Effect of physical activity on bone strength and body composition in breast cancer premenopausal women during endocrine therapy.

BACKGROUND: Breast cancer endocrine therapy (ET) is one of the most basic therapeutic methods in oncology. Well-balanced physical activity exerts positive influence on bone strength (BS) and body composition (BC), which has been confirmed by the clinical research regarding osteoporosis, prevention and treatment alike. Accordingly, in the following study, an attempt was made to assess the selected parameters of young, premenopausal women's clinical state under the influence of breast cancer ET, as well as to define the influence of physical activity on the studied parameters. AIM: The assessment of the influence of aerobic and resistance training (AT and RT) on BS and BC in premenopausal women during breast cancer ET. DESIGN: This was a nonrandomized, prospective clinical study. SETTING AND POPULATION: The study was performed in 41 outpatients in the Greater Poland Cancer Centre. METHODS: The examinations were made with the anthropometric and dual energy X-ray absorptiometry measurements. The examinations were conducted according to the schedule: at the baseline, II-after 6 months of ET, III-after 6 months of AT (in 12 months of ET), IV- after following 6 months AT and RT (18 months of ET). RESULTS: After 6 months of the ET without physical activity the bone mineral density (BMD) in all regions and the hip structure parameters were lower in comparison to the baseline and there was a significant increase in fatty tissue. After 6 months of AT the BMD of all regions was lower than in 6 months ET. An introduction of RT caused the analyzed values of BS parameters to increase. Also a significant growth of lean body mass and free fat body mass was observed and so was an insignificant fall in fat. CONCLUSION: The breast cancer ET is related to the changes in BS and BC in premenopausal women. The introduction of AT caused a slowdown in negative changes in bones, and body fat was reduced. The introduction of RT reversed an adverse tendency for BS and sarcopenia. CLINICAL REHABILITATION IMPACT: The study results show that mixed type physical activity (AT and RT) during breast cancer ET could prevent negative changes, of this treatment, in body build in premenopausal women.

Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer.

BACKGROUND: This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). PATIENTS AND METHODS: Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. RESULTS: ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). CONCLUSIONS: Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

Experiences with the shikimate-pathway enzymes as targets for rational drug design.

The background and current context of work on the shikimate-pathway enzymes as potential targets for anti-bacterial, anti-fungal and anti-parasitic drugs is reviewed. Recent work on the third enzyme of the pathway, dehydroquinase, which occurs in two structurally and mechanistically distinct forms, is used to illustrate the present state of studies into rational drug design.

High-throughput screens for postgenomics: studies of protein crystallization using microsystems technology.

This paper describes the fabrication of a micromachined miniaturized array of chambers in a 2-mm-thick single crystal (100) silicon substrate for the combinatorial screening of the conditions required for protein crystallization screening (including both temperature and the concentration of crystallization agent). The device was fabricated using standard photolithography techniques, reactive ion etching (RIE) and anisotropic silicon wet etching to produce an array of 10 x 10 microchambers, with each element having a volume of 5 microL. A custom-built temperature controller was used to drive two peltier elements in order to maintain a temperature gradient (between 12 and 40 degrees C) across the device. The performance of the microsystem was illustrated by studying the crystallization of a model protein, hen egg white lysozyme. The crystals obtained were studied using X-ray diffraction at room temperature and exhibited 1.78 A resolution. The problems of delivering a robust crystallization protocol, including issues of device fabrication, delivery of a reproducible temperature gradient, and overcoming evaporation are described.

[Analysis of epidemiologic risk factors for endometrial cancer]. / Analiza czynników epidemiologicznych u chorych z rakiem blony sluzowej trzonu macicy leczonych w Wielkopolskim Centrum Onkologii.

