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1.
Front Oncol ; 13: 1270498, 2023.
Article in English | MEDLINE | ID: mdl-38023175

ABSTRACT

Simple summary: Stereotactic body radiotherapy (SBRT) of 35-36.25 Gy in five fractions with the CyberKnife System yields excellent control with low toxicity in low-intermediate-risk prostate cancer patients. We found no differences in biochemical control and overall survival in relation to dose. There were no significant differences in toxicity or quality of life between the two groups. Aims: Stereotactic body radiotherapy (SBRT) is an emerging therapeutic approach for low- and intermediate-risk prostate cancer. We present retrospective data on biochemical control, toxicity, and quality of life of CyPro Trial. Materials and methods: A total of 122 patients with low- and intermediate-risk prostate cancer were treated with the CyberKnife System at a dose of 35 Gy or 36.25 Gy in five fractions. Biochemical failure (BF)/biochemical disease-free survival (bDFS) was defined using the Phoenix method (nadir + 2 ng/ml). Acute/late rectal and urinary toxicities were assessed by the Radiation Therapy Oncology Group (RTOG) toxicity scale. Quality of life (QoL) was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and PR25. International Erectile Function Index-5 (IIEF5) and International Prostate Symptom Score (IPSS) questionnaires were administered at baseline, every 3 months after treatment during the first years, and then at 24 months and 36 months. Results: The 1-, 2-, and 5-year DFS rates were 92.9%, 92.9%, and 92.3%, respectively, while the 1-, 2-, and 5-year bDFS rates were 100%, 100%, and 95.7%, respectively. With regard to risk groups or doses, no statistically significant differences were found in terms of DFS or bDFS. Grade 2 urinary toxicity was acute in 10% and delayed in 2% of patients. No Grade 3 acute and late urinary toxicity was observed. Grade 2 rectal toxicity was acute in 8% and late in 1% of patients. No Grade 3-4 acute and late rectal toxicity was observed. Grade 2 acute toxicity appeared higher in the high-dose group (20% in the 36.25-Gy group versus 3% in the 35-Gy group) but was not statistically significant. Conclusion: Our study confirms that SBRT of 35-36.25 Gy in five fractions with the CyberKnife System produces excellent control with low toxicity in patients with low-intermediate-risk prostate cancer. We found no dose-related differences in biochemical control and overall survival. Further confirmation of these results is awaited through the prospective phase of this study, which is still ongoing.

2.
Cancers (Basel) ; 14(13)2022 Jun 29.
Article in English | MEDLINE | ID: mdl-35804958

ABSTRACT

The management of prostate cancer recurrence following external beam radiotherapy is not defined yet. Stereotaxic body reirradiation therapy showed encouraging results for local and biochemical control. From April 2017 to December 2020, 29 patients with prostate cancer recurrence were collected, joining the retrospective studies CyPro (prot. 46/19 OSS) and CLARO (Prot. 19/20 OSS) trials. Patients received Cyberknife® treatment (17 pts) or alternatively VMAT (Volumetric Modulated Arc Technique) therapy by IGRT (Image-Guided Radiation Therapy)/Clarity® (12 pts). By comparing the reirradiation of two groups, urinary (GU), rectal (GI) toxicities, and biochemical control were investigated. Further, the two techniques were dosimetrically compared by rival plans. The VMAT-IGRT Clarity® treatments were replanned with an optimized template developed for prostate VMAT-SBRT in FFF mode keeping the same dose and fractionation scheduled for Cyberknife Group (30 Gy in 5 fx, at 80% isodose). In the CK group, 23% of patients experienced grade 2 acute GU, while 6% grade 2 acute GI. In the VMAT-Clarity® group, acute GU toxicity was recorded in 17%, while for 8% grade 2 late toxicity was recorded. The dosimetric analysis shows that the VMAT-FFF allows to deliver a biological equivalent dose to CK, with the advantage of reducing the likelihood of toxicities arising.

