Showing papers by "Rakesh K. Jain published in 2008"
TL;DR: Human bone marrow-derived mesenchymal stem cells (hMSCs) are perivascular cell precursors and may serve as an attractive source of cells for use in vascular tissue engineering and for the study of periv vascular cell differentiation.
538 citations
TL;DR: It is found that umbilical cord blood EPCs form normal-functioning blood vessels that last for more than 4 months, and these vessels exhibit normal blood flow, perm-selectivity to macromolecules, and induction of leukocyte-endothelial interactions in response to cytokine activation similar to normal vessels.
334 citations
TL;DR: It is proposed that studies report both radiographic and clinical response rates, use volumetric rather than cross-sectional area to measure lesion size, and incorporate findings from mechanistic imaging and blood biomarker studies more frequently, and also suggest that investigators recognize the limitations of imaging biomarkers as surrogate end points.
Abstract: The current method for assessing the response to therapy of glial tumors was described by Macdonald et al. in 1990. Under this paradigm, response categorization is determined on the basis of changes in the cross-sectional area of a tumor on neuroimaging, coupled with clinical assessment of neurological status and corticosteroid utilization. These categories of response have certain limitations; for example, cross-sectional assessment is not as accurate as volumetric assessment, which is now feasible. Disentangling antitumor effects of therapies from their effects on blood-brain barrier permeability can be challenging. The use of insufficient response criteria might be overestimating the true benefits of drugs in early-stage studies, and, therefore, such therapies could mistakenly move forward into later phases, only to result in disappointment when overall survival is measured. We propose that studies report both radiographic and clinical response rates, use volumetric rather than cross-sectional area to measure lesion size, and incorporate findings from mechanistic imaging and blood biomarker studies more frequently, and also suggest that investigators recognize the limitations of imaging biomarkers as surrogate end points.
179 citations
TL;DR: An argument for designing and implementing multidisciplinary mechanistic trials and lessons the team at the Massachusetts General Hospital Cancer Center has learned from two such trials in cancer patients with locally advanced rectal carcinomas and recurrent glioblastomas are presented.
Abstract: The importance of multidisciplinary translational clinical trials is obvious; however, making them work is complex and challenging. Here I present an argument for designing and implementing multidisciplinary mechanistic trials and present the lessons our team at the Massachusetts General Hospital Cancer Center has learned from two such trials in cancer patients with locally advanced rectal carcinomas and recurrent glioblastomas.
168 citations
TL;DR: Restoring the balance of pro‐ and anti‐angiogenic factors in tumors may “normalize” tumor vasculature and thus improve its function, and administration of cytotoxic therapy during the vascular normalization would enhance its efficacy.
Abstract: Intravital microscopy has provided unprecedented insights into tumor pathophysiology, including angiogenesis and the microenvironment. Tumor vasculature shows an abnormal organization, structure, and function. Tumor vessels are leaky, blood flow is heterogeneous and often compromised. Vascular hyperpermeability and the lack of functional lymphatic vessels inside tumors causes elevation of interstitial fluid pressure in solid tumors. These abnormalities form physiological barriers to the delivery of therapeutic agents to tumors and also lead to a hostile microenvironment characterized by hypoxia and acidosis, which hinders the effectiveness of anti-tumor treatments such as radiation therapy and chemotherapy. In addition, host-tumor interactions regulate expression of pro- and anti-angiogenic factors, resulting in pathophysiological characteristics of the tumor. On the other hand, in a physiological setting, angiogenic vessels become mature and form long-lasting functional units. Restoring the balance of pro- and anti-angiogenic factors in tumors may "normalize" tumor vasculature and thus improve its function. Administration of cytotoxic therapy during the vascular normalization would enhance its efficacy.
167 citations
TL;DR: Important strategies adopted for PAH bioremediation are summarized, the potential for their improvement is discussed and several approaches such as improvement in PAH solubilization and entry into the cell, pathway and enzyme engineering and control of enzyme expression etc are discussed.
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are compounds of intense public concern due to their persistence in the environment and potentially deleterious effects on human, environmental and ecological health. The clean up of such contaminants using invasive technologies has proven to be expensive and more importantly often damaging to the natural resource properties of the soil, sediment or aquifer. Bioremediation, which exploits the metabolic potential of microbes for the clean-up of recalcitrant xenobiotic compounds, has come up as a promising alternative. Several approaches such as improvement in PAH solubilization and entry into the cell, pathway and enzyme engineering and control of enzyme expression etc. are in development but far from complete. Successful application of the microorganisms for the bioremediation of PAH-contaminated sites therefore requires a deeper understanding of the physiology, biochemistry and molecular genetics of potential catabolic pathways. In this review, we briefly summarize important strategies adopted for PAH bioremediation and discuss the potential for their improvement.
