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Biomedical subjects

G de Pinieux

Publications and source records attributed to G de Pinieux.

At least 19 recordsLinked to original sources
PubMed2007

Potentiation of antitumour activity of docetaxel by combination with trastuzumab in a human prostate cancer xenograft model and underlying mechanisms.

Antitumour activity of docetaxel (Taxotere) in hormone-dependent (HD) and hormone-independent (HID) prostate cancer PAC120 xenograft model was previously reported, and its level was associated with HER2 protein expression. In the present study, we evaluate the antitumour effects of docetaxel combined with trastuzumab (Herceptin), an anti-HER2 antibody. Although trastuzumab alone had no effect on tumour growth, it potentiated the antitumour activity of docetaxel in HD tumours and more strongly in HID variants. Using the HID28 variant, we show that docetaxel treatment of tumour-bearing mice induces an increased HER2 mRNA expression of the tyrosine kinase receptor of 25-fold 24 h after docetaxel treatment, while HER2 protein and p-AKT decreased. This was followed by an increase of HER2 protein 3 days (two-fold) after docetaxel treatment and by a strong HER2 release in the serum of treated mice; expression of phospho-ERK, p27, BCL2 and HSP70 concomitantly increased. Similar molecular alterations were induced by docetaxel plus trastuzumab combination, except for that there was a transient and complete disappearance of AR and HSP90 proteins 24 h after treatment. We show that in addition to its known effects on tubulin and mitotic spindles, docetaxel induces complex signalisation pathway mechanisms in surviving cells, including HER2, which can be pharmacologically targeted. This study suggests that the docetaxel/trastuzumab combination may prove an effective therapeutic approach for HER2-expressing hormone-refractory prostate cancer.

Antibodies, Monoclonal↗
PubMed2004

Mucinous differentiation features associated with hormonal escape in a human prostate cancer xenograft.

Many theories mention hypersensitive, promiscuous, outlaw or bypass signalling pathways to explain the acquisition of hormone independence in prostate cancer. Hormonal escape of prostate tumours is marked by many biological changes, including mucinous and neuroendocrine differentiation. Since expression of several mucins has been linked to carcinoma tumour progression, we have characterised the expression of mucins at both RNA and protein levels in an in vivo model of prostate cancer in hormonal escape. Using PAC120, a xenograft of a human hormone-dependent prostate tumour, and its hormone-independent variants, we analysed the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUC5B, MUC6) by immunohistochemistry or reverse transcriptase (RT)-PCR. While the parental PAC120 tumour was a compact poorly-differentiated tumour of Gleason score 9 (5+4), hormone-independent variants displayed mucinous, neuroendocrine-like or mixed histological changes; these changes were stable through serial transplantations or after testosterone supply. MUC1 mRNA was expressed in both PAC120 and the hormone-independent variants, although at variable levels. All tumours displayed a high and constant expression of MUC2 and no expression of MUC4 mRNA. While MUC1 was expressed in all xenografts whatever their hormone dependence status, MUC2, MUC5B and MUC6 were preferentially expressed in hormone-independent variants. The loss of hormone dependence in this prostate cancer xenograft model is therefore marked by irreversible histological alterations, mucinous or neuro-endocrine, associated with an expression of secretory MUC2, MUC5B and MUC6, independent of the histological differentiation subtype. These data point to mucinous differentiation as an important step in the acquisition of hormone independence in this cancer, and suggest that secretory mucins might participate in an unknown pathway of hormonal escape in prostate cancer.

Androgen Antagonists↗
PubMed2003

[A new model of human prostate cancer, the PAC120 xenograft].

Prostate cancer is the second cause of cancer death in men. Often, initialy hormono-independent, escape from anti-androgen therapy is a key event of tumoral progression showing an hormone-independent phenotype. To study morphological, genetic and molecular bases associated with the hormono-dependence escape, a new model of human adenocarcinoma prostate xenograft, PAC120, was established with its hormono-dependent and independent variants. Its growth was strongly inhibited by surgical castration or by administration of the new gonadotrophin-releasing hormone antagonist, FE 200486 (Ferring, San Diego, CA). Evolution to hormono-independence was frequently associated with a mucoid differentiation or a neuroendocrine-like pattern, with the apparition of new chromosomic alterations and variations of human gene expressions. PAC120 xenograft is a new model of hormone-dependent prostate cancer, opening the opportunity to study the hormone dependence escape mechanism and to evaluate the efficacity of new therapeutics.

