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Biomedical subjects

R Blom

Publications and source records attributed to R Blom.

10 recordsLinked to original sources
PubMed2000

Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results.

BACKGROUND: A randomized trial conducted by the Gynecologic Oncology Group (GOG, study #111) in the United States showed a better outcome for patients with advanced ovarian cancer on the paclitaxel-cisplatin regimen than for those on a standard cyclophosphamide-cisplatin regimen. Before considering the paclitaxel-cisplatin regimen as the new "standard," a group of European and Canadian investigators planned a confirmatory phase III trial. METHODS: This intergroup trial recruited 680 patients with broader selection criteria than the GOG #111 study and administered paclitaxel as a 3-hour instead of a 24-hour infusion; progression-free survival was the primary end point. Patient survival was analyzed by use of the Kaplan-Meier technique. Treatment effects on patient survival were estimated by Cox proportional hazards regression models. All statistical tests were two-sided. RESULTS: The overall clinical response rate was 59% in the paclitaxel group and 45% in the cyclophosphamide group; the complete clinical remission rates were 41% and 27%, respectively; both differences were statistically significant (P =.01 for both). At a median follow-up of 38.5 months and despite a high rate of crossover (48%) from the cyclophosphamide arm to the paclitaxel arm at first detection of progression of disease, a longer progression-free survival (log-rank P =.0005; median of 15.5 months versus 11.5 months) and a longer overall survival (log-rank P =. 0016; median of 35.6 months versus 25.8 months) were seen in the paclitaxel regimen compared with the cyclophosphamide regimen. CONCLUSIONS: There is strong and confirmatory evidence from two large randomized phase III trials to support paclitaxel-cisplatin as the new standard regimen for treatment of patients with advanced ovarian cancer.

Adult↗
PubMed2000

Stem cell factor and interleukin-4 increase responsiveness of mast cells to substance P.

The response of mast cells (MC) to non-IgE-mediated stimulation is critically dependent on the population of MC examined. The neuropeptide Substance P (SP) has been reported to activate connective tissue-type MC (CTMC), while mucosal MC (MMC) are not activated by SP. We examined the effect of stem cell factor (SCF) plus interleukin-4 (IL-4) on SP-initiated activation of bone marrow-derived MC (BMMC). Mouse MC, derived from a culture of BM cells with IL-3, were subsequently treated with recombinant SCF plus IL-4 for 6 days. Responsiveness to SP was monitored measuring beta-hexosaminidase and lipid mediator release. Histochemical staining, histamine analysis, and granule protease expression were achieved to characterize the cells. In contrast to IL-3 grown cells, SCF/IL-4-exposed cells showed functional responsiveness to release beta-hexosaminidase (42.25% +/- 1.46% at SP concentration of 100 microM) and produce leukotriene C(4) (LTC(4)) (7.4 +/- 1.5 ng/10(6) cells)/prostaglandin D(2) (PGD(2)) (2.0 +/- 0.3 ng/10(6) cells) upon stimulation by SP. The increase in sensitivity of the cells to SP was not due to differentiation into CTMC, as the cells remained heparin negative. Both SCF and IL-4 were needed because SCF or IL-4 alone were insufficient to keep cells viable after 3 to 4 days post coculture. SP-induced secretion from BMMC cultured in medium containing SCF plus IL-4 (25.76% +/- 1.83%) was higher in comparison with cells cultured with SCF plus IL-3 (8.85% +/- 0.68%).These findings indicate that temporal changes in cytokine expression can influence the sensitivity of MC to non-immunologic stimuli. Local cytokine production leading to an increase in MC responsiveness to SP and inducing secretion of granule content and lipid generation may, therefore, propagate and worsen inflammatory conditions.

Animals↗
PubMed1998

Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases.

AIM: The authors analyzed in a retrospective manner the prognostic significance of p53 and mdm-2 expression, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathological prognostic factors in patients with uterine leiomyosarcomas. MATERIAL: Forty-nine patients were diagnosed with uterine leiomyosarcoma (25 stage I, 4 stage II, 8 stage III, and 12 stage IV). DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors. RESULTS: Of the 49 patients, 35 (71%) died of disease and 2 died of intercurrent disease. The 5-year survival rate was 33%. FIGO surgical stage, DNA ploidy, SPF, mitotic index, cellular atypia, and tumor grade obtained significance (P < 0.05) in a univariate survival analysis of the leiomyosarcomas. In a multivariate analysis with survival as the end point, stage was found to be the most important factor (P = 0.007); DNA ploidy (P = 0. 045) and SPF (P = 0.041) also had independent prognostic significance. For FIGO stage I tumors, DNA ploidy (P = 0.04) and tumor grade (P = 0.01) were statistically significant in a univariate analysis, while only grade had independent prognostic significance (P = 0.01) in a multivariate analysis. In a univariate analysis including only FIGO stage I and II tumors with disease-free survival as the end point, p53 overexpression (P = 0.0016), DNA ploidy (P = 0.042), and tumor grade (P = 0.008) obtained significance. In a multivariate analysis, only p53 had independent statistical significance (P = 0.01). All p53 immunopositive stage I-II tumors recurred within 28 months from diagnosis. CONCLUSION: This study found that stage represents the most important prognostic factor for uterine leiomyosarcomas. DNA ploidy and SPF had independent prognostic value. DNA flow cytometry is useful in gaining additional prognostic information. In stage I patients, tumor grade gives significant information regarding clinical outcome. In addition, p53 overexpression may predict a higher risk of recurrence in early stage leiomyosarcomas.

