scholarly journals New Applications of HBOC-201: A 25-Year Review of the Literature

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Cao ◽  
Yong Zhao ◽  
Hongli He ◽  
Ruiming Yue ◽  
Lingai Pan ◽  
...  
Keyword(s):  
Side Effects ◽  
Oxygen Carrier ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Blood Substitute ◽  
Perioperative Period ◽  
Patient Specific ◽  
Bovine Hemoglobin ◽  
Tissue Ischemia ◽  
Clinical Scenarios

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.

Abstract 4030: Resuscitation with Intraosseous Infusion of Artificial Oxygen Carrier of Liposome-Encapsulated Hemoglobin (LHb) from Lethal Hemorrhagic Shock and Its Effect on Cytokines

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Bonpei Takase ◽  
Satoshi Shono ◽  
Manabu Kinoshita ◽  
Yashiro Nogami ◽  
Yoshitaka Ogata ◽  
...  
Keyword(s):  
Renal Function ◽  
Side Effects ◽  
Hemorrhagic Shock ◽  
Oxygen Carrier ◽  
Femoral Vein ◽  
Survival Rates ◽  
Blood Substitute ◽  
Disaster Medicine ◽  
Mice Model ◽  
Artificial Oxygen Carrier

Liposome-encapsulated hemoglobin (LHb), which is structurally similar to red blood cells (RBC) except smaller size (250 nm), can serve as blood substitute comparable to RBC. We have reported that intraosseous blood infusion (IOI) is effective treatment in shock mice model. IOI is alternative to peripheral i.v. infusion and is expected as an important field treatment in civilian emergency because of no collapse of intramedullary blood vessels in the bone marrow in shock. However, we did not evaluate the side effects of LHb in IOI. Total 70% hemorrhagic shock was induced by femoral vein bleeding. Immediately after bleeding, 17 mice were resuscitated with tibial bone IOI of 5% albumin (5% albumin), 18 mice resuscitated with mouse-washed RBC (Wash RBC) and 14 mice resuscitated with LHb (LHb-group). Survival rates were compared and the temporal changes in cytokins (TNF, INFγ) as well as liver and renal function (s-ALT, s-creatinine) were measured. All mice survived 48 h after IOI of LHb whereas only 47% and 45% mice survived in 5% albumin and Wash RBC, respectively (Fig. 1 ). The changes in TNF and INFγlevels after IOI were not statistically different among 3 groups (Fig. 2 ) and no side effects were found on liver and renal function.. Conclusions: LHb has a better anti-shock effect than RBC by using IOI probably due to smaller size and IOI of LHb could be useful in disaster medicine. In addition, IOI of LHb shows no significant effects on cytokins, liver and renal function. Figure 1 Figure 2

Appropriateness of adjuvant systemic therapy for axillary node-negative breast cancer: a physician opinion survey.

1995 ◽  
Vol 13 (6) ◽  
pp. 1459-1469 ◽  
Author(s):  
C A Sawka ◽  
A M O'Connor ◽  
H A Llewellyn-Thomas ◽  
T To ◽  
S P Pinfold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Combination Chemotherapy ◽  
Current Knowledge ◽  
Menopausal Status ◽  
Specific Treatment ◽  
Patient Specific ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Clinical Scenarios

PURPOSE To examine variations in physicians' recommendations for systemic adjuvant therapy in the treatment of women with node-negative breast cancer (NNBC) and to determine factors used in making specific recommendations. MATERIALS AND METHODS A questionnaire was sent by mail to all 149 Ontario physicians who actively treated breast cancer in 1993. The questionnaire described 48 clinical scenarios of women with NNBC, which included all possible combinations of the following factors: menopausal status, tumor size, hormone receptor status, histologic and nuclear grade, and lymphatic and/or vascular invasion. Respondents rated the appropriateness of administering tamoxifen, combination chemotherapy, or both tamoxifen and combination chemotherapy on a nine-point scale from extremely inappropriate to extremely appropriate. Respondent agreement and disagreement were tabulated for each scenario, and factors associated with specific treatment ratings were analyzed by logistic regression. RESULTS The response rate was 87%. Agreement for the appropriateness of specific therapies was most evident where clinical trials have demonstrated efficacy, whereas disagreement was observed in scenarios in which support for a specific treatment is not available in the current literature. Relevant tumor- and patient-specific factors were used in decision-making; personal characteristics of the respondents had no statistically significant impact on appropriateness ratings. CONCLUSION The physicians surveyed had good knowledge of NNBC prognostic factors, but had a range of opinion on optimal therapy for many clinical scenarios, which reflects current knowledge of the benefits of adjuvant therapy for NNBC.