Adenocarcinoma↗
PubMed2001

Primary mixed tumor of bone.

Mixed tumors occur most commonly in major salivary glands. They may rarely appear in other sites, such as skin, breast, and lung. There have been rare reports of similar tumors occurring in bone. We report on a patient with a primary mixed tumor of bone. No other primary site has become apparent on follow-up of 5 years. Although mixed tumors detected by bone biopsy are likely to be metastatic, they may rarely represent primary bone neoplasms.

Adult↗
PubMed2001

Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach.

We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient's tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. It formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp(6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp(6)-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. Independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOXB9 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.

Animals↗
PubMed2001

[Chromophobe cell renal cancer, a distinct entity. Report of a series of 35 cases].

OBJECTIVE: To describe the clinical and histological characteristics and natural history of clear cell renal carcinoma. PATIENTS AND METHODS: The case files of 35 patients (22 men and 13 women, with a mean age of 58 +/- 13.8 years) operated for clear cell renal carcinoma were reviewed. The circumstances of diagnosis and the histological features of the tumour were analysed. The outcome of the patients was studied with a mean follow-up of 70 +/- 20.2 months. RESULTS: The diagnosis was incidental in 66% of cases. The macroscopic appearance of the tumour was characteristic: homogeneous and beige or white colour. On light microscopy, tumours were composed of variable proportions of clear cells and eosinophilic cells. The were classified as 15 predominantly eosinophilic tumours (43%), 9 predominantly clear cell tumours (26%) and 11 tumours composed of equal number of clear cells and eosinophilic cells (31%). Nuclei were irregular and indented. Hale stain was positive in every case. The majority of tumours were confined to the kidney (T1: 65% and T2: 29%) with a low nuclear grade (91% of grades 1 and 2). No patient developed local recurrence or metastasis during follow-up. The overall 5-year survival rate was 92%. No death related to the disease was reported. CONCLUSION: The histological diagnosis of clear cell renal cancer is now easy and can be suggested even on macroscopic examination of the operative specimen. This tumour appears to have a good prognosis, as it is usually confined to the kidney with a low nuclear grade.

Adenocarcinoma↗
PubMed1999

Hemorrhagic necrosis due to peliosis hepatis: imaging findings and pathological correlation.

Peliosis hepatis is an uncommon liver condition characterized by blood-filled cavities. We report the CT, angiographic and MR features of a case of peliosis hepatis with no obvious etiology and spontaneously regressing hemorrhagic necrosis. Helical CT showed multiple peripheral low-density regions with foci of spontaneous high density suggesting the presence of blood component. On MR imaging, the multiple peripheral lesions were hypointense on T1-weighted and hyperdense on T2-weighted images, with bright foci on all sequences suggesting subacute blood. Angiography showed no evidence of tumor or vascular malformation; multiple nodular vascular lesions filling in the parenchymal phase and persisting in the venous phase suggested blood-filled cavities. Pathological examination showed blood-filled spaces with no endothelial lining, characteristic of the parenchymal type of peliosis. Knowledge of the imaging features of hemorrhagic necrosis due to peliosis hepatis is important since it can be responsive to antibiotic therapy. Furthermore, differentiating hemorrhagic necrosis from hepatic abscess avoids dangerous and sometimes fatal percutaneous drainage.

Adult↗
PubMed1999

Localized oral Fusarium infection in an AIDS patient with malignant lymphoma.

We report here a case of localized oral Fusarium infection in an AIDS patient who developed an ulceration in the soft palate. Fusarium solani was identified by histopathology and culture. We believe this to be the second reported case of oral Fusarium infection in a patient with haematological malignancy and the first reported association of oral Fusarium infection with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1999

Testicular fibroma of gonadal stromal origin with minor sex cord elements: clinicopathologic and immunohistochemical study of 2 cases.

