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J C Noel

Publications and source records attributed to J C Noel.

At least 19 recordsLinked to original sources

An immunohistochemical study of abnormal keratinocyte proliferation in molluscum contagiosum.

BACKGROUND: Molluscum contagiosum is a common cutaneous tumour that is characterized by usually spontaneous involution and self-limited spreading in immunocompetent individuals. OBJECTIVE: We aimed to investigate the apoptosis and the expression of cell-cycle proteins in molluscum contagiosum lesions. METHODS: The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL)-based apoptotic index and the expression of the cell-cycle proteins Ki-67, p53, p21WAF and Bcl-2 were investigated in molluscum contagiosum lesions obtained from the trunk of 20 immunocompetent patients and in normal skin samples from the trunk of six healthy volunteers. RESULTS: Whereas molluscum contagiosum lesions displayed a TUNEL-based apoptotic index similar to that of normal skin, they exhibited an increased Ki-67 index, which was confined to the basal and first suprabasal layers (P < 0.001). Compared with normal non-sun-exposed skin, molluscum contagiosum lesions also exhibited increased p53 staining in basal cells (P < 0.01), increased p21WAF in suprabasal cells (P < 0.001) and loss of Bcl-2 expression. CONCLUSIONS: These results indicate that molluscum contagiosum lesions exhibit an increased proliferation rate of keratinocytes, which is likely to be partially counteracted by accumulation of p53.

Apoptosis↗

Persisting active and proliferative intrinsic ureteral endometriosis under GNRH agonists therapy: a case with immunohistological study.

We report the case of a 30-year-old patient who underwent a segmental ureteral resection with ureteroureterostomy because of the presence of a left ureterohydronephrosis caused by an intrinsic ureteral endometriotic lesion. Preoperatively, the patient received a 3 months course of GNRH agonists. The serum estradiol level was at 12 pg/ml at the moment of surgery. Histology and immunohistochemistry performed on the resected specimen showed the presence of numerous large haemorrhagic endometriotic foci containing very high levels of alpha-estrogen and progesterone nuclear receptors, a high Ki-67 labeling index and a strong positivity for EGF-receptor. This is the first report of immunohistochemical study performed on ureteral endometriosis preoperatively treated with GNRH agonists. Because hormonal treatments are often prescribed in the treatment of ureteral endometriosis, clinicians should be aware of the possibility of persisting very active and proliferative ureteral endometriotic lesions even under treatment with GNRH agonists and very low levels of circulating estradiol.

Adult↗

Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Cell Division↗

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

Cell Line↗

Cidofovir, a new approach for the treatment of cervix intraepithelial neoplasia grade III (CIN III).

Cervix intraepithelial neoplasia grade III (CIN III) is an intraepithelial proliferative process with different levels of severity depending on both the extension of the proliferation in the epithelium and the presence of cellular atypia. Human papillomavirus (HPV) has been clearly associated with such lesions. The results of a preliminary study are described on the local application of cidofovir, an acyclic nucleoside phosphonate derivative with broad-spectrum anti-DNA virus activity for the treatment of CIN III. Cidofovir 1% in gel was applied three times, every other day, on the cervix of each of 15 women with biopsy proven CIN III. Within 1 month after the start of treatment, the cervix was removed surgically. Histology and human papillomavirus polymerase chain reaction (HPV-PCR) were carried out. In 7 of the 15 patients the histology showed a complete response, whereas 5 patients had a partial response characterized by the persistence of CIN II-III lesions, 1 patient had a dysplasia of lower grade (CIN I), and 2 patients did not show differences in the histology. Complete response was confirmed by PCR in 4 of the 7 patients, with complete response histologically. Cidofovir was not toxic to the normal epithelium. Cidofovir 1% gel was able to inhibit partially or completely cervical dysplasia lesions after only three applications (every other day). This effect was specific and tissue other than the dysplastic epithelium was not affected by the treatment.

Adult↗

Multinucleate cell angiohistiocytoma: report of two cases with no evidence of human herpesvirus-8 infection.

