfully treated by hysterectomy with bilateral salpingo-oophorectomy. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. PMID:28208949
O'Donnell, E F; Koch, D C; Bisson, W H; Jang, H S; Kolluri, S K
Identification of new molecular targets for the treatment of breast cancer is an important clinical goal, especially for triple-negative breast cancer, which is refractory to existing targeted treatments. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, and thus may be a potential anticancer target. To investigate the AhR as an anticancer target, we conducted a small molecule screen to discover novel AhR ligands with anticancer properties. We identified raloxifene, a selective estrogen receptor (ER) modulator currently used in the clinic for prevention of ER-positive breast cancer and osteoporosis in post-menopausal women, as an AhR activator. Raloxifene directly bound the AhR and induced apoptosis in ER-negative mouse and human hepatoma cells in an AhR-dependent manner, indicating that the AhR is a molecular target of raloxifene and mediates raloxifene-induced apoptosis in the absence of ER. Raloxifene selectively induced apoptosis of triple-negative MDA-MB-231 breast cancer cells compared with non-transformed mammary epithelial cells via the AhR. Combined with recent data showing that raloxifene inhibits triple-negative breast cancer xenografts in vivo (Int J Oncol. 43(3):785-92, 2013), our results support the possibility of repurposing of raloxifene as an AhR-targeted therapeutic for triple-negative breast cancer patients. To this end, we also evaluated the role of AhR expression on survival of patients diagnosed with breast cancer. We found that higher expression of the AhR is significantly associated with increased overall survival and distant metastasis-free survival in both hormone-dependent (ER-positive) and hormone-independent (ER and progesterone receptor (PR)-negative) breast cancers. Together, our data strongly support the possibility of using the Ah
O'Donnell, E F; Koch, D C; Bisson, W H; Jang, H S; Kolluri, S K
Identification of new molecular targets for the treatment of breast cancer is an important clinical goal, especially for triple-negative breast cancer, which is refractory to existing targeted treatments. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known primarily as the mediator of dioxin toxicity. However, the AhR can also inhibit cellular proliferation in a ligand-dependent manner and act as a tumor suppressor in mice, and thus may be a potential anticancer target. To investigate the AhR as an anticancer target, we conducted a small molecule screen to discover novel AhR ligands with anticancer properties. We identified raloxifene, a selective estrogen receptor (ER) modulator currently used in the clinic for prevention of ER-positive breast cancer and osteoporosis in post-menopausal women, as an AhR activator. Raloxifene directly bound the AhR and induced apoptosis in ER-negative mouse and human hepatoma cells in an AhR-dependent manner, indicating that the AhR is a molecular target of raloxifene and mediates raloxifene-induced apoptosis in the absence of ER. Raloxifene selectively induced apoptosis of triple-negative MDA-MB-231 breast cancer cells compared with non-transformed mammary epithelial cells via the AhR. Combined with recent data showing that raloxifene inhibits triple-negative breast cancer xenografts in vivo (Int J Oncol. 43(3):785-92, 2013), our results support the possibility of repurposing of raloxifene as an AhR-targeted therapeutic for triple-negative breast cancer patients. To this end, we also evaluated the role of AhR expression on survival of patients diagnosed with breast cancer. We found that higher expression of the AhR is significantly associated with increased overall survival and distant metastasis-free survival in both hormone-dependent (ER-positive) and hormone-independent (ER and progesterone receptor (PR)-negative) breast cancers. Together, our data strongly support the possibility of using the Ah
Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag
In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields
Beck-Peccoz, Paolo; Persani, Luca; Mannavola, Deborah; Campi, Irene
Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism and account for less than 2% of all pituitary adenomas. In the last years, the diagnosis has been facilitated by the routine use of ultra-sensitive TSH immunometric assays. Failure to recognise the presence of a TSHoma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumour volume to further expand. The diagnosis mainly rests on dynamic testing, such as T3 suppression tests and TRH, which are useful in differentiating TSHomas from the syndromes of thyroid hormone resistance. The first therapeutical approach to TSHomas is the pituitary neurosurgery. The medical treatment of TSHomas mainly rests on the administration of somatostatin analogues, such as octreotide and lanreotide, which are effective in reducing TSH secretion in more than 90% of patients with consequent normalisation of FT4 and FT3 levels and restoration of the euthyroid state.
Ruberti, R F; Carmagnani, A L
Thirty-one cases of intraspinal tumours in the African have been described, with age, sex incidence, frequency, site and histopathology shown. Intraspinal tumours in this series are compared with the larger series. Extradural and intramedullary tumours together with cervical spine tumours appear to be more frequent in this series. There is a high incidence of dumbell tumours in the neurinomas. Sarcomas are the most common type of tumours and mainly affect the thoracic spine.
Karhunen, P J
In a consecutive medicolegal necropsy series benign hepatic tumours and tumour like conditions occurred in 52% of the 95 men aged 35-69 years. The incidence increased with age, mainly due to small bile duct tumours (n = 26; mean age 56.7 years; p less than 0.01; mean size 1.3 mm). The next most common tumours were cavernous hemangiomas (n = 19; mean age 53.9 years; mean size 5.2 mm) that were not related to age. Focal nodular hyperplasia (n = 3; mean size 8.0 mm) tended to occur in a younger age group (mean age 40.3 years; p less than 0.001). Multiple bile duct tumours were present in 46% and hemangiomas in 50% of the men studied. Liver cell adenoma, nodular regenerative hyperplasia, and peliosis hepatis were incidental findings (one case of each). Nodular regenerative hyperplasia was associated with the consumption of alcohol and a total dose of 21.5 g of testosterone. These results indicate that benign hepatic tumours and tumour like conditions are not rare in men but may remain undetected because of their small size. Images PMID:3950039
Misdorp, W.; Van Der Heul, R. O.
Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157
Rajendran, Simon; Salwa, Slawomir; Gao, Xuefeng; Tabirca, Sabin; O'Hanlon, Deirdre; O'Sullivan, Gerald C.; Tangney, Mark
This video describes the establishment of liver metastases in a mouse model that can be subsequently analysed by bioluminescent imaging. Tumour cells are administered specifically to the liver to induce a localised liver tumour, via mobilisation of the spleen and splitting into two, leaving intact the vascular pedicle for each half of the spleen. Lewis lung carcinoma cells that constitutively express the firefly luciferase gene (luc1) are inoculated into one hemi-spleen which is then resected 10 minutes later. The other hemi-spleen is left intact and returned to the abdomen. Liver tumour growth can be monitored by bioluminescence imaging using the IVIS whole body imaging system. Quantitative imaging of tumour growth using IVIS provides precise quantitation of viable tumour cells. Tumour cell death and necrosis due to drug treatment is indicated early by a reduction in the bioluminescent signal. This mouse model allows for investigating the mechanisms underlying metastatic tumour-cell survival and growth and can be used for the evaluation of therapeutics of liver metastasis. PMID:20689502
Barbieri, Antonio; Palma, Giuseppe; Rosati, Alessandra; Giudice, Aldo; Falco, Antonia; Petrillo, Antonella; Petrillo, Mario; Bimonte, Sabrina; Benedetto, Maria Di; Esposito, Giuseppe; Stiuso, Paola; Abbruzzese, Alberto; Caraglia, Michele; Arra, Claudio
Abstract Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the β-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS−/− mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth. PMID:21722303
Stünzi, H.; Hauser, B.
Tumours of the nasal cavity are rare in domestic animals, most cases occurring in the dog. Epithelial tumours are the most common type in carnivores (dogs and cats). In general, the same types of tumour occur in domestic animals as occur in man. There was no significant predisposition for breed in dogs, but in both dogs and cats far more males than females were affected. Metastases occurred only rarely. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12Fig. 5Fig. 6Fig. 7Fig. 8 PMID:1086156
ZHENG, LIXIANG; ZHOU, BUGAO; MENG, XIANMING; ZHU, WEIFENG; ZUO, AIREN; WANG, XIAOMIN; JIANG, RUNDE; YU, SHIPING
Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women. PMID:25230850
As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.
Richard, Elodie; Grellety, Thomas; Velasco, Valerie; MacGrogan, Gaetan; Bonnefoi, Hervé; Iggo, Richard
There is a paucity of models for hormone receptor-positive (HR+) breast cancer because of the difficulty of establishing xenografts from these tumours. We show that this obstacle can be overcome by injecting human tumour cells directly into the mammary ducts of immunodeficient mice. Tumours from 31 patients were infected overnight with a lentiviral vector expressing tdTomato and injected through the nipple into the mammary ducts of NOD-SCID-IL2RG-/- mice. Tumours formed in the mice in 77% of cases after the first injection (6/8 luminal A, 15/20 luminal B, and 3/3 molecular apocrine). Four luminal A and one molecular apocrine graft were tested in secondary and tertiary grafts: all were successfully passaged in secondary and 4/5 in tertiary grafts. None of the samples engrafted when injected subcutaneously. The morphology, oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki-67 profiles of the clinical samples were maintained in the tertiary grafts. We also show that the intraductal approach can be used to test the response to targeted therapy with fulvestrant and palbociclib, using a genetically defined ER+ model. We conclude that the mammary ducts create a microenvironment that is uniquely favourable to the survival and growth of tumours derived from mammary hormone-sensing cells. This approach opens the door to testing genomically targeted treatment of HR+ tumours in precision medicine programmes. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Tsang, Y P; Lang, Brian H H; Tam, S C; Wong, K P
Ewing's sarcoma, also called primitive neuroectodermal tumour of the adrenal gland, is extremely rare. Only a few cases have been reported in the literature. We report on a woman with adult-onset primitive neuroectodermal tumour of the adrenal gland presenting with progressive flank pain. Computed tomography confirmed an adrenal tumour with invasion of the left diaphragm and kidney. Radical surgery was performed and the pain completely resolved; histology confirmed the presence of primitive neuroectodermal tumour, for which she was given chemotherapy. The clinical presentation of this condition is non-specific, and a definitive diagnosis is based on a combination of histology, as well as immunohistochemical and cytogenic analysis. According to the literature, these tumours demonstrate rapid growth and aggressive behaviour but there are no well-established guidelines or treatment strategies. Nevertheless, surgery remains the mainstay of local disease control; curative surgery can be performed in most patients. Adjuvant chemoirradiation has been advocated yet no consensus is available. The prognosis of patients with primitive neuroectodermal tumours remains poor.
Lee, Hong Jin; Paul, Shiby; Atalla, Nadi; Thomas, Paul E; Lin, Xinjie; Yang, Ill; Buckley, Brian; Lu, Gang; Zheng, Xi; Lou, You-Rong; Conney, Allan H; Maehr, Hubert; Adorini, Luciano; Uskokovic, Milan; Suh, Nanjoo
Numerous preclinical, epidemiologic, and clinical studies have suggested the benefits of vitamin D and its analogues for the prevention and treatment of cancer. However, the hypercalcemic effects have limited the use of 1alpha,25(OH)(2)D(3), the hormonally active form of vitamin D. To identify vitamin D analogues with better efficacy and low toxicity, we have tested >60 novel Gemini vitamin D analogues with a unique structure of two side chains for growth inhibition of breast cancer cells. Our initial studies found that some Gemini analogues are 5-15 times more active than 1alpha,25(OH)(2)D(3) in growth inhibition assay. In vivo experiments were designed to study the inhibitory effect of selected Gemini vitamin D analogues against mammary carcinogenesis by using (a) an N-methyl-N-nitrosourea-induced estrogen receptor (ER)-positive mammary tumor model and (b) an MCF10DCIS.com xenograft model of ER-negative mammary tumors. Among vitamin D analogues we tested, Gemini 0072 [1alpha,25-dihydroxy-20S-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] and Gemini 0097 [1alpha,25-dihydroxy-20R-21(3-trideuteromethyl-3-hydroxy-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-19-nor-cholecalciferol] administration inhibited by 60% the NMU-induced mammary tumor burden compared with the NMU-treated control group, but these compounds were devoid of hypercalcemia toxicity. In an ER-negative xenograft model, Gemini 0097 significantly suppressed tumor growth without hypercalcemia toxicity. We found that the inhibitory effect of Gemini 0097 was associated with an increased level of cyclin-dependent kinase inhibitor p21 and the insulin-like growth factor binding protein 3 in both ER-positive and ER-negative mammary tumors. Our results suggest that Gemini vitamin D analogues may be potent agents for the prevention and treatment of both ER-positive and ER-negative breast cancer without hypercalcemia toxicity.
, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions. PMID:20412586
Lazzereschi, D; Palmirotta, R; Ranieri, A; Ottini, L; Verì, M C; Cama, A; Cetta, F; Nardi, F; Colletta, G; Mariani-Costantini, R
Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases. © 1999 Cancer Research Campaign PMID:9888478
Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan
Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485
Heimann, H.; Bornfeld, N.; Vij, O.; Coupland, S.; Bechrakis, N.; Kellner, U.; Foerster, M.
BACKGROUND—Vasoproliferative tumours of the retina (VPTR) are benign tumours of unknown origin, occurring mostly in otherwise healthy patients. VPTR may be associated with other chorioretinal diseases, such as uveitis. The tumours, which histologically represent reactive gliovascular proliferations, are characterised by a pink to yellow appearance on funduscopy and are accompanied by exudative and haemorrhagic changes of the retina. METHODS—22 cases of VPTR in 21 patients were examined with a follow up period between 1 month and 6 years. Ophthalmological changes associated with VPTR were intraretinal and subretinal exudations (n=18), exudative detachments of the surrounding sensory retina (n=13), intraretinal and subretinal haemorrhages (n=10), exudative changes within the macula (n=10), hyperpigmentation of the retinal pigment epithelium at the border of the exudative retinal changes (n=9), and vitreous haemorrhages (n=4). Tumour biopsy was performed in two cases. Treatment consisted of plaque radiotherapy (n=14), plaque radiotherapy and cryotherapy (two), cryotherapy only (two), observation (three), and enucleation in one case of a blind and painful eye. RESULTS—Regression of the tumour and the associated exudative changes could be observed in all treated cases. Visual acuity at last follow up improved two lines or more in two cases, remained within two lines of the initial visual acuity in 15 cases, and worsened in the remaining five. Histopathological examination of the biopsy specimens and the tumour of the enucleated eye showed massive capillary proliferation with perivascular spindle-shaped glial cells of retinal origin. CONCLUSION—The correct diagnosis of VPTR is of importance as these lesions may lead to visual loss. Further, VPTR must be differentiated from angiomas associated with von Hippel-Lindau disease as well as from ocular and systemic malignancies. Regression of tumour thickness and associated retinal changes can be achieved with
Morente, M M; de Alava, E; Fernandez, P L
In the last decade the technical advances in high throughput techniques to analyze DNA, RNA and proteins have had a potential major impact on prevention, diagnosis, prognosis and treatment of many human diseases. Key pieces in this process, mainly thinking about the future, are tumour banks and tumour bank networks. To face these challenges, diverse suitable models and designs can be developed. The current article presents the development of a nationwide design of tumour banks in Spain based on a network of networks, specially focusing on its harmonization efforts mainly regarding technical procedures, ethical requirements, unified quality control policy and unique sample identification. We also describe our most important goals for the next years. This model does not correspond to a central tumour bank, but to a cooperative and coordinated network of national and regional networks. Independently from the network in which it is included, sample collections reside in their original institution, where it can be used for further clinical diagnosis, teaching and research activities of each independent hospital. The herein described 'network of networks' functional model could be useful for other countries and/or international tumour bank activities.
Toh, Y F; Cheah, P L; Looi, L M; Teoh, K H; Tan, P H
Taking cognizance of the purported variation of phyllodes tumours in Asians compared with Western populations, this study looked at phyllodes tumours of the breast diagnosed at the Department of Pathology, University of Malaya Medical Centre over an 8-year period with regards to patient profiles, tumour parameters, treatment offered and outcome. Sixty-four new cases of phyllodes tumour were diagnosed during the period, however only 30 (21 benign, 4 borderline and 5 malignant) finally qualified for entry into the study. These were followed-up for 4-102 months (average = 41.7 months). Thirteen cases (8 benign, 3 borderline, 2 malignant) were Chinese, 9 (all benign) Malay, 7 (4 benign, 1 borderline, 2 malignant) Indian and 1 (malignant) Indonesian. Prevalence of benign versus combined borderline and malignant phyllodes showed a marginally significant difference (p=0.049) between the Malays and Chinese. Patients' ages ranged from 21-70 years with a mean of 44.9 years with no significant difference in age between benign, borderline or malignant phyllodes tumours. Except for benign phyllodes tumours (mean size = 5.8 cm) being significantly smaller at presentation compared with borderline (mean size = 12.5 cm) and malignant (mean size = 15.8 cm) (p<0.05) tumours, history of previous pregnancy, breast feeding, hormonal contraception and tumour laterality did not differ between the three categories. Family history of breast cancer was noted in 2 cases of benign phyllodes. Local excision was performed in 17 benign, 2 borderline and 3 malignant tumours and mastectomy in 4 benign, 2 borderline and 2 malignant tumours. Surgical clearance was not properly recorded in 10 benign phyllodes tumours. Six benign and all 4 borderline and 5 malignant tumours had clearances of <10 mm. Two benign tumours recurred locally at 15 and 49 months after local excision, however information regarding surgical clearance was not available in both cases. One patient with a malignant tumour developed
Lowe, D; Fletcher, C D; Gower, R L
Tumour eosinophilia is an uncommon but striking phenomenon which has been found in many tumours, mostly of large cell type or squamous differentiation. The incidence, appearance and importance of tumour eosinophilia in the bladder are described. Eosinophilia is commoner in deeply invasive tumours and in tumours showing squamous metaplasia. Transitional cell carcinomas with eosinophilia have a better prognosis than those without, but this improvement is not seen in squamous cell carcinomas of the bladder. When eosinophilia is found on superficial biopsies of a bladder tumour, the possibility of muscle invasion should be considered. PMID:6725595
Schalenbourg, A; Zografos, L
Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.
Li, Hui-Hui; Zhu, Hui; Liu, Li-Sheng; Huang, Yong; Guo, Jun; Li, Jie; Sun, Xin-Ping; Chang, Chun-Xiao; Wang, Zhe-Hai; Zhai, Kan
Tumour necrosis factor-α (TNF-α) is critical in the regulation of inflammation and tumour progression. TNF-α-308G > A is associated with constitutively elevated TNF-α expression. The purpose of this study was to assess the association between TNF-α-308G > A and breast cancer (BC) risk by subtype and the connection between genotypes and clinical features of BC. A total of 768 patients and 565 controls were enrolled in this study, and genotypes were detected using the TaqMan assay. No effect on susceptibility for any BC subtype was found for the TNF-α-308 polymorphism in our study or in the pooled meta-analysis. This polymorphism was shown to be associated with age at menarche in all BC and in progesterone receptor-negative BC. Interestingly, triple negative breast cancer (TNBC) patients with TNF-α-308A had an increased risk of distant tumour metastasis (OR = 3.80, 95% CI: 1.31–11.02, P = 0.009). Multi-regression analysis showed that TNF-α-308A was also a risk factor for distant tumour metastasis after adjustment for tumour size and lymph node metastasis status (OR = 6.26, 95% CI: 1.88–20.87, P = 0.003). These findings indicate that TNF-α might play a distinct role in the progression of TNBC, especially in distant tumour metastasis of TNBC. PMID:26165253
Siddiqui, T H; Amin, M R; Bashar, M A; Ahmed, Z; Matin, A; Hasan, G Z; Islam, M D; Hossain, M Z
Melanotic neuroectodermal tumour in infancy is rare, mainly benign with little tendency to recur after excision or effective curettage. This pigmented neoplasm of neural crest origin occurring in infants before 1 year of age. The most common site of occurrence is the anterior maxillary alveolar ridge (70%), following by the skull, brain and mandible. The genital organ is the most frequent extra cranial site. We report a 6 months old male baby with a similar tumour arising from right half of cheek involving the maxilla. We diagnosed the case after histological report. We remove the tumour through a sub-labial incision. The mass was blackish in colour, and was mobilized from all side including from the maxillary sinuses. The author thought that this should be reported for improving the clinical awareness and treatment of pigmented soft tissue mass in children. Almost one year follow up of the patients showed no recurrence.
Chan, D A; Giaccia, A J
Originally identified as the enzymes responsible for catalysing the oxidation of specific, conserved proline residues within hypoxia-inducible factor-1α (HIF-1α), the additional roles for the prolyl hydroxylase domain (PHD) proteins have remained elusive. Of the four identified PHD enzymes, PHD2 is considered to be the key oxygen sensor, as knockdown of PHD2 results in elevated HIF protein. Several recent studies have highlighted the importance of PHD2 in tumourigenesis. However, there is conflicting evidence as to the exact role of PHD2 in tumour angiogenesis. The divergence seems to be because of the contribution of stromal-derived PHD2, and in particular the involvement of endothelial cells, vs tumour-derived PHD2. This review summarises our current understanding of PHD2 and tumour angiogenesis, focusing on the influences of PHD2 on vascular normalisation and neovascularisation. PMID:20461086
Cove, D. H.; Woods, K. L.; Smith, S. C.; Burnett, D.; Leonard, J.; Grieve, R. J.; Howell, A.
The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers. PMID:92331
Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko
Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191
Taylor, Anthony H.; Marczylo, Timothy H.; Willets, Jonathon M.; Konje, Justin C.
The “endocannabinoid system (ECS)” comprises the endocannabinoids, the enzymes that regulate their synthesis and degradation, the prototypical cannabinoid receptors (CB1 and CB2), some noncannabinoid receptors, and an, as yet, uncharacterised transport system. Recent evidence suggests that both cannabinoid receptors are present in sex steroid hormone-dependent cancer tissues and potentially play an important role in those malignancies. Sex steroid hormones regulate the endocannabinoid system and the endocannabinoids prevent tumour development through putative protective mechanisms that prevent cell growth and migration, suggesting an important role for endocannabinoids in the regulation of sex hormone-dependent tumours and metastasis. Here, the role of the endocannabinoid system in sex steroid hormone-dependent cancers is described and the potential for novel therapies assessed. PMID:24369462
Calderón, María Del Rosario; Delgado, Elvira; García Campos, Francisco
Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients.
Ricard, Damien; Idbaih, Ahmed; Ducray, François; Lahutte, Marion; Hoang-Xuan, Khê; Delattre, Jean-Yves
Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.
Colborn, T.; Dumanoski, D.; Myers, J.P.
This article discusses the accumulating evidence that some synthetic chemicals disrupt hormones in one way or another. Some mimic estrogen and others interfere with other parts of the body`s control or endocrine system such as testosterone and thyroid metabolism. Included are PCBs, dioxins, furans, atrazine, DDT. Several short sidebars highlight areas where there are or have been particular problems.
Shen1, G. F.; Chen, Y. Z.; Ren, G. X.
In tumour hyperthermia therapy, the research on measurement and control of tumour temperature is very important. Based on the hardware platform of superficial tumour ultrasound hyperthermia therapeutic system, an improved tumour temperature measurement and control method is presented in this paper. The experiment process, data and results are discussed in detail. The improved method will greatly reduce the pain and dread of the patients during the therapy period on the tumour temperature measurement and control by using the pinhead sensor.
Goel, Vandana; Verma, Amit Kumar; Batra, Vineeta; Puri, Sunil Kumar
Wilms' tumour (nephroblastoma), the most common abdominal malignancy of childhood, occurs primarily as a malignant renal tumour. Extrarenal Wilms' tumour is rare with occasional reports from the Indian subcontinent. The various locations of extrarenal Wilms' tumour include retroperitoneum, uterus, skin and thorax. In this report we will discuss the imaging features highlighting the imaging differential diagnosis in a case of retroperitoneal (extrarenal) primary Wilms' tumour.
Zhao, Xiao-Dan; Dong, Ni; Man, Hong-Tao; Fu, Zhong-Lin; Zhang, Mei-Hong; Kou, Shuang; Ma, Shi-Liang
Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway.
Lindsten, T; Yaffe, L J; Thompson, C B; Guelde, G; Berning, A; Scher, I; Kenny, J J
Both complement receptor positive (CR+) and complement receptor negative (CR-) B cells have been shown to be involved in the primary immune response to PC-Hy (phosphocholine conjugated hemocyanin), a thymus dependent (TD) antigen which preferentially induces antibody secretion in Lyb-5+ B cells during a primary adoptive transfer assay. CR+ and CR- B cells also responded in a primary adoptive transfer assay to TNP-Ficoll, a thymus independent type 2 (TI-2) antigen which activates only Lyb-5+ B cells. When the secondary immune response to PC-Hy and TNP-Ficoll were analyzed, it was found that most of the immune memory to both antigens was present in the CR- B cell subset. The CR- B cell subset also dominated the secondary immune response to PC-Hy in immune defective (CBA/N X DBA/2N)F1 male mice. These data indicate that CR- B cells dominate the memory response in both the Lyb-5+ and Lyb-5- B cell subsets of normal and xid immune defective mice and suggest that Lyb-5+ and Lyb-5- B cells can be subdivided into CR+ and CR- subsets.
ZHAO, XIAO-DAN; DONG, NI; MAN, HONG-TAO; FU, ZHONG-LIN; ZHANG, MEI-HONG; KOU, SHUANG; MA, SHI-LIANG
Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway. PMID:24649031
Ma, Yun-Feng; Chen, Chen; Li, Dongqing; Liu, Min; Lv, Zhuang-Wei; Ji, Yanhong; Xu, Jiru
The expression of IL-17A and programmed death ligand 1 (PDL1) is increased in estrogen receptor-negative breast cancer. IL-17A promotes tumor cell survival and invasiveness and inhibits the antitumor immune response. The PDL1-PD1 (programmed death protein 1) signaling pathway promotes escape from immune surveillance in tumor cells. The pro-tumor properties of IL-17A and PDL1 in various cancers have been previously examined; however, the relationship and roles of IL-17A and PDL1 in ER-negative breast cancer have not been evaluated. Therefore, we assessed whether IL-17A promotes PDL1 expression in tumor cells and whether targeting of IL-17A could inhibit ER-negative breast cancer progression in a murine model. Our study revealed that IL-17A promoted PDL1 expression in human and mouse cells. In the murine cancer model, targeting of IL-17A inhibited PDL1 expression in the tumor microenvironment, decreased the percentage of Treg cells in tumor-infiltrating lymphocytes, and promoted CD4+ and CD8+ T cells to secrete interferon gamma. More importantly, treatment with combined anti-IL-17A and anti-PDL1 antibodies enhanced antitumor effects in favor of tumor eradication. Thus, our study established a pro-tumor role of IL-17A in promoting tumor immune escape and supports the development of a novel cytokine immunotherapy against breast cancer.
Polak, Marta E
Inflammatory cells are present in many tumours, and understanding their function is of increasing importance, particularly to studies of tumour immunology. The tumour-infiltrating leukocytes encompass a variety of cell types, e.g. T lymphocytes, macrophages, dendritic cells, NK cells, and mast cells. Choice of the isolation method greatly depends on the tumour type and the leukocyte subset of interest, but the protocol usually includes tissue disaggregation and cell enrichment. We recommend density centrifugation for initial enrichment, followed by specific magnetic bead negative or positive panning with leukocyte and tumour cell selective antibodies.
Stålberg, P; Westin, G; Thirlwell, C
Neuroendocrine tumour of the small intestine (SI-NET), formerly known as midgut carcinoid tumour, is the most common small intestinal malignancy. The incidence is rising, with recent reports of 0.67 per 100 000 in the USA and 1.12 per 100 000 in Sweden. SI-NETs often present a challenge in terms of diagnosis and treatment, as patients often have widespread disease and are beyond cure by surgery. Somatostatin analogues provide the mainstay of medical treatment to control hormonal excess and increase the time to progression. Despite overall favourable prognosis (5-year overall survival of 65%), there is a need to find markers to identify both patients with worse outcome and new targets for therapy. Loss on chromosome 18 has been reported in 60-90% of SI-NETs, but mutated genes on this chromosome have failed detection. Recently, a putative tumour suppressor role has been suggested for TCEB3C occurring at 18q21 (encoding elongin A3), which may undergo epigenetic repression. CDKN1B has recently been revealed as the only recurrently mutated gene in SI-NETs but, with a frequency as low as 8%, its role as a driver in SI-NET development may be questioned. Integrated genomewide analysis including exome and whole-genome sequencing, gene expression, DNA methylation and copy number analysis has identified three novel molecular subtypes of SI-NET with differing clinical outcome. DNA methylation analysis has demonstrated that SI-NETs have significant epigenetic dysregulation in 70-80% of tumours. In this review, we focus on understanding of the genetic, epigenetic and molecular events that lead to development and progression of SI-NETs.
Nowell, Craig S; Radtke, Freddy
The Notch signalling cascade is an evolutionarily conserved pathway that has a crucial role in regulating development and homeostasis in various tissues. The cellular processes and events that it controls are diverse, and continued investigation over recent decades has revealed how the role of Notch signalling is multifaceted and highly context dependent. Consistent with the far-reaching impact that Notch has on development and homeostasis, aberrant activity of the pathway is also linked to the initiation and progression of several malignancies, and Notch can in fact be either oncogenic or tumour suppressive depending on the tissue and cellular context. The Notch pathway therefore represents an important target for therapeutic agents designed to treat many types of cancer. In this Review, we focus on the latest developments relating specifically to the tumour-suppressor activity of Notch signalling and discuss the potential mechanisms by which Notch can inhibit carcinogenesis in various tissues. Potential therapeutic strategies aimed at restoring or augmenting Notch-mediated tumour suppression will also be highlighted.
Nano, Rosanna; Lascialfari, Alessandro; Corti, Maurizio; Paolini, Alessandro; Pasi, Francesca; Corbella, Franco; DI Liberto, Riccardo
Glioblastoma multiforme, the most common type of primary brain tumour, remains an unsolved clinical problem. A great deal of work has been done in an effort to understand the biology and genetics of glioblastoma multiforme, but clinically effective treatments remain elusive. It is well known that malignant gliomas develop resistance to chemo- and radiotherapy. In this review we evaluated the literature data regarding therapeutic progress for the treatment of astrocytic tumours, focusing our attention on new frontiers for glioblastoma. The research studies performed in in vitro and in vivo models show that the application of hyperthermia using magnetic nanoparticles is safe and could be a promising tool in the treatment of glioblastoma patients. Our efforts are focused towards new fields of research, for example nanomedicine and the study of the uptake and cytotoxic effects of magnetic nanoparticles. The improvement of the quality of life of patients, by increasing their survival rate is the best result to be pursued, since these tumours are considered as ineradicable.
Pattanayak Mohanty, Sweta; Ray, Jay Gopal; Richa; Mukherjee, Sanjit; Mandal, Chitra; Chaudhuri, Keya
Melanotic neuroectodermal tumour of infancy (MNTI) is a rare benign tumour of neural crest origin that was first described by Krompecher in 1918.1 It is predominantly found in infancy, with about 92% of cases below the age of 12 months and 82% below the age of 6 months. The predominant site of origin is in the premaxilla though it is reported at other sites also including the skull, the mandible, the epididymis and the brain.2 The lesions often have areas of bluish discolouration on the surface and are characterised by displacement of the involved tooth bud and local aggressiveness. The present report deals with two cases of MNTI, a 5-month-old baby girl and a 6-month-old baby boy who reported to the Department of Oral and Maxillofacial Pathology, Dr R Ahmed Dental College and Hospital, Kolkata, India. The clinical, radiological, histological and immunohistochemical findings, confirmed the diagnosis of MNTI. Flow cytometry was performed to analyse aneuploidy. The tumours were treated surgically with no history of recurrence to date.
Ivarsson, K; Myllymäki, L; Jansner, K; Stenram, U; Tranberg, K-G
Previous studies in our laboratory have shown that interstitial laser thermotherapy (ILT) of an experimental liver tumour is superior to surgical excision, at least partly due to a laser-induced immunological effect. The aim of the present study was to investigate the time–response relationship of the ILT-induced immunisation and the cellular response of macrophages and lymphocytes. A dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of syngeneic rats. Rats with tumour were treated 6–8 days later (tumour size 0.25–0.40 cm3) with ILT of tumour or resection of the tumour-bearing lobe. Two groups of rats without tumour were treated with resection of a normal liver lobe or ILT of normal liver. A challenging tumour was implanted into the liver of each rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days (or earlier due to their condition) after challenge (n=8 in all groups). Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and macrophages (ED1, ED2) in rats having had treatment of a primary tumour. Interstitial laser thermotherapy of the first tumour was followed by eradication of challenging tumour and absence of tumour spread. This contrasted with rapid growth and spread of challenging tumour in the other groups. In the challenging vital tumour tissue and in the interface between the tumour and surroundings, the number of ED1 macrophages and CD8 lymphocytes was higher in rats having been treated with the ILT of tumour than in those having undergone resection of the tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low and did not vary between these two groups. Interstitial laser thermotherapy elicited an immune response that eradicated a challenging tumour and was associated with increased numbers of tumour-infiltrating macrophages and CD8 lymphocytes. PMID:16091763
Walls, G V; Stevenson, M; Lines, K E; Newey, P J; Reed, A A C; Bowl, M R; Jeyabalan, J; Harding, B; Bradley, K J; Manek, S; Chen, J; Wang, P; Williams, B O; Teh, B T; Thakker, R V
The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73(+/-)) and conditional parathyroid-specific (Cdc73(+/L)/PTH-Cre and Cdc73(L/L)/PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73(+/+) and Cdc73(+/+)/PTH-Cre) littermates. Survival of Cdc73(+/-) mice, when compared to Cdc73(+/+) mice was reduced (Cdc73(+/-)=80%; Cdc73(+/+)=90% at 18 months of age, P<0.05). Cdc73(+/-), Cdc73(+/L)/PTH-Cre and Cdc73(L/L)/PTH-Cre mice developed parathyroid tumours, which had nuclear pleomorphism, fibrous septation and increased galectin-3 expression, consistent with atypical parathyroid adenomas, from 9 months of age. Parathyroid tumours in Cdc73(+/-), Cdc73(+/L)/PTH-Cre and Cdc73(L/L)/PTH-Cre mice had significantly increased proliferation, with rates >fourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73(+/-), Cdc73(+/L)/PTH-Cre and Cdc73(L/L)/PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73(+/-) mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73(+/-) mice did not develop bone or renal tumours but female Cdc73(+/-) mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73(+/-) mice
Kubota, K.; Yamada, S.; Kondo, T.; Yamada, K.; Fukuda, H.; Fujiwara, T.; Ito, M.; Ido, T.
Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours. Images Figure 1 Figure 2 PMID:8611400
Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; LiVolsi, V A; Johnson, S W
There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT–PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers. PMID:16969345
Biade, S; Marinucci, M; Schick, J; Roberts, D; Workman, G; Sage, E H; O'Dwyer, P J; Livolsi, V A; Johnson, S W
There is currently a lack of reliable diagnostic and prognostic markers for ovarian cancer. We established gene expression profiles for 120 human ovarian tumours to identify determinants of histologic subtype, grade and degree of malignancy. Unsupervised cluster analysis of the most variable set of expression data resulted in three major tumour groups. One consisted predominantly of benign tumours, one contained mostly malignant tumours, and one was comprised of a mixture of borderline and malignant tumours. Using two supervised approaches, we identified a set of genes that distinguished the benign, borderline and malignant phenotypes. These algorithms were unable to establish profiles for histologic subtype or grade. To validate these findings, the expression of 21 candidate genes selected from these analyses was measured by quantitative RT-PCR using an independent set of tumour samples. Hierarchical clustering of these data resulted in two major groups, one benign and one malignant, with the borderline tumours interspersed between the two groups. These results indicate that borderline ovarian tumours may be classified as either benign or malignant, and that this classifier could be useful for predicting the clinical course of borderline tumours. Immunohistochemical analysis also demonstrated increased expression of CD24 antigen in malignant versus benign tumour tissue. The data that we have generated will contribute to a growing body of expression data that more accurately define the biologic and clinical characteristics of ovarian cancers.
Chaurasia, Jai Kumar; Afroz, Nishat; Maheshwari, Veena; Naim, Mohammed
A 7-year-old Indian girl presented with symptoms of excessive development of breasts, early menarche, growth of pubic hairs, accelerated growth and abdominal distension. On clinical examination, a large right abdominopelvic mass was palpable. MRI revealed a large, heterogeneous, solid and cystic tumour in the right adnexal region, suggestive of an ovarian neoplasm. The hormonal profile showed markedly elevated oestradiol and low follicle-stimulating hormone levels. Clinical diagnosis of precocious puberty with right ovarian mass was concluded. Right-sided salpingo-oophorectomy was performed. Histopathology showed features consistent with sclerosing stromal tumour of the ovary. Postoperatively, signs and symptoms of precocity gradually regressed and her serum oestradiol level came down to normal. This is the first reported case from India.
Halttunen, P; Meurala, H; Standertskjöld-Nordenstam, C-G
Four cases of benign endobronchial tumour are reported which were successfully treated by bronchial resection. In two cases (of fibroma and leiomyoma respectively) a cylinder of bronchus alone was resected; in one case (lipoma) a healthy right upper lobe was preserved by a bronchoplastic procedure and in the other (chondroma) the tumour was removed with the right lower lobe, which was irreversibly damaged. It is important to recognise that such tumours are unsuitable for treatment by endoscopic means alone. Images PMID:7157223
Bloomer, Steven A; Brown, Kyle E
Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver.
Popiel, M; Gulie, L; Turculeţ, C; Beuran, M
First transcatheter embolization of hepatic artery has been materializing in 1974, in France, for unresectable hepatic tumours. Then, this treatment has become use enough in many countries, especially in Japan, where primary hepatic tumours are very frequent. In this article, we present procedures of interventional endovascular treatment for primary hepatic tumours: chemoembolization, intra–arterial chemotherapy. The study comprises patients with primary hepatic tumours investigated by hepatic–ultrasound and contrast–enhanced CT or MRI. DSA–hepatic angiography is very important to verify the accessory hepatic supply. It has been performed selective catheterization of right/left hepatic branches followed by cytostatics injection. Most of the patients have benefit by hepatic chemoembolization (cytostatics, Lipiodol and embolic materials). The selective intra–arterial chemotherapy (cytostatics without Lipiodol) was performing in cases with contraindications for Lipiodol or embolic materials injection (cirrhosis–Child C, thrombosis of portal vein, hepatic insufficiency). For treatment of primary hepatic tumours we use 5–F–Uracil, Farmarubicin and Mytomicin C. Less numbers of the reservoirs were placed because financial causes. Chemoembolization was better than procedures without Lipiodol or embolic materials. Lipiodol reached in tumoural tissue and the distribution of Lipiodol harmonises with degree of vascularisation. After the chemoembolization procedure, the diameter of tumours decreased gradually depending on the size of tumour. Effective alternative for unresectable primary hepatic tumours (big size, hepatic dysfunction, and other surgical risk factors) is endovascular interventional treatment. PMID:20108517
Head, K. W.
Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147
Clarke, T J
The histogenesis of ovarian malignant mixed mesodermal tumours, which includes the concept of metaplastic carcinoma, is controversial. Four such tumours were examined for evidence of metaplastic transition from carcinoma to sarcoma using morphology and reticulin stains. Consecutive sections were stained immunohistochemically using cytokeratin and vimentin to determine whether cells at the interface between carcinoma and sarcoma expressed both cytokeratin and vimentin. There was no evidence of morphological, architectural, or immunohistochemical transitions from carcinoma to sarcoma in the four tumours studied. This suggests that ovarian malignant mixed mesodermal tumours are not metaplastic carcinomas but are composed of histogenetically different elements. Images PMID:2160478
Harvey, Philip W; Everett, David J
This issue of Journal of Applied Toxicology publishes the paper Concentrations of Parabens in Human Breast Tumours by Darbre et al. (2004), which reports that esters of p-hydroxybenzoic acid (parabens) can be detected in samples of tissue from human breast tumours. Breast tumour samples were supplied from 20 patients, in collaboration with the Edinburgh Breast Unit Research Group, and analysed by high-pressure liquid chromatography and tandem mass spectrometry. The parabens are used as antimicrobial preservatives in underarm deodorants and antiperspirants and in a wide range of other consumer products. The parabens also have inherent oestrogenic and other hormone related activity (increased progesterone receptor gene expression). As oestrogen is a major aetiological factor in the growth and development of the majority of human breast cancers, it has been previously suggested by Darbre that parabens and other chemicals in underarm cosmetics may contribute to the rising incidence of breast cancer. The significance of the finding of parabens in tumour samples is discussed here in terms of 1). Darbre et al's study design, 2). what can be inferred from this type of data (and what can not, such as the cause of these tumours), 3). the toxicology of these compounds and 4). the limitations of the existing toxicology database and the need to consider data that is appropriate to human exposures.
Burón Pust, Andrea; Alison, Rupert; Blanks, Roger; Pirie, Kirstin; Gaitskell, Kezia; Barnes, Isobel; Gathani, Toral; Reeves, Gillian; Beral, Valerie
Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK‐based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow‐up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types. PMID:27859268
Kjersem, Bård; Krohn, Jørgen
The purpose of this paper is to discuss a recently described modification of a standard photo slit lamp system for ocular transillumination, with special emphasis on the light transmission through the eye wall and the photographic technique. Transillumination photography was carried out with the Haag-Streit Photo-Slit Lamp BX 900 (Haag-Streit AG, Koeniz, Switzerland). After having released the background lighting optic fibre cable from its holder, the patient was positioned at the slit lamp, and the fibre tip was gently pressed against the sclera or the cornea of the patient's eye. During about 1/1000 of a second, the eye was illuminated by the flash and the scleral shadow of the tumour was exposed to the camera sensor. The images were of good diagnostic quality, making it easy to outline the tumours and to evaluate the involvement of intraocular structures. None of the examined patients experienced discomfort or negative side effects. The method is recommended in cases where photographic transillumination documentation of intraocular pathologies is considered important.