UNLABELLED: The aim of this study was an analyse of several risk factors for women with endometrial cancer and their influence on overall survival. MATERIALS AND METHODS: A retrospective analysis covered 160 women treated with the primary surgery and adjuvant radiotherapy because of endometrial cancer. Age, lifestyle, age of menarche and menopause, parity, body size, hypertension and diabetes mellitus were determined. RESULTS: The 5-year survival rate were: 87% for the women younger then 60 and 70% for the older ones (p = 0.0026), 81% for the city women and 73% for the country women (p = 0.2034), 91% for the educated women and 70% for the women with elementary education (p = 0.0102), 85% for 1-2 x parous women and 65% for nulliparous (p = 0.0433), 79% for women without miscarriage and 63% for women with 2 or more miscarriages (p = 0.3265), 82% for women with menarche above age of 15 and 66% with menarche under age of 13 (p = 0.1989), 82% for women without obesity, diabetes, hypertension and 72% for women with hypertension, 64% with obesity, 50% for women with all analysed diseases (p = 0.0104). CONCLUSION: An analyse show that age, lifestyle, parity, body size and hypertension modify the overall survival of women with endometrial cancer.

Probing the interface between membrane proteins and membrane lipids by X-ray crystallography.

Biological membranes are composed of a complex mixture of lipids and proteins, and the membrane lipids support several key biophysical functions, in addition to their obvious structural role. Recent results from X-ray crystallography are shedding new light on the precise molecular details of the protein-lipid interface.

Estimation of neovascularisation in hyperplasia and carcinoma of endometrium using a "power" angio-Doppler technique.

The aim of this study was to estimate neovascularisation in hyperplasia and carcinoma of the endometrium using a "power" angio-Doppler technique. One hundred and eighty-two postmenopausal patients with irregular bleeding from the sexual organs were investigated. Age of the patients ranged between 46 and 78 years. No neovascularisation in a control group of women with normal histopathological results of the endometrium was observed. The sensitivity of this method with reference to the diagnosis of hyperplasia and cancer of the endometrium was 12.2% and 81.2%, respectively. The specificity and positive prediction values were equal to 100% each in both pathologies. The values of the analysed flow indices in the neovascular arteries in endometrial cancer were significantly lower (p<0.05) (properly PI-0.92+/-0.12; RI-0.46+/-0.08) in comparison to the corresponding values in hyperplasia of the endometrium (PI-1.38+/-0.28 and RI-0.66+/-0.18). In conclusion, using a "power" angio-Doppler technique irregular vascularity of the endometrium in a group of patients with hyperplasia was observed in 12.2% of all patients and in 81.2% of those with cancer of the endometrium. The analysis of the values of the blood flow qualitative parameters in the neovascularisation areas in the endometrium at the significance level of PI < or = 1.0; RI < or = 0.5 and TAMV > 18.0 cm can help determine the essential element in the differential diagnosis of benign and malicious lesions. Transvaginal ultrasonography with a "power" angio-Doppler technique can be a valuable diagnostic method in hyperplasia and cancer of the endometrium, especially useful in the early stages of these pathologies.

Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution.

The three-dimensional structure of the R form of rabbit liver fructose 1,6-bisphosphatase (Fru-1,6-Pase; E.C. 3.1.3.11) has been determined by a combination of heavy-atom and molecular-replacement methods. A model, which includes 2394 protein atoms and 86 water molecules, has been refined at 2.3 A resolution to a crystallographic R factor of 0.177. The root-mean-square deviations of bond distances and angles from standard geometry are 0.012 A and 1.7 degrees, respectively. This structural result, in conjunction with recently redetermined amino-acid sequence data, unequivocally establishes that the rabbit liver enzyme is not an aberrant bisphosphatase as once believed, but is indeed homologous to other Fru-1,6-Pases. The root-mean-square deviation of the Calpha atoms in the rabbit liver structure from the homologous atoms in the pig kidney structure complexed with the product, fructose 6-phosphate, is 0.7 A. Fru-1,6-Pases are homotetramers, and the rabbit liver protein crystallizes in space group I222 with one monomer in the asymmetric unit. The structure contains a single endogenous Mg2+ ion coordinated by Glu97, Asp118, Asp121 and Glu280 at the site designated metal site 1 in pig kidney Fru-1,6-Pase R-form complexes. In addition, two sulfate ions, which are found at the positions normally occupied by the 6-phosphate group of the substrate, as well as the phosphate of the allosteric inhibitor AMP appear to provide stability. Met177, which has hydrophobic contacts with the adenine moiety of AMP in pig kidney T-form complexes, is replaced by glycine. Binding of a non-hydrolyzable substrate analog, beta-methyl-fructose 1,6-bisphosphate, at the catalytic site is also examined.