163 citations
TL;DR: It is shown that eliminating nitric oxide production from tumor cells via neuronal NO synthase silencing or inhibition establishes perivascular gradients of NO in human glioma xenografts in mice and normalizes the tumor vasculature, resulting in improved tumor oxygenation and response to radiation treatment.
Abstract: Normalization of tumor vasculature is an emerging strategy to improve cytotoxic therapies. Here we show that eliminating nitric oxide (NO) production from tumor cells via neuronal NO synthase silencing or inhibition establishes perivascular gradients of NO in human glioma xenografts in mice and normalizes the tumor vasculature, resulting in improved tumor oxygenation and response to radiation treatment. Creation of perivascular NO gradients may be an effective strategy for normalizing abnormal vasculature.
157 citations
TL;DR: This review describes examples of enzymes possessing the major activities employed in the bioremediation of pesticide residues, and some of the strategies by which they are employed.
Abstract: Enzymes are central to the biology of many pesticides, influencing their modes of action, environmental fates and mechanisms of target species resistance. Since the introduction of synthetic xenobiotic pesticides, enzymes responsible for pesticide turnover have evolved rapidly, in both the target organisms and incidentally exposed biota. Such enzymes are a source of significant biotechnological potential and form the basis of several bioremediation strategies intended to reduce the environmental impacts of pesticide residues. This review describes examples of enzymes possessing the major activities employed in the bioremediation of pesticide residues, and some of the strategies by which they are employed. In addition, several examples of specific achievements in enzyme engineering are considered, highlighting the growing trend in tailoring enzymatic activity to a specific biotechnologically relevant function.
141 citations
TL;DR: Researchers found that if they could normalize the blood vessels, the cancer medications would get into the tumors and work more effectively.
Abstract: This article updates readers on promising developments in the treatment of cancer. Abnormal and malfunctioning blood vessels are a standard of solid tumors and they contribute to the malignancy of a cancer and prevent treatments from attacking the rogue tumor cells. Researchers found that if they could normalize the blood vessels, the cancer medications would get into the tumors and work more effectively. INSETS: ABNORMAL VESSELS MAKE TROUBLE;Vessel Repair: Beyond Cancer.
118 citations
TL;DR: Data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatics metastasis, independent of the effect of the TKI on blood vessels.
Abstract: Blood vessels are required for a tumor to grow and functional lymphatic vessels are required for it to disseminate to lymph nodes. In an attempt to eradicate both the primary tumor and its lymphatic metastasis, we targeted both blood and lymphatic vessels using two different vascular endothelial growth factor receptor (VEGFR)-2 and -3 tyrosine kinase inhibitors (TKIs), cediranib and vandetanib. We found that while both cediranib and vandetanib slowed the growth rate of primary tumors and reduced blood vessel density, neither agent was able to prevent lymphatic metastasis when administered after tumor cells had seeded the lymph node. However, when administered during tumor growth, cediranib reduced the diameters of the draining lymphatic vessels, the number of tumor cells arriving in the draining lymph node and the incidence of lymphatic metastasis. On the other hand, vandetanib had minimal effect on any of these parameters, suggesting that vandetanib did not effectively block VEGFR-3 on lymphatic endothelial cells in our animal model. Collectively, these data indicate that the response of lymphatic vessels to a TKI can determine the incidence of lymphatic metastasis, independent of TKI's effect on blood vessels.
101 citations
TL;DR: Findings show that the induction of cancer cell death before the injection of oncolytic HSV enhances intratumoral virus delivery/penetration and antitumor efficacy.