Somerhausen, Nicolas De Saint Aubain
Purpose. To study the evolution of concepts concerning gastrointestinal stromal tumours (GISTs) over 30 years. Discussion. GISTs have been, for more than 30 years, the subject of considerable controversy regarding their line of differentiation as well as the prediction of their behaviour. Furthermore, once they spread within the peritoneal cavity, they are extremely hard to control. The recent findings of c-Kit mutations and the immunohistochemical detection of the product of this gene, KIT or CD117, in the mainly non-myogenic subset of this family of tumours, has led to a reappraisal of this group of lesions, which, with some exceptions, is now thought to be derived from the interstitial cells of Cajal, and this has facilitated a clearer definition of their pathological spectrum. In this article, we review chronologically the evolution of the concept of GIST with the gradual application of electron microscopy, immunohistochemistry, DNA ploidy analysis. We discuss the impact of these techniques on the pathological assessment and clinical management of GISTs. PMID:18521245
Li, Christopher I; Daling, Janet R; Porter, Peggy L; Tang, Mei-Tzu C; Malone, Kathleen E
Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor-negative contralateral tumors. We conducted a population-based nested case-control study including 367 women diagnosed with both first primary estrogen receptor (ER)-positive invasive breast cancer and second primary contralateral breast cancer and 728 matched control women diagnosed only with a first breast cancer. Data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors were ascertained through telephone interviews and medical record abstractions. Two-sided statistical tests using conditional logistic regression were conducted to quantify associations between adjuvant hormonal therapy and risk of hormone receptor-specific subtypes of contralateral breast cancer (n = 303 ER+ and n = 52 ER- cases). Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for >or=5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3-0.7], but a 4.4-fold (95% CI, 1.03-19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5 years was not associated with ER- contralateral breast cancer risk. Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER- contralateral breast cancer may now need to be tallied among its risks. This is of clinical concern given the poorer prognosis of ER- compared with ER+ tumors.
Khan, Muhammad Babar; Soares, Delvene; Tahir, Muhammad Zubair; Kumar, Rajesh; Minhas, Khurram; Bari, Muhammad Ehsan
Melanotic neuroectodermal tumour of infancy is a rare, mostly benign but locally aggressive tumour of neural crest cell origin occurring in infants. The most commonly affected anatomic site is the maxilla. Such tumours of the brain and skull are very rare. We present the case of an 8 months old baby girl whose presenting complaint was a swelling in the scalp for 6 months. She was otherwise asymptomatic. CT imaging confirmed the presence of an osteolytic tumour in the anterior parasagittal skull with dural involvement. The tumour was surgically excised enbloc. The patient has been well at 2 years follow-up without any evidence of recurrence.
HRT - deciding; Estrogen replacement therapy - deciding; ERT- deciding; Hormone replacement therapy - deciding; Menopause - deciding; HT - deciding; Menopausal hormone therapy - deciding; MHT - deciding
Van de Wiele, Christophe
Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637
Dilman, V. M.; Berstein, L. M.; Ostroumova, M. N.; Tsyrlina, Y. V.; Golubev, A. G.
The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer). PMID:7248149
Cole, I E; Keene, Malcolm
Three cases of CSF rhinorrhoea due to pituitary tumours are reported and the literature reviewed. The treatment of choice appears to be trans-sphenoidal exploration of the pituitary fossa with insertion of a free muscle graft followed by radiotherapy. The probability of the tumour being a prolactin-secreting adenoma is discussed. PMID:7017123
Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica
Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach.
Philipsen, Hans Peter; Reichart, Peter A
Using the term odontome for any tumour arising from the dental formative tissues, Broca suggested a classification of odontogenic tumours (OTs) in 1869. From 1888 to 1914, Bland-Sutton and Gabell, James and Payne modified tumour terminology, while maintaining Broca's odontome concept. Thoma and Goldman's classification (1946) divided the OTs into tumours of ectodermal, mesodermal and mixed origin and abolished the general term odontome. The Pindborg and Clausen classification (1958) based on the idea that the reciprocal epithelial-mesenchymal tissue interactions were also operating in the pathogenesis of OTs. In 1966, WHO established a Collaborating Centre for the Histological Classification of Odontogenic Tumours and Allied Lesions (including jaw cysts) headed by Dr Jens Pindborg. In 1971, the first authoritative WHO guide to the classification of OTs and cysts appeared followed in 1992 by a second edition. In 2002, Philipsen and Reichart produced a revision of the 1992-edition and in 2003, the editors of the WHO Blue Book series: 'WHO Classification of Tumours' decided to produce a volume on the Head and Neck Tumours including a chapter on Odontogenic Tumours and Bone Related Lesions. In July of 2005 this volume was published by IARC, Lyon.
The heterogeneity of tumours is now beginning to be documented precisely by single-cell new-generation sequencing. Recently published results on breast tumours show that each of the cells analysed displays a unique pattern of point mutations. This extensive genetic diversity is present before any treatment, and is likely to cause resistance to initially successful targeted therapies.
Bartz, C; Ziske, C; Wiedenmann, B; Moelling, K
Neuroendocrine pancreatic tumours grow slower and metastasise later than ductal and acinar carcinomas. The expression of the p53 tumour suppressor gene in pancreatic neuroendocrine tumour cells is unknown. Pancreatic neuroendocrine cell lines (n = 5) and human tumour tissues (n = 19) were studied for changed p53 coding sequence, transcription, and translation. Proliferative activity of tumour cells was determined analysing Ki-67 expression. No mutation in the p53 nucleotide sequence of neuroendocrine tumour cell was found. However, an overexpression of p53 could be detected in neuroendocrine pancreatic tumour cell lines at a protein level. As no p53 mutations were seen, it is suggested that post-translational events can also lead to an overexpression of p53. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8675094
Mammary tumours are the most common tumours in the female dog. The tumours have a complex histology and exist in epithelial, mixed and mesenchymal forms. To study the biology of canine mammary tumours, five cell lines have been established and characterized. The results indicate that canine mammary tumours might be derived from mammary stem cells and that the tumour growth is independent of oestrogens. The established canine mammary tumour cell lines will be valuable tools in further studies of the histogenesis and pathogenesis of these tumours.
Modi, Sunny; Tiang, Kor Woi; Inglis, Po; Collins, Stuart
Wilms' tumour (nephroblastoma) is the most common renal tumour in children. Wilms' tumour in adults is extremely rare and has a poorer prognosis than paediatric Wilms' tumour. It is difficult to differentiate adult Wilms' tumour from renal cell carcinoma based on radiological findings alone. The diagnosis in adults is often serendipitous following nephrectomy for presumed renal cell carcinoma. Because of the paucity of literature, there are no standard protocols for the management of adult Wilms' tumour, and therefore, it is managed as per paediatric Wilms' tumour. Herein, we report the case of adult Wilms' tumour in a 43-year-old man, which was diagnosed unexpectedly following nephrectomy for presumed renal cell carcinoma.
Roque, Pedro; Mankin, Henry J; Rosenberg, Andrew
Adamantinoma is a rare tumour, which most often affects the tibia and produces lytic and sometimes destructive lesions, which can cause fractures. The lesions occur principally in adults and are more common in males. A small percentage of the patients develop metastases, sometimes quite late in the course. Our institution has treated 42 patients with adamantinomas since 1972 and has evaluated them by imaging studies and histology. The majority of the patients were treated by resection of the lesion and insertion of an intercalary allograft. Only three of the patients died of disease with the time until death ranging from 10 to 17 years. Recurrence occurred in only three patients and the allograft success rate in terms of function was 71% at a mean time of 10 years.
Karaca, P; Desailloud, R
Because of antidiuretic hormone (ADH) disorder on production or function we can observe dysnatremia. In the absence of production by posterior pituitary, central diabetes insipidus (DI) occurs with hypernatremia. There are hereditary autosomal dominant, autosomal recessive or X- linked forms. When ADH is secreted but there is an alteration on his receptor AVPR2, it is a nephrogenic diabetes insipidus in acquired or hereditary form. We can make difference on AVP levels and/or on desmopressine response which is negative in nephrogenic forms. Hyponatremia occurs when there is an excess of ADH production: it is a euvolemic hypoosmolar hyponatremia. The most frequent etiology is SIADH (syndrome of inappropriate secretion of ADH), a diagnostic of exclusion which is made after eliminating corticotropin deficiency and hypothyroidism. In case of brain injury the differential diagnosis of cerebral salt wasting (CSW) syndrome has to be discussed, because its treatment is perfusion of isotonic saline whereas in SIADH, the treatment consists in administration of hypertonic saline if hyponatremia is acute and/or severe. If not, fluid restriction demeclocycline or vaptans (antagonists of V2 receptors) can be used in some European countries. Four types of SIADH exist; 10 % of cases represent not SIADH but SIAD (syndrome of inappropriate antidiuresis) due to a constitutive activation of vasopressin receptor that produces water excess. c 2013 Published by Elsevier Masson SAS.
Cardoso, José C; Calonje, Eduardo
Cutaneous adnexal tumours can be a diagnostic challenge for the pathologist. This is particularly true in the case of tumours with sweat gland differentiation, due to a large number of rare entities, a multiplicity of names to designate the same neoplasms and consequent lack of consensus regarding their classification and nomenclature. In the traditional view, sweat gland tumours were divided into eccrine and apocrine. However, this has been challenged in recent years, and in fact many of these tumours may have both eccrine and apocrine variants. Some display more complex features and defy classification, due to the presence of other lines of differentiation, namely follicular and/or sebaceous (in the case of apocrine tumours, due to the close embryological relationship between apocrine glands, hair follicles and sebaceous glands). The present paper reviews and updates the basic concepts regarding the following malignant sweat gland tumours: apocrine carcinoma, porocarcinoma, hidradenocarcinoma, spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and related entities, squamoid eccrine ductal carcinoma, digital papillary adenocarcinoma, primary cutaneous mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma and primary cutaneous signet ring cell carcinoma. Particular emphasis is put in recent findings that may have implications in the diagnosis and management of these tumours.
Szilágyi, Tünde; Brady, Michael; Berényi, Ervin
Computer Aided Diagnostic (CAD) systems are already of proven value in healthcare, especially for surgical planning, nevertheless much remains to be done. Gliomas are the most common brain tumours (70%) in adults, with a survival time of just 2-3 months if detected at WHO grades III or higher. Such tumours are extremely variable, necessitating multi-modal Magnetic Resonance Images (MRI). The use of Gadolinium-based contrast agents is only relevant at later stages of the disease where it highlights the enhancing rim of the tumour. Currently, there is no single accepted method that can be used as a reference. There are three main challenges with such images: to decide whether there is tumour present and is so localize it; to construct a mask that separates healthy and diseased tissue; and to differentiate between the tumour core and the surrounding oedema. This paper presents two contributions. First, we develop tumour seed selection based on multiscale multi-modal texture feature vectors. Second, we develop a method based on a local phase congruency based feature map to drive level-set segmentation. The segmentations achieved with our method are more accurate than previously presented methods, particularly for challenging low grade tumours.
Ribba, Benjamin; Watkin, Emmanuel; Tod, Michel; Girard, Pascal; Grenier, Emmanuel; You, Benoît; Giraudo, Enrico; Freyer, Gilles
Optimising the delivery of antiangiogenic drugs requires the development of drug-disease models of vascular tumour growth that incorporate histological data indicative of cytostatic action. In this study, we formulated a model to analyse the dynamics of tumour progression in nude mice xenografted with HT29 or HCT116 colorectal cancer cells. In 30 mice, tumour size was periodically measured, and percentages of hypoxic and necrotic tissue were assessed using immunohistochemistry techniques on tumour samples after euthanasia. The simultaneous analysis of histological data together with longitudinal tumour size data prompted the development of a semi-mechanistic model integrating random effects of parameters. In this model, the peripheral non-hypoxic tissue proliferates according to a generalised-logistic equation where the maximal tumour size is represented by a variable called 'carrying capacity'. The ratio of the whole tumour size to the carrying capacity was used to define the hypoxic stress. As this stress increases, non-hypoxic tissue turns hypoxic. Hypoxic tissue does not stop proliferating, but hypoxia constitutes a transient stage before the tissue becomes necrotic. As the tumour grows, the carrying capacity increases owing to the process of angiogenesis. The model is shown to correctly predict tumour growth dynamics as well as percentages of necrotic and hypoxic tissues within the tumour. We show how the model can be used as a theoretical tool to investigate the effects of antiangiogenic treatments on tumour growth. This model provides a tool to analyse tumour size data in combination with histological biomarkers such as the percentages of hypoxic and necrotic tissue and is shown to be useful for gaining insight into the effects of antiangiogenic drugs on tumour growth and composition.
Kumar, Pratap; Sharma, Alok
Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) analogs induces both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Pituitary gonadotropin secretions are blocked upon desensitization when a continuous GnRH stimulus is provided by means of an agonist or when the pituitary receptors are occupied with a competitive antagonist. GnRH antagonists were not available originally; therefore, prolonged daily injections of agonist with its desensitizing effect were used. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge and thus to cause desensitization. This review provides an overview of the use of GnRH analogs which is potent therapeutic agents that are considerably useful in a variety of clinical indications from the past to the future with some limitations. These indications include management of endometriosis, uterine leiomyomas, hirsutism, dysfunctional uterine bleeding, premenstrual syndrome, assisted reproduction, and some hormone-dependent tumours, other than ovulation induction.
D'Onofrio, Mirko; Crosara, Stefano; Dal Corso, Flavia; Barbi, Emilio; Canestrini, Stefano; Mucelli, Roberto Pozzi
Abstract Indication/purpose: To review contrast‐enhanced ultrasound features of the most common pancreatic tumours. Methods: Contrast‐enhanced ultrasound (CEUS) can provide distinctive features of pancreatic tumours that are reported in the present paper, providing radiologic‐pathological correlations and clarifying the main differential diagnosis. Conclusion: Contrast‐enhanced ultrasound plays a well‐established role in the evaluation of pancreatic tumours. When possible, CEUS should be always performed after the initial US diagnosis, in order to improve the accuracy of the first line examination. PMID:28191218
Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.
Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636
Durmus, K; Apuhan, T; Ozer, E
The retromolar trigone is a challenging transoral surgical site due to the difficulty of visualization. Our aim is to report a new technique of transoral robotic resection of retromolar trigone tumours. We present three patients with retromolar trigone tumours with pathological diagnosis of squamous cell carcinoma who underwent successful transoral robotic resection. Robotic retromolar trigone resection and concurrent supraomohyoid neck dissections were performed in all patients without any complication. In conclusion, transoral robotic surgery is a safe and feasible technique for resection of malignant retromolar trigone tumours with minimal complications and favourable outcomes.
Gill, Roop Ms; Mehra, Vedika; Milford, Emma; Dhoot, Gurtej K
The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling.
Hermes, Robert; Schwarzenberger, Franz; Göritz, Frank; Oh, Serena; Fernandes, Teresa; Bernardino, Rui; Leclerc, Antoine; Greunz, Eva; Mathew, Abraham; Forsyth, Sarah; Saragusty, Joseph; Hildebrandt, Thomas Bernd
Reproductive tract tumours, specifically leiomyoma, are commonly found in female rhinoceroses. Similar to humans, tumour growth in rhinoceroses is thought to be sex hormone dependent. Tumours can form and expand from the onset of ovarian activity at puberty until the cessation of sex-steroid influences at senescence. Extensive tumour growth results in infertility. The aim of this study was to down regulate reproductive function of tumour-diseased and infertile females to stop further tumour growth using a Gonadotropin releasing factor (GnRF) vaccine. Four infertile southern white (Ceratotherium simum simum) and three Greater one-horned rhinoceroses (rhinoceros unicornis) with active ovaries and 2.7 ± 0.9 and 14.0 ± 1.5 reproductive tract tumours respectively were vaccinated against GnRF (Improvac®, Zoetis, Germany) at 0, 4 and 16 weeks and re-boostered every 6–8 months thereafter. After GnRF vaccination ovarian and luteal activity was suppressed in all treated females. Three months after vaccination the size of the ovaries, the number of follicles and the size of the largest follicle were significantly reduced (P<0.03). Reproductive tract tumours decreased significantly in diameter (Greater-one horned rhino: P<0.0001; white rhino: P<0.01), presumably as a result of reduced sex-steroid influence. The calculated tumour volumes were reduced by 50.8 ± 10.9% in Greater one-horned and 48.6 ± 12.9% in white rhinoceroses. In conclusion, GnRF vaccine effectively down regulated reproductive function and decreased the size of reproductive tract tumours in female rhinoceros. Our work is the first to use down regulation of reproductive function as a symptomatic treatment against benign reproductive tumour disease in a wildlife species. Nonetheless, full reversibility and rhinoceros fertility following GnRF vaccination warrants further evaluation. PMID:27403662
Kwiecien, Renata; Robert, Christophe; Cannon, Robert; Vigues, Stephan; Arnoux, Annie; Kordon, Claude; Hammond, Constance
Cells derived from a rat pituitary tumour (GC cell line) that continuously release growth hormone behave as endogenous pacemakers. In simultaneous patch clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they displayed rhythmic action potentials (44.7 ± 2.7 mV, 178 ± 40 ms, 0.30 ± 0.04 Hz) and concomitant [Ca2+]i transients (374 ± 57 nM, 1.0 ± 0.2 s, 0.27 ± 0.03 Hz). Action potentials and [Ca2+]i transients were reversibly blocked by removal of external Ca2+, addition of nifedipine (1 μM) or Ni2+ (40 μM), but were insensitive to TTX (1 μM). An L-type Ca2+ current activated at -33.6 ± 0.4 mV (holding potential (Vh), −40 mV), peaked at -1.8 ± 1.3 mV, was reduced by nifedipine and enhanced by S-(+)-SDZ 202 791. A T/R-type Ca2+ current activated at -41.7 ± 2.7 mV (Vh, -80 or -60 mV), peaked at -9.2 ± 3.0 mV, was reduced by low concentrations of Ni2+ (40 μM) or Cd2+ (10 μM) and was toxin resistant. Parallel experiments revealed the expression of the class E calcium channel α1-subunit mRNA. The K+ channel blockers TEA (25 mM) and charybdotoxin (10–100 nM) enhanced spike amplitude and/or duration. Apamin (100 nM) also strongly reduced the after-spike hyperpolarization. The outward K+ tail current evoked by a depolarizing step that mimicked an action potential reversed at −69.8 ± 0.3 mV, presented two components, lasted 2–3 s and was totally blocked by Cd2+ (400 μM). The slow pacemaker depolarization (3.5 ± 0.4 s) that separated consecutive spikes corresponded to a 2- to 3-fold increase in membrane resistance, was strongly Na+ sensitive but TTX insensitive. Computer simulations showed that pacemaker activity can be reproduced by a minimum of six currents: an L-type Ca2+ current underlies the rising phase of action potentials that are repolarized by a delayed rectifier and Ca2+-activated K+ currents. In between spikes, the decay of Ca2+-activated K+ currents and a persistent inward cationic current depolarize the membrane
Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.
Radermacher, J; Burlet, O; Sylvestre, R M; Wetz, P; Delvenne, Ph
A 28 year old woman has suffered over the previous month from a post-traumatic swelling sensation of the left breast. Ultrasonography demonstrates a 9 cm, sharply-cut, rounded, hypo-echogenic lesion. Surgery is performed, with the hypothesis of an haematoma. The pathological analysis of the lesion shows a malignant phyllodes tumour with heterologous rhabdomyosarcomatous features. No metastasis is found. A radical mastectomy is performed and the patient benefits from an adjuvant radio-chemotherapy. Phyllodes tumours represent up to 1 % of all mammary cancers, with 10-20 % of malignant lesions. These tumours behave differently from usual breast cancers. This atypical case, arising in a traumatic context, provides the opportunity to discuss the treatment and classification of phyllodes tumours of the breast.
Junginger, J; Röthlisberger, A; Lehmbecker, A; Stein, V M; Ludwig, D C; Baumgärtner, W; Seehusen, F
A 1-year-old German shepherd dog was presented with paraparesis quickly progressing to paraplegia. Magnetic resonance imaging revealed a large mass beneath the thoracolumbar vertebral column infiltrating the spinal canal and resulting in severe extradural compression of the spinal cord. Microscopically, this comprised a cell-rich unencapsulated tumour supported by fine bands of a fibrovascular stroma and occasionally forming primitive rosettes. Immunohistochemistry showed the tumour cells to express synaptophysin and neuron-specific enolase. Ultrastructurally, the neoplastic cells had low to moderate numbers of intracytoplasmic neurosecretory granules. A peripheral primitive neuroectodermal tumour was diagnosed. This is a rare embryonal tumour of neural origin that may have arisen from adrenal medulla, autonomic ganglia or peripheral nerves.
MacDonald-Jankowski, D S
Objectives The aim of this review is to evaluate the principal clinical and conventional radiographic features of non-syndromic keratocystic odontogenic tumour (KCOT) by systematic review (SR), and to compare the frequencies between four global groups. Methods The databases searched were the PubMed interface of Medline and LILACS. Only those reports of KCOTs that occurred in a series of consecutive cases, in the reporting authors' caseload, were considered. Results 51 reports, of 49 series of cases, were included in the SR. 11 SR-included series were in languages other than English. KCOTs affected males more frequently and were three times more prevalent in the mandible. Although the mean age at first presentation was 37 years, the largest proportion of cases first presented in the third decade. The main symptom was swelling. Over a third were found incidentally. Nearly two-thirds displayed buccolingual expansion. Over a quarter of cases recurred. Only a quarter of all SR-included reported series of cases included details of at least one radiological feature. The East Asian global group presented significantly as well-defined, even corticated, multilocular radiolucencies with buccolingual expansion. The KCOTs affecting the Western global group significantly displayed an association with unerupted teeth. Conclusions Long-term follow-up of large series that would have revealed detailed radiographic description and long-term outcomes of non-syndromic KCOT was lacking. PMID:21159911
Dev, DP Arul; Michael, Manoj Joseph; Akhilesh, AV; Das, Bindu
Calcifying Epithelial Odontogenic Tumour (CEOT) or Pindborg tumour is a rare odontogenic tumour of epithelial origin. They constitute less than 1% of odontogenic tumours. Intra-ossseous variant of CEOT are more common compared to extra-osseous variant. Although benign, these can exhibit deceptively aggressive presentation. Here we report a rare case of CEOT in a 36-year-old female patient who presented with aggressive intra-osseous lesion with cortical breach and exuberant soft tissue proliferation. The lesion was treated with resection and reconstructed with titanium reconstruction plate. PMID:27790590
Verma, Ritu; Singhal, Mitali; Pandey, Rakesh
Primitive neuroectodermal tumour (PNET) is a neural crest tumour derived from neuroectoderm. Renal PNET is a very rare tumour occurring during childhood or adolescence. We report two cases of PNET involving kidney in adults. Presenting signs and symptoms include abdominal/flank pain and/or haematuria. Microscopy reveals the tumour consisted of small round cells with round nuclei and scant cytoplasm. Diagnosis was confirmed by immunohistochemistry with diffuse membranous positivity of tumour cells with CD99. As these tumours have an aggressive clinical course with rapid death in many reported cases, it is important to differentiate them from other small round-cell tumours.
Lammers, T; Hennink, W E; Storm, G
Drug targeting systems are nanometre-sized carrier materials designed for improving the biodistribution of systemically applied (chemo)therapeutics. Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents. Here, we briefly summarise the most important targeting systems and strategies, and discuss recent advances and future directions in the development of tumour-targeted nanomedicines. PMID:18648371
Frascoli, Federico; Kim, Peter S; Hughes, Barry D; Landman, Kerry A
A coupled ordinary differential equation model of tumour-immune dynamics is presented and analysed. The model accounts for biological and clinical factors which regulate the interaction rates of cytotoxic T lymphocytes on the surface of the tumour mass. A phase plane analysis demonstrates that competition between tumour cells and lymphocytes can result in tumour eradication, perpetual oscillations, or unbounded solutions. To investigate the dependence of the dynamic behaviour on model parameters, the equations are solved analytically and conditions for unbounded versus bounded solutions are discussed. An analytic characterisation of the basin of attraction for oscillatory orbits is given. It is also shown that the tumour shape, characterised by a surface area to volume scaling factor, influences the size of the basin, with significant consequences for therapy design. The findings reveal that the tumour volume must surpass a threshold size that depends on lymphocyte parameters for the cancer to be completely eliminated. A semi-analytic procedure to calculate oscillation periods and determine their sensitivity to model parameters is also presented. Numerical results show that the period of oscillations exhibits notable nonlinear dependence on biologically relevant conditions.
Diamond, T.; Danton, M. H.; Parks, T. G.
Neoplasms arising from smooth muscle of the gastrointestinal (GI) tract are uncommon, comprising only 1% of gastrointestinal tumours. A total of 51 cases of smooth muscle tumour of the GI tract were analysed; 44 leiomyomas and 7 leiomyosarcomas. Lesions occurred in all areas from the oesophagus to the rectum, the stomach being the commonest site. Thirty-six patients had clinical features referable to the tumour. The tumour was detected during investigation or management of an unrelated disease process in 15 patients. The clinical presentation varied depending on tumour location, but abdominal pain and GI bleeding were the commonest presenting symptoms. The lesion was demonstrated preoperatively, mainly by endoscopy and barium studies, in 27 patients. Surgical excision was the treatment of choice, where possible. There was no recurrence in the leiomyoma group but four patients died in the leiomyosarcoma group. Although rare, smooth muscle tumours should be considered in situations where clinical presentation and investigations are not suggestive of any common GI disorder. The preoperative assessment and diagnosis is difficult because of the variability in clinical features and their inaccessibility to routine GI investigation. It is recommended that, where possible, the lesion, whether symptomatic or discovered incidentally, should be excised completely to achieve a cure and prevent future complications. Images Figure 3 Figure 4 PMID:2221768
Standardization of hormone determinations is important because it simplifies interpretation of results and facilitates the use of common reference values for different assays. Progress in standardization has been achieved through the introduction of more homogeneous hormone standards for peptide and protein hormones. However, many automated methods for determinations of steroid hormones do not provide satisfactory result. Isotope dilution-mass spectrometry (ID-MS) has been used to establish reference methods for steroid hormone determinations and is now increasingly used for routine determinations of steroids and other low molecular weight compounds. Reference methods for protein hormones based on MS are being developed and these promise to improve standardization.
Fritsche, E; Hug, U; Winterholer, D
Phyllodes tumours of the breast are rare occurrences, but they can reach huge dimensions. Descriptions of tumours whereby the women are immobilised as a consequence of the size of the tumour, are hard to find in the literature. In this presentation we show a case of a woman in otherwise healthy condition with a giant phyllodes tumour of her left breast. Because of the weight of the tumour, the patient could not leave her bed for more than 6 months.
Putta, Tharani; Gibikote, Sridhar; Madhuri, Vrisha; Walter, Noel
Summary Background It is imperative that bone tumour margin and extent of tumour involvement are accurately assessed pre-operatively in order for the surgeon to attain a safe surgical margin. In this study, we comprehensively assessed each of the findings that influence surgical planning, on various MRI sequences and compared them with the gold standard – pathology. Material/Methods In this prospective study including 21 patients with extremity bone tumours, margins as seen on various MRI sequences (T1, T2, STIR, DWI, post-gadolinium T1 FS) were measured and biopsies were obtained from each of these sites during the surgical resection. The resected tumour specimen and individual biopsy samples were studied to assess the true tumour margin. Margins on each of the MRI sequences were then compared with the gold standard – pathology. In addition to the intramedullary tumour margin, we also assessed the extent of soft tissue component, neurovascular bundle involvement, epiphyseal and joint involvement, and the presence or absence of skip lesions. Results T1-weighted imaging was the best sequence to measure tumour margin without resulting in clinically significant underestimation or overestimation of the tumour extent (mean difference of 0.8 mm; 95% confidence interval between −0.9 mm to 2.5 mm; inter-class correlation coefficient of 0.998). STIR and T1 FS post-gadolinium imaging grossly overestimated tumour extent by an average of 16.7 mm and 16.8 mm, respectively (P values <0.05). Post-gadolinium imaging was better to assess joint involvement while T1 and STIR were the best to assess epiphyseal involvement. Conclusions T1-weighted imaging was the best sequence to assess longitudinal intramedullary tumour extent. We suggest that osteotomy plane 1.5 cm beyond the T1 tumour margin is safe and also limits unwarranted surgical bone loss. However, this needs to be prospectively proven with a larger sample size. PMID:28058070
Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to
... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... to hormones! Download our Free App! Understand the endocrine system and its related conditions with our 3D Patient ...
... dosage of the medicine. Serious side effects of growth hormone treatment are rare. Common side effects include: Headache Fluid ... years. The rate of growth then slowly decreases. Growth hormone therapy does not work for all children. Left untreated, ...
... Balance › Hormones and Obesity Fact Sheet Hormones and Obesity March, 2010 Download PDFs English Espanol Editors Caroline Apovian, MD Judith Korner, MD, PhD What is obesity? Obesity is a chronic (long-term) medical problem ...
Rasul, Fahid Tariq; Jaunmuktane, Zane; Khan, Akbar Ali; Phadke, Rahul; Powell, Michael
Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.
Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.
It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.
Gorman, N T
There are many clinical presentations of neoplastic disease in the dog and cat. Some relate to the presence of a solid mass but many relate to the systemic effect that the tumour has on the animal. This paper covers the broad categories of the systemic metabolic and haematological effects that are associated with tumours in the dog and cat.
Thyroid hormone resistance syndromes are a group of genetic conditions characterized by decreased tissue sensitivity to thyroid hormones. Three syndromes, in which resistance to hormone action is respectively due to mutations in the gene encoding for thyroid hormone receptor TRβ, impaired T4 and T3 transport, and impaired conversion of T4 to T3 mediated by deiodinases. An updated review of each of these forms of resistance is provided, and their pathogenetic mechanisms and clinical approaches are discussed.
Trost, M E; Inkelmann, M A; Galiza, G J N; Silva, T M; Kommers, G D
The skeletons of 110 dogs with malignant tumours of different origins were examined by necropsy examination over a 3-year period to identify bone metastases. Twenty-one cases of metastatic or multicentric tumours with bone involvement were recorded. In general, more female dogs presented with bony metastases; however, when the dogs with mammary tumours were omitted, the gender distribution of the cases was approximately equivalent. The mammary gland was the primary site of most of the metastatic bone lesions, followed by the musculoskeletal system and the respiratory system. The majority (77%) of metastases were grossly visible and present in multiple bones. However, in 23% of the cases, the metastases could be diagnosed only at the microscopical level. The vertebrae and the humerus were the most frequently affected bones regardless of the primary site and the histogenesis of the tumours. The results of this study revealed a high prevalence of bone metastases and/or bone involvement in dogs with multicentric tumours.
Serrano Fernádez, María José; Alvarez Merino, Juan Carlos; Martínez Zubiaurre, Iñigo; Fernández García, Ana; Sánchez Rovira, Pedro; Lorente Acosta, José Antonio
The distant growth of tumour cells escaping from primary tumours, a process termed metastasis, represents the leading cause of death among patients affected by malignant neoplasias from breast and colon. During the metastasis process, cancer cells liberated from primary tumour tissue, also termed circulating tumour cells (CTCs), travel through the circulatory and/or lymphatic systems to reach distant organs. The early detection and the genotypic and phenotypic characterisation of such CTCs could represent a powerful diagnostic tool of the disease, and could also be considered an important predictive and prognostic marker of disease progression and treatment response. In this article we discuss the potential relevance in the clinic of monitoring CTCs from patients suffering from solid epithelial tumours, with emphasis on the impact of such analyses as a predictive marker for treatment response.
Hoeger, P H; Colmenero, I
Vascular anomalies can be subdivided into vascular tumours and vascular malformations (VMs). While most VMs are present at birth and do not exhibit significant postnatal growth, vascular tumours are characterized by their dynamics of growth and (sometimes) spontaneous regression. This review focuses on benign vascular tumours other than infantile haemangiomas (IHs), namely pyogenic granuloma, eruptive pseudoangiomatosis, glomangioma, rapidly involuting and noninvoluting congenital haemangioma, verrucous haemangioma and spindle cell haemangioma. While some of them bear clinical resemblance to IH, they can be separated by age of appearance, growth characteristics and/or negative staining for glucose transporter 1. Separation of these tumours from IH is necessary because their outcome and therapeutic options are different. Semimalignant and malignant vascular tumours will be addressed in a separate review.
Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.
Goncharov, Alexey I; Maslakova, Aitsana A; Polikarpova, Anna V; Bulanova, Elena A; Guseva, Alexandra A; Morozov, Ivan A; Rubtsov, Petr M; Smirnova, Olga V; Shchelkunova, Tatiana A
Recent studies suggest that progesterone may possess anti-tumorigenic properties. However, a growth-modulatory role of progestins in human cancer cells remains obscure. With the discovery of a new class of membrane progesterone receptors (mPRs) belonging to the progestin and adipoQ receptor gene family, it becomes important to study the effect of this hormone on proliferation of tumor cells that do not express classical nuclear progesterone receptors (nPRs). To identify a cell line expressing high levels of mPRs and lacking nPRs, we examined mRNA levels of nPRs and three forms of mPRs in sixteen human tumor cell lines of different origin. High expression of mPR mRNA has been found in pancreatic adenocarcinoma BxPC3 cells, while nPR mRNA has not been detected in these cells. Western blot analysis confirmed these findings at the protein level. We revealed specific binding of labeled progesterone in these cells with affinity constant similar to that of human mPR expressed in yeast cells. Progesterone at high concentration of 20 μM significantly reduced the mRNA levels of proliferation markers Ki67 and PCNA, as well as of cyclin D1, and increased the mRNA levels of cyclin dependent kinase inhibitors p21 and p27. Progesterone (1 μM and 20 μM) significantly inhibited proliferative activity of BxPC3 cells. These results point to anti-proliferative effects of the progesterone high concentrations on BxPC3 cells and suggest that activation of mPRs may mediate this action. Our data are a starting point for further investigations regarding the application of progesterone in pancreatic cancer.
Dhar, Arjun; Pawar, Sumeet; Prasad, Apurva; Ramani, P S
Neurogenic tumours of the paraspinal space can occur in all age groups. It is common in adult population and relatively rare in elderly group. Usually they are benign, but in children, arising from the autonomic system, tends to be malignant in nature. Usually in adults, they arise from peripheral nerve sheath and are labelled as schwannomas. For a given tumour, determination of a correct surgical approach is mandatory to achieve a successful surgical outcome. Several factors like tumour size, histology, involvement of the bony spinal canal, etc. are some of the deciding factors for a correct surgical approach. Since many such tumours are benign, total excision is possible with a correct surgical approach. If the tumour involves the integrity of the spine then additionally a stabilization procedure may have to be carried out. Unfortunately, there are still no guidelines regarding the choice of surgical approach for the excision of such tumors. Presented here is a series of five patients managed by us over a period of 10 years. Four patients were adults and one female child was three years old. Four patients were operated upon successfully and the fifth one is waiting for surgery.
Serpell, J. W.; Fish, S. H.; Fisher, C.; Thomas, J. M.
We prospectively analysed methods of diagnosis in 118 patients referred for definitive treatment with documented or presumed soft tissue sarcoma (STS). Of 65 patients with primary STS, 54 were biopsied before referral. Of these, 5 (9%) were biopsied by Tru-cut biopsy, 17 (32%) by incisional biopsy and 32 (59%) by excisional biopsy. The remaining 11 patients with primary STS, referred without biopsy, were all diagnosed by Tru-cut biopsy. An additional eight patients suspected of having STS were referred without biopsy and were found to have malignant tumours other than STS involving soft tissue by Tru-cut biopsy. Nineteen patients were proved to have benign soft tissue tumours; in 13 presumed to have STS, the diagnosis was unknown at referral. In four of these, biopsy was inappropriate. Of nine submitted to Tru-cut biopsy, an unequivocal diagnosis was made in 5 (56%) and incisional biopsy was required in the other four. Therefore, paradoxically, benign soft tissue tumours may be more difficult to diagnose with Tru-cut biopsy than malignant tumours. This study confirms the high degree of accuracy of Tru-cut biopsy in diagnosing malignant soft tissue tumours and highlights the disadvantages of open biopsy techniques. PMID:1416683
Zbar, Andrew P; Maor, Yaakov; Czerniak, Abraham
Although comparatively rare, ampullary tumours tend to be more readily curable than periampullary lesions and pancreatic carcinomas, consequent upon an earlier presentation, a lower likelihood of involved lymph nodes or vascular infiltration and a less aggressive histology. Recently, selected early cases have been able to resected endoscopically making accurate preoperative tumour (T) staging critical in such decision making. The most commonly available imaging methods are endoscopic ultrasound (EUS) and CT scanning where in the former case there is variable accuracy for larger (T2/T3) ampullary tumours particularly where the patient has undergone preoperative common bile duct stenting. CT scanning has consistent shown inferior T staging of ampullary tumours when compared with EUS, although it provides information concerning visceral and nodal metastatic disease. Transpapillary intraductal ultrasound (where available) has shown high accuracy for early T1 tumours potentially suitable for endoscopic or local ampullary excision with the added advantage that it may be conducted without preliminary sphincterotomy. Recently, our group has been using intraoperative transduodenal ultrasound which assists surgical decision making concerning local excision or radical pancreaticoduodenal resection. Very recent images using 3-dimensional endoduodenal ultrasound has provided exquisite images of the ampulla and remain to be validated in ampullary neoplasms.
Wohlschläger, J; Wittekind, C; Theegarten, D
The staging system for lung tumours is now recommended for the classification of both non-small-cell and small-cell lung cancer as well as for carcinoid tumours of the lung. The T classifications have been redefined: T1 has been subclassified as T1a (≤ 2 cm in size) and T1b (> 2-3 cm in size). T2 has been subclassified as T2a (> 3-5 cm in size) and T2b (> 5-7 cm in size). T2 (> 7 cm in size) has been reclassified as T3. Multiple tumour nodules in the same lobe have been reclassified from T4 to T3. Multiple tumour nodules in the same lung but a different lobe have been reclassified from M1 to T4. No changes have been made in the N classification. The M classification has been redefined: M1 has been subdivided into M1a and M1b. Malignant pleural and pericardial effusions have been reclassified from T4 to M1a. Separate tumour nodules in the contralateral lung have been reclassified from T4 to M1a. M1b designates distant metastasis.
Krishnamoorthy, Ramakrishnan; Savasere, Thejas; Prabhuswamy, Vinod Kumar; Babu, Rajashekhara; Shivaswamy, Sadashivaiah
The term phyllodes tumour includes lesions ranging from completely benign tumours to malignant sarcomas. Clinically phyllodes tumours are smooth, rounded, and usually painless multinodular lesions indistinguishable from fibroadenomas. Percentage of phyllodes tumour classified as malignant ranges from 23% to 50%. We report a case of second largest phyllodes tumour in a 35-year-old lady who presented with swelling of right breast since 6 months, initially small in size, that progressed gradually to present size. Examination revealed mass in the right breast measuring 36×32 cms with lobulated firm surface and weighing 10 kgs. Fine needle aspiration cytology was reported as borderline phyllodes; however core biopsy examination showed biphasic neoplasm with malignant stromal component. Simple mastectomy was done and specimen was sent for histopathological examination which confirmed the core biopsy report. Postoperatively the patient received chemotherapy and radiotherapy. The patient is on follow-up for a year and has not shown any evidence of metastasis or recurrence.
Tommerup, N; Lothe, R
The types of malignancy reported in carriers of constitutional ring chromosomes r(11), r(13), and r(22) are concordant with the chromosomal assignment of tumour suppressor loci associated with Wilms' tumour, retinoblastoma, and meningioma. It is suggested that the somatic instability of ring chromosomes may play a role in this association and that constitutional ring chromosomes may be a source for mapping of tumour suppressor loci with the potential for covering most or all of the human genome. The hypothesis predicts the presence of a locus on chromosome 10 associated with follicular carcinoma of the thyroid, in line with previous cytogenetic findings of rearrangements involving chromosome 10 in thyroid tumours, and a locus on chromosome 22 associated with testicular cancer. Development of neurofibromatoses (NF) that do not fulfil the clinical criteria of neurofibromatosis type 2 (NF2) in carriers with r(22) suggests either the presence of an additional NF locus on chromosome 22 or that ring chromosome mediated predisposition to somatic mutation of a specific tumour suppressor may be associated with atypical development of features usually associated with germline mutations. PMID:1336057
Hansen, Jean M; Coleman, Robert L; Sood, Anil K
The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy.
Schwarz, Roland F.; Trinh, Anne; Sipos, Botond; Brenton, James D.; Goldman, Nick; Markowetz, Florian
Intra-tumour genetic heterogeneity is the result of ongoing evolutionary change within each cancer. The expansion of genetically distinct sub-clonal populations may explain the emergence of drug resistance, and if so, would have prognostic and predictive utility. However, methods for objectively quantifying tumour heterogeneity have been missing and are particularly difficult to establish in cancers where predominant copy number variation prevents accurate phylogenetic reconstruction owing to horizontal dependencies caused by long and cascading genomic rearrangements. To address these challenges, we present MEDICC, a method for phylogenetic reconstruction and heterogeneity quantification based on a Minimum Event Distance for Intra-tumour Copy-number Comparisons. Using a transducer-based pairwise comparison function, we determine optimal phasing of major and minor alleles, as well as evolutionary distances between samples, and are able to reconstruct ancestral genomes. Rigorous simulations and an extensive clinical study show the power of our method, which outperforms state-of-the-art competitors in reconstruction accuracy, and additionally allows unbiased numerical quantification of tumour heterogeneity. Accurate quantification and evolutionary inference are essential to understand the functional consequences of tumour heterogeneity. The MEDICC algorithms are independent of the experimental techniques used and are applicable to both next-generation sequencing and array CGH data. PMID:24743184
Cao, Z; Joseph, W R; Browne, W L; Mountjoy, K G; Palmer, B D; Baguley, B C; Ching, L-M
5,6-Dimethylxanthenone-4-acetic acid (DMXAA), synthesized in this laboratory and currently in phase I clinical trial, is a low molecular weight inducer of tumour necrosis factor-α (TNF-α). Administration of DMXAA to mice with established transplantable tumours elicits rapid vascular collapse selectively in the tumour, followed by extensive haemorrhagic necrosis mediated primarily through the production of TNF-α. In this report we have investigated the synthesis of TNF-α mRNA in hepatic, splenic and tumour tissue. Co-administration of thalidomide with DMXAA increased anti-tumour activity and increased intra-tumoural TNF-α production approximately tenfold over that obtained with DMXAA alone. Thalidomide increased splenic TNF-α production slightly but significantly decreased serum and hepatic levels of TNF-α induced with DMXAA. Lipopolysaccharide (LPS) induced 300-fold higher serum TNF-α than did DMXAA at the maximum tolerated dose, but induced similar amounts of TNF-α in spleen, liver and tumour. Splenic TNF-α activity induced with LPS was slightly increased with thalidomide, but serum and liver TNF-α levels were suppressed. Thalidomide did not increase intra-tumoural TNF-α production induced with LPS, in sharp contrast to that obtained with DMXAA. While thalidomide improved the anti-tumour response to DMXAA, it had no effect on the anti-tumour action of LPS that did not induce a significant growth delay or cures against the Colon 38 tumour. The increase in the anti-tumour action by thalidomide in combination with DMXAA corresponded to an increase in intra-tumoural TNF-α production. Co-administration of thalidomide may represent a novel approach to improving selective intra-tumoural TNF-α production and anti-tumour efficacy of DMXAA. © 1999 Cancer Research Campaign PMID:10360649
Hadi, Yousaf Bashir; Sohail, Abdul Malik Amir Humza; Haider, Zishan
Autoimmune pancreatitis (AIP) is categorised into two distinct types, AIP type 1 and 2. Although there can be multisystem involvement, rarely, the cholangitis associated with AIP can present radiologically in a manner similar to that of Klatskin tumour. We present the case of a 65-year-old man who was almost misdiagnosed with a Klatskin tumour because of the similarity in radiological features of the two aforementioned clinical entities. The patient presented with a history of jaundice, pruritus and abdominal pain, and work up showed deranged liver function tests, elevated cancer antigen 19-9 levels and positive antinuclear antibodies. CT scan of the abdomen showed findings suggestive of Klatskin tumour but due to diffuse enlargement of the pancreas and surrounding low-attenuation halo found on a closer review, a diagnosis of AIP was performed. The patient was started on standard corticosteroid therapy and responded well, with complete resolution of the radiological findings.
