Oncolytic Viral Therapies for Soft Tissue Sarcomas
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Questions and Answers

What is the median 5-year survival rate for adult patients with Rhabdomyosarcoma receiving both chemotherapy and radiotherapy?

  • 27%
  • 61%
  • 40%
  • 31% (correct)

    • What percentage of cancers in children are classified as sarcomas?

  • 7% (correct)
  • 1%
  • 10%
  • 4%

    • Which type of sarcoma occurs at a higher rate in the population?

  • Soft Tissue Sarcomas (correct)
  • Breast sarcomas
  • Lung sarcomas
  • Bone sarcomas

    • In which age range does Rhabdomyosarcoma represent 50% of all soft tissue sarcoma tumors?

    <p>0-14 years</p> Signup and view all the answers

    What is the common response to therapeutic modalities for Rhabdomyosarcoma as indicated by the 10-year disease-free survival rate?

    <p>40-41%</p> Signup and view all the answers

    Why is treatment for Rhabdomyosarcoma considered inefficient?

    <p>Highly metastatic nature and tumor chemoresistance</p> Signup and view all the answers

    Which therapeutic approach is cited as one of the best for Rhabdomyosarcoma?

    <p>HSV-Tk/GCV suicide gene therapy</p> Signup and view all the answers

    What is one of the significant challenges in studying Rhabdomyosarcoma?

    <p>Rarity of the tumor and low prevalence</p> Signup and view all the answers

    What is the primary role of E1A transcripts in cellular processes?

    <p>Inhibit cAMP-mediated transcription</p> Signup and view all the answers

    How do E1B proteins interact with p53?

    <p>They induce its degradation</p> Signup and view all the answers

    What outcome results from the deletion of the E1B-19kDa gene?

    <p>Induction of apoptosis in tumorigenic cells</p> Signup and view all the answers

    What mechanism does E1B-19kDa use to prevent apoptosis?

    <p>Inhibiting Bax/Bak signaling</p> Signup and view all the answers

    What effect does the E1B-55 kDa deletion have in p53 dysfunctional cells?

    <p>Preferential adenoviral replication</p> Signup and view all the answers

    What is the role of P/CAF in relation to E1A?

    <p>Is completely inhibited by E1A</p> Signup and view all the answers

    In clinical trials, what effect has the combination of E1B-19kDa deleted adenovirus and cisplatin shown?

    <p>Higher efficacy in inducing apoptosis</p> Signup and view all the answers

    What defines the pro-apoptotic function of E1A transcripts?

    <p>Processing procaspase-3</p> Signup and view all the answers

    What is a notable feature of germline p53 mutations in children?

    <p>They are frequently detected in rhabdomyosarcoma.</p> Signup and view all the answers

    What does the study by Düzgüneş focus on in relation to gene therapy?

    <p>Origins of suicide gene therapy.</p> Signup and view all the answers

    Which agent is a selective inhibitor for herpes virus replication?

    <p>9-(2-hydroxyethoxymethyl)guanine.</p> Signup and view all the answers

    Which publication provides information about the response to chemotherapy in adult rhabdomyosarcoma?

    <p>Annals of Surgery.</p> Signup and view all the answers

    What effect do polymer-coated adenoviruses have as per the research by Fisher et al.?

    <p>They allow retargeting and evade neutralizing antibodies.</p> Signup and view all the answers

    Which study discusses the adenovirus vector and its modified fibers?

    <p>Dmitriev et al. 1998.</p> Signup and view all the answers

    Which outcome is linked to the selectivity of action of an antiherpetic agent studied by Elion et al.?

    <p>Specific targeting of herpes viruses.</p> Signup and view all the answers

    What is the primary focus of the research conducted by Schupak and colleagues regarding soft tissue sarcoma?

    <p>Comprehensive understanding and treatment protocols.</p> Signup and view all the answers

    What is the primary focus of the database compiled by Sauerbrei and colleagues?

    <p>Natural polymorphisms and resistance-related mutations</p> Signup and view all the answers

    What is the primary focus of the research conducted by R. Roop in 1995?

    <p>Inhibition of melanoma growth</p> Signup and view all the answers

    Which type of cancer is specifically analyzed in the work of Shern and colleagues?

    <p>Rhabdomyosarcoma</p> Signup and view all the answers

    Which adenoviral modification enhances protein product levels for certain transgenes, as noted in the research by Mel Campbell and colleagues?

    <p>Incorporation of an arg–gly–asp (rgd) motif</p> Signup and view all the answers

    What method was utilized by Smythe and his team in transferring the herpes simplex virus thymidine kinase gene?

    <p>Recombinant adenovirus</p> Signup and view all the answers

    What was the focus of the publication by Stahlwood and colleagues regarding adenovirus?