3.
Life (Basel) ; 12(5)2022 May 10.
Article in English | MEDLINE | ID: mdl-35629378

ABSTRACT

In recent years, stereotactic body radiation therapy (SBRT) has gained popularity among clinical methods for the treatment of medium and low risk prostate cancer (PCa), mainly as an alternative to surgery. The hypo-fractionated regimen allows the administration of high doses of radiation in a small number of fractions; such a fractionation is possible by exploiting the different intrinsic prostate radiosensitivity compared with the surrounding healthy tissues. In addition, SBRT treatment guaranteed a better quality of life compared with surgery, avoiding risks, aftermaths, and possible complications. At present, most stereotactic prostate treatments are performed with the CyberKnife (CK) system, which is an accelerator exclusively dedicated for stereotaxis and it is not widely spread in every radiotherapy centre like a classic linear accelerator (LINAC). To be fair, a stereotactic treatment is achievable also by using a LINAC through Volumetric Modulated Arc Therapy (VMAT), but some precautions must be taken. The aim of this work is to carry out a dosimetric comparison between these two methodologies. In order to pursue such a goal, two groups of patients were selected at Instituto Nazionale Tumori-IRCCS Fondazione G. Pascale: the first group consisting of ten patients previously treated with a SBRT performed with CK; the second one was composed of ten patients who received a hypo-fractionated VMAT treatment and replanned in VMAT-SBRT flattening filter free mode (FFF). The two SBRT techniques were rescaled at the same target coverage and compared by normal tissue sparing, dose distribution parameters and delivery time. All organs at risk (OAR) constraints were achieved by both platforms. CK exhibits higher performances in terms of dose delivery; nevertheless, the general satisfying dosimetric results and the significantly shorter delivery time make VMAT-FFF an attractive and reasonable alternative SBRT technique for the treatment of localized prostate cancer.

4.
Cancers (Basel) ; 13(16)2021 Aug 23.
Article in English | MEDLINE | ID: mdl-34439390

ABSTRACT

BACKGROUND: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions ("abscopal effect") through stimulation of anti-tumor immune effects ("radiation-induced immunity"). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. AIMS: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses' duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. METHODS: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p0 = 0.0077, with α = 0.05 and 1-ß = 0.60, the final sample size is 25 patients.

5.
In Vivo ; 35(3): 1849-1856, 2021.
Article in English | MEDLINE | ID: mdl-33910872

ABSTRACT

BACKGROUND: The use of intra-fractional monitoring and correction of prostate position with the Image Guided Radio Therapy (IGRT) system can increase the spatial accuracy of dose delivery. Clarity is a system used for intrafraction prostate-motion management, it provides a real-time visualization of prostate with a transperineal ultrasound. The aim of this study was to evaluate the use of Clarity-IGRT on proper intrafraction alignment and monitoring, its impact on Planning Tumor Volume margin and on urinary and rectal toxicity in elderly patients not eligible for surgery. PATIENTS AND METHODS: Twenty-five elderly prostate cancer patients, median age=75 years (range=75-90 years) were treated with Volumetric Radiotherapy and Clarity-IGRT using 3 different schemes: A) 64.5/72 Gray (Gy) in 30 fractions on prostate and seminal vesicles (6 patients); B) 35 Gy in 5 fractions on prostate and seminal vesicles (12 patients); C): 35 Gy in 5 fractions on prostate (7 patients). Ultrasound identification of the overlapped structures to the detected ones during simulation has been used in each session. A specific software calculates direction and entity of necessary shift to obtain the perfect match. The average misalignment in the three-dimensional space has been determined and shown in a box-plot. RESULTS: All patients completed treatment with mild-moderate toxicity. During treatment, genitourinary toxicity was 32% Grade 1; 4% Grade 2, rectal was 4% Grade 1. At follow-up of 3 months, genitourinary toxicity was 20% Grade 1; 4% Grade 2, rectal toxicity was 4% Grade 2. At follow-up of 6 months, genitourinary toxicity was 4% Grade 1; 4% Grade 2. Rectal toxicity was 4% Grade 2. CONCLUSION: Radiotherapy with the Clarity System allows a reduction of PTV margins, the amount of fractions can be reduced increasing the total dose, not exacerbating urinary and rectal toxicity with greater patient's compliance.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Image-Guided , Aged , Humans , Male , Prostatic Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Radiotherapy, Image-Guided/adverse effects , Ultrasonography
6.
Medicine (Baltimore) ; 99(50): e23574, 2020 Dec 11.
Article in English | MEDLINE | ID: mdl-33327317