[Malignant vulvar melanoma]. / Czerniak zlosliwy sromu.

Vulvar malignant melanoma is a rare neoplasm with mostly poor prognosis. As compared with malignant melanoma of the skin vulvar melanoma infiltrates early deep into tissues and into abundant lymph and blood vascularisation. Epidemiology, clinical and histopathological data of primary vulvar melanoma are presented. Currently used methods of treatment are analysed. According to many authors the radical vulvar excision with bilateral lymphangiectomy in all stages of melanoma is a treatment of choice. Due to small population of patients with vulvar melanoma the randomized trials comparing different methods of treatment are not existing. Vulvar melanoma remains controversial medical problem with poor prognosis.

[A case of metastatic malignant melanoma of the vagina with a background of primary vaginal melanoma--clinical case]. / Przypadek przerzutowego czerniaka zlosliwego pochwy na tle czerniaka pierwotnego pochwy--przypadek kliniczny.

Primary vaginal malignant melanoma is an uncommon disease with poor prognosis. As compared with malignant melanoma of the skin, vaginal melanoma infiltrates early deep into tissues and in the abundant lymph and blood vascularisation. Epidemiology, clinical and histopathological data and treatment methods of primary and metastatic vaginal melanoma are discussed. A case of 53 years old women with malignant melanoma of the skin with metastasis to vagina treated in Wielkopolska Center of Oncology is presented. According to the literature aggressive surgical therapy can improve greatly the outlook for patients with vaginal melanoma.

[Intracavitary brachytherapy method using after-loading for treatment of women with endometrial uterine neoplasm]. / Metoda brachyterapii dojamowej technika after-loading w leczeniu kobiet z rakiem blony sluzowej macicy.

We would like to introduce intracavitary brachytherapy using double rod-shaped applicators. The women who are treated with this method are evaluated in III FIGO stage and the patients in stage I and II who could not undergo the operation. This method allows to distribute equally the dose in whole uterus, insertion of the applicators is not difficult. The brachytherapy treatment is well tolerated.

[Evaluation of SCC antigen in patients with advanced cervix cancer treated with radiation]. / Ocena antygenu SCC u chorych na zaawansowanego raka szyjki macicy, leczonych promieniami.

The TA-4 antigen was isolated and described in 1977 by Kato and Torigoe. The antigen called SCC-squamous cell carcinoma is subfraction TA-4 isolated of liver metastases from cervix uteri. The cut-off limits for SCC-antigen is counted as 1.5-2.5 ng/ml. The level of SCC-antigen was determined in the serum of 41 women with advanced cervix uteri cancer-IIIB and IV FIGO stage. The value of SCC-antigen was evaluated twice: before and after the treatment. The increasing of SCC-level was observed in the serum of 80% women. The conclusion are: There was the lowering of SCC-antigen value in patients after the irradiation. In cases of patients who still had high SCC-antigen level after the treatment and it exceeded 8 ng/ml., progression of cancer also was found. The progression of cancer after the treatment was found in women with pretreatment level of SCC-antigen higher than 30 ng/ml.

[Combined dose distribution in the small pelvis of postsurgical radiotherapy patients with cancer of the endometrium]. / Laczne rozklady dawek w miednicy mniejszej w pooperacyjnej radioterapii pacjentek z rakiem blony sluzowej macicy.

X-ray's doses in the pelvis area was published and discussed in this paper. On the CT scan base, doses was calculated by the treatment planning system Target 2 plus. The analysis of dose distribution was performed on 26 patients with the postsurgical cancer of endometrium. The treatment was combined teletherapy and brachytherapy techniques.

