The Experts below are selected from a list of 20511 Experts worldwide ranked by ideXlab platform
Haifa Shen - One of the best experts on this subject based on the ideXlab platform.
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Abstract 5697: Multistage vectored nanotherapeutics of breast cancer lung metastasis
Cancer Research, 2012Co-Authors: Haifa ShenAbstract:Breast cancer metastasis to remote organs is the major cause of cancer death. Although significant progresses have been made on survival of patients with Stage I-III breast cancer, the situation with breast cancer metastasis is discouraging. Nanotechnology has played an important role in the fight against breast cancer in the last decade. The first nano-liposomal formulation of doxorubicin (Dox), Doxil, was FDA approved in 1994, and is currently used to treat multiple cancer types including recurrent and refractory breast cancers. More nano-formulated drugs have since been approved. These nanotherapeutics work based on the enhanced permeability and retention (EPR) effect, and still cause severe toxicity to the body, however. To overcome these defects of the first generation of nanotherapeutics, we have developed a silicon-based multistage vector (MSV) system with the aim to specifically delivery drugs to cancer tissues with the least toxicity to the normal organs. We have demonstrated highly reproducible therapeutic efficacy with this system to deliver the conventional chemotherapy drugs and siRNA oligos in nanoparticles. We have generated mouse lung metastasis models with the human breast cancer cell line MDA-MB-231 which was engineered with a luciferase gene, and used multiple doxorubicin formulations to treat the Tumor mice. These included free doxorubicin (3 mg/kg weekly), Doxil (6 mg/kg biweekly), a doxorubicin prodrug (proDox, 6 mg/kg biweekly), and proDox in MSV (MSV/proDox, 6 mg/kg biweekly). Tumor growth in the lung was monitored by bioluminescence with a Xenogen IVIS200 optical in vivo imaging system. As expected, treatment with free Dox caused significant weight loss indicating drug toxicity, most likely to the Heart. Tumor growth in the free Dox treatment group halted initially, but resumed two weeks later. The Tumor cells in these animals might have developed resistance to Dox during the treatment. Doxil treatment also triggered weight loss initially. This correlates with reduced the cardiac side effect of the drug observed in clinic comparing to free Dox. Neither proDox nor MSV/proDox caused weight loss. Fifty percent of the untreated mice died of lung metastasis by 11 weeks. The free Dox- and proDox-treated mice extended life by 2 weeks. Half of Doxil-treated mice died by 15 weeks, when all MSV/proDox-treated mice have survived. These results indicate that we have developed a powerful system for Tumor-specific delivery of therapeutic in the treatment of breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5697. doi:1538-7445.AM2012-5697
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P1-15-03: Multistage Vectored Nanotherapeutics for Breast Cancer Metastasis.
Cancer Research, 2011Co-Authors: Haifa ShenAbstract:Significant progresses have been made on overall survival rates in breast cancer. The five-year survival rate of women diagnosed with Stage I-III breast cancer has been steadily improving decades over decades. These improvements in survival have primarily been attributed to availability of modern diagnostic tools that allow for early detection, and the increased use of adjuvant systemic therapies. However, the situation with breast cancer metastasis is discouraging, with only marginal improvement in some reports to no improvement at all in other studies in survival of the relapsed metastatic patients. More breast cancer patients are killed by cancer metastasis than by the primary cancer. Nanotechnology has played an important role in the fight against breast cancer in the last decade. The first nano-liposomal formulation of doxorubicin (Dox), Doxil, was FDA approved in 1994, and is currently used to treat multiple cancer types including recurrent and refractory breast cancers. More nano-formulated drugs have since been approved. These nanotherapeutics work based on the enhanced permeability and retention (EPR) effect, and still cause severe toxicity to the body, however. To overcome these defects of the first generation of nanotherapeutics, we have developed a silicon-based multistage vector (MSV) system with the aim to specifically delivery drugs to cancer tissues with the least toxicity to the normal organs. These are particle-in-particle “Russian Doll” systems with each stage designed to provide transport across a set of sequential biological barriers, and provide associated levels of targeting specificity. We have demonstrated highly reproducible therapeutic efficacy with this system to deliver the conventional chemotherapy drugs and siRNA oligos. We have generated mouse lung