scholarly journals EXTH-52. GLIOBLASTOMA-TARGETING AUTOLOGOUS INDUCED NEURAL STEM CELL THERAPY: EVALUATING SAFETY, TOXICITY, PERSISTENCE, AND TRANSPLANT METHODS IN A POST-SURGICAL CANINE MODEL

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii98-ii98
Author(s):  
Hunter Bomba ◽  
Kevin Sheets ◽  
Alain Valdivia ◽  
Simon Khagi ◽  
Laura Ruterbories ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Survival ◽  
Tumor Resection ◽  
Canine Model ◽  
Improve Patient Survival ◽  
Mri Sequences ◽  
Xenograft Models ◽  
Induced Neural Stem Cell ◽  
Acute Injection ◽  
Induced Neural Stem Cells

Abstract BACKGROUND Glioblastoma patient survival statistics have remained unchanged for more than three decades. Despite tumor resection and chemoradiotherapy, recurrence is inevitable. Moreover, the invasive behavior of glioblastoma confounds treatment. To improve patient survival statistics, a targeted therapy that can home to distant tumor foci is desperately needed. Induced neural stem cells (iNSCs) armed with cytotoxic payloads have proven efficacious against human xenograft models of glioblastoma. To further propel iNSCs to human clinical trials, we investigated the safety, toxicity, and persistence of iNSCs in a canine model. METHODS Autologous iNSCs generated from the skin of four non-tumor-bearing, purpose-bred, male beagles were engineered to express TRAIL and thymidine kinase (TK). iNSCs were loaded with ferumoxytol to facilitate MRI-tracking. Canines were divided into two cohorts to denote iNSC administration route: scaffold encapsulation or intracerebroventricular (ICV). Two dose levels were investigated: 1′106 iNSCs/kg or 3′106 iNSCs/kg. The scaffold cohort received a single dose of iNSCs while the ICV cohort received three doses of iNSCs via a Rickham reservoir. To activate TK, canines were administered valganciclovir. Canine health was assessed via neurological exams, MRI, and serial blood, urine, and CSF analyses. RESULTS No acute injection reactions were observed. Three of four canines exhibited surgery-induced blindness. Urine and CSF analyses were unremarkable. Unexpectedly, blood analyses showed transient neutropenia. Hypodense signal was observed on all MRI sequences through endpoint. Post-mortem histopathology of the spleen, liver, and lung were unremarkable. As expected, brain tissues exhibited gliosis, fibrous thickening, and inflammation. Spinal cords exhibited acute hemorrhaging, attributed to perimortem CSF draws. Surprisingly, significant testicular degeneration was observed; this was confirmed to be caused by valganciclovir. In conclusion, iNSCs exhibit limited toxicity and warrant further exploration. FUTURE DIRECTIONS Prospective studies will investigate the efficacy of autologous iNSCs in a spontaneous canine glioma model in preparation for human clinical trials.

Using a program that computes tumor decay (d) and regrowth (g) rates and the fraction (Φ) of tumor killed to assist in clinical trials and improve patient survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22213-e22213
Author(s):  
Julia Wilkerson ◽  
Susan Elaine Bates ◽  
Wilfred Donald Stein ◽  
Tito Fojo
Keyword(s):  
Clinical Trials ◽  
Patient Survival ◽  
Drug Action ◽  
Treatment Modalities ◽  
Targeted Therapeutics ◽  
Improve Patient Survival ◽  
Metastatic Setting ◽  
Rate Of Decay ◽  
Mathematical Equations ◽  
Improve Patient