Natural antibodies (NAb) are found in the serum of healthy individuals. These antibodies are produced without any apparent specific antigenic stimulation. They are one part of the circulating immunoglobulins and are found in virtually all vertebrate species. NAb react to various self- and non-self antigens. A protective function in different infection models could be demonstrated. Several groups have reported the ability of NAb to bind to tumour cells. Their possible role in tumour defence is documented in mice. The present status of attempts to characterise the role of NAb in tumour defence is discussed, particularly as regards the human immune system. This paper focuses on antibody cell interactions and discusses the genetic background of the Nab-producing B-cells.
Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris
Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485
Khan, Zeeshan; Hussain, Shakir; Carter, Simon R
Sarcomas are rare tumours and particularly rarer in the foot and ankle region. The complex anatomy of the foot and ankle makes it unique and hence poses a challenge to the surgeon for limb salvage surgery. Other lesions found in the foot and ankle region are benign bone and soft tissue tumours, metastasis and infection. The purpose of this article is to discuss the relevance of the complex anatomy of the foot and ankle in relation to tumours, clinical features, their general management principles and further discussion about some of the more common bone and soft tissue lesions. Discussion of every single bone and soft tissue lesion in the foot and ankle region is beyond the scope of this article.
Background The conversion of arginine into citrulline, termed citrullination, has important consequences for the structure and function of proteins. Studies have found PADI4, an enzyme performing citrullination, to be highly expressed in a variety of malignant tumours and have shown that PADI4 participates in the process of tumorigenesis. However, as citrullinated proteins have not been systematically investigated in tumours, the present study aimed to identify novel citrullinated proteins in tumours by 2-D western blotting (2-D WB). Methods Two identical two-dimensional electrophoresis (2-DE) gels were prepared using extracts from ECA, H292, HeLa, HEPG2, Lovo, MCF-7, PANC-1, SGC, and SKOV3 tumour cell lines. The expression profiles on a 2-DE gel were trans-blotted to PVDF membranes, and the blots were then probed with an anti-citrulline antibody. By comparing the 2-DE profile with the parallel 2-D WB profile at a global level, protein spots with immuno-signals were collected from the second 2-DE gel and identified using mass spectrometry. Immunoprecipitation was used to verify the expression and citrullination of the targeted proteins in tumour cell lines. Results 2-D WB and mass spectrometry identified citrullinated α-enolase (ENO1), heat shock protein 60 (HSP60), keratin 8 (KRT8), tubulin beta (TUBB), T cell receptor chain and vimentin in these cell lines. Immunoprecipitation analyses verified the expression and citrullination of ENO1, HSP60, KRT8, and TUBB in the total protein lysates of the tumour cell lines. Conclusions The citrullination of these proteins suggests a new mechanism in the tumorigenic process. PMID:24099319
Hentic, Olivia; Vullierme, Marie-Pierre; Lagadec, Matthieu; Ronot, Maxime; Ruszniewski, Philippe; Vilgrain, Valérie
Background Visual semi-quantitative assessment of liver tumour burden for neuroendocrine tumour liver metastases is often used in patient management and outcome. However, published data on the reproducibility of these evaluations are lacking. Objective The aim of this study was to evaluate the interobserver and intraobserver agreement of a visual semi-quantitative assessment of liver tumour burden using CT scan. Methods Fifty consecutive patients (24 men and 26 women, mean aged 54 years) were retrospectively reviewed by four readers (two senior radiologists, one junior radiologist and one gastroenterologist) who assessed the liver tumour burden based on a visual semi-quantitative method with four classes (0–10, 11–25, 26–50 and ≥50%). Interobserver and intraobserver agreement were assessed by weighted kappa coefficient and percentage of agreement. The intraclass correlation was calculated. Results Agreement among the four observers for the evaluation of liver tumour burden was substantial, ranging from 0.62 to 0.73 (P < 0.0001). The intraclass coefficient was 0.977 (P < 0.0001). Intraobserver agreement was 0.78 and ICC was 0.97. Conclusion Reproducibility of the visual semi-quantitative evaluation of liver tumour burden is good and is independent of the level of experience of the readers. We therefore suggest that clinical studies in patients with neuroendocrine liver metastases use this method to categorise liver tumour burden. PMID:28069898
Levin-Plotnik, D; Hamilton, R J
We find the dose distribution that maximizes the tumour control probability (TCP) for a fixed mean tumour dose per fraction. We consider a heterogeneous tumour volume having a radiation response characterized by the linear quadratic model with heterogeneous radiosensitivity and repopulation rate that may vary in time. Using variational calculus methods a general solution is obtained. We demonstrate the spatial dependence of the optimal dose distribution by explicitly evaluating the solution for different functional forms of the tumour properties. For homogeneous radiosensitivity and growth rate, we find that the dose distribution that maximizes TCP is homogeneous when the clonogen cell density is homogeneous, while for a heterogeneous initial tumour density we find that the first dose fraction is inhomogeneous, which homogenizes the clonogen cell density, and subsequent dose fractions are homogeneous. When the tumour properties have explicit spatial dependence, we show that the spatial variation of the optimized dose distribution is insensitive to the functional form. However, the dose distribution and tumour clonogen density are sensitive to the value of the repopulation rate. The optimized dose distribution yields a higher TCP than a typical clinical dose distribution or a homogeneous dose distribution.
Laoui, Damya; Keirsse, Jiri; Morias, Yannick; Van Overmeire, Eva; Geeraerts, Xenia; Elkrim, Yvon; Kiss, Mate; Bolli, Evangelia; Lahmar, Qods; Sichien, Dorine; Serneels, Jens; Scott, Charlotte L.; Boon, Louis; De Baetselier, Patrick; Mazzone, Massimiliano; Guilliams, Martin; Van Ginderachter, Jo A.
Various steady state and inflamed tissues have been shown to contain a heterogeneous DC population consisting of developmentally distinct subsets, including cDC1s, cDC2s and monocyte-derived DCs, displaying differential functional specializations. The identification of functionally distinct tumour-associated DC (TADC) subpopulations could prove essential for the understanding of basic TADC biology and for envisaging targeted immunotherapies. We demonstrate that multiple mouse tumours as well as human tumours harbour ontogenically discrete TADC subsets. Monocyte-derived TADCs are prominent in tumour antigen uptake, but lack strong T-cell stimulatory capacity due to NO-mediated immunosuppression. Pre-cDC-derived TADCs have lymph node migratory potential, whereby cDC1s efficiently activate CD8+ T cells and cDC2s induce Th17 cells. Mice vaccinated with cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural TAMs and a reduction of MDSCs, while cDC1 vaccination strongly induces anti-tumour CTLs. Our data might prove important for therapeutic interventions targeted at specific TADC subsets or their precursors. PMID:28008905
Lo, C F
In this communication, based upon the deterministic Gompertz law of cell growth, a stochastic model in tumour growth is proposed. This model takes account of both cell fission and mortality too. The corresponding density function of the size of the tumour cells obeys a functional Fokker--Planck equation which can be solved analytically. It is found that the density function exhibits an interesting "multi-peak" structure generated by cell fission as time evolves. Within this framework the action of therapy is also examined by simply incorporating a therapy term into the deterministic cell growth term.
Bavle, Radhika M.; Muniswamappa, Sudhakara; Narasimhamurthy, Srinath
Odontogenic keratocysts (OKCs) are developmental cysts which occur typically in the jawbones. They present more commonly in the posterior mandible of young adults than the maxilla. OKCs have been reclassified under odontogenic tumours in 2005 by the WHO and have since been termed as keratocystic odontogenic tumours (KCOTs). Here we report a case of a recurrent buccal lesion in a 62-year-old man which was provisionally diagnosed as a space infection (buccal abscess) but surprisingly turned out to be a soft tissue KCOT in an unusual location on histopathologic examination. PMID:26770859
Merkel cell tumour is an aggressive neuroendocrine neoplasm arising in the dermis. Although only a few hundred cases have been reported worldwide, nine were seen in Nottingham between 1985 and early 1994. The patients were five women and four men age 63-88. One was the first Afro-Caribbean reported to have such a tumour. In no case was the diagnosis made clinically; histological and histochemical examination was necessary. Three of the patients died quickly with metastatic disease. The primary treatment is surgical excision. For advanced disease, radiotherapy is commonly beneficial. Images Figure 1 Figure 2 Figure 3 PMID:9306997
Gabrilovich, Dmitry I; Ostrand-Rosenberg, Suzanne; Bronte, Vincenzo
Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.
Morcos, Basem B; Baker, Bilal; Hashem, Sameh A
A patient with phyllodes tumour of the breast is discussed. During follow-up, she presented with intestinal obstruction caused by ileocaecal intussusception. The cause of the intussusception was metastatic phyllodes tumour, which is a unique presentation.
Tiang, Kor Woi; Inglis, Po; Collins, Stuart
Wilms’ tumour (nephroblastoma) is the most common renal tumour in children. Wilms’ tumour in adults is extremely rare and has a poorer prognosis than paediatric Wilms’ tumour. It is difficult to differentiate adult Wilms’ tumour from renal cell carcinoma based on radiological findings alone. The diagnosis in adults is often serendipitous following nephrectomy for presumed renal cell carcinoma. Because of the paucity of literature, there are no standard protocols for the management of adult Wilms’ tumour, and therefore, it is managed as per paediatric Wilms’ tumour. Herein, we report the case of adult Wilms’ tumour in a 43-year-old man, which was diagnosed unexpectedly following nephrectomy for presumed renal cell carcinoma. PMID:28326278
Caraguel, Flavien; Lesart, Anne-Cécile; Estève, François; van der Sanden, Boudewijn
The design of a patient-specific virtual tumour is an important step towards Personalized Medicine. However this requires to capture the description of many key events of tumour development, including angiogenesis, matrix remodelling, hypoxia, and cell state heterogeneity that will all influence the tumour growth kinetics and degree of tumour invasiveness. To that end, an integrated hybrid and multiscale approach has been developed based on data acquired on a preclinical mouse model as a proof of concept. Fluorescence imaging is exploited to build case-specific virtual tumours. Numerical simulations show that the virtual tumour matches the characteristics and spatiotemporal evolution of its real counterpart. We achieved this by combining image analysis and physiological modelling to accurately described the evolution of different tumour cases over a month. The development of such models is essential since a dedicated virtual tumour would be the perfect tool to identify the optimum therapeutic strategies that would make Personalized Medicine truly reachable and achievable. PMID:28096895
Kallinowski, F.; Vaupel, P.
Spontaneous mammary tumours of the rat with various degrees of malignancy exhibit similar tissue pH distributions. The mean pH (+/- s.d.) of dysplasia is 7.05 +/- 0.20. In benign tumours the mean pH is 6.95 +/- 0.19 and in malignant tumours it is 6.94 +/- 0.19. In contrast, tumours with the same degree of malignancy but different histologies show different pH distributions. Benign tumours with a higher percentage of fibrous tissue exhibit less acidic pH values than those with larger portions of epithelial cells (delta pH = 0.38 pH units). The pH distribution in the benign tumours is independent of the tumour wet weight up to stages of very advanced growth. In the malignant tumours, a trend towards more acidic pH values is observed as the tumour mass enlarges. However, in tissue areas within a malignant tumour with gross, long-established necrosis the pH distribution is shifted towards more alkaline pH values. The pH distributions in spontaneous rat tumours are not significantly different from those obtained in isotransplanted Yoshida sarcomas (6.87 +/- 0.21). In the Yoshida sarcomas, mean pH values do not correlate with tumour size. However, a pH gradient from the rim to the centre of the tumours is found which coincides with the development of small, disseminated necroses in the tumour centre. It is concluded that pathology-related variations of tumour pH may be more important than the mode of tumour origin or the degree of malignancy. PMID:3179183
Tam, Jessica; Cheung, Wa Sham; Senger, Christof; Reichman, Mark; Campbell, Karen M
Melanotic neuroectodermal tumour of infancy is a rare benign pigmented tumour that typically appears in the first year of life. We report an atypical presentation of this tumour, associated with an erupted primary tooth in a 7-month-old boy. We discuss the clinical, radiographic and histologic features of this rare tumour, as well as its surgical management and the follow-up treatment plan.
Scholsem, Martin; Scholtes, Felix
We describe the complete removal of a foramen magnum solitary fibrous tumour in a 36-year-old woman. It originated on a caudal vagus nerve rootlet, classically described as the 'cranial' accessory nerve root. This ninth case of immunohistologically confirmed cranial or spinal nerve SFT is the first of the vagus nerve.
Jonsdottir, Asta Bjork; Stefansson, Olafur Andri; Bjornsson, Johannes; Jonasson, Jon G; Ogmundsdottir, Helga M; Eyfjord, Jorunn E
Tetraploidy and aneuploidy can be caused by cell division errors and are frequently observed in many human carcinomas. We have recently reported delayed cytokinesis in primary human fibroblasts from BRCA2 mutation carriers, implying a function for the BRCA2 tumour suppressor in completion of cell division. Here, we address ploidy aberrations in breast tumours derived from BRCA2 germline mutation carriers. Ploidy aberrations were evaluated from flow cytometry histograms on selected breast tumour samples (n=236), previously screened for local BRCA mutations. The ploidy between BRCA2-mutated (n=71) and matched sporadic (n=165) cancers was compared. Differences in ploidy distribution were examined with respect to molecular tumour subtypes, previously defined by immunohistochemistry on tissue microarray sections. Tetraploidy was significantly 3 times more common in BRCA2 breast cancers than sporadic. However, no differences were found in the overall ploidy distribution between BRCA2-mutation carriers and non-carriers. In BRCA2 cancers, tetraploidy was associated with luminal characteristics. The increased frequency of tetraploidy in BRCA2 associated cancers may be linked to cell division errors, particularly cytokinesis. Additionally, tetraploidy emerges predominantly in BRCA2 breast cancers displaying luminal rather than triple-negative phenotypes.
Kamath, Panduranga M; Sreedharan, Suja S; Majeed, Nazeem A; Shenoy, Vijendra S
Among the parapharyngeal tumours, salivary gland tumours are the commonest, followed by schwannomas, which are slow growing benign tumours. Half of the parapharyngeal schwannomas originate from the vagus. Complete surgical excision is the treatment of choice. We hereby present two cases of parapharyngeal schwannomas, one which had presented as an intraoral mass and the other as a swelling in the neck. The first case, a 57-year-old female patient complained of a slowly increasing swelling in the left side of the throat since 3 months, associated with pain and dysphagia. In the Contrast Enhanced CT scan of the neck, a well-defined cystic lesion with central enhancing solid components (4cm X 4.5cm X 3cm) was seen in the left parapharyngeal region. The second case, a 39-year-old male patient complained of a painless, gradually increasing swelling below the lobule of the right ear since one month. Examination revealed a solitary, nontender, firm and mobile swelling of 2cm X 2cm below the lobule of the right ear. In Contrast Enhanced CT scan of the neck, an enhancing lesion was seen involving the right parapharyngeal space, post-styloid compartment. Both the patients underwent trans-cervical surgical excision. Vagal nerve schwannoma is rare. The majority of the cases present with a slow growing neck swelling without neurological deficit. Complete surgical excision of the tumour is important to prevent recurrence. PMID:27190844
Wilhelm, Stefan; Tavares, Anthony J.; Dai, Qin; Ohta, Seiichi; Audet, Julie; Dvorak, Harold F.; Chan, Warren C. W.
Targeting nanoparticles to malignant tissues for improved diagnosis and therapy is a popular concept. However, after surveying the literature from the past 10 years, only 0.7% (median) of the administered nanoparticle dose is found to be delivered to a solid tumour. This has negative consequences on the translation of nanotechnology for human use with respect to manufacturing, cost, toxicity, and imaging and therapeutic efficacy. In this article, we conduct a multivariate analysis on the compiled data to reveal the contributions of nanoparticle physicochemical parameters, tumour models and cancer types on the low delivery efficiency. We explore the potential causes of the poor delivery efficiency from the perspectives of tumour biology (intercellular versus transcellular transport, enhanced permeability and retention effect, and physicochemical-dependent nanoparticle transport through the tumour stroma) as well as competing organs (mononuclear phagocytic and renal systems) and present a 30-year research strategy to overcome this fundamental limitation. Solving the nanoparticle delivery problem will accelerate the clinical translation of nanomedicine.
Pigott, H. W. S.
Two cases of malignant tumour are reported in phenotypically male hermaphrodites. The importance of establishing the presence of persistent Müllerian duct structures in pseudo-hermaphrodites is discussed in relation to prophylactic castration in anticipation of malignant change. ImagesFig. 1Fig. 2 PMID:1197157
Romero, Ricardo; Castano, Ananda; Abelairas, Jose; Peralta, Jesus; Garcia-Cabezas, Miguel A; Sanchez-Orgaz, Margarita; Arbizu, Alvaro; Vallejo-Garcia, Jose
Peripheral primitive neuroectodermal tumours (pPNETs) are a group of soft-tissue tumours of neuroepithelial origin that arise outside the central and sympathetic nervous system. Orbital location is infrequent, and to the best of the authors' knowledge only 16 cases have been reported in the literature. With this article, the authors report the demographics and clinical characteristics, diagnostic features, differential diagnosis, prognosis and therapeutic options of primary orbital peripheral primitive neuroectodermal tumour, based on their patients and on the cases reported in the literature to date. A differential diagnosis should be made with other small round cell tumours; immunohistochemical and ultrastructural techniques are essential for this purpose. Although bone invasion and extraorbital extension are possible, systemic metastases are uncommon in the cases of orbital pPNETs. Surgery has been the initial treatment in most cases; chemotherapy with or without radiotherapy is considered the best additional treatment. The orbital pPNET could be less aggressive than other forms of pPNETs, since most of the patients reported were alive after the follow-up period (at least 6 months).
Seregni, Ettore; Coli, Antonio; Mazzucca, Nicola
A large number of markers have been proposed for breast cancer, but among them only CA 15.3, CEA and cytokeratins (i.e. TPA, TPS and Cyfra 21.1) are currently used in clinical practice. Serum marker levels reflect tumour burden and for this reason they are not sensitive enough to be used for screening and early diagnosis of primary breast cancer. By contrast, the role of tumour markers is established in the diagnosis of recurrent disease and in the evaluation of response to treatment. In the former case, however, prospective randomised studies are required to demonstrate any survival benefit when earlier therapeutic interventions are instituted upon elevation of serum markers. In the second case, tumour marker evaluation represents a simple, objective method for monitoring of therapeutic response that seems to offer significant advantages over conventional imaging methods (e.g. objectivity, modifications in tumour biology). Furthermore, research studies are ongoing to identify and validate new biochemical parameters which can be of use not only in advanced disease but also in other stages of the diagnostic work-up of breast cancer.
Wong, D K C; Ramli, R; Muhaizan, W M; Primuharsa Putra, S H A
Congenital epulis is a rare benign pedunculated tumour of the oral cavity arising from the alveolar ridges. It is usually detected in newborns and can be successfully resected surgically. We report a case of a newborn baby who had a 5x3x3cm pedunculated lobar mass arising from the upper alveolar ridge.
Patel, S. K.; Mullins, W. A.; O'Neil, S. H.; Wilson, K.
Background: The purpose of this study is to evaluate the relationship between brain tumour location and core areas of cognitive and behavioural functioning for paediatric brain tumour survivors. The extant literature both supports and refutes an association between paediatric brain tumour location and neurocognitive outcomes. We examined…
Mediastinal germinal tumours are composed of tissues resembling those that follow one another during embryo development, by differentiation of the primordial and extraembryonic layers. Such practice separates the mature teratomas (benign), seminomas and non-seminomatous germinal tumours (NSGT). Platin-based chemotherapy has shattered the prognosis of such tumours.
Purohit, Bela S; Vargas, Maria Isabel; Ailianou, Angeliki; Merlini, Laura; Poletti, Pierre-Alexandre; Platon, Alexandra; Delattre, Bénédicte M; Rager, Olivier; Burkhardt, Karim; Becker, Minerva
Although the orbit is a small anatomical space, the wide range of structures present within it are often the site of origin of various tumours and tumour-like conditions, both in adults and children. Cross-sectional imaging is mandatory for the detection, characterization, and mapping of these lesions. This review focuses on multiparametric imaging of orbital tumours. Each tumour is reviewed in relation to its clinical presentation, compartmental location, imaging characteristics, and its histological features. We herein describe orbital tumours as lesions of the globe (retinoblastoma, uveal melanoma), optic nerve sheath complex (meningioma, optic nerve glioma), conal-intraconal compartment (hemangioma), extraconal compartment (dermoid/epidermoid, lacrimal gland tumours, lymphoma, rhabdomysarcoma), and bone and sinus compartment (fibrous dysplasia). Lesions without any typical compartmental localization and those with multi-compartment involvement (veno-lymphatic malformation, plexiform neurofibroma, idiopathic orbital pseudotumour, IgG4 related disease, metastases) are also reviewed. We discuss the role of advanced imaging techniques, such as MR diffusion-weighted imaging (DWI), diffusion tensor imaging, fluoro-2-deoxy-D-glucose positron emission tomography CT (FDG-PET CT), and positron emission tomography MRI (MRI PET) as problem-solving tools in the evaluation of those orbital masses that present with non-specific morphologic imaging findings. Main messages/Teaching points • A compartment-based approach is essential for the diagnosis of orbital tumours. • CT and MRI play a key role in the work-up of orbital tumours. • DWI, PET CT, and MRI PET are complementary tools to solve diagnostic dilemmas. • Awareness of salient imaging pearls and diagnostic pitfalls avoids interpretation errors.
Habets, Thomas H. P. M.; Oth, Tammy; Houben, Ans W.; Huijskens, Mirelle J. A. J.; Senden-Gijsbers, Birgit L. M. G.; Schnijderberg, Melanie C. A.; Brans, Boudewijn; Dubois, Ludwig J.; Lambin, Philippe; De Saint-Hubert, Marijke; Germeraad, Wilfred T. V.; Tilanus, Marcel G. J.; Mottaghy, Felix M.
Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production. We selected the 67NR mammary carcinoma model since this tumour showed spontaneous antibody production in all tumour-bearing mice. Fractionated RT to the primary tumour was associated with a survival benefit and a delayed growth of a non-irradiated (contralateral) secondary tumour. Notably, fractionated RT did not affect anti-tumour antibody titers and the composition of the immunoglobulin (Ig) isotypes. Likewise, we demonstrated that treatment of tumour-bearing Balb/C mice with DC stimulating growth factor Flt3-L did neither modulate the magnitude nor the composition of the humoral immune response. Finally, we evaluated the immune infiltrate and Ig isotype content of the tumour tissue using flow cytometry and found no differences between treatment groups that were indicative for local antibody production. In conclusion, we demonstrate that the 67NR mammary carcinoma in Balb/C mice is associated with a pre-existing antibody response. And, we show that in tumour-bearing Balb/C mice with abscopal tumour regression such pre-existing antibody responses are not altered upon fractionated RT and/or DC stimulation with Flt3-L. Our research indicates that evaluating the humoral immune response in the setting of abscopal tumour regression is not invariably associated with therapeutic effects. PMID:27427766
Blackstein, Martin Elliot
Hormonal therapy is the first systemic therapy to have been used successfully in the treatment of cancer. Developments in steroid hormone receptor assays in the last decade have resulted in the first predictable assays for cancer therapy. The role of hormones, in both the development and treatment of breast, prostate and uterine cancer, is reviewed. Because hormonal therapy is generally a less toxic palliative treatment than other treatments (e.g., chemotherapy and radiation), it has been used for malignancies such as malignant melanoma, hypernephroma, and carcinoid. PMID:21278945
Bhat, Amoolya; V., Geethamani; C., Vijaya
“Soft tissue giant cell tumour of low malignant potential” is considered as the soft tissue counterpart of osteoclastoma of the bone. It is a primary soft tissue tumour which is classified under the category of fibrohistiocytic tumours of intermediate malignancy.Seventy percent of the tumours involve the extremities and only about seven percent of them arise in head and neck region. They are composed of nodules of histiocytes in a vascular stroma, with multinucleated osteoclast-like giant cells positive for vimentin, smooth muscle actin (SMA), CD68 and Tarterate Resistant Acid Phosphatase (TRAP). We are presenting a case of a 75-year-old man who had a nodule on the ala of the nose. Histopathology showed a histiocytic lesion. Benign fibrous histiocytoma, plexiform fibrohistiocytic tumour, solitary reticulohistiocytoma and histioid leprosy were ruled out by using special stains and immunostains. Expression of smooth muscle actin and CD68 confirmed the diagnosis of a soft tissue giant cell tumour with a low malignant potential. PMID:24551690
Rau, D; Alt, W; Kälble, T
Neoplasms of the seminal vesicles are rare. Here we report on a patient with a low-grade phyllodes tumour of the seminal vesicle. The patient was admitted to our hospital with a tumour in the excavatio rectovesicalis diagnosed by CT scan. He had no symptoms. For further diagnosis we took transrectal ultrasound-guided biopsies, the histopathological examination showed no malignant features. One month later a follow-up CT scan demonstrated a significant enlargement of the tumour. Therefore we decided to perform a surgical exploration. During surgery we found a partially necrotic mass involving the prostate, the urinary bladder and the rectum. Both radical cystoprostatectomy with ileal conduit and anterior resection of the rectum with colostomy were necessary. Histologically the specimen showed a low-grade phyllodes tumour of the left seminal vesicle. One year after surgery the follow-up was completely normal without any residual or recurrent tumour. Frequency, histology, diagnostic investigations, therapy and prognosis of this rare tumour entity are discussed with respect to the actual literature.
Ryland, Georgina L; Hunter, Sally M; Doyle, Maria A; Rowley, Simone M; Christie, Michael; Allan, Prue E; Bowtell, David D L; Gorringe, Kylie L; Campbell, Ian G
Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts.
Dittrich, C.; Jakesz, R.; Wrba, F.; Havelec, L.; Haas, O.; Spona, J.; Holzner, H.; Kolb, R.; Moser, K.
A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01). PMID:4027163
Tang, C.; Biemond, I.; Offerhaus, G. J.; Verspaget, W.; Lamers, C. B.
Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas. This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of human pancreas (n = 10) and pancreatic ductal adenocarcinomas (n = 12) with storage phosphor autoradiography using radioligands. CCK-B receptors, present in control pancreata, were not detected in any of the pancreatic cancers. BBS receptors were visualized in control pancreata, but they were absent in 10 of 12 pancreatic cancers. In 5 of 12 pancreatic cancers, receptors for secretin were visualized, while binding for secretin was present in all tumour-free pancreata. Conversely, no specific binding of VIP was detected in control pancreata but was identified in 3 of 12 pancreatic cancer specimens. It is concluded that the expression of gut peptide receptors in pancreatic cancer differs from that in tumour-free pancreas. Receptors for these peptides are present in only a minority of pancreatic cancer specimens. Images Figure 1 PMID:9166939
Bulow, V V; Weiland, F
Chickens could be protected against lethal lymphoblastic leukaemia due to the nonproducer JMV Marek's disease (MD) tumour transplant by infection with the herpesvirus of turkeys (HVT) or various strains of MD virus. However, solid JMV tumours developed in MD virus-infected birds at the site of intramuscular or subcutaneous transplantation, but tumours never developed at the site of MD virus inoculation. The incidence and extent of local tumour growth, the development of metastases and the inhibition of tumour regression were related to the pathogenicity of the MD virus strains used for pre-treatment of the chickens. Infection of chickens with reticulo-endotheliosis virus (REV-C) or with chick syncytial virus (CSV), which are nonprotective against MD virus or JMV transplants, stimulated local tumour development of the attenuated JMV-A variant of the JMV transplant. Chickens which did not reject local tumours died of visceral JMV tumour metastases. A direct helper mechanism of viral infection on the oncogenicity of transplants was excluded. The results suggested that virus-induced immunosuppression stimulated the development of local JMV tumours which never occurred in normal chickens. Immunity to the JMV transplant, including resistance to lethal leukaemia and successful regression of local tumours, did not coincide with immunity to MD virus-induced visceral lymphomas or nerve lesions. Vaccinal induced tumour immunity evidently was defective. The significance of these results is discussed with reference to immunological functions of MD tumour-specific antigens.
Allen, Frederick M.; Kaplan, Martin M.; Meranze, David R.; Gradess, Morton
Previous work in some human cases and in laboratory animals has indicated that temporary local ligation of spontaneous tumours has a selective destructive effect on these tumours, with only temporary inflammation resulting in normal tissues. In the experiments described in this paper, 49 spontaneous accessible tumours in dogs were treated by this method, with periods of ligation of from 4 to 11 hours. Success, as measured by selective necrosis of tumour tissue as compared with normal tissue, was achieved in 29 out of 41 benign tumours, including lipomas, angiomas, adenomas and mixed mammary tumours. Treatment failures were encountered in two cases each of papillomas and fibromas, six mixed mammary tumours and two testicular tumours. Total necrosis of tumour cells occurred in all eight malignant tumours encountered in this series. The outstanding feature was the specific destruction of tumour tissue by a bodily process without participation of any outside agent. Emphasis was placed on an adequate inflammatory response following temporary anoxia, although a precise definition of this inflammation could not be offered. Post-ligation bacterial multiplication, which may be expected to occur in necrotic tumour tissue, is considered to be a secondary effect rather than a possible primary cause of regression and disappearance of the tumour. If ligation treatment can be shown to be successful for a particular type of tumour, it may be possible to apply it to human patients for the treatment of areas not amenable to surgery. The results reported here warrant new experimental approaches to the study of neoplasms at the cellular level to define more precisely the anoxic and inflammatory processes involved in the selective lethal effect on tumour tissues; and the authors suggest that trials should be undertaken of combinations of chemotherapy or irradiation with ligation to reduce ligation time and extend the possible benefits. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7
Teoh, Seong Lin; Das, Srijit
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.
With the advances of cross-sectional imaging radiologists gained an increasing responsibility in the management of patients with skull base pathology. As this anatomic area is hidden to clinical exam, surgeons and radiation oncologists have to rely on imaging studies to plan the most adequate treatment. To fulfil these endeavour radiologists need to be knowledgeable about skull base anatomy, about the main treatment options available, their indications and contra-indications and needs to be aware of the wide gamut of pathologies seen in this anatomic region. This article will provide a radiologists' friendly approach to the central skull base and will review the most common central skull base tumours and tumours intrinsic to the bony skull base.
Warnes, T W; Smith, A
The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease
Atkinson, J M; Siller, C S; Gill, J H
Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards ‘normal' cells and a lack of tumour selective targeting, resulting in a therapeutic index which is modest at best. Consequently, the development of more tumour selective cancer treatments, with better discrimination between tumour and normal cells is unequivocally an important goal for cancer drug discovery. One such strategy is to exploit the tumour phenotype as a mechanism for tumour-selective delivery of potent therapeutics. An exciting approach in this area is to develop anticancer therapeutics as prodrugs, which are non-toxic until activated by enzymes localized specifically in the tumour. Enzymes suitable for tumour-activated prodrug development must have increased activity in the tumour relative to non-diseased tissue and an ability to activate the prodrug to its active form. One class of enzyme satisfying these criteria are the tumour endoproteases, particularly the serine- and metallo-proteases. These proteolytic enzymes are essential for tumour angiogenesis, invasion and metastasis, the major defining features of malignancy. This review describes the concept behind development of tumour-endoprotease activated prodrugs and discusses the various studies to date that have demonstrated the huge potential of this approach for improvement of cancer therapy. PMID:18204490
Araya, Juan; Martinez, René; Niklander, Sven; Marshall, Maureen
Background To determine the incidence and prevalence of salivary gland tumours in the province of Valparaíso, Chile. Material and Methods Retrospective review of salivary gland tumours diagnosed between the years 2000 and 2011 from four local pathology services. Information on demographics and histopathology were retrieved from the medical records. Results The study sample consisted of 279 salivary gland tumours. Prevalence and incidence rates per 100.000 persons were 15.4 and 2.51, respectively. Most of the neoplasms corresponded to benign tumours (70.3%). The most affected gland was the parotid gland. Pleomorphic adenoma was the most common benign tumour (53.8%) and mucoepidermoid carcinoma was the most common malignant tumour (7.2%). Conclusions Salivary gland tumours are uncommon neoplasms that usually arise in the parotid gland. Pleomorphic adenoma and mucoepidermoid carcinoma were the most common benign and malignant tumours reported in this series. Key words:Salivary gland tumours, benign tumours, malignant tumours, salivary glands neoplasms, cancer, neoplasia. PMID:26034925
Thews, O; Kelleher, D K; Vaupel, P
Perfusion and oxygenation of experimental tumours were studied during angiotensin II (AT II) administration whereby the rate of the continuous AT II infusion was chosen to increase the mean arterial blood pressure (MABP) by 50–70 mmHg. In subcutaneous DS- sarcomas the red blood cell (RBC) flux was assessed using the laser Doppler technique and the mean tumour oxygen partial pressure (p O 2) was measured polarographically using O 2-sensitive catheter and needle electrodes. Changes in RBC flux with increasing MABP depended mainly on tumour size. In small tumours, RBC flux decreased with rising MABP whereas in larger tumours RBC flux increased parallel to the MABP. As a result of these volume-dependent effects on tumour blood flow, the impact of AT II on tumour p O 2 was also mainly tumour volume-related. In small tumours oxygenation decreased with increasing MABP during AT II infusion, whereas in large tumours a positive relationship between blood pressure and O 2 status was found. This disparate behaviour might be the result of the co-existence of two functionally distinct populations of tumour vessels. In small tumours, perfusion decreases presumably due to vasoconstriction of pre-existing host vessels feeding the tumour. In larger malignancies, newly formed tumour vessels predominate and seem not to have this vasoresponsive capability (lack of smooth muscle cells and/or AT receptors), resulting in an improvement of perfusion which is not tumour-related per se, but is due to the increased perfusion pressure. © 2000 Cancer Research Campaign PMID:10901375
Martorana, Eugenio; Micali, Salvatore; Pirola, Giacomo Maria; Reggiani Bonetti, Luca; Clò, Vera; Ghaith, Ahmed; Bianchi, Giampaolo
Ductal adenocarcinoma is a rare subtype of prostate cancer with a worse prognosis.Histologically, it is characterized by the presence of tall, pseudostratified columnar epithelium with abundant cytoplasm organized in a papillary or cribriform-papillary pattern. Several clinical differences distinguish this subtype of prostate cancer by the conventional acinar adenocarcinoma: exophytic growth into the prostatic urethra, different clinical presentation, different sites of metastasis and more aggressiveness. The rarity of this tumour forced to base our knowledge on small case series or on individual case reports, and does not help to establish appropriate guidelines. Therefore, the diagnosis of this tumour masks clinical implications that are still not well-understood.We report the case of a 69-year-old Caucasian man with a diagnosis of pure prostate ductal adenocarcinoma that early developed multiple metastases after radical prostatectomy. The patient started hormonal therapy with a fast biochemical and radiologic (positron emission tomography-computed tomography, PET-CT) hormonal escape. Therefore, we took the decision to perform chemotherapy with Taxotere along with prednisolone with a relative stability of prostate-specific antigen (PSA) level, but a new PET-CT scan showed a further progression of the disease. Finally, the patient underwent therapy with Abiraterone acetate that did not stop the cancer progression.No therapeutic options available showed a good control of disease progression. PSA proved to be a poor marker while, on the contrary, PET-CT scan has proved to be particularly useful in the management of the disease progression. More efforts are required to add new knowledge about this tumour and assess what is known until now.
Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul
We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour. PMID:27807495
Muppalla, Jaya Nagendra Krishna; Muddana, Keerthi; Dorankula, Shyam Prasad Reddy; Thokala, Madhusudan Rao; Pasupula, Ajay Prakash
In addition to malignant cells, solid tumours comprise supporting stromal tissue that consists of Extra Cellular Matrix (ECM), connective tissue cells, inflammatory cells and blood vessels. The stromal compartment and the malignant cells together shape the tumour microenvironment that in turn determines tumour progression and efficacy of anti-tumour treatments. It is now recognized that the host microenvironment undergoes extensive change during the evolution and progression of cancer. This involves the generation of Tumour-Associated Fibroblasts (TAFs), which, through release of growth factors and cytokines, lead to enhanced angiogenesis, increased tumour growth and invasion. It has also been demonstrated that TAFs may modulate the Cancer Stem Cell (CSC) phenotype, which has therapeutic implications. Understanding the various components in the tumour microenvironment may afford us the opportunity to develop new drugs that target these reversible nonmutational events in the prevention and treatment of cancer. PMID:24179956
Garona, Juan; Pifano, Marina; Pastrian, Maria B; Gomez, Daniel E; Ripoll, Giselle V; Alonso, Daniel F
[V(4)Q(5)]dDAVP is a novel 2nd generation vasopressin analogue with robust antitumour activity against metastatic breast cancer. We recently reported that, by acting on vasopressin V2r membrane receptor present in tumour cells and microvascular endothelium, [V(4)Q(5)]dDAVP inhibits angiogenesis and metastatic progression of the disease without overt toxicity. Despite chemotherapy remaining as a primary therapeutic option for aggressive breast cancer, its use is limited by low selectivity and associated adverse effects. In this regard, we evaluated potential combinational benefits by adding [V(4)Q(5)]dDAVP to standard-of-care chemotherapy. In vitro, combination of [V(4)Q(5)]dDAVP with sub-IC50 concentrations of paclitaxel or carmustine resulted in a cooperative inhibition of breast cancer cell growth in comparison to single-agent therapy. In vivo antitumour efficacy of [V(4)Q(5)]dDAVP addition to chemotherapy was first evaluated using the triple-negative MDA-MB-231 breast cancer xenograft model. Tumour-bearing mice were treated with i.v. injections of [V(4)Q(5)]dDAVP (0.3 μg/kg, thrice weekly) in combination with weekly cycles of paclitaxel (10 mg/kg i.p.). After 6 weeks of treatment, combination regimen resulted in greater tumour growth inhibition compared to monotherapy. [V(4)Q(5)]dDAVP addition was also associated with reduction of local aggressiveness, and impairment of tumour invasion and infiltration of the skin. Benefits of combined therapy were confirmed in the hormone-independent and metastatic F3II breast cancer model by combining [V(4)Q(5)]dDAVP with carmustine (25 mg/kg i.p.). Interestingly, [V(4)Q(5)]dDAVP plus cytotoxic agents severely impaired colony forming ability of tumour cells and inhibited breast cancer metastasis to lung. The present study shows that [V(4)Q(5)]dDAVP may complement conventional chemotherapy by modulating metastatic progression and early stages of microtumour establishment, and thus supports further preclinical testing of
... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...
Kenemans, P; Bosman, A
From the introduction of post-menopausal hormone replacement therapy (HRT) there has been great concern that HRT could possibly increase the risk of breast cancer. Prolonged exposure to endogenous oestrogens undeniably increases the risk of breast cancer. Questions that are important and until now only partly answered, are the following. Are oestrogens tumour promoters, as they induce mitosis, lead to proliferation and, therefore, accelerated growth of clinically occult pre-existing tumours? In addition to this, are they genotoxic mutagenic carcinogens, or could they initiate tumours by way of accumulation of incessant DNA-replication damage mechanism? Opinions vary as to the effect of the addition of a progestogen. There is a multitude of different progestogens which could bind with differing affinity to progesterone receptor PR-A or PR-B, and which have different physiological functions via differential gene regulation. The action of a progestogen on the oestrogen-induced cellular mitotic activity could be synergistic or antagonistic (by different pathways: oestrogen receptor downregulation, activating of metabolic pathways within the breast or stimulation of apoptosis)? Over 60 observational studies and two randomized trials provide evidence that the small but significant increase in risk appears with long-term current post-menopausal hormone use. The addition of a progestogen does not decrease the risk as seen with oestrogens alone and might increase the risk further. It is not clear whether there is a difference in risk with sequentially combined versus continuously combined HRT. Many questions nevertheless still remain. Is the risk increase limited to lean women only? What about risk-modifying factors such as alcohol use and a positive family history for breast cancer? Are tumours detected under HRT less aggressive, is there a better prognosis and is the mortality not increased while morbidity is? And is HRT contraindicated for women with a positive family
Bibby, M. C.; Double, J. A.; Mughal, M. A.
Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND. PMID:7295514
Smith, G.; Harrison, D. J.; East, N.; Rae, F.; Wolf, H.; Wolf, C. R.
