Tight control: a new therapeutic strategy in the management of osteoporotic patients.

BMD changes in patients under tight control (monitored at 3-month intervals with adjustment of therapy guided by bone turnover markers) and routine management (controlled once a year) were compared. After 1 year, the femoral neck BMD increased significantly in the tight control compared to the routine management group. INTRODUCTION: We intended to ascertain whether tight control (i.e., follow-up visits and bone turnover markers/BTM/and parathyroid hormone/PTH/monitoring at 3-month intervals) strategy achieves a statistically greater increase in bone mineral density over the observation period than standard follow-up care (i.e., bone densitometry at 1-year intervals, without BTM monitoring). METHODS: We studied involutional osteoporotic patients newly enrolled into chronic care. One hundred and eleven patients underwent tight control, while another 113 received routine treatment (with follow-up visits scheduled at > 1-year intervals). We compared the changes in bone mineral density reflected by the results of bone mineral density (BMD) measurements of the lumbar spine and of the left femoral neck. Statistical analyses were performed with version 22 of the SPSS software package. RESULTS: In the group of patients under tight control, baseline and follow-up median BMD values were 0.842/0.881 g/cm2 at the L1-4 vertebrae and 0.745/0.749 g/cm2 at the femoral neck. In the group under routine care, the corresponding values were 0.903/0.915 g/cm2 and 0.742/0.72 g/cm2, respectively. The relative changes of the bone mineral density of the femoral neck was significantly (p = 0.041) higher in patients under tight control than in those receiving routine care; however, BMD changes in the lumbar spine were not statistically different. CONCLUSION: Our findings suggest that adopting tight control as a new therapeutic strategy might be justified in the osteoporosis management. In fact, a greater improvement of BMD can be achieved by treatment according to these principles.

Characterizing d-dimensional quantum channels by means of quantum process tomography.

In this Letter, we propose a simple optical architecture based on phase-only programmable spatial light modulators, in order to characterize general processes on photonic spatial quantum systems in a d>2 Hilbert space. We demonstrate the full reconstruction of typical noises affecting quantum computing, such as amplitude shifts, phase shifts, and depolarizing channels in dimension d=5. We have also reconstructed simulated atmospheric turbulences affecting a free-space transmission of qudits in dimension d=4. In each case, quantum process tomography was performed in order to obtain the matrix χ that fully describes the corresponding quantum channel, E. Fidelities between the states are experimentally obtained after going through the channel, and the expected ones are above 97%.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

OBJECTIVES: Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. METHODS: We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. RESULTS: Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). CONCLUSIONS: We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

Partial p53-dependence of anisomycin-induced apoptosis in PC12 cells.

The bacterial antibiotic anisomycin is known to induce apoptosis by activating several mitogen-activated protein kinases and by inhibiting protein synthesis. In this study, the influence of p53 protein on the apoptosis-inducing effect of anisomycin was investigated. The effect of protein synthesis-inhibiting concentration of anisomycin on apoptotic events was analyzed using Western blot, DNA fragmentation, and cell viability assays in wild-type PC12 and in mutant p53 protein expressing p143p53PC12 cells. Anisomycin stimulated the main apoptotic pathways in both cell lines, but p143p53PC12 cells showed lower sensitivity to the drug than their wild-type counterparts. Anisomycin caused the activation of the main stress kinases, phosphorylation of the p53 protein and the eukaryotic initiation factor eIF2α, proteolytic cleavage of protein kinase R, Bid, caspase-9 and -3. Furthermore, anisomycin treatment led to the activation of TRAIL and caspase-8, two proteins involved in the extrinsic apoptotic pathway. All these changes were stronger and more sustained in wtPC12 cells. In the presence of the dominant inhibitory p53 protein, p53- dependent genes involved in the regulation of apoptosis may be less transcribed and this can lead to the decrease of apoptotic processes in p143p53PC12 cells.

