Expression of IAP family proteins and its clinical importance in breast cancer patients.

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

Membrane expression of trail receptors DcR1 and DcR2 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

We aimed to evaluate the membrane expression of DcR1 and DcR2 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). The study comprised 101 patients: 20 NE, 14 EAH and 67 EEC. Membrane expression of DcR1 and DcR2 was examined and presented as total score (TS). The membrane expression of both DcR1 and DcR2 was more common in EEC than in NE (p < 0.001; p < 0.001). A strong correlation was found between type of endometrial tissue (NE/EAH/EEC) and the TS of DcR1 (p = 0.001) and DcR2 (p < 0.001). In EEC, the TS of DcR1 and DcR2 was not related to grading and survival. The TS of DcR1 negatively correlated with staging (p = 0.018), but DcR2 did not. The membrane expression of decoy receptors for TRAIL DcR1 and DcR2 is greater in NE than EEC. In EEC patients, membrane expression of DcR1 and DcR2 are not independent predictors of survival.

Membrane expression of the death ligand trail receptors DR4 and DR5 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

To assess membrane expression of DR4 and DR5 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the study examined 101 patients: 20 NE, 14 EAH and 67 EEC. The expression of DR4 and DR5 was examined and presented as the total score (TS). DR4 expression was seen in 18 NE, 11 EAH and 10 EEC. DR5 expression was seen in 20 NE, 13 EAH and 21 EEC. A strong correlation between type of endometrial tissue and TS of both receptors was identified. In EEC TS of DR4 and DR5 was not related to grading, staging or survival. Malignant transformation in the endometrium is related to reduction of membrane DR4 and DR5 expression. The level of membrane staining of the receptors in EEC is not dependent on grading and staging, and is not sufficient to predict survival in EEC patients.

The effects of weight cycling on lifespan in male C57BL/6J mice.

OBJECTIVE: With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives. METHODS: Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed. RESULTS: Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice. CONCLUSIONS: This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

Construction of a tissue microarray with two millimeters cores of endometrioid endometrial cancer: factors affecting the quality of the recipient block.

The tissue microarray (TMA) method currently is not used to render a primary diagnosis of cancer, but its scientific value has been proved in studies of various cancer types. TMA technology still is not used often for uterine tumors, however. We investigated the repeatability of histological diagnosis of endometrioid endometrial cancer (EEC) using conventional histology and TMA using 2 mm cores. We examined EEC tissues from 171 patients. Formalin fixed, paraffin embedded tissue donor blocks from EEC specimens were selected and examined histologically. Duplicate 2 mm tissue cores were inserted into a TMA recipient block. EEC tissues were examined as hematoxylin-eosin stained sections from the TMAs. EEC tissue was identified in the TMAs in 158 cases (92.4%) and not found in 13 cases (7.6%). On the TMA slides, both EEC positive cores were identified in 129 cases (75.4%), but only one core in 29 cases (17.0%). Among 342 biopsies of the donor blocks (each case in duplicate), EEC was found in 287 cases (83.9%) using the TMA: 124/146 (84.9%) with superficial infiltration, 153/178 (86.0%) with deep myometrial infiltration, and 10/18 (55.6%) without myometrial infiltration. We concluded that two 2 mm tissue cores from a biopsy of a donor block inserted into a TMA recipient block were sufficient to diagnose EEC in more than 90% of cases. EEC was identified in the TMAs with similar frequency with respect to superficial and deep myometrial infiltration. Cases without myometrial infiltration were identified less often.

Central nervous system metastases from epithelial ovarian cancer.

The aim of the study was to assess the clinical features and prognosis in patients with epithelial ovarian cancer (EOC) metastasised to the central nervous system (CNS). A total of 15 patients were studied retrospectively. Clinical and pathological data and follow-up were analysed. It was found that at the diagnosis of primary EOC, the patients were 41-69 years old (56.6 ± 8.3). The interval from diagnosis of primary EOC until the relapse was 2-39 months (19.1 ± 10.5). Palliative radiotherapy was the treatment of the CNS relapse in 13 patients (86.7%). The follow-up after CNS relapse varied 0.5-15 months (4.7 ± 4.2). At the time of retrospective analysis, none of the patients were still alive. Multifocality of the CNS metastases, the presence of synchronous extracranial metastases and locations in the brain were not associated with survival. It was concluded that the development of the CNS metastases seems to be not uncommon in patients with advanced ovarian cancer. Despite oncological treatment, they are indicators of poor prognosis, and most of the patients do not survive beyond the first year of follow-up.

Bone metastases from gynaecological epithelial cancers.

