Tumoural Process Research Articles

Charcot arthropathy in the spine. Experience in our centre. About 13 cases. Review of the literature

Charcot arthropathy of the spine is a neuropathic affectation of the spine, it is considered rare, has a destructive and progressive evolution. It is usually due to a previous traumatic injury, but it has also been described as secondary to other infectious or tumoural processes. Initially, surgical treatment has always been considered for possible complications such as pain control and trunk instability. We present a series of 13 cases diagnosed with Charcot arthropathy at the Institut Guttmann, in which the following variables are described: aetiology (traumatic, infectious, iatrogenic), clinical features (pain, loss of trunk control, vegetatism, spasticity), interval of onset of the clinical features, location (L2-L3), treatment (surgical or conservative) and the evolution they presented, with the aim of evaluating conservative treatment as the first option, instead of surgery. In our sample, 61.5% (8/13) were treated surgically with posterior instrumentation (7/8), except for one case which was anterior and posterior; 38.5% (5/13) were treated conservatively and none required subsequent surgery. In conclusion, our line of action would initially be to consider conservative treatment, and to use surgery for cases in which the clinical evolution was not as expected, either due to poor pain control and/or limitation of mobility secondary to the deformity limitation of mobility secondary to the deformity of the trunk, or when the spinal involvement or the patient's symptoms are not tolerated and require a quicker and more aggressive solution.

Artropatía de Charcot en el raquis. Experiencia en nuestro centro. A propósito de 13 casos. Revisión de la literatura

Charcot arthropathy of the spine is a neuropathic affectation of the spine, it is considered rare, has a destructive and progressive evolution. It is usually due to a previous traumatic injury, but it has also been described as secondary to other infectious or tumoural processes. Initially, surgical treatment has always been considered for possible complications such as pain control and trunk instability. We present a series of 13 cases diagnosed with Charcot arthropathy at the Institut Guttmann, in which the following variables are described: aetiology (traumatic, infectious, iatrogenic), clinical features (pain, loss of trunk control, vegetatism, spasticity), interval of onset of the clinical features, location (L2-L3), treatment (surgical or conservative) and the evolution they presented, with the aim of evaluating conservative treatment as the first option, instead of surgery. In our sample, 61.5% (8/13) were treated surgically with posterior instrumentation (7/8), except for one case which was anterior and posterior; 38.5% (5/13) were treated conservatively and none required subsequent surgery. In conclusion, our line of action would initially be to consider conservative treatment, and to use surgery for cases in which the clinical evolution was not as expected, either due to poor pain control and/or limitation of mobility secondary to the deformity limitation of mobility secondary to the deformity of the trunk, or when the spinal involvement or the patient's symptoms are not tolerated and require a quicker and more aggressive solution.

DNA methylome in visceral adipose tissue can discriminate patients with and without colorectal cancer

ABSTRACT Adipose tissue dysfunction, particularly the visceral (VAT) compartment, has been proposed to play a relevant role in colorectal cancer (CRC) development and progression. Epigenetic mechanisms could be involved in this association. The current study aimed to evaluate if specific epigenetic marks in VAT are associated with colorectal cancer (CRC) to identify epigenetic hallmarks of adipose tissue-related CRC. Epigenome-wide DNA methylation was evaluated in VAT from 25 healthy participants and 29 CRC patients, using the Infinium HumanMethylation450K BeadChip. The epigenome-wide methylation analysis identified 170,184 sites able to perfectly separate the CRC and healthy samples. The differentially methylated CpG sites (DMCpGs) showed a global trend for increased methylated levels in CRC with respect to healthy group. Most of the genes encoded by the DMCpGs belonged to metabolic pathways and cell cycle, insulin resistance, and adipocytokine signalling, as well as tumoural transformation processes. In gene-specific analyses, involved genes biologically relevant for the development of CRC include PTPRN2, MAD1L1, TNXB, DIP2C, INPP5A, HDCA4, PRDM16, RPTOR, ATP11A, TBCD, PABPC3, and IER2. The methylation level of some of them showed a discriminatory capacity for detecting CRC higher than 90%, showing IER2 to have the highest capacity. This study reveals that a specific methylation pattern of VAT is associated with CRC. Some of the epigenetic marks identified could provide useful tools for the prediction and personalized treatment of CRC connected to excess adiposity.