scholarly journals Long-term survival of an adolescent glioblastoma patient under treatment with vinblastine and valproic acid illustrates importance of methylation profiling

2021 ◽  
Author(s):  
Catena Kresbach ◽  
Annika Bronsema ◽  
Helena Guerreiro ◽  
Stefan Rutkowski ◽  
Ulrich Schüller ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Patient Specific ◽  
Low Grade ◽  
Methylation Array ◽  
Term Survival ◽  
Clinical Prognosis ◽  
Dismal Prognosis ◽  
Good Clinical Condition

AbstractGlioblastoma (GBM) is an exceptionally aggressive brain tumor with a dismal prognosis, demanding fast and precise classification as a base for patient-specific treatment strategies. Here, we report on an adolescent patient with a histologically bona fide GBM that shows a molecular methylation profile suggesting a low-grade glioma-like subgroup. Despite an early relapse, intolerance of temozolomide, and change of treatment strategy to vinblastine and valproic acid (VPA), the patient is now in good clinical condition after more than 5 years since initial diagnosis. This case stresses the merit of methylation array data for clinical prognosis and treatment planning.

Comparison of treatment plans feasible through AI enabled multidisciplinary online tumor board solution versus NCCN-based clinical decision support system (CDSS).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 816-816
Author(s):  
Bhawna Sirohi ◽  
Sushil Beriwal ◽  
C. S. Pramesh ◽  
Supriya Chopra ◽  
Mahesh Goel ◽  
...  
Keyword(s):  
Large Scale ◽  
Treatment Plan ◽  
Specific Treatment ◽  
Treatment Decisions ◽  
Added Value ◽  
Tumor Board ◽  
Patient Specific ◽  
Clinical Scenarios ◽  
Tumor Boards ◽  
Treatment Plans

816 Background: Multidisciplinary tumor boards at Academic Medical Centers (AMC) maximize cancer outcomes. Guidelines based CDSS are alternatives to determine care pathways. Since 2015, 300 AMC cancer experts in USA and India use an AI enabled online tumor board solution, “NAVYA,” to scale low cost access to multidisciplinary expertise, on 1-2 minutes of expert time per decision (ASCO 2017). Methods: GI patients who used NAVYA between 5/1/15-8/31/19 were analyzed. Actionable treatment plans generated by NAVYA were compared to NCCN. Actionable treatment plans include chemotherapy protocols (doses, frequencies), radiation protocols (sites, fractions), etc. Inactionable specialty level decisions (CT-RT vs. surgery) lack specificity. Results: 1302 patients (4638 treatment decisions) were analyzed: 61% (794) male, 80% between age 45 to 75, mostly with Colon, Pancreas, Gallbladder, Rectum, or Stomach cancer; 49.7% non-metastatic. Cohort was comparable to GLOBOCAN estimates. In 82.2% (3812/4638) decisions, NAVYA added value beyond NCCN. First, in 4.5% (212/4638), NAVYA recommended a patient-specific treatment plan that was not part of NCCN. Second, in 3.2% (148/4638), NAVYA recommended treatments plan for clinical scenarios not covered by NCCN, (for eg. 3rd line therapies). Third, in 74.5% (3452/4638), NAVYA used patient specific criteria including resource constraints and patient preference to choose a treatment plan amongst the multiple pathways provided by NCCN and added actionable treatment details. Conclusions: Guideline based CDSS are insufficient to make the vast majority of actionable treatment decisions. Scaling rapid access to multidisciplinary experts is critical. Leapfrogging existing guidelines based CDSS, NAVYA online tumor board makes actionable expert treatment plans possible at a large scale.

