scholarly journals Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment

2021 ◽  
Vol 22 (7) ◽  
pp. 3495
Author(s):  
Katarzyna M. Terlikowska ◽  
Bożena Dobrzycka ◽  
Sławomir J. Terlikowski
Keyword(s):  
Ovarian Cancer ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
Cell Surface Antigens ◽  
Extrinsic Factors ◽  
Molecular Therapies ◽  
Targeted Molecular Therapies

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.

scholarly journals Targeted molecular therapies for ovarian cancer: An update and future perspectives (Review)

2012 ◽  
Vol 28 (2) ◽  
pp. 395-408 ◽  
Author(s):  
HIROSHI SHIGETOMI ◽  
YUMI HIGASHIURA ◽  
HIROTAKA KAJIHARA ◽  
HIROSHI KOBAYASHI
Keyword(s):  
Ovarian Cancer ◽  
Future Perspectives ◽  
Molecular Therapies ◽  
Targeted Molecular Therapies

Molecular Profiling and Commercial Predication Assays in Ovarian Cancer: Still Not Ready for Prime Time?

2014 ◽  
pp. 139-147 ◽  
Author(s):  
Elise C. Kohn
Keyword(s):  
Ovarian Cancer ◽  
Germ Line ◽  
Molecular Profiling ◽  
Added Value ◽  
Prime Time ◽  
Cancer Type ◽  
Brca1 And Brca2 ◽  
Major Barrier ◽  
The Individual

Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach—rather than undergoing rigorous scientific examination—is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

Randomized, multicenter, two-dose level, open-label, phase IIa study with the intraperitoneally infused trifunctional bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) to select the better dose level in platinum refractory epithelial ovarian cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5556-5556 ◽  
Author(s):  
A. Belau ◽  
J. Pfisterer ◽  
P. Wimberger ◽  
C. Kurzeder ◽  
A. Du Bois ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Dose Level ◽  
Dose Effect ◽  
High Dose ◽  
Specific Cell ◽  
Open Label ◽  
Platinum Refractory

5556 Background: The trifunctional antibody catumaxomab specifically binds EpCAM+ tumor cells, CD3+ T lymphocytes and accessory cells via the Fcγ RI/III thereby inducing a tumor specific cell mediated cytotoxicity in vitro and in vivo. This study was conducted to evaluate efficacy and safety of two different regimens of catumaxomab. Methods: Women with platinum-refractory (progressing during or ≤ 6 mos. after the last platinum containing regimen) epithelial ovarian cancer and measurable recurrent disease were randomized to receive either 10 -10 -10 - 10 μg or 10–20–50–100 μg of catumaxomab over 6h i.p on days 0, 3, 7 and 10. Results: 45 pts. were entered (22 high dose (HD)-arm, 23 low dose (LD)-arm). Both groups were well balanced concerning ECOG-perfomance score, with a median age of 65.6y in the HD- and 57.6y in the LD-arm and with a median diameter of measurable lesions of 90mm in the HD- and 104mm in the LD-arm. Based on the AEs, changes in laboratory parameters and other safety variables observed in the safety population in the course of this study, the accumulated safety experience is consistent with the key features of the mode of action of catumaxomab. Their intensity on median level was mostly mild to moderate. A clinical benefit was detectable in 27.3% of pts. for the HD- (1PR/5SD) and 8.7% of pts. for the LD-arm (2SD). After a median follow-up of 4.96 months, the median overall survival time was 182 d for the HD- and 114 d for the LD-arm. Conclusion: The results demonstrate that catumaxomab is safe with acceptable toxicity when administered as a sequence of 4 IP infusions at 10, 20, 50 and 100 μg. A modest dose effect is observed for the higher doses of catumaxomab. No significant financial relationships to disclose.

BRCA1 and BRCA2 Mutations in Breast and Ovarian Cancer Syndrome: Reflection on the Creighton University Historical Series of High Risk Families

2006 ◽  
Vol 5 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Olga M. Sinilnikova ◽  
Sylvie Mazoyer ◽  
Colette Bonnardel ◽  
Henry T. Lynch ◽  
Steven A. Narod ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Cancer Syndrome ◽  
Breast And Ovarian Cancer ◽  
Brca1 And Brca2 ◽  
Historical Series ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations ◽  
High Risk Families

scholarly journals Behavior of Mesenchymal Stem Cells Obtained From Dental Tissues: A Review of the Literature

2019 ◽  
Vol 21 (1) ◽  
pp. 31-40
Author(s):  
Mariné Ortiz-Magdaleno DDS, MSc, PhD ◽  
Ana Isabel Romo-Tobías DDS ◽  
Fernando Romo-Ramírez DDS, MSc ◽  
Diana María Escobar DDS, MSc, PhD ◽  
Héctor Flores-Reyes DDS, MSc, PhD ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Evidence ◽  
Periodontal Regeneration ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Key Factors ◽  
Dental Tissues