It is extremely difficult to identify the factors which regulate the expression of drug-metabolising enzymes in man. To address this problem, we have developed a model involving the use of human tumours grown as xenografts in immune deficient mice. Mice bearing human colon or breast tumours as xenografts were challenged with a range of compounds, known from animal studies to be inducers of cytochrome P450s from a variety of gene families. Almost all of the compounds tested could induce human tumour P450 expression, measured either by Western blot or immunohistochemical analysis. Indeed, the levels of P450s from several distinct gene families or subfamilies including CYP2A, CYP2B, CYP2C, CYP3A and CYP4A were induced. Of particular interest was the profound induction of human P450s by 1,4 bis 2-(3,5dichloro-pyridyloxybenzene)(TCPOBOP), a compound which exhibits a marked species specificity in its ability to induce P450 expression in experimental animals. Induction of a human CYP2B protein by this compound was confirmed by Northern blot analysis and in situ hybridisation for mRNA, indicating that induction occurred at the level of transcription. These studies have a variety of implications: they provide a method for approaching the previously intractable problem of how environmental, hormonal and metabolic factors regulate human P450 genes and other genes involved in drug metabolism; they demonstrate that human tumours express P450s constitutively and that the levels of these proteins can be modulated by exogenous agents. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8318421
Mitchard, Terri L; Klein, Stephanie
A study using vehicle administration in 104 female rats investigated reproductive aging in Han Wistar rats as a useful tool to interprete carcinogenicity studies where hormonal patterns are perturbated. From 16 weeks of age oestrous cycles were monitored every 6 weeks to investigate reproductive ageing. A subset of 20 females was used to assess fertility at 21 months of age. The animals were necropsied after 106-107 weeks on study and female reproductive organs, mammary glands and pituitary glands were examined for hyperplasias and/or tumours. The majority of rats had regular oestrous cycles up to 6 months of age. After this age, there was a rapid decline in the number of rats with regular oestrous cycles and an increase in irregular cycles and cycles in persistent di-oestrus with an occasional pro-oestrus. By the end of the study, the majority of animals were acyclic and the few remaining cyclic animals had irregular cycles. In the fertility assessment, 19/20 animals mated but only four animals became pregnant. These pregnant animals had normal numbers of corpora lutea of pregnancy but had high pre-implantation losses and could not sustain a viable pregnancy. 65 animals (62.5%) showed adenomas and/or pituitary hyperplasia in the pituitary gland at necropsy. The pituitary tumours were likely to be prolactin secreting that give rise to pseudopregnancy and mammary tumours, demonstrated by the fact that 43/65 (66%) of the affected animals had histopathological signs of these conditions. Multiple corpora lutea were found in 61% of all animals at time of termination. Only one uterine tumour was seen in this study probably due to lack of persistent oestrus seen in these animals.
Moona, Mohammad Shafi; Mehdi, Itrat
A 32 year Libyan male presented with the complaints of headache and diplopia. He was diagnosed with a cavernous sinus meningioma on the basis of MRI findings but no initial biopsy was taken. Depending on the radiologic diagnosis the patient was treated with gamma knife surgery twice, abroad. During follow up he developed left ear deafness and left cervical lymph adenopathy. An ENT evaluation with biopsy from the nasopharynx and cervical lymph node was taken. The histopathologic diagnosis of the resected tumour showed a nasopharyngeal carcinoma with cervical lymph node metastasis (poorly differentiated lympho-epithelial carcinoma). The cavernous sinus tumour which was initially treated as a meningioma was in fact metastasis from the nasopharyngeal carcinoma, making this an interesting and rare occurrence.
Nasit, Jitendra G.; Shah, Payal; Zalawadia, Himanshu
Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal tumour. DNET is classified as Grade I neoplasm in revised World Health Organization classification of tumors of the nervous system. DNET is commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant complex partial seizures. Tumors arising in association with DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are reported. Surgical excision is the only successful management with favourable prognosis. The development of recurrence and malignancy after subtotal or even after complete excision challenges the premise of stability and highlights the importance of close clinical follow up. Here, a case of DNET with area of PA is described which helps in understanding the pathogenesis and biological behavior of DNET. PMID:27695565
Kaur, J; Madan, R; Singh, L; Sharma, D N; Julka, P K; Rath, G K; Roy, S
Malignant peripheral nerve sheath tumour (MPNST) is a rare variety of soft tissue sarcoma that originates from Schwann cells or pluripotent cells of neural crest origin. They have historically been difficult tumours to diagnose and treat. Surgery is the mainstay of treatment with a goal to achieve negative margins. Despite aggressive surgery and adjuvant therapy, the prognosis of patients with MPNST remains poor. MPNST arising from penis is a very rare entity; thus, it presents a diagnostic and therapeutic challenge. We present a case of penile MPNST in a 38-year-old man in the absence of neurofibromatosis treated with surgery followed by post-operative radiotherapy to a dose of 60 Gray in 30 fractions and adjuvant chemotherapy with ifosfamide and adriamycin.
Scott, Si; Antwi-Yeboah, Y; Bucur, Sd
Carcinoid tumours are rare with an incidence of 5.25/100,000. They predominantly originate in the gastrointestinal tract (50-60%) or bronchopulmonary system (25-30%). Common sites of metastasis are lymph nodes, liver, lungs and bone. Spinal metastasis are rare, but has been reported in patients with symptoms of spinal cord compression including neurological deficits. We report a rare case of carcinoid metastasis with spinal cord compression, in a 63-year-old man, presenting with a one-year history of back pain without any neurological symptoms. The patient underwent a two-level decompressive laminectomy of T10 and T11 as well as piecemeal tumour resection. Post-operatively the patient made a good recovery without complications.
Scott, SI; Antwi-Yeboah, Y; Bucur, SD
Carcinoid tumours are rare with an incidence of 5.25/100,000. They predominantly originate in the gastrointestinal tract (50-60%) or bronchopulmonary system (25-30%). Common sites of metastasis are lymph nodes, liver, lungs and bone. Spinal metastasis are rare, but has been reported in patients with symptoms of spinal cord compression including neurological deficits. We report a rare case of carcinoid metastasis with spinal cord compression, in a 63-year-old man, presenting with a one-year history of back pain without any neurological symptoms. The patient underwent a two-level decompressive laminectomy of T10 and T11 as well as piecemeal tumour resection. Post-operatively the patient made a good recovery without complications. PMID:24960730
Chauvet, N; Romanò, N; Meunier, A-C; Galibert, E; Fontanaud, P; Mathieu, M-N; Osterstock, G; Osterstock, P; Baccino, E; Rigau, V; Loiseau, H; Bouillot-Eimer, S; Barlier, A; Mollard, P; Coutry, N
Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, β-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.
Bainbridge, Hannah E; Larbi, Emmanuel; Middleton, Gary
Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, increases progression-free survival in patients with advanced neuroendocrine tumours. Patients with neuroendocrine tumours and symptomatic carcinoid have inferior health-related quality of life than those without symptoms. We aimed to evaluate the effect of everolimus on symptomatic control of neuroendocrine tumours. Fifteen patients with metastatic neuroendocrine disease pre-treated with depot octreotide received combination everolimus and octreotide (midgut = 8, pancreatic = 3, other = 4). Reasons for initiation of everolimus were progressive disease (PD) by response evaluation criteria in solid tumours (n = 5), worsening syndromic symptomology (n = 5), or both (n = 5). Symptomatic and objective response and toxicity were evaluated using standard criteria. 7/10 patients who were syndromic had improvements in symptomology, with a mean duration of symptom control 13.9 months (range 1-39). All 10 symptomatic patients had non pancreatic neuroendocrine (pNET) primaries, and with everolimus, 6/10 had reduced stool frequency, 3/7 had a reduction of asthenia, and 5/7 had reduced frequency and severity of flushing. Sixty percent of patients experienced any grade toxicities, including the following: 40% grade 1/2 stomatitis, 7% grade 3/4 stomatitis, 20% grade 1/2 rash, 13% diarrhoea, and one case of pneumonitis. In this cohort of 15 patients, we demonstrated that 70% of non pNET individuals with common carcinoid syndrome symptoms resistant to depot octreotide had improvement in these symptoms on institution of everolimus, with meaningful durations of symptom control. Although this data is observational, to our knowledge, this represents the largest analysis of carcinoid syndrome control with combined everolimus and octreotide.
Hétet, J F; Rigaud, J; Dorel-Le Théo, M; Láuté, F; Karam, G; Blanchet, P
Kidney cancer occurs rarely and late in renal transplants. The lack of grafts and the increasing age of the cadaver donors are likely to result in an increasing number of such cancers. To date, the treatment of choice is the transplant removal. Nevertheless partial nephrectomy may be discussed in selected cases. Ultrasonographic screening should allow detection of low volume tumours suitable for partial nephrectomy. Alternative techniques (radiofrequency, cryoablation) are to be assessed in such patients.
Insulinoma is a deceptive endocrine tumour that can easily mislead even an astute clinician because of its bizarre and nonspecific symptom complex. A 45 year old woman presented with altered behaviour, seizures and spells of coma and was being treated as a case of hysterical neurosis. Biochemical and radiological investigations revealed fasting hypoglycaemia, endogenous hyperinsulinism, and a pancreatic parenchymal lesion. Removal of the pancreatic lesion resulted in abrupt restoration of euglycaemia and complete disappearance of patients' symptoms.
Wojtyła-Buciora, Paulina; Więckowska, Barbara; Krzywinska-Wiewiorowska, Małgorzata; Gromadecka-Sutkiewicz, Małgorzata
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
Matzku, S.; Moldenhauer, G.; Kalthoff, H.; Canevari, S.; Colnaghi, M.; Schuhmacher, J.; Bihl, H.
Internalization of monoclonal antibody (MAb) conjugates is an important feature of tumour targeting, both with respect to the therapeutic action of substances coupled to the antibody and to retention of radionuclides. Problems of analysing internalization in vitro and in vivo, of manipulating internalization, and of evaluating the involvement of normal tissues are illustrated by recent experimental data and are discussed in the light of published evidence. Images Figure 4 PMID:2383472
Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Tesic Mark, Milica; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M; Dumont-Cole, Vanessa D; Kramer, Kimberly; Wexler, Leonard H; Narendran, Aru; Schwartz, Gary K; Healey, John H; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H; Grandgenett, Paul M; Hollingsworth, Michael A; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K; Jarnagin, William R; Brady, Mary S; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J; Bissell, Mina J; Garcia, Benjamin A; Kang, Yibin; Rajasekhar, Vinagolu K; Ghajar, Cyrus M; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David
Ever since Stephen Paget's 1889 hypothesis, metastatic organotropism has remained one of cancer's greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.
Rück, A.; Hauser, C.; Lorenz, S.; Mosch, S.; Rotte, S.; Kessler, M.; Kalinina, S.
Fluorescence guided diagnosis of tumour tissue is in many cases insufficient, because false positive results are interfering with the outcome. Discrimination between tumour and inflammation could be therefore difficult. Improvement of fluorescence diagnosis through observation of cell metabolism could be the solution, which needs a detailed understanding of the origin of autofluorescence. However, a complex combination of fluorophores give rise to the emission signal. Also in PDD (photodynamic diagnosis) different photosensitizer metabolites contribute to the fluorescence signal. Therefore, the fluorescence decay in many cases does not show a simple monoexponential profile. In those cases a considerable improvement could be achieved when time-resolved and spectral-resolved techniques are simultaneously incorporated. The discussion will focus on the detection of NADH, FAD and 5-ALA induced porphyrins. With respect to NADH and FAD the discrimination between protein bound and free coenzyme was investigated with multispectral FLIM in normal oral keratinocytes and squamous carcinoma cells from different origin. The redox ratio, which can be correlated with the fluorescence lifetimes of NADH and FAD changed depending on the state of the cells. Most of the investigations were done in monolayer cell cultures. However, in order to get information from a more realistic in vivo situation additionally the chorioallantoismembrane (CAM) of fertilized eggs was used where tumour cells or biopsies were allowed to grow. The results of theses measurements will be discussed as well.
Lopes, Lisandro F; Bacchi, Carlos E
Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.
Lopes, Lisandro F; Bacchi, Carlos E
Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734
Hoshino, Ayuko; Costa-Silva, Bruno; Shen, Tang-Long; Rodrigues, Goncalo; Hashimoto, Ayako; Mark, Milica Tesic; Molina, Henrik; Kohsaka, Shinji; Di Giannatale, Angela; Ceder, Sophia; Singh, Swarnima; Williams, Caitlin; Soplop, Nadine; Uryu, Kunihiro; Pharmer, Lindsay; King, Tari; Bojmar, Linda; Davies, Alexander E.; Ararso, Yonathan; Zhang, Tuo; Zhang, Haiying; Hernandez, Jonathan; Weiss, Joshua M.; Dumont-Cole, Vanessa D.; Kramer, Kimberly; Wexler, Leonard H.; Narendran, Aru; Schwartz, Gary K.; Healey, John H.; Sandstrom, Per; Labori, Knut Jørgen; Kure, Elin H.; Grandgenett, Paul M.; Hollingsworth, Michael A.; de Sousa, Maria; Kaur, Sukhwinder; Jain, Maneesh; Mallya, Kavita; Batra, Surinder K.; Jarnagin, William R.; Brady, Mary S.; Fodstad, Oystein; Muller, Volkmar; Pantel, Klaus; Minn, Andy J.; Bissell, Mina J.; Garcia, Benjamin A.; Kang, Yibin; Rajasekhar, Vinagolu K.; Ghajar, Cyrus M.; Matei, Irina; Peinado, Hector; Bromberg, Jacqueline; Lyden, David
Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis. PMID:26524530
Harjes, U; Bridges, E; Gharpure, K M; Roxanis, I; Sheldon, H; Miranda, F; Mangala, L S; Pradeep, S; Lopez-Berestein, G; Ahmed, A; Fielding, B; Sood, A K; Harris, A L
Fatty acid binding protein 4 (FABP4) is a fatty acid chaperone, which is induced during adipocyte differentiation. Previously we have shown that FABP4 in endothelial cells is induced by the NOTCH1 signalling pathway, the latter of which is involved in mechanisms of resistance to antiangiogenic tumour therapy. Here, we investigated the role of FABP4 in endothelial fatty acid metabolism and tumour angiogenesis. We analysed the effect of transient FABP4 knockdown in human umbilical vein endothelial cells on fatty acid metabolism, viability and angiogenesis. Through therapeutic delivery of siRNA targeting mouse FABP4, we investigated the effect of endothelial FABP4 knockdown on tumour growth and blood vessel formation. In vitro, siRNA-mediated FABP4 knockdown in endothelial cells led to a marked increase of endothelial fatty acid oxidation, an increase of reactive oxygen species and decreased angiogenesis. In vivo, we found that increased NOTCH1 signalling in tumour xenografts led to increased expression of endothelial FABP4 that decreased when NOTCH1 and VEGFA inhibitors were used in combination. Angiogenesis, growth and metastasis in ovarian tumour xenografts were markedly inhibited by therapeutic siRNA delivery targeting mouse endothelial FABP4. Therapeutic targeting of endothelial FABP4 by siRNA in vivo has antiangiogenic and antitumour effects with minimal toxicity and should be investigated further. PMID:27568980
Keane, Fergus; Navin, Patrick; Brett, Francesca; Dennedy, Michael C
Summary Pituitary apoplexy represents an uncommon endocrine emergency with potentially life-threatening consequences. Drug-induced pituitary apoplexy is a rare but important consideration when evaluating patients with this presentation. We describe an unusual case of a patient with a known pituitary macroadenoma presenting with acute-onset third nerve palsy and headache secondary to tumour enlargement and apoplexy. This followed gonadotropin-releasing hormone (GNRH) agonist therapy used to treat metastatic prostate carcinoma. Following acute management, the patient underwent transphenoidal debulking of his pituitary gland with resolution of his third nerve palsy. Subsequent retrospective data interpretation revealed that this had been a secretory gonadotropinoma and GNRH agonist therapy resulted in raised gonadotropins and testosterone. Hence, further management of his prostate carcinoma required GNRH antagonist therapy and external beam radiotherapy. This case demonstrates an uncommon complication of GNRH agonist therapy in the setting of a pituitary macroadenoma. It also highlights the importance of careful, serial data interpretation in patients with pituitary adenomas. Finally, this case presents a unique insight into the challenges of managing a hormonal-dependent prostate cancer in a patient with a secretory pituitary tumour. Learning points While non-functioning gonadotropinomas represent the most common form of pituitary macroadenoma, functioning gonadotropinomas are exceedingly rare. Acute tumour enlargement, with potential pituitary apoplexy, is a rare but important adverse effect arising from GNRH agonist therapy in the presence of both functioning and non-functioning pituitary gonadotropinomas. GNRH antagonist therapy represents an alternative treatment option for patients with hormonal therapy-requiring prostate cancer, who also have diagnosed with a pituitary gonadotropinoma. PMID:27284452
Bignold, L P
The pathological characteristics of tumour cells often include variation of their histopathological features (i.e. "degrees of de-differentiation") between cases of the same tumour type and between different foci within individual tumours. Usually, only a few cell lines from tumours are immortal. Currently, somatic mutation, replicative infidelity of DNA and aneuploidy are suggested as alternative mechanisms of genomic disturbance underlying tumours. Nevertheless, apart from Hansemann's ideas of "anaplasia" and "de-differentiation" (proposed in the 1890s), and supposed "evolutionary themes" in cancer cell biology, little has been published concerning how histopathologic variation and immortality in tumour cells might arise. This paper reviews applications of the concepts of "variation" to tumours, including concepts of "evolution" and "cellular Darwinism". It is proposed that combinations of somatic mutation, DNA replicative infidelity and aneuploidy may explain the variabilities in tumours, and provide immortality in occasional tumour cells. A possible model involves (i) an initial somatic mutation causing reduced replicative fidelity of DNA, which could be variable in intensity, and thus give rise to variations between cases; (ii) a phase of replicative infidelity of DNA causing daughter cells lines to develop various abnormalities to different degrees, and hence provide for variation between areas of the same tumour. As a last event (iii) occasional asymmetric chromosomal distributions (aneuploidy) might "refresh" the ability of a daughter cell to replicate DNA faithfully causing them to become immortal. Thus extensively mutant and variable, hyperploid, and occasionally immortal cells might arise.
Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W
Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.
Immunohistochemical demonstration of oestrogen and progesterone receptors: correlation of standards achieved on in house tumours with that achieved on external quality assessment material in over 150 laboratories from 26 countries
Rhodes, A; Jasani, B; Balaton, A; Miller, K
Aims—To investigate the sensitivity of immunohistochemical (IHC) assays for oestrogen receptors (ER) and progesterone receptors (PR) achieved by laboratories on breast tumours fixed and processed in their own department, and to compare this with the degree of sensitivity they achieve on tumours circulated as part of an external quality assessment (EQA) programme. Methods—On 10 occasions between April 1994 and June 1998, histological sections from breast cancers showing various degrees of expression of ER and PR were circulated for IHC staining to laboratories participating in the UK national external quality assessment scheme for immunocytochemistry (UK NEQAS-ICC). The staining of these tumours, in addition to that of tumours fixed and processed in the participants own laboratories (in house tumours), was assessed by a panel of four assessors, using the established UK NEQAS-ICC scoring system. For a selected assessment run, the degree of expression of participants in house tumours was evaluated by means of the semiquantitative quick score method. Results—Although the scores awarded for the staining of in house tumours were generally higher than those awarded for the staining of UK NEQAS tumours, there was also a significant positive correlation between the two sets of scores. Using the quick score method of evaluation for one of the assessment runs, 47% of in house tumours were classified as having a high degree of ER expression. Of the remaining cases, a significant proportion initially classified as having only low or medium expression of ER were found to have higher expression when stained by the organising laboratory. The UK NEQAS-ICC centre's routine assay for hormonal receptors was found to be 90–100% efficient in achieving optimal demonstration of breast tumours from over 150 different laboratories. Conclusions—The significant positive correlation between the results obtained on the UK NEQAS tumours and the in house tumours provides evidence for
Ibebuike, K E; Pather, S; Emereole, O; Ndolo, P; Kajee, A; Gopal, R; Naidoo, S
Dural-based brain tumours, apart from meningiomas, are rare. Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) is a documented but rare disease that occurs in immunocompromized patients. These tumours may be located at unusual sites including the brain. We present a 37-year-old patient, positive for the human immunodeficiency virus (HIV), who was admitted after generalized tonic-clonic seizures. MRI and CT scan revealed a dural-based brain tumour, intraoperatively thought to be a meningioma, but with an eventual histological diagnosis of EBV-SMT. Clinically the patient was well postoperatively with a Glasgow coma scale score of 15/15 and no focal neurologic deficit. This case confirms the association between EBV and SMT in patients with HIV/acquired immunodeficiency syndrome (AIDS). It also highlights the need to include EBV-SMT in the differential diagnosis of intracranial mass lesions in patients with HIV/AIDS.
Cowan, M; Davies, J; Brookes, K; Billstrom, M; McLeish, P; Buchan, A; Skinner, G R
Inoculation of herpesviruses and encephalomyocarditis virus into subcutaneous tumours in hamsters and mice reduced the rate of tumour growth compared to untreated tumours or secondary tumours which had arisen following surgical excision of the primary tumour; in addition, survival times were increased in animals whose tumours were inoculated with virus. It is suggested that the role of virus in the modification of tumour growth merits further exploration.
... made products. These are made in a compounding pharmacy(a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...
... made products. These are made in a compounding pharmacy (a pharmacy that mixes medications according to a doctor’s instructions). ... that bioidentical hormones, whether prepared by a compounding pharmacy or pharmaceutical company, are safer to use than ...
... the participating organizations that have assisted in its reproduction and distribution. Learn More about Menopause and Hormones ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products
... abnormal uterine bleeding is caused by a hormone imbalance. DUB is more common in teenagers or in women who are approaching menopause. DUB is unpredictable. The bleeding may be very heavy or light and can occur often or randomly.
... under the skin) Infection (a slight risk any time the skin is broken) Alternative Names GH test Images Growth hormone stimulation test - series References Ali O. Hyperpituitarism, tall stature, and overgrowth ...
Liu, Yu-Jie; Dou, Xiao-Qian; Wang, Fang; Zhang, Jing; Wang, Xiao-Lin; Xu, Gui-Li; Xiang, Shen-Si; Gao, Xin; Fu, Jie; Song, Hai-Feng
Tumour immunosuppressive microenvironments inhibit antigen-specific cellular responses and interfere with CpG-mediated immunotherapy. Overcoming tumour microenvironment (TME) immunosuppression is an important strategy for effective therapy. This study investigated the ability of a tumour-targeting IL-4Rα aptamer-liposome-CpG ODN delivery system to introduce CpG into tumours and overcome the immunosuppressive TME. The IL-4Rα-liposome-CpG delivery system was prepared. FAM-CpG visualisation was used to demonstrate tumour targeting in vitro and in vivo. Anti-tumour effects of this delivery system were evaluated in CT26 tumour-bearing mice. Mechanisms for conquering the TME were investigated. FAM-CpG was better distributed into the tumours upon treatment with IL-4Rα-liposome-FAM-CpG compared to distribution in the control group in vitro and in vivo. IL-4Rα-aptamer-liposome-CpG treatment inhibited distinct myeloid-derived suppressor cell populations in tumours and bone marrow. Similar profiles were observed for regulatory T cells in tumours. In CT26 tumour-bearing mice, IL-4Rα-liposome-CpG treatment exhibited enhanced anti-tumour activity. Increased mRNA levels of TNF-α, IL-2, and IL-12, and decreased mRNA levels of VEGF, IL-6, IL-10, MMP9, arginase-1, inducible NOS, CXCL9, p-Stat3, and NF-κB were observed in tumours upon IL-4R-liposome-CpG-treatment. The results suggested that pharmacologic targeting by the IL-4R aptamer-liposome-CpG system improves TME therapeutic benefit and provides a rationale for cancer immunotherapies.
Zaffryar-Eilot, Shelly; Marshall, Derek; Voloshin, Tali; Bar-Zion, Avinoam; Spangler, Rhyannon; Kessler, Ofra; Ghermazien, Haben; Brekhman, Vera; Suss-Toby, Edith; Adam, Dan; Shaked, Yuval; Smith, Victoria; Neufeld, Gera
Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours.
Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.
Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases. PMID:28117293
Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron
A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and
Feiden, S; Sartorius, E; Feiden, W
Inherited cancer syndromes often involve the central and peripheral nervous system. For the surgical neuropathologist the possibility in individual patients of a familial tumour syndrome needs to be considered in the case of special tumours such as malignant peripheral nerve sheath tumour (MPNST), medulloblastoma with extensive nodularity (MBEN) or even atypical teratoid/rhabdoid tumour (AT/RT) of the brain. Furthermore, tumour location and patient age may point to a familial tumour syndrome as in the case of neurofibromatosis type 2 (NF2) with typical bilateral vestibular schwannoma in young age. This short review discusses some of the diagnostic aspects in this field relating to neurofibromatosis type 1 and 2 (NF1, NF2), as well as the two rare tumors MBEN in Gorlin-Goltz syndrome and AT/RT in particular.
Liloia, Concetta; Piscioneri, Jessica; Ugolini, Clara; Strambi, Silvia
Krukenberg tumours are rare metastatic tumours of the ovaries characterized by the presence of mucin-producing neoplastic Signet Ring Cell Carcinoma (SRCC). At first glance, this tumour may be confused with a primary ovarian tumour. Surgery and chemotherapy combination have led to improvement in prognosis, but it still remains severe. We report the case of a 60-year-old woman with a Krukenberg tumour rising from a low differentiated gastric adenocarcinoma. The patient was clinically stable for 26 months after surgery until she experienced a prompt decline and died of cerebral haemorrhage within two weeks. The aim of this article was to give an overview of the Krukenberg tumour starting from our case report and comparing it with clinicopathological characteristics of this pathology derived from a review of recent literature. PMID:27891398
Alonso, Guillermo; Varsavsky, Mariela
Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies.
Milotti, Edoardo; Stella, Sabrina; Chignola, Roberto
Hypoxia is central to tumour evolution, growth, invasion and metastasis. Mathematical models of hypoxia based on reaction-diffusion equations provide seemingly incomplete descriptions as they fail to predict the measured oxygen concentrations in the tumour microenvironment. In an attempt to explain the discrepancies, we consider both the inhomogeneous distribution of oxygen-consuming cells in solid tumours and the dynamics of blood flow in the tumour microcirculation. We find that the low-frequency oscillations play an important role in the establishment of tumour hypoxia. The oscillations interact with consumption to inhibit oxygen diffusion in the microenvironment. This suggests that alpha-blockers–a class of drugs used to treat hypertension and stress disorders, and known to lower or even abolish low-frequency oscillations of arterial blood flow –may act as adjuvant drugs in the radiotherapy of solid tumours by enhancing the oxygen effect.
Gniadecka, M.; Nielsen, O. F.; Wulf, H. C.
Analysis of the low frequency region of Raman spectra enables determination of water structure. It has been previously demonstrated by various techniques that water content and possibly also the water structure is altered in some malignant tumours. To further elucidate possible change in water structure in tumours we performed NIR FT Raman spectroscopy on biopsies from selected benign and malignant skin tumours (benign: seborrheic keratosis, pigmented nevi; malignant: malignant melanoma, basal cell carcinoma). We did not observe any differences in water content between malignant and benign skin tumours with an exception of seborrheic keratosis, in which the water content was decreased. Increase in the tetrahedral (free) water was found in malignant skin tumours and sun-damaged skin relative to normal young skin and benign skin tumours. This finding may add to the understanding of molecular alterations in cancer.
Wabada, S; Abubakar, A S; Adamu, A I; Kabir, A; Gana, L B
Wilms' tumour originates predominantly in the renal tissue; in rare cases it can also arise from extra-renal sites accounting for 0.5-1% of cases of Wilms' tumours seen. A diagnosis of extra-renal Wilms' cannot be easily established with clinical and radiological features except when the histological facts are provided. Wilms' tumours arising from extra-renal sites may not be different in clinical features, protocol of treatment and outcome from a typical intra renal Wilms' tumour. A 2-year-old boy presented with an asymptomatic abdominal swelling for 3 months. Abdominal ultrasound and CT scans revealed an extra-renal mass. Intravenous urogram (IVU) showed prompt excretion bilaterally. Post excision histology of the tumour confirmed a Wilms' tumour.
Milotti, Edoardo; Stella, Sabrina; Chignola, Roberto
Hypoxia is central to tumour evolution, growth, invasion and metastasis. Mathematical models of hypoxia based on reaction-diffusion equations provide seemingly incomplete descriptions as they fail to predict the measured oxygen concentrations in the tumour microenvironment. In an attempt to explain the discrepancies, we consider both the inhomogeneous distribution of oxygen-consuming cells in solid tumours and the dynamics of blood flow in the tumour microcirculation. We find that the low-frequency oscillations play an important role in the establishment of tumour hypoxia. The oscillations interact with consumption to inhibit oxygen diffusion in the microenvironment. This suggests that alpha-blockers–a class of drugs used to treat hypertension and stress disorders, and known to lower or even abolish low-frequency oscillations of arterial blood flow –may act as adjuvant drugs in the radiotherapy of solid tumours by enhancing the oxygen effect. PMID:28045083
Fridlyand, Leonid E.; Tamarina, Natalia A.; Schally, Andrew V.; Philipson, Louis H.
Growth hormone-releasing hormone (GHRH) is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition, GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR) has been demonstrated in different peripheral tissues and cell types, including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggest that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications. PMID:27777568
Johnstone, Cameron N; Smith, Yvonne E; Cao, Yuan; Burrows, Allan D; Cross, Ryan S N; Ling, Xiawei; Redvers, Richard P; Doherty, Judy P; Eckhardt, Bedrich L; Natoli, Anthony L; Restall, Christina M; Lucas, Erin; Pearson, Helen B; Deb, Siddhartha; Britt, Kara L; Rizzitelli, Alexandra; Li, Jason; Harmey, Judith H; Pouliot, Normand; Anderson, Robin L
The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53) tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR). Only 67NR displayed nuclear estrogen receptor alpha (ERα) positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3), parathyroid hormone-like hormone (Pthlh) and S100 calcium binding protein A8 (S100a8) and downregulation of the thrombospondin receptor (Cd36) might be causally involved in metastatic dissemination of breast cancer.
Johnstone, Cameron N.; Smith, Yvonne E.; Cao, Yuan; Burrows, Allan D.; Cross, Ryan S. N.; Ling, Xiawei; Redvers, Richard P.; Doherty, Judy P.; Eckhardt, Bedrich L.; Natoli, Anthony L.; Restall, Christina M.; Lucas, Erin; Pearson, Helen B.; Deb, Siddhartha; Britt, Kara L.; Rizzitelli, Alexandra; Li, Jason; Harmey, Judith H.; Pouliot, Normand; Anderson, Robin L.
The translation of basic research into improved therapies for breast cancer patients requires relevant preclinical models that incorporate spontaneous metastasis. We have completed a functional and molecular characterisation of a new isogenic C57BL/6 mouse model of breast cancer metastasis, comparing and contrasting it with the established BALB/c 4T1 model. Metastatic EO771.LMB tumours were derived from poorly metastatic parental EO771 mammary tumours. Functional differences were evaluated using both in vitro assays and spontaneous metastasis assays in mice. Results were compared to non-metastatic 67NR and metastatic 4T1.2 tumours of the 4T1 model. Protein and transcript levels of markers of human breast cancer molecular subtypes were measured in the four tumour lines, as well as p53 (Tp53) tumour-suppressor gene status and responses to tamoxifen in vivo and in vitro. Array-based expression profiling of whole tumours identified genes and pathways that were deregulated in metastatic tumours. EO771.LMB cells metastasised spontaneously to lung in C57BL/6 mice and displayed increased invasive capacity compared with parental EO771. By immunohistochemical assessment, EO771 and EO771.LMB were basal-like, as was the 4T1.2 tumour, whereas 67NR had a luminal phenotype. Primary tumours from all lines were negative for progesterone receptor, Erb-b2/Neu and cytokeratin 5/6, but positive for epidermal growth factor receptor (EGFR). Only 67NR displayed nuclear estrogen receptor alpha (ERα) positivity. EO771 and EO771.LMB expressed mutant p53, whereas 67NR and 4T1.2 were p53-null. Integrated molecular analysis of both the EO771/EO771.LMB and 67NR/4T1.2 pairs indicated that upregulation of matrix metalloproteinase-3 (MMP-3), parathyroid hormone-like hormone (Pthlh) and S100 calcium binding protein A8 (S100a8) and downregulation of the thrombospondin receptor (Cd36) might be causally involved in metastatic dissemination of breast cancer. PMID:25633981
Cancer cells exhibit metabolic alterations that distinguish them from healthy tissues and make their metabolic processes susceptible to pharmacological targeting. Although typical cell-autonomous features of cancer metabolism have been emerging, it is increasingly appreciated that extrinsic factors also influence the metabolic properties of tumours. This review highlights evidence from the recent literature to discuss how conditions within the tumour microenvironment shape the metabolic character of tumours. PMID:28006817
Czirják, S; Bábel, B
Experience with more than 500 tumour cases operated in one year in the National Institute of Neurosurgery and the relevant oncological literature point to an important role of neurosurgery in the treatment of cerebral tumours. After reviewing the dramatic advances of neuroimaging and neurosurgical methods the main problems of neuro-oncology will be brought to light and the new directions of brain tumour research will be shown.
Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M
Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.
Jardel, P; Caujolle, J-P; Gastaud, L; Maschi, C; Sauerwein, W; Thariat, J
Malignant tumours of the eye are not common, barely representing 1 % of all cancers. This article aims to summarise, for each of the main eye malignant diseases, aspects of epidemiology, diagnostic methods and treatments, with a focus on radiation therapy techniques. The studied tumours are: eye metastasis, intraocular and ocular adnexal lymphomas, uveal melanomas, malignant tumours of the conjunctive, of the lids, and retinoblastomas. The last chapter outlines ocular complications of radiation therapy and their management.
Iqbal, Ahmed; Lubina-Solomon, Alexandra; Kew, Fiona M; Webster, Jonathan
of an oestrogen-secreting tumour.JGCTs are rare hormonally active ovarian neoplasms mostly secreting steroid hormones.Serum inhibin can be used as a granulosa cell-specific tumour marker.JGCTs have an excellent prognosis in the early stages of the disease. PMID:27047664
Sin, Eliza I-Lin; Wong, Chow Yin; Yong, Wei Sean; Ong, Kong Wee; Madhukumar, Preetha; Tan, Veronique Kiak Mien; Thike, Aye Aye; Tan, Puay Hoon; Tan, Benita Kiat Tee
Malignant transformation of the epithelial component of phyllodes tumours (PT) is rare and only reported in literature as sporadic cases of carcinoma associated with PTs. We report the clinicopathological characteristics of in situ and invasive carcinoma coexisting with PT in 10 patients treated in our institution over an 11-year period from 1992 to 2012. Ten patients with coexisting PT and in situ or invasive carcinoma were identified from our records. Six had carcinoma found within the PT. All were female with a median age of 47 (43-72) years. One patient had a history of PT in the same breast while another had a history of PT in the same breast as well as invasive ductal carcinoma in the contralateral breast. The rest did not have any risk factors of breast cancer. Five patients had a preoperative core needle biopsy performed with the report of a fibroepithelial lesion. The rest of the patients had surgery upfront for their breast masses. Two patients who had ER/PR positive invasive carcinoma received adjuvant hormonal therapy. Patients were followed up for a mean of 3.6 years (9 months-10 years) and all patients were alive and recurrence free. PT associated with carcinoma is rare, and we present a series of cases that add to the limited current literature. It is often difficult to detect the presence of the carcinomatous component preoperatively. Hence, close examination of resected PT specimens must be carried out to allow prompt detection of any associated carcinomas, however rare, such that adequate treatment can be given.
Møller, A P; Erritzøe, J; Soler, J J
Cancer and tumours may evolve in response to life-history trade-offs between growth and duration of development on one hand, and between growth and maintenance of immune function on the other. Here, we tested whether (i) bird species with slow developmental rates for their body size experience low incidence of tumours because slow development allows for detection of rapid proliferation of cell lineages. We also test whether (ii) species with stronger immune response during development are more efficient at detecting tumour cells and hence suffer lower incidence of tumours. Finally, we tested Peto's paradox, that there is a positive relationship between tumour incidence and body mass. We used information on developmental rates and body mass from the literature and of tumour incidence (8468 birds) and size of the bursa of Fabricius for 7659 birds brought to a taxidermist in Denmark. We found evidence of the expected negative relationship between incidence of tumours and developmental rates and immunity after controlling for the positive association between tumour incidence and body size. These results suggest that evolution has modified the incidence of tumours in response to life history and that Peto's paradox may be explained by covariation between body mass, developmental rates and immunity.
Pouysségur, Jacques; Dayan, Frédéric; Mazure, Nathalie M.
Tumour cells emerge as a result of genetic alteration of signal circuitries promoting cell growth and survival, whereas their expansion relies on nutrient supply. Oxygen limitation is central in controlling neovascularization, glucose metabolism, survival and tumour spread. This pleiotropic action is orchestrated by hypoxia-inducible factor (HIF), which is a master transcriptional factor in nutrient stress signalling. Understanding the role of HIF in intracellular pH (pHi) regulation, metabolism, cell invasion, autophagy and cell death is crucial for developing novel anticancer therapies. There are new approaches to enforce necrotic cell death and tumour regression by targeting tumour metabolism and pHi-control systems.
Lay, Angelina J.; Jiang, Xing-Mai; Kisker, Oliver; Flynn, Evelyn; Underwood, Anne; Condron, Rosemary; Hogg, Philip J.
Disulphide bonds in secreted proteins are considered to be inert because of the oxidizing nature of the extracellular milieu. An exception to this rule is a reductase secreted by tumour cells that reduces disulphide bonds in the serine proteinase plasmin. Reduction of plasmin initiates proteolytic cleavage in the kringle 5 domain and release of the tumour blood vessel inhibitor angiostatin. New blood vessel formation or angiogenesis is critical for tumour expansion and metastasis. Here we show that the plasmin reductase isolated from conditioned medium of fibrosarcoma cells is the glycolytic enzyme phosphoglycerate kinase. Recombinant phosphoglycerate kinase had the same specific activity as the fibrosarcoma-derived protein. Plasma of mice bearing fibrosarcoma tumours contained several-fold more phosphoglycerate kinase, as compared with mice without tumours. Administration of phosphoglycerate kinase to tumour-bearing mice caused an increase in plasma levels of angiostatin, and a decrease in tumour vascularity and rate of tumour growth. Our findings indicate that phosphoglycerate kinase not only functions in glycolysis but is secreted by tumour cells and participates in the angiogenic process as a disulphide reductase.
Kumarguru, B.N.; Bhat, Balachandra; Ramaswamy, A.S.; Kumar, M. Udaya
The peripheral Primitive Neuroectodermal Tumour (PNET) is a member of the family of small round cell tumours. PNET is more aggressive in kidney when compared to the other sites. It usually presents in childhood or adolescence. It has an aggressive clinical course and may process towards metastatic disease culminating in death. A 24-year-old female presented with left sided abdominal swelling. Abdominal ultrasound confirmed a heterogeneous left renal mass. Consequently the patient underwent nephrectomy of left kidney and left oophorectomy. Grossly, the tumour involved almost entire kidney, showed multi-lobular, grey, glistening appearance with focal haemorrhagic areas. Histologically, the tumour cells were arranged in diffuse infiltrating sheets, cohesive lobules, Homer-Wright rosettes and perivascular pseudo-rosettes. Individual tumour cells were small round cells with scant cytoplasm and round nuclei having dispersed chromatin. Features were suggestive of PNET. Immunohistochemistry showed tumour cells displaying strong membrane positivity for MIC 2. Renal PNET needs to be differentiated from other primary and metastatic renal round-cell tumours. Most of the cases of renal PNET have poor response to standard treatment of combined surgical resection, post-operative irradiation, and chemotherapy. PNET is a rare primary tumour in the kidney. Histopathological diagnosis has to be confirmed by immunophenotyping of the tumour cells. PMID:28384877
Nieboer, P; de Vries, E G E; Mulder, N H; van der Graaf, W T A
Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.
Turley, Shannon J; Cremasco, Viviana; Astarita, Jillian L
A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.
Reeves, Emma; James, Edward
The MHC class I and II antigen processing and presentation pathways display peptides to circulating CD8(+) cytotoxic and CD4(+) helper T cells respectively to enable pathogens and transformed cells to be identified. Once detected, T cells become activated and either directly kill the infected / transformed cells (CD8(+) cytotoxic T lymphocytes) or orchestrate the activation of the adaptive immune response (CD4(+) T cells). The immune surveillance of transformed/tumour cells drives alteration of the antigen processing and presentation pathways to evade detection and hence the immune response. Evasion of the immune response is a significant event tumour development and considered one of the hallmarks of cancer. To avoid immune recognition, tumours employ a multitude of strategies with most resulting in a down-regulation of the MHC class I expression at the cell surface, significantly impairing the ability of CD8(+) cytotoxic T lymphocytes to recognize the tumour. Alteration of the expression of key players in antigen processing not only affects MHC class I expression but also significantly alters the repertoire of peptides being presented. These modified peptide repertoires may serve to further reduce the presentation of tumour-specific/associated antigenic epitopes to aid immune evasion and tumour progression. Here we review the modifications to the antigen processing and presentation pathway in tumours and how it affects the anti-tumour immune response, considering the role of tumour-infiltrating cell populations and highlighting possible future therapeutic targets.
Tellez-Gabriel, Marta; Ory, Benjamin; Lamoureux, Francois; Heymann, Marie-Francoise; Heymann, Dominique
Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In previous years, many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e., RNA, DNA, protein and epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study, paying specific attention to those able to assess heterogeneity at the single cell level. PMID:27999407
Ledesma-Montes, C; Garces-Ortiz, M
Salivary gland tumours are an important part of the Oral and Maxillofacial Pathology, unfortunately, only few studies on these tumours have been done in Latin-American population. The aim of this study was to compare demographic data on salivary gland tumours in a Mexican sample with those previously published from Latin American and non-Latin American countries. All cases of salivary gland tumours or lesions diagnosed in our service were reviewed. Of the reviewed cases,67 were confirmed as salivary gland tumours. Out of these 64.2% were benign neoplasms, 35.8% were malignant and a slight female predominance (56.7%) was found. The most common location was palate followed by lips and floor of the mouth. Mean age for benign tumours was 40.6 years with female predominance (60.5%). Mean age for malignant tumours was 41 years and female predominance was found again. Palate followed by retromolar area were the usual locations. Pleomorphic adenoma (58.2%), mucoepidermoid carcinoma (17.9%) and adenoid cystic carcinoma (11.9%) were the more frequent neoplasms. All retromolar cases were malignant and all submandibular gland tumours were benign. We found a high proportion of salivary gland neoplasms in children. Our results showed that differences of the studied tumours among our sample and previously reported series exist. These differences can be related to race and geographical location.