Shear-wave elastography of the testicle: potential role of the stiffness value in various common testicular diseases

To assess the value and efficacy of real-time shear-wave elastography (SWE) of normal testicular parenchyma and various common testicular diseases in clinical practice. SWE was undertaken in 338 patients (mean age: 43.2±17.2 years, range 17-78 years) comprising normal testicles (n=358), testicular microlithiasis (n=40), and various testicular diseases (n=208) and the stiffness was recorded. The final diagnosis was correlated with the clinical context, long-term follow-up, or histopathology. Statistical evaluation was performed to provide a stiffness threshold for pathological diagnosis. The mean size of testicular lesions was 2.6±1.5 cm (range: 10-42 mm). The mean Young's modulus value for normal testis was recorded at 4.55±2.54 kPa. Whatever the stage of microlithiasis, a higher statistically significant stiffness value was recorded. For acute orchitis, the mean stiffness value was slightly higher, but not statistically significantly. The testicular tumoural processes presented a median stiffness value of 21.02 kPa with a cut-off of 16.1 kPa. Fibrosis presented the highest median stiffness value of 30.03 kPa with a cut-off of 26.3 kPa. By analysing the distribution of the different pathological groups, the difference was statistically significant between fibrosis and tumoural processes (p=0.001). SWE is a feasible technique in the exploration of the testicular parenchyma. SWE values can be used to differentiate testicular fibrosis from a tumoural process with confidence.

Keratin 36, a specific marker of tongue filiform papillae, is downregulated in squamous cell carcinoma of the mobile tongue.

Human keratin 36 (K36) is a member of the hair keratin family and is a marker of hair cortex differentiation. The human KRT36 gene is located on the long arm of chromosome 17 and belongs to the cluster of structurally unrelated acidic hair keratins. Recently, it has been reported that KRT36 mRNA is specifically expressed in normal tongue epithelium and downregulated in squamous cell carcinomas of the mobile tongue. Furthermore, KRT36 levels have been reported to be downregulated in clinically normal mobile tongue tissue that is adjacent to tumours, suggesting it could be a marker of pre-neoplastic changes. However, the exact role and the potential role of K36 in tongue tumour formation remains unclear. The aim of the present study was to investigate expression of K36 in a series of squamous cell carcinomas of the mobile tongue, normal mobile tongue and a small panel of other human tissues (normal tissue from the appendix, cervix, hair, lip, mamilla, nail, oesophagus, skin, thymus and vagina) and selected cancer tissue (cervical cancer, melanoma and basal cell carcinoma). Affinity purified polyclonal antibodies against K36 were generated and used for immunohistochemical analysis. The results revealed that in the normal tongue, K36 was detected specifically in the filiform papillae of the dorsal surface of the tongue. Additionally, none of the tongue cancer tissue samples were K36-positive. Immunostaining also revealed that K36 was expressed in nail beds, Hassal's corpuscles in the thymus and the hair cortex. However, K36 was not expressed in the squamous epithelia of the skin, cervix and oesophagus, and the squamous cells of cervical carcinomas, basal cell carcinoma or melanoma. The present data indicated that K36 may be inactivated in tumours of the tongue. However, whether this is part of the tumoural process or if it is an effect of the tumour itself remains to be elucidated.