scholarly journals TMOD-25. GLIOBLASTOMA ORGANOIDS: A MODEL SYSTEM FOR PATIENT-SPECIFIC THERAPEUTIC TESTING

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi268-vi268
Author(s):  
Ryan Salinas ◽  
Daniel Zhang ◽  
Fadi Jacob ◽  
Phuong Nguyen ◽  
Saad Sheikh ◽  
...  
Keyword(s):  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Patient Specific ◽  
Molecular Heterogeneity ◽  
Ras Signaling ◽  
Sequencing Data ◽  
Mtor Inhibition ◽  
Primary Tumors ◽  
Egfr Inhibition

Abstract Glioblastoma treatment options remain limited due to its aggressive and invasive nature. It is increasingly appreciated that molecular heterogeneity between tumors and within tumors likely contributes to the lack of therapeutic advances. To maintain the inherent heterogeneity of glioblastoma, we employed a novel method to rapidly culture glioblastoma organoids (GBOs) directly from neurosurgical resection. GBOs are routinely generated around two weeks following initial resection. Comprehensive histologic and sequencing analyses demonstrated similarity to primary tumors. Leveraging clinical molecular and sequencing data, selected GBOs were treated with radiation/temozolamide and targeted inhibitor therapies. The effect on proliferation was measured by the percentage of KI67+ cells and gene set enrichment (GSEA) analysis was performed to compare the pre-treated expression signature amongst responsive and non-responsive tumors. Treatment of organoids with radiation/temozolamide led to a decrease in the percentage of KI67+ cells in four of eight patient-derived organoid lines with some evidence of correlative radiographic response Gene sets associated with radiation response and TNF signaling were enriched in radiation/temozolamide sensitive GBOs. GBO response to EGFR inhibition via gefitinib treatment was specific to EGFR altered tumors, whose expression also enriched for EGF signaling pathway expression. Two GBOs had downstream NF1 mutations that responded to the MEK inhibitor trametinib. On GSEA, gene expression of NF1 mutated GBOs enriched for RAS signaling. One GBO line was found to have a PI3K mutation and responded dramatically to mTOR inhibition via everolimus. Dichotomous efficacy of MEK and mTOR inhibition was also noted by tumor-specific changes in GBO diameter following treatment. This novel culturing method of GBOs maintains intertumoral and intratumoral heterogeneity and allows for therapeutic testing within two weeks of neurosurgical resection. As clinical sequencing because increasingly prevalent, GBOs may become a valuable tool to functionally test mutation-specific treatment strategies in a patient-specific manner within a clinically relevant time frame.

scholarly journals An update on unilateral sporadic small vestibular schwannoma

2012 ◽  
Vol 33 (3) ◽  
pp. E1 ◽  
Author(s):  
Jai Deep Thakur ◽  
Anirban Deep Banerjee ◽  
Imad Saeed Khan ◽  
Ashish Sonig ◽  
Cedric D. Shorter ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Therapeutic Option ◽  
Treatment Protocol ◽  
Specific Treatment ◽  
Maximum Diameter ◽  
Patient Specific ◽  
Hypothetical Case ◽  
Level Of Evidence ◽  
Advantages And Disadvantages ◽  
Clinical Scenarios

Advances in neuroimaging have increased the detection rate of small vestibular schwannomas (VSs, maximum diameter < 25 mm). Current management modalities include observation with serial imaging, stereotactic radiosurgery, and microsurgical resection. Selecting one approach over another invites speculation, and no standard management consensus has been established. Moreover, there is a distinct clinical heterogeneity among patients harboring small VSs, making standardization of management difficult. The aim of this article is to guide treating physicians toward the most plausible therapeutic option based on etiopathogenesis and the highest level of existing evidence specific to the different cohorts of hypothetical case scenarios. Hypothetical cases were created to represent 5 commonly encountered scenarios involving patients with sporadic unilateral small VSs, and the literature was reviewed with a focus on small VS. The authors extrapolated from the data to the hypothetical case scenarios, and based on the level of evidence, they discuss the most suitable patient-specific treatment strategies. They conclude that observation and imaging, stereotactic radiosurgery, and microsurgery are all important components of the management strategy. Each has unique advantages and disadvantages best suited to certain clinical scenarios. The treatment of small VS should always be tailored to the clinical, personal, and social requirements of an individual patient, and a rigid treatment protocol is not practical.