Budhy, T I; Soenarto, S D; Yaacob, H B; Ngeow, W C
A total of 2193 tumours of the mouth and jaw diagnosed at the Laboratorium Patologi Anatomi Fakultas Kedokteran Universitas Airlangga, Indonesia from 1987 to 1992, inclusive, was studied. Malignant tumours constituted 45.3% of the lesions. Almost 71% of the malignant tumours were squamous cell carcinomas. The remainder were salivary gland tumours (21.5%) and sarcomas (4.5%). The male to female ratio for malignant tumours was 5.1:4.7. The incidence of malignant tumours per 100,000 population over the 6-year study period was 2.64. The yearly incidence seemed to increase except in 1990, when it dropped. The incidence of squamous cell carcinoma over the 6 years was 2.1. Calculation of the odds ratio suggested that people aged 40 and over are 5.8 times more likely to develop squamous cell carcinoma.
Fluegen, Georg; Avivar-Valderas, Alvaro; Wang, Yarong; Padgen, Michael R; Williams, James K; Nobre, Ana Rita; Calvo, Veronica; Cheung, Julie F; Bravo-Cordero, Jose Javier; Entenberg, David; Castracane, James; Verkhusha, Vladislav; Keely, Patricia J; Condeelis, John; Aguirre-Ghiso, Julio A
Hypoxia is a poor-prognosis microenvironmental hallmark of solid tumours, but it is unclear how it influences the fate of disseminated tumour cells (DTCs) in target organs. Here we report that hypoxic HNSCC and breast primary tumour microenvironments displayed upregulation of key dormancy (NR2F1, DEC2, p27) and hypoxia (GLUT1, HIF1α) genes. Analysis of solitary DTCs in PDX and transgenic mice revealed that post-hypoxic DTCs were frequently NR2F1(hi)/DEC2(hi)/p27(hi)/TGFβ2(hi) and dormant. NR2F1 and HIF1α were required for p27 induction in post-hypoxic dormant DTCs, but these DTCs did not display GLUT1(hi) expression. Post-hypoxic DTCs evaded chemotherapy and, unlike ER(-) breast cancer cells, post-hypoxic ER(+) breast cancer cells were more prone to enter NR2F1-dependent dormancy. We propose that primary tumour hypoxic microenvironments give rise to a subpopulation of dormant DTCs that evade therapy. These post-hypoxic dormant DTCs may be the source of disease relapse and poor prognosis associated with hypoxia.
Raposo, T P; Pires, I; Carvalho, M I; Prada, J; Argyle, D J; Queiroga, F L
Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.
Clavo, Bernardino; Pérez, Juan L; López, Laura; Suárez, Gerardo; Lloret, Marta; Morera, Jesús; Macías, David; Martínez, José C; Santana, Maite; Hernández, María A; Robaina, Francisco; Günderoth, Martina
Haemoglobin concentrations and tumour-pO(2) were evaluated pre-therapy in 30 patients with head and neck cancers. Anterior tibialis muscle-pO(2) was additionally measured in 16 of these patients. Tumour-pO(2) was lower in the most anaemic patients (P=0.032) and correlated with muscle-pO(2) (r=0.809, P<0.001). These results suggest that haemoglobin concentration influences tumour-oxygenation.
Singh, Ajay Kr; Shubham, Swasti; Maan, Pratibha; Chauhan, Udit
Granular Cell Tumour (GCT), also known as Abrikossoff’s tumour is a rare neural tumour, mostly benign and solitary but rare malignant and multifocal occurrence are also reported. Location of tumour varies widely within body with tongue, skin and subcutaneous tissue being the most common sites. We report a case of malignant GCT in a 17-year-old male presented with a paravertebral swelling. Radiological and histopathological findings along with immunohistochemistry were of malignant GCT. We emphasize this case for its uncommon age and site of presentation in addition to invasive nature.
Mahmood, Muhammad Muzaffar; John, Kurien
Hypokalaemia is a common and often benign observation. There is usually an obvious underlying cause for the anomaly. However, hypokalaemia can very rarely be the sole presentation of a more sinister disease. A high index of suspicion and a systematic approach are therefore required to avoid delays in the management, especially in the context of presentation to a medical team. We present a case of a patient with severe and persistent hypokalaemia due to ectopic adrenocorticotropic hormone (ACTH) secretion secondary to a carcinoid tumour. The case report is followed by a brief discussion on the approach to the management of hypokalaemia and additional tests to confirm ectopic ACTH.
Matyakhina, L; Pack, S; Kirschner, L; Pak, E; Mannan, P; Jaikumar, J; Taymans, S; Sandrini, F; Carney, J; Stratakis, C
Carney complex (CNC) is an autosomal dominant multiple endocrine neoplasia and lentiginosis syndrome characterised by spotty skin pigmentation, cardiac, skin, and breast myxomas, and a variety of endocrine and other tumours. The disease is genetically heterogeneous; two loci have been mapped to chromosomes 17q22–24 (the CNC1 locus) and 2p16 (CNC2). Mutations in the PRKAR1A tumour suppressor gene were recently found in CNC1 mapping kindreds, while the CNC2 and perhaps other genes remain unidentified. Analysis of tumour chromosome rearrangements is a useful tool for uncovering genes with a role in tumorigenesis and/or tumour progression. CGH analysis showed a low level 2p amplification recurrently in four of eight CNC tumours; one tumour showed specific amplification of the 2p16-p23 region only. To define more precisely the 2p amplicon in these and other tumours, we completed the genomic mapping of the CNC2 region, and analysed 46 tumour samples from CNC patients with and without PRKAR1A mutations by fluorescence in situ hybridisation (FISH) using bacterial artificial chromosomes (BACs). Consistent cytogenetic changes of the region were detected in 40 (87%) of the samples analysed. Twenty-four samples (60%) showed amplification of the region represented as homogeneously stained regions (HSRs). The size of the amplicon varied from case to case, and frequently from cell to cell in the same tumour. Three tumours (8%) showed both amplification and deletion of the region in their cells. Thirteen tumours (32%) showed deletions only. These molecular cytogenetic changes included the region that is covered by BACs 400-P-14 and 514-O-11 and, in the genetic map, corresponds to an area flanked by polymorphic markers D2S2251 and D2S2292; other BACs on the centromeric and telomeric end of this region were included in varying degrees. We conclude that cytogenetic changes of the 2p16 chromosomal region that harbours the CNC2 locus are frequently observed in tumours from CNC
Darbre, P D; Aljarrah, A; Miller, W R; Coldham, N G; Sauer, M J; Pope, G S
Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.
Bölling, T; Hardes, J; Dirksen, U
The management of bone tumours in paediatric oncology requires careful multidisciplinary planning due to the need for multimodal therapy approaches. The non-specific symptoms often lead to a delayed definitive diagnosis of a bone tumour. Imaging procedures are of major importance for an individualised and optimised treatment planning. They have to be carried out before any surgery, including biopsies. The introduction of multi-agent chemotherapy has led to a significant improvement in survival rates in patients suffering from Ewing's sarcomas and osteosarcomas. However, local therapy still remains indispensable in order to achieve long-term survival. For osteosarcoma, surgery remains the only adequate local therapy modality. Radiotherapy may be considered if surgery is not feasible. In these cases, high radiation doses need to be applied. The choice for local therapy modality is not as clear in patients with Ewing's sarcoma. Today, surgery is often preferred if a wide or at least marginal resection can be carried out. Additional radiotherapy is advised in patients with marginal/intralesional resection or poor histological response to induction chemotherapy. Definitive radiotherapy is recommended for inoperable lesions. In the future, new radiotherapy approaches, such as intensity-modulated radiotherapy or proton therapy, may yield better results with minor risks of late effects.
Jakhetiya, Ashish; Garg, Pankaj Kumar; Prakash, Gaurav; Sharma, Jyoti; Pandey, Rambha; Pandey, Durgatosh
Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs. PMID:27231512
Germain, D; Chevallier, P; Laurent, A; Saint-Jalmes, H
Thermal therapy of tumour including hyperthermia and thermal ablation by heat or cold delivery requires on line monitoring. Due to its temperature sensitivity, Magnetic Resonance Imaging (MRI) allows thermal mapping at the time of the treatment. The different techniques of MR temperature monitoring based on water proton resonance frequency (PRF), longitudinal relaxation time T1, diffusion coefficient and MR Spectroscopic Imaging (MRSI) are reviewed and debated. The PRF method appears the most widely used and the most efficient at high magnetic field in spite of important drawbacks. The T1 method is the easiest method of visualisation of qualitative temperature distribution and quantitative measurement seems possible in the tissue surrounding the tumour up to a temperature of 45-65 degrees C. Despite its high temperature sensitivity, application of the diffusion method in vivo is restricted due to its high motion sensitivity. The recent MRSI technique seems very promising provided acquisition times can be reduced. Results from the literature indicate that MR temperature monitoring in vivo can be achieved in vivo with a precision of about 3 degrees C in 13 s for a voxel of 16 mm3 (1.5 x 1.5 x 7 mm) in 1.5 T scanners.
Skeldon, Anne C.; Chaffey, Gary; Lloyd, David J. B.; Mohan, Vineet; Bradley, David A.; Nisbet, Andrew
Tumours that are low in oxygen (hypoxic) tend to be more aggressive and respond less well to treatment. Knowing the spatial distribution of oxygen within a tumour could therefore play an important role in treatment planning, enabling treatment to be targeted in such a way that higher doses of radiation are given to the more radioresistant tissue. Mapping the spatial distribution of oxygen in vivo is difficult. Radioactive tracers that are sensitive to different levels of oxygen are under development and in the early stages of clinical use. The concentration of these tracer chemicals can be detected via positron emission tomography resulting in a time dependent concentration profile known as a tissue activity curve (TAC). Pharmaco-kinetic models have then been used to deduce oxygen concentration from TACs. Some such models have included the fact that the spatial distribution of oxygen is often highly inhomogeneous and some have not. We show that the oxygen distribution has little impact on the form of a TAC; it is only the mean oxygen concentration that matters. This has significant consequences both in terms of the computational power needed, and in the amount of information that can be deduced from TACs. PMID:22761687
Ward, J P; King, J R
A system of nonlinear partial differential equations is proposed as a model for the growth of an avascular-tumour spheroid. The model assumes a continuum of cells in two states, living or dead, and, depending on the concentration of a generic nutrient, the live cells may reproduce (expanding the tumour) or die (causing contraction). These volume changes resulting from cell birth and death generate a velocity field within the spheroid. Numerical solutions of the model reveal that after a period of time the variables settle to a constant profile propagating at a fixed speed. The travelling-wave limit is formulated and analytical solutions are found for a particular case. Numerical results for more general parameters compare well with these analytical solutions. Asymptotic techniques are applied to the physically relevant case of a small death rate, revealing two phases of growth retardation from the initial exponential growth, the first of which is due to nutrient-diffusion limitations and the second to contraction during necrosis. In this limit, maximal and "linear' phase growth speeds can be evaluated in terms of the model parameters.
Castro, Arturo; Jenkins, Lawrence C; Salas, Nelson; Lorber, Gideon; Leveillee, Raymond J
Improvements in imaging technology have resulted in an increase in detection of small renal masses (SRMs). Minimally invasive ablation modalities, including cryoablation, radiofrequencey ablation, microwave ablation and irreversible electroporation, are currently being used to treat SRMs in select groups of patients. Cryoablation and radiofrequency ablation have been extensively studied. Presently, cryoablation is gaining popularity because the resulting ice ball can be visualized easily using ultrasonography. Tumour size and location are strong predictors of outcome of radiofrequency ablation. One of the main benefits of microwave ablation is that microwaves can propagate through all types of tissue, including desiccated and charred tissue, as well as water vapour, which might be formed during the ablation. Irreversible electroporation has been shown in animal studies to affect only the cell membrane of undesirable target tissues and to spare adjacent structures; however, clinical studies that depict the efficacy and safety of this treatment modality in humans are still sparse. As more experience is gained in the future, ablation modalities might be utilized in all patients with tumours <4 cm in diameter, rather than just as an alternative treatment for high-risk surgical patients.
Mir, L. M.; Glass, L. F.; Sersa, G.; TeissiÃ©, J.; Domenge, C.; Miklavcic, D.; Jaroszeski, M. J.; Orlowski, S.; Reintgen, D. S.; Rudolf, Z.; Belehradek, M.; Gilbert, R.; Rols, M. P.; Belehradek, J.; Bachaud, J. M.; DeConti, R.; Stabuc, B.; Cemazar, M.; Coninx, P.; Heller, R.
Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate. PMID:9649155
Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi
The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions.
Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.
Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.
In in vitro experiments, active transport of thyroid hormones had been repeatedly demonstrated. The membrane transporters for thyroid hormones which have been identified include the organic anion transporting polypeptide, heterodimeric amino acid transporters and the monocarboxylate transporters (MCT) which are the focus of this chapter. The gene encoding MCT8 which was identified as a specific thyroid hormone transporter is located on chromosome Xq13.2. The expression pattern of MCT8 indicates that MCT8 plays an important role in the development of the central nervous system by transporting thyroid hormone into neurons as its main target cells. Mutational analysis of the MCT8 gene revealed mutations or deletions in the MCT8 gene in unrelated male patients with severe psychomotor retardation and biochemical findings consistent with thyroid hormone resistance. Indeed, thyroid function tests in patients with MCT8 mutations demonstrated marked elevations of serum T3 (in the thyrotoxic range), a significant decrease in serum T4 or fT4 and normal to elevated TSH levels.
Amory, J K
Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.
Zych, Sławomir; Szatkowska, Iwona; Czerniawska-Piatkowska, Ewa
The substantial improvement in the studies on a very complicated mechanism-- growth hormone signaling in a cell, has been noted in last decade. GH-induced signaling is characterized by activation of several pathways, including extracellular signal-regulated kinase (ERK), the signal transducer and activator of transcription and phosphatidylinositol-3 kinase (PI3) pathways. This review shows a current model of the growth hormone receptor dimerization, rotation of subunits and JAK2 kinase activation as the initial steps in the cascade of events. In the next stages of the signaling process, the GH-(GHR)2-(JAK2)2 complex may activate signaling molecules such as Stat, IRS-1 and IRS-2, and particularly all cascade proteins that activate MAP kinase. These pathways regulate basal cellular functions including target gene transcription, enzymatic activity and metabolite transport. Therefore growth hormone is considered as a major regulator of postnatal growth and metabolism, probably for mammary gland growth and development too.
Schlienger, J L; Perrin, A E; Grunenberger, F; Goichot, B
Fibromyalgia is a syndrome characterized by chronic musculoskeletal pain and fatigue without biological detectable disturbances. The mechanisms of this disease are unknown. It has been postulated that it can be the consequence of a chronic stress mediated mainly through the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system. These fields have been extensively studied. Results were scattered and non convincing. A reduction of growth hormone and IGF-1 levels described in a third of patients has led to a double blind random clinical trial with biogenetic growth hormone. Results were equivocal . Other hormonal systems are grossly normals and circadian rhythms are unaltered. Despite some arguments in favour of a CRH neurons hyperactivity, these results are not able to consolide a particular physiopathological mechanism and to argument for a new therapeutic approach. Many of the abnormalities may be the consequence of psychological disturbances.
Gajjar, Ketan; Martin-Hirsch, Pierre L; Martin, Francis L
Cancers in hormone-responsive tissues (e.g., breast, ovary, endometrium, prostate) occur at high incidence rates worldwide. However, their genetic basis remains poorly understood. Studies to date suggest that endogenous/exogenous oestrogen and environmental carcinogens may play a role in development and/or progression of hormone-induced cancers via oxidative oestrogen metabolism. Cytochrome P450 1B1 is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Although CYP1B1 is expressed in many cancers, particularly high levels of expression are observed in oestrogen-mediated disease. CYP1B1 is more readily found in tumour tissue compared to normal. Given the role of CYP1B1 in pro-carcinogen and oestrogen metabolism, polymorphisms in CYP1B1 could result in modifications in its enzyme activity and subsequently lead to hormone-mediated carcinogenesis. CYP1B1 may also be involved in progression of the disease by altering the tissue response to hormones and clinical response to chemotherapy. The exact mechanism behind these events is complex and unclear. Only a few functional single nucleotide polymorphisms of CYP1B1 are known to result in amino acid substitutions and have been extensively investigated. Studies examining the contribution of different CYP1B1 alleles to hormone-mediated cancer risks are inconsistent. The main focus of this review is to appraise the available studies linking the pathogenesis of the hormone-induced cancers to various CYP1B1 polymorphisms. Additionally, we explore the role of a neuronal protein, γ-synuclein, in CYP1B1-mediated pathogenesis.
Ferreira, Ana Carolina Franco; Martins, Eivor; Afeche, Solange Castro; Cipolla-Neto, José; Costa Rosa, Luís Fernando Bicudo Pereira
The pineal gland is involved in the regulation of tumour growth through the anticancer activity of melatonin, which presents immunomodulatory, anti-proliferative and anti-oxidant effects. In this study we measured melatonin content directly in the pineal gland, in an attempt to clarify the modulation of pineal melatonin secretory activity during tumour growth. Different groups of Walker 256 carcinosarcoma bearing rats were sacrificed at 12 different time points during 24h (12h:12h light/dark cycle) on different days during the tumour development (on the first, seventh and fourteenth day after tumour inoculation). Melatonin content in the pineal gland was determined by high-performance liquid chromatography with electrochemical detection. During tumour development the amount of melatonin secreted increased from 310.9 ng/mg of protein per day from control animals, to 918.1 ng/mg of protein per day 14 days after tumour implantation, and there were changes in the pineal production profile of melatonin. Cultured pineal glands obtained from tumour-bearing rats turned out to be less responsive to noradrenaline, suggesting the existence, in vivo, of putative factor(s) modulating pineal melatonin production. The results demonstrated that during tumour development there is a modification of pineal melatonin production daily profile, possibly contributing to cachexia, associated to changes in pineal gland response to noradrenaline stimulation.
Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas
The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial. PMID:24567746
Kumar, A. Sathish Selva; Padmini, R; Veena, G; Murugesan, N
Stromal tumours occurring in areas other than the GastroIntestinal Tract (GIT) are known as Extra GastroIntestinal Stromal Tumours (EGISTs). They usually arise in the mesentery, omentum or retroperitoneum, while EGISTs which occur in the abdominal wall are very rare. Both gastrointestinal stromal tumours (GISTs) and EGISTs are histologically and immunophenotypically similar. We are reporting a case of EGIST, which occurred in the anterior abdominal wall in a twenty five-year-old female patient. The tumour was present in the right loin and imaging studies suggested that it was a desmoid tumour. It was surgically excised by doing an abdominal wall mesh repair. The histological examinations revealed a tumour with spindle cell morphology, with <2 mitoses per 50 High Power Field (HPF) and no necrosis, with tumour free margins. Immunohistochemistry was strongly positive for CD117 and Smooth Muscle Actin (SMA), while it was negative for β-catenin and S100. The patient is well post operatively and is on close follow up. EGISTs should be considered in the differential diagnosis of mesenchymal tumours which occur in the abdominal wall, inspite of their rarity, as the high risk patients may need Imatinib chemotherapy. PMID:24551695
Ujvari, Beata; Pearse, Anne-Maree; Swift, Kate; Hodson, Pamela; Hua, Bobby; Pyecroft, Stephen; Taylor, Robyn; Hamede, Rodrigo; Jones, Menna; Belov, Katherine; Madsen, Thomas
The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.
van Crevel, H
The presence or absence of papilloedema and the cisternal CSF pressure were compared with the RIHSA cisternograms in 24 patients with supratenotorial tumours. It was found that severe subarachnoid obstruction of CSF flow, leading to impaired CSF absorption at the superior sagittal sinus, was the main cause of raised CSF pressure and papilloedema associated with supratentorial tumours. Images PMID:469556
Navin, Nicholas; Kendall, Jude; Troge, Jennifer; Andrews, Peter; Rodgers, Linda; McIndoo, Jeanne; Cook, Kerry; Stepansky, Asya; Levy, Dan; Esposito, Diane; Muthuswamy, Lakshmi; Krasnitz, Alex; McCombie, W Richard; Hicks, James; Wigler, Michael
Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse 'pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.
... Isolated growth hormone deficiency Educational Resources (10 links) Boston Children's Hospital CLIMB: Growth Hormone Deficiency Information Sheet (PDF) Disease InfoSearch: Isolated growth hormone deficiency ...
van Bunderen, Christa C; van Varsseveld, Nadège C; Erfurth, Eva Marie; Ket, Johannes C F; Drent, Madeleine L
Due to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant end-points seems feasible. In this review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded, but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and nonfatal malignancies were not more prevalent in GH-treated adults compared to the general population. However, follow-up time is still relatively short. The studies on diabetes are difficult to interpret, and more evidence is awaited. In clinical practice, a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes.
Lauriola, Mattia; Enuka, Yehoshua; Zeisel, Amit; D’Uva, Gabriele; Roth, Lee; Sharon-Sevilla, Michal; Lindzen, Moshit; Sharma, Kirti; Nevo, Nava; Feldman, Morris; Carvalho, Silvia; Cohen-Dvashi, Hadas; Kedmi, Merav; Ben-Chetrit, Nir; Chen, Alon; Solmi, Rossella; Wiemann, Stefan; Schmitt, Fernando; Domany, Eytan; Yarden, Yosef
Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR’s positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR’s feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy. PMID:25278152
Matveev, V B; Volkova, M I; Figurin, K M; Faĭnshteĭn, I A; Mitin, A B; Seryeev, Iu S
The first stage in the treatment of disseminated germinogenic ovarian tumours (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group. Dynamic observation is indicated in case of incomplete induction in patients with seminoma excepting those with PET-positive residual tumours bigger than 3 cm to whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated. Ablation of residual tumour of any localization is indicated to patients with disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of tumour markers. The necessity of adjuvant chemotherapy in case of a viable malignant HOT in the removed tissues remains debatable. Refractory and recurring HOT are usually treated with a combination of fosfamide and vinblastine. Residual tumours need to be removed after salvation chemotherapy. Surgical treatment is the preferred option for the management of late NHOT relapses.
Dean, B J F; Reed, D W; Matthews, J J; Pandit, H; McNally, E; Athanasou, N A; Gibbons, C L M H
Hoffa's fat pad (HFP) of the knee is affected by a variety of tumours and tumour-like conditions. HFP can be affected by diffuse or solitary, focal disease. This paper reports a consecutive series of 19 cases of solitary symptomatic HFP tumours. The commonest presenting symptom was anterior knee pain. All patients underwent open excision after diagnostic magnetic resonance imaging (MRI). Histology revealed varied diagnoses with the commonest being pigmented villonodular synovitis (PVNS) and ganglia. American Knee Society scores improved from 76 pre-operatively to 96 post-operatively with an improvement in functional scores from 92 to 100. In conclusion the majority of solitary HFP tumours are benign and may be either cystic or solid. MRI and plain radiographs are the imaging of choice. The definitive treatments of both cystic and solid tumours should be selective arthrotomy and excision biopsy. All patients in this series reported substantial improvement in symptoms following surgery.
Sánchez-Danés, Adriana; Hannezo, Edouard; Larsimont, Jean-Christophe; Liagre, Mélanie; Youssef, Khalil Kass; Simons, Benjamin D; Blanpain, Cédric
The changes that occur in cell dynamics following oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the impact of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, were competent to initiate tumour formation upon oncogenic hedgehog signalling. Interestingly, this difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase of symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is not only dependent on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin. PMID:27459053
Astreidis, Ioannis T.; Kontos, Konstantinos I.; Lazaridou, Maria N.; Bourlidou, Eleni T.; Gerasimidou, Domniki K.; Vladika, Natalia P.; Mangoudi, Doxa L.
ABSTRACT Background Metastatic tumours to the oral cavity from distant organs are uncommon and represent approximately 1 - 3% of all oral malignancies. Such metastases can occur to the bone or to the oral soft tissues. Almost any malignancy from any site is capable of metastasis to the oral cavity and a wide variety of tumours have been reported to spread to the mouth. Methods Careful examination of the oral cavity and a high degree of clinical suspicion as well as a multidisciplinary approach are suggested. Results In this article we present three patients, a female and two males with metastatic tumours to the oral cavity, who were referred to our Department. The primary tumours were invasive lobular breast carcinoma, gastric adenocarcinoma and small cell lung carcinoma respectively. Conclusions Metastases to the oral cavity are quite uncommon among population. They usually present with symptoms similar to odontogenic infections and benign tumours, causing a delayed diagnosis and treatment. PMID:26904182
Cornelis, F; Balageas, P; Le Bras, Y; Rigou, G; Boutault, J-R; Bouzgarrou, M; Grenier, N
Thermal ablation techniques for renal tumours have become the norm in surgically at-risk patients. These percutaneous treatments are locally effective, particularly for tumours measuring less than 4cm. Larger tumours may be treated by adapting the technique and strategy. Multidisciplinary discussion is essential before any decision, in order to decide on the most appropriate technique. Radiofrequency is simple, effective and inexpensive. Cryotherapy is more complex and should be preferred when the tumour is large or there is vascular or urinary tract contact. Microwaves can be used to treat larger tumours. Morbidity is low, but good knowledge of these techniques and of dissection is required to avoid injury to neighbouring digestive or urinary structures.
Chen, Ji-an; Splenser, Andres; Guillory, Bobby; Luo, Jiaohua; Mendiratta, Meenal; Belinova, Blaga; Halder, Tripti; Zhang, Guohua; Li, Yi-Ping; Garcia, Jose M
Background Cachexia and muscle atrophy are common consequences of cancer and chemotherapy administration. The novel hormone ghrelin has been proposed as a treatment for this condition. Increases in food intake and direct effects on muscle proteolysis and protein synthesis are likely to mediate these effects, but the pathways leading to these events are not well understood. Methods We characterized molecular pathways involved in muscle atrophy induced by Lewis lung carcinoma (LLC) tumour implantation in c57/bl6 adult male mice and by administration of the chemotherapeutic agent cisplatin in mice and in C2C12 myotubes. The effects of exogenous ghrelin administration and its mechanisms of action were examined in these settings. Results Tumour implantation and cisplatin induced muscle atrophy by activating pro-inflammatory cytokines, p38-C/EBP-β, and myostatin, and by down-regulating Akt, myoD, and myogenin, leading to activation of ubiquitin-proteasome-mediated proteolysis and muscle weakness. Tumour implantation also increased mortality. In vitro, cisplatin up-regulated myostatin and atrogin-1 by activating C/EBP-β and FoxO1/3. Ghrelin prevented these changes in vivo and in vitro, significantly increasing muscle mass (P < 0.05 for LLC and P < 0.01 for cisplatin models) and grip strength (P = 0.038 for LLC and P = 0.001 for cisplatin models) and improving survival (P = 0.021 for LLC model). Conclusion Ghrelin prevents muscle atrophy by down-regulating inflammation, p38/C/EBP-β/myostatin, and activating Akt, myogenin, and myoD. These changes appear, at least in part, to target muscle cells directly. Ghrelin administration in this setting is associated with improved muscle strength and survival. PMID:26136189
Gescher, Andreas; Pastorino, Ugo; Plummer, Simon M; Manson, Margaret M
The concept that cancer can be prevented, or its onset postponed, by certain diet-derived substances is currently eliciting considerable interest. Agents which interfere with tumour development at the stage of promotion and progression in particular are of potential clinical value. As chemopreventive agents have to be administered over a long period of time in order to establish whether they possess efficacy in humans, it is of paramount importance to establish their lack of toxicity. The desire to select the best chemopreventive drug candidates for clinical trial, and the necessity to monitor efficacy in the short and intermediate term, render the identification of specific mechanism-based in vivo markers of biological activity a high priority. Antioxidation, inhibition of arachidonic acid metabolism, modulation of cellular signal transduction pathways, inhibition of hormone and growth factor activity and inhibition of oncogene activity are discussed as mechanisms by which the soya constituent genistein, the curry ingredient curcumin and the vitamin A analogue 13-cis retinoic acid exert tumour suppression. A better understanding of these mechanisms will help the establishment of screens for the discovery of new and better chemopreventive agents and the identification of surrogate markers to assess the outcome of clinical chemoprevention trials. PMID:9489587
Münzberg, Christin; Höhn, Katharina; Krndija, Denis; Maaß, Ulrike; Bartsch, Detlef K; Slater, Emily P; Oswald, Franz; Walther, Paul; Seufferlein, Thomas; von Wichert, Götz
Hypersecretion is the major symptom of functional neuroendocrine tumours. The mechanisms that contribute to this excessive secretion of hormones are still elusive. A key event in secretion is the exit of secretory products from the Golgi apparatus. ADP-ribosylation factor (Arf) GTPases are known to control vesicle budding and trafficking, and have a leading function in the regulation of formation of secretory granula at the Golgi. Here, we show that Arf1 is the predominant Arf protein family member expressed in the neuroendocrine pancreatic tumour cell lines BON and QGP-1. In BON cells Arf1 colocalizes with Golgi markers as well as chromogranin A, and shows significant basal activity. The inhibition of Arf1 activity or expression significantly impaired secretion of chromogranin A. Furthermore, we show that the insulin-like growth factor 1 (IGF-1), a major regulator of growth and secretion in BON cells, induces Arf1 activity. We found that activation of Arf1 upon IGF-1 receptor stimulation is mediated by MEK/ERK signalling pathway in BON and QGP-1 cells. Moreover, the activity of Arf1 in BON cells is mediated by autocrinely secreted IGF-1, and concomitantly, autocrine IGF1 secretion is maintained by Arf1 activity. In summary, our data indicate an important regulatory role for Arf1 at the Golgi in hypersecretion in neuroendocrine cancer cells. PMID:25754106
Münzberg, Christin; Höhn, Katharina; Krndija, Denis; Maaß, Ulrike; Bartsch, Detlef K; Slater, Emily P; Oswald, Franz; Walther, Paul; Seufferlein, Thomas; von Wichert, Götz
Hypersecretion is the major symptom of functional neuroendocrine tumours. The mechanisms that contribute to this excessive secretion of hormones are still elusive. A key event in secretion is the exit of secretory products from the Golgi apparatus. ADP-ribosylation factor (Arf) GTPases are known to control vesicle budding and trafficking, and have a leading function in the regulation of formation of secretory granula at the Golgi. Here, we show that Arf1 is the predominant Arf protein family member expressed in the neuroendocrine pancreatic tumour cell lines BON and QGP-1. In BON cells Arf1 colocalizes with Golgi markers as well as chromogranin A, and shows significant basal activity. The inhibition of Arf1 activity or expression significantly impaired secretion of chromogranin A. Furthermore, we show that the insulin-like growth factor 1 (IGF-1), a major regulator of growth and secretion in BON cells, induces Arf1 activity. We found that activation of Arf1 upon IGF-1 receptor stimulation is mediated by MEK/ERK signalling pathway in BON and QGP-1 cells. Moreover, the activity of Arf1 in BON cells is mediated by autocrinely secreted IGF-1, and concomitantly, autocrine IGF1 secretion is maintained by Arf1 activity. In summary, our data indicate an important regulatory role for Arf1 at the Golgi in hypersecretion in neuroendocrine cancer cells.
Eriksen, Kathrine Olaussen; Johal, Navroop Singh
Minimally invasive surgery (MIS) in the management of malignant and benign renal tumours in children is gradually becoming more common. Experience is limited and restricted to case reports, retrospective chart reviews and a few cohort studies. There are currently no randomized controlled trials or controlled clinical trials comparing the laparoscopic and open surgical approach for the management of renal tumours in children. MIS may offer the same oncologic outcome in malignant renal tumours whilst providing the advantages associated with MIS in correctly selected cases. The technique for tumour resection has been shown to be feasible in regards to the recommended oncologic principles, although lymph node sampling can be inadequate in some cases. Preliminary reports do not show an increased risk of tumour rupture or inferior oncologic outcomes after MIS. However, the sample size remains small and duration of follow-up inadequate to draw any firm conclusions. Implementation of MIS is lacking in the protocols of the major study groups, and standardized recommendations for the indications and contra-indications remain undefined. The objective of this article is to present a review of the literature on the role of MIS in the management of renal tumours in children, with the main focus on Wilms’ tumour (WT). Further studies on MIS in renal tumours are required to evaluate the incidence of oncological complications such as complete tumour resection and intra-operative tumour spillage. A long-term follow-up of patients managed by MIS is essential to compare recurrence rates and overall survival rates. PMID:27867856
Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria
Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098
Zhan, Wenbo; Gedroyc, Wladyslaw
Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours. PMID:28212385
Koyama, Satoshi; Matsunaga, Shinji; Imanishi, Masaki; Maekawa, Yoichi; Kitano, Hiroya; Takeuchi, Hiromi; Tomita, Shuhei
Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy. PMID:28361934
Koyama, Satoshi; Matsunaga, Shinji; Imanishi, Masaki; Maekawa, Yoichi; Kitano, Hiroya; Takeuchi, Hiromi; Tomita, Shuhei
Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.
Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A
Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.
Advances in cross-sectional imaging, surgical technique and adjuvant treatment have largely contributed to ameliorate the prognosis, lessen the morbidity and mortality of patients with skull base tumours and to the growing medical investment in the management of these patients. Because clinical assessment of the skull base is limited, cross-sectional imaging became indispensable in the diagnosis, treatment planning and follow-up of patients with suspected skull base pathology and the radiologist is increasingly responsible for the fate of these patients. This review will focus on the advances in imaging technique; contribution to patient's management and on the imaging features of the most common tumours affecting the anterior skull base. Emphasis is given to a systematic approach to skull base pathology based upon an anatomic division taking into account the major tissue constituents in each skull base compartment. The most relevant information that should be conveyed to surgeons and radiation oncologists involved in patient's management will be discussed.
de Carvalho, Carla C C R; Caramujo, Maria José
Inorganic phosphate (Pi) is a vital component of nucleotides, membrane phospholipids, and phosphorylated intermediates in cellular signalling. The Growth Rate Hypothesis (GRH) states that fast growing organisms should be richer in phosphorus (relatively low C:P and N:P cell content) than slow developing organisms as a result of high ribosome biogenesis. Cells that proliferate rapidly, such as cancer cells, require a high amount of ribosomes and other P-rich RNA components that are necessary to manufacture proteins. The GRH hypothesis may be applied to cancer predicting that tumour cells are richer in phosphorus than the surrounding tissue, and that they resort to metastasis in order to meet their nutrient demands. Considering that the cells most P-deprived should be located in the inner parts of the tumour we propose that changes in the membrane of these cells favour the detachment of the more peripheral cells.
Indrasena, Buddhike Sri Harsha
It is worthwhile to measure serum thyroglobulin (TG) level in thyroid cancer before subjecting patients to surgery for two reasons. Firstly, if the level is high, it may give a clue to the local and metastatic tumour burden at presentation; secondly, if the level is normal, it identifies the patients who are unlikely to show rising TG levels in the presence of thyroid cancer. Those who have high serum TG before surgery will show up recurrence as rising serum TG during the postoperative period. Those who do not have high serum TG before surgery will not show up rising serum TG in the presence of recurrent disease. In the latter situation, normal TG level gives only a false reassurance regarding recurrence of disease. Nevertheless, rising serum TG during the postoperative period must be interpreted cautiously because this could be due to the enlargement of non-cancerous residual thyroid tissue inadvertently left behind during surgery. PMID:28289520
Kees, Ursula R
Lymphoid tumours comprise the acute and chronic leukaemias, the broad spectrum of lymphomas, including Hodgkin's disease, and multiple myeloma. The subdivision of the acute leukaemias according to the proliferating type of white blood cells has had a major impact on the care of these patients. More recently, specific chromosomal translocations have been used to identify patients who may benefit from more intensive therapies. The novel high-throughput genomic technologies, such as microarrays, provide new avenues for the molecular diagnosis of the haematological malignancies. Rapid advances in genome sequencing and gene expression profiling provide unprecedented opportunities to identify specific genes involved in complex biological processes, including tumorigenesis. The features of microarray technology and the variety of experimental approaches to elucidate lymphoid malignancies are discussed. Microarray technology has the potential to lead to more accurate prognostic assessment for patients and is expected to ultimately allow the clinician to select therapies optimally suited to each patient.
Vieira, Helena; Brain, Caroline
Cushing syndrome (CS) in children is a rare disorder that is most frequently caused by an adrenal tumour or a pituitary corticotrophin-secreting adenoma. The management is challenging and requires an individualised approach and multidisciplinary care. We present the case of a 23-month-old female child with a history of excessive weight gain, growth failure, hirsutism, acne and behavioural difficulties. Investigations revealed elevated serum midnight cortisol and 24 h urinary free cortisol. Overnight dexamethasone suppression testing showed no suppression of cortisol levels. Abdominal imaging revealed a right-sided suprarenal mass. She underwent right adrenalectomy and the histology showed an adrenal cortical carcinoma. There was clinical improvement with catch-up growth and weight normalisation. Despite being rare in clinical practice, in a child with weight gain, hirsuitism and growth failure the diagnosis must be considered. The overall prognosis of CS in childhood is good, but challenges remain to ensure normal growth and body composition. PMID:22927284
Vieira, Helena; Brain, Caroline
Cushing syndrome (CS) in children is a rare disorder that is most frequently caused by an adrenal tumour or a pituitary corticotrophin-secreting adenoma. The management is challenging and requires an individualised approach and multidisciplinary care. We present the case of a 23-month-old female child with a history of excessive weight gain, growth failure, hirsutism, acne and behavioural difficulties. Investigations revealed elevated serum midnight cortisol and 24 h urinary free cortisol. Overnight dexamethasone suppression testing showed no suppression of cortisol levels. Abdominal imaging revealed a right-sided suprarenal mass. She underwent right adrenalectomy and the histology showed an adrenal cortical carcinoma. There was clinical improvement with catch-up growth and weight normalisation. Despite being rare in clinical practice, in a child with weight gain, hirsuitism and growth failure the diagnosis must be considered. The overall prognosis of CS in childhood is good, but challenges remain to ensure normal growth and body composition.
Choi, Hak Soo; Liu, Wenhao; Liu, Fangbing; Nasr, Khaled; Misra, Preeti; Bawendi, Moungi G.; Frangioni, John V.
Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale. Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge. Here, we show that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5-10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys.
Riechelmann, Rachel P; Weschenfelder, Rui F; Costa, Frederico P; Andrade, Aline Chaves; Osvaldt, Alessandro Bersch; Quidute, Ana Rosa P; dos Santos, Allan; Hoff, Ana Amélia O; Gumz, Brenda; Buchpiguel, Carlos; Vilhena Pereira, Bruno S; Lourenço Junior, Delmar Muniz; da Rocha Filho, Duilio Reis; Fonseca, Eduardo Antunes; Riello Mello, Eduardo Linhares; Makdissi, Fabio Ferrari; Waechter, Fabio Luiz; Carnevale, Francisco Cesar; Coura-Filho, George B; de Paulo, Gustavo Andrade; Girotto, Gustavo Colagiovanni; Neto, João Evangelista Bezerra; Glasberg, João; Casali-da-Rocha, Jose Claudio; Rego, Juliana Florinda M; de Meirelles, Luciana Rodrigues; Hajjar, Ludhmila; Menezes, Marcos; Bronstein, Marcello D; Sapienza, Marcelo Tatit; Fragoso, Maria Candida Barisson Villares; Pereira, Maria Adelaide Albergaria; Barros, Milton; Forones, Nora Manoukian; do Amaral, Paulo Cezar Galvão; de Medeiros, Raphael Salles Scortegagna; Araujo, Raphael L C; Bezerra, Regis Otaviano França; Peixoto, Renata D’Alpino; Aguiar, Samuel; Ribeiro, Ulysses; Pfiffer, Tulio; Hoff, Paulo M; Coutinho, Anelisa K
Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards. PMID:28194228
Riechelmann, Rachel P; Weschenfelder, Rui F; Costa, Frederico P; Andrade, Aline Chaves; Osvaldt, Alessandro Bersch; Quidute, Ana Rosa P; Dos Santos, Allan; Hoff, Ana Amélia O; Gumz, Brenda; Buchpiguel, Carlos; Vilhena Pereira, Bruno S; Lourenço Junior, Delmar Muniz; da Rocha Filho, Duilio Reis; Fonseca, Eduardo Antunes; Riello Mello, Eduardo Linhares; Makdissi, Fabio Ferrari; Waechter, Fabio Luiz; Carnevale, Francisco Cesar; Coura-Filho, George B; de Paulo, Gustavo Andrade; Girotto, Gustavo Colagiovanni; Neto, João Evangelista Bezerra; Glasberg, João; Casali-da-Rocha, Jose Claudio; Rego, Juliana Florinda M; de Meirelles, Luciana Rodrigues; Hajjar, Ludhmila; Menezes, Marcos; Bronstein, Marcello D; Sapienza, Marcelo Tatit; Fragoso, Maria Candida Barisson Villares; Pereira, Maria Adelaide Albergaria; Barros, Milton; Forones, Nora Manoukian; do Amaral, Paulo Cezar Galvão; de Medeiros, Raphael Salles Scortegagna; Araujo, Raphael L C; Bezerra, Regis Otaviano França; Peixoto, Renata D'Alpino; Aguiar, Samuel; Ribeiro, Ulysses; Pfiffer, Tulio; Hoff, Paulo M; Coutinho, Anelisa K
Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Clinical Trials Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...
ICSH - blood test; Luteinizing hormone - blood test; Interstitial cell stimulating hormone - blood test ... to temporarily stop medicines that may affect the test results. Be sure to tell your provider about ...
... as: Testosterone-estrogen Binding Globulin; TeBG Formal name: Sex Hormone Binding Globulin Related tests: Testosterone , Free Testosterone, ... I should know? How is it used? The sex hormone binding globulin (SHBG) test may be used ...
Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth
Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied ‘off label’ to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies. PMID:27668795
Olsson, A. R.; Sheng, Y.; Pero, R. W.; Chaplin, D. J.; Horsman, M. R.