P0143 Diagnostic possibilities of an echodopplerography in an assessment of prevalence of a tumoural invasion of a stomach cancer

Background We sought to study the diagnostic efficiency of an echodopplerography in the assessment of prevalence of tumoural invasion in patients with cancer of the stomach at a presurgical stage. Methods The study included 32 patients with cancer of the stomach of various localisations. Findings At the site of the stomach tumour, blood flow in the celiac artery was increased by 1.5 times in 23 (72%) patients. In the superior mesenteric artery, blood flow increased by 1.2 times in 18 (56%) patients and in the left gastric artery and splenic vein, blood flow increased by 1.3 times in 15 (47%) patients. This increase was accompanied by a tendency towards a decrease in the resistance index. In 15 (47%) patients, strengthened hypervascularisation of the affected stomach wall with involvement of all layers and a simultaneous decrease in blood flow in the main vessels was observed, indicative of germination of the tumoural process in the surrounding structures. Characteristic symptoms of stomach cancer included existence of an atypical vascularisation of various intensities in stomach and tumour walls at CDM (PD). Interpretation Echodopplerography improves diagnostic efficiency and facilitates decision making regarding the operability of a stomach tumour and treatment planning.

Diversity and abnormalities of cyclopoid copepods around hydrothermal vent fluids, Kueishantao Island, north-eastern Taiwan

The diversity and abundance of cyclopoid copepods were investigated at four stations along the hydrothermal vent at Kueishantao Island, north-eastern Taiwan. Zooplankton samples were collected by surface tows. Qualitatively, 21 species of cyclopoids belonging to five genera and three families were observed. Our analysis revealed a number of abnormal protrusions (TLAs) on cyclopoid copepods, which were more frequent on the dorsal body surface and in members of the family Corycaeidae. The number of TLAs was highest at the hydrothermal vent plume (HVP) zone and among adult copepods. The potentially high levels of toxic minerals erupting from the hydrothermal vents as well as low pH and high temperatures may weaken the copepods' exoskeletons, thereby increasing susceptibility to infections, indicated by the HVP-related increase of tumoural processes. It is suggested that some of these abnormalities are related to the occurrence of symbiotic tantulocarids, a topic yet to be studied in this interesting environment.

Massive pericardial effusion caused by “Inflammatory Myofibroblastic Tumour” in a 3-month-old child

Tumours originating from cardiac tissues are rarely encountered during childhood, and fortunately most of these tumours are benign in nature. Inflammatory myofibroblastic tumour, which has unique clinical, pathological, and molecular characteristics, is a relatively new entity compared with previously mentioned tumoural processes originating from the heart. Most of the cardiac intima-media thickness patients are in the age group of 4 months to 17 years. This rarely seen tumoural process has not been subject of any specific research and the prognosis is not well known. Here we present the case of a 3-month-old child who was admitted to our outpatient clinic with massive pericardial effusion and who has shown excellent progress after surgical resection of over 1 year.

Gastric carcinoma associated with Menetrier's‐like disease in a West Highland white terrier

A seven-year-old West Highland white terrier was presented for chronic vomiting associated with mild regenerative anaemia and hypoalbuminaemia. Further examination showed a giant polypoid cerebriform mass located in the lesser curvature of the stomach. Partial gastrectomy was performed and histology was consistent with hypertrophic gastritis with typical features of Ménétrier's disease. Five years after surgery, the dog was re-examined for recurrence of vomiting episodes. Endoscopy showed ulceration of the lesser curvature of the stomach and histological analysis revealed a poorly differentiated superficial gastric carcinoma surrounded by hypertrophic gastritis. To the authors' knowledge, this is the second time that coexistence of these two types of lesions is reported, suggesting that recurrence of gastritis could be the starting point of the tumoural process.

Mammary renin–angiotensin system-regulating aminopeptidase activities are modified in rats with breast cancer