Polyphasic taxonomy of Aspergillus section Aspergillus (formerly Eurotium), and its occurrence in indoor environments and food.

Aspergillus section Aspergillus (formerly the genus Eurotium) includes xerophilic species with uniseriate conidiophores, globose to subglobose vesicles, green conidia and yellow, thin walled eurotium-like ascomata with hyaline, lenticular ascospores. In the present study, a polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of this section. Over 500 strains from various culture collections and new isolates obtained from indoor environments and a wide range of substrates all over the world were identified using calmodulin gene sequencing. Of these, 163 isolates were subjected to molecular phylogenetic analyses using sequences of ITS rDNA, partial ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) genes. Colony characteristics were documented on eight cultivation media, growth parameters at three incubation temperatures were recorded and micromorphology was examined using light microscopy as well as scanning electron microscopy to illustrate and characterize each species. Many specific extrolites were extracted and identified from cultures, including echinulins, epiheveadrides, auroglaucins and anthraquinone bisanthrons, and to be consistent in strains of nearly all species. Other extrolites are species-specific, and thus valuable for identification. Several extrolites show antioxidant effects, which may be nutritionally beneficial in food and beverages. Important mycotoxins in the strict sense, such as sterigmatocystin, aflatoxins, ochratoxins, citrinin were not detected despite previous reports on their production in this section. Adopting a polyphasic approach, 31 species are recognized, including nine new species. ITS is highly conserved in this section and does not distinguish species. All species can be differentiated using CaM or RPB2 sequences. For BenA, Aspergillus brunneus and A. niveoglaucus share identical sequences. Ascospores and conidia morphology, growth rates at different temperatures are most useful characters for phenotypic species identification.

Polyphasic taxonomy of Aspergillus section Cervini.

Species belonging to Aspergillus section Cervini are characterised by radiate or short columnar, fawn coloured, uniseriate conidial heads. The morphology of the taxa in this section is very similar and isolates assigned to these species are frequently misidentified. In this study, a polyphasic approach was applied using morphological characters, extrolite data, temperature profiles and partial BenA, CaM and RPB2 sequences to examine the relationships within this section. Based on this taxonomic approach the section Cervini is resolved in ten species including six new species: A. acidohumus, A. christenseniae, A. novoguineensis, A. subnutans, A. transcarpathicus and A. wisconsinensis. A dichotomous key for the identification is provided.

Aspergillus section Nidulantes (formerly Emericella): Polyphasic taxonomy, chemistry and biology.

Aspergillus section Nidulantes includes species with striking morphological characters, such as biseriate conidiophores with brown-pigmented stipes, and if present, the production of ascomata embedded in masses of Hülle cells with often reddish brown ascospores. The majority of species in this section have a sexual state, which were named Emericella in the dual name nomenclature system. In the present study, strains belonging to subgenus Nidulantes were subjected to multilocus molecular phylogenetic analyses using internal transcribed spacer region (ITS), partial ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) sequences. Nine sections are accepted in subgenus Nidulantes including the new section Cavernicolus. A polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of section Nidulantes. Based on this approach, section Nidulantes is subdivided in seven clades and 65 species, and 10 species are described here as new. Morphological characters including colour, shape, size, and ornamentation of ascospores, shape and size of conidia and vesicles, growth temperatures are important for identifying species. Many species of section Nidulantes produce the carcinogenic mycotoxin sterigmatocystin. The most important mycotoxins in Aspergillus section Nidulantes are aflatoxins, sterigmatocystin, emestrin, fumitremorgins, asteltoxins, and paxillin while other extrolites are useful drugs or drug lead candidates such as echinocandins, mulundocandins, calbistrins, varitriols, variecolins and terrain. Aflatoxin B1 is produced by four species: A. astellatus, A. miraensis, A. olivicola, and A. venezuelensis.

Aspergillus is monophyletic: Evidence from multiple gene phylogenies and extrolites profiles.