In vivo DNA damage and repair was induced by nicotinamide (NAM) in adenotype 12 virus-induced mouse sarcoma A12B3 and sarcoma F inoculated into CBA mice. DNA damage, NAM and NAD concentrations were measured after in vivo exposure to NAM, in tumours and spleens by alkaline elution and by HPLC analysis. Our results indicate that NAM between 100-1000 mg kg-1 causes a high level of in vivo DNA strand breaks in tumours and normal tissues in mice bearing the immunogenic sarcoma A12B3 but not in the non-immunogenic sarcoma F. The repair process was also delayed by the NAM treatment probably owing to inhibition of the DNA repair enzyme, poly(ADP-ribose)polymerase, as evidenced by accumulation of NAM and NAD. These data are consistent with NAM having a mechanism of action as a radiosensitiser at least in part by DNA repair inhibition. In addition, it should also be considered that high doses of NAM might cause considerable complications to normal tissue in tumour-bearing individuals. PMID:8695350
Zanganeh, Saeid; Hutter, Gregor; Spitler, Ryan; Lenkov, Olga; Mahmoudi, Morteza; Shaw, Aubie; Pajarinen, Jukka Sakari; Nejadnik, Hossein; Goodman, Stuart; Moseley, Michael; Coussens, Lisa Marie; Daldrup-Link, Heike Elisabeth
Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses. In vivo, ferumoxytol significantly inhibited growth of subcutaneous adenocarcinomas in mice. In addition, intravenous ferumoxytol treatment before intravenous tumour cell challenge prevented development of liver metastasis. Fluorescence-activated cell sorting (FACS) and histopathology studies showed that the observed tumour growth inhibition was accompanied by increased presence of pro-inflammatory M1 macrophages in the tumour tissues. Our results suggest that ferumoxytol could be applied 'off label' to protect the liver from metastatic seeds and potentiate macrophage-modulating cancer immunotherapies.
Wang, Yan; Jia, Haiquan; Lin, Huiyun; Tan, Xiaogang; Du, Zhiyan; Chen, Huihua; Xu, Yuanji; Han, Xiaoxi; Zhang, Jiakai; Zhao, Siyang; Yu, Xiaodan; Lu, Yinglin
Metastasis is a major cause of death from malignant diseases, and the underlying mechanisms are still largely not known. A detailed probe into the factors which may regulate tumour invasion and metastasis contributes to novel anti-metastatic therapies. We previously identified a novel metastasis-associated gene 1 (mag-1) by means of metastatic phenotype cloning. Then we characterized the gene expression profile of mag-1 and showed that it promoted cell migration, adhesion and invasion in vitro. Importantly, the disruption of mag-1 via RNA interference not only inhibited cellular metastatic behaviours but also significantly reduced tumour weight and restrained mouse breast cancer cells to metastasize to lungs in spontaneous metastatic assay in vivo. Furthermore, we proved that mag-1 integrates dual regulating mechanisms through the stabilization of HIF-1α and the activation of mTOR signalling pathway. We also found that mag-1-induced metastatic promotion could be abrogated by mTOR specific inhibitor, rapamycin. Taken together, the findings identified a direct role that mag-1 played in metastasis and implicated its function in cellular adaptation to tumour microenvironment.
Müller, Maren; Munné-Bosch, Sergi
Plant hormones are for a long time known to act as chemical messengers in the regulation of physiological processes during a plant's life cycle, from germination to senescence. Furthermore, plant hormones simultaneously coordinate physiological responses to biotic and abiotic stresses. To study the hormonal regulation of physiological processes, three main approaches have been used (1) exogenous application of hormones, (2) correlative studies through measurements of endogenous hormone levels, and (3) use of transgenic and/or mutant plants altered in hormone metabolism or signaling. A plant hormone profiling method is useful to unravel cross talk between hormones and help unravel the hormonal regulation of physiological processes in studies using any of the aforementioned approaches. However, hormone profiling is still particularly challenging due to their very low abundance in plant tissues. In this chapter, a sensitive, rapid, and accurate method to quantify all the five "classic" classes of plant hormones plus other plant growth regulators, such as jasmonates, salicylic acid, melatonin, and brassinosteroids is described. The method includes a fast and simple extraction procedure without time consuming steps as purification or derivatization, followed by optimized ultrahigh-performance liquid chromatography coupled to electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) analysis. This protocol facilitates the high-throughput analysis of hormone profiling and is applicable to different plant tissues.
Cooke, Paul S.; Nicoll, Charles S.
Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…
Vilanova, Guillermo; Colominas, Ignasi; Gomez, Hector
Cancerous tumours have the ability to recruit new blood vessels through a process called angiogenesis. By stimulating vascular growth, tumours get connected to the circulatory system, receive nutrients and open a way to colonize distant organs. Tumour-induced vascular networks become unstable in the absence of tumour angiogenic factors (TAFs). They may undergo alternating stages of growth, regression and regrowth. Following a phase-field methodology, we propose a model of tumour angiogenesis that reproduces the aforementioned features and highlights the importance of vascular regression and regrowth. In contrast with previous theories which focus on vessel remodelling due to the absence of flow, we model an alternative regression mechanism based on the dependency of tumour-induced vascular networks on TAFs. The model captures capillaries at full scale, the plastic dynamics of tumour-induced vessel networks at long time scales, and shows the key role played by filopodia during angiogenesis. The predictions of our model are in agreement with in vivo experiments and may prove useful for the design of antiangiogenic therapies.
Tan, Benjamin Y; Acs, Geza; Apple, Sophia K; Badve, Sunil; Bleiweiss, Ira J; Brogi, Edi; Calvo, José P; Dabbs, David J; Ellis, Ian O; Eusebi, Vincenzo; Farshid, Gelareh; Fox, Stephen B; Ichihara, Shu; Lakhani, Sunil R; Rakha, Emad A; Reis-Filho, Jorge S; Richardson, Andrea L; Sahin, Aysegul; Schmitt, Fernando C; Schnitt, Stuart J; Siziopikou, Kalliopi P; Soares, Fernando A; Tse, Gary M; Vincent-Salomon, Anne; Tan, Puay Hoon
Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours. PMID:26768026
Maccalli, Cristina; Volontè, Andrea; Cimminiello, Carolina; Parmiani, Giorgio
Cancer stem cells (CSCs) represent a minor subpopulation of tumour cells that share some features with the normal stem cells of the tissue from which tumour derives and have the properties of self-renewal, multiple differentiation and tumour initiation (tumour-initiating cells, TICs). Thus CSCs/TICs need to survive cancer therapies in order to provide new, more differentiated, metastatic-prone tumour cells. This occurs through different signals delivered within the tumour microenvironment. The immune system of cancer patients may recognise CSCs/TICs and kill them though it is unclear whether this may occur in vivo during spontaneous tumour growth. This review summarises findings on the immunological profile of CSCs/TICs as compared with neoplastic non-stem cells and discusses the possible antigens recognised by the patients' immune system, the in vitro and the potential in vivo immunogenicity of such antigens and the ability of human CSCs/TICs to down-regulate the immune response by the release of a variety of suppressive factors. We conclude that available data on immunological characterisation of CSCs/TICs may be useful in the perspective of designing new translational immunotherapy protocols targeting CSCs/TICs.
Klopfleisch, R; Kohn, B; Gruber, A D
Several classes of chemotherapy drugs are used as first line or adjuvant treatment of the majority of tumour types in veterinary oncology. However, some types of tumour are intrinsically resistant to several anti-cancer drugs, and others, while initially sensitive, acquire resistance during treatment. Chemotherapy often significantly prolongs survival or disease free interval, but is not curative. The exact mechanisms behind intrinsic and acquired chemotherapy resistance are unknown for most animal tumours, but there is increasing knowledge on the mechanisms of drug resistance in humans and a few reports on molecular changes in resistant canine tumours have emerged. In addition, approaches to overcome or prevent chemotherapy resistance are becoming available in humans and, given the overlaps in molecular alterations between human and animal tumours, these may also be relevant in veterinary oncology. This review provides an overview of the current state of research on general chemotherapy resistance mechanisms, including drug efflux, DNA repair, apoptosis evasion and tumour stem cells. The known resistance mechanisms in animal tumours and the potential of these findings for improving treatment efficacy in veterinary oncology are also explored.
Peracaula, Rosa; Barrabés, Sílvia; Sarrats, Ariadna; Rudd, Pauline M.; de Llorens, Rafael
The lack of specific and sensitive tumour markers for early detection of cancer is driving a search for new approaches that could identify biomarkers. Markers are needed to alert clinicians at the early stages of tumourogenesis, before the cancer has metastasized, when the therapeutic drugs are more effective. Most tumour markers currently used in clinics are serum glycoproteins, frequently highly glycosylated mucins. Typically, the disease marker is the protein and not the glycan moiety of the corresponding glycoprotein or mucin. The increasing knowledge of the role of glycans in cancer suggests that further studies may assist both in determining their role in every step of tumour progression, and in the design of new therapeutic and diagnosic approaches. Detection of the altered glycans in serum tumour glycoproteins could be a way to achieve specificity in tumour detection. In this review, we focus on the glycan changes of two serum glycoproteins, prostate specific antigen - currently used as a tumour marker of prostate cancer - and human pancreatic ribonuclease in pancreatic adenocarcinoma. The detection of glycan changes, associated with subsets of glycoforms in serum glycoproteins that are specific to the tumour situation, could be the basis for developing more specific biomarkers. PMID:19126965
Reinauer, Hans; Wood, William Graham
This review shows the current analytical quality for the following analytes used as tumour markers in the external quality assessment (EQA)-programmes of Instand e.V., a national EQA-organiser in Germany: Corticotropin (ACTH), growth hormone (GH, hGH), prolactin (PRL), chorionic gonadotropin (CG, hCG), calcitonin (CT, hCT), thyroglobulin (Tg), carcinoembryonic antigen (CEA), CA-Antigens 125, 72-4, 15-3 and 19-9, alpha foetoprotein (AFP) and prostate-specific antigen (PSA). The results from the participants show a large variation in the precision of the methods used as well as in the comparability of results between methods for the same analyte. In general, the hormones used as tumour markers show better performance than the "CA-markers", which are often inadequately standardised and defined. In the case of one CA-marker (CA 72-4/TAG 72-4), the differences between the lowest kit median concentration and highest kit median concentration for one sample pair were 440% and 580%. The corresponding figures for ACTH were 123% and 156% and for CEA 180% and 184%. The classical tumour markers such as carcinoembryonic antigen (CEA) and alpha foetoprotein (AFP) performed markedly better than the CA-markers and PSA with regards to both inter- and intra-method comparability. The inter-laboratory precision for a given kit and marker was acceptable in many cases. The results show that only results from the same kit/method for each tumour marker can be used for cumulative or time-dependent comparison of results - for example pre-operative and post-operative follow up. In the case of prostate specific antigen (PSA), the kits used for free and total PSA must come from the same producer, if the generally accepted ratios are to have any diagnostic value. The need for kit- and laboratory-specific reference ranges and cut-off values for setting diagnostic specificity and sensitivity is highlighted from the EQA-results. The situation for inter-method comparability for the CA-Markers has
Pratesi, G; Perego, P; Polizzi, D; Righetti, S C; Supino, R; Caserini, C; Manzotti, C; Giuliani, F C; Pezzoni, G; Tognella, S; Spinelli, S; Farrell, N; Zunino, F
Multinuclear platinum compounds were rationally designed to bind to DNA in a different manner from that of cisplatin and its mononuclear analogues. A triplatinum compound of the series (BBR 3464) was selected for preclinical development, since, in spite of its charged nature, it was very potent as cytotoxic agent and effective against cisplatin-resistant tumour cells. Anti-tumour efficacy studies were performed in a panel of human tumour xenografts refractory or poorly responsive to cisplatin. The novel platinum compound exhibited efficacy in all tested tumours and an impressive efficacy (including complete tumour regressions) was displayed in two lung carcinoma models, CaLu-3 and POCS. Surprisingly, BBR 3464 showed a superior activity against p53-mutant tumours as compared to those carrying the wild-type gene. The involvement of p53 in tumour response was investigated in an osteosarcoma cell line, SAOS, which is null for p53 and is highly sensitive to BBR 3464, and in the same cells following introduction of the wild-type p53 gene. Thus the pattern of cellular response was investigated in a panel of human tumour cells with a different p53 gene status. The results showed that the transfer of functional p53 resulted in a marked (tenfold) reduction of cellular chemosensitivity to the multinuclear platinum complex but in a moderate sensitization to cisplatin. In addition, in contrast to cisplatin, the triplatinum complex was very effective as an inducer of apoptosis in a lung carcinoma cell line carrying mutant p53. The peculiar pattern of anti-tumour activity of the triplatinum complex and its ability to induce p53-independent cell death may have relevant pharmacological implications, since p53, a critical protein involved in DNA repair and induction of apoptosis by conventional DNA-damaging agents, is defective in several human tumours. We suggest that the peculiar DNA binding properties of the triplatinum complex may contribute to the striking profile of anti-tumour
Farina, Antonietta Rosella; Mackay, Andrew Reay
Since its original identification as a leukocyte gelatinase/type V collagenase and tumour type IV collagenase, gelatinase B/matrix metalloproteinase (MMP)-9 is now recognised as playing a central role in many aspects of tumour progression. In this review, we relate current concepts concerning the many ways in which gelatinase B/MMP-9 influences tumour biology. Following a brief outline of the gelatinase B/MMP-9 gene and protein, we analyse the role(s) of gelatinase B/MMP-9 in different phases of the tumorigenic process, and compare the importance of gelatinase B/MMP-9 source in the carcinogenic process. What becomes apparent is the importance of inflammatory cell-derived gelatinase B/MMP-9 in tumour promotion, early progression and triggering of the “angiogenic switch”, the integral relationship between inflammatory, stromal and tumour components with respect to gelatinase B/MMP-9 production and activation, and the fundamental role for gelatinase B/MMP-9 in the formation and maintenance of tumour stem cell and metastatic niches. It is also apparent that gelatinase B/MMP-9 plays important tumour suppressing functions, producing endogenous angiogenesis inhibitors, promoting inflammatory anti-tumour activity, and inducing apoptosis. The fundamental roles of gelatinase B/MMP-9 in cancer biology underpins the need for specific therapeutic inhibitors of gelatinase B/MMP-9 function, the use of which must take into account and substitute for tumour-suppressing gelatinase B/MMP-9 activity and also limit inhibition of physiological gelatinase B/MMP-9 function. PMID:24473089
Bradshaw, T. D.; Wrigley, S.; Shi, D. F.; Schultz, R. J.; Paull, K. D.; Stevens, M. F.
2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory effects against a panel of oestrogen receptor-positive (ER+) and oestrogen receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding IC50 values in the nM range. Substitutions adjacent to the amino group in the 2-phenyl ring with a halogen atom or methyl group enhance potency in sensitive breast lines (pM IC50 values). Transient biphasic dose responses were induced but rapidly eradicated after specific drug exposure periods. Two human prostate carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4-aminophenyl)benzothiazoles; IC50 values > 30 microM were obtained. Potency and selectivity were confirmed when compounds were examined in the National Cancer Institute's Developmental Therapeutics screen; the spectrum of activity included specific ovarian, renal, colon as well as breast carcinoma cell lines. Moreover, comparing 6-day and 48-h incubations, the exposure time-dependent nature of the biphasic response was corroborated. Differential perturbation of cell cycle distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4-aminophenyl)benzothiazoles. In MDA 468 populations only, accumulation of events in G2/M phase was observed. Two MCF-7 cell lines were established with acquired resistance to CJM 126 (IC50 values > 20 microM), which exhibit cross-resistance to substituted benzothiazoles, but equal sensitivity to tamoxifen and doxorubicin. Compared with standard anti-tumour agents evaluated in the National Cancer Institute in vitro cell panel, benzothiazoles revealed unique profiles of growth inhibition, suggesting a mode(s) of action shared with no known clinically active class of chemotherapeutic agents. PMID:9514053
Nilsson, Maria; Adamo, Hanibal; Bergh, Anders; Halin Bergström, Sofia
Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth. Conversely, treatment that was started after the tumours were established resulted in unaffected or increased tumour growth. Moreover, treatment with BAPN did not suppress the formation of spontaneous lymph node metastases, or lung tumour burden, when tumour cells were injected intravenously. A temporal decrease in collagen fibre content, which is a target for LOX, was observed in tumours and in the tumour-adjacent prostate tissue. This may explain why early BAPN treatment is more effective in inhibiting tumour growth compared to treatment initiated later. Our data suggest that the enzymatic function of the LOX family is context-dependent, with both tumour-suppressing and tumour-promoting properties in prostate cancer. Further investigations are needed to understand the circumstances under which LOX inhibition may be used as a therapeutic target for cancer patients.
Griffith, R W; Turkalj, I; Braun, P
1 Out of 805 previously infertile women in whom pregnancy was achieved on bromocriptine treatment, 137 were diagnosed as having pituitary tumours. 2 In nine of these, tumour-related complications occurred during pregnancy, chiefly visual field impairment. Surgical intervention was considered necessary in two patients. In a third patient reinstitution of bromocriptine produced remission of symptoms. 3 Although the frequency of serious complications was low, the present state of knowledge indicates that surgery or irradiation of pituitary tumours should be preferred, at least as the first line of treatment, for patients contemplating pregnancy. PMID:444358
Knudsen, Erik S.; Knudsen, Karen E.
The retinoblastoma tumour suppressor (RB) is a crucial regulator of cell-cycle progression that is invoked in response to a myriad of anti-mitogenic signals. It has been hypothesized that perturbations of the RB pathway confer a synonymous proliferative advantage to tumour cells; however, recent findings demonstrate context-specific outcomes associated with such lesions. Particularly, loss of RB function is associated with differential response to wide-ranging therapeutic agents. Thus, the status of this tumour suppressor may be particularly informative in directing treatment regimens. PMID:19143056
Muscatello, L V; Avallone, G; Benazzi, C; Sarli, G; Porcellato, I; Brachelente, C; Brunetti, B
In human medicine, squamomelanocytic tumour is a malignant cutaneous neoplasm composed of closely intermingled neoplastic squamous cells and melanocytes. A multinodular gingival tumour in a 16-year-old, mixed breed neutered female dog was examined microscopically. Two populations of neoplastic cells, melanocytic and squamous epithelial cells were intermingled. The melanocytic cells were melan-A positive and cytokeratin AE1-AE3 negative and the squamous component was cytokeratin AE1-AE3 positive and melan-A negative. Bovine papillomavirus was not identified by immunohistochemistry or polymerase chain reaction. A diagnosis of squamomelanocytic tumour was made.
Blackmore, Christopher; Coppes, Max J; Narendran, Aru
Wilms' tumour (WT) is the most common malignant renal tumour of childhood. During the past two decades or so, molecular studies carried out on biopsy specimens and tumour-derived cell lines have identified a multitude of chromosomal and epigenetic alterations in WT. In addition, a significant amount of evidence has been gathered to identify the genes and signalling pathways that play a defining role in its genesis, growth, survival and treatment responsiveness. As such, these molecules and mechanisms constitute potential targets for novel therapeutic strategies for refractory WT. In this report we aim to review some of the many candidate genes and intersecting pathways that underlie the complexities of WT biology.
Chemotherapy use against solid tumours often results in the resistance of the cancer cells to the molecule used. In this paper, we will set up and analyse an ODE model for heterogeneous in vitro tumours, consisting of cells that are sensitive or resistant to a certain drug. We will then use this model to develop different protocols, that aim at reducing the tumour volume while preserving its heterogeneity. These drug administration schedules are determined through analysis of the system dynamics, and optimal control theory.
Barker, Holly E.; Paget, James T. E.; Khan, Aadil A.; Harrington, Kevin J.
Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focussed on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes induced in the tumour microenvironment by irradiation and discuss how they may promote radioresistance and tumour recurrence. Subsequently, we highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy. PMID:26105538
Magadum, Dilip; Sanadi, Appasab; Agrawal, Jiwanasha Manish; Agrawal, Manish Suresh
Lipoma is the commonest benign tumour occurring at any anatomical site where fat is present, but occurrence in the oral cavity is rare. Tongue which is totally devoid of fat cells is a rare site for lipoma. This is one such rare case of the universal tumour, presenting at the lateral margin of the tongue, for which complete tumour excision was done. Macroscopically the mass had a hard consistency and measured 3.0×2.0 cm. From microscopic examination, diagnosis of lipoma was made. Recurrence of tongue lipoma is rare. PMID:23370950
Cole, Steven W.; Nagaraja, Archana S.; Lutgendorf, Susan K.; Green, Paige A.; Sood, Anil K.
The peripheral autonomic nervous system (ANS) is known to regulate gene expression in primary tumours and their surrounding microenvironment. Activation of the sympathetic division of the ANS in particular modulates gene expression programs that promote metastasis of solid tumours by stimulating macrophage infiltration, inflammation, angiogenesis, epithelial-mesenchymal transition, and tumour invasion, and by inhibiting cellular immune responses and programmed cell death. Haematological cancers are modulated by sympathetic nervous system (SNS) regulation of stem cell biology and hematopoietic differentiation programs. In addition to identifying a molecular basis for physiologic stress effects on cancer, these findings have also identified new pharmacologic strategies to inhibit cancer progression in vivo. PMID:26299593
Bartosch, Carla; Vieira, Joana; Teixeira, Manuel R; Lopes, José Manuel
Uterine primitive neuroectodermal tumours are extremely rare tumours. They can occur in pure form or combined with another component including endometrioid adenocarcinoma. We aimed to review the clinical impact of neuroectodermal phenotype in uterine tumours, after we recently diagnosed one such case. A 58-year-old female presented with irregular vaginal bleeding. Ultrasonography and CT showed the presence of a large uterine mass with irregular contours. At laparotomy it was found to extend to the right ureter, sigmoid colon and some small intestinal loops. Microscopic examination revealed that the tumour consisted of an endometrioid adenocarcinoma component merging with an extensive neuroectodermal component. No EWSR1 or FUS rearrangement was found in the two tumour components. The patient received two courses of chemotherapy but died 11 months after the initial diagnosis. We reviewed the morphological and molecular criteria for the diagnosis of uterine primitive neuroectodermal tumours published in the literature. We conclude that regardless of the detection of an EWSR1 rearrangement, the presence of a neuroectodermal differentiation component in these rare uterine tumours is a marker of aggressive behaviour, and its presence should be highlighted in the diagnosis.
Lai, Li; Liu, Junchen; Zhai, Dong; Lin, Qingxiang; He, Lijun; Dong, Yanmin; Zhang, Jing; Lu, Binbin; Chen, Yihua; Yi, Zhengfang; Liu, Mingyao
BACKGROUND AND PURPOSE Angiogenesis-based therapy is an effective anti-tumour strategy and previous reports have shown some beneficial effects of a naturally occurring bioactive compound plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone). Here, we sought to determine the biological effects of plumbagin on signalling mechanisms during tumour angiogenesis. EXPERIMENTAL APPROACH The effects of plumbagin were evaluated in various in vitro assays which utilised human umbilical vein endothelial cells (HUVEC) proliferation, migration and tube formation. Plumbagin was also evaluated in vivo using chicken embryo chorioallantoic membrane (CAM) and mouse corneal micropocket models., Human colon carcinoma and prostate cancer xenograft mouse models were used to evaluate the effects of plumbagin on angiogenesis. Immunofluorescence, GST pull-down and Western blotting were employed to explore the underlying mechanisms of VEGF receptor (VEGFR)2-mediated Ras signalling pathways. KEY RESULTS Plumbagin not only inhibited endothelial cell proliferation, migration and tube formation but also suppressed chicken chorioallantoic membrane neovascularzation and VEGF-induced mouse corneal angiogenesis. Moreover, plumbagin suppressed tumour angiogenesis and tumour growth in human colon carcinoma and prostate cancer xenograft mouse models. At a molecular level, plumbagin blocked the Ras/Rac/cofilin and Ras/MEK signalling pathways mediated by VEGFR2 in HUVECs. CONCLUSIONS AND IMPLICATIONS Plumbagin inhibited tumour angiogenesis and tumour growth by interference with the VEGFR2-mediated Ras signalling pathway in endothelial cells. Our findings demonstrate a molecular basis for the effects of plumbagin and suggest that this compound might have therapeutic ant-tumour effects. PMID:21658027
Jaffrain-Rea, M L; Di Stefano, D; Minniti, G; Esposito, V; Bultrini, A; Ferretti, E; Santoro, A; Faticanti Scucchi, L; Gulino, A; Cantore, G
Pituitary tumours are usually benign neoplasia, but may have a locally aggressive or malignant evolution. This study aimed to identify factors which mostly influence their proliferative activity, in order to clarify its value for clinical and research purposes. The proliferative index was determined in a prospective series of 132 pituitary tumours as the percentage of monoclonal antibody MIB-1-immunopositive cells and referred to as the MIB-1 labelling index (LI). Its distribution was analysed according to both univariate and multivariate models. A life-threatening pituitary tumour is presented separately. The mean LI was 1.24+/-1.59%, with significant differences between clinically secreting (CS) and clinically non-secreting (CNS) adenomas. In CS adenomas (n=65), LI was highly variable and markedly influenced by pre-operative pharmacological treatment (0.80+/-1.03 vs 2.06+/-2.39% in treated vs untreated cases, P=0.009); it decreased with patient's age (P=0.025, r=0.28) and increased with tumour volume and invasiveness. The influence of pre-operative treatment and macroscopic features on LI in this group was confirmed by multivariate analysis. In CNS adenomas (n=67), LI distribution was less variable than in CS adenomas (P<0.0001), it was age-independent and correlations with tumour volume, invasiveness or recurrence did not reach significance. In a rapidly growing parasellar tumour, the mean LI was 24% at first surgery and exceeded 50% at second surgery performed 4 months later. LI should be interpreted according to hormone secretion and pre-operative treatment. Unusually high LI values deserve particular attention.
Koo, Abraham J.K.; Howe, Gregg A.
Plant tissues are highly vulnerable to injury by herbivores, pathogens, mechanical stress, and other environmental insults. Optimal plant fitness in the face of these threats relies on complex signal transduction networks that link damage-associated signals to appropriate changes in metabolism, growth, and development. Many of these wound-induced adaptive responses are triggered by de novo synthesis of the plant hormone jasmonate (JA). Recent studies provide evidence that JA mediates systemic wound responses through distinct cell autonomous and nonautonomous pathways. In both pathways, bioactive JAs are recognized by an F-box protein-based receptor system that couples hormone binding to ubiquitin-dependent degradation of transcriptional repressor proteins. These results provide a new framework for understanding how plants recognize and respond to tissue injury. PMID:19695649
Jansson, J O; Svensson, J; Bengtsson, B A; Frohman, L A; Ahlman, H; Wängberg, B; Nilsson, O; Nilsson, M
A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive
Han, Song-Hee; Kim, Hyun Jeong; Gwak, Jae Moon; Kim, Mimi; Chung, Yul Ri
Purpose The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. Results High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer. PMID:28382093
Munsell, Mark F.; Sprague, Brian L.; Berry, Donald A.; Chisholm, Gary; Trentham-Dietz, Amy
To assess the joint relationships among body mass index, menopausal status, and breast cancer according to breast cancer subtype and estrogen-progestin medication use, we conducted a meta-analysis of 89 epidemiologic reports published in English during 1980–2012 identified through a systematic search of bibliographic databases. Pooled analysis yielded a summary risk ratio of 0.78 (95% confidence interval (CI): 0.67, 0.92) for hormone receptor–positive premenopausal breast cancer associated with obesity (body mass index (weight (kg)/height (m)2) ≥30 compared with <25). Obesity was associated with a summary risk ratio of 1.39 (95% CI: 1.14, 1.70) for receptor-positive postmenopausal breast cancer. For receptor-negative breast cancer, the summary risk ratios of 1.06 (95% CI: 0.70, 1.60) and 0.98 (95% CI: 0.78, 1.22) associated with obesity were null for both premenopausal and postmenopausal women, respectively. Elevated postmenopausal breast cancer risk ratios associated with obesity were limited to women who never took estrogen-progestin therapy, with risk ratios of 1.42 (95% CI: 1.30, 1.55) among never users and 1.18 (95% CI: 0.98, 1.42) among users; too few studies were available to examine this relationship according to receptor subtype. Future research is needed to confirm whether obesity is unrelated to receptor-negative breast cancer in populations of postmenopausal women with low prevalence of hormone medication use. PMID:24375928
Ju, Qiang; Tao, Tao; Hu, Tingting; Karadağ, Ayşe Serap; Al-Khuzaei, Safaa; Chen, WenChieh
The skin is an endocrine organ with the expression of metabolizing enzymes and hormone receptors for diverse hormones. The sebaceous gland is the main site of hormone biosynthesis, especially for androgens, and acne is the classical androgen-mediated dermatosis. In sebocytes, conversion of 17-hydroxyprogesterone directly to dihydrotestosterone bypassing testosterone has been demonstrated, while type II 17β-hydroxysteroid dehydrogenase can inactivate the action of testosterone and dihydrotestosterone. The androgen receptor-dependent genomic effect of dihydrotestosterone on sebocytes is confirmed. Further evidence supports the PI3 K/Akt/FoxO1/mTOR signaling in the involvement of the interplay between androgens, insulin, insulin-like growth factor, and hyperglycemic diet in acne. Androgens not only regulate embryology and lipogenesis/sebum synthesis in sebocytes but also influence inflammation in acne. Genetic studies indicate that regulation of the androgen receptor is an important factor in severe acne. Further studies are required to understand the effect of estrogen and progesterone on sebaceous gland and comedogenesis, considering the change of acne in pregnancy and postmenopausal acne. Special attention should be paid to nonobese patients with polycystic ovarian syndrome and hyperandrogenism-insulin resistance-acanthosis nigricans syndrome. In spite of extensive gynecologic experience in the use of combined oral contraceptives for acne, evidence based on dermatologic observation should be intensified.
Androgens stimulate sebum production which is necessary for the development of acne. Acne in women may thus be considered as a manifestation of cutaneous androgenization. Most of acnes may be related to an idiopathic skin hyperandrogenism due to in situ enzyme activity and androgen receptor hypersensitivity, as also noted in idiopathic hirsutism. Some acne may correspond to elevated ovarian or adrenal androgen secretion. The presence of acne in women may lead to a diagnosis of functional hyperandrogenism, either polycysticovary syndrome or nonclassical 21-hydroxylase deficiency. Plasma level assays for testosterone, delta 4 androstenedione and 17-OH progesterone and ovarian echography are necessary to determine the possibility for an ovarian or adrenal hyperandrogenism, but not to better treat acne. The goal of hormonal therapy in acne is to oppose the effects of androgens on the sebaceous gland. Hormones may be used in female acne in the absence of endocrine abnormalities. Antiandrogens (cyproterone acetate or aldactone) may be useful in severe acne, hormonal contraceptives with cyproterone acetate or non androgenic progestins in mild or common acne often in association with other anti-acneic drugs. Glucocorticoids have to be administered in acne fulminans and other forms of acute, severe, inflammatory acne, for their anti-inflammatory properties.
Garrido, F; Ruiz-Cabello, F; Cabrera, T; Pérez-Villar, J J; López-Botet, M; Duggan-Keen, M; Stern, P L
HLA class I downregulation is a frequent event associated with tumour invasion and development. Altered HLA class I tumour phenotypes can have profound effects on T-cell and natural killer (NK)-cell antitumour responses. Here, Federico Garrido and colleagues analyse these altered tumour phenotypes in detail, indicating their potential relevance for implementation of immunotherapeutic protocols and strategies to overcome tumour escape mechanisms.
Somasundaram, Soundappan; Khajanchi, Monty; Vaja, Tejas; Jajoo, Bhushan; Dey, Amit Kumar
Benign multicystic peritoneal mesothelioma: a rare tumor of the abdomen, is a diagnostic dilemma. This report emphasizes the importance of diagnostic laparoscopy in the diagnosis of the tumour. PMID:25866695
Phua, Kyle K. L.; Nair, Smita K.; Leong, Kam W.
Use of mRNA-based vaccines for tumour immunotherapy has gained increasing attention in recent years. A growing number of studies applying nanomedicine concepts to mRNA tumour vaccination show that the mRNA delivered in nanoparticle format can generate a more robust immune response. Advances in the past decade have deepened our understanding of gene delivery barriers, mRNA's biological stability and immunological properties, and support the notion for engineering innovations tailored towards a more efficient mRNA nanoparticle vaccine delivery system. In this review we will first examine the suitability of mRNA for engineering manipulations, followed by discussion of a model framework that highlights the barriers to a robust anti-tumour immunity mediated by mRNA encapsulated in nanoparticles. Finally, by consolidating existing literature on mRNA nanoparticle tumour vaccination within the context of this framework, we aim to identify bottlenecks that can be addressed by future nanoengineering research.
Trott, K. R.
During a course of radiotherapy or chemotherapy the number of clonogenic cells in a tumour decreases exponentially. After one third of the treatment period more than 99% of the remaining tumour consists of doomed cells. Therefore, it would appear to be impossible to assess the therapeutic response of tumours directly from biopsy material taken during treatment. Nevertheless, attempts to study the therapeutic response during treatment have been made in order to obtain prognostic information on individuals so as to individualize treatment. A variety of approaches have been used. In carcinoma of the cervix a close correlation has been established between the results of some of these assays and local tumour control or long term survival of patients. Even without a complete understanding of the undelying mechanisms, these methods may be useful for the selection of patients for unconventional treatments like fast neutrons or other modalities which are not available to all patients. PMID:7000119
Kauczor, Hans-Ulrich; Plathow, Christian
Novel technology has made dynamic magnetic resonance imaging (MRI) of lung motion and lung tumour mobility during continuous respiration feasible. This might be beneficial for planning of radiotherapy of lung tumours, especially when using high precision techniques. This paper describes the recent developments to analyze and visualize pulmonary nodules during continuous respiration using MRI. Besides recent dynamic two-dimensional approaches to quantify motion of pulmonary nodules during respiration novel three-dimensional techniques are presented. Beyond good correlation to pulmonary function tests MRI also provides regional information about differences between tumour-bearing and non-tumour bearing lung and the restrictive effects of radiotherapy as well as the compensation by the contralateral lung. PMID:17114068
Fasano, A; Mancini, A; Primicerio, M
The role of cancer stem cells (CSC) in tumour growth has received increasing attention in the recent literature. Here we stem from an integro-differential system describing the evolution of a population of CSC and of ordinary (non-stem) tumour cells formulated and studied in a previous paper, and we investigate an approximation in which the system reduces to a pair of nonlinear coupled parabolic equation. We prove that the new system is well posed and we examine some general properties. Numerical simulations show more on the qualitative behaviour of the solutions, concerning in particular the so-called tumour paradox, according to which an increase of the mortality rate of ordinary (non-stem) tumour cells results asymptotically in a faster growth.
Izumi, Yotaro; Xu, Lei; di Tomaso, Emmanuelle; Fukumura, Dai; Jain, Rakesh K.
Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.
Taleb, C; Gouzou, S; Mantovani, G; Liverneaux, P
Curettage and bone grafting are used traditionally to treat benign bone tumours of the hand. Some authors are proposing minimally invasive treatment using endoscopy. Our purpose is to standardise this technique based on a study of the number and locations of entry points. This is a report on three benign metacarpal bone tumours treated with three different endoscopic approaches: multiportal, extended uniportal and oblique uniportal. In theory, the multiportal approach has several drawbacks: weakening of the bone cortex, a limited visual field and seepage of injectable phosphocalcic cement. The extended uniportal approach causes cortical defects, unacceptable in a minimally invasive technique. The oblique uniportal approach seems less troublesome; vision of the bone cavity is good, curettage of the tumour is complete, the bone cortex is undamaged and there is no leakage of injectable phosphocalcic cement. All things considered, the oblique osteoscopic uniportal approach seems to be the best option for the management of benign bone tumours of the hand.
Zhao, Yiming; Fay, Francois; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphael; de Lange Davies, Catharina; Bjorkoy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Perez-Medina, Carlos; Mulder, Willem J. M.
A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug–carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug–carrier compatibility affects drug release in a tumour mouse model. We found the drug’s hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug’s compatibility; as a result, we achieved better antitumour efficacy. Lastly, our results help elucidate nanomedicines’ in vivo fate and provide guidelines for efficient drug delivery.
Zhao, Yiming; Fay, François; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphaël; de Lange Davies, Catharina; Bjørkøy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Pérez-Medina, Carlos; Mulder, Willem J. M.
A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery.
Mangiola, Stefano; Hong, Matthew K. H.; Cmero, Marek; Kurganovs, Natalie; Ryan, Andrew; Costello, Anthony J.; Corcoran, Niall M.; Macintyre, Geoff; Hovens, Christopher M.
The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extraprostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extraprostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage. PMID:27653089
Zhao, Yiming; Fay, Francois; Hak, Sjoerd; ...
A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug–carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug–carrier compatibility affects drug release in a tumour mouse model. We found the drug’s hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, wemore » applied these findings to improve chemotherapeutic delivery by augmenting the parent drug’s compatibility; as a result, we achieved better antitumour efficacy. Lastly, our results help elucidate nanomedicines’ in vivo fate and provide guidelines for efficient drug delivery.« less
Hicks, J; Platt, S; Kent, M; Haley, A
Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.
Boultwood, J.; Kaklamanis, L.; Gatter, K. C.; Wainscoat, J. S.
The application of pulsed field gel electrophoresis (PFGE) to the molecular genetic analysis of solid tumours has been restricted by the requirement for whole single cells as a DNA source. A simple technique which allows for the direct analysis of histologically characterised solid tumour material by pulsed field gel electrophoresis was developed. Single frozen tissue sections obtained from colonic carcinoma specimens were embedded without further manipulation in molten, low melting temperature agarose. The tumour DNA contained within the agarose plug was subjected to restriction enzyme digestion and PFGE. Sufficient high molecular weight DNA is yielded by this method to obtain a hybridisation signal with a single copy probe. Histological examination of adjacent tissue sections may also be carried out, permitting correlation between molecular analysis and tumour histology. Images PMID:1401187
Chavez-Uribe, Elisabet; Rodriguez, Beatriz Fernandez; Muñoz, Catuxa Celeiro; Redondo, Carmen M.; Fernandez, Maite Peña; Dominguez, Alejandro Novo; Pereira, Carina Doris; Martínez, María Elena; García-Caballero, Tomás; Rodriguez, Máximo Fraga; Antúnez, José; Carracedo, Angel; Forteza-Vila, Jerónimo; Gago-Dominguez, Manuela
Background Breast cancer is a heterogenous disease that impacts racial/ethnic groups differently. Differences in genetic composition, lifestyles, reproductive factors, or environmental exposures may contribute to the differential presentation of breast cancer among Hispanic women. Materials and Methods A population-based study was conducted in the city of Santiago de Compostela, Spain. A total of 645 women diagnosed with operable invasive breast cancer between 1992 and 2005 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics of the tumors were collected. Hormone receptor negative tumors were compared with hormone receptor postive tumors on their clinico-pathological characteristics as well as risk factor profiles. Results Among the 645 breast cancer patients, 78% were estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+), and 22% were ER−&PR−. Women with a family history of breast cancer were more likely to have ER−&PR− tumors than women without a family history (Odds ratio, 1.43; 95% confidence interval, 0.91–2.26). This association was limited to cancers diagnosed before age 50 (Odds ratio, 2.79; 95% confidence interval, 1.34–5.81). Conclusions An increased proportion of ER−&PR− breast cancer was observed among younger Spanish women with a family history of the disease. PMID:22238615
Altura, R A; Olshefski, R S; Jiang, Y; Boué, D R
Survivin is a gene that is widely expressed throughout the development of the normal mammalian embryo. Subcellular localisation of Survivin to both the nucleus and cytoplasm has suggested multiple functional roles, including inhibition of cell death, especially as demonstrated within a variety of malignant cell types, as well as regulation of the mitotic spindle checkpoint. The expression of Survivin has been associated with an adverse clinical outcome in a large number of malignancies. However, nuclear Survivin expression has been described as an independent variable of favourable prognosis in two large clinical studies of breast and gastric carcinomas. Reports of Survivin expression in normal postnatal, differentiated tissues have been restricted to cell types with high proliferative capacities, including vascular endothelium, endometrium, colonic epithelium, and activated lymphocytes. Prior to this report, expression within the normal human brain had not been characterised. Here, we analyse the expression of Survivin in human brain sections obtained from perinatal and paediatric autopsy cases. We report a strikingly high level of expression of Survivin within normal ependyma and choroid plexus (CP). Analysis of corresponding neoplastic tissue in paediatric ependymomas and CP tumours shows that expression of the nuclear form of Survivin correlates with morphologic tumour grade, with a loss of nuclear expression associated with progressive cytologic anaplasia. This pattern of expression supports a hypothesis that Survivin plays a functional role in normal ependymal growth and/or neural stem cell differentiation, and that abnormally low levels of expression of the nuclear form of this protein may be a marker of more aggressive disease and/or higher morphologic grade in ependymal and CP tumours.
Krymskaya, Vera P
Tumour suppressors hamartin and tuberin, encoded by tuberous sclerosis complex 1(TSC1) and TSC2 genes, respectively, are critical regulators of cell growth and proliferation. Mutations in TSC1 and TSC2 genes are the cause of an autosomal dominant disorder known as tuberous sclerosis complex (TSC). Another genetic disorder, lymphangioleiomyomatosis (LAM), is also associated with mutations in the TSC2 gene. Hamartin and tuberin control cell growth by negatively regulating S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E binding protein 1 (4E-BP1), potentially through their upstream modulator mammalian target of rapamycin (mTOR). Growth factors and insulin promote Akt/PKB-dependent phosphorylation of tuberin, which in turn, releases S6K1 from negative regulation by tuberin and results in the activation of S6K1. Although much has been written regarding the molecular genetics of TSC and LAM, which is associated with either the loss of or mutation in the TSC1 and TSC2 genes, few reviews have addressed the intracellular signalling pathways regulated by hamartin and tuberin. The current review will fill the gap in our understanding of their role in cellular signalling networks, and by improving this understanding, an integrated picture regarding the normal function of tuberin and hamartin is beginning to emerge.
Clark, W. H.