The aim of this study was to investigate the clinical features and prognosis in patients with gynaecological epithelial cancers metastasised to bones. A total of 26 patients were studied retrospectively. Clinical and pathological data were analysed along with a follow-up. It was found that the interval from primary diagnosis of cancer until bony relapse varied between 0 and 163 months (31.4 ± 36.8). Bone metastases were solitary in 11 cases and multifocal in 15 cases. A total of 14 patients demonstrated only bony metastases while 12 had both bony and non-bony metastases. The time to follow-up from the diagnosis of osseous relapse varied between 1 and 43 months (10.0 ± 10.4). During follow-ups, 13 patients died and 13 patients survived. In both univariate and multivariate analyses, synchronous non-bony metastases and symptomatic treatment without oncological therapy impaired prognosis. It was concluded that even in the presence of multiple bone metastases, some patients may benefit from radiotherapy, chemotherapy or a combination of both, rather than palliative care alone, providing they do not have additional soft tissue metastases.

Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients.

Smac/DIABLO protein promotes caspase-dependent apoptosis by inhibition of inhibitor of apoptosis protein (IAP) family members. The role of Smac/DIABLO in breast cancer has not been yet established. Therefore, the aim of the study was to assess the expression of this protein in tumor cells from breast cancer patients. The expression of Smac/DIABLO was analyzed in 62 breast cancer patients by flow cytometry. The obtained results were compared with expression of this protein in benign breast tumor tissue, which served as the control (11 patients with fibroadenoma). Expression of caspase-3 proteins in breast cancer was also evaluated. Smac/DIABLO expression in breast cancer was correlated with clinical and pathological data. Although the expression of Smac/DIABLO protein was found in all examined samples of both the breast cancer and fibroadenoma patients, the median expression of Smac/Diablo in breast cancer was significantly lower than in the control (39.1% vs. 48.1%; p=0.0047). Smac/DIABLO expression correlated with expression of caspase-3 (p=0.000008). In pT1 breast cancer patients, expression of Smac/DIABLO protein was higher than in those with pT2-3 (p=0.02). Diffuse cancer infiltration significantly correlated with lower expression of Smac/DIABLO protein (p=0.02). Moreover, there was a loose correlation between low expression of Smac/DIABLO protein and cancer embolus in minor blood and lymphatic vessels (p=0.08). Our results indicate that expression of Smac/DIABLO inversely correlates with the tumor stage, which may suggest that this protein may play an important role in the breast cancer development.

[Tumors of the oropharynx and oral cavity: MR, CT, PET-CT imaging]. / Imagerie des tumeurs de l'oropharynx et de la cavité orale: IRM, TDM, TEP-scan.

Pretherapeutic imaging plays a central role in the management of tumors of the oropharynx and oral cavity. MR and, to a lesser extent, CT and F-18 FDG PET-CT are the imaging modalities of choice for pretherapeutic work-up of these lesions. Imaging protocols should be simple and reproducible, and should provide the key elements for treatment planning.

[Imaging of the post-irradiation larynx for laryngeal and hypopharyngeal carcinomas]. / L'imagerie dans le suivi post-thérapeutique des cancers pharyngo-laryngés.

Imaging has a key role in the follow-up of patients treated for laryngeal or hypopharyngeal carcinoma. Imaging is complementary to clinical evaluation and has three goals: evaluation of chemo and radiation therapy; differentiation between complications and tumour recurrence; early detection of tumour recurrence, prior to clinical manifestations. Imaging may allow early detection of recurrences, when salvage treatment may still be less radical.

Astonishingly rapid growth of malignant cystosarcoma phyllodes tumor in a pregnant woman--a case report.

There are very few reports concerning the presence of malignant cystosarcoma phyllodes (CSP) in breasts of pregnant women. In the hereby described case, a 28-year-old woman presented in our department with huge (18 x 11 x 8 cm) tumor of left breast, 2 weeks after labor. The patient discovered a tumor in 34th week of pregnancy, 6 weeks before labor. Histopatholgic examination of excised tumor revealed the presence of malignant CSP tumor. Simple mastectomy was proposed to patient as a best treatment modality. However, the patient refused. She underwent excision of tumor bed (2-cm tumor-free margin was achieved). Despite insufficient treatment, she remains free of disease 20 months after the wide excision of breast malignancy. It is not known how pregnancy influences prognosis of patients with malignant CSP. Lack of such information prompted us to describe the clinical course of our patient.

Does fecal diversion offer any chance for spontaneous closure of the radiation-induced rectovaginal fistula?