Aspergillus is one of the economically most important fungal genera. Recently, the ICN adopted the single name nomenclature which has forced mycologists to choose one name for fungi (e.g. Aspergillus, Fusarium, Penicillium, etc.). Previously two proposals for the single name nomenclature in Aspergillus were presented: one attributes the name "Aspergillus" to clades comprising seven different teleomorphic names, by supporting the monophyly of this genus; the other proposes that Aspergillus is a non-monophyletic genus, by preserving the Aspergillus name only to species belonging to subgenus Circumdati and maintaining the sexual names in the other clades. The aim of our study was to test the monophyly of Aspergilli by two independent phylogenetic analyses using a multilocus phylogenetic approach. One test was run on the publicly available coding regions of six genes (RPB1, RPB2, Tsr1, Cct8, BenA, CaM), using 96 species of Penicillium, Aspergillus and related taxa. Bayesian (MrBayes) and Ultrafast Maximum Likelihood (IQ-Tree) and Rapid Maximum Likelihood (RaxML) analyses gave the same conclusion highly supporting the monophyly of Aspergillus. The other analyses were also performed by using publicly available data of the coding sequences of nine loci (18S rRNA, 5,8S rRNA, 28S rRNA (D1-D2), RPB1, RPB2, CaM, BenA, Tsr1, Cct8) of 204 different species. Both Bayesian (MrBayes) and Maximum Likelihood (RAxML) trees obtained by this second round of independent analyses strongly supported the monophyly of the genus Aspergillus. The stability test also confirmed the robustness of the results obtained. In conclusion, statistical analyses have rejected the hypothesis that the Aspergilli are non-monophyletic, and provided robust arguments that the genus is monophyletic and clearly separated from the monophyletic genus Penicillium. There is no phylogenetic evidence to split Aspergillus into several genera and the name Aspergillus can be used for all the species belonging to Aspergillus i.e. the clade comprising the subgenera Aspergillus, Circumdati, Fumigati, Nidulantes, section Cremei and certain species which were formerly part of the genera Phialosimplex and Polypaecilum. Section Cremei and the clade containing Polypaecilum and Phialosimplex are proposed as new subgenera of Aspergillus. The phylogenetic analysis also clearly shows that Aspergillus clavatoflavus and A. zonatus do not belong to the genus Aspergillus. Aspergillus clavatoflavus is therefore transferred to a new genus Aspergillago as Aspergillago clavatoflavus and A. zonatus was transferred to Penicilliopsis as P. zonata. The subgenera of Aspergillus share similar extrolite profiles indicating that the genus is one large genus from a chemotaxonomical point of view. Morphological and ecophysiological characteristics of the species also strongly indicate that Aspergillus is a polythetic class in phenotypic characters.

Subclinical cardiovascular disease and it's improvement after long-term TNF-α inhibitor therapy in severe psoriatic patients.

BACKGROUND: There are conflicting data on the occurrence of subclinical myocardial dysfunction in psoriatic patients and on the impact of long-term tumour necrosis factor-alpha (TNF-α) inhibitor therapy on cardiac function. OBJECTIVE: In this study, we explored whether there are any signs of subclinical cardiovascular disease (echocardiographic abnormalities) in severe psoriatic patients without clinically overt heart disease. As a second objective, the influence of long-term treatment with TNF-α inhibitors on the ventricular functions of psoriatic patients was also investigated. METHODS: Clinical and echocardiographic data from 44 psoriatic patients and 45 age- and sex-matched controls were processed. As a first step, the echocardiographic parameters of psoriatic patients obtained before anti-TNF-α treatment were compared with controls. As a second step, to detect the effect of long-term anti-TNF-α treatment on echocardiographic parameters, data of patients before and after therapy were analysed. RESULTS: The right ventricular Tei index was higher (P < 0.001), whereas the tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall peak systolic velocity were lower (P < 0.001 and P < 0.0001, respectively) in the psoriatic patients than in the controls. Following treatment with TNF-α inhibitors, TAPSE and right ventricular free wall peak systolic velocity significantly improved (P < 0.0001 for both parameters). The Tei index of both ventricles improved during biological therapy; however, this change did not reach statistical significance. CONCLUSION: Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-α therapy has a potentially beneficial effect on these signs.