The nature of neoplasia and its sometime end result, cancer, has been studied by exposition and explanation of the sequential lesions of tumour progression. Neoplastic lesions were divided into four classes on the basis of growth characteristics and whether lesional growth is confined to one or more tissue compartments. Class IA, the initial lesion, an orderly, probably clonal growth, usually differentiates and disappears. Class IB: Failure to differentiate accompanied by disorderly growth. Class IC: Randomly dispersed atypical cells, constituting a precursor state. Class II, intermediate lesions, apparently arising from the atypical cells, show temporally unrestricted growth within the tissue compartment of origin. Class III lesions, primary invasive cancers, show temporally unrestricted growth in two or more tissue compartments and metastasise along different paths, a property associated with extracellular matrix interaction. The metastatic pathways may result from different subsets of cells in the primary cancer. Class IV lesions are the metastases. It was concluded that, all neoplasms develop in the same way, have the same general behavioural characteristics, and, when malignant, all interact with the extracellular matrix of the primary and the secondary sites. The origins and development of cancer are considered to be pluralistic and not due to a discrete change in a cell, whose progeny, as a result of that discrete change, carries all of the information required to explain the almost limitless events of a neoplastic system. Images Figure 4 PMID:1911211
Hinrichs, U; Rutteman, G R; Nederbragt, H
To contribute to the investigation of the composition of the extracellular matrix in epithelial tumours, mammary gland tissues of dogs (including tumours, hyperplasias and normal tissue as well as metastatic lesions in lymph nodes and lung) were studied histochemically and immunohistochemically for distribution of sulphated glycosaminoglycans (s-GAGs). The formaline-fixed tissue was stained by alcian blue at pH 5.8, using the ‘critical electrolyte concentration’ to study the degree of sulphation of s-GAGs. s-GAGs were characterized by degradation with enzymes and nitrous acid and by immunohistochemistry with two anti-chondroitin sulphate monoclonal antibodies. The light microscopic investigation of s-GAG deposits revealed a limited number of patterns of their distribution. The main s-GAGs found in the mammary gland tumours of dogs and in metastatic lesions were chondroitin sulphate (CS) and heparin/heparan sulphate (HEP/HS). CS accumulated in diffuse structures between epithelial cells as well as around clusters of tumour cells. The latter pattern, possibly representing a mesenchymal reaction to the tumour, was present in 74% of the tumours, and in 67% of these, highly sulphated CS was present. A diffuse accumulation of CS was present almost exclusively in complex and mixed tumours; because of the expression of the 3B3 epitope for CS in immature cartilage the spindle cells of complex tumours are argued to be the precursors of the cartilage in mixed tumours. HEP/HS was stored mainly in mast cells that were found in increased numbers in hyperplasias and tumours. By pretreatment of microscopic slides with chondroitinase AC or ABC immunostaining of fibronectin could be made possible in areas in which CS was abundantly present, suggesting that CS may mask fibronectin epitopes. It is concluded that CS with different degrees of sulphation is the most important s-GAG in the extracellular matrix of mammary tumours of dogs. CS and other s-GAGs accumulate at different
Söderquist, Fanny; Janson, Eva Tiensuu; Rasmusson, Annica J.; Ali, Abir; Stridsberg, Mats; Cunningham, Janet L.
Background/Aims Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. Methods Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs. Results Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038). Conclusion Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin’s endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function. PMID:27736994
Rivera, S; Azcón-Bieto, J; López-Soriano, F J; Miralpeix, M; Argilés, J M
Mice bearing the Lewis lung carcinoma showed a high tumour glutaminase activity and significantly higher concentrations of most amino acids than in both the liver and the skeletal muscle of the host. Tumour tissue slices showed a marked preference for glutamine, especially for oxidation of its skeleton to CO2. It is proposed that the metabolism of this particular carcinoma is focused on amino acid degradation, glutamine being its preferred substrate. PMID:3342022
Alder, L.S.; Elver, G.; Foo, F.J.; Dobson, M.
Gastrointestinal stromal tumour (GIST are the most common mesenchymal tumours; however, rectal GISTs account for <5%. In the pelvis they represent a diagnostic challenge with giant GISTs likely to be malignant. They may present with urological, gynaecological or rectal symptoms. Sphincter-preserving surgery can be aided by neoadjuvant therapy. We present an uncommon case of giant rectal GIST masquerading as acute urinary retention. PMID:24968434
Wessel, Carolina; Schnabel, Julia A; Brady, Michael
We develop a biomechanical model of an isolated stellate breast tumour under mammographic compression forces for a range of reported mechanical properties, both linear elastic and hyperelastic. We also introduce different volumes of increased density/stiffness around the tumour as well as a solid pressure effect. We show that each of these issues--well known to clinicians but ignored to date in models--has a non-negligible effect on stresses and strains/deformations.
Verellen, D; Depuydt, T; Gevaert, T; Linthout, N; Tournel, K; Duchateau, M; Reynders, T; Storme, G; De Ridder, M
The limited ability to control for a tumour's location compromises the accuracy with which radiation can be delivered to tumour-bearing tissue. The resultant requirement for larger treatment volumes to accommodate target uncertainty restricts the radiation dose because more surrounding normal tissue is exposed. With image-guided radiation therapy (IGRT), these volumes can be optimized and tumouricidal doses may be delivered, achieving maximum tumour control with minimal complications. Moreover, with the ability of high precision dose delivery and real-time knowledge of the target volume location, IGRT has initiated the exploration of new indications in radiotherapy such as hypofractionated radiotherapy (or stereotactic body radiotherapy), deliberate inhomogeneous dose distributions coping with tumour heterogeneity (dose painting by numbers and biologically conformal radiation therapy), and adaptive radiotherapy. In short: "individualized radiotherapy". Tumour motion management, especially for thoracic tumours, is a particular problem in this context both for the delineation of tumours and organs at risk as well as during the actual treatment delivery. The latter will be covered in this paper with some examples based on the experience of the UZ Brussel. With the introduction of the NOVALIS system (BrainLAB, Feldkirchen, Germany) in 2000 and consecutive prototypes of the ExacTrac IGRT system, gradually a hypofractionation treatment protocol was introduced for the treatment of lung tumours and liver metastases evolving from motion-encompassing techniques towards respiratory-gated radiation therapy with audio-visual feedback and most recently dynamic tracking using the VERO system (BrainLAB, Feldkirchen, Germany). This evolution will be used to illustrate the recent developments in this particular field of research.
Jin, Ke; Li, Tong; van Dam, Hans; Zhou, Fangfang; Zhang, Long
Metastasis of malignant cells to vital organs remains the major cause of mortality in many types of cancers. The tumour invasion-metastasis cascade is a stepwise and multistage process whereby tumour cells disseminate from primary sites and spread to colonize distant sites through the systemic haematogenous or lymphatic circulations. The general steps of metastasis may be similar in almost all tumour types, but metastasis to different tissues seems to require distinct sets of regulators and/or an 'educated' microenvironment which may facilitate the infiltration and colonization of tumour cells to specific tissues. Moreover, interactions of tumour cells with stromal cells, endothelial cells, and immune cells that they encounter will also aid them to gain survival advantages, evade immune surveillance, and adapt to the new host microenvironment. Due to the high correlation between tumour metastasis and survival rate of patients, a deeper understanding of the molecular participants and processes involved in metastasis could pave the way towards novel, more effective and targeted approaches to prevent and treat tumour metastasis. In this review, we provide an update on the regulation networks orchestrated by the dominant regulators of different stages throughout the metastatic process including, but not limited to, epithelial-mesenchymal transition in local invasion, resistance to anoikis during migration, and colonization of different distant sites. We also put forward some suggestions and problems concerning the treatment of tumour metastasis that should be solved and/or improved for better therapies in the near future. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Edwan, Ghazi Al; Ghai, Sangeet; Margel, David; Kulkarni, Girish; Hamilton, Rob; Toi, Ants; Haidar, Masoom A.; Finelli, Antonio; Fleshner, Neil E.
Introduction: Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have previously described our initial experience with magnetic resonance imaging (MRI)-based detection of tumours in the anterior prostate gland. In this report, we update and expand our experience with these tumours in terms of multiparametric-MRI findings, staging, and grading. Furthermore, we report early treatment outcomes with these unique cancers. Methods: We reviewed our prostate MRI dataset of 1117 cases from January 2006 until December 2012 and identified 189 patients who fulfilled criteria for prostate evasive anterior tumors (PEATS). Descriptive analyses were performed on multiple covariates. Kaplan-Meier actuarial technique was used to plot the treatment-related outcomes from PEATS tumours. Results: Among the 189 patients who had MRI-detectable anterior tumours, 148 had biopsy proven disease in the anterior zone. Among these tumours, the average PSA was 18.3 ng/mL and most cancers were Gleason 7. In total, 68 patients chose surgical therapy. Among these men, most of their cancers had extra prostatic extension and 46% had positive surgical margins. Interestingly, upgrading of tumours that were biopsy Gleason 6 in the anterior zone was common, with 59% exhibiting upgrading to Gleason 7 or higher. Biochemical-free survival among men who elected surgery was not ideal, with 20% failing by 20 months. Conclusion: PEATS tumours are found late and are disproportionally high grade tumours. Careful consideration to MRI testing should be given to men at risk for PEATS. PMID:26029293
Hardell, L; Hallquist, A; Mild, K Hansson; Carlberg, M; Påhlson, A; Lilja, A
Microwave exposure from the use of cellular telephones has been discussed in recent years as a potential risk factor for brain tumours. We included in a case-control study 1617 patients aged 20-80 years of both sexes with brain tumour diagnosed between 1 January 1997 and 30 June 2000. They were alive at the study time and had histopathologically verified brain tumour. One matched control to each case was selected from the Swedish Population Register. The study area was the Uppsala-Orebro, Stockholm, Linköping and Göteborg medical regions of Sweden. Exposure was assessed by a questionnaire that was answered by 1429 (88%) cases and 1470 (91%) controls. In total, use of analogue cellular telephones gave an increased risk with an odds ratio (OR) of 1.3 (95% confidence interval (CI) 1.02-1.6). With a tumour induction period of >10 years the risk increased further: OR 1.8 (95% CI 1.1-2.9). No clear association was found for digital or cordless telephones. With regard to the anatomical area of the tumour and exposure to microwaves, the risk was increased for tumours located in the temporal area on the same side of the brain that was used during phone calls; for analogue cellular telephones the OR was 2.5 (95% CI 1.3-4.9). Use of a telephone on the opposite side of the brain was not associated with an increased risk for brain tumours. With regard to different tumour types, the highest risk was for acoustic neurinoma (OR 3.5, 95% CI 1.8-6.8) among analogue cellular telephone users.
Dewhirst, M W; Prescott, D M; Clegg, S; Samulski, T V; Page, R L; Thrall, D E; Leopold, K; Rosner, G; Acker, J C; Oleson, J R
Hydralazine is an antihypertensive drug which theoretically could increase tumour temperatures during hyperthermia via reduction in tumour blood flow from a vascular 'steal' phenomenon. Doses that are therapeutically effective in reducing blood pressure in hypertensive patients would probably cause postural hypotension and other side-effects in normotensive patients beyond the hyperthermia treatment session, however. This study was designed to evaluate whether hydralazine, when administered at a safe dose for normotensive patients (0.125 mg/kg, i.v.) would be effective in increasing tumour temperatures during hyperthermia. The working hypothesis was that hydralazine at a dose of 0.125 mg/kg would be effective in raising tumour temperatures during hyperthermia treatment with minimal change in blood pressure. Fourteen human and five canine subjects were given hydralazine (0.125 mg/kg, i.v.) at the midpoint of a hyperthermia session. Temperatures and blood pressures were monitored before and after drug administration. Although hydralazine resulted in slight reduction in blood pressure, it was ineffective in increasing tumour temperatures in human patients (average maximum rise in median temperature was 0.26 +/- 0.32 degrees C). In canine subjects the same dose of hydralazine was effective in reducing blood pressure in four of five subjects studied (mean maximum drop was 22.7 +/- 4.1 mmHg) and the median temperature rose 0.8 +/- 0.7 degrees C. In the canine subjects the greater the decrease in blood pressure, the greater the increase in temperature. These results suggest that a rise in tumour temperature induced by hydralazine is dependent on creating a drop in blood pressure. Future studies in this laboratory will include tumour blood flow manipulation with antihypertensives which have a shorter half-life and a titratable effect. Using this approach, hypotension, which seems to be required to raise tumour temperature, will be more controllable in terms of magnitude
Hamede, Rodrigo K; McCallum, Hamish; Jones, Menna
The Tasmanian devil is threatened with extinction by devil facial tumour disease (DFTD), a unique infectious cancer in which the tumour cells themselves, which derive from a single long-dead host devil, are the infective agent and the tumour is an infectious parasitic cell line. Transmission is thought to occur via direct inoculation of tumour cells when susceptible and infected individuals bite each other or by fomitic transfer of tumour cells. The nature of transmission and the extent to which biting behaviour and devil ecology is associated with infection risk remains unclear. Until our recent study in north-west Tasmania showed reduced population and individual impacts, DFTD had caused massive population declines in all populations monitored. In this paper, we investigate seasonal patterns of injuries resulting from bites between individuals, DFTD infection status and tumour location in two populations to determine whether the number of bites predicts the acquisition of DFTD and to explore the possibility that the reduced impacts of DFTD in north-west Tasmania are attributed to reduced bite rates. Devils with fewer bites were more likely to develop DFTD and primary tumours occurred predominantly inside the oral cavity. These results are not consistent with transmission occurring from the biter to the bitten animal but suggest that dominant individuals delivering bites, possibly by biting the tumours of other devils, are at higher risk of acquiring infection than submissive individuals receiving bites. Bite rates, which were higher during autumn and winter, did not differ between sites, suggesting that the reduced population impacts in north-west Tasmania cannot be explained by lower bite rates. Our study emphasizes the importance of longitudinal studies of individually marked animals for understanding the ecology and transmission dynamics of infectious diseases and parasites in wild populations.
Amirjamshidi, A; Ghodsi, M; Edraki, K
An hour-glass-shaped multidensity lesion found by CT in a 6-year-old boy who had been admitted to the emergency department after a mild car accident. This lesion turned out to be a congenital dermoid tumour of the right cerebellopontine angle-tentorial notch region containing 12 mature teeth and 14 pseudocarilagenous structures. This is the first case of dermoid tumour containing so many teeth, reported in an asymptomatic person and located off the midline.
Shikhare, Sumer; Chacko, Julio K; Chuah, Khoon L
Intramuscular haemangiomas are benign soft-tissue tumours, commonly located in the extremities. We present a right-leg intramuscular haemangioma with florid periosteal reaction in adjacent tibia, mimicking a primary bone tumour. Plain radiograph and magnetic resonance imaging features are illustrated with the surgical and histopathological findings. Radiologists need to be familiar with reactive bone changes secondary to deep-seated intramuscular haemangiomas to avoid potential misdiagnosis.
Tariq, Naima; Qureshi, Asim; Dian, Asifa
Solid pseudo-papillary tumour of pancreas is a rare neoplasm having a low malignant potential. It mostly affects young adolescent females. We report an unusual case of an 18 year old male with a mass in the mesocolon which was reported as solid pseudo-papillary tumour of pancreas. This case is unusual by virtue of extra pancreatic location and male gender of the patient.
Ródenas, Sergio; Pumarola, Marti; Gaitero, Lluís; Zamora, Angels; Añor, Sònia
Magnetic resonance (MR) images of 40 dogs with histologically confirmed primary and secondary intracranial tumours were reviewed. Forty-one tumours were diagnosed by means of MR imaging (MRI). MRI findings allowed diagnosis of a neoplastic lesion in 37/41 cases. Based on MRI features, differentiation between neoplastic and non-neoplastic lesions was possible in 24/27 (89%) primary brain tumours and in 13/14 (92%) secondary brain tumours. Diagnosis of tumour type based on MRI features was correct in 19/27 (70%) primary tumours and in 13/14 secondary tumours. The results of this study show that MRI is a good diagnostic imaging modality to detect neoplastic lesions and to diagnose tumour type in dogs. However, as some neoplasms show equivocal MRI features the technique has limitations in the detection of some intracranial tumours and in predicting tumour type.
Gerlee, Philip; Anderson, Alexander R. A.
The morphology of solid tumours is known to be affected by the background oxygen concentration of the tissue in which the tumour grows, and both computational and experimental studies have suggested that branched tumour morphology in low oxygen concentration is caused by diffusion-limited growth. In this paper we present a simple hybrid cellular automaton model of solid tumour growth aimed at investigating this phenomenon. Simulation results show that for high consumption rates (or equivalently low oxygen concentrations) the tumours exhibit branched morphologies, but more importantly the simplicity of the model allows for an analytic approach to the problem. By applying a steady-state assumption we derive an approximate solution of the oxygen equation, which closely matches the simulation results. Further, we derive a dispersion relation which reveals that the average branch width in the tumour depends on the width of the active rim, and that a smaller active rim gives rise to thinner branches. Comparison between the prediction of the stability analysis and the results from the simulations shows good agreement between theory and simulation. PMID:20462295
Axelsson, G; Rylander, R; Schmidt, A
ABSTRACT An investigation was carried out to determine the cause of death and the incidence of tumours among 1932 workers in a ferrochromium plant in Sweden. The workers had been exposed mainly to metallic and trivalent chromium (Cr3+); hexavalent chromium (Cr6+) was also present in certain working operations. The population was defined as all men employed at the plant for at least one year during 1930-75, and were classified according to their occupation within the industry. The causes of death were initially obtained from parish registers. For deaths occuring between 1951 and 1975, death certificates were collected from the National Central Bureau of Statistics. Data on the incidence of cancer during 1958-75 were obtained from the Swedish National Cancer Registry. Expected death rates and incidence of tumours were calculated, based on the rates for the county in which the factory was situated. The total number of deaths from tumours was less than expected (69 versus 76·7). Five cases of respiratory cancer were found, against an expected 7·2. Among maintenance workers, an increased death rate from all tumours and an increased number of respiratory tumours were found. Two of the latter were mesotheliomas and could be connected with asbestos exposure. No increase was found for respiratory tumours among the heavily exposed workers at the arc-furnaces; one case of mesothelioma was found in this group. PMID:7426462
Liang, E Y; Chan, A; Chung, S C; Metreweli, C
A CT technique for measuring oesophageal cancer tumour volume in the monitoring of local disease response following radiotherapy or chemotherapy is described. Patients with newly diagnosed oesophageal carcinoma were referred for pre- and post-chemotherapy CT scans. IV Buscopan was given to abolish peristalsis. Patients were scanned in prone position. Effervescent gas granules and Calogen (a negative contrast of fat density) were given. Spiral scanning was performed. The area of tumour on each 1 cm slice was measured. The sum of these areas gave tumour volume in cubic centimetres. The accuracy of the method was tested on patients who had had surgery. The volume of the segment of oesophagus containing tumour was measured by its weight and water displacement. Lumenal distention proximal and distal to the tumour was achieved in all patients. 10 gross surgical specimens were available for comparison with pre-operative CT. The correlation coefficient was 0.95. In conclusion, accurate tumour volume assessment was achieved with our technique.
Chung, Il Yong; Park, Yu Rang; Min, Yul Ha; Lee, Yura; Yoon, Tae In; Sohn, Guiyun; Lee, Sae Byul; Kim, Jisun; Kim, Hee Jeong; Ko, Beom Seok; Son, Byung Ho; Ahn, Sei Hyun
The aim of this study was to determine the relationship between the body mass index (BMI) at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS) and breast-cancer-specific survival (BCSS) outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029), and BCSS (P = 0.013) in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48) and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99). In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19) and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44). Being underweight (BMI < 18.50 kg/m2) with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00–3.95) and BCSS (HR = 2.24, 95% CI = 1.12–4.47). There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer. PMID:28248981
Allavena, P; Mantovani, A
Mononuclear phagocytes are cells of the innate immunity that defend the host against harmful pathogens and heal tissues after injury. Contrary to expectations, in malignancies, tumour-associated macrophages (TAM) promote disease progression by supporting cancer cell survival, proliferation and invasion. TAM and related myeloid cells [Tie2(+) monocytes and myeloid-derived suppressor cells (MDSC)] also promote tumour angiogenesis and suppress adaptive immune responses. These divergent biological activities are mediated by macrophages/myeloid cells with distinct functional polarization, which are ultimately dictated by microenvironmental cues. Clinical and experimental evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of macrophages in tumours is considered a promising therapeutic strategy: depletion of TAM or their 're-education' as anti-tumour effectors is under clinical investigation and will hopefully contribute to the success of conventional anti-cancer treatments.
MALEKINEJAD, Hassan; REZABAKHSH, Aysa
Background: The presence of hormones in milk and dairy foods was discussed decades ago but rather more concerns attended to that with respect to finding hormones as biomarkers in milk for diseases and pregnancy diagnosis. Moreover, considerable amount of studies demonstrated that existing of hormones in humans and animals milk are essential for infants growing and immunity. During the last couple of years, increasing body of evidence are indicating another property of hormones in dairy products as possible impact on human health including the role of some estrogens and insulin-like growth factor-1 in initiation and provoking of breast, prostate and endometrial tumours. Methods: Data was gathered from the published articles in database such as MEDLINE, science direct, Google scholar and web of science. We put no limitation on date of published date. Moreover, our own published and conducted methods and results also are presented. In this review we concentrated on several aspects of presence of hormones in dairy foods with especial emphasize on cow’s milk as a major source of consuming milk for humans especially for children. Results: The collected data from other researchers and our own data are indicating that the presence of steroid hormones in dairy products could be counted as an important risk factor for various cancers in humans. Conclusion: Our gathered data in this review paper may suggest more sophisticate analytical detection methods for oestrogens determination and also could be considered as a remarkable concern for consumers, producers and public health authorities. PMID:26258087
Yacoub, M. H.; Simon, G.; Ohnsorge, J.
Three cases of pulmonary osteoarthropathy secondary to pulmonary metastases from extrathoracic tumours are described. Analysis of the reported cases shows that most of them were secondary to osteosarcoma, nasopharyngeal tumour, fibrosarcoma, and uterine tumour. Fibrous tumours and tumours with a predominantly fibrous stroma tend to be associated with osteoarthropathy more than others. This suggests that the fibrous stroma may be a factor in the stimulation of the reflex mechanism responsible for osteoarthropathy. Images PMID:6033389
Santoro, M; Stacy, B A; Morales, J A; Gastezzi-Arias, P; Landazuli, S; Jacobson, E R
A well-differentiated cutaneous mast cell tumour was diagnosed in a subadult female giant Galapagos tortoise. The tumour was a pedunculated, verrucose mass located near the base of the neck. The histological features, which were diagnostic for a mast cell tumour, included abundant intracytoplasmic granules that were stained metachromatically with Giemsa and toluidine blue stains. Mast cell tumours are rare in reptiles, and this is the first description of a mast cell tumour in a chelonian.
Arya, Neha; Sardana, Viren; Saxena, Meera; Rangarajan, Annapoorni; Katti, Dhirendra S.
Owing to the reduced co-relationship between conventional flat Petri dish culture (two-dimensional) and the tumour microenvironment, there has been a shift towards three-dimensional culture systems that show an improved analogy to the same. In this work, an extracellular matrix (ECM)-mimicking three-dimensional scaffold based on chitosan and gelatin was fabricated and explored for its potential as a tumour model for lung cancer. It was demonstrated that the chitosan–gelatin (CG) scaffolds supported the formation of tumoroids that were similar to tumours grown in vivo for factors involved in tumour-cell–ECM interaction, invasion and metastasis, and response to anti-cancer drugs. On the other hand, the two-dimensional Petri dish surfaces did not demonstrate gene-expression profiles similar to tumours grown in vivo. Further, the three-dimensional CG scaffolds supported the formation of tumoroids, using other types of cancer cells such as breast, cervix and bone, indicating a possible wider potential for in vitro tumoroid generation. Overall, the results demonstrated that CG scaffolds can be an improved in vitro tool to study cancer progression and drug screening for solid tumours. PMID:22977099
Colin, Pieter; De Smet, Lieselotte; De Bock, Lies; Goeteyn, Wim; Boussery, Koen; Vervaet, Chris; Van Bocxlaer, Jan
Paclitaxel is a good compound for regional (intraperitoneal) chemotherapy of peritoneal carcinomatosis. During IPEC, a cytotoxic solution is circulated in the peritoneal cavity, thereby promoting close contact between the cytotoxic agent and the exposed (residual) tumour tissue. To further explore the role of PTX in this type of treatment and study the impact of treatment modalities on tumour tissue penetration, in-vivo animal experiments were set-up. In literature, PTX tumour uptake is frequently studied using autoradiography and/or fluorescence microscopy techniques. Owing to their semi-quantitative nature on one hand and the difficulty of incorporating imaging data within a pharmacokinetic-pharmacodynamic modelling framework on the other hand, we set out to develop a validated assay for the quantification of PTX in tumour tissue samples. Furthermore, in order to maximise spatial resolution, care was taken to minimise the sample weight necessary for the analysis. Based on an enzymatic tumour tissue digestion protocol, an easy, less labour-intensive, when compared to mechanical tissue disruption techniques, method was developed. Through validation experiments we showed that our method reliably quantifies PTX in a working range of 30-8000 ng/g tumour tissue. Finally, using samples from the in-vivo experiments we demonstrated the suitability of the developed method.
Verdorfer, I; Höllrigl, A; Strasser, U; Susani, M; Hartmann, A; Rogatsch, H; Mikuz, G
Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.
Mandara, M T; Fabriani, E; Pavone, S; Pumarola, M
Feline cutaneous nerve sheath tumours (CNSTs) are uncommonly reported in the skin, since they are underestimated relative to the more common spindle cell tumours of soft tissue. In this study, 26 nerve sheath tumours selected from 337 skin neoplasms of cats were examined. Histologically, they were classified into malignant (MPNSTs) and benign tumours (BPNSTs) based on degree of cellular atypia and polymorphism as well as mitotic rate and diffuse necrosis. CPNSTs were tipically characterised by Antoni A pattern, in some cases associated with Antoni B pattern. In the malignant peripheral nerve sheath tumours (MPNSTs) the polymorphism was marked, while it was mild to moderate in the benign forms (BPNSTs). In the MPNSTs the mitotic activity was generally higher than in the BPNSTs. In five cases, including three MPNSTs and two BPNSTs, there were multinucleated giant cells. Necrotic foci occurred in a BPNST and in two MPNSTs, while osseous/chondroid metaplasia was found in two cases. Immunohistochemically, all the tumours showed a marked diffuse vimentin expression. S-100 protein was expressed in 17 cases, including 81.8% of BPNSTs and 57.14% of MPNSTs. Twenty-five tumours expressed NSE and twenty-four cases showed immunoreaction for laminin. Thirteen tumours were positive for GFAP, while five tumours were positive for SMA. PGP 9.5 expression was detected in all cases, except for two MPNSTs. NGFR was expressed in eleven cases, including four MPNSTs and seven BPNSTs. Ki67 was expressed in twenty tumours without any relationship with morphologic malignancy of the neoplasm. In this case series we confirmed neoplastic spindloid cells with wavy cytoplasm arranged in compact areas, with occasional nuclear palisading or whirls, and interchanged with loosely arranged areas, as the morphological features supporting a diagnosis of CPNST. A constant concurrent expression of vimentin, NSE, and laminin might confirm the diagnosis of PNST in the absence of clear S-100 protein
Investigators, The PARITY
Objective Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. Methods We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. Results We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. Conclusions It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162 PMID:26423584
O’Mara, Daniel M.; Aschner, Michael
Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal neurodevelopment. Thyroid hormone tissue activation and inactivation in brain, liver, and other tissues is controlled by the deiodinases through the removal of iodine atoms. Selenium, an essential element critical for deiodinase activity, is sensitive to mercury and, therefore, when its availability is reduced, brain development might be altered. This review addresses the possibility that high exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function. PMID:18716716
Bräuner, Elvira V.; Andersen, Zorana J.; Andersen, Claus E.; Pedersen, Camilla; Gravesen, Peter; Ulbak, Kaare; Hertel, Ole; Loft, Steffen; Raaschou-Nielsen, Ole
Background Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist. Objective To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort. Methods During 1993–1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed. Results Median estimated radon was 40.5 Bq/m3. The adjusted IRR for primary brain tumour associated with each 100 Bq/m3 increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution. Conclusions We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies. PMID:24066143
Allen, J. A.; O'Brien, F.; Tuthill, A.; Power, D. G.
A 37-year-old male presented with a traumatic injury to the scrotal region necessitating emergency surgery. Evacuation of a haematoma and bilateral orchidectomy were performed. A left sided nonseminomatous germ cell tumour (NSGCT), predominantly yolk sac, was identified. Microscopic margins were positive for tumour. Initial tumour markers revealed an AFP of 22,854 ng/mL, HCG of <1 mIU/mL, and LDH of 463 IU/L. Eight weeks after surgery, AFP levels remained elevated at 11,646 ng/mL. Computed tomography (CT) scanning demonstrated left inguinal adenopathy, 1.5 cm in max dimension. On review, extensive evidence of scrotal involvement was evident. His tumour was staged as stage IIIC, poor risk NSGCT. He was treated with 4 cycles of bleomycin, etoposide, and cisplatin over a 12-week period. His tumour markers normalised after 3 cycles. There was a marked improvement noted clinically. Follow-up CT scans demonstrated complete resolution of his tumour. He later underwent further surgery to remove a small amount of remaining spermatic cord. Histology revealed no malignant tissue. The patient suffered many complications including testosterone deficiency, osteopenia, infertility, and psychological distress. Discussion. A small proportion of testicular cancer may present in an atypical manner. The scrotum and testicle have markedly different embryonic origins and therefore a distinct anatomic separation. As a result the scrotum is not a typical site of spread of testicular cancer. Case reports have been described that were managed in a similar manner with good outcomes. Therefore, even with significant scrotal involvement, if timely and appropriate treatment is administered, complete resolution of the tumour may be achieved. PMID:27830100
Fukai, Shiho; Akishita, Masahiro
The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.
Li, Li; Grausam, Katie B.; Wang, Jun; Lun, Melody P.; Ohli, Jasmin; Lidov, Hart G. W.; Calicchio, Monica L.; Zeng, Erliang; Salisbury, Jeffrey L.; Wechsler-Reya, Robert J.; Lehtinen, Maria K.; Schüller, Ulrich; Zhao, Haotian
Aberrant Notch signaling has been linked to many cancers including choroid plexus (CP) tumours, a group of rare and predominantly pediatric brain neoplasms. We developed animal models of CP tumours by inducing sustained expression of Notch1 that recapitulate properties of human CP tumours with aberrant NOTCH signaling. Whole transcriptome and functional analyses showed that tumour cell proliferation is associated with Sonic Hedgehog (Shh) in the tumour microenvironment. Unlike CP epithelial cells, which have multiple primary cilia, tumour cells possess a solitary primary cilium as a result of Notch-mediated suppression of multiciliate diffferentiation. A Shh-driven signaling cascade in the primary cilium occurs in tumour cells but not in epithelial cells. Lineage studies show that CP tumours arise from mono-ciliated progenitors in the roof plate characterized by elevated Notch signaling. Abnormal SHH signaling and distinct ciliogenesis are detected in human CP tumours, suggesting SHH pathway and cilia differentiation as potential therapeutic avenues. PMID:26999738
Schwarz, M.; Teske, H.; Stoll, M.; Bendl, Rolf
Purpose: Conformal radiation of moving tumours is a challenging task in radiotherapy. Tumour motion induced by respiration can be visualized in fluoroscopic images recorded during patients breathing. Markerless methods making use of registration techniques can be used to estimate tumour motion. However, registration methods might fail when the tumour is hidden by ribs. Using motion of anatomical surrogates, like the diaphragm, is promising to model tumour motion. Methods: A sequence of 116 fluoroscopic images was analyzed and the tumour positions were manually defined by three experts. A block matching (BM) technique is used to calculate the displacement vector relatively to a selected reference image of the first breathing cycle. An enhanced method was developed: Positions, when the tumour is not located behind a rib, are taken as valid estimations of the tumour position. Furthermore, these valid estimations are used to establish a linear model of tumour position and diaphragm motion. For invalid estimations the calculated tumour positions are not taken into consideration, and instead the model is used to determine tumour motion. Results: Enhancing BM with a model of tumour motion from diaphragm motion improves the tracking accuracy when the tumour moves behind a rib. The error (mean ± SD) in longitudinal dimension was 2.0 ± 1.5mm using only BM and 1.0 ± 1.1mm when the enhanced approach was used. Conclusion: The enhanced tracking technique is capable to improve tracking accuracy compared to BM in the case that the tumour is occluded by ribs.
Freeman, C; Browne, A M; Parish, C R
In order to enter tissues, blood-borne metastatic tumour cells and leucocytes need to extravasate through the vascular basal lamina (BL), a process which involves a battery of degradative enzymes. A key degradative enzyme is the endoglycosidase heparanase, which cleaves heparan sulphate (HS), an important structural component of the vascular BL. Previously, tumour-derived heparanase activity (which has been shown to be related to the metastatic potential of murine and human melanoma cell lines) was reported to cleave HS and be inhibited by heparin, as distinct from human platelet heparanase, which cleaved both substrates [Nakajima, Irimura and Nicolson (1988) J. Cell Biochem. 36, 157-167]. We recently reported the purification of human platelet heparanase and showed that the enzyme is a 50-kDa endoglucuronidase [Freeman and Parish (1998) Biochem. J. 330, 1341-1350]. We now report the purification and characterization of heparanase activity from highly metastatic rat 13762 MAT mammary adenocarcinoma and human HCT 116 colonic carcinoma cells and from rat liver using essentially the same procedure that was reported for purification of the human platelet enzyme. The rat 13762 MAT tumour enzyme, which has a native M(r) of 45 kDa when analysed by gel-filtration chromatography and by SDS/PAGE, was observed to be an endoglucuronidase that degraded heparin and HS to fragments of the same sizes as the human platelet enzyme does. N-deglycosylation of both the human platelet and rat 13762 MAT tumour enzymes gave, in each case, a 41-kDa band by SDS/PAGE analysis, demonstrating that the observed difference in M(r) between the platelet and tumour enzymes may have been due largely to differences in the relative amounts of N-glycosylation. Two peptides were isolated following Endoproteinase Lys-C digestion of both the human platelet and rat 13762 MAT tumour heparanases and were shown to be highly similar. Both the rat liver and human colonic carcinoma heparanases also degraded both
Funovics, P T; Dominkus, M; Kotz, R
Malignant lesions of the bones and soft tissues require radical or wide resection to achieve adequate therapy. Due to the many developments in terms of adjuvant modalities, diagnostics and surgical expertise today there are several modes of therapy as alternatives to amputation in the treatment of malignant tumours of the shoulder and upper arm. After resection of smaller tumours excellent functional results can be obtained by the use of modular endoprostheses, whereas large neoplasms adjacent to the neurovascular bundle require resection-replantation to allow salvage of the hand. Within the Vienna Bone Tumour Registry, 100 patients out of a total of more than 6500 have been treated for such lesions: 62 received an endoprostheses, 18 resection-replantation and 20 amputation. In cases of primary malignant tumours the incidence of lung metastases was higher in the resection-replantation group (50 %) and amputation group (42 %) than in the prostheses group (11 %), which has been linked to larger tumour size in the former two groups. Radical or wide resections were obtained in 95 % of the prostheses group, as compared to 75 % and 78 % in the amputation group and the resection-replantation group, respectively, due to invasion into the neurovascular bundle. Over time the number of amputations decreased simultaneously with the increase of endoprostheses whereas the number of resection-replantations remained equal at our institution. Amputation today still plays a crucial role in the treatment of intralesionally resected tumours, as surgical contamination can make limb salvage impossible. Therefore, the importance of biopsy in the therapeutical algorithm of bone and soft tissue tumours has to be emphasised again.
Nouri, A. M.; dos Santos, A. V.; Crosby, D.; Oliver, R. T.
Analysis of tissue sections from transurethrally resected bladder tumours using anti-CD3 antibody showed the presence of T lymphocytes in intra-epithelial layers in eight of 12 cases investigated. In a larger group of patients, Tumour Infiltrating Lymphocyte (TIL) growth was established from six of 19 cases using Interleukin-2 (IL-2) and conditioned medium (CM) and resulted in the expansion of TILs up to 100-fold. TILs from these individuals were phenotyped with W6/32 (anti-HLA-A,B,C), HB55 (anti-DR) and anti-CD3 antibodies using FAC sorter. The mean +/- s.d. frequency of positive staining with these antibodies were 96.7 +/- 4.0%, 87.5 +/- 10.0% and 82.5 +/- 7.8% respectively, indicating the activated nature of these T cells. The cytotoxic activity of these TILs against Daudi (ie, LAK activity) cell line at 25/1 E/T ratios varied from 26.3 +/- 3.2 to 62.8 +/- 5.2%. In one case where TILs and autologous tumour cell line were established, cytotoxicity studies showed low level of cytotoxicity against the autologous tumour cells (15.8 +/- 1.6%) compared with 62.8 +/- 5.2% against Daudi. Staining of tumour sections from these 19 individuals with W6/32 and BBM.1 revealed positive staining in six of six that developed TILs but only six of 13 (46%) cases, whose tumour failed to grow TILs (P less than 0.02, Fisher exact test). These results are indicative of the presence of IL-2 passageable T cells in bladder cancer biopsy and demonstrate that the successful expansion of these cells correlates with the normal expression of class I antigens on the tumour cells. Images Figure 5 PMID:1764393
Chaussemy, D; Cebulla, H; Coca, A; Chibarro, S; Proust, F; Kehrli, P
Endoscopy of pineal region tumours has been developed since the year 2000 either via a transventricular or extracerebral approach. The initial purpose of applying neuroendoscopy in the management of pineal region tumours was to resolve the obstructive hydrocephalus, and identify the pathological characteristics of the tumour. Based on this approach, a piecemeal resection of the tumour can be performed. The approaches, derived from the microsurgical pathway using an endoscope to expose the operative field, have been proposed either via an infratentorial supracerebellar approach or posterior transtentorial interhemispheric approach. Neuroendoscopic procedures can be considered as a therapeutic alternative to the microsurgical approach when CSF markers are negative. This procedure is considered mini-invasive for the approach along the surgical corridor access but extensive and in depth at the interface between the tumour and the surrounding neurological parenchyma. The limitations and complications are related to the type of procedure (mono- or bimanual) as well as the tumoral characteristics. Different approaches are presented in detail in order to avoid the occurrence of any surgical complications.
Chaklin, A. V.
Malignant tumours are encountered among all races and in every type of geographical zone, but there are marked differences in different areas in the prevalence of particular forms of tumour—differences that are to a greater or lesser extent dependent on factors such as the climate and geography of the region and the habits, customs and occupations of the people. The study of these factors in relation to the occurrence of malignant tumours is of great importance in reaching an understanding of the etiology of tumours in man. In this paper the author discusses the many problems involved in the study of regional features in the prevalence of malignant tumours, with special reference to the difficulties of ensuring comparability of the data from widely differing regions and population groups. He concludes the paper with a review of some known facts regarding the distribution of malignant tumours at various sites in which he compares data obtained in surveys in the USSR with those obtained in other countries. PMID:14019866
James, Tharappel C.; Bond, Ursula
A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as “self”, and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as ‘proof of principle’ we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1) from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides. PMID:23166757
Yang, Ying; Sulé-Suso, Josep; El Haj, Alicia J; Hoban, Paul R; Wang, Ruikang
Morbidity of many tumour types is associated with invasion of tumour cells through the basement membrane and subsequent metastasis to vital organs. Tumour invasion is frequently detected late on as many patients present with advanced disease. The method of detecting invasion is through conventional histological staining techniques, which are time consuming and require processing of the sample. This can affect interpretation of the results. In this study, a new imaging technique, optical coherence tomography (OCT), was used to monitor lung tumour cell growth in two artificial membranes composed of either collagen type I or Matrigel. In parallel, standard histological section analysis was performed to validate the accuracy of the monitoring by OCT. Cross-sectional images from OCT revealed that lung tumour cells infiltrated only when low cell seeding density (5 x 10(5)) and low collagen concentration (1.5 mg/ml) were combined. The cells could be easily differentiated from the artificial membranes and appeared as either a brighter layer on the top of the membrane or brighter foci embedded within the darker membrane. These cell-membrane morphologies matched remarkably to the standard histological section images. Our results suggest that OCT has a great potential to become a useful tool for fast and robust imaging of cell growth in vivo and as a potential assessment of cell invasion.
Kadoury, Samuel; Vorontsov, Eugene; Tang, An
The early detection, diagnosis and monitoring of liver cancer progression can be achieved with the precise delineation of metastatic tumours. However, accurate automated segmentation remains challenging due to the presence of noise, inhomogeneity and the high appearance variability of malignant tissue. In this paper, we propose an unsupervised metastatic liver tumour segmentation framework using a machine learning approach based on discriminant Grassmannian manifolds which learns the appearance of tumours with respect to normal tissue. First, the framework learns within-class and between-class similarity distributions from a training set of images to discover the optimal manifold discrimination between normal and pathological tissue in the liver. Second, a conditional optimisation scheme computes non-local pairwise as well as pattern-based clique potentials from the manifold subspace to recognise regions with similar labelings and to incorporate global consistency in the segmentation process. The proposed framework was validated on a clinical database of 43 CT images from patients with metastatic liver cancer. Compared to state-of-the-art methods, our method achieves a better performance on two separate datasets of metastatic liver tumours from different clinical sites, yielding an overall mean Dice similarity coefficient of 90.7+/- 2.4 in over 50 tumours with an average volume of 27.3 mm3.
Singh, Prafull K.; Doley, Juwar; Kumar, G. Ravi; Sahoo, A.P.; Tiwari, Ashok K.
Cancer is one of the major causes of death worldwide. In spite of achieving significant successes in medical sciences in the past few decades, the number of deaths due to cancer remains unchecked. The conventional chemotherapy and radiotherapy have limited therapeutic index and a plethora of treatment related side effects. This situation has provided an impetus for search of novel therapeutic strategies that can selectively destroy the tumour cells, leaving the normal cells unharmed. Viral oncotherapy is such a promising treatment modality that offers unique opportunity for tumour targeting. Numerous viruses with inherent anti-cancer activity have been identified and are in different phases of clinical trials. In the era of modern biotechnology and with better understanding of cancer biology and virology, it has become feasible to engineer the oncolytic viruses (OVs) to increase their tumour selectivity and enhance their oncolytic activity. In this review, the mechanisms by which oncolytic viruses kill the tumour cells have been discussed as also the development made in virotherapy for cancer treatment with emphasis on their tumour specific targeting. PMID:23168697
Powlesland, R M; Charles, A K; Malik, K T A; Reynolds, P A; Pires, S; Boavida, M; Brown, K W
Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, LOH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaign PMID:10646884
Rashid, Mamoon; Tamimy, Muhammad Sarmad; Ehtesham-Ul-Haq; Sarwar, Saad Ur Rahman; Rizvi, Syed Taokeer Ahmed
The majority of the paediatric oral and maxillofacial tumours are benign and the mandible is involved in one-third of these cases. A review of the literature reveals only a handful of studies pertaining exclusively to benign paediatric mandibular tumours. The basis of this study was to fulfil the need to assess the suitability of major mandibular reconstructions using a vascularised fibular graft in cases of benign tumours in children. From April 1999 to April 2011 we have managed 18 cases of benign paediatric mandibular tumours. All the reconstructions were done using vascularised fibular graft. The age of these patients ranged from 8 to 16 years. The most common pathology seen in our series was Ameloblastoma, followed by Giant Cell Granuloma and vascular malformation. Other cases included fibrous dysplasia, aneurysmal bone cyst and odontogenic myxoma. Five of these were recurrent lesions. The mean length of the fibula harvested was 12 ± 2 cm. All the flaps in this series survived. Bone union occurred in all cases by 6 weeks. All the patients have maintained a satisfactory chin contour of the mandible during the follow-up period with minimal distortion occurring secondary to contralateral native mandibular growth in two cases. We conclude that, for benign paediatric mandibular tumours requiring major bone resection, the vascularised fibula is an excellent reconstructive option with the advantages of having a good bone stock, possibility for osteotomy, long pedicle length and potential for growth along with the possibility of dental rehabilitation.