Analysis of the clinical course of patients with postirradiation rectovaginal fistula after fecal diversion. The studied group included 17 women with postirradiation rectovaginal fistula who underwent fecal diversion as a sole mode of treatment, between January 1987 and December 2002, in our department. All patients were subjected to radiotherapy due to cancer of the uterine cervix, administered 5-107 months before the fistula appearance (mean, 22.9 months). In 3 of 17 patients (18%), spontaneous closure of fistula was observed after 5, 6, and 9 months, respectively, from fecal diversion. Closure was confirmed by endoscopy. Length of follow-up after fecal diversion ranged from 0.5 to 122 months. The actuarial probability of spontaneous closure of postradiotherapy rectovaginal fistula was 0.24 at 9 months of follow-up and then remained stable thereafter. In conclusion, colostomy alone gives hardly a chance for closure of the postradiotherapy rectovaginal fistula. Additional surgical measures are necessary.

Studies on antioxidant properties of polyphenol-rich extract from berries of Aronia melanocarpa in blood platelets.

The antioxidant properties of extract from berries of Aronia melanocarpa (chokeberry) containing: anthocyanidines, phenolic acids and quercetine glycosides on oxidative/nitrative stress induced by peroxynitrite (ONOO(-), a powerful physiological oxidant, nitrating species and inflammatory mediator) in human blood platelets were studied in vitro. The extract from A. melanocarpa (5 - 50 microg/mL) significantly inhibited platelet protein carbonylation (measured by ELISA method) and thiol oxidation estimated with 5,5'-dithio-bis(2-nitro-benzoic acid) (DTNB) induced by peroxynitrite (0.1 mM) (IC(50)--35 microg/mL for protein carbonylation, and IC(50)--33 microg/mL for protein thiol oxidation). The tested extract only slightly reduced platelet protein nitration (measured by C- ELISA method). The extract also caused a distinct reduction of platelet lipid peroxidation induced by peroxynitrite. Moreover, in our preliminary experiments we observed that the extract (50 microg/mL) reduced oxidative/nitrative stress in blood platelets from patients with breast cancer. The obtained results indicate that in vitro the extract from A. melanocarpa has the protective effects against peroxynitrite-induced oxidative/nitrative damage to the human platelet proteins and lipids. The extract from A. melanocarpa seems to be also useful as an antioxidant in patients with breast cancer.

Expression of tumour necrosis factor-related apoptosis-inducing ligand and caspase-3 in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.

AIM: To assess whether the distribution of the recently described proapoptotic ligand, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and the apoptosis effector, caspase-3 alters with the degree of inflammation and fibrosis present in liver biopsy specimens from patients with chronic hepatitis C virus infection. METHODS AND RESULTS: Expression of TRAIL and caspase-3 was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of TRAIL in hepatocytes correlated inversely with stage of fibrosis (P = 0.001), classified according to the Scheuer score; expression of caspase-3 in hepatocytes correlated with grade of inflammation (P = 0.012). Expression of TRAIL in hepatocytes was not correlated with grade of inflammation (P > 0.05); expression of caspase-3 was not correlated with stage of fibrosis (P > 0.05). Maximum expression of proapoptotic TRAIL protein was observed in cases with low grade inflammation (G0) and low stage fibrosis (S1). Maximum expression of caspase-3 in hepatocytes was observed in cases with high grade inflammation (G3-4) and high stage fibrosis (S3), but not with liver cirrhosis (S4). CONCLUSIONS: There is a significant decrease in TRAIL expression with increasing grade of inflammation, whereas caspase-3 expression is significantly increased with advanced fibrosis, short of cirrhosis.

Expression of Bax, Bcl-xL and Bcl-2 proteins in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.

AIMS: To determine the expression of regulators of apoptosis in chronic hepatitis C. METHODS AND RESULTS: Expression of Bax, Bcl-xL and Bcl-2 proteins was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of Bax in hepatocytes correlated inversely with grade of inflammation (P < 0.001) and stage of fibrosis (P = 0.011), classified according to the Scheuer score; expression of Bcl-xL in hepatocytes did not correlate with grade of inflammation (P = 0.106) or stage of fibrosis (P = 0.078); maximum Bcl-xL expression was observed in grade 3 inflammation and stage 4 fibrosis. Expression of Bcl-2 protein in hepatocytes was present in only two cases (both with advanced disease); the expression of Bcl-2 protein in interlobular bile duct epithelial cells correlated with the grade of inflammation (P = 0.018), but not with stage of fibrosis (P = 0.154). The expression of Bcl-2 protein in lymphoid cells infiltrating portal zones and lobules did not correlate with grade of inflammation (P = 0.113) or stage of fibrosis (P = 0.815). CONCLUSION: Major differences in expression of studied proteins were observed in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.