Abstract: The success of tumor oncolytic virotherapy is limited by the poor penetration of virus in tumors. Interstitial collagen fibers and the narrow spacing between cancer cells are major barriers hindering the movement of large viral particles. To bypass the cellular barrier, we tested the hypothesis that the void space produced by cancer cell apoptosis enhances the initial spread and efficacy of oncolytic herpes simplex virus (HSV). In mice with mammary tumors, apoptosis was induced by doxycycline-regulated expression/activation of CD8/caspase-8, paclitaxel, or paclitaxel plus tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In both collagen-poor and collagen-rich tumors, apoptosis or necrosis increased the initial intratumoral spread of HSV. Compared with the isolated pattern of HSV infection generally located in the center of control tumors, apoptosis induction and a single i.t. injection of virus produced an interconnected and diffuse pattern of infection, which extended from the tumor center to the periphery. This interconnected pattern of viral infection correlated with the formation of void spaces and channel-like structures in apoptosis-rich tumor areas. We also show that the i.t. injection of HSV after caspase-8 activation or paclitaxel-TRAIL pretreatment retards tumor growth, whereas HSV administration before tumor cell death induction did not improve therapeutic efficacy. Hence, our findings show that the induction of cancer cell death before the injection of oncolytic HSV enhances intratumoral virus delivery/penetration and antitumor efficacy.
TL;DR: In this paper, the authors report on the growth of low-defect thick films of AlN and AlGaN on trenched AlGAN/sapphire templates using migration enhanced lateral epitaxial overgrowth.
Abstract: We report on the growth of low-defect thick films of AlN and AlGaN on trenched AlGaN/sapphire templates using migration enhanced lateral epitaxial overgrowth. Incoherent coalescence-related defects were alleviated by controlling the tilt angle of growth fronts and by allowing Al adatoms sufficient residence time to incorporate at the most energetically favorable lattice sites. Deep ultraviolet light emitting diode structures (310nm) deposited over fully coalesced thick AlN films exhibited cw output power of 1.6mW at 50mA current with extrapolated lifetime in excess of 5000hours. The results demonstrate substantial improvement in the device lifetime, primarily due to the reduced density of growth defects.
TL;DR: Duloxetine 60 mg/day and venlafaxine XR 150mg/day have similar benefit-risk profiles on the basis of a comparison utilizing GBR assessment, and there were few significant differences in safety measures found between treatment groups during 6 and 12 weeks of therapy.
TL;DR: New neuroimaging techniques, particularly MRI and PET imaging, that can be used to assess brain tumor growth and angiogenesis are summarized to allow development of patient-specific therapy to improve outcome in patients with gliomas.
Abstract: PURPOSE OF REVIEW This review will summarize new neuroimaging techniques, particularly MRI and PET imaging, that can be used to assess brain tumor growth and angiogenesis. RECENT FINDINGS Glioma tumor vasculature is abnormal, and advances in MRI now permit visualization of the hemodynamic properties of gliomas including cerebral blood volume and blood flow, vascular permeability, and blood vessel diameter. New radiolabeled PET tracers have allowed more specific interrogation of glioma physiology such as hypoxia assessment or tumor proliferation rate. These two techniques are complementary and will likely yield important information on tumor response to therapy, particularly in the setting of antiangiogenic agents, which confound the interpretation of standard contrast-enhanced MRI scans. SUMMARY These techniques may allow development of patient-specific therapy to improve outcome in patients with gliomas.
Journal Article•
TL;DR: For a female, type 2 diabetic patient, with 4 years duration of diabetes, Exenatide (Byetta) was prescribed as glycaemic control was not satisfactory along with Glimepiride and Metformin, but from the eighth day she developed signs of acute pancreatitis.
Abstract: For a female, type 2 diabetic patient, with 4 years duration of diabetes, Exenatide (Byetta) was prescribed as glycaemic control was not satisfactory along with Glimepiride and Metformin. She had gastrointestinal disturbances, since the first day of the injection. From the eighth day she developed signs of acute pancreatitis which was confirmed with CT-Scan and biochemical investigations. Byetta was withdrawn, the patient was treated for acute pancreatitis and the symptoms subsided.
TL;DR: Eight bacterial strains designated ARI 1-8 were isolated from soil and water samples collected from selenium-contaminated sites in India using the enrichment culture technique and belonged to the classes β-Proteobacteria and Bacilli, which could be further used for bioremediation of contaminated sites.
Abstract: Eight bacterial strains designated ARI 1-8 were isolated from soil and water samples collected from selenium-contaminated sites in India using the enrichment culture technique. They exhibited very high MIC values ranging from 300 to 750 mM for different forms of selenium (selenite and selenate). On the basis of various biochemical tests, fatty acid methyl ester profile and 16S rRNA gene sequencing, these isolates were identified belonging to the classes β-Proteobacteria and Bacilli. These microorganisms could be further used for bioremediation of contaminated sites.
