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Biomedical subjects

J Markowska

Publications and source records attributed to J Markowska.

At least 19 recordsLinked to original sources

Preliminary results of mitomycin C local application as post-treatment prevention of vaginal radiation-induced morbidity in women with cervical cancer.

PURPOSE: To determine the usefulness of local mitomycin C application in the prophylaxis of vaginal narrowing after irradiation. MATERIAL AND METHODS: 31 patients with advanced cervical cancer qualified for the study. They underwent brachytherapy with iridium-192 isotope and external beam therapy with linear accelerators. In a blind probe method 16 patients were chosen to have an aqueous solution of mitomycin C applied to the vagina. RESULTS: Radiotherapy caused a shortening of vaginal length in both groups (study and control). In the "mitomycin C group" complete vaginal occlusion was visibly less frequent as were solid fibrotic vault changes. CONCLUSIONS: This mode of morbidity prevention can potentially diminish the occurrence of local vaginal fibrosis and thus may improve patients' quality of life. Further investigations are needed to confirm these results.

Antibiotics, Antineoplastic↗

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

Adult↗

Inhibitors of angiogenesis in therapy of ovarian cancers.

The capacity to induce growth of blood vessels represents one of the phenotypic traits of neoplastic cells. Several preclinical studies prove that the inhibition of growth of peri-neoplastic blood vesssels leads to restricted growth of primary tumours and of metastases. Nevertheless, clinical studies indicate that angiogenesis inhibitors are not such effective drugs as might be expected on the basis of studies conducted on animals. In this article we would like to draw the readers' attention to divergencies between preclinical and clinical results, in particular to those related to ovarian cancers. In the treatment of ovarian cancers, angiogenesis inhibitors combined with other drugs may prove to represent a relatively effective therapeutic approach.

Angiogenesis Inhibitors↗

Cytokines and endometriosis.

INTRODUCTION: Abnormal expression of cytokines is considered to be involved in the pathogenesis of endometriosis. MATERIAL AND METHODS: In 63 women with various stages of endometriosis preoperative levels of cytokines, including IL-6, IL-8, BVEGF, b-FGF, of TNF RI and TNF RII were analysed employing ELISA tests (R&D kits). RESULTS: In the sera of endometriosis patients significantly augmented levels of IL-6 and of b-FGF were detected as well as a trend for elevated IL-8 levels. CONCLUSION: Elevated serum levels of cytokines may show poor correspondence to the localized pathological process. Endometriosis would find a stricter reflection in cytokine levels in fluids or tissues of the pelvis minor.

Adolescent↗

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Adult↗

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Adult↗

Monoclonal antibodies in the treatment of ovarian cancer.

Monoclonal antibody application in ovarian cancer started eight years after the discovery of Köhler and Milstein, with the studies of Bast et al. which led to the introduction of CA 125 antigen estimation to everyday clinical routine. At present, monoclonal antibodies serve as a therapeutic tool for variable targets with the potential to be applied in multiple clinical situations. In the coming decade, the drug market is likely to be flooded with monoclonal antibodies. Most of the available monoclonal antibodies will be produced in bioreactors, using transgenic plants or transgenic animals. Apart from mouse antibodies, chimeric, humanised or human antibodies, oncology will certainly employ chimeric structures with antibody fragments built into the structures of receptors or growth factors. Irrespective of their origin, they will constitute an integral part of medical practice.

Antibodies, Monoclonal↗

Frequent disease progression and early recurrence in patients with familial ovarian cancer primarily treated with paclitaxel and cis- or carboplatin (preliminary report).

PURPOSE: To evaluate frequencies of early disease progressions and recurrences in patients with familial vs sporadic ovarian cancers following primary paclitaxel/cis- or carboplatin chemotherapy. METHODS: The frequencies of disease progression up to six months following primary paclitaxel/cis- or carboplatin and of early disease recurrences were analysed in 18 Stage III patients with familial ovarian cancers, both carriers and non-carriers of 5382 insC BRCA1 mutation, and in 35 patients with Stage III sporadic ovarian tumors. RESULTS: Progressive disease within first six months following chemotherapy developed in 5/18 patients with familial cancers vs. 5/35 patients with sporadic tumors. Early disease recurrences (up to 6 months after treatment) occurred in 3/18 patients with familial vs. 2/35 patients with sporadic tumors. Recurrences after 7-12 months following treatment occurred, respectively, in 3/13 and 3/31 patients from these groups. CONCLUSION: The results of this preliminary report may suggest that patients with familial ovarian tumors respond less favourably to paclitaxel/cis- or carboplatin treatment than patients with sporadic ovarian tumors. These findings should be however confirmed in a prospective study on a larger group of patients.