ABSTRACT

Hypofractionation for localized prostate cancer treatment is rapidly spreading in the medical community and it is supported by radiobiological evidences (lower α/ß ratio compared with surrounding tissues). Stereotactic body radiation therapy (SBRT) is a technique to administer high doses with great precision, which is commonly performed with CyberKnife (CK) in prostate cancer treatment. Since the CyberKnife (CK) is not available at all radiotherapy center, alternative SBRT techniques are available such as Volumetric Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). The aim of the present study was to compare the dosimetric differences between the CK, VMAT, and HT plans for localized prostate cancer treatment.Seventeenpatients have been recruited and replanned using VMAT and HT to this purpose: they received the treatment using the CK with a prescription of 36.25 Gy in 5 fractions; bladder, rectum and penis bulb were considered as organs at risk (OAR). In order to compare the techniques, we considered DVHs, PTV coverage, Conformity Index and new Conformity Index, Homogeneity Index, beam-on time and OARs received dose.The 3 treatments methods showed a comparable coverage of the lesion (PTV 95%: 99.8 ± 0.4% CK; 98.5 ± 0.8% VMAT; 99.4 ±â€Š0.5% HT. P < .05) and good sparing of OARs. Nevertheless, the beam-on time showed a significant difference (37 ±â€Š9 m CK; 7.1 ±â€Š0.3 m VMAT; 17 ±â€Š2 m HT. P < .05).Our results showed that, although CK is the best SBRT technique for prostate cancer treatment, in case this technology is not available, it can be replaced by a similar treatment delivered by VMAT technique. VMAT can be administrated only if it has an appropriate Image Guided Radiation Therapy (IGRT) tracking system.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiation Dose Hypofractionation , Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Magnetic Resonance Imaging , Male , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Radiometry/methods , Radiosurgery/methods
7.
Radiother Oncol ; 148: 126-132, 2020 07.
Article in English | MEDLINE | ID: mdl-32361572

ABSTRACT

PURPOSE: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). METHODS: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. RESULTS: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D15% and Dmean were reduced by 8.1% and 17.9%, bladder D25% and Dmean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable. CONCLUSION: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.


Subject(s)
Prostatic Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Male , Organs at Risk , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
8.
Mol Med Rep ; 21(3): 1501-1508, 2020 03.
Article in English | MEDLINE | ID: mdl-32016459