Incidental tubal endometrioid adenocarcinoma - case report.

The fallopian tubes represent a highly important structure for ovarian carcinogenesis. They provide the passage of eutopic endometrium from the uterus, as well as metastatic cells from the ovaries. A direct source of tumor cells for ovarian cancer was also recently confirmed in the fallopian tubes. The authors present a case report of an incidental tubal endometrioid carcinoma with the coexistence of adenomyosis.

Ochratoxin production and taxonomy of the yellow aspergilli (Aspergillus section Circumdati).

Aspergillus section Circumdati or the Aspergillus ochraceus group, includes species with rough walled stipes, biseriate conidial heads, yellow to ochre conidia and sclerotia that do not turn black. Several species are able to produce mycotoxins including ochratoxins, penicillic acids, and xanthomegnins. Some species also produce drug lead candidates such as the notoamides. A polyphasic approach was applied using morphological characters, extrolite data and partial calmodulin, ß-tubulin and ITS sequences to examine the evolutionary relationships within this section. Based on this approach the section Circumdati is revised and 27 species are accepted, introducing seven new species: A. occultus, A. pallidofulvus, A. pulvericola, A. salwaensis, A. sesamicola, A. subramanianii and A. westlandensis. In addition we correctly apply the name A. fresenii (≡ A. sulphureus (nom. illeg.)). A guide for the identification of these 27 species is provided. These new species can be distinguished from others based on morphological characters, sequence data and extrolite profiles. The previously described A. onikii and A. petrakii were found to be conspecific with A. ochraceus, whilst A. flocculosus is tentatively synonymised with A. ochraceopetaliformis, despite extrolite differences between the two species. Based on the extrolite data, 13 species of section Circumdati produce large amounts of ochratoxin A: A. affinis, A. cretensis, A. fresenii, A. muricatus, A. occultus, A. ochraceopetaliformis (A. flocculosus), A. ochraceus, A. pseudoelegans, A. pulvericola, A. roseoglobulosus, A. sclerotiorum, A. steynii and A. westerdijkiae. Seven additional species produce ochratoxin A inconsistently and/or in trace amounts: A. melleus, A. ostianus, A. persii, A. salwaensis, A. sesamicola, A. subramanianii and A. westlandensis. The most important species regarding potential ochratoxin A contamination in agricultural products are A. ochraceus, A. steynii and A. westerdijkiae.

Identification and nomenclature of the genus Penicillium.

Penicillium is a diverse genus occurring worldwide and its species play important roles as decomposers of organic materials and cause destructive rots in the food industry where they produce a wide range of mycotoxins. Other species are considered enzyme factories or are common indoor air allergens. Although DNA sequences are essential for robust identification of Penicillium species, there is currently no comprehensive, verified reference database for the genus. To coincide with the move to one fungus one name in the International Code of Nomenclature for algae, fungi and plants, the generic concept of Penicillium was re-defined to accommodate species from other genera, such as Chromocleista, Eladia, Eupenicillium, Torulomyces and Thysanophora, which together comprise a large monophyletic clade. As a result of this, and the many new species described in recent years, it was necessary to update the list of accepted species in Penicillium. The genus currently contains 354 accepted species, including new combinations for Aspergillus crystallinus, A. malodoratus and A. paradoxus, which belong to Penicillium section Paradoxa. To add to the taxonomic value of the list, we also provide information on each accepted species MycoBank number, living ex-type strains and provide GenBank accession numbers to ITS, ß-tubulin, calmodulin and RPB2 sequences, thereby supplying a verified set of sequences for each species of the genus. In addition to the nomenclatural list, we recommend a standard working method for species descriptions and identifications to be adopted by laboratories working on this genus.