metastasis models with the human breast cancer cell line MDA-MB-231 which was engineered with a luciferase gene, and used multiple doxorubicin formulations to treat the Tumor mice. These included free doxorubicin (3 mg/kg weekly), Doxil (6 mg/kg biweekly), a new formulation of doxorubicin in micelles (miDox, 6 mg/kg biweekly), and miDox in MSV (MSV/Dox, 6 mg/kg biweekly). Tumor growth in the lung was monitored by bioluminescence with a Xenogen IVIS200 optical in vivo imaging system. As expected, treatment with free Dox caused significant weight loss indicating drug toxicity, most likely to the Heart. Tumor growth in the free Dox treatment group halted initially, but resumed two weeks later. The Tumor cells in these animals might have developed resistance to Dox during the treatment. Doxil treatment also triggered weight loss initially. This correlates with the cardiac side effect of the drug observed in clinic. Neither miDox or MSV/Dox caused weight loss. Tumor growth was also inhibited in mice treated with both formulations. The result was much more significant with MSV/Dox than with miDox. No Tumor cells were observed in the lung after a 6-week treatment with MSV/Dox, while 40% of the miDox-treated mice still had residue, but detectable Tumor cells in the lung. These results indicate that we have developed a powerful system for Tumor-specific delivery of therapeutic in the treatment of breast cancer metastasis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-15-03.
Alfonso Medina - One of the best experts on this subject based on the ideXlab platform.
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Cardiac rhabdomyoma and tuberous sclerosis. Survival after the surgical resection of the cardiac Tumor
Revista espanola de cardiologia, 1991Co-Authors: Abad C, Trillo M, Olalla E, Suárez P, Antúnez M, Romero T, Enrique Hernández, Alfonso MedinaAbstract:A 3-month-old boy with tuberous sclerosis was diagnosed of biventricular Heart Tumor by means of 2D-echocardiogram. Three masses of Tumor were excised from the right ventricle with the aid of cardiopulmonary bypass. Pathologic examination disclosed a cardiac rhabdomyoma. The boy is symptoms-free after 5 years of the operation. An echocardiogram taken at this time showed no-evidence of Heart Tumor. Pathology, diagnostic methods and surgical indications are commented. A review of selected surgically resected cases is also presented.
Piroze Minoo Davierwala - One of the best experts on this subject based on the ideXlab platform.
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Minimally invasive mitral valve repair
Indian Journal of Thoracic and Cardiovascular Surgery, 2020Co-Authors: Mateo Marin Cuartas, Piroze Minoo DavierwalaAbstract:Minimally invasive mitral valve (MV) repair is being increasingly performed over the last 2 decades due to the constantly growing patient demand, since it offers a shorter recovery, less restriction and faster return to normal physical activities, reduction in pain, and superior cosmetic results. However, such procedures have to be performed through small incisions which limit visualization and the freedom of movement of the surgeon, in contrast to conventional operations that are performed through a sternotomy. Therefore, special long surgical instruments are required, and visualization is usually enhanced with advanced port-access two-dimensional (2D) or three-dimensional (3D) thoracoscopic cameras. This makes performance of a minimally invasive MV repair more challenging for the surgeon and is thereby associated with a steep learning curve. Nonetheless, the vast majority of patients who require MV repair are usually good candidates for this less invasive technique, though adequate patient selection is of utmost importance for success. Concomitant cardiac procedures such as ablation surgery for atrial fibrillation or right-sided interventions such as tricuspid valve surgery, Heart Tumor resection, and atrial septal defect closure can easily be performed using this approach. Short- and long-term results after minimally invasive MV repair are excellent and comparable with those achieved through a sternotomy approach. There are few drawbacks associated with minimally invasive MV repair such as the high technical demands of working through a constrained space and development of complications associated with peripheral cannulation and seldom unilateral pulmonary edema. Nonetheless, high-volume centers have been able to achieve similar operating times, postoperative complication rates, and mid-/long-term outcomes to those obtained through conventional sternotomy. Up-to-date evidence is needed in order to improve recommendations supporting minimally invasive MV repair. Future innovations should concentrate on decreasing complexity and improving reproducibility of minimally invasive procedures in low-volume centers.
Roni Mamluk - One of the best experts on this subject based on the ideXlab platform.
