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Biomedical subjects

P A van Dam

Publications and source records attributed to P A van Dam.

At least 19 recordsLinked to original sources
PubMed2001

The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer.

OBJECTIVE: The present study was designed to analyse the relationship between apoptosis related proteins (bcl-2 and bax), tumour suppressor protein p53, proliferation markers (PCNA and mitotic index), human papillomavirus (HPV) and angiogenesis in cervical cancer and their impact on clinical outcome. STUDY DESIGN: Tumours from 111 patients were assessed by immunohistochemistry for the expression of bcl-2, bax, p53 and PCNA, by PCR for the presence of HPV-DNA, for the quantification of the mitotic index and the microvessel density (CD 31). The results were correlated with various histopathologic characteristics and survival. RESULTS: The multiple Cox's regression analysis for overall survival of all prognostic variables gave as best model: bcl-2 (P<0.001), lymphovascular permeation (P=0.004), mitotic index (P=0.019), tumour grade (P=0.048) and FIGO stage (P=0.070). Subanalysis was performed for the patients where the lymph node status was known (n=79). Adding the lymph node status gave as best model for overall survival bcl-2 (P=0.001), lymphovascular permeation (P=0.003) and mitotic index (P=0.044). However, they hardly influenced the association. CONCLUSION: In the apoptotic pathway of cervical cancer, bcl-2 is one of most important proteins. It can probably not only mediate cell death but also regulate cell growth. A better understanding of their relations will probably provide the basis for more rational cancer therapies in the future.

Adult↗
PubMed1999

Epithelioid sarcoma of the vulva.

We report a case of a 23-year-old woman diagnosed as having an epithelioid sarcoma of the vulva. She was treated by a clitoris-sparing hemivulvectomy and lymph node sampling of the ipsilateral groin. Vulvar reconstruction was performed with a rectus abdominis myocutaneous flap. Four years after the operation there is no evidence of disease and the patient has a normal sex life. The English literature on this subject is reviewed with special attention to the biological behavior and therapeutic approach.

Adult↗
PubMed1999

Trocar implantation metastasis after laparoscopy in patients with advanced ovarian cancer: can the risk be reduced?

OBJECTIVE: The purpose of this study was to determine risk factors for trocar implantation metastasis after diagnostic laparoscopy in patients with primary or recurrent advanced ovarian cancer. STUDY DESIGN: Eighty-three women with primary advanced ovarian cancer and 21 women with recurrent ovarian cancer undergoing a laparoscopy for a tissue diagnosis and for assessment of operability were included in the study. The occurrence of implantation metastasis at the trocar incision scars was analyzed according to clinicopathologic characteristics. RESULTS: A recurrence developed at the trocar site in 7 (58%) of 12 patients undergoing a laparoscopy in which only the skin was closed at the end of the procedure and in 2 (2%) of 92 patients undergoing a laparoscopy with closure of all layers (odds ratio, 63; 95% confidence interval, 10.3-385; P <.001). The International Federation of Gynecology and Obstetrics stage at initial presentation, tumor histologic type, tumor differentiation, maximal tumor diameter at the time of diagnosis, estimated weight of the metastatic tumor, residual tumor after cytoreductive surgery, surgical characteristics, and type of chemotherapy were well balanced among both groups. Patients with implantation metastasis had significantly more ascites (median, 700 mL vs 300 mL; P =.032) and a longer interval between the start of platinum-based chemotherapy or cytoreductive surgery (median, 6 days vs 17 days; P <.01) compared with patients without abdominal wall recurrence. A palpable abdominal wall metastasis developed in none of the patients undergoing a laparoscopy with closure of all layers of the abdomen followed by cytoreductive surgery or chemotherapy within 1 week after the laparoscopy. Kaplan-Meier survival analysis showed that patients with abdominal wall implantation metastasis had a survival rate similar to that of the other patients. CONCLUSIONS: Laparoscopy with careful closure of the peritoneum, rectus sheath, and skin followed by chemotherapy or cytoreductive surgery with excision of the trocar trajectories within 1 week is safe in patients with disseminated ovarian cancer.