Phylogeny, identification and nomenclature of the genus Aspergillus.

Aspergillus comprises a diverse group of species based on morphological, physiological and phylogenetic characters, which significantly impact biotechnology, food production, indoor environments and human health. Aspergillus was traditionally associated with nine teleomorph genera, but phylogenetic data suggest that together with genera such as Polypaecilum, Phialosimplex, Dichotomomyces and Cristaspora, Aspergillus forms a monophyletic clade closely related to Penicillium. Changes in the International Code of Nomenclature for algae, fungi and plants resulted in the move to one name per species, meaning that a decision had to be made whether to keep Aspergillus as one big genus or to split it into several smaller genera. The International Commission of Penicillium and Aspergillus decided to keep Aspergillus instead of using smaller genera. In this paper, we present the arguments for this decision. We introduce new combinations for accepted species presently lacking an Aspergillus name and provide an updated accepted species list for the genus, now containing 339 species. To add to the scientific value of the list, we include information about living ex-type culture collection numbers and GenBank accession numbers for available representative ITS, calmodulin, ß-tubulin and RPB2 sequences. In addition, we recommend a standard working technique for Aspergillus and propose calmodulin as a secondary identification marker.

Preparing arbitrary pure states of spatial qudits with a single phase-only spatial light modulator.

Spatial qudits are D-dimensional (D ≥ 2) quantum systems carrying information encoded in the discretized transverse momentum and position of single photons. We present a proof-of-principle demonstration of a method for preparing arbitrary pure states of such systems by using a single phase-only spatial light modulator (SLM). The method relies on the encoding of the complex transmission function corresponding to a given spatial qudit state onto a preset diffraction order of a phase-only grating function addressed at the SLM. Fidelities of preparation above 94% were obtained with this method, which is simpler, less costly, and more efficient than those that require two SLMs for the same purpose.

Borderline ovarian tumor - a case report with genetic testing.

Despite an accurate classification, the borderline category of ovarian tumors is one of the most controversial topics in gynecologic oncology and is confusing to both clinicians and patients. The treatment is often confronted with the necessity of a fertility-sparing approach, although under-treatment increases the risk of disease recurrence. The clear definition of a group of patients with low or high risk of relapse requiring more or less extensive treatment is lacking. Currently, the main criteria affecting the treatment extent include histopathological features, particularly the presence of microinvasion, and invasive implants. Expansion of knowledge about genetic nature of the tumor characteristics may more closely specify the scope of therapeutic approach for individual patients. The authors report a case report of serous borderline ovarian tumor patient with tumor cell dispersion into the gastrointestinal tract. The genes of tumor vascular markers GPM6B and DR6 were also studied and compared to a group of healthy patients.

Palliative treatment of the advanced gastric cancer by means of surgery and HIPEC.

OBJECTIVES: We demonstrate a case report of the patient who suffered from advanced gastric cancer and was treated by means of surgery and HIPEC. BACKGROUND: Gastric cancer is a therapeutic challenge in the European countries due to late diagnosis, advanced stages of the disease in time of diagnosis and early recurrence in cases where a radical surgery is possible. METHOD: The patient with an advanced gastric cancer (pT3N2M1 - peritoneal and ovarian metastases) was treated by means of radical surgery in combination with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC). Surgical treatment was followed by a standard chemotherapy. Due to recurrence, there was the second look surgery one year later again with HIPEC procedure. RESULTS: Patient survived 32 months after diagnosis and despite intraperitoneal recurrence she never developed clinically significant ascites and she never suffered from intestinal obstruction. CONCLUSION: This case demonstrate a potential benefit of new oncosurgical approach -radical surgery + HIPEC + EPIC in the treatment of gastric cancers (Tab. 2, Fig. 6, Graph 4, Ref. 18). Text in PDF www.elis.sk.