ABSTRACT

Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide. It is also the second most common cause of cancer­associated mortality; it accounted for about 9.2% of all cancer deaths in 2018, most of which were due to resistance to therapy. The main treatment for CRC is surgery, generally associated with chemotherapy, radiation therapy and combination therapy. However, while chemo­radiotherapy kills differentiated cancer cells, mesenchymal stem­like cells are resistant to this treatment, and this can give rise to therapy­resistant tumors. Our previous study isolated T88 primary colon cancer cells from a patient with sporadic colon cancer. These cells exhibited mesenchymal and epithelial features, high levels of epithelial­to­mesenchymal transition transcription factors, and stemness markers. In addition, it was revealed that lithium chloride (LiCl), a specific glycogen synthase kinase (GSK)­3ß inhibitor, induced both the mesenchymal­to­epithelial transition and differentiation, and also reduced cell migration, stemness features and cell plasticity in these primary colon cancer cells. The aim of the present study was to investigate the effect of LiCl treatment on the viability of primary colon cancer cells exposed to 7 Gy delivered by high­energy photon beams, which corresponds to 6 megavolts of energy. To achieve this aim, the viability of irradiated T88 cells was compared with that of irradiated T88 cells pre­treated with LiCl. As expected, it was observed that LiCl sensitized primary colon cancer cells to high­energy photon irradiation treatment. Notably, the decrease in cell viability was greater with combined therapy than with irradiation alone. To explore the molecular basis of this response, the effect of LiCl on the expression of Bax, p53 and Survivin, which are proteins involved in the apoptotic mechanism and in death escape, was analyzed. The present study revealed that LiCl upregulated the expression of pro­apoptotic proteins and downregulated the expression of proteins involved in survival. These effects were enhanced by high­energy photon irradiation, suggesting that LiCl could be used to sensitize colon cancer cells to radiation therapy.


Subject(s)
Lithium Chloride/pharmacology , Photons , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Cell Survival/drug effects , Colonic Neoplasms/diagnosis , Colonic Neoplasms/drug therapy , Colonic Neoplasms/radiotherapy , Humans , Radiotherapy, High-Energy/methods , Signal Transduction/drug effects
9.
Neuroradiol J ; 31(1): 18-26, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29206077

ABSTRACT

Objective The aim of this work was to evaluate the impact of stereotactic radiosurgery/fractionated stereotactic radiotherapy with the Cyberknife system on local disease control, clinical outcome and toxicity in patients with meningioma, according to the site and histological grade of lesion. From January 2013 to April 2017, 52 patients with intracranial meningiomas were treated with the Cyberknife system. Twenty-four patients had undergone previous surgery: 38% gross total resection, 10% subtotal resection; 27 patients underwent no surgery; 22 patients had a recurrence of meningioma. Methods Radiosurgery was used for lesions smaller than 2 cm, stereotactic radiotherapy for lesions larger than 2 cm, or smaller but close to a critical site such as the optical chiasm, optic pathway or brainstem. Results Local control and clinical outcomes were analysed. Median follow-up was 20 months: six patients died, one after re-surgery died from post-surgical sepsis, three from heart disease. Progression-free survival had a mean value of 38.3 months and overall survival of 41.6 months. We evaluated at 12 months 28 patients (100% local control); at 24 months 19 patients (89% local control); at 36 months nine patients (89% local control). At baseline, 44/52 patients (85%) were symptomatic: 19 visual disorders, 17 motor disorders, six hearing disorders, 10 headache and six epilepsy. Visual symptoms remained unchanged in 52%, improved in 32%, resolved in 16%. Headache was improved in 40%, resolved in 10%, unchanged in 50%. Epilepsy was resolved in 17%, unchanged in 33%, worsened in 33%. Conclusions Stereotactic radiosurgery/fractionated stereotactic radiotherapy with Cyberknife provides a good local disease control, improving visual, hearing and motor symptoms.


Subject(s)
Meningeal Neoplasms/radiotherapy , Meningioma/radiotherapy , Radiosurgery/instrumentation , Adolescent , Adult , Aged , Dose Fractionation, Radiation , Female , Humans , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Neoplasm Grading , Treatment Outcome
11.
Int J Med Sci ; 14(6): 554-559, 2017.
Article in English | MEDLINE | ID: mdl-28638271