Multinucleate cell angiohistiocytoma (MCA) is a vascular tumor of unknown pathogenesis. Possible misinterpretation of this disorder with Kaposi's sarcoma (KS), a human herpesvirus-8 (HHV-8)-associated tumor, prompted us to look for this virus in two women with MCA. None of the multiple skin specimens obtained from both our patients produced amplified HHV-8 DNA. Using a cell culture methodology similar to that used for KS, we established cell cultures from MCA lesions. While KS spindle cells are known to exhibit in vitro invasive properties and can be grown up to more than 20 passages, the MCA-derived cells were short-lived and were not able to traverse basement membranes. Taken together, our data support the hypothesis that MCA is not a neoplasm but a benign vascular proliferation which is clearly distinguishable from KS.

Aged↗

Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors.

Iron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, iron may be involved in the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular origin. This study was designed to investigate the effect of iron deprivation on Kaposi's sarcoma. The effects of iron chelators and iron deprivation associated with serum withdrawal were investigated on Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells, which are the probable progenitors of Kaposi's sarcoma cells. Desferrioxamine and deferiprone, two chemically unrelated iron chelators, induced a time- and concentration-dependent inhibition of endothelial and Kaposi's sarcoma cell growth. The inhibition of cell growth was associated with a decrease in Ki-67 and in both stable and total proliferating cell nuclear antigen expression. Inhibition of the progression through the G1-phase of the cell cycle was further evidenced by decreased expression of cyclin D1 and of p34 cyclin-dependent kinase 4. Terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end labeling assay, flow cytometry with annexin-V-fluorescein and morphologic analysis indicated that iron chelation also induced a time- and concentration-dependent apoptosis. This apoptotic effect was prevented by the addition of exogenous iron. Induction of iron deprivation in the culture medium by serum withdrawal led to similar cell cycle effects, which, however, could only be partly reverted by the addition of exogenous iron. In conclusion, these results show that iron deprivation inhibits the growth and induces the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. This suggests that iron chelators may represent a potential therapeutic approach for the treatment of Kaposi's sarcoma.

Apoptosis↗

Sigmoid endometriosis and ovarian stimulation.

In-vitro fertilization (IVF) and ovarian stimulation are frequently performed in patients with endometriosis. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low. We report four cases of severe digestive complications due to the rapid growth of sigmoid endometriosis under ovarian stimulation. In three patients, sigmoid endometriosis was diagnosed at laparoscopy for sterility. Because of the absence of digestive symptoms or repercussion on the bowel, no bowel resection was performed before ovarian stimulation. All patients experienced severe digestive symptoms during ovarian stimulation, and a segmental sigmoid resection had to be performed. Analysis of endoscopic and radiological data demonstrated that bowel lesions of small size may rapidly enlarge and become highly symptomatic under ovarian stimulation. At immunohistochemistry, these infiltrating lesions displayed high populations of steroid receptors and a high proliferative index (Ki-67 activity), suggesting a strong dependence on circulating ovarian hormones and a potential for rapid growth under supraphysiological oestrogen concentrations. Clinicians should be aware of this rare but severe digestive complication of ovarian stimulation. The early diagnosis of such lesions may help the patients to avoid months of morbidity falsely attributed to ovarian stimulation side effects. Further experience is necessary to determine the optimal attitude when diagnosing a small and asymptomatic endometriotic bowel lesion before ovarian stimulation.

Adult↗

Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules.

The histological relationships between fibrotic tissue, endometriotic foci and nerves in the rectovaginal septum endometriotic or adenomyotic nodule were studied. This is considered to be one of the most severe forms of deep endometriosis. Masson's trichrome staining for fibrosis detection and immunohistochemistry with the S100 monoclonal antibody for nerve detection were performed in 28 rectovaginal endometriotic nodules from patients presenting with severe dysmenorrhoea and deep dyspareunia (23 patients with no other endometriotic location or potential cause of pain at laparoscopy and ultrasonography; five patients with multiple pelvic endometriotic localizations and other potential causes of pain at laparoscopy). Patients were allocated to two groups on the basis of their preoperative pain scores for pelvic pain, dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7). For each symptom, the mean number of nerves and endometriotic lesions per high-power field and the mean largest diameter of the lesions were not statistically different in groups 1 and 2. The mean percentages of nerves located within the fibrosis of the nodule and within endometriotic lesions were significantly higher in group 1 than in group 2. Among nerves located within endometriotic lesions, there was a significantly higher proportion showing intraneurial and perineurial invasion by endometriosis in group 1 than in group 2. In rectovaginal endometriotic nodules, there was a close histological relationship between nerves and endometriotic foci, and between nerves and the fibrotic component of the nodule. We postulate that such topographical relationships could at least partially explain the strong association between this lesion and pain.