Angiotensin II in particular and/or the local renin-angiotensin system in general could have an important role in epithelial tissue growth and modelling; therefore, it is possible that it may be involved in breast cancer. In this sense, previous works of our group showed a predominating role of angiotensin II in tumoral tissue obtained from women with breast cancer. However, although classically angiotensin II has been considered the main effector peptide of the renin-angiotensin system cascade, several of its catabolism products such as angiotensin III and angiotensin IV also possess biological functions. These peptides are formed through the activity of several proteolytic regulatory enzymes of the aminopeptidase type, also called angiotensinases. The aim of this work was to analyse several specific angiotensinase activities involved in the renin-angiotensin system cascade in mammary tissue from control rats and from rats with mammary tumours induced by N-methyl-nitrosourea (NMU), which may reflect the functional status of their target peptides under the specific conditions brought about by the tumoural process. The results show that soluble and membrane-bound specific aspartyl aminopeptidase activities and membrane-bound glutamyl aminopeptidase activity increased in mammary tissue from NMU-treated animals and soluble aminopeptidase N and aminopeptidase B activities significantly decreased in mammary tissue from NMU-treated rats. These changes support the existence of a local mammary renin-angiotensin system and that this system and its putative functions in breast tissue could be altered by the tumour process, in which we suggest a predominant role of angiotensin III. All described data about the renin-angiotensin system in mammary tissue support the idea that it must be involved in normal breast tissue functions, and its disruption could be involved in one or more steps of the carcinogenesis process.

MDM2 Dependant Induction of Error Prone DNA Polymerase beta by EBV-LMP1 Oncoprotein.

Epstein Barr Virus (EBV) is able to immortalise B lymphocytes in vitro and is associated with several human tumours, such as Hodgkin's disease (HD), suggesting that this virus could play a role in the initiation of the tumoural process. The LMP1 protein of EBV, coded by the LMP1-BNLF1 gene, was rapidly suspected to be involved in this process due to its oncogenic characteristics. LMP1 functions as a constitutively activated member of the tumour necrosis factor receptor superfamily, and activates trough its carboxyterminal cytoplasmic region several signalling pathways, including NF-kappa B. In order to identify new LMP1 target genes, we studied the transcriptome of the B lymphoid Ba/F3 cell line stably transfected with LMP1-BNLF1 genes from HD Reed-Sternberg tumour cells as well as from normal cells, using the cDNA microarray technique.We show that the expression of several genes was modulated by the LMP1 protein, independently of the cellular origin of the LMP1 protein. Among overexpressed genes, we focused on the DNA polymerase-beta (beta-pol) gene. To confirm and extend this cDNA result, we demonstrated in different cell lines that the beta-pol protein expression was under the control of LMP1. In vivo and in vitro functional tests showed that LMP1 induced overexpression of beta-pol paralleled its increase in activity.Regulatory sequences of the human beta-pol gene includes three motives that match the Sp1 factor binding site motive. LMP1 did not modulate Sp1 RNA neither protein expression. By contrast, we observed that MDM2 and beta-pol RNA expression were increased in parallel by LMP1, an effect trigerred by the carboxyterminal region of LMP1. Then, we demonstrated that MDM2 protein overexpression was associated with increased beta-pol protein expression.Since MDM2 promoter is regulated by NF-kappaB, we investigated whether up-regulation of MDM2 and beta-pol were NF-kappaB pathway dependant. We show that inhibition of NF-kappaB by overexpression of an I-kappaB dominant negative down-regulated both MDM2 and beta-pol expression.In conclusion, we demonstrated that the oncoprotein LMP1 regulates overexpression of beta-pol through NF-kappaB signaling pathway and the MDM2 protein, and that MDM2 was itself regulated by NF-kappaB. Beta-pol is the more error prone of all the known eucaryotic DNA polymerases. Elevated expression of beta-pol, an event found in many human tumours, has been shown to generate a mutator phenotype which is extensively associated with cancers. Our work leads to the hypothesis that LMP1 protein could play a role in the genetic instability in EBV associated malignant diseases such as HD through over-expression of beta-pol.

In vitro Assessment of Renal Toxicity and Inflammatory Events of Two Protein Phosphatase Inhibitors Cantharidin and Nor‐Cantharidin*