Cell Cycle↗
PubMed1998

Malignant mixed Müllerian tumors of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 44 cases.

AIM: The authors retrospectively analyzed the prognostic significance of p53, mdm-2, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathologic factors in patients with malignant mixed Müllerian tumors (MMMT) of the uterus. METHODS: Between 1970 and 1995, 44 uterine tumors were diagnosed as MMMT (21 stage I, 2 stage II, 10 stage III, and 11 stage IV). Thirty-two were homologous type and 12 were heterologous type. DNA flow cytometry and immunohistochemical analysis for p53 and mdm-2 overexpression were performed on paraffin-embedded archival tissue. RESULTS: 68% of the tumors were nondiploid and 61% had an SPF greater than 10%. Sixty-one percent overexpressed p53 and 25% were mdm-2-positive. Furthermore, 91% of the tumors had a mitotic count greater than 10/10 hpf and 95% had high-grade cytologic atypia. Twenty-seven (61%) patients died of tumor and 6 (14%) died of intercurrent disease. Eleven (25%) patients are alive with no evidence of disease. The median follow-up for patients still alive was 59 months (range, 28-178 months). The overall 5-year survival rate was 38%. In a univariate analysis that included stage, histologic type, DNA ploidy, SPF, p53, mdm-2, mitotic index, and age, and with survival as the end point, only stage reached statistically prognostic significance. CONCLUSION: The majority of the tumors had obvious signs of aggressiveness such as high grade, high mitotic count, nondiploid pattern, high SPF, and overexpression of p53. This study found that stage is the most important prognostic factor for survival in MMMTs of the uterus.

Aged↗
PubMed1996

Paclitaxel (Taxol) monotherapy in the treatment of progressive and recurrent ovarian carcinoma after platinum-based chemotherapy.

This retrospective study evaluates paclitaxel (Taxol) monotherapy in the treatment of advanced ovarian cancer, previously treated with cisplatin. Forty-six patients with FIGO stage IC to IV were given Taxol in doses of 175 mg/m2 and 135 mg/m2 as a 3-h continuous infusion. All patients were given premedication (prednisone, clemastin, cimetidine) to prevent hypersensitivity reactions. One allergic reaction was observed. Thirty-nine patients showed progress of their disease during treatment and seven showed a response (overall response rate 15.2%; 95% c.i. 4.8-25.6%). There were five total (10.9%) and two partial responses. Among 20 patients who had progressed during or within 6 months of prior cisplatin-based therapy two were responders and two showed partial response (10%). Among 26 patients who had responded to cisplatin but suffered recurrence more than 6 months after cisplatin treatment, there were five total responders (19.2%). We conclude that Taxol treatment does not alter the fact that advanced ovarian carcinoma still carries a grave prognosis. Taxol monotherapy treatment of patients not responding to first line platinum treatment or having relapse within six months of completed therapy, seems to have a limited effect. For those patients responding to the first line platinum treatment that lasts for at least six months the effect of Taxol treatment is more encouraging.

Adult↗
PubMed1993

Death rate and recurrence pattern among 841 clinical stage I endometrial cancer patients with special reference to uterine papillary serous carcinoma.

Eight hundred thirty-nine clinical stage I endometrial carcinoma patients diagnosed between 1979 and 1988 were treated at the University Hospital in Linköping. Forty-two (5%) had uterine papillary serous carcinoma of which 52% died of their disease. The recurrence rate, defined as new evidence of disease 6 months or more after termination of the initial treatment, was 31% among the UPSC patients compared to 6% in the non-UPSC group. The site of recurrence also differed significantly between the two groups, with the abdomen as the most common site among UPSC patients (46%) and the vagina (34%) among the ordinary adenocarcinoma patients. All UPSC patients with recurrence died of their malignancy compared to 61% of the ordinary adenocarcinoma patients. Ninety percent of isolated vaginal recurrences in ordinary adenocarcinoma patients (17) were diagnosed at a scheduled outpatient checkup. Of these, 13 are alive with no known disease after treatment.

Adenocarcinoma↗
PubMed1989

Successful hemisterilization in a patient with uterus didelphus.

Women with uterine malformations frequently present with reproductive impairment. This case addresses the opposite problem, a woman with uterus didelphus who conceived with ease. Following three consecutive cesarean sections in the left uterine horn, she was offered sterilization for medical reasons, but refused on religious grounds. As a compromise, she accepted unilateral tubal closure in order to force future pregnancies to the right uterine horn. She has now had three pregnancies with two cesarean sections on that side.

Adult↗
PubMed1988

Primary hepatic pregnancy.

Abdominal pregnancies are a small fraction of ectopic pregnancies. They usually implant on the peritoneal surface after partial disruption of the initial implantation site in the tubes. The pelvic cavity is the preferential site, but they have been reported from all over the peritoneal cavity. In the present case the pregnancy was situated on the surface of the right liver lobe. Abdominal pregnancies usually present with acute hemoperitoneum and the pre-operative diagnosis is extremely difficult. The possible role of IUDs as an etiological factor is briefly discussed.

Adult↗
PubMedDate not supplied

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