Nesfatin-1 exerts long-term effect on food intake and body temperature.

OBJECTIVE: To determine whether the anorexigenic peptide, nesfatin-1 affects energy expenditure, and to follow the time course of its effects. DESIGN: Food intake duration, core body temperature, locomotor activity and heart rate of rats were measured by telemetry for 48 h after a single intracerebroventricular injection of 25 or 100 pmol nesfatin-1 applied in the dark or the light phase of the day. Body weight, food and water intake changes were measured daily. Furthermore, cold-responsive nesfatin-1/NUCB2 neurons were mapped in the brain. RESULTS: Nesfatin-1 reduced duration of nocturnal food intake for 2 days independently of circadian time injected, and raised body temperature immediately, or with little delay depending on the dose and circadian time applied. The body temperature remained higher during the next light phases of the 48 h observation period, and the circadian curve of temperature flattened. After light phase application, the heart rate was elevated transiently. Locomotion did not change. Daily food and water intake, as well as body weight measurements point to a potential decrease in all parameters on the first day and some degree of compensation on the second day. Cold-activated (Fos positive) nesfatin-1/NUCB2 neurones have been revealed in several brain nuclei involved in cold adaptation. Nesfatin-1 co-localised with prepro-thyrotropin-releasing hormone in cold responsive neurones of the hypothalamic paraventricular nucleus, and in neurones of the nucleus raphe pallidus and obscurus that are premotor neurones regulating brown adipose tissue thermogenesis and skin blood flow. CONCLUSION: Nesfatin-1 has a remarkably prolonged effect on food intake and body temperature. Time course of nesfatin-1's effects may be varied depending on the time applied. Many of the nesfatin-1/NUCB2 neurones are cold sensitive, and are positioned in key centres of thermoregulation. Nesfatin-1 regulates energy expenditure a far more potent way than it was recognised before making it a preferable candidate anti-obesity drug.

[New and clinically used oncomarkers of bladder cancer]. / Nové a klinicky vyuzívané onkomarkery karcinómu mocového mechúra.

Bladder cancer is the fourth most common cancer in men and the eighth most common cancer in women. Oncomarkers play a crucial role in early detection of bladder cancer, as well as in treatment response monitoring and prognosis. Search for a new marker by molecular analysis is in progress because any diagnostic sensitivity and specificity enhancement is a great benefit for clinical practice.

Congenital absence of vasopressin and age-dependent changes in ACTH and corticosterone stress responses in rats.

The hypothalamic components of the hypothalamo-pituitary-adrenal axis (HPA) are corticotropin-releasing hormone (CRH) and vasopressin. To test the hypothesis that HPA regulation changes with age, we compared ether and bacterial lipopolysaccharide (LPS) injection induced stress reactions in adult and 10-day-old Brattleboro rats, which naturally lack vasopressin owing to mutation of the gene (di/di). The LPS stimulus was used also with V(1b) receptor antagonist pretreatment (SSR149415). In adult di/di or V(1b) pretreated rats, we observed normal pituitary and adrenocortical secretory responses, while in all 10-day-old rats stress-induced serum corticosterone increases were marked, but adrenocorticotropin (ACTH) increases were significantly smaller. Compared to control pups the adenohypophysis of the 10-day-old di/di rats responded normally to CRH, but their adrenal glands were hyper-responsive to ACTH, while in adults there was greater secretion at both levels with no difference between the genotypes. The serum transcortin level was higher in adults than pups, with the di/di pups having higher transcortin levels than controls. Hence, using the same stressors in adults and pups with both a genetic model and pharmacological pretreatment, we have shown that the role of vasopressin in ACTH regulation is more important during the neonatal period than in adulthood. Blunted hypophysial sensitivity to CRH and similar adrenal gland sensitivity to ACTH in the pups compared to adults suggest that hypothalamic factors could be responsible for the neonatal stress hyporesponsive period.

Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.

Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 µM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.