e22213 Background: Clinical trials collect much data on tumor quantity as therapy proceeds. From this data progression endpoints and response rates are reported and used to evaluate efficacy. But there is much information contained therein that allows us to understand mechanisms of drug action and how to best administer therapies. Methods: We have developed mathematical equations that enable extraction of the rates of tumor decay (d) and regrowth (g) and also the fraction (Φ) of tumor killed. Results: We have analyzed data from >3,000 cases of various tumor histologies including prostate, breast, renal, and medullary thyroid cancers as well as multiple myeloma (MM). These malignancies have been treated with “cytotoxic” and “targeted” therapeutics as well as vaccines. Across all treatment modalities, overall survival does not correlate with the rate of decay, d, but correlates strongly with the growth rate, g. In some drug/tumor combinations, Φ can also be extracted and its role in the drug’s action ascertained. Most therapies developed in metastatic cancers such as ixabepilone in breast cancer and sunitinib in renal cancer are “g therapies”. Such therapies reduce g, impact survival favorably and could further impact survival if administered beyond conventional endpoints for progression. In contrast, “Φ therapies”, such as bortezomib in MM and ATTP in prostate cancer kill a larger fraction of tumor and are proposed to be effective as adjuvant and neo-adjuvant treatments, with little benefit from extending treatment in the metastatic setting. Furthermore, the data suggest resistance in most is likely intrinsic since tumor growth rates on therapy do not change appreciably over time. Conclusions: We have developed an analytical method that characterizes a tumor’s response to a therapy and enables extraction of tumor decay (d) and regrowth (g) rates and the fraction (Φ) of tumor killed. Both g and Φ, but not d, determine the effectiveness of a therapy. Use of these parameters should allow for the conduct of smaller trials and may also help improve patient survival. A stand-alone computer program has been built, is available to the research community and will be demonstrated.

scholarly journals Primary Malignant Melanoma of the Vagina without Metastasis: A Rare Case and Review of Literature

2020 ◽  
Author(s):  
Wilson Bizimana ◽  
Gloria Akimana ◽  
Arthur Semedo Insumbo ◽  
Hounayda Jerguigue ◽  
Rachida Latib ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Patient Survival ◽  
Rare Condition ◽  
Primary Malignant Melanoma ◽  
Imaging Features ◽  
Review Of Literature ◽  
Pelvic Magnetic Resonance Imaging ◽  
Improve Patient Survival ◽  
Appropriate Treatment ◽  
Improve Patient

AbstractMalignant melanoma of vagina is a rare condition. Its histogenesis has been debated and the positive diagnosis is based on immunohistochemistry. Pelvic magnetic resonance imaging remains the gold standard for assessing locoregional extension status and post-treatment surveillance of melanoma of vagina. The observation concerned a 53-year-old woman with no specific history who presented a primary malignant melanoma of vagina without secondary locations. To date, the case is the second one reported in the literature. Early diagnosis of the malignant melanoma of vagina may improve patient survival because late diagnoses are punctuated by poor prognosis. We have presented epidemiological with etiopathogenic characteristics and described all imaging features to stage the tumor and to conduct the appropriate treatment.

The Role of Visceral Transplantation for Neoplastic Disease

2020 ◽  
Vol 04 (03) ◽  
pp. 273-281
Author(s):  
Masato Fujiki ◽  
Amit Nair ◽  
Giuseppe D'amico ◽  
Mohammed Osman
Keyword(s):  
Patient Survival ◽  
Ex Vivo ◽  
Tumor Resection ◽  
Case Series ◽  
National Database ◽  
Neuroendocrine Neoplasms ◽  
Neoplastic Disease ◽  
Desmoid Tumors ◽  
Post Transplant ◽  
Recipient Tissue

AbstractVisceral transplantation has been utilized as the most radical surgical treatment for neoplasms not amenable to conventional resection. The main indications for this procedure include mesenteric desmoid tumors threatening the root of mesentery and metastatic neuroendocrine neoplasms. Published case-series of visceral transplantation for such indications are reviewed in this article. Patients with desmoid tumors associated with familial adenomatous polyposis are transplanted with intestinal or multivisceral allografts. With surgical modification of technique, the native spleen is preserved while duodenopancreatic complex is removed to obviate the risk of malignant transformation of duodenal polyposis after transplantation. Preservation of spleen decreased incidence of post-transplant lymphoproliferative disorder, conferring therapeutic advantage. Patient survival is comparable to that of other indications, and desmoid tumor recurrence has been observed in the recipient tissue but not in the donor allograft. For visceral transplantation of metastatic neuroendocrine neoplasms, the majority of these patients have diffuse liver involvement, thus requiring full multivisceral transplantation. Post-transplant patient survival is acceptable with limited data available on recurrence. Autotransplantation following ex vivo tumor resection using visceral allografts has been also performed in a limited, select cohort of patients with various pathologies. Adenocarcinomas are associated with a prohibitive recurrence rate following the procedure, and its use for this indication is therefore not recommended. A national database of visceral transplantation undertaken for neoplastic disease should be developed to better understand predictors of outcomes and to help produce and standardize selection criteria.

