Bizarre presentation of choriocarcinoma: A case report / Philippine Journal of Obstetrics and Gynecology

@#Choriocarcinoma is a malignant subtype of gestational trophoblastic disease that follows any type of pregnancy. It is characterized by rapid hematogenous spread to multiple organs, associated with high human chorionic gonadotropin levels with good response to chemotherapy. We present the case of a 31‑year‑old Filipina who initially presented with severe headaches and blurring of vision 3 years after an unremarkable term pregnancy. The transvaginal ultrasound was normal. After a series of diagnostic tests, the initial working impression was a primary brain tumor with metastases to the lungs, adrenal, kidney, and vulva. Emergency craniotomy was done due to deteriorating status secondary to an intracranial hemorrhage. The histopathology report showed choriocarcinoma. Chemotherapy using Etoposide‑Methotrexate‑Actinomycin D‑Cyclophosphamide‑Vincristine with high‑dose methotrexate and concomitant whole‑brain irradiation was then instituted with good response. This case highlights the importance of having a high index of suspicion for gestational trophoblastic neoplasia to prevent the performance of unnecessary procedures, leading to a delay in diagnosis and the institution of the appropriate treatment.

Super-sensitive bifunctional nanoprobe: Self-assembly of peptide-driven nanoparticles demonstrating tumor fluorescence imaging and therapy

The development of nanomedicine has recently achieved several breakthroughs in the field of cancer treatment; however, biocompatibility and targeted penetration of these nanomaterials remain as limitations, which lead to serious side effects and significantly narrow the scope of their application. The self-assembly of intermediate filaments with arginine-glycine-aspartate (RGD) peptide (RGD-IFP) was triggered by the hydrophobic cationic molecule 7-amino actinomycin D (7-AAD) to synthesize a bifunctional nanoparticle that could serve as a fluorescent imaging probe to visualize tumor treatment. The designed RGD-IFP peptide possessed the ability to encapsulate 7-AAD molecules through the formation of hydrogen bonds and hydrophobic interactions by a one-step method. This fluorescent nanoprobe with RGD peptide could be targeted for delivery into tumor cells and released in acidic environments such as endosomes/lysosomes, ultimately inducing cytotoxicity by arresting tumor cell cycling with inserted DNA. It is noteworthy that the RGD-IFP/7-AAD nanoprobe tail-vein injection approach demonstrated not only high tumor-targeted imaging potential, but also potent antitumor therapeutic effects in vivo. The proposed strategy may be used in peptide-driven bifunctional nanoparticles for precise imaging and cancer therapy.

A spectrum of gestational trophoblastic neoplasia

Gestational trophoblastic disease is a spectrum of diseases caused by overgrowth of chorionic villi of placenta. They range from most Benign to most Malignant. Those with local invasion or metastasis are labelled as Gestational trophoblastic Neoplasia (GTN). We have conducted a retrospective observational study of various Gestational trophoblastic neoplasias (GTN) at NRIGH for a period of 3 years, out of which, one example of each variety is being presented. All these varieties have been successfully treated and all the patients are under follow up.

Chemotherapy outcome of patients with choriocarcinoma / Монголын Анагаах Ухаан

Background: Choriocarcinoma 15-20 new cases per year diagnosed at National Cancer Center of Mongolia. Due to insufficient necessary new drugs for choriocarcinoma patients, cancer center cannot provide the most useful treatment EMA/CO so patients were treated MAC or metothrexate, Adriamycin and cyclophosphamide. The outcomes of patients with choriocarcinoma treated with combined chemo drugs never been studied in Mongolia. Goal: To evaluate the results of combined chemotherapy in choriocarcinoma at National Cancer Center of Mongolia. Methods: Retrospective cohort review of 42 patients with choriocarcinoma who treated with MAC combination chemotherapy at NCC of Mongolia during 2004-2007. Based on MAC ppatients charts we evaluated clinical characteristics, level of HCG during treatment cycles, ultrasound changes and other lab tests. Results: We treated 42 patients with choriocarcinoma from 2004 through 2007. All patients were treated with MAC combination chemotherapy at NCC. The number of cases with choriocarcinoma is increasing in each year. 37.5% of these patients were aged between 30-34 years old, so it shows maximum incidence occurs during child bearing years. The most common clinical characteristics were 44% bleeding, 32% lower abdominal quadrant pain related to disease stages, 36% cough, and 28% fever. Out of 42 patients 35% of them had lung metastasis which was significantly different than other gynecological cancer metastasis. Conclusion: MAC combination treatment offers long-term disease-free survival and potential cure in patients with choriocarcinoma. The reported median survival in these group patients is 5 years. Importantly, 56% of patients were lived up to 5 years in remission.