ABSTRACT

The gold standard for the detection of urothelial carcinoma is represented by urethro-cystoscopy and biopsy. Both procedures are invasive and expensive and therefore cytology is often used as first approach to investigate on a possible neoplasia, being a safe and cost-effective diagnostic modality of evaluation. Because cytology alone is not highly sensitive for detection of low grade urothelial carcinoma and recurrence of the disease, several adjunct markers and urine based tests for urothelial carcinoma have been developed, which can help in the final diagnosis. In particular, ProEx C is an immunohistochemical cocktail containing antibodies direct against topoisomerase IIα (TOP2A) and minichromosome maintenance 2 (MCM2) proteins. It proved to be a valid biomarker especially in detecting squamous intraepithelial lesions in cervical liquid-based samples and in discerning these lesions from their mimickers, as well as in ovarian, endometrial, vulvar, primary and metastatic melanomas, breast, pancreatic and renal cell carcinomas. This brief review covers the effective utility of ProEx C as adjunct tool in assessing the urothelial lesions in urine cytology, also providing prognostic and therapeutic information to help in clinical decisions.


Subject(s)
Biomarkers, Tumor/genetics , DNA Topoisomerases, Type II/genetics , Minichromosome Maintenance Complex Component 2/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Urologic Neoplasms/diagnosis , Antibodies/immunology , Biomarkers, Tumor/immunology , Cytodiagnosis , DNA Topoisomerases, Type II/immunology , Female , Humans , Minichromosome Maintenance Complex Component 2/immunology , Poly-ADP-Ribose Binding Proteins/immunology , Prognosis , Reagent Kits, Diagnostic , Urologic Neoplasms/genetics , Urologic Neoplasms/pathology , Vaginal Smears
12.
Oncotarget ; 8(30): 50240-50251, 2017 Jul 25.
Article in English | MEDLINE | ID: mdl-28445135

ABSTRACT

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.


Subject(s)
Biomarkers, Tumor/genetics , Genes, Tumor Suppressor/physiology , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Humans , Male , Prostatic Neoplasms/pathology
13.
Oncotarget ; 8(18): 30606-30616, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28389628

ABSTRACT

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

14.
Oncotarget ; 8(10): 17383-17395, 2017 Mar 07.
Article in English | MEDLINE | ID: mdl-28129649

ABSTRACT

PURPOSE: The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. METHODS: PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. RESULTS: The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. CONCLUSIONS: Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.


Subject(s)
Dose Fractionation, Radiation , Prostatic Neoplasms/radiotherapy , Radiation Injuries/etiology , Radiotherapy, Intensity-Modulated/methods , Humans , Male , Radiotherapy, Intensity-Modulated/adverse effects , Randomized Controlled Trials as Topic , Rectal Diseases/etiology , Rectum/pathology , Rectum/radiation effects , Urination Disorders/etiology
15.
Oncotarget ; 7(51): 85641-85649, 2016 Dec 20.
Article in English | MEDLINE | ID: mdl-27821802

ABSTRACT

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.


Subject(s)
DNA Damage , DNA Repair , Neoplasms, Germ Cell and Embryonal/genetics , Testicular Neoplasms/genetics , Tumor Suppressor Protein p53/genetics , Animals , Cisplatin/therapeutic use , DNA Repair/drug effects , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Humans , Male , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/metabolism , Neoplasms, Germ Cell and Embryonal/pathology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Signal Transduction , Testicular Neoplasms/drug therapy , Testicular Neoplasms/metabolism , Testicular Neoplasms/pathology , Tumor Suppressor Protein p53/metabolism
16.
Angle Orthod ; 84(4): 665-72, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24308528