Abdominal Muscles↗
PubMed1999

Vaccination with HPV16 peptides of patients with advanced cervical carcinoma: clinical evaluation of a phase I-II trial.

A phase I-II clinical trial was performed involving vaccination with HPV16 E7 peptides of patients suffering from HPV16 positive cervical carcinoma which was refractory to conventional treatment. Patients receiving the vaccine were HLA-A*0201 positive with HPV16 positive cervical carcinoma. The clinical trial was designed as a dose-escalation study, in which successive groups of patients received 100 micrograms, 300 micrograms or 1000 micrograms of each peptide, respectively. The vaccine consisted of two HPV16 E7 peptides and one helper peptide emulsified in Montanide ISA 51 adjuvant. 19 patients were included in the study, no adverse side-effects were observed. 2 patients showed stable disease for 1 year after vaccination; 15 patients showed progressive disease of whom 1 died during the vaccination treatment due to progressive disease; and 2 patients showed tumour-regression after chemotherapy following vaccination. A relative low count of lymphocytes before and after vaccination was present in 11/19 patients indicating that these patients were immunocompromised. This study shows that HPV16 E7 peptide vaccination is feasible, even in a group of patients with terminal disease. This paves the way for vaccinating patients with less advanced disease, whose immune system is less compromised by progressive disease.

Adult↗
PubMed1996

Ultraradical debulking of epithelial ovarian cancer with the ultrasonic surgical aspirator: a prospective randomized trial.

OBJECTIVE: Our purpose was to evaluate the effectiveness, benefits, and potential side effects of the use of the cavitational ultrasonic surgical aspirator for cytoreduction of advanced ovarian cancer. STUDY DESIGN: Forty patients with stage IIC to IV ovarian carcinoma were randomized to undergo ultraradical cytoreductive surgery with (group 1, 20 patients) or without (group 2, 20 patients) the use of the CUSA 200 cavitational ultrasonic surgical aspirator (Valleylab, Boulder, Colo). Preoperative and postoperative information and follow-up data were collected prospectively and compared between both groups. RESULTS: The amount of residual tumor after debulking surgery, the duration of the operation, and the rate of perioperative complications were comparable in both study groups. The amount of perioperative blood loss was significantly lower (1450 ml vs 1650 ml, p=0.02) in group 1. These patients had less morbidity (p<0.05), and could be discharged from the hospital significantly sooner (14 days vs 16 days, p=0.031). CA 125 levels 1 and 2 months after surgery were significantly lower in the group with cavitational ultrasonic surgical aspirator (p<0.01 and p<0.01, respectively), suggesting more successful cytoreduction. However, this is not reflected in a better disease-free or overall survival. CONCLUSION: Cavitational ultrasonic surgical aspirator-assisted cytoreductive surgery of advanced ovarian carcinoma is more effective in eradicating disease, reduces morbidity, and is cost beneficial.

Aged↗
PubMed1995

Primary extrauterine müllerian adenosarcoma of the peritoneum.

A case of an extrauterine Müllerian adenosarcoma of the pelvic peritoneum is described. The patient, a 16-year-old girl, presented with abdominal distension and pain. At laparotomy, a tumor was found originating from the left pelvic side wall. Light microscopic examination revealed a Müllerian adenosarcoma. Postoperatively she was treated with polychemotherapy. Seventy months after initial presentation she is still free of tumor.

Adenosarcoma↗
PubMed1995

Prognostic value of bcl-2 expression in invasive breast cancer.

Expression of the bcl-2 proto-oncogene was studied immunohistochemically in 251 invasive ductal breast carcinomas (median follow-up time 91 months, range 24-186 months) and the results were correlated with clinicopathological data and prognostic variables. Sixty-three (25%) tumours were scored bcl-2 negative and 188 (75%) tumours were bcl-2 positive. No relationship could be observed between bcl-2 status and tumour grade, pTNM staging or menopausal status. A strong positive relationship was demonstrated between bcl-2 immunoreactivity and oestrogen receptor status (P < 0.001) and progesterone receptor status (P < 0.001). No prognostic value was demonstrated for bcl-2 expression on disease-free survival and overall survival in axillary node-negative breast cancer patients. However, in axillary node-positive breast cancer patients multivariate analysis demonstrated absence of bcl-2 expression to be independently related to shortened disease-free survival (P = 0.003) and shortened overall survival (P < 0.001). Our results suggest a potential important role for bcl-2 expression as a modulator of response to adjuvant therapy in breast cancer.