Adult↗

Adenoid cystic carcinoma of Bartholin's gland: what is the optimal approach?

AIMS AND METHODS: We report the case of a locally advanced adenoid cystic carcinoma of Bartholin's gland which required posterior pelvic exenteration, radical vulvectomy and ablation of the ischiorectal fossa in order to obtain tumour clearance with negative margins. Including this case, only three pelvectomies have been performed for this disease. This is the first reported case in which a controlateral unsuspected intravulvar metastasis was found on histology. RESULTS AND CONCLUSIONS: No consensus exists on the adequate surgical management of this particular disease. Nevertheless, a review of the literature and this reported case suggest that radical vulvectomy with negative margins should be preferred to wide local excision as the primary surgical procedure. It also suggests that inguinofemoral lymph-node dissection should only be performed when suspect lymph nodes are found at clinical examination.

Bartholin's Glands↗

Early- and late-stage Kaposi's sarcoma lesions exhibit similar proliferation fraction.

There are few studies on the proliferative activity of cells in Kaposi's sarcoma. It remains unclear whether the different progressive histologic stages of Kaposi's sarcoma correlate with the proliferative activity of the tumor. To clarify this issue, we studied the Ki-67 proliferation index in 40 specimens of acquired immune deficiency syndrome-related Kaposi's sarcoma in correlation with the histologic stage of the lesions. The mean proliferation index in our combined material was rather low (8%, range 1-20%) and there was no significant difference among the different stages of the disease. Contrary to a common and probably misleading concept, our results suggest that the histologic progression of the Kaposi's sarcoma is not related to an increase of the proliferative compartment.

Acquired Immunodeficiency Syndrome↗

Penile intraepithelial neoplasia overlying Kaposi's sarcoma lesions: role of viral synergy?

Several viral agents have been detected in the lesional tissue of Kaposi's sarcoma (KS). Their precise oncogenic role remains to be determined. A 32-year-old heterosexual man with acquired immunodeficiency syndrome (AIDS) who had penile lesions of KS with overlying epithelial changes characteristic of intraepithelial neoplasia associated with concurrent infection by human papillomavirus (HPV) and human herpesvirus 8 (HHV-8) is reported. The absence of viral DNA from uninvolved skin suggests that this coinfection is more than coincidental and may involve synergy between these viruses, as has already been suggested for HPV and herpes simplex 2 virus.

Acquired Immunodeficiency Syndrome↗

Dual phase helical CT of a primary malignant fibrous histiocytoma of the right renal vein.

A case is reported of primary malignant fibrous histiocytoma of the right renal vein involving the ipsilateral kidney which showed early enhancement on dual phase helical CT. The correct diagnosis of a primary tumour of the renal vein involving the kidney was not made but in retrospect could have been achieved pre-operatively by considering several CT features.

Histiocytoma, Benign Fibrous↗

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy.

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Adjuvants, Immunologic↗

Sporadic carcinoid of the stomach: a highly proliferative disease with a probable role for p53 protein dysregulation.

We describe here one case of sporadic carcinoid of the stomach, occurring in a 65-year-old man. It is a rare, recently recognized entity, with only few cases reported in the literature. We were able to detect strong MIB-1 and p53 expression in this tumour, with 86 and 80% of tumoral cells positive, respectively. These data suggest that gastric sporadic carcinoids are a highly proliferative entity probably induced by dysregulation of p53 function.

Aged↗