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Biomedical subjects

H R Franke

Publications and source records attributed to H R Franke.

15 recordsLinked to original sources

Differential effects of bisphosphonates on breast cancer cell lines.

Bisphosphonates may induce direct anti-tumor effects in breast cancer cells in vitro. In this study, six bisphosphonates were administered to three breast cancer cell lines. Cell proliferation was measured by quantification of the expression of Cyclin D1 mRNA. Apoptosis was determined by flow cytometry of a DNA fragmentation assay. We demonstrated that bisphosphonates have direct effects on cell proliferation and apoptosis in different breast cancer cell lines. However, not all bisphosphonates act equally on breast cancer cells in vitro. Zoledronate seems to be the most potent of the six bisphosphonates. This in vitro study showed that bisphosphonates possess promising anti-tumor potential.

Alendronate↗

Apoptosis and proliferation in breast cancer cells, cultured in vitro: effects of SERMs.

OBJECTIVE: Selective estrogen receptor modulators (SERMs) decrease the risk of developing breast cancer. As an antagonistic effect, SERMs may aggravate or induce climacteric symptoms. Hormone therapy (HT) would be able to alleviate these symptoms. The present in vitro study tries to elucidate the effects of several HT preparations combined with SERMs on estrogen receptor-positive (ER +) (i.e. MCF-7 and T-47D) and -negative (ER-) (i.e. MDA-MB-231) human breast cancer cells in vitro. METHODS: We performed experiments with various HT preparations (estradiol (E2)/E2 + progesterone/E2 + dihydrodydrogesterone /E2 + norethisterone acetate/E2 + medroxyprogesterone acetate/tibolone) in the concentration of 10(-6) mol/l together with SERMs (raloxifene or tamoxifen) added to different breast cancer cell lines in vitro. After an incubation period of 144 h, proliferation and apoptosis were measured. The first was measured by quantification of the expression of cyclin D1 mRNA, the latter by the Nicoletti method. RESULTS: This in vitro study clearly demonstrates differences in results if various HT preparations, combined with SERMs, are added to ER + and ER- breast cancer cell lines. CONCLUSIONS: Adding estradiol/progestogens in combination with a SERM to estrogen receptor-positive breast cancer cell lines does not obligatorily lead to proliferation of tumor cells. Not all progestogens act equally.

Apoptosis↗

In vitro effects of estradiol, dydrogesterone, tamoxifen and cyclophosphamide on proliferation vs. death in human breast cancer cells.

The effects of 17 beta-estradiol, dihydrodydrogesterone, tamoxifen and cyclophosphamide upon parameters of cell maturation (Mucine1 expression), cell proliferation (Cyclin D1 expression) and apoptosis (loss of nuclear DNA) were studied in estrogen receptor positive (ER+) and negative (ER-) human breast cancer cells. Tamoxifen was the most potent inducer of apoptosis in ER+ and ER- breast cancer cells. 17 beta-estradiol in a concentration of 10(-6) M induced proliferation in ER+ cells after 144 h. incubation, while equimolar co-incubation with dihydrodydrogesterone prevented this effect and even induced a significant increase of cell death. It is speculated that the continuous use of combined 17 beta-estradiol plus dihydrodydrogesterone might be given as hormone replacement therapy without increased risk of breast cancer and even may reduce the relapse rate in breast cancer patients.

Antineoplastic Agents, Alkylating↗

A randomized placebo-controlled study of the effect of transdermal vs. oral estradiol with or without gestodene on homocysteine levels.

OBJECTIVE: To assess the effect of transdermal vs. oral administration of E2 on plasma homocysteine levels and to evaluate the impact of adding a progestogen to these regimens. DESIGN: Prospective, double-blind, double-dummy, placebo-controlled study. SETTING: Outpatient clinics in two university hospitals and two teaching hospitals in The Netherlands. PATIENT(S): One hundred fifty-two healthy hysterectomized postmenopausal women. INTERVENTION(S): Thirteen 28-day treatment cycles with placebo (n = 49); transdermal 17beta-E2, 50 microg (n = 33), oral E2, 1 mg (n = 37), or oral E2, 1 mg, plus gestodene, 25 microg (n = 33), followed by four cycles of placebo in each group. MAIN OUTCOME MEASURE(S): Fasting plasma total homocysteine concentrations at baseline and cycle 4, 13, and 17. RESULT(S): Mean (+/-SD) homocysteine concentrations in the oral E2 group decreased from baseline to cycle 4 (9.0 +/- 2.5 micromol/L vs. 8.2 +/- 2.0 micromol/L; mean change, -7.6%). Homocystine values in the oral E2 plus gestodene group did not change substantially from baseline to cycle 4 (8.9 +/- 1.6 micromol/L vs. 8.6 +/- 2.0 micromol/L; mean change, -4.4%). No significant changes were observed in the transdermal E2 group. After four washout cycles, the homocysteine concentration had returned to baseline values in all groups. CONCLUSION(S): Oral E2 therapy reduced the homocysteine concentration more than did therapy with transdermal E2 or oral E2 plus gestodene. This finding may indicate a role of liver metabolism and suggests that gestodene has a negative effect on these changes.