The success of tissue engineering in combination with tissue regeneration depends on the behavior and cellular activity in the biological processes developed within a structure that functions as a support, better known as scaffolds, or directly at the site of the injury. The cell-cell and cell-biomaterial interaction are key factors for the induction of a specific cell behavior, together with the bioactive factors that allow the formation of the desired tissue. Mesenchymal Stem Cells (MSC) can be isolated from the umbilical cord and bone marrow; however, the behavior of Dental Pulp Stem Cells (DPSC) has been shown to have a high potential for the formation of bone tissue, and these cells have even been able to induce the process of angiogenesis. Advances in periodontal regeneration, dentin-pulp complex, and craniofacial bone defects through the induction of MSC obtained from tooth structures in in vitro-in vivo studies have permitted the obtaining of clinical evidence of the achievements obtained to date.

scholarly journals Breast ovarian cancer syndrome

2021 ◽  
Vol 8 (8) ◽  
pp. 2454
Author(s):  
Abhirup H. R. ◽  
Priyanka Kenchetty ◽  
Aishwarya K. Chidananda
Keyword(s):  
Ovarian Cancer ◽  
Early Stage ◽  
Radical Mastectomy ◽  
Abdominal Distension ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Care Patient ◽  
Human Beings ◽  
Cancer Syndrome ◽  
Brca1 And Brca2

BRCA1 and BRCA2, known as breast and ovarian cancer predisposition genes, were discovered in the 1990s. As part of a normal genetic structure, these genes are intrinsic to all human beings, but they are mutated in some individuals increasing the risk for breast and ovarian cancers development. BRCA1 is not only expressed in endocrine tissues but is also detected in other cells such as the neuroepithelial cells in the early stage of cell development. Like BRCA1, BRCA2 is also expressed in a wide variety of tissues and is observed with higher rates in the breast and thymus and with lower rates in the lung, ovary and spleen. We presented to you a case of 40 year old female admitted in surgical ward with lump in the left breast since 2 months with ipsilateral discrete axillary lymphadenopathy. Bilateral sono-mammography showed BIRADS V lesion in left breasts with satellite nodules. Ultrasonography of abdomen and pelvis showed large left adnexal solid mass lesion and right sided ovarian cyst with retrocaval, preaortic lymphadenopathy. Patient underwent a diagnostic laparoscopy which was converted to a laparotomy. Total abdominal hysterectomy with bilateral salphingo-oophorectomy was done. For the breast lump, patient underwent left sided modified radical mastectomy. Gene testing for revealed BRCA1 positivity. Chemotherapy was given to cover both breast and ovarian carcinoma. Patient came back with abdominal distension after 9 months and was offered palliative care. Patient succumbed for disease after 1 year after diagnosis. We reviewed the literature for the same.

scholarly journals Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Haihai Liang ◽  
Xiaoguang Zhao ◽  
Chengyu Wang ◽  
Jian Sun ◽  
Yingzhun Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Expression Profiles ◽  
In Vivo Studies ◽  
Clinical Samples ◽  
Orthotopic Mouse Model ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Protein Coding Genes

Abstract Background A deeper mechanistic understanding of epithelial-to-mesenchymal transition (EMT) regulation is needed to improve current anti-metastasis strategies in ovarian cancer (OvCa). This study was designed to investigate the role of lncRNAs in EMT regulation during process of invasion-metastasis in serous OvCa to improve current anti-metastasis strategies for OvCa. Methods We systematically analyzes high-throughput gene expression profiles of both lncRNAs and protein-coding genes in OvCa samples with integrated epithelial (iE) subtype and integrated mesenchymal (iM) subtype labels. Mouse models, cytobiology, molecular biology assays and clinical samples were performed to elucidate the function and underlying mechanisms of lncRNA PTAF-mediated promotion of EMT and invasion-metastasis in serous OvCa. Results We constructed a lncRNA-mediated competing endogenous RNA (ceRNA) regulatory network that affects the expression of many EMT-related protein-coding genes in mesenchymal OvCa. Using a combination of in vitro and in vivo studies, we provided evidence that the lncRNA PTAF-miR-25-SNAI2 axis controlled EMT in OvCa. Our results revealed that up-regulated PTAF induced elevated SNAI2 expression by competitively binding to miR-25, which in turn promoted OvCa cell EMT and invasion. Moreover, we found that silencing of PTAF inhibited tumor progression and metastasis in an orthotopic mouse model of OvCa. We then observed a significant correlation between PTAF expression and EMT markers in OvCa patients. Conclusions The lncRNA PTAF, a mediator of TGF-β signaling, can predispose OvCa patients to metastases and may serve as a potential target for anti-metastatic therapies for mesenchymal OvCa patients.

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