ABSTRACT

OBJECTIVE: To evaluate the effects of intraoral aging on surface properties of esthetic and conventional nickel-titanium (NiTi) archwires. MATERIALS AND METHODS: Five NiTi wires were considered for this study (Sentalloy, Sentalloy High Aesthetic, Superelastic Titanium Memory Wire, Esthetic Superelastic Titanium Memory Wire, and EverWhite). For each type of wire, four samples were analyzed as received and after 1 month of clinical use by an atomic force microscope (AFM) and a scanning electronic microscope (SEM). To evaluate sliding resistance, two stainless steel plates with three metallic or three monocrystalline brackets, bonded in passive configuration, were manufactured; four as-received and retrieved samples for every wire were pulled five times at 5 mm/min for 1 minute by means of an Instron 5566, recording the greatest friction value (N). Data were analyzed by one-way analysis of variance and by Student's t-test. RESULTS: After clinical use, surface roughness increased considerably. The SEM images showed homogeneity for the as-received control wires; however, after clinical use esthetic wires exhibited a heterogeneous surface with craters and bumps. The lowest levels of friction were observed with the as-received Superelastic Titanium Memory Wire on metallic brackets. When tested on ceramic brackets, all the wires exhibited an increase in friction (t-test; P < .05). Furthermore, all the wires, except Sentalloy, showed a statistically significant increase in friction between the as-received and retrieved groups (t-test; P < .05). CONCLUSION: Clinical use of the orthodontic wires increases their surface roughness and the level of friction.


Subject(s)
Coated Materials, Biocompatible/chemistry , Dental Alloys/chemistry , Mouth/physiology , Nickel/chemistry , Orthodontic Appliance Design , Orthodontic Wires , Titanium/chemistry , Ceramics/chemistry , Dental Stress Analysis/instrumentation , Friction , Gold Alloys/chemistry , Humans , Materials Testing , Microscopy, Atomic Force , Microscopy, Electron, Scanning , Orthodontic Brackets , Platinum/chemistry , Polymers/chemistry , Stainless Steel/chemistry , Surface Properties , Time Factors
17.
Clin Oral Investig ; 18(2): 571-8, 2014.
Article in English | MEDLINE | ID: mdl-23604784

ABSTRACT

OBJECTIVES: The purpose of the study was to evaluate by micro-computerized tomography (microCT) areas and volumes of post, cement, and voids/bubbles in the post space of oval-shaped premolars restored either with oval or circular posts. MATERIALS AND METHODS: Twelve extracted premolars were divided into two groups according to the drill-fiber post system used: (1) GC Fiber Post Drill + circular post GC Fiber Post; (2) Ellipson tip(TM) + oval post Ellipson post(TM). Each tooth was scanned using microCT, and areas and volumes of canal, post space, post, cement, and voids at coronal, medium, and apical level were calculated by using a three-dimensional visualization software. Two-way analyses of variance and Tukey tests were used for statistical analysis (p < 0.05). RESULTS: The area of voids was significantly greater at apical level of oval posts, but no difference was found between the levels among the groups. Regardless of post shape, the volume of voids and of cement was significantly higher at the coronal level. With oval posts, the total volume of cement was twice as much as with circular posts, and the difference was statistically significant. CONCLUSIONS: Our results indicate that the volume of voids does not depend on post shape. Moreover, the microCT analysis demonstrated that the volume of cement was greater with oval posts compared to circular posts. CLINICAL RELEVANCE: The microCT analysis provided interesting information on voids distribution and on the ratio between post shape and cement thickness. These results might address the clinician in the reconstruction of teeth with fiber posts.


Subject(s)
Bicuspid/diagnostic imaging , Post and Core Technique , X-Ray Microtomography/methods , Humans
18.
Open Dent J ; 8: 229-35, 2014.
Article in English | MEDLINE | ID: mdl-25614768