In China, cantharidin has been reported to be active against various human cancers, but with severe side effects such as nephrotoxicity. In order to reduce this toxicity, its demethylated analogue nor-cantharidin has been synthesized and used in cancer therapy, but with only few data regarding safety assessment. The aim of this study was to compare the in vitro effects of cantharidin and nor-cantharidin on renal toxicity and on inflammatory events associated with tumoural process where protein phosphatases could be involved (energy status, prostanoid production, glutathione and nitrite contents) on RAW 264.7 and LLC-PK1 cells. In macrophages, both cantharidin and nor-cantharidin decreased cell viability, in a concentration- and time-dependent manner. However, IC50 was lower with cantharidin than with nor-cantharidin. These two drugs significantly decreased the ATP level after 24 hr incubation. However, ATP decreased much more with cantharidin (up to 4 times) than with nor-cantharidin. When control macrophages were activated with lipopolysaccharide+interferon-gamma for 24 hr a significant increase in nitrite content and in prostanoids were observed. Addition of either drug decreased nitrite generation and prostanoids, however these decreases were greater with cantharidin than with nor-cantharidin. In LLC-PK1 cells, incubated with either cantharidin or nor-cantharidin, our results show significant differences between the two drugs, similar to those observed in peritoneal macrophages, except for GSH content with opposite variations in both cells. We provide a better understanding of the various mechanisms of cantharidin side effects, allowing an easier comparison with nor-cantharidin which could be an attractive therapeutic potential in cancer chemotherapy in western countries.

Imagerie des tumeurs de l'oreille

Tumoural processes of the temporal bone are rare except for vestibular schwannomas of the acoustic-facial bundle and External Auditory Canal (EAC) exostosis. Both CT and MRI should be performed to establish a correct diagnosis and delineate potential trans spatial extension. MRI using pre- and post-contrast T1-weighted sequences, perfusion, SE T2-WI is an excellent method to characterise space occupying lesions such as tumours. MRI delineates better than CT tissular components differentiating vascular processes, tumour with matrix and epidermoid tumours. Unenhanced HRCT depicts excellently osseous lesions such as osteomas, fibrous dysplasias, and chondromas.

Endometriosis de la pared abdominal tras cirugía ginecológica

Summary Endometriosis of the abdominal wall following obstetric or gynaecological surgery is a rare condition that may confuse differential diagnosis with other abdominal inflammatory or tumoural processes. The most common presentation is an abdominal wall mass associated with pain during the menstual cycle, and diagnosis is only confirmed by histology. Surgical excision is the treatment of choice providing both diagnosis and cure. Gonadotrophin analogues may be useful following surgery.

Activity and properties of α- l-fucosidase are dependent on the state of enterocytic differentiation of HT-29 colon cancer cells

Previously we have demonstrated an impairment in the activity of α- l-fucosidase in colon tumours. In order to establish an in vitro model to study this enzyme in colon cancer, we have determined the activity and properties of the enzyme during the differentiation of HT-29 colon cancer cells. Cultures were committed to differentiate into enterocyte-like cells by placing them in a culture medium without glucose for 18–21 days. The state of differentiation was evaluated by assaying the activity of enterocytic marker enzymes, and the acquisition of enterocyte morphology was assessed by electron microscopy. The α- l-fucosidase activity was determined using a fluorometric method. Intracellular levels of α- l-fucosidase activity are lower in non-differentiated cells (3.0±1.01 U/mg) than in differentiated ones (9.2±4.09 U/mg) ( P<0.001). This variation is not due to a greater secretion of the enzyme to the culture medium, and properties such as pH optimum or the affinity towards substrate are not dependent on differentiation. The enzyme however, is more stable at acidic pH and at high temperatures, and V max is higher in differentiated cells. Moreover, in undifferentiated cells the enzyme is mainly in a monomeric form whereas multimeric forms of the enzyme appear only upon differentiation. Most of these changes are very similar to those previously observed between normal colon tissue and colon tumours. Thus, we suggest that differentiation of HT-29 colon cancer cells could be used as a model to study the alterations of the enzyme α- l-fucosidase during the progression of the tumoural process.