Kurtova, Antonina V.; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P.; Chen, Fengju; Roh, Terrence T.; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson
Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival1–3. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to re-populate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair4–7. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation. PMID:25470039
Kurtova, Antonina V; Xiao, Jing; Mo, Qianxing; Pazhanisamy, Senthil; Krasnow, Ross; Lerner, Seth P; Chen, Fengju; Roh, Terrence T; Lay, Erica; Ho, Philip Levy; Chan, Keith Syson
Cytotoxic chemotherapy is effective in debulking tumour masses initially; however, in some patients tumours become progressively unresponsive after multiple treatment cycles. Previous studies have demonstrated that cancer stem cells (CSCs) are selectively enriched after chemotherapy through enhanced survival. Here we reveal a new mechanism by which bladder CSCs actively contribute to therapeutic resistance via an unexpected proliferative response to repopulate residual tumours between chemotherapy cycles, using human bladder cancer xenografts. Further analyses demonstrate the recruitment of a quiescent label-retaining pool of CSCs into cell division in response to chemotherapy-induced damages, similar to mobilization of normal stem cells during wound repair. While chemotherapy effectively induces apoptosis, associated prostaglandin E2 (PGE2) release paradoxically promotes neighbouring CSC repopulation. This repopulation can be abrogated by a PGE2-neutralizing antibody and celecoxib drug-mediated blockade of PGE2 signalling. In vivo administration of the cyclooxygenase-2 (COX2) inhibitor celecoxib effectively abolishes a PGE2- and COX2-mediated wound response gene signature, and attenuates progressive manifestation of chemoresistance in xenograft tumours, including primary xenografts derived from a patient who was resistant to chemotherapy. Collectively, these findings uncover a new underlying mechanism that models the progressive development of clinical chemoresistance, and implicate an adjunctive therapy to enhance chemotherapeutic response of bladder urothelial carcinomas by abrogating early tumour repopulation.
Elbashier, S H A; Nazarina, A R; Looi, L M
Ewing sarcoma (ES)/ primitive neuroectodermal tumour (PNET) is an aggressive malignant neoplasm affecting mainly children and young adults. The tumour is included with other primitive neoplasms under the category of small round cell tumour. Cytokeratin expression in ES/PNET has been described in sporadic case reports as well as a few systemic series. We studied this feature in Malaysian patients diagnosed in University Malaya Medical Centre on the basis of typical morphology and immunohistochemical assays. Immunohistochemical staining for AE1/AE3 and MNF116 were performed in 43 cases. Cytokeratin was expressed in 17 cases (39.5%) in focal, intermediate or diffuse patterns. There was no significant association between cytokeratin immunoreactivity and the following parameters: patient age, sex, skeletal and extraskeletal primary location as well as primary, metastastic or recurrent tumours or chemotherapy treatment. A significant association between cytokeratin and neuron specific enolase (NSE) expression was demonstrated. Our study supports evidence of epithelial differentiation in ES/PNET and emphasizes that the expression of cytokeratin does not exclude ES/PNET in the differential diagnosis of small round cell tumours.
Teo, Z L; Provenzano, E; Dite, G S; Park, D J; Apicella, C; Sawyer, S D; James, P A; Mitchell, G; Trainer, A H; Lindeman, G J; Shackleton, K; Cicciarelli, L; Buys, S S; Andrulis, I L; Mulligan, A M; Glendon, G; John, E M; Terry, M B; Daly, M; Odefrey, F A; Nguyen-Dumont, T; Giles, G G; Dowty, J G; Winship, I; Goldgar, D E; Hopper, J L; Southey, M C
Background: Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status. Methods: Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations. Results: Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0–64.6; P=5 × 10−7). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers. Conclusion: This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2. PMID:23787919
Yuguang, Liu; Meng, Liu; Shugan, Zhu; Yuquan, Jiang; Gang, Li; Xingang, Li; Chengyuan, Wu
In order to study the computerized tomographic (CT) appearances and clinical characteristics of intracranial tumoural haemorrhage (ITH), we analyzed retrospectively fifty-eight patients with ITH and reviewed the literature. As a result, 91% patients had acute or subacute onset and 26% manifested haemorrhage as their first symptoms. CT scanning indicated that intratumoural bleeding occurred in 23 cases, bleeding into parenchyma 18 cases, subarachnoid space 6 cases, ventricle 3 cases and subdural space 8 cases. Thirty-eight patients had emergency operations and the others had selective operations. Both tumours and haematomas were removed all together in all patients. Fifty-five patients were cured or improved and three died during the perioperative stage in our series. Among the patients with ITH, there were 21 metastatic tumours, 19 gliomas, 10 meningiomas, 6 pituitary adenomas, 1 melanoma and 1 acoustic neurilemoma. The onset of most ITH resembled that of cerebrovascular diseases. The location of ITH and the CT appearances of ITH varied in different cerebral tumours. Radical removal of brain tumours with haemorrhage is an effective treatment for ITH, which can greatly decrease the perioperative mortality rate and improve the prognoses of patients.
Wu, M K; Sabbaghian, N; Xu, B; Addidou-Kalucki, S; Bernard, C; Zou, D; Reeve, A E; Eccles, M R; Cole, C; Choong, C S; Charles, A; Tan, T Y; Iglesias, D M; Goodyer, P R; Foulkes, W D
DICER1 is an endoribonuclease central to the generation of microRNAs (miRNAs) and short interfering RNAs (siRNAs). Germline mutations in DICER1 have been associated with a pleiotropic tumour predisposition syndrome and Wilms tumour (WT) is a rare manifestation of this syndrome. Three WTs, each in a child with a deleterious germline DICER1 mutation, were screened for somatic DICER1 mutations and were found to bear specific mutations in either the RNase IIIa (n = 1) or the RNase IIIb domain (n = 2). In the two latter cases, we demonstrate that the germline and somatic DICER1 mutations were in trans, suggesting that the two-hit hypothesis of tumour formation applies for these examples of WT. Among 191 apparently sporadic WTs, we identified five different missense or deletion somatic DICER1 mutations (2.6%) in four individual WTs; one tumour had two very likely deleterious somatic mutations in trans in the RNase IIIb domain (c.5438A>G and c.5452G>A). In vitro studies of two somatic single-base substitutions (c.5429A>G and c.5438A>G) demonstrated exon 25 skipping from the transcript, a phenomenon not previously reported in DICER1. Further we show that DICER1 transcripts lacking exon 25 can be translated in vitro. This study has demonstrated that a subset of WTs exhibits two 'hits' in DICER1, suggesting that these mutations could be key events in the pathogenesis of these tumours.
Sajjad, Jahangir; Kaliaperumal, Chandrasekaran; O'Sullivan, Michael
A 62-year-old woman presented with a 4-month history of central lower backache and a 2-week history of progressive bilateral leg weakness. She also complained of numbness on her left thigh and gluteal region, associated with urinary hesitancy and constipation. On examination, she had bilateral partial foot drop, absent knee and ankle reflexes and a negative Babinski's reflex and associated hyperaesthesia in L3 distribution bilaterally with decreased anal tone. Laboratory results revealed normal inflammatory markers. MRI scan demonstrated a large uniformly enhancing lesion in the filum terminale suggestive of a lumbar spinal tumour. An emergency spinal laminectomy from L3 to S2 was performed. Per operatively, the duramater was thickened and hyperaemic. The histopathology report suggested inflammation with no evidence of malignancy. Tissue specimen of cultured Staphylococcus aureus was sensitive to flucloxacillin. A final diagnosis of lumbar spinal abscess was made and subsequent antibiotic treatment led to good clinical recovery.
Tobet, Stuart A; Lara, Hernan E; Lucion, Aldo B; Wilson, Melinda E; Recabarren, Sergio E; Paredes, Alfonso H
Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function. PMID:22700441
Eck, K. M.; Yuan, L.; Duffy, L.; Ram, P. T.; Ayettey, S.; Chen, I.; Cohn, C. S.; Reed, J. C.; Hill, S. M.
Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken
Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.
The growth hormone (GH) is a protein hormone released from the anterior pituitary gland under the control of the hypothalamus. ... performed on infants and children to identify human growth hormone (hGH) deficiency as a cause of growth retardation. ...
Tarkowská, Danuše; Novák, Ondřej; Floková, Kristýna; Tarkowski, Petr; Turečková, Veronika; Grúz, Jiří; Rolčík, Jakub; Strnad, Miroslav
Plant hormones act as chemical messengers in the regulation of myriads of physiological processes that occur in plants. To date, nine groups of plant hormones have been identified and more will probably be discovered. Furthermore, members of each group may participate in the regulation of physiological responses in planta both alone and in concert with members of either the same group or other groups. The ideal way to study biochemical processes involving these signalling molecules is 'hormone profiling', i.e. quantification of not only the hormones themselves, but also their biosynthetic precursors and metabolites in plant tissues. However, this is highly challenging since trace amounts of all of these substances are present in highly complex plant matrices. Here, we review advances, current trends and future perspectives in the analysis of all currently known plant hormones and the associated problems of extracting them from plant tissues and separating them from the numerous potentially interfering compounds.
Many transgender men and women seek hormone therapy as part of the transition process. Exogenous testosterone is used in transgender men to induce virilization and suppress feminizing characteristics. In transgender women, exogenous estrogen is used to help feminize patients, and anti-androgens are used as adjuncts to help suppress masculinizing features. Guidelines exist to help providers choose appropriate candidates for hormone therapy, and act as a framework for choosing treatment regimens and managing surveillance in these patients. Cross-sex hormone therapy has been shown to have positive physical and psychological effects on the transitioning individual and is considered a mainstay treatment for many patients. Bone and cardiovascular health are important considerations in transgender patients on long-term hormones, and care should be taken to monitor certain metabolic indices while patients are on cross-sex hormone therapy. PMID:28078219
Tentori, Lucio; Graziani, Grazia
Anabolic steroid and peptide hormones or growth factors are utilized to increase the performance of athletes of professional or amateur sports. Despite their well-documented adverse effects, the use of some of these agents has significantly grown and has been extended also to non-athletes with the aim to improve appearance or to counteract ageing. Pre-clinical studies and epidemiological observations in patients with an excess of hormone production or in patients chronically treated with hormones/growth factors for various pathologies have warned about the potential risk of cancer development and progression which may be also associated to the use of certain doping agents. Anabolic steroids have been described to provoke liver tumours; growth hormone or high levels of its mediator insulin-like growth factor-1 (IGF-1) have been associated with colon, breast, and prostate cancers. Actually, IGF-1 promotes cell cycle progression and inhibits apoptosis either by triggering other growth factors or by interacting with pathways which have an established role in carcinogenesis and cancer promotion. More recently, the finding that erythropoietin (Epo) may promote angiogenesis and inhibit apoptosis or modulate chemo- or radiosensitivity in cancer cells expressing the Epo receptor, raised the concern that the use of recombinant Epo to increase tissue oxygenation might favour tumour survival and aggressiveness. Cancer risk associated to doping might be higher than that of patients using hormones/growth factors as replacement therapy, since enormous doses are taken by the athletes often for a long period of time. Moreover, these substances are often used in combination with other licit or illicit drugs and this renders almost unpredictable all the possible adverse effects including cancer. Anyway, athletes should be made aware that long-term treatment with doping agents might increase the risk of developing cancer.
Andrade, Neelam Noel; Mathai, Paul C; Sahu, Vyankatesh; Aggarwal, Neha; Andrade, Tanvi
Melanotic neuroectodermal tumour of infancy (MNTI) is rare, rapidly growing, pigmented neoplasm of neural crest origin. It is generally accepted as a benign tumour despite of its rapid and locally destructive growth. It primarily affects the maxilla of infants during the first year of life. Surgical excision is considered as the treatment of choice. The recurrence rate varies between 10% and 15%, and malignant behaviour has been reported in 6.5% of cases. We report a case of MNTI, associated with an erupted primary tooth in a 5-month-old male child. We discuss the clinical, radiographic and histologic features of this rare tumour, as well as its surgical management and the follow-up.
Wilson, A. P.; Neal, F. E.
The in vitro chemosensitivity of primary monolayer cultures of human ovarian tumours to a wide range of chemotherapeutic agents has been determined using 3H-leucine incorporation as an index of cytotoxicity. Of 67 specimens received, 35 have been successfully cultured and tested for chemosensitivity. Drugs tested included alkylating agents, antibiotics, antimitotics, antimetabolites and progestogens. The overall incidence of efficacy of the drugs corresponded with the incidence which might be expected from data on the clinical response rates produced by the various drugs. Cultures from the tumour cells of treated patients generally showed greater resistance than tumours of untreated patients. Correlation between in vitro results and in vivo response was positive in all 8 patients receiving first-line chemotherapy and in 57% (4/7) patients receiving second-line chemotherapy. PMID:6791675
Hadi, Rahat; Mehrotra, Kiranpreet; Rastogi, Shivani; Masood, Shakeel
Non-Islet Cell Tumour Induced Hypoglycaemia (NICTH), presenting with recurrent fasting hypoglycaemia is a very rare paraneoplastic syndrome. It usually presents with large metastatic mesenchymal tumours. NICTH secondary to Gastrointestinal Stromal Tumour (GIST) is even rarer. Diagnosis of NICTH is based on the low serum insulin level, low serum concentrations of Insulin Like Growth Factor (IGF-I) and IGF binding protein- III (IGFBP-III) in combination with elevated concentrations of pro-IGF-II. Various Immunohistochemical (IHC) markers are integral to diagnosis of GIST namely 2-deoxyglucose-6-phosphate phosphatase -1(DOG-1), Cluster Differentiation 34 (CD 34), Cluster Differentiation 117 (CD117). The management requires prompt intravenous hydration and glucose infusions followed by surgical resection. We hereby, report a rare case of a 65-year-old female with intractable fasting hypoglycaemia due to overproduction of "big" insulin-like growth factor II diagnosed to have pelvic GIST and managed by Steroids and Imatinib.
Drake, Charles G.
Advances in basic immunology have led to an improved understanding of the interactions between the immune system and tumours, generating renewed interest in approaches that aim to treat cancer immunologically. As clinical and preclinical studies of tumour immunotherapy illustrate several immunological principles, a review of these data is broadly instructive and is particularly timely now that several agents are beginning to show evidence of efficacy. This is especially relevant in the case of prostate cancer, as recent approval of sipuleucel-T by the US Food and Drug Administration marks the first antigen-specific immunotherapy approved for cancer treatment. Although this Review focuses on immunotherapy for prostate cancer, the principles discussed are applicable to many tumour types, and the approaches discussed are highlighted in that context. PMID:20651745
Colangelo, Tommaso; Polcaro, Giovanna; Muccillo, Livio; D'Agostino, Giovanna; Rosato, Valeria; Ziccardi, Pamela; Lupo, Angelo; Mazzoccoli, Gianluigi; Sabatino, Lina; Colantuoni, Vittorio
The network of bidirectional homotypic and heterotypic interactions established among parenchymal tumour cells and surrounding mesenchymal stromal cells generates the tumour microenvironment (TME). These intricate crosstalks elicit both beneficial and adverse effects on tumour initiation and progression unbalancing the signals and responses from the neighbouring cells. Here, we highlight the structure, activities and evolution of TME cells considering a novel colorectal cancer (CRC) classification based on differential stromal composition and gene expression profiles. In this scenario, we scrutinise the molecular pathways that either change or become corrupted during CRC development and their relative prognostic value. Finally, we survey the therapeutic molecules directed against TME components currently available in clinical trials as well as those with stronger potential in preclinical studies. Elucidation of dynamic variations in the CRC TME cell composition and their relative contribution could provide novel diagnostic or prognostic biomarkers and allow more personalised therapeutic strategies.
Chen, Lin; Yang, Shengyu; Jakoncic, Jean; Zhang, J Jillian; Huang, Xin-Yun
Tumour metastasis is the primary cause of death of cancer patients. Development of new therapeutics preventing tumour metastasis is urgently needed. Migrastatin is a natural product secreted by Streptomyces, and synthesized migrastatin analogues such as macroketone are potent inhibitors of metastatic tumour cell migration, invasion and metastasis. Here we show that these migrastatin analogues target the actin-bundling protein fascin to inhibit its activity. X-ray crystal structural studies reveal that migrastatin analogues bind to one of the actin-binding sites on fascin. Our data demonstrate that actin cytoskeletal proteins such as fascin can be explored as new molecular targets for cancer treatment, in a similar manner to the microtubule protein tubulin.
Rao, S R; Snaith, A E; Marino, D; Cheng, X; Lwin, S T; Orriss, I R; Hamdy, F C; Edwards, C M
Background: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. Methods: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. Results: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. Conclusions: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression. PMID:28006818
Graf, R; Grüntzig, K; Boo, G; Hässig, M; Axhausen, K W; Fabrikant, S; Welle, M; Meier, D; Guscetti, F; Folkers, G; Otto, V; Pospischil, A
Cancer registries are valuable sources for epidemiological research investigating risk factors underlying different types of cancer incidence. The present study is based on the Swiss Feline Cancer Registry that comprises 51,322 feline patient records, compiled between 1965 and 2008. In these records, 18,375 tumours were reported. The study analyses the influence of sex, neutering status, breed, time and age on the development of the most common tumour types and on their locations, using a multiple logistic regression model. The largest differences between breeds were found in the development of fibrosarcomas and squamous cell carcinomas, as well as in the development of tumours in the skin/subcutis and mammary gland. Differences, although often small, in sex and neutering status were observed in most analyses. Tumours were more frequent in middle-aged and older cats. The sample size allowed detailed analyses of the influence of sex, neutering status, breed and age. Results of the study are mainly consistent with previous analyses; however, some results cannot be compared with the existing literature. Further investigations are necessary, since feline tumours have not been investigated in depth to date. More accurate comparisons would require the definition of international standards for animal cancer registries.
Terlizzi, Michela; Di Crescenzo, Vincenzo Giuseppe; Perillo, Giuseppe; Galderisi, Antonio; Pinto, Aldo; Sorrentino, Rosalinda
Background and Purpose Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. Experimental Approach To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced lung cancer. Key Results Healthy and cancerous NSCLC samples had similar levels of the active form of caspase-8. Similarly, lung tumour-bearing mice had high levels of the active form of caspase-8. Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduced tumour outgrowth and this was closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-α, IL-18, IL-1α, IL-33, but not IL-1β. Furthermore, inhibition of caspase-8 reduced the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice. However, despite the well-known role of caspase-8 in cell death, the apoptotic cascade (caspase-3, caspase-9 and Bcl-2 dependent) was not active in lungs of z-IETD-treated tumour-bearing mice, but instead higher levels of the short segment of c-FLIP (c-FLIPs) were detected. Similarly, human healthy lung samples had higher levels of c-FLIPs than cancerous samples. Conclusions and Implications Our data suggest that caspase-8 is an important orchestrator of cancer-associated inflammation and the presence of short segment of c-FLIP determines whether caspase-8 induces tumour proliferation or tumour arrest/regression in the lung. PMID:25917370
Mitry, E; Baudin, E; Ducreux, M; Sabourin, J-C; Rufié, P; Aparicio, T; Lasser, P; Elias, D; Duvillard, P; Schlumberger, M; Rougier, P
The purpose of this study was to evaluate by a retrospective analysis of 53 patients the efficacy of chemotherapy combining etoposide and cisplatin in the treatment of neuroendocrine tumours. The regimen was a combination of etoposide 100 mg m–2 day–1 for 3 days and cisplatin 100 mg m–2 on day 1, given by 2-h intravenous infusion, administered every 21 days. Twelve patients had a well-differentiated and 41 a poorly differentiated neuroendocrine tumour. Toxicity of treatment was assessed in 50 patients and efficacy in 52 patients. Among the 11 patients with a well-differentiated tumour evaluable for tumoural response, only one (9.4%) had a partial response for 8.5 months. Forty-one patients with a poorly differentiated tumour showed an objective response rate of 41.5% (four complete and 13 partial responses); the median duration of response was 9.2 months, the median overall survival 15 months and the median progression-free survival 8.9 months. Haematological grade 3–4 toxicity was observed in 60% of the cases with one treatment-related death, digestive grade 3–4 toxicity in 40% and grade 3 alopecia was constant. No severe renal, hearing and neurological toxicities were observed (grade 1 in 6%, 14%, 72% respectively and no grade >1). We confirm that poorly differentiated neuroendocrine tumours are chemosensitive to the etoposide plus cisplatin combination. However, the prognosis remains poor with a 2-year survival lower than 20% confirming that new therapeutic strategies have to be developed. © 1999 Cancer Research Campaign PMID:10604732
Gangeh, Mehrdad J.; Raheem, Abdul; Tadayyon, Hadi; Liu, Simon; Hadizad, Farnoosh; Czarnota, Gregory J.
Breast cancer is one of the most common cancer types accounting for 29% of all cancer cases. Early detection and treatment has a crucial impact on improving the survival of affected patients. Ultrasound (US) is non-ionizing, portable, inexpensive, and real-time imaging modality for screening and quantifying breast cancer. Due to these attractive attributes, the last decade has witnessed many studies on using quantitative ultrasound (QUS) methods in tissue characterization. However, these studies have mainly been limited to 2-D QUS methods using hand-held US (HHUS) scanners. With the availability of automated breast ultrasound (ABUS) technology, this study is the first to develop 3-D QUS methods for the ABUS visualization of breast tumours. Using an ABUS system, unlike the manual 2-D HHUS device, the whole patient's breast was scanned in an automated manner. The acquired frames were subsequently examined and a region of interest (ROI) was selected in each frame where tumour was identified. Standard 2-D QUS methods were used to compute spectral and backscatter coefficient (BSC) parametric maps on the selected ROIs. Next, the computed 2-D parameters were mapped to a Cartesian 3-D space, interpolated, and rendered to provide a transparent color-coded visualization of the entire breast tumour. Such 3-D visualization can potentially be used for further analysis of the breast tumours in terms of their size and extension. Moreover, the 3-D volumetric scans can be used for tissue characterization and the categorization of breast tumours as benign or malignant by quantifying the computed parametric maps over the whole tumour volume.
Chandrasekar, Coonoor R; Grimer, Robert J; Carter, Simon R; Tillman, Roger M; Abudu, Adesegun T
Background and aims Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. Methods 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. Results and conclusion There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0–77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads). 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis) was 83.1% with revision as end point. The mean TESS score was 64% (54%–82%). We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related complications and
Pistilli, B; Grana, CM; Fazio, N; Cavaliere, A; Ferrari, ME; Bodei, L; Baio, SM; Scambia, G; Paganelli, G; Peccatori, FA
Neuroendocrine tumours (NET) are a heterogeneous group of neoplasms commonly occurring in the gastrointestinal tract or lungs but can occur in other regions. Primary ovarian NET account for 5% of all NET and 0.1% of all ovarian malignancies. In metastatic disease, the therapeutic goal is to extend survival and to improve quality of life. As these tumours express somatostatin receptors, somatostatin analogues are frequently used to control symptoms. Here we present a case of a pregnant woman with an ovarian NET with liver metastases and carcinoid syndrome who was treated with the somatostatin analogue, Octreotide LAR. We also summarize reported data of the use of somatostatin analogues during pregnancy. PMID:22331988
McLeod, H L; McKay, J A; Collie-Duguid, E S; Cassidy, J
Tumour metastasis is the major cause of morbidity and mortality from colorectal cancer. While improvements in quality of life and patient survival have been made over the past 10 years, the majority of patients with metastatic colorectal cancer will die from their disease. As knowledge of the biology of colon cancer and its invasion/metastasis programme evolve, this presents new therapeutic opportunities for pharmacological and genetic intervention. This review discusses the current approaches to metastatic colorectal cancer therapy, details genomic and biological variance between primary and metastatic tumours, and highlights approaches for harnessing these differences to improve therapy.
Arizmendi, Carlos; Sierra, Daniel A; Vellido, Alfredo; Romero, Enrique
The development, implementation and use of computer-based medical decision support systems (MDSS) based on pattern recognition techniques holds the promise of substantially improving the quality of medical practice in diagnostic and prognostic tasks. In this study, the core of a decision support system for brain tumour classification from magnetic resonance spectroscopy (MRS) data is presented. It combines data pre-processing using Gaussian decomposition, dimensionality reduction using moving window with variance analysis, and classification using artificial neural networks (ANN). This combination of techniques is shown to yield high diagnostic classification accuracy in problems concerning diverse brain tumour pathologies, some of which have received little attention in the literature.
Friedman, W A; Foote, K D
Radiosurgery is an increasingly popular method for treating a variety of intracranial tumours. A great deal of treatment data has been accumulated suggesting that radiosurgery may be the treatment of choice for small acoustic schwannomas. Moreover, radiosurgery promises excellent tumour control and minimal risk in the treatment of small meningiomas in risky surgical locations such as the cavernous sinus. Radiosurgery offers superior local control rates for many metastatic neoplasms and has promise as an adjuvant 'boost' technique in certain malignant gliomas. This article presents a brief description of the linear accelerator, LINAC, radiosurgical technique, followed by a review of the more common applications of stereotactic radiosurgery in the treatment of intracranial neoplastic disease.
Adhikarla, Vikram; Jeraj, Robert
Tumour growth, angiogenesis and oxygenation vary substantially among tumours and significantly impact their treatment outcome. Imaging provides a unique means of investigating these tumour-specific characteristics. Here we propose a computational model to simulate tumour-specific oxygenation changes based on the molecular imaging data. Tumour oxygenation in the model is reflected by the perfused vessel density. Tumour growth depends on its doubling time (T d) and the imaged proliferation. Perfused vessel density recruitment rate depends on the perfused vessel density around the tumour (sMVDtissue) and the maximum VEGF concentration for complete vessel dysfunctionality (VEGFmax). The model parameters were benchmarked to reproduce the dynamics of tumour oxygenation over its entire lifecycle, which is the most challenging test. Tumour oxygenation dynamics were quantified using the peak pO2 (pO2peak) and the time to peak pO2 (t peak). Sensitivity of tumour oxygenation to model parameters was assessed by changing each parameter by 20%. t peak was found to be more sensitive to tumour cell line related doubling time (~30%) as compared to tissue vasculature density (~10%). On the other hand, pO2peak was found to be similarly influenced by the above tumour- and vasculature-associated parameters (~30-40%). Interestingly, both pO2peak and t peak were only marginally affected by VEGFmax (~5%). The development of a poorly oxygenated (hypoxic) core with tumour growth increased VEGF accumulation, thus disrupting the vessel perfusion as well as further increasing hypoxia with time. The model with its benchmarked parameters, is applied to hypoxia imaging data obtained using a [64Cu]Cu-ATSM PET scan of a mouse tumour and the temporal development of the vasculature and hypoxia maps are shown. The work underscores the importance of using tumour-specific input for analysing tumour evolution. An extended model incorporating therapeutic effects can serve as a powerful tool for analysing
Sjödahl, Gottfrid; Eriksson, Pontus; Liedberg, Fredrik; Höglund, Mattias
Global mRNA expression analysis is efficient for phenotypic profiling of tumours and has been used to define molecular subtypes for almost every major tumour type. A key limitation is that most tumours are communities of both tumour and non-tumour cells. This problem is particularly pertinent when analysing advanced invasive tumours, known to induce major changes and responses in both the tumour and the surrounding tissue. To identify bladder cancer tumour-cell phenotypes and compare classification by tumour-cell phenotype with classification by global gene expression analysis, we analysed 307 advanced bladder cancers (cystectomised) both by genome gene expression analysis and by immunohistochemistry using antibodies for 28 proteins. By systematic analysis of gene and protein expression data, focusing on key molecular processes, we describe five tumour-cell phenotypes of advanced urothelial carcinoma; Urothelial-like, Genomically Unstable, Basal/SCC-like, Mesenchymal-like, and Small cell/Neuroendocrine like. We provide molecular pathological definitions for each subtype. Tumours expressing urothelial differentiation factors show inconsistent and abnormal protein expression of terminal differentiation markers, suggesting pseudo-differentiation. Cancers with different tumour-cell phenotypes may co-cluster (converge), and cases with identical tumour-cell phenotypes may cluster apart (diverge) in global mRNA analyses. This divergence/convergence suggests that broad global commonalities related to the invasive process may exist between muscle-invasive tumours regardless of specific tumour-cell phenotype. Hence, there is a systematic disagreement in subtype classification determined by global mRNA profiling and by IHC profiling at the tumour-cell level. We suggest that a combination of molecular pathology (tumour cell phenotype) and global mRNA profiling (context) is required for adequate subtype classification of muscle-invasive bladder cancer.
Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma
Kang, M-S; Park, M-S; Kwon, S-W; Ma, S-A; Cho, D-Y; Kim, D-Y; Kim, Y
A 13-year-old male tiger (Panthera tigris tigris) had a marked mandibular swelling noticed 12 months earlier and associated with progressive anorexia and weight loss. Radiological and post-mortem examination revealed a mass (13x15 cm) which was firm and poorly defined, with destruction of the adjacent bone tissue. Histologically, the mass was poorly demarcated, with infiltrative growth, and composed of nests, cords and islands of epithelial cells with characteristic basal cell features. Also observed were extensive squamous metaplasia, ghost cells, stellate reticulum, and fibroblastic connective tissue stroma containing inflammatory cells. A prominent feature of this tumour consisted of abundant nodular deposits of congophilic amyloid-like material with partial mineralization (Liesegang rings). Immunohistochemically, the neoplastic cells and the amyloid-like material were positive for pancytokeratin and negative for vimentin. The findings supported the diagnosis of an amyloid-producing odontogenic tumour (APOT), also known as calcifying epithelial odontogenic tumour in man and animals.
Lau, On Sun; Deng, Xing Wang
Light is an important environmental signal that regulates diverse growth and developmental processes in plants. In these light-regulated processes, multiple hormonal pathways are often modulated by light to mediate the developmental changes. Conversely, hormone levels in plants also serve as endogenous cues in influencing light responsiveness. Although interactions between light and hormone signaling pathways have long been observed, recent studies have advanced our understanding by identifying signaling integrators that connect the pathways. These integrators, namely PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), PIF4, PIF3-LIKE 5 (PIL5)/PIF1 and LONG HYPOCOTYL 5 (HY5), are key light signaling components and they link light signals to the signaling of phytohormones, such as gibberellin (GA), abscisic acid (ABA), auxin and cytokinin, in regulating seedling photomorphogenesis and seed germination. This review focuses on these integrators in illustrating how light and hormone interact.
Durbak, Amanda; Yao, Hong; McSteen, Paula
Hormone signaling plays diverse and critical roles during plant development. In particular, hormone interactions regulate meristem function and therefore control formation of all organs in the plant. Recent advances have dissected commonalities and differences in the interaction of auxin and cytokinin in the regulation of shoot and root apical meristem function. In addition, brassinosteroid hormones have recently been discovered to regulate root apical meristem size. Further insights have also been made into our understanding of the mechanism of crosstalk among auxin, cytokinin, and strigolactone in axillary meristems.
To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post-menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.
Mendoza-Schulz, A; Solano-Agama, C; Arreola-Mendoza, L; Reyes-Márquez, B; Barbier, O; Del Razo, L M; Mendoza-Garrido, M E
The consumption of drinking water rich in fluoride has toxic effects on the central nervous system. In cell biology research, fluoride is currently used as a phosphatase inhibitor. The aim of the present study was to evaluate the effect of fluoride on different physiological processes in GH4C1 pituitary tumour cells. We used a range of different fluoride concentrations, from levels below normal human serum concentrations (0.23 and 1.2 micromol/L) to those observed in chronically exposed persons (10.7 micromol/L) and above (107 and 1072 micromol/L). Treatment of 10.7 micromol/L fluoride resulted in a discrete induction of DNA synthesis, without a change in cell number. Cell migration, a behaviour stimulated by growth factors, was increased in cells treated with 2.4 micromol/L. At this fluoride concentration, changes in phosphorylation status of both cytoskeletal and cytosolic protein fractions, as well as in actin cytoskeletal arrangements were observed. The GH4C1 fluoride treated cells had significantly less cellular protein than control cells, suggesting an effect of fluoride on hormone secretion and protein synthesis in this endocrine cell. The bioreduction of MTT was significantly increased with a wide range of fluoride concentrations. With the highest fluoride concentration, 1072 micromol/L, all of the analysed parameters were significantly reduced, suggesting that this dose is highly toxic in GH4C1 cells. Our results show that biologically relevant concentrations of fluoride are capable of increasing cell migration in tumour cells, suggesting that exposure to fluoride could stimulate tumour invasion.
Lo Vasco, Vincenza Rita
Deletions in the distal region of the short arm of chromosome 1 (1p36) are widely diffuse, both in congenital 1p36 Deletion Syndrome and as somatic abnormalities in tumours. Rearrangements in 1p36 have been described in a broad spectrum of human neoplasias in addition to other chromosomal abnormalities. In neuroblastomas, wide hemizygous deletions in 1p36.23-1p36.32 have been described suggesting that the 1p36 region contains a tumour-suppressor gene involved in malignancy. A role for phosphoinositide (PI)-specific phospholipase C (PLC) η2, whose gene maps on 1p36.32, was suggested. PI-PLC η2 belongs to a family of enzymes related to the phosphoinositide signalling pathway, which provide an important intracellular signalling system involved in a variety of cell functions such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, regulation of the cytoskeleton, cell cycle control and apoptosis. Expression of PI-PLC η2 occurs after birth and continues throughout the life. Synapse formation occurs during a short period of postnatal development. Thus, it is likely that PI-PLC η2 acts in formation and maintenance of the neuronal network in the brain. The fact that PI-PLC η2, a highly neuron-specific isozyme, is abundantly expressed in the postnatal brain suggests the importance of PI-PLC η2 in formation and maintenance of the neuronal network in the postnatal brain. Further studies are required to verify the possible involvement of PI-PLC η2 mutation/deletion in central nervous tumour tissues presenting abnormalities of the 1p36 chromosomal band.
Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna
Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477
Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna
Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.
Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C
ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.
Kempermann, G; Neumann, H P; Scheremet, R; Volk, B; Mann, W; Gilsbach, J; Laszig, R
A case of bilateral endolymphatic sac tumours is reported. In a patient with von Hippel-Lindau syndrome, tumour growth in the right cerebellopontine angle caused deafness. The tumour was removed and classified as a metastasis from a thyroid carcinoma. However, on thyroidectomy no primary neoplasm could be found. Eight years later a similar tumour was operated on in the left petrosal bone. Histological appearance, immunocytochemical findings, and the clinical context gave evidence that the tumours had to be reclassified as endolymphatic sac tumours--extremely rare entities. The report supports the hypothesis, suggested by the few earlier case reports, that endolymphatic sac tumours could be one of the inherent tumour manifestations in von Hippel-Lindau syndrome. Images PMID:8795608
Bremner, J. C.; Counsell, C. J.; Adams, G. E.; Stratford, I. J.; Wood, P. J.; Dunn, J. F.; Radda, G. K.
The effect of hydralazine on tumours appears to vary depending on tumour type. Blood flow and radiation sensitivity decrease more in murine tumours than human tumour xenografts. In this study a comparison between various tumour types has been made using in vivo 31P nuclear magnetic resonance spectroscopy (NMRS) to follow the metabolic responses occurring after clamping or intravenous administration of hydralazine (5 mg kg-1). Large increases in the Pi/total phosphate ratio were found with the murine sarcomas, KHT and RIF-1 implanted into C3H/He mice. However little or no effect was seen for the two human xenografted tumours, HX118 and HT29 implanted in MFI nu/nu/01a mice. An intermediate response was observed for KHT tumours grown in nu/nu mice. All tumours showed a large response to clamping. The anaesthetic Hypnorm/Hypnovel has a great influence on the response of the tumour metabolism to hydralazine appearing to both prolong and increase the changes induced. There is evidence to support the theory that the changes in 31P spectra are related to the oxygen status of the tumours. PMID:1931606
Tomasin, Rebeka; Gomes-Marcondes, Maria Cristina Cintra
Cancer is diagnosed in approximately 11 million people and is responsible for almost 8 million deaths worldwide every year. Research in cancer control has shown the importance of co-adjuvant therapies. Aloe vera may reduce tumour mass and metastasis rates, while honey may inhibit tumour growth. This study verified the influence of Aloe vera and honey on tumour growth and in the apoptosis process by assessing tumour size, the cell proliferation rate (Ki67-LI) and Bax/Bcl-2 expression at 7, 14 and 20 days after Walker 256 carcinoma implant in Wistar rats distributed into two groups: the WA group - tumour-bearing rats that received a gavage with a 670 µL/kg dose of Aloe vera and honey solution daily, and the CW group - tumour-bearing rats which received only a 0.9% NaCl solution. The effect of Aloe vera and honey against tumour growth was observed through a decrease in relative weight (%) and Ki67-LI in tumours from the WA group compared with those from the CW group. The Bax/Bcl-2 ratio increased in tumours from the WA group at all tested timepoints. These data suggest Aloe vera and honey can modulate tumour growth by reducing cell proliferation and increasing apoptosis susceptibility.
Gouty-Colomer, Laurie-Anne; Méry, Pierre-François; Storme, Emilie; Gavois, Elodie; Robinson, Iain C; Guérineau, Nathalie C; Mollard, Patrice; Desarménien, Michel G
Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.
Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails.
Pluchino, N; Russo, M; Santoro, A N; Litta, P; Cela, V; Genazzani, A R
Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer's and Parkinson's diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women. Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases. This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.
Verhaeghe, J; Bouillon, R
This review summarizes the reported effects of the menstrual cycle, pregnancy and lactation on serum concentration of the calciotropic hormones PTH and 1,25(OH)2D. A midcycle rise in PTH and 1,25(OH)2D has been observed, but in the majority of studies there was no change in PTH and 1,25(OH)2D concentrations throughout the menstrual cycle. Both total and free 1,25(OH)2D levels are increased during pregnancy. The renal 1,25(OH)2D production is stimulated, and there is some evidence of 1,25(OH)2D production by decidua/placenta and fetal kidney in vitro; the decidual/placental production should not be overestimated in vivo. The increased renal 1 alpha-hydroxylase activity is possibly mediated by estrogens and PTH, although the effect of pregnancy on PTH remains uncertain. Increased serum 1,25(OH)2D concentrations probably result in a rise of intestinal calcium absorption during pregnancy. There is a postdelivery drop in PTH and 1,25(OH)2D levels, but they are increased when lactation is prolonged, or in mothers nursing twins. The l alpha-hydroxylase activity during lactation may be stimulated by PTH, but also by prolactin.
Du, X; Tao, Z; Qu, J
In 1986-1996, four childish patients with parapharyngeal space tumour were treated in our hospital. In the beginning, we ought to define the size and range by CT scanning. The second, we excized it from neck-flank. The patients had a satisfying effect after surgical operation. Meantimes, it's necessary to protect the important vessel and nerve in surgical operation.
Kam, B L R; Teunissen, J J M; Krenning, E P; de Herder, W W; Khan, S; van Vliet, E I; Kwekkeboom, D J
Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours.
Szabo, Vanessza; Bugyik, Edina; Dezso, Katalin; Ecker, Nora; Nagy, Peter; Timar, Jozsef; Tovari, Jozsef; Laszlo, Viktoria; Bridgeman, Victoria L; Wan, Elaine; Frentzas, Sophia; Vermeulen, Peter B; Reynolds, Andrew R; Dome, Balazs; Paku, Sandor
The appearance of lung metastases is associated with poor outcome and the management of patients with secondary pulmonary tumours remains a clinical challenge. We examined the vascularization process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (ie vessel co-option). During the initial phase of vessel co-option, the incorporated capillaries were still sheathed by pneumocytes, but these incorporated vessels subsequently underwent different fates dependent on the model. In five of the models examined (B16, HT1080, HT25, C26, and MAT B-III), the tumour cells gradually stripped the pneumocytes from the vessels. These dissected pneumocytes underwent fragmentation, but the incorporated microvessels survived. In the sixth model (C38), the tumour cells failed to invade the alveolar walls. Instead, they induced the development of vascularized desmoplastic tissue columns. Finally, we examined the process of arterialization in lung metastases and found that they became arterialized when their diameter grew to exceed 5 mm. In conclusion, our data show that lung metastases can vascularize by co-opting the pulmonary microvasculature. This is likely to have important clinical implications, especially with respect to anti-angiogenic therapies.
Giverso, Chiara; Ciarletta, Pasquale
The hypoxic conditions within avascular solid tumours may trigger the secretion of chemical factors, which diffuse to the nearby vasculature and promote the formation of new vessels eventually joining the tumour. Mathematical models of this process, known as tumour angiogenesis, have mainly investigated the formation of the new capillary networks using reaction-diffusion equations. Since angiogenesis involves the growth dynamics of the endothelial cells sprouting, we propose in this work an alternative mechanistic approach, developing a surface growth model for studying capillary formation and network dynamics. The model takes into account the proliferation of endothelial cells on the pre-existing capillary surface, coupled with the bulk diffusion of the vascular endothelial growth factor (VEGF). The thermo-dynamical consistency is imposed by means of interfacial and bulk balance laws. Finite element simulations show that both the morphology and the dynamics of the sprouting vessels are controlled by the bulk diffusion of VEGF and the chemo-mechanical and geometric properties at the capillary interface. Similarly to dendritic growth processes, we suggest that the emergence of tree-like vessel structures during tumour angiogenesis may result from the free boundary instability driven by competition between chemical and mechanical phenomena occurring at different length-scales. PMID:26948692
Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.
Cuitiño, M C; Massone, A R; Idiart, J R
The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours.