ABSTRACT
Our purpose was to compare the acute toxicity of ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy (SBRT Arm) and conventional radiotherapy (EBRT Arm) in prostate cancer patients. Two-hundred-sixteen men with prostate cancer were enrolled in our prospective studies. One-hundred and nine were irradiated using CyberKnife to total dose of 36,25 Gy in 5 fractions. One-hundred and seven were irradiated conventionally to total dose of 76 Gy in 38 fractions. Mean age of patients was 69. Acute genitourinary (GU) and gastrointestinal (GI) adverse-events were collected. The maximal acute toxicity EORTC/RTOG score was assumed. A total of 41%, 44%, 12% and 3% of patients presented grade 0, 1, 2 and 3 acute genitourinary toxicity in SBRT arm, respectively. A total of 21%, 33%, 43% and 3% of patients demonstrated acute grade 0, 1, 2 and 3 genitourinary toxicity in EBRT arm. A significant difference between number of patients with grade 2 GU toxicity was observed (p-0.000) and between patients without any toxicity (p-0.0017).A significant difference in frequency of acute GI toxicity between both groups was observed, too. 71% vs. 44% had no toxicity (p-0.0001), and 3% vs. 18% (p-0.0004) presented grade 2 GI toxicity in SBRT and EBRT arms respectively.The acute toxicity rates of fractionated stereotactic radiotherapy is lower compared to conventional irradiation.
Subject(s)
Prostatic Neoplasms/radiotherapy , Aged , Dose Fractionation, Radiation , Humans , Male , Prospective Studies , Radiosurgery/methods , Radiotherapy DosageABSTRACT
Our purpose was to evaluate the efficacy of stereotactic radiotherapy (SRT) for intracranial and extracranial metastases in patients with renal cell carcinoma. The retrospective analysis of 85 patients (151 tumors) treated with SRT was performed. SRT was the sole treatment in 35% of tumors, the other 65% had received additional treatment such as surgery, palliative radiotherapy, immunotherapy or chemotherapy. In 60% and 40% of patients SRT was delivered to brain and extracranial lesions, respectively. The assessment of the efficacy of SRT was based on a radiological imaging (Computed Tomography or Magnetic Resonance Imaging) and estimation of Local Control (LC) as well as Overall Survival (OS). Single fraction was used for 104 tumors and fractionated treatment for 47 tumors. The crude LC for evaluable lesions was 81%, stratified by tumor location: brain LC=94%, extracranial tumors LC=70% (p=0.049). The median OS was 9.4 months; 1-year and 2-year OS were 40% and 29%, respectively. The additional treatment did not lead to a better local response (p=0,543), but resulted in a benefit in OS (7 vs 13 months, p=0,01). A positive relationship between the biologically effective dose (BED) and local response was noted, but the BED was influenced by a tumor volume (R=-0,38; p<0,00001). The presence of multi-organ metastases reduced the OS rate (8.7 vs 19.1 months; p=0,01). The interval between the diagnosis of the metastasis and its treatment with SRT was inversely related to OS (P=0.0001). SRT results in a good local response, which is more beneficial for brain than extracranial lesions. The local efficacy of the SRT depends on the radiation dose. Multidisciplinary treatment and earlier application of SRT improves the prognosis of patients.
Subject(s)
Brain Neoplasms/radiotherapy , Carcinoma, Renal Cell/radiotherapy , Kidney Neoplasms/pathology , Radiosurgery , Brain Neoplasms/secondary , Carcinoma, Renal Cell/secondary , Humans , Neoplasm Metastasis/radiotherapy , Prognosis , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Our purpose was to evaluate the toxicity of CyberKnifeTM based fractionated stereotactic radiotherapy (FSRT) in prostate cancer patients. One-hunred-thirty-two men with low (62) and intermediate (70) prostate cancer were enrolled in our prospective study. Mean age was 69. Total dose of 36,25 Gy in 5 fractions was prescribed. Image guided FSRT was performed on CyberKnife. Minimum follow-up ranged from 3 to 28 months. EORTC/RTOG scale was used to evaluate toxicity. A total of 47%, 10% and 2% of patients presented grade 1, 2 and 3 acute genitourinary toxicity, respectively. In 25% and 3% of patients, respectively, grade 1 and 2 acute gastrointestinal toxicity was observed. No significant association between acute grade ≥ 2 toxicity and clinical factors: age, androgen deprivation therapy or infections were found. Neither CTV nor PTV volumes had significant impact on acute grade ≥ 2 toxicity. Late toxicity was assessed in 104 patients. In 16% and 1% of patients late GU toxicity in grade 1 and 2, respectively, was presented. Late GI toxicity grade 1, 2 and 3 occurred in 8%, 3% and 1% of patients, respectively. The acute toxicity rates of fractionated stereotactic radiotherapy are low. Early data suggest also low late toxicity rates.
ABSTRACT
UNLABELLED: Our purpose was to evaluate interfractional organ and patient movement during radiotherapy of prostate cancer and to calculate the necessary CTV to PTV margins. Fifty patients irradiated between 2009 and 2011were included into the prospective study. The 2D-2D KV system combined with the intraprostatic fiducial marker were used for daily position verification. Based on the 8629 measurements of isocentre displacement an interfractional motion of pelvis and prostate was evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed. Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are necessary in case of no IGRT.There was no clinically relevant changes in patient/target mobility throughout the whole treatment. The IGRT is essential for state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are much bigger in case of no IGRT performed. Changing of margins size throughout regular treatment is not necessary. KEYWORDS: IGRT, prostate cancer, fiducial marker.
ABSTRACT
BACKGROUND: The precise analysis of tumour markers in blood such as circulating cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring of patients after initial therapy. Although high levels of total cfDNA in plasma of cancer patients are consistently demonstrated, a low sensitivity of DNA alterations is reported. OBJECTIVE: The major question regards the recovery of tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of human papillomavirus (HPV16). METHODS: TaqMan technology was used for detection of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. RESULTS: Comparison of four different column-based commercial kits shows that the cfDNA purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity of detection of KRAS mutation and HPV16. The optimized method was used to follow the reduction in cancer-specific cfDNA after therapy. We found that large volume extractions with low volume of DNA eluate enabled trace amounts of tumour-specific cfDNA from cancer patients to be effectively identified. CONCLUSIONS: Data presented in this study facilitate detection of tumour-specific cfDNA and improve standards needed for the implementation of cfDNA technology into routine clinical practice.
Subject(s)
Biomarkers, Tumor/isolation & purification , DNA, Neoplasm/isolation & purification , DNA, Viral/isolation & purification , Human papillomavirus 16/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/virology , Chromatography, Liquid , DNA Mutational Analysis/methods , DNA, Neoplasm/blood , DNA, Neoplasm/genetics , DNA, Viral/blood , DNA, Viral/genetics , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/virology , Humans , Lung Neoplasms/blood , Lung Neoplasms/genetics , Lung Neoplasms/virology , Mutation, Missense , Proto-Oncogene Proteins p21(ras)ABSTRACT
Mono(ADP-ribosyl)transferases regulate the function of target proteins by attaching ADP-ribose to specific amino acid residues in their target proteins. The purpose of this study was to determine the structure, chromosomal localization, and expression profile of the gene for mouse ecto-ADP-ribosyltransferase ART5. Southern blot analyses indicate that Art5 is a single copy gene which maps to mouse chromosome 7 at offset 49.6 cM in close proximity to the Art1, Art2a and Art2b genes. Northern blot and RT-PCR analyses demonstrate prominent expression of Art5 in testis, and lower levels in cardiac and skeletal muscle. Sequence analyses reveal that the Art5 gene encompasses six exons spanning 8 kb of genomic DNA. The 5' end of the Art5 gene overlaps with that of the Art1 gene. A single long exon encodes the predicted ART5 catalytic domain. Separate exons encode the N-terminal leader peptide and a hydrophilic C-terminal extension. Sequencing of RT-PCR products and ESTs identified six splice variants. The deduced amino acid sequence of ART5 shows 87% sequence identity to its orthologue from the human, and 37 and 32% identity to its murine paralogues ART1 and ART2. Unlike ART1 and ART2, ART5 lacks a glycosylphosphatidylinositol-anchor signal sequence and is predicted to be a secretory enzyme. This prediction was confirmed by transfecting an Art5 cDNA expression construct into Sf9 insect cells. The secreted epitope-tagged ART5 protein resembled rat ART2 in exhibiting potent NAD-glycohydrolase activity. This study provides important experimental tools to further elucidate the function of ART5.
Subject(s)
ADP Ribose Transferases/genetics , Genes/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern , Cell Line , Chromosome Mapping , DNA/chemistry , DNA/genetics , DNA, Complementary/chemistry , DNA, Complementary/genetics , Exons , Female , Gene Expression , Introns , Isoenzymes/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Inbred Strains , Molecular Sequence Data , Muridae , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Tissue DistributionABSTRACT
Mono(ADP-ribosyl)transferases regulate the function of target proteins by attaching ADP-ribose to specific amino acid residues in the proteins. We have characterized the gene for mouse arginine-specific ADP-ribosyltransferase, Art1. Southern blot analyses indicate that Art1 is a single-copy gene. Northern blot and reverse transcription-PCR analyses demonstrate prominent expression of Art1 in cardiac and skeletal muscle, and lower levels in spleen, lung, liver and fetal tissues. While human ART1 is not represented in the public expressed sequence tag (EST) database, the database contains 14 mouse Art1 ESTs. The Art1 gene encompasses four exons spanning 20 kb of genomic DNA. The deduced amino acid sequence of Art1 exhibits the characteristic features of a glycosylphosphatidylinositol-anchored membrane protein. It shows 75-77% sequence identity with its orthologues from the human and rabbit, and 33-34% identity with its paralogues from the mouse, Art2-1 and Art2-2. Separate exons encode the N- and C-terminal signal peptides, and a single long exon encodes the entire predicted native polypeptide chain. We expressed Art1 in 293T cells as a recombinant fusion protein with the Fc portion of human IgG1. This soluble protein exhibits enzyme activities characteristic of arginine-specific ADP-ribosyltransferases. The availability of the Art1 gene provides the basis for applying transgene and knockout technologies to further probe the function of this gene product.
Subject(s)
ADP Ribose Transferases/biosynthesis , ADP Ribose Transferases/genetics , Amino Acid Sequence , Animals , Autoimmune Diseases/enzymology , Autoimmune Diseases/genetics , Base Sequence , Blotting, Southern , Cloning, Molecular , Humans , Mice , Molecular Sequence Data , Muscle, Skeletal/enzymology , Myocardium/enzymology , Polymerase Chain Reaction , RNA Splicing , Rabbits , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/chemistry , Sequence AlignmentABSTRACT
El objetivo del presente trabajo fue conocer la prevalencia de anticuerpos en poblaciones de riesgo a los Flavivirus. Se analizaron 189 sueros humanos provenientes de 3 localidades de la Provincia de Formosa. La región estudiada fue seleccionada por su proximidad a Brasil y Paraguay con el fin de verificar la probable introducción de Flavivirus de estos pa1ses, especialmente dengue y fiebre amarilla o la emergencia de los ya existentes en nuestro país. Se realizaron las pruebas de inhibición de la hemoaglutinación (IH), fijación del Complemento (FC) y neutralización (NT), utilizando los virus de la encefalitis de San Luis (ESL), Bussuquara, Ilheus, fiebre amarilla (FA)y dengue subtipos 1 y 2. Todos los sueros fueron negativos por IH para dengue e Ilheus. Por esta prueba un suero fue positivo sólo para FA, y dos sólo para Bussuquara, confirmándose uno por NT. Un total de 22 sueros fue positivo para ESL por IH y 40 sueros reaccionaron por la prueba de NT contra el mismo virus. La prevalencia de anticuerpos IH y NT fue similar para las tres localidades estudiadas. Estos resultados muestran que el virus ESL circula efectivamente en la zona estudiada con un valor de prevalencia de anticuerpos IH y NT significativo y que el mencionado virus podría cumplir un rol importante en infecciones febriles de etiología viral no confirmados en esa zona de nuestro país(AU)
Subject(s)
Flavivirus/isolation & purification , Flavivirus Infections/epidemiology , Flavivirus Infections/immunology , Flavivirus Infections/diagnosis , Encephalitis Virus, St. Louis/isolation & purification , Dengue Virus/isolation & purification , Antibodies, Viral/isolation & purification , Risk Groups , Prevalence , Fever of Unknown Origin , ArgentinaABSTRACT
El objetivo del presente trabajo fue conocer la prevalencia de anticuerpos en poblaciones de riesgo a los Flavivirus. Se analizaron 189 sueros humanos provenientes de 3 localidades de la Provincia de Formosa. La región estudiada fue seleccionada por su proximidad a Brasil y Paraguay con el fin de verificar la probable introducción de Flavivirus de estos pa1ses, especialmente dengue y fiebre amarilla o la emergencia de los ya existentes en nuestro país. Se realizaron las pruebas de inhibición de la hemoaglutinación (IH), fijación del Complemento (FC) y neutralización (NT), utilizando los virus de la encefalitis de San Luis (ESL), Bussuquara, Ilheus, fiebre amarilla (FA)y dengue subtipos 1 y 2. Todos los sueros fueron negativos por IH para dengue e Ilheus. Por esta prueba un suero fue positivo sólo para FA, y dos sólo para Bussuquara, confirmándose uno por NT. Un total de 22 sueros fue positivo para ESL por IH y 40 sueros reaccionaron por la prueba de NT contra el mismo virus. La prevalencia de anticuerpos IH y NT fue similar para las tres localidades estudiadas. Estos resultados muestran que el virus ESL circula efectivamente en la zona estudiada con un valor de prevalencia de anticuerpos IH y NT significativo y que el mencionado virus podría cumplir un rol importante en infecciones febriles de etiología viral no confirmados en esa zona de nuestro país
Subject(s)
Antibodies, Viral/isolation & purification , Dengue Virus/isolation & purification , Encephalitis Virus, St. Louis/isolation & purification , Fever of Unknown Origin , Flavivirus Infections/diagnosis , Flavivirus Infections/epidemiology , Flavivirus Infections/immunology , Flavivirus/isolation & purification , Prevalence , Risk Groups , ArgentinaABSTRACT
The aim of the present study was to investigate the seroprevalence to Flavivirus, in young people living in risk areas. We analyzed 189 human sera from 3 towns in the Province of Formosa. This area corresponds to the border that limits Brasil and Paraguay and the aim was to search for a possible introduction of Dengue and Yellow Fever from these countries. Serological tests such as haemagglutination inhibition (HI), complement fixation (CF) and neutralization (NT) were performed using St. Louis encephalitis (SLE), Bussuquara, Ilheus, Yellow fever and dengue 1 and 2 viruses. No definite evidence for HI antibodies to dengue and Ilheus was obtained. One serum cross-reacted only with yellow fever and two sera only for Bussuquara by the HI test. Only one serum was confirmed to be positive for Bussuquara by NT test. A total of 22 sera from 189 were positive for SLE by the HI test and 40 were also reactive by the NT test. The seroprevalence measured by HI and NT antibodies was similar in the three departments studied. These results show that SLE virus is present in the North of Argentina with an important value of prevalence so that this agent could play an important role in the febrile infections not virologically confirmed.
Subject(s)
Antibodies, Viral/analysis , Flavivirus/isolation & purification , Adult , Argentina/epidemiology , Complement Fixation Tests , Dengue/epidemiology , Flavivirus/immunology , Hemagglutination Tests , Humans , Military Personnel , Neutralization Tests , Risk Factors , Seroepidemiologic Studies , Yellow Fever/epidemiologySubject(s)
Estrogen Replacement Therapy , Estrogens/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Aged , Estrogen Replacement Therapy/adverse effects , Estrogens/biosynthesis , Female , Humans , Male , Middle Aged , Odds Ratio , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporosis/epidemiology , Osteoporosis, Postmenopausal/diagnosis , Osteoporosis, Postmenopausal/epidemiology , PrevalenceSubject(s)
Estrogens/therapeutic use , Osteoporosis/drug therapy , Adult , Aged , Calcium/metabolism , Female , Humans , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/etiologySubject(s)
Fallopian Tubes/surgery , Sterilization Reversal , Surgical Wound Dehiscence , Adult , Female , Humans , Laser Therapy , Pregnancy , Sterilization, TubalABSTRACT
Because of the success of a previous pilot program developed to introduce laparoscopy as a diagnostic and therapeutic tool to residents and attending physicians not previously familiar with the instrument and procedures, a similar program was initiated in laser surgery in gynecology. With a similar format of didactic lectures, journal clubs reviewing the literature on laser surgery and supervision of the attendings learning the procedures, it was thought, the attending could then be certified to perform laser surgery independently and could be used as a teaching resource with other attendings and residents. To date, 15 attendings and 5 senior residents have been so certified. This program is an excellent alternative to laser courses and perhaps a superior method of introducing the instrument and procedure to practicing gynecologists and those in training. Since certification by the Joint Commission of Hospital Accreditation must be obtained, this program allows teaching and certification sessions simultaneously.
Subject(s)
Gynecology/education , Laser Therapy , Medical Staff, Hospital/education , Certification , Female , Genital Neoplasms, Female/surgery , Humans , Joint Commission on Accreditation of Healthcare OrganizationsABSTRACT
The conservative use of estrogens for prevention and treatment of osteoporosis is discussed. The author stresses the importance of thorough pelvic examination to detect inflammatory processes, possible generative tract prolapses, and/or growths.