Adult↗

Chlamydia trachomatis infection in women with CIN and invasive uterine cervix cancer. Significance of hormonal status.

In women with CIN at fertile age and those over 50 years of age, EGFR expression is lower in the presence of Chlamydia trachomatis (Cht) infection. In all Cht infected women over 50 years of age expression of Ki 67 is higher; the increase is significant among women with invasive carcinoma. In these groups of women with CIN and invasive carcinoma TGF-alpha expression is insignificantly augmented. Chronic Cht infection is associated with cervical hypertrophy.

Adult↗

[Microheterogeneity of two acute phase proteins in patients with ovarian carcinoma].

Concentrations of two acute phase proteins: alpha 2-macroglobulin (alpha 2M) and transferrin (Tf) as well as glycosylation profiles of alpha 2M and Tf were studied in sera samples from 13 patients suffering from ovarian cancer. In the observed group of patients with ovarian cancer in whom the progression of disease was noticed low concentrations of both investigated proteins were present. On the contrary, the microheterogeneity of both alpha 2M and Tf was changed towards variants of both proteins more weakly reacting with ConA, what was previously described for AGP and ACT in all chronic inflammatory conditions including cancer.

Adult↗

Detection of Chlamydia trachomatis infection in women with CIN and invasive carcinoma. Controversial results of different methods.

Chlamydia (Ch.) trachomatis infection as a sexually transmitted disease is highly important, but reliable methods of diagnosing it remain to be worked out. We used three methods of detection: an immunoenzymatic technique for detection of Ch. trachomatis antigen in endocervical material, in situ PCR, and enzyme-immuno assay for detection of IgG class anti-Ch. trachomatis antibodies in serum. We have compared the IS-PCR technique and method of detection of the endocervical antigen. We have not confirmed compatibility of the results obtained in these two methods. Parallel positive results obtained in patient serum and detection of chlamydial DNA by IS-PCR have been accepted to be indicative of persistent infection of Ch. Trachomatis.

Adult↗

Prognostic significance of CA 125 and TPS levels after 3 chemotherapy courses in ovarian cancer patients.

OBJECTIVE: To evaluate the prognostic significance of and predictive value for survival of CA 125 and TPS levels after three chemotherapy courses in ovarian cancer patients. METHODS: We analyzed in a prospective multicenter study the 1- and 2-year overall survival (OS) in ovarian carcinoma patients. The prognostic significance of CA 125 and TPS levels above the discrimination value (25 kU/L and 100 U/L, respectively) was examined by univariate and multivariate analyses. RESULTS: Of the 213 cases included, 64 patients were staged as FIGO I + II and 149 patients were staged as FIGO III + IV. Tumor marker levels in stage I + II were not correlated with survival. However, stage III and IV patients with elevated levels of CA 125 or TPS after three chemotherapy courses had a worse 2-year OS (69% vs 26%, P < 0.0001 and 57% vs 20%, P < 0.0001, respectively) than patients with normal levels of the markers. In univariate analysis the result of operation (staging laparatomy and partial debulking) and advanced FIGO stage (IV) were also adverse prognostic factors. Independent factors predictive of low 2-year OS by multivariate analysis were staging laparotomy, TPS elevated, and CA 125 elevated. The only factors predictive of low 1-year OS were TPS elevated and staging laparotomy. CONCLUSIONS: Ovarian cancer patients with elevated CA 125 levels after three chemotherapy courses have a poor prognosis. However, the prognostic accuracy can be significantly increased by the parallel determination of serum TPS.

Antineoplastic Combined Chemotherapy Protocols↗

[Total or subtotal hysterectomy?].

UNLABELLED: We compared the risk and benefits subtotal (supracervical) hysterectomy and total hysterectomy in women with nonmalignant conditions (perioperative mortality, intra- and postoperative complications, quality of life, long-term effects on other diseases). The main disadvantage of subtotal hysterectomy over total one is the fact, that in 1 per 1000 women develops carcinoma in cervical stump. CONCLUSION: Total hysterectomy is recommended in benign conditions of the uterine corpus.

Adult↗

Factors influencing period of time between negative second-look laparotomy and ovarian carcinoma recurrence. Multicenter study in Poland.