scholarly journals The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy

Oncogene ◽  
2021 ◽  
Author(s):  
Jian Chen ◽  
Risi Na ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Patient Survival ◽  
Serine Hydroxymethyltransferase ◽  
First Line ◽  
Xenograft Models ◽  
Potential Opportunity ◽  
First Line Treatment ◽  
Novel Therapeutic

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.

scholarly journals Novel Marine Compounds: Anticancer or Genotoxic?

2004 ◽  
Vol 2004 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Jamal M. Arif ◽  
Amal A. Al-Hazzani ◽  
Muhammed Kunhi ◽  
Fahad Al-Khodairy
Keyword(s):  
Clinical Trials ◽  
Anticancer Agents ◽  
Screening Tests ◽  
Tumor Xenograft ◽  
Anticancer Compounds ◽  
Early Exit ◽  
Marine Compounds ◽  
Xenograft Models ◽  
Pharmaceutical Industries ◽  
Carcinogenesis Models

In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

Abstract A56: Identification of a micro RNA profile to predict response to therapy and improve patient survival in ovarian cancer

2013 ◽  
Author(s):  
Marina Rigau ◽  
Blanca Majem ◽  
Tatiana Altadill ◽  
Lucia Lanau ◽  
José-Luis Sánchez-Iglesias ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Patient Survival ◽  
Response To Therapy ◽  
Micro Rna ◽  
Improve Patient Survival ◽  
Improve Patient

Regurgitant Commissure Flow Through a Closed Polymeric Heart Valve

2010 ◽  
Author(s):  
Scott C. Corbett ◽  
Hamid N.-Hashemi ◽  
Ahmet U. Coskun
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Structural Changes ◽  
Patient Survival ◽  
Improve Patient Survival ◽  
Flow Disturbances ◽  
Limited Life ◽  
Flow Through ◽  
Valve Prostheses ◽  
Improve Patient

While heart valve prostheses have been used successfully since 1960, outcomes are far from ideal. The underlying problem with bioprostheses is a limited life from structural changes such as calcification and leaflet wear, leading to valve failure. The underlying problem with mechanical heart valves is the presence of flow disturbances which necessitate anticoagulation. A polyurethane valve has the potential to improve upon the shortcomings of existing valves and ultimately improve patient survival.

scholarly journals Surgical Resection and Pazopanib Treatment for Recurrent Cardiac Angiosarcoma

2019 ◽  
Vol 12 ◽  
pp. 2632010X1983126
Author(s):  
Yuki Nakamura ◽  
Koichi Toda ◽  
Shigeru Miyagawa ◽  
Yasushi Yoshikawa ◽  
Hiroki Hata ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Poor Prognosis ◽  
Tumor Recurrence ◽  
Kinase Inhibitor ◽  
Patient Survival ◽  
Optimal Management ◽  
Improve Patient Survival ◽  
Cardiac Angiosarcoma ◽  
Sarcoma Treatment ◽  
Improve Patient

Cardiac sarcoma treatment is challenging for surgeons because of frequent tumor recurrence and poor prognosis. In addition, optimal management of recurrences is not well established. The multi-targeted tyrosine kinase inhibitor, pazopanib, was recently approved for soft-tissue sarcoma. Herein, we present a case involving recurrent cardiac angiosarcoma where the patient survived for 2 years with complete remission of disease after repeated surgical resection and treatment with oral pazopanib. Based on our experience, aggressive surgical resection combined with pazopanib may be a valid treatment for recurrent cardiac angiosarcoma to improve patient survival.

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