Journal Article•
TL;DR: A database of spontaneous tumors in retired FVB/N breeders is initiated, the histopathologic characteristics of these tumors are analyzed, and novel tumor lines are established in vivo and in vitro for use in this relatively new but widely used mouse strain.
Abstract: The inbred FVB mouse strain is used extensively in cancer research. Transgenic mice with an FVB/N background in which the expression of green fluorescent protein is under the control of various promoters have been used widely for the last decade. However, little is known about the incidence and characteristics of spontaneous tumors in these mice. In addition, only a few tumor lines have been established for use in this particular mouse strain. Our aim was to initiate a database of spontaneous tumors in our retired FVB/N breeders, analyze the histopathologic characteristics of these tumors, and establish novel tumor lines in vivo and in vitro. A total of 234 (40 male, 194 female) breeder mice were observed during their natural lifespans. The incidence of spontaneous tumors was 45.0% in male mice and 52.8% in female mice. All tumors in male mice were lung alveolar-bronchiolar (AB) neoplasms, except for 1 testis interstitial cell tumor. In female mice, histopathologic examination revealed 48 lung AB tumors, 27 mammary gland tumors, 13 ovarian tumors, and 14 other tumors. Several of these spontaneous tumors have been transplanted into FVB/N mice. One mammary adenocarcinoma (MCaP0008) and 1 lung AB carcinoma (LAP0297) were successfully transplanted subcutaneously and passaged serially in vivo. Subsequently, we established cell lines from both tumors, which were maintained in monolayer in vitro. Both of the grafted tumors and cell lines are tumorigenic in VEGF(P)-GFP/FVB and Tie2(P)-GFP/FVB mice. Establishment of these novel tumor lines will benefit both in vivo and in vitro studies on the pathophysiology of cancer in this relatively new but widely used mouse strain.
TL;DR: DLCP with a titrated energy protocol needs resulted in lower energy in Asian Indian eyes compared to that reported in literature, and different energy levels are needed for different diseases.
Abstract: To study the treatment parameters for diode laser cyclophotocoagulation (DLCP) in Asian Indian eyes using laser energy titrated to clinical response. This prospective interventional longitudinal study included 66 eyes of 66 patients with varied aetiology refractory glaucoma, no previous cycloablation, and minimum 1 year follow-up. DLCP was performed using the Oculight® Diode laser system (IRIS© Medical Instruments Inc., CA, USA). Power used per spot was titrated according to the audible ‘pops’ indicating tissue microexplosion. The mean laser energy delivered, post-laser intraocular pressure (IOP) reduction, complications, and requirement of re-treatment in various subgroups were analyzed. Differences in energy delivered in each subgroup were assessed by analysis of variance with post hocBonferroni corrections. Linear regression analysis was used to identify possible predictive factors for failure of cyclodiode therapy. The mean total energy delivered per eye was 87.80±31.8 J (range 105.4±36.8 J in neovascular glaucoma (NVG) to 61.5±8.8 J in uveitic glaucoma (P=0.134)). Mean pre treatment IOP was 36.4±10.7 mmHg, which reduced to 19.4±9.8 mmHg (P<0.001) at 1 week, and 15.6±6.6 mmHg at 1 year. At 1 year, 58 of 66 patients had IOP<22.0 mmHg (response rate 87.8%), and six patients had hypotony (success rate 78.8%). The uveitic glaucoma group had 100% success rate. NVG group required maximum re-treatments. DLCP with a titrated energy protocol needs resulted in lower energy in Asian Indian eyes compared to that reported in literature, and different energy levels are needed for different diseases. ‘Standard treatment parameters’ for DLCP may be inappropriate for all diseases and all races.
TL;DR: A new study of a paracrine regulatory circuit centered on PDGF receptor signaling in cancer-associated fibroblasts and pericytes of a mouse model of cervical carcinoma is discussed.
Abstract: Cervical cancer is one of the most prevalent malignancies in women worldwide and is the leading cause of cancer death for women in developing countries [1]. While early detection via the Pap test as well as treatment by surgery and chemoradiotherapy has reduced mortality from this disease, the prognosis is poor if the disease is detected at an advanced stage [2]. Thus new treatment strategies for cervical cancer are needed.
In this issue of PLoS Medicine, Kristian Pietras and colleagues, using a mouse model of cervical carcinogenesis, provide compelling evidence that targeting platelet-derived growth factor (PDGF) signaling, primarily in carcinoma-associated fibroblasts (CAFs), can slow the progression of this disease and even impair the growth of invasive carcinomas [3]. By offering preliminary evidence for the presence of PDGF receptors in a limited number of human cervical cancer biopsies, these authors also suggest that the drugs approved by the United States Food and Drug Administration (FDA) that target PDGF signaling, such as imatinib mesylate (Gleevec in the US; Glivec in Europe and Australia, Novartis), be tested in the clinic for this malignancy.