Adult↗
PubMed1995

Immunohistochemical study of topoisomerase II-alpha expression in primary ductal carcinoma of the breast.

AIMS: To study the patterns of expression of topoisomerase II-alpha in primary invasive ductal breast carcinomas; to correlate this expression with clinicopathological data and prognosis. METHODS: Cryostat sections from 63 primary invasive ductal breast carcinomas were stained immunohistochemically for topoisomerase II-alpha. Nuclear immunoreactivity was quantified by counting at least 500 cells in different random fields and results were expressed as per cent of cells staining positively for topoisomerase II-alpha. RESULTS: Topoisomerase II-alpha nuclear immunoreactivity (median 14% of nuclei; range 2-62%) was detected in all tumours with highly variable intertumour and intratumour nuclear reactivity. Higher levels of topoisomerase II-alpha expression were strongly related to higher tumour grade, larger tumour size, nodal status, and the presence of distant metastases at diagnosis. No correlation was found with menopausal status, steroid hormone receptor status, disease free survival, or overall survival. CONCLUSIONS: Expression of topoisomerase II-alpha is related to the presence of poor prognostic factors. Immunohistochemical assessment of topoisomerase II-alpha expression in breast cancer could be potentially useful for tailoring chemotherapy with topoisomerase II inhibitors.

Adult↗
PubMed1994

Is there an increased risk for tumor dissemination using ultrasonic surgical aspiration in patients with vulvar carcinoma?

The ultrasonic surgical aspirator (USA) is a new surgical instrument that allows precise and selective tissue dissection. Ultrasonic cell destruction is combined with continuous irrigation causing a cloud of fine droplets, which sometimes contains viable tumor cells, hanging above the operative field. We present a patient who developed massive recurrent vulvar carcinoma in the subcutaneous tissue in the proximity of the incisions of the vulva and both groins 3.5 months after a USA-assisted radical vulvectomy and inguinal lymphadenectomy. The atypical pattern of recurrence in the entire operative field suggests that tumor cells might have been spread by the irrigation fluid of the USA. Further investigation is needed to assess the risk of tumor dissemination with USA before the instrument can be used safely in patients with early cancer.

Carcinoma, Squamous Cell↗
PubMed1994

Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma.

AIMS: To assess whether the overexpression of five dominant oncogene encoded proteins is crucial to the pathogenesis of ovarian carcinoma and whether this provides any useful prognostic information. METHODS: The expression of the insulin-like growth factor 1 receptor (ILGFR 1), epidermal growth factor receptor (EGFR), and the c-erbB-2, c-ras, and c-myc products was studied by multiparameter flow cytometry in 80 patients with epithelial ovarian cancer for whom long term follow up was available. RESULTS: Overexpression of ILGFR 1, EGFR, c-erbB-2, c-ras and c-myc was found in, respectively, nine of 80 (11%), 10 of 80 (12%), 19 of 80 (24%), 16 of 80 (20%) and 28 of 80 (35%) ovarian carcinomas. The levels of expression of ILGFR 1, EGFR, c-erbB-2 and c-ras were significantly higher in the tumours of patients with recurrent or persistent disease after chemotherapy than in the tumours of patients at initial presentation (p < 0.02). Multivariate analysis showed that residual tumour (p < 0.001), FIGO stage (p = 0.002), EGFR overexpression (p = 0.030) and previous chemotherapy (p = 0.034) were independent variables for predicting survival. CONCLUSIONS: Overexpression of these oncoproteins only occurs in a small proportion of ovarian carcinomas but may have an important role in the progression of the disease.

Carcinoma↗
PubMed1992

Comparative evaluation of fresh, fixed, and cryopreserved solid tumor cells for reliable flow cytometry of DNA and tumor associated antigen.