Insulin and cancer (Review)

Although the molecular mechanisms of insulin action on many physiological and biochemical processes are far from being completely understood, little doubt exists about the involvement of insulin in tumoural processes. Indeed, increased insulin production (either directly by the tumour in an ectopic fashion, or indirectly by stimulation of the pancreatic secretion) is a common phenomenon during cancer development. Paradoxically, the increased production and circulating levels of the hormone are associated with a decrease in sensitivity which leads to insulin resistance in the non-tumoural tissues, resulting in hyperlipaemia and profound alterations in carbohydrate and lipid metabolism. In addition to these effects on the host, insulin can actually increase the incidence of neoplasias and promote tumour growth. This is probably related to the signaling pathway of the hormone, which shares many elements with that of several growth factors. In addition, insulin signaling directly interacts with that of the ras oncogene. We review the involvement of insulin in cancer from a multidisciplinary point of view, with the aim of encouraging the design of future therapeutic options for cancer treatment.

Gliomatosis Cerebri: A Brain Tumour Which is too Difficult to Treat?

Gliomatosis cerebri is a rare form of primary diffuse brain tumour first described by Nevin in 1938. It was originally considered to be a post-mortem diagnosis before Troost et al reported a clinically diagnosed case in 1987. However antemortem diagnosis remains difficult due to vague clinical symptoms and often non-specific findings on CT scanning. Gliomatosis cerebri has been classified by the World Health Organization as an infiltrative tumoural process, which involves at least two, and usually three, lobes of the brain. Magnetic resonance (MR) imaging shows a diffuse infiltrative process with possible mass effect but no necrosis. Histology is usually of a low grade astrocytic neoplasm which seemingly infiltrates out of proportion to the degree of anaplasia. We report two patients who presented over the past year, whose clinical and radiological features prompted a preoperative diagnosis of gliomatosis cerebri, confirmed by biopsy.

7 Thyroid dysfunction in HIV infection

During infection with HIV, overt clinical or biochemical thyroid dysfunctions are rare. When present, thyroid failure generally results from the destruction of the thyroid gland by opportunistic infections such as Pneumocystis carinii, or tumoural processes such as KS. Less frequently, hypothalamic-pituitary failure due to central nervous system infections is involved. Some cases of thyroiditis with thyrotoxicosis or hypothyroidism due to Pneumocystis carinii have also been reported. Subtle alterations of thyroid function tests are more common in HIV infection and are sometimes already detectable in the early phase of the disease. Contrary to what is observed in severe non-thyroidal illnesses, the low T3 syndrome and the sick euthyroid syndrome are less marked; these changes are mainly present in the final stage of the disease, when anorexia and weight loss occur, and indicate a poor outcome. Unique abnormalities of thyroid function indices have also been recently documented. A progressive elevation in serum TBG--but not in other binding proteins such as CBG and SHBG--accompanying the decline of the CD4 lymphocyte count, and associated with a concomitant increase in the serum T4 value, has been reported. An unusual prolonged maintenance of normal T3 levels with a paradoxical decrease in serum rT3 values has also been recognized. Finally, a hypothyroid-like regulation of the pituitary-thyroid axis, possibly directed to limit hypermetabolism in HIV infection, has been observed. The recognition of these particular thyroid profiles is of clinical importance as serum TBG appears to be a specific marker of the progression of HIV infection and serum T3 a reliable prognostic indicator for AIDS.

Treatment of hyperprolactinaemic patients with pergolide.

Eighteen hyperprolactinaemic patients were orally treated for up to 16 months with pergolide mesylate, a new potent long-lasting dopaminergic ergot derivative. In all cases, Prl normalization (less than 25 ng/ml) was achieved at a once-a-day dose of 50-300 micrograms. All women recovered and/or exhibited normal menstrual function. Among the 6 women wishing to become pregnant, 4 of them conceived within 4 months; there were other causes for infertility than hyperprolactinaemia in the 2 other couples. A macroprolactinoma man experienced important improvement in well-being as well as objective regression of his visual fields defect. This suggests a shrinkage effect of pergolide on the tumoural process. Another man regained normal potency and normal testosterone within 2 weeks. While 10 patients were completely free of any side effect, 7 experienced transiently mild gastro-intestinal side effects or postural hypotension. Only one patient discontinued her treatment because of dizziness. The present study demonstrates the high potency, the good tolerance and the excellent efficacy of pergolide in the treatment of hyperprolactinaemia.