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the role of neuropilin in vascular and Tumor biology
Advances in Experimental Medicine and Biology, 2002Co-Authors: Michael Klagsbrun, Seiji Takashima, Roni MamlukAbstract:Neuropilin-1 (NRP1) and NRP2 are related transmembrane receptors that function as mediators of neuronal guidance and angiogenesis. NRPs bind members of the class 3 semaphorin family, regulators of neuronal guidance, and of the vascular endothelial growth factor (VEGF) family of angiogenesis factors. There is substantial evidence that NRPs serve as mediators of developmental and Tumor angiogenesis. NRPs are expressed in endothelial cells (EC) and bind VEGF165. NRP1 is a co-receptor for VEGF receptor-2 (VEGFR2) that enhances the binding of VEGF165 to VEGFR2 and VEGF165-mediated chemotaxis. NRP1 expression is regulated in EC by Tumor necrosis factor-alpha, the transcription factors dHAND and Ets-1, and vascular injury. During avian blood vessel development NRP1 is expressed only in arteries whereas NRP2 is expressed in veins. Transgenic mouse models demonstrate that NRP1 plays a critical role in embryonic vascular development. Overexpression of NRP1 results in the formation of excess capillaries and hemorrhaging. NRP1 knockouts have defects in yolk sac, embryo and neuronal vascularization, and in development of large vessels in the Heart. Tumor cells express NRPs and bind VEGF165. NRP1 upregulation is positively correlated with the progression of various Tumors. Overexpression of NRPI in rat Tumor cells results in enlarged Tumors and substantially enhanced Tumor angiogenesis. On the other hand, soluble NRP1 (sNRP1) is an antagonist of Tumor angiogenesis. Semaphorin 3A binds to EC and Tumor cells. It also inhibits EC motility and capillary sprouting in vitro. VEGF165 and Sema3A are competitive inhibitors for NRP1 mediated functions in EC and neurons. These results suggest that NRP1 is a novel regulator of the vascular system.
Lesław Szydłowski - One of the best experts on this subject based on the ideXlab platform.
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Echocardiography and Newer Imaging Techniques in Diagnosis and Long-Term Follow-Up of Primary Heart Tumors in Children.
International journal of environmental research and public health, 2020Co-Authors: Aleksandra Morka, Joanna Kohut, Beata Radzymińska-chruściel, Tomasz Mroczek, Marcin Gładki, Piotr Weryński, Andrzej Rudziński, Janusz Skalski, Lesław SzydłowskiAbstract:Background: Primary Heart Tumors (PHTs) in the pediatric population are very rare and do not manifest any characteristic symptoms. Methods: A retrospective analysis of 61 cases was undertaken. Data from three centers for the years 2003–2018 were gathered. The Tumors’ clinical course, location, number, hemodynamic, treatment, and follow-up were evaluated. Echocardiography was complemented with magnetic resonance imaging, computer tomography, and histopathological examination. Results: Out of 61 PHT diagnoses, 56 (91.8%) were circumstantial including all 16 (26.2%) prenatal Tumors. The reasons for cardiological consultations were arrhythmia, syncopes, lowered physical performance, and murmurs. Only five patients (8.2%) were suspected of Tumors based on previous symptoms of sclerosis tuberosa. Rhabdomyoma was the most frequently found PHT (60.7%). The Tumors were predominantly located in the ventricles (49.1%) and intraventricular septum (14.9%) and tended to be single (70.5%). About 37.7% of patients suffered from coexistent multi-organ problems, two (3.28%) from congenital Heart defects and one (1.64%) from Carney’s syndrome. Tumor resection was performed on 26 (42.7%) patients, of which 16 (61.5%) underwent total and 10 (38.5%) partial Tumor resection. During the follow-up (mean 4.3 years), 54 patients (88.5%) have improved or were stable, while seven (11.5%) died. Conclusions: Primary pediatric Heart Tumors are diagnosed completely circumstantially, and the most common is rhabdomyoma, although arrhythmia may suggest fibroma. Diagnosis of a Heart Tumor in children is not synonymous with fatal prognosis, and most of them require only constant observation. Life-saving operation allows improvement, while the prognosis for malignant Tumors in children is definitely unfavorable.