Administration, Cutaneous↗

Gonadotropin-releasing hormone agonist plus "add-back" hormone replacement therapy for treatment of endometriosis: a prospective, randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effect of add-back therapy with continuous combined estrogen-progestin on the GnRH agonist-induced hypoestrogenic state and its effectiveness in healing of endometriotic lesions. DESIGN: A prospective, randomized, placebo-controlled, double-blind trial. SETTING: Multiple centers in The Netherlands. PATIENT(S): 41 premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Society scores >/=2). INTERVENTION(S): Patients were randomly assigned to receive a subcutaneous depot formulation of goserelin, 3. 6 mg, every 4 weeks, plus oral placebo or oral continuous combined estradiol-norethisterone acetate add-back therapy daily for 24 weeks. MAIN OUTCOME MEASURE(S): Endometriosis response, bone mineral density, transvaginal ultrasonographic changes, endocrinologic effects, and subjective side effects. RESULT(S): The number of endometriotic implants was significantly reduced in both groups. In the group that received GnRH agonist plus placebo, bone mineral density of the lumbar spine decreased by 5.02%. CONCLUSION(S): The effectiveness of GnRH agonist treatment for endometriosis was not decreased by the addition of add-back continuous combined hormone replacement therapy. Bone mineral density of the lumbar spine was maintained and subjective side effects were diminished.

Adult↗

Endocervical curettage by Vabra aspiration as part of colposcopic evaluation.

Endocervical curettage as routine part of colposcopic examination in patients with abnormal cervical cytology is recommended by many experts. Endocervical curettage (ECC) by Vabra aspiration has never been reported in literature. The results of Vabra ECC in 103 patients are analyzed and compared to the results of a second endocervical specimen, obtained by conventional curettage, cone biopsy, or hysterectomy. An accordance of over 98% is demonstrated and the difference is discussed. In 88% and 71% adequate Vabra ECC specimens were available for cytological and histological examination, respectively. In any patient at least one result was present. Both cytological and histological specimens are of reliable quality. No cases of invasive (adeno)carcinoma were missed. In addition, the results are compared to literature data concerning Vabra aspiration for endometrial disease and ECC by other techniques. Vabra ECC is considered an efficient, safe, and well-tolerated diagnostic outpatient method and recommended as a standard part of colposcopic evaluation.

Adult↗

Invasive mole.

A case of persistent trophoblastic disease with resistance to chemotherapy is presented. The value of continued and frequent serum hCG measurements in such cases is discussed as well as the indications for performing hysterectomy.

Adult↗

Quantitative morphology. A study of the trophoblast.

It is difficult to predict the possible development of a malignant trophoblastic tumor after the evacuation of a hydatidiform mole. In order to help resolve this difficulty, a morphometric study has been carried out. The mean nuclear area of the trophoblast in a group of hydatidiform moles, followed by a trophoblastic malignancy, was found to be statistically significantly larger than that of the trophoblast in a group of hydatidiform moles which were not followed by malignant trophoblastic disease. However, the mean trophoblast/nontrophoblast ratio in villi demonstrated no statistically significant difference between those 2 groups of hydatidiform moles. Therefore it is not advisable to grade hydatidiform moles on the basis of trophoblastic proliferation alone. It is suggested that the trophoblastic lining of hydropic villi in the placental tissue of hydatidiform moles has malignant features already, but these are more pronounced in those hydatidiform moles which are subsequently followed by a choriocarcinoma.

Choriocarcinoma↗

Epidemiologic features of hydatidiform mole in the Netherlands.

The presented study is a report of epidemiologic data collected between 1978 and 1980 from patients with gestational trophoblastic disease in the Netherlands. Review of curettings from 344 patients with hydatidiform mole and 33 patients with partial mole resulted in review diagnoses of hydatidiform mole in 283 women, of partial mole in 25 women, and of mere hydropic degeneration in 69 women. Upon review of the initial diagnosis of complete and partial hydatidiform mole, 18% of the cases were considered false-positive. After the evacuation of a molar pregnancy, 10% of the patients needed chemotherapy because of the diagnosis of persistent trophoblastic disease. In patients with a review diagnosis of hydropic degeneration, this was never necessary.

Adolescent↗

Plasma human chorionic gonadotropin disappearance in hydatidiform mole: a central registry report from the Netherlands.

The disappearance time of serum human chorionic gonadotropin (hCG) after the evacuation of hydatidiform mole, partial mole, and hydropic degeneration was investigated. A statistically significant difference existed between the disappearance time of serum hCG after the evacuation of hydatidiform mole as compared with partial mole and hydropic degeneration. The average disappearance time of serum hCG after hydatidiform mole was 99.3 days, after partial mole 58.9 days, and after hydropic degeneration 50.7 days. It is not recommended to start chemotherapy for persistent trophoblastic disease before 100 days after the evacuation of hydatidiform mole, provided there is a steady downward course of the serum hCG level. It is advised to submit cases of supposed hydatidiform and partial moles to a tissue committee for a second opinion.

Chorionic Gonadotropin↗