OBJECTIVE: To report the histologic and immunohistochemical features of 2 cases of intratesticular fibromatous tumors. RESULTS: Microscopically, these tumors were composed of short, randomly interweaving fascicles of spindle cells dispersed within a fibrocollagenous stroma. A sex cord component was detected in one case by microscopic examination and in both cases by immunohistochemical study using MIC2 and anti-inhibin antibodies. CONCLUSIONS: The presence of minor sex cord elements, morphologically or by immunohistochemistry, suggests that these fibromatous tumors are related to and are a subset of sex cord-stromal tumors. Intratesticular fibromatous tumors, of which 11 other cases lacking sex cord elements have been reported, could be considered as the testicular equivalent of ovarian fibroma. These tumors could then be referred to as testicular fibroma of gonadal stromal origin, with or without minor sex cord component.

Adolescent↗
PubMed1999

[Renal medullary carcinoma, a new clinico-pathological entity. Immunohistochemical, ultrastructural, flow cytometric and cytogenetic study of a case].

The renal medullary carcinoma is a rare tumor. We report a case in a black patient with sickle cell trait. The tumor was located in the lower pole of the left kidney. It had a tubular and microcystic architecture. It was composed of large eosinophilic cells with vesicular nuclei containing prominent nucleoli, in a desmoplastic and inflammatory stroma. By immunohistochemistry, the tumoral cells were positive for cytokeratin and Ulex europaeus lectin. Electron microscopy revealed small intracytoplasmic lumina with microvilli. The flow cytometric study showed DNA-multiploidy. The cytogenetic study revealed tetraploidy without structural abnormality. The renal medullary carcinoma is often reported in young black patients with sickle cell trait. Its microscopic, immunohistochemical and ultrastructural features favor its identification as a particular variety of Bellini duct carcinoma. Its link with sickle cell trait has to be defined.

Adult↗
PubMed1999

[Tissue reactions to wear debris of joint prostheses. Diagnostic problems. Apropos of 2 cases].

We report two cases of tissue reactions to wear debris after large joint prostheses. In the first case, a septic loosening of a hip arthroplasty was suspected after emergence of an inguinal mass. In the second case, a patient with loose hip prosthesis had surgery for a prostatic adenocarcinoma and pelvic lymph nodes were discovered during surgery. They were first suspected to be metastatic carcinoma. These two diagnostic problems were resolved by histology which revealed sinusal histiocytic reaction to wear debris. The peculiar sign of this reaction is the presence of birefringent components such as polyethylene seen with polarized light. These problems will become more frequent in the future because of the increasing number of elderly patients who have had hip replacement and will undergo surgery for pelvic cancer. A close medico-surgical collaboration should help pathologists in such cases.

Adenocarcinoma↗
PubMed1999

[Palmar localization of epithelioid sarcoma mimicking Dupuytren's disease].

A case of epithelioid sarcoma localized in the palm of the left hand in a 32-year-old woman is reported. The tumor evolved for many years, clinically and microscopically simulating palmar fibromatosis. Epithelioid sarcoma is an uncommon malignant tumor, often misdiagnosed by surgeons and pathologists. It occurs in young patients and is often localized at the upper distal extremity. Microscopically, epithelioid sarcoma shows nodules manifesting fibrous hyaline cores with central necrosis. It contains epithelioid and spindle cells immunoreactive to keratin, epithelial membrane antigen and vimentin. Recurrences, lymph node metastases and lung metastases are frequent. Surgical literature tends to recommend wide "en bloc" excision or amputation, combined or not with adjuvant radiation therapy.

Adult↗
PubMed1998

[A case of hyalinizing spindle cell tumor with giant rosettes in the presacral region. Immunohistochemical and ultrastructural study].

Hyalinizing spindle cell tumor with giant rosettes is a slowly growing tumor with a risk of local recurrence in case of incomplete surgical excision that could be regarded as a distinctive type of low-grade fibroblastic tumor. We report a case involving the presacral area. This tumor was composed of areas of bland spindle cell proliferation with a fascicular pattern in a fibrous or myxoid stroma, intermixed with giant rosettes consisting of rounded cells surrounding a central collagen core. The tumor expressed vimentin, and, for cells comprising the rosettes, S-100 protein, NSE and CD-57. These latter cells exhibited ultrastructural features of Schwann cells, the tumoral cells of fascicular area exhibiting features of fibroblastic cells. Flow cytometry showed DNA-aneuploidy and a very low S-phase fraction. This tumor appeared to be composed of two cellular components, fibroblastic and Schwann cells, located, at the opposite of neurofibroma, in two distinct areas.

Aneuploidy↗