Production of actinomycin-D by the mutant of a new isolate of Streptomyces sindenensis / Produção de actinomicina-D por um mutante de uma nova cepa de Streptomyces sindenensis

An actinomycin-D producing strain was isolated from soil and characterized as Streptomyces sindenensis. The culture was subjected to UV irradiation and a mutant with 400 percent higher actinomycin-D production was isolated (400 mg/l-1 as compared to 80 mg/l-1 produced by the parent). Production medium was optimized and antibiotic yield with the mutant was enhanced to 850 mg/l-1 which is 963 percent higher as compared with the parent.

Uma cepa produtora de actinomicina-D foi isolada de solo e caracterizada como Streptomyces sindenensis. A cultura foi submetida à radiação UV, e um mutante capaz de produzir 400 por cento mais actinomicina-D foi isolado (400mg/L comparado a 80mg/L produzido pela cepa parental). O meio de produção do antibiótico foi otimizado e o rendimento aumentou para 850 mg/L, ou seja, 963 por cento mais alto que a cepa parental.

Roles of HSP 70 in Actinomycin D-Induced Inhibition of Proliferation and Apoptosis in Lung Adenocarcinoma Cell / 生物化学与生物物理进展

It had been proved by many evidences that several heat shock proteins (HSPs) expression is up-regulated in tissue-derived primary lung cancer, and HSPs may play important roles in development, in resistant to drugs and in prognosis of lung cancer. However, there have not still systemic research on which HSPs,especially HSP70 can be or not thought as a new biological target in the therapy to lung cancer. In order to address the expression and roles of heat shock protein 70 (HSP70) in lung adenocarcinoma, immunoblotting was performed to detect the expression of HSP70 in tissue specimens from lung adenocarcinoma which were diagnosed unambiguously by branch fibromicroscopy and were excised. It showed that in the normal lung tissues, the expression of HSP70 was less then that in cancer tissues. After down-regulation of HSP70 protein by HSP70 anti-sense oligonucleotides in A549 cell line, MTT assay showed that the proliferation of A549 cells was inhibited remarkably after the treatment with HSP70 antisense oligonucleotides and Act D. There had significant differential in HSP70 antisense treatment group followed by Act D treatment and Act D treatment group. Results of Hoechst33258 staining revealed that HSP70 antisense oligonucleotides could promote Act D-mediated apoptosis in A549 cells with a higher percentage of apoptotic cells (26.91?3.73)% than that of Act D-treated group (16.83?3.41)% (P

Hepatic Veno-occlusive Disease after Combination Chemotherapy with Vincristine, Actinomycin-D, Cyclophosphamide: Successful Treatment with Glutathione and Vitamin E / 대한소아혈액종양학회지

Hepatic veno-occlusive disease (VOD) is characterized by the narrowing or fibrous obliteration of terminal hepatic venules and small sublobular veins. The obliteration of blood flow may lead to tender hepatomegaly, ascites, hepatocellular necrosis, and possibly encephalopathy. Hepatic VOD is a well described complication after allogeneic and autologous stem cell transplantation (SCT) for malignancy. The intergroup rhabdomyosarcoma study (IRS) group has extensively used the combination chemotherapy of vincristine, actinomycin-D, and cyclophosphamide (VAC) for the treatment of rhabdomyosarcoma and hepatic VOD was rarely reported after the administration of VAC chemotherapy. We report a case of severe hepatic VOD which occurred in a 7 year-old boy with stage III rhabdomyosarcoma after VAC chemotherapy according to IRS-IV regimen. He developed persistent thrombocytopenia, tender hepatomegaly, jaundice, weight gain due to ascites and generalized edema, and was treated successfully with N-acetylcysteine, nitrate, green tea polyphenol, glutathione and vitamin E.