TL;DR: Sunitinib (SU) as discussed by the authors is an oral, multitargeted tyrosine molecule that is used to treat HCC and angiogenic pathways such as VEGF and IL-6.
Abstract: 4521 Background: HCC is a highly vascular tumor and angiogenic pathways such as VEGF and IL-6 play a key role in proliferation and angiogenesis. Sunitinib (SU) is an oral, multitargeted tyrosine ki...
TL;DR: It is shown that coimplanting endothelial cells and perivascular cells in a scaffold in vivo can lead to the formation of a vascular network that anastomoses to the host circulatory system.
Abstract: Tissue engineering has attracted wide interest as a potential method to alleviate the shortage of transplantable organs (1). To date, almost all of the successfully engineered tissues/organs have relatively thin and/or avascular structures [e.g., skin (2), cartilage (3), and bladder (4)], where postimplantation vascularization from the host (angiogenesis) is sufficient to meet the implant's demand for oxygen and nutrients. Vascularization remains a critical obstacle impeding attempts to engineer thicker, metabolically demanding organs, such as heart and liver. One approach in vascularizing an engineered tissue is to add the cellular components of blood vessels (endothelial and perivascular cells) directly to the tissue-engineered construct. We have shown that coimplanting endothelial cells and perivascular cells in a scaffold in vivo can lead to the formation of a vascular network that anastomoses to the host circulatory system. The engineered vessels are stable and functional, and they persist for more than 1 year in vivo. This approach may potentially lead to the creation of a well-vascularized-engineered tissue.
TL;DR: On the basis of differential phenotypic characteristics and genotypic distinctiveness, strain IPL-1(T), capable of oxidizing indole was isolated from a lindane-contaminated site and subjected to a polyphasic taxonomic study, should be classified within the genus Pseudomonas as a novel species, for which the name Pseudoms indoloxydans is proposed.
TL;DR: An ANN taking varied diagnostic imaging inputs was able to separate POAG eyes from normal subjects and POAG suspects, but the network had reasonable sensitivity with three outputs; however, it had a tendency to mislabelPOAG suspects as POAG.
Abstract: PURPOSE. To develop, train, and test an artificial neural network (ANN) for differentiating among normal subjects, primary open angle glaucoma (POAG) suspects, and persons with POAG in Asian-Indian eyes using inputs from clinical parameters, optical coherence tomography (OCT), visual fields, and GDx nerve fiber analyzer. METHODS. One hundred eyes were classified using optic disc examination and perimetry into normal (n=35), POAG suspects (n=30), and POAG (n=35). EasyNN-plus simulator was used to develop an ANN model with inputs including age, sex, myopia, intraocular pressure (IOP), optic nerve head, and retinal nerve fiber layer (RNFL) parameters on OCT, Octopus 30-2 full threshold visual field, and GDx parameters. RESULTS. With two outputs (POAG or normal), specificity was 80% and sensitivity was 93.3%. Ninety percent of POAG suspects were labeled as abnormal in this analysis. ANN assigned the highest importance to Smax/lmax RNFL on OCT followed by cup-area (OCT) and other RNFL parameters (OCT) for two outputs. With three outputs (normal, POAG, and POAG suspect), ANN gave an overall classification rate of 65%, specificity of 60%, and sensitivity of 71.4% with a target error rate of the training set at 1%. The parameters for three outputs, in decreasing order of relative importance, were Savg, vertical cup-disc ratio, cup-volume, and cup-area on OCT. CONCLUSIONS. An ANN taking varied diagnostic imaging inputs was able to separate POAG eyes from normal subjects and POAG suspects. The network had reasonable sensitivity with three outputs; however, it had a tendency to mislabel POAG suspects as POAG.
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TL;DR: The pathophysiology, diagnosis, and treatment of pain and mood disorders are discussed in this video, which features case studies of and expert commentary on patients with diabetic neuropathy, lower back pain, and chronic widespread pain.