Clinical significance of CK5/6 and PTEN protein expression in patients with bilateral breast carcinoma.

AIMS: To assess the expression of cytokeratin (CK) 5/6 in bilateral breast cancers and to assess the relationship between its expression and other prognostic variables, as well as between CK5/6 expression and patients' survival. METHODS AND RESULTS: The expression of CK5/6, PTEN protein, oestrogen receptor, progesterone receptor, p53 and c-erbB-2 protein were evaluated by immunohistochemistry in 88 primary breast cancers diagnosed in 44 women. To assess the prognostic value of studied factors, Cox regression analysis was performed. Expression of CK5/6 was found in 23 of 88 primary breast carcinomas (23/88; 26%). The hazard ratio of development of distant metastasis in patients in whom at least one cancer was CK5/6+ was 99.8 (P=0.037) and in patients with at least one carcinoma with reduced PTEN expression it was 10.8 (P=0.044). CK5/6 expression was correlated with absence of oestrogen (P<0.0001) and progesterone receptors (P<0.0001) and very strong expression of p53 (P<0.05). Reduced PTEN expression was correlated with presence of axillary metastases (P<0.01), with very strong expression of c-erbB-2 (P<0.05) and with reduced expression of oestrogen receptor (P<0.05). CONCLUSIONS: Analysis of expression of CK5/6 and PTEN protein in bilateral breast carcinomas may be of value in clinical practice and warrant further studies.

[Sonography of the eye and orbit with a multipurpose ultrasound unit]. / Echographie de l'oeil et de l'orbite avec un échographe polyvalent.

Our goal is to help echographists and radiologists become familiar with the various possibilities indications, technique and results of ophtalmic ultrasonography. We used a multipurpose ultrasound unit. The frequency of the transducer has to be equal or superior to 7.5 MHz. Color Doppler allowing the study of low flows is useful. The study must be standardized: the first step is to obtain measurements of both eyes. Then the entire globe is systematically evaluated. Finally, the orbital structures and vessels of the eye and orbit are analized. After a review of the anatomy and the normal sonographic features, the main indications are described as well as the main pathologies. Special attention is paid to intravitreal hemorrhage, retinal and choroidal detachments, intraocular tumors and orbital space occupying lesions.

[Inflammatory presentation of a cavernous dural fistula: diagnosis with color and pulse Doppler imaging]. / Fistule durale caverneuse d'allure inflammatoire: diagnostic avec écho-Doppler couleur et pulsé.

We report a case of a cavernous dural fistula in a 54-year-old man the source of inflammatory ocular symptoms. Poorly adapted treatment with corticosteroids led to iatrogenic complications. We will attempt to show the advantage of color Doppler imaging for the diagnosis of this infrequent lesion. The only indication of digitalized angiography is for endovascular treatment.

Sentinel node biopsy in patients with breast cancer--evaluation of exposure to radiation of medical staff.

AIM: To measure the absorbed doses of radiation to hands of medical staff performing sentinel node biopsy in breast cancer patients. METHODS: The study was conducted in 2004, during sentinel node biopsies in 13 breast cancer patients (T1/T2N0). Sentinel nodes were identified with the use of combined radiotracer/blue dye technique (lymphoscintigraphy--99mTc on albumin carrier, surgery after 24 h; blue dye; intraoperative detection of gamma radiation). Highly sensitive thermoluminescent dosimeters (TLD) made of LiF were used to assess the absorbed doses of radiation during the procedure. During lymphoscintigraphy and during surgical procedure a total of 57 TLDs was placed on different parts of hands of medical staff. RESULTS: Maximal dose recorded during lymphoscintigraphy by TLDs placed on the hands of the physician injecting the radiotracer was 164 microSv. Mean recorded doses were higher for non-dominant hand, especially for distal parts of the index finger, third finger and thumb. During the surgical procedure, TLDs placed on the hands of medical staff recorded much lower doses of radiation than during lymphoscintigraphy. The highest dose was recorded by TLD placed on the pulp of the dominant hand index finger (22 microSv) of the operating surgeon. Mean doses recorded by TLDs placed on the hands of the operating surgeon ranged from 2 to 8 microSv. The absorbed dose of radiation to hands of the scrub nurse was similar to that absorbed to hands of the operating surgeon. CONCLUSION: The maximum recorded dose during sentinel node biopsy in this study was 2200 times smaller than current 1-year dose limit.