OBJECTIVE: The aim of our study was to evaluate factors such as primary clinical stage, presence of ascites, serum CA 125 antigen level, histological type of ovarian cancer, cell differentiation and number of chemotherapy cycles influencing the time of recurrence after negative second-look operations. MATERIAL AND METHODS: Having observed complete clinical remission in 356 patients with ovarian cancer, second-look laparotomy was performed. In 180 patients complete pathologic remission was detected and in 73 recurrence was observed. Correlation analysis between time of recurrence and the above-mentioned prognostic factors was carried out by means of the Mann-Whitney and Kruskal-Wallis tests. RESULTS: The time from the second-look operation till diagnosis of relapse ranged from 7 to 36 months (average 21 months). The statistical analysis showed a correlation between the presence of ascites, increased serum CA 125 antigen level, the administration of six chemotherapy courses and the time of recurrence. In all those cases relapse occurred earlier than in patients without ascites, with normal CA 125 antigen levels and after ten courses of chemotherapy. CONCLUSION: Our findings suggest that the stage of clinical advancement and histologic grading do not influence the time of recurrence. The presence of ascites, increased serum CA 125 antigen level and the administration of fewer chemotherapy courses (6 versus 10) after primary surgery affects the earlier relapse of disease.

Adenocarcinoma↗

[A grid pattern type of photocoagulation in treatment of diabetic maculopathy--personal experience].

PURPOSE: The aim of the present study was the evaluation of visual outcome of 425 eyes in 283 patients treated by focal and grid pattern photocoagulation for clinically significant macular edema according to the recommendations of the Early Treatment Diabetic Retinopathy Study (ETDRS). MATERIAL AND METHODS: On the basis of baseline status of macula, eyes were classified into three groups: group I--eyes treated by focal photocoagulation (39 eyes), group II--eyes treated by focal photocoagulation and/or modified grid (84 eyes), group III--eyes treated by focal photocoagulation and/or grid pattern (302 eyes). Eligibility criteria for this retrospective study included a diagnosis of clinically significant macular edema according to the ETDRS scale. The baseline examination for all patients presented in this review included: the best corrected visual acuity (VA), slit lamp with contact lens indirect ophthalmoscopy, fundus color photography and fluorescein angiography. All patients were treated with argon green by grid with Nidek 2300 laser. Modified grid or focal photocoagulation according to the ETDRS recommendations were performed. Patients with proliferative diabetic retinopathy (PDR) were transferred to panretinal photocoagulation (PRP) after treatment of maculopathy. Development of VA from the baseline to last checkup in treated eyes was reported and compared. Follow-up ranged widely from 6 to 45 months. RESULTS: General stabilization was achieved in 51.3%, improvement in 10.1% and deterioration in 38.6% of eyes. The best results were achieved after selective and focal and/or modified grid treatment: in the Ist group stabilization of VA was achieved in 43.6% and improvement in 41% of eyes; in the IInd group: stabilization in 60.7% and improvement in 21.4% were stated; in the IIIrd group: stabilization in 49.7% and improvement only in 3.0%. In 164 (38.6%) cases supplemental treatment was administered. CONCLUSION: Photocoagulation has proved effective in the treatment of diabetic clinically significant macular edema.

Adult↗

The role of Chlamydia trachomatis infection in cervical cancer development.

Previous Chlamydia trachomatis infection elevates expression of: 1. TGFalpha in CIN I, CIN II, CIN III; 2. HPV 16 in CIN I, CIN II, CIN III and invasive carcinoma; 3. Ki 67 in CIN III and invasive carcinoma. Chronic Chlamydial infection is very often associated with cervical hypertrophy.

Case-Control Studies↗

Estimation of the usefulness of neoplastic markers TPS and CA 125 in diagnosis and monitoring of ovarian cancer.

PURPOSE: We have undertaken an attempt to compare the suitability of tumor markers TPS (tissue polypeptide specific antigen) and CA125 for diagnosis and monitoring of ovarian cancer patients. METHODS AND MATERIAL: The studies were performed on 33 patients treated for ovarian cancer in the Department of Oncology, Karol Marcinkowski School of Medicine, Poznań from 1995-1996, Serum levels of TPS and CA125 were determined before surgery and at each chemotherapy course. CONCLUSION: Estimation of the neoplastic markers TPS and CA125 is suitable for diagnosis of ovarian cancer. Parallel use of TPS and CA125 in ovarian cancer patients increases sensitivity of the diagnosis. Estimation of TPS is highly suitable and estimation of CA125 is of low value in detection of mucinous ovarian cancer. Serum levels of the neoplastic markers TPS and CA125 decrease after total or debulking surgery for ovarian cancer. Serum TPS and CA125 levels reflect the course of the neoplastic process during chemotherapy.

Adult↗

[Spontaneous tumor regression].

Spontaneous remission of cancer is a rare but definitely observed phenomenon. Spontaneous remission is defined by partial or total disappearance of a proven malignant tumor, without adequate medical treatment. It has been estimated that it occurs no more than once in 60,000 to 100,000. The cause of phenomenon is multifold: immunologic, hormonal and psychological mechanism as well as elimination of carcinogen (action of oncogenes, growth factors, cytokines) and apoptosis are postulated. In gynecological malignancies, excluding chorionepithelioma and breast cancer, spontaneous remission is rare.

Breast Neoplasms↗