Abstract: Chronic pain is difficult to diagnose and treat, and is often comorbid with psychiatric conditions. Pain and mood disorders may share neurologic pathways and a neurochemical base. For example, depression is associated with abnormalities in serotonin and norepinephrine, neurotransmitters that also modulate the endogenous analgesic system. Further, co-occurring depression and pain may obscure a diagnosis of the other, secondary condition. Agents that inhibit pain signals and boost serotonin and norepinephrine levels, such as serotonin-norepinephrine reuptake inhibitors (SNRIs), may provide pain relief as well as alleviate psychiatric symptom. Psychotherapies and education should also be considered to help patients achieve optimal functioning. The pathophysiology, diagnosis, and treatment of pain and mood disorders are discussed in this video, which features case studies of and expert commentary on patients with diabetic neuropathy, lower back pain, and chronic widespread pain.
TL;DR: Tammela et al. in Nature show that VEGFR-3, via Notch regulation, is present on endothelial tip cells and is critical to sprouting angiogenesis.
TL;DR: Analysis of cells by high-resolution imaging and fluorescence-activated flow cytometry in an in vivo rodent model of pulmonary microvascular remodeling will characterize their phenotype, quantify their number and identify their role in the assembly of vascular channels.
Abstract: The goal of many current studies of neovascularization is to define the phenotype of vascular cell populations of different origins and to determine how such cells promote assembly of vascular channel. Here, we describe a protocol to immunophenotype vascular cells by high-resolution imaging and by fluorescence-activated flow cytometry in an in vivo rodent model of pulmonary microvascular remodeling. Analysis of cells by this combined approach will characterize their phenotype, quantify their number and identify their role in the assembly of vascular channels.
TL;DR: It is demonstrated that functional correlation of sequence motifs of HC-Pro is an important source to predict its role in deubiqutinylation pathway and rescuing viral proteins from degradation.
Abstract: Helper component proteinase (HC-Pro) is a multifunctional protein responsible for multiple molecular events in viral cycle. Here, we demonstrate that functional correlation of sequence motifs of HC-Pro is an important source to predict its role in deubiqutinylation pathway and rescuing viral proteins from degradation. The sequence of papaya ringspot viral HC-Pro was compared with respect to both inter and intea-species across different potyviruses. This study suggested that highly conserved domains involved in post transcriptional gene silencing (PTGS) suppression and proteolytic activity are essential functions in plant-virus cycle. In contrast, mechanisms primed for differentiation such as host specificity and virus replication are less conserved. Also, they contribute substantially to the differences among HC-Pro, derived from different potyviruses. The results obtained from this study provide a framework for new hypothesis and research directions in the area of differential role of potyviral HC-Pro.
TL;DR: This work retrospectively analyzed Gd-MRI and FLAIR MRI sequences of 24 patients who demonstrated either focal or both focal and distal recurrence while treated with bevacizumab and irinotecan, and observed the development of distant and new foci of increased FLAIR signals that do not correlate with changes seen on gadolinium-enhanced sequences.
Abstract: 13013 Background: Glioblastoma multiforme (GBM) is characterized by diffuse parenchymal infiltration and regional angiogenesis. Bevacizumab, an anti-VEGF recombinant humanized monoclonal antibody, has shown remarkable response to treatment rates in patients with recurrent GBM. The best way to assess tumor recurrence via MRI studies has yet to be determined. We have observed the development of distant and new foci of increased FLAIR signals that do not correlate with changes seen on gadolinium-enhanced sequences (Gd-MRI). Methods: We retrospectively analyzed Gd-MRI and FLAIR MRI sequences of 24 patients who demonstrated either focal (a new enhancing lesion or FLAIR signal 2 cm outside original tumor) or both focal and distal recurrence while treated with bevacizumab and irinotecan. Results: Ten patients (10/24) demonstrated only focal recurrence, one patient (1/24) only distant recurrence (to cerebellum) and nine patients (9/24) both focal and distant r...
TL;DR: In this paper, a protocol was proposed to analyze, in an in vivo rodent model, vessel and capillary remodeling (reorganization and growth) in the injured lung, and to study the molecular and cellular determinants of lung neovascularization.
Abstract: By providing insight into the cellular events of vascular injury and repair, experimental model systems seek to promote timely therapeutic strategies for human disease The goal of many current studies of neovascularization is to identify cells critical to the process and their role in vascular channel assembly We propose here a protocol to analyze, in an in vivo rodent model, vessel and capillary remodeling (reorganization and growth) in the injured lung Sequential analyses of stages in the assembly of vascular structures, and of relevant cell types, provide further opportunities to study the molecular and cellular determinants of lung neovascularization