Five different protocols for the short-term preservation of cells used for multiparameter flow cytometric assay of tumour associated antigens (TAA) and DNA were assessed in cell suspensions prepared by mechanical disaggregation of 15 gynecological tumors. The protocols at 4 degrees C were 1) storage in buffer, 2) storage in 50% methanol, and 3) storage in buffer after formalin fixation. Tissues were also cryopreserved as cell suspensions and tissue blocks. When the TAA expression and DNA histograms of the preserved cells were compared with those in fresh cell suspensions, cryopreservation was found to be the best method: TAA expression was well preserved and there was a good correlation between TAA expression and the quality of the DNA histograms, respectively, in fresh and cryopreserved cells (RS: 0.82-0.91, P less than 0.001 for all TAAs). The cell suspensions preserved at 4 degrees C all showed a significant increase in background fluorescence (P less than 0.05) and a reduction in the TAA specific fluorescence (P less than 0.011). Methanol fixation was better than buffered formalin for the proteins studied, though both gave significantly worse results than cryopreservation. The quality of these cell suspensions and the correlation with TAA measurements in fresh cell suspensions deteriorated progressively with time, particularly if they were stored more than a week.

Antigens, Neoplasm↗
PubMed1992

Flow cytometry.

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Cell Division↗
PubMed1992

Flow cytometric measurement of cell components other than DNA: virtues, limitations, and applications in gynecologic oncology.

Flow cytometry is a high-precision technique for rapid analysis and sorting of cells and particles. In theory, it can be used to measure any cell constituent, provided that a fluorescent tracer is available that reacts specifically and stoichiometrically with that constituent. The technique provides statistical accuracy, reproducibility, and sensitivity and allows simultaneous measurement of several constituents on a cell-to-cell basis. The main drawback of flow cytometry is the lack of visual control and structural information in solid tissues. Careful sample preparation, quality control of all staining and instrumentation procedures, and the use of immunohistologic or cytologic controls are essential for high-quality flow cytometric analysis. The technique has been used successfully for simultaneous measurement of DNA and tumor-associated antigens, oncogene products, proliferation markers, and markers for multidrug resistance in cultured cell lines and in cell suspensions prepared from solid tumors and cervical smears. Flow cytometry has the potential to play an important role in the study of carcinogenesis. With an appropriate panel of monoclonal antibodies, the technique can be used for screening, "biochemical" diagnosis of neoplasia, and rapid drug, hormone, and radiotherapy sensitivity tests.

Biomarkers, Tumor↗
PubMed1991

Multi-parameter flow cytometric quantitation of the expression of the tumor-associated antigen SM3 in normal and neoplastic ovarian tissues. A comparison with HMFG1 and HMFG2.

SM3 is a monoclonal antibody that reacts with a peptide epitope in the core protein of polymorphic epithelial mucin. Multi-parameter flow cytometry was used to characterize the expression of SM3 and compare it with two related tumor-associated antigens, HMFG1 and HMFG2, in cell suspensions of 44 malignant ovarian tumors, 15 benign ovarian tumors, and 16 normal ovaries. Tumor-associated antigen expression was significantly higher in malignant ovarian neoplasms than in benign neoplasms (P less than 0.001 for all three antigens). SM3 was expressed more specifically in malignant than benign tumors but had a lower affinity than HMFG1 and HMFG2. Multi-parameter flow cytometric evaluation of a panel of monoclonal antibodies can be used to help in choosing the best antibody for immunohistochemistry, imaging, and eventually treatment of ovarian tumors.

Antibodies, Monoclonal↗
PubMed1991

DNA ploidy and the expression of tissue-carcinoembryonic antigen in grade III carcinoma of the breast.

A series of 50 Stage I and II, Grade III ductal carcinomas of the breast was characterized by DNA flow cytometry and further analyzed with a monoclonal antibody for carcinoembryonic antigen (CEA). The antigen was detected with the indirect immunoperoxidase technique on paraffin sections and on cytologic smears of the cell suspensions that were used for flow cytometric DNA analysis. A significant higher incidence of CEA-positivity in cytologic smears and tissue sections was found in DNA-diploid tumors (13/18 and 12/18, respectively) than in DNA-aneuploid tumors (13/22 and 12/32, respectively) (P less than 0.05 and P less than 0.025, respectively).

Breast Neoplasms↗