[Studies of human papillomavirus infection (HPV) and expression of oncoprotein p 21 in cervix neoplasms]. / Badania nad zakazeniem wirusem ludzkiego brodawczaka (HPV) i ekspresja onkoproteiny p 21 w rakach szyjki macicy.

Frequencies of HPV type 16 and 18, evaluated by in situ hybridization technique in uterine cervix carcinomas of the IIIrd stage of clinical advancement, were 54% and 36.5% respectively. Presence of p 21 protein was detected in 85.3% cases of the cancers and showed no relation to HPV infection.

[Role of second-look surgery in treatment of ovarian neoplasms]. / Rola operacji second-look w leczeniu raka jajnika.

The operation second-look was carried out on 66 women with ovarian cancer without any clinical symptoms of disease. 14 of them (21.2%) showed persistent cancer, including 5-cancer in early stages. The level of CA 125 didn't exceed 35 U/ml in 60 women, and in 5 women persistent cancer wasn't detected during the second-look operation. Negative result of second-look operation doesn't inform about recovery because in 8 women out of 52 recurrence of cancer reported.

Relation between infection with human papilloma viruses and expression of p21 and p53 oncoproteins in patients with cancer of the uterine cervix.

Infection with HPV type 16 was demonstrated in 54% of the cases and infection with HPV type 18 in 36.5% of the cases of uterine cervix carcinoma. Both types of viruses were present in 24.3% of the patients. P53 protein accumulation in cell nuclei was observed in 12.2% of the cases of uterine cervix carcinomas and the cases were mostly HPV negative while the cytoplasmic expression of p53 protein was present in 39% of the cases and was frequently accompanied by HPV infection. Presence of p21 protein was detected in 85.3% of the cases, independently of HPV infection or expression of p53 protein.

Diagnostic evaluation of cancer antigens RAK .1. Cervical and ovarian cancer.

Cancer antigens RAK-p120, p42, and p25, which exhibit biological, immunological and molecular similarity to the proteins expressed by Human Immunodeficiency Virus 1 (HIV-1), were found in 47 of 47 tested cases of serous adenocarcinoma of the ovary, and 45 of 45 tested cases of squamous carcinoma of the cervix. Normal ovary and cervix did not express antigens RAK. High molecular weight protein (RAK-p160) was detected in the blood of over 61% of ovarian and 72% of cervical cancer patients, and in 14.3% of healthy women with family history of breast and/or gynecological cancer. Antigens RAK might represent new diagnostic markers.

[Evaluation of blood flow in uterine arteries in patients with cancer of the cervix uteri using transvaginal color doppler ultrasonography]. / Ocena przeplywu krwi w tetnicach macicznych u chorych z rakiem szyjki macicy przy wykorzystaniu ultrasonografii dopochwowej z kolorowym Dopplerem.

The purpose of the study was to estimate blood flow in uterine arteries in patients with uterus cervix invasive carcinoma. In the study the colour Doppler ultrasonography was used. It was found out that in the group of patients with uterus cervix carcinoma pulsation index (PI)--1.82 +/- 1.44 as well as resistance index (RI)--0.72 +/- 0.12 are statistically significantly lower than adequate indices in the control group (PI)--3.36 +/- 1.04 and (RI)--0.81 +/- 0.17 (p < 0.05).

[The quality of life in particular phases of disease in women treated for genital neoplasms]. / Jakosc zycia w poszczególnych fazach choroby u kobiet leczonych z powodu nowotworów narzadów plciowych.

The authors have performed psychological analysis in women with diagnosed neoplasma of the genital organs. All of them were treated with radiotherapy. The quality of life depended on the phase of the disease in which they had been.

[Combined calculation of dosage for brachytherapy and external beam therapy in radiation treatment of cervix cancer]. / Laczne obliczenia dawek z brachy i teleterapii w leczeniu radiacyjnym raka szyjki macicy.

In this paper authors present complex doses of ionizing radiation from brachytherapy and external beam therapy. Doses were determined on Computerized Planning System--Target 2 plus for patients with cancer of cervix.