scholarly journals Identification of Brain-Specific Treatment Effects in NPC1 Disease by Focusing on Cellular and Molecular Changes of Sphingosine-1-Phosphate Metabolism

2020 ◽  
Vol 21 (12) ◽  
pp. 4502 ◽  
Author(s):  
Anne Gläser ◽  
Franziska Hammerl ◽  
Markus H. Gräler ◽  
Sina M. Coldewey ◽  
Christin Völkner ◽  
...  
Keyword(s):  
Side Effects ◽  
Treatment Effects ◽  
Human Fibroblasts ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Brain Regions ◽  
Recessive Trait ◽  
Lysosomal Storage ◽  
Npc1 Gene ◽  
Sphingosine 1 Phosphate

Niemann–Pick type C1 (NPC1) is a lysosomal storage disorder, inherited as an autosomal-recessive trait. Mutations in the Npc1 gene result in malfunction of the NPC1 protein, leading to an accumulation of unesterified cholesterol and glycosphingolipids. Beside visceral symptoms like hepatosplenomegaly, severe neurological symptoms such as ataxia occur. Here, we analyzed the sphingosine-1-phosphate (S1P)/S1P receptor (S1PR) axis in different brain regions of Npc1−/− mice and evaluated specific effects of treatment with 2-hydroxypropyl-β-cyclodextrin (HPβCD) together with the iminosugar miglustat. Using high-performance thin-layer chromatography (HPTLC), mass spectrometry, quantitative real-time PCR (qRT-PCR) and western blot analyses, we studied lipid metabolism in an NPC1 mouse model and human skin fibroblasts. Lipid analyses showed disrupted S1P metabolism in Npc1−/− mice in all brain regions, together with distinct changes in S1pr3/S1PR3 and S1pr5/S1PR5 expression. Brains of Npc1−/− mice showed only weak treatment effects. However, side effects of the treatment were observed in Npc1+/+ mice. The S1P/S1PR axis seems to be involved in NPC1 pathology, showing only weak treatment effects in mouse brain. S1pr expression appears to be affected in human fibroblasts, induced pluripotent stem cells (iPSCs)-derived neural progenitor and neuronal differentiated cells. Nevertheless, treatment-induced side effects make examination of further treatment strategies indispensable.

scholarly journals Mathematical Modeling to Address Challenges in Pancreatic Cancer

2020 ◽  
Vol 20 (5) ◽  
pp. 367-376 ◽  
Author(s):  
Prashant Dogra ◽  
Javier R. Ramírez ◽  
María J. Peláez ◽  
Zhihui Wang ◽  
Vittorio Cristini ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Early Diagnosis ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Chemotherapeutic Agents ◽  
Current Status ◽  
Ductal Adenocarcinoma ◽  
Patient Specific ◽  
Therapeutic Outcomes ◽  
The Status

Pancreatic Ductal Adenocarcinoma (PDAC) is regarded as one of the most lethal cancer types for its challenges associated with early diagnosis and resistance to standard chemotherapeutic agents, thereby leading to a poor five-year survival rate. The complexity of the disease calls for a multidisciplinary approach to better manage the disease and improve the status quo in PDAC diagnosis, prognosis, and treatment. To this end, the application of quantitative tools can help improve the understanding of disease mechanisms, develop biomarkers for early diagnosis, and design patient-specific treatment strategies to improve therapeutic outcomes. However, such approaches have only been minimally applied towards the investigation of PDAC, and we review the current status of mathematical modeling works in this field.

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