    <p>Adenovirus infectivity neutralisation by ascitic fluid</p> Signup and view all the answers

    What immune response was primarily the subject of the 1999 research by N. Chirmule and colleagues?

    <p>Responses to adenoviral vectors</p> Signup and view all the answers

    Which treatment method was explored by K. Culver and colleagues in relation to brain tumors?

    <p>Retroviral vector-producer cells</p> Signup and view all the answers

    What aspect of rhabdomyosarcoma was examined in the study by Sultan and colleagues?

    <p>Differences between adult and pediatric cases</p> Signup and view all the answers

    Which of the following best describes the type of mutations studied by Sauerbrei and colleagues?

    <p>Non-synonymous mutations</p> Signup and view all the answers

    What is a significant characteristic of adenoviruses as described by A.J. Davison?

    <p>Their genetic content is stable and well-characterized.</p> Signup and view all the answers

    Which effect does the fiber knob modification have on adenovirus gene transfer efficiency for human rhabdomyosarcoma cells?

    <p>It overcomes low, heterogeneous expression.</p> Signup and view all the answers

    Which research area does the publication by Steegenga and colleagues pertain to?

    <p>Cellular responses to viral infections</p> Signup and view all the answers

    In the 2001 publication by Timothy P. Cripe and colleagues, what limitation of adenovirus gene transfer is addressed?

    <p>Low transduction efficiency in certain cell types</p> Signup and view all the answers

    What statistical period does Sultan's analysis of rhabdomyosarcoma cases cover?

    <p>1973 to 2005</p> Signup and view all the answers

    Which journal featured research on the immune responses to adenoviruses as mentioned in the studies?

    <p>Gene Therapy</p> Signup and view all the answers

    What plays a crucial role in myoblast fusion during early muscle development?

    <p>Connexin43 (Cx43)</p> Signup and view all the answers

    What consequence does a reduction in Cx43 expression in breast cancer imply?

    <p>Potential role in tumorigenicity</p> Signup and view all the answers

    Which connexin is highlighted for its enhanced bystander effect when expressed?

    <p>Connexin26 (Cx26)</p> Signup and view all the answers

    What is indicated by the heterogeneous distribution of connexins in human malignancy?

    <p>Complex functional regulation</p> Signup and view all the answers

    What is under investigation to improve therapies like HSVtk/GCV?

    <p>Manipulation of connexin expression</p> Signup and view all the answers

    What is the proposed function of the recombinant viral vector mentioned?

    <p>To phosphorylate GCV and maximize bystander cell transfer</p> Signup and view all the answers

    What condition is particularly relevant to disruptions in Cx43 dynamics?

    <p>Rhabdomyosarcoma (RMS)</p> Signup and view all the answers

    What does the interaction between Pannexin1 (PANX1) and Cx43 suggest?

    <p>A complex network influencing RMS malignancy</p> Signup and view all the answers

    Study Notes

    Comparing Various Oncolytic Viral Therapies with an Optimised HSV-Tk Approach for Soft Tissue Sarcomas

    • This study compares various oncolytic viral therapies for soft tissue sarcomas, focusing on optimizing the HSV-Tk approach, particularly for rhabdomyosarcoma (RMS).

    • Sarcomas are rare mesenchymal tumors, comprising less than 1% of all cancers and 7% of childhood cancers. Rhabdomyosarcoma (RMS) is the most common type, accounting for 50% of soft tissue sarcomas in children aged 0-14.

    • The study investigates the current understanding of the mechanism of GCV-induced apoptosis in HSV-Tk+ cells, highlighting the importance of HSV-1 Tk as the ideal suicide gene, and the need for a viral strain with the highest catalytic activity toward GCV.

    • It examines various delivery vehicles, including lentiviruses, adenoviruses and RNA-based retroviruses, focusing on their viability as vectors for delivering the HSV-Tk gene and determining the ideal choice for RMS-specific gene transduction.

    • The study discusses the role of prodrug choice, specifically ganciclovir (GCV) and its potential for optimization through alteration of its pharmacokinetics, to maximize its efficiency and reduce toxicity.

    • Optimization strategies include the modification of the thymidine kinase (Tk) gene through mutagenesis at specific sites to improve its catalytic activity toward GCV. The use of tumor-specific promoters to limit expression to tumor cells, also increasing specificity and efficacy, and enhancing the bystander effect through connexin transfection.

    • This work examines the effectiveness of different strategies in the context of cancer cell death by apoptosis.

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    Description

    This quiz explores the comparison of various oncolytic viral therapies tailored for soft tissue sarcomas, with a special emphasis on the optimized HSV-Tk approach for rhabdomyosarcoma (RMS). Dive into the mechanisms of GCV-induced apoptosis and evaluate the effectiveness of different delivery vehicles in gene therapy.

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