The treatment of bladder tumors by the intravesical instillation of thio-TEPA or of actinomycin D

Thio-TEPA weekly instillations of 30-60 mg. in 30-60 ml. of sterile water or saline were employed in 20 patients with bladder papilloma or various stages of bladder carcinoma. Two of 6 patients with papilloma showed complete disappearance of the tumor after an average of 8 instillations and two of six (2/6) patients with papilloma showed partial destruction of the tumor. In 10 patients with deeply infiltrating cancers practically no response was observedActinomycin D was employed in 7 patients using a weekly topical dose of 1.0 mg. in 30 ml. of sterile water or saline. In the four patients with papilloma, one showed necrotic changes without apparent decrease in size of the tumor. In no instance was disappearance of a papilloma observedAs employed in this series, topical actinomycin D instillation for bladder tumor was of no value. Topical thio-TEPA may be useful for patients who are poor surgical risks and for patients whose lesions are diffuse and not amendable to surgical attack less than a cystectomy. For solitary or few papillary tumors conventional methods of transurethral treatment are preferable. (Summary)

Simultaneous Three Color Detection of Surface Antigen (My 7), Intracellular Antigen (c-myc), and DNA Content using Single Laser Flow Cytometry / 대한산부인과학회잡지

Flow cytometry, a useful tool for measuring DNA content and cell differentiation as expressed by cell surface markers, is utilized to measure multiple antigens, especially surface antigen, intracellular oncoprotein, and DNA content, simultaneously. For this simultaneous detection, several methods off ixation and permeabilization have been used with limited values. In this study, 20 ng/ml of lysolecithin in 1% paraformaldehyde solution was utilized for fixation and permeabilization of cultured promyelocytic leukemic cells(HL 60). The cells were first stained with phycoerythrin (PE)-conjugated monoclonal antibody to the cell surface My 7 antigen and then were fixed and permeabilized with 20 ng/ml of lysolecithin in 1% partormaldehyde solution. After incubation, the fixed and permeabilized cells were stained with monoclonal antibody to intracellular c-myc antigen, which were followed by fluorescein isothiocyanate (FITC)-conjugated secondary antibody. The c-myc stained cells were finally stained for DNA content with 7-amino-actinomycin D(7-AAD). This procedure permits excellent staining for intracellular oncoproteins and preservation of surface antigens with relatively low cofficients of variation (CV) for the G0G1 peak of the DNA histograms and suggests that the sequential staining procedure of surface antigen, intracellular antigen, and DNA content will be extended for the study of correlations with cellular differentiation, expression of oncoproteins, and cell cycle analysis in the cells which are obtained from human malignant diseases using a 488 nm single laser flow cytometry.

Effects of actinomycin D and cycloheximide on gonadotropin- or 17α., 20β-dihydroxy-4- pregnen-3-one-induced in vitro maturation in oocytes of the catfish, Clarias batrachus.

The effect of inhibitors in the oocyte maturation of Clarias batrachus, was investigated in vitro using actinomycin D and cycloheximide. Full-grown immature oocytes incubated with salmon gonadotropin (SG-G100) and 17α, 20ß-dihydroxy-4-pregnen-3-one at the concentration of 1 μg/ml induced 86·0 ± 1·2% and 91·3 ± 2·4% of germinal vesicle breakdown, respectively. When the oocytes were incubated with SG-G100 (1 μg/ml) + different concentrations of actinomycin D or cycloheximide, a significant drop in the frequency of germinal vesicle breakdown was observed. Thus, gonadotropin-induced maturation was inhibited by both transcriptional and translational inhibitors. When the oocytes were incubated with 17α, 20ß-dihydroxy-4-pregnen-3-one (1μg/ml) + different concentrations of cycloheximide, a significant inhibition of germinal vesicle breakdown was recorded. However, the maturation was not inhibited when the oocytes were incubated in the presence of 17α, 20ß-dihydroxy-4-pregnen-3-one (1 μg/ml) and different concentrations of actinomycin D. This suggests that mRNA synthesis is not obligatory for 17α, 20β- dihydroxy-4-pregnen-3-one induced oocyte maturation. Based on the time course experiment, it was observed that the inhibition of maturation in cycloheximide treated oocytes extends up to 12 h after which the effect becomes slowly subdued.

Structural and mode of action studies on bio-active molecules.

The technique of nuclear Overhauser effect difference spectroscopy allows the determination, from 1H nuclear magnetic resonance spectra, of those protons in a structure which are near in space to a selected, irradiated proton. The experiment is extremely powerful in the determination of structure in solution, and is sufficiently precise often to give stereochemical detail. The method was used in determination of the structures of the antibiotics of the teicoplanin complex (members of the vancomycin group), and the principles are briefly illustrated. Additionally, nuclear magnetic resonance pulse sequences can be used to edit 13C spectra (separate the spectrum into four spectra, containing C, CH, CH2, and CH3 carbons), and this technique also aided the structure elucidation of the teicoplanin complex. Finally, it is emphasised that nuclear Overhauser effect difference spectroscopy can be used to determine the molecular details of drug binding sites, and an example is given.