ABSTRACT

OBJECTIVES: To evaluate temperature profiles developing in the root during warm compaction of gutta-percha with the heat sources System B and System MB Obtura (Analityc Technology, Redmond, WA, USA). Thirty extracted human incisor teeth were used. Root canals were cleaned and shaped by means of Protaper rotary files (Dentsply-Maillefer, Belgium), and imaging was performed by micro-CT (Skyscan 1072, Aartselaar, Belgium). METHODS: Teeth were instrumented with K-type thermocouples, and the roots were filled with thermoplastic gutta-percha. Vertical compaction was achieved through the heat sources System B and System MB, and temperature profiles were detect-ed by means of NI Dac Interface controlled by the LabView System. With both heat sources, higher temperature levels were recorded in the region of the root far from the apex. When the warm plugger tip was positioned at a distance of 3 mm from the root apex, temperature levels of about 180°C were used to soften gutta-percha, and no statistically significant differences were observed between peak temperatures developed by the two heating sources at the root apex. However, a temperature level higher than 40°C was maintained for a longer time with System MB. RESULTS: Statistically significant differences were observed in peak temperature levels recorded far from the root apex. Thus, with a temperature of about 180°C and the warm plugger positioned at 3 mm from the root apex, both heating sources led to a temperature slightly higher than 40°C at the apex of the root, suggesting that the gutta-percha was properly softened. SIGNIFICANCE: A temperature level higher than 40°C was maintained for a longer time with System MB, thus providing an ad-equate time for warm compaction of the gutta-percha.

19.
Recenti Prog Med ; 104(7-8): 420-4, 2013.
Article in Italian | MEDLINE | ID: mdl-24042421

ABSTRACT

Cleaning and shaping are important section for the root canal treatment. A number of different methodologies have been developed to overcome these problems, including the introduction of rotary instruments nickel-titanium (NiTi). In endodontics NiTi have been shown to significantly reduce procedural errors compared to manual techniques of instrumentation. The efficiency of files is related to many factor. Although previous investigations that have used µCT analysis were hampered by insufficient resolution or projection incorrect. The new generation of µCT performance best offer, as micron resolution and accurate measurement software for evaluating the accurate anatomy of the root canal. The aim the paper was to evaluate the efficiency of Reciproc files in root canal treatment, evaluated before and after instrumentation by using µ-CT analysis.


Subject(s)
Dental Instruments , Dental Pulp Cavity/diagnostic imaging , Molar/diagnostic imaging , Odontometry/methods , Root Canal Preparation/methods , X-Ray Microtomography/methods , Adult , Dentin/diagnostic imaging , Female , Humans , Imaging, Three-Dimensional , Male , Mandible , Middle Aged , Molar/ultrastructure , Nickel , Organ Size , Root Canal Preparation/instrumentation , Titanium , Tooth, Nonvital/diagnostic imaging
20.
Open Dent J ; 6: 118-25, 2012.
Article in English | MEDLINE | ID: mdl-22905069

ABSTRACT

OBJECTIVE: Aim of the study was to determined by microcomputed tomography (µCT) the horizontal distance between the main (MB1) and the second mesiobuccal canal (MB2) orifices, the vertical distance between the MB1 and MB2 orifices planes, and the distance between the anatomic apex and major apical foramen (AF). Furthermore, we characterized the entire internal and external anatomy of the MB, distalbuccal (DB) and palatal (P) maxillary first molars roots. MATERIALS AND METHODS: Twenty-two intact extracted first maxillary molars were scanned by X-ray computed transaxial µCT and then 2D and 3D images were processed and analyzed. RESULTS: The results showed that 77.27% of the mesiobuccal (MB) roots presented a second MB canal, and 29.41% of the MB2 were independent from the MB1 canals. In 15 teeth, there were three root canal orifices on the chamber floor, and 10 of these teeth presented MB2 canals. The mean vertical distance between the MB1 and MB2 planes was 1.68 ± 0.83 mm. Seven teeth had four orifices. The mean horizontal interorificial distance between the MB1 and MB2 orifices was 1.21 ± 0.5 mm. Accessory canals were observed in 33.33% of the roots, loops in 6.06%, while isthmuses were found in 15 of the 22 MB roots. Of the total roots, 74.24% presented one foramen, while all of the roots showed a major apical foramen that was not coincident with the anatomic apex. CONCLUSIONS: Our µCT analysis provided interesting features on the horizontal and vertical distance between the MB1 and MB2 orifices and on the distance of AF and anatomic apex. CLINICAL RELEVANCE: These results have an important clinical value because might support the endodontist in the recruitment, negotiation and obturation of maxillary first molar canal system.

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