scholarly journals Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 595 ◽  
Author(s):  
Kim ◽  
Lee ◽  
Jeon ◽  
Kim ◽  
Kang ◽  
...  

Temozolomide is the current first-line treatment for glioblastoma patients but, because many patients are resistant to it, there is an urgent need to develop antitumor agents to treat temozolomide-resistant glioblastoma. Gossypol, a natural polyphenolic compound, has been studied as a monotherapy or combination therapy for the treatment of glioblastoma. The combination of gossypol and temozolomide has been shown to inhibit glioblastoma, but it is not clear yet whether gossypol alone can suppress temozolomide-resistant glioblastoma. We find that gossypol suppresses the growth of temozolomide-resistant glioblastoma cells in both tumor sphere and adherent culture conditions, with tumor spheres showing the greatest sensitivity. Molecular docking and binding energy calculations show that gossypol has a similar affinity to the Bcl2 (B-cell lymphoma 2) family of proteins and several dehydrogenases. Gossypol reduces mitochondrial membrane potential and cellular ATP levels before cell death, which suggests that gossypol inhibits several dehydrogenases in the cell’s metabolic pathway. Treatment with a Bcl2 inhibitor does not fully explain the effect of gossypol on glioblastoma. Overall, this study demonstrates that gossypol can suppress temozolomide-resistant glioblastoma and will be helpful for the refinement of gossypol treatments by elucidating some of the molecular mechanisms of gossypol in glioblastoma.

2019 ◽  
Vol 19 (9) ◽  
pp. 681-687 ◽  
Author(s):  
Linqing Zou ◽  
Guoqi Song ◽  
Siyu Gu ◽  
Lingling Kong ◽  
Shiqi Sun ◽  
...  

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype B non-Hodgkin lymphoma in adults. After rituximab being introduced to treat DLBCL, the current first-line treatment is R-CHOP regimen. This regimen greatly improves patient's prognosis, however, relapsed or refractory cases are commonly seen, mainly due to the resistance to rituximab. Although a large number of experiments have been conducted to investigate rituximab resistance, the exac mechanisms and solutions are still unclear. This review mainly explores the possible mechanisms oft rituximab resistance and current new effective treatments for rituximab resistance in DLBCL.


2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
L. Pezzullo ◽  
G. Cassiordor0 ◽  
R. Rosamilio ◽  
I. Ferrara ◽  
S. Luponio ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Huang ◽  
Sheng Ye ◽  
Yabing Cao ◽  
Zhiming Li ◽  
Jiajia Huang ◽  
...  

Diffuse large B-cell lymphoma (DLBCL) can be molecularly subtyped as either germinal center B-cell (GCB) or non-GCB. The role of rituximab(R) in these two groups remains unclear. We studied 204 patients with de novo DLBCL (107 treated with first-line CHOP; 97 treated with first-line R-CHOP), patients being stratified into GCB and non-GCB on the basis of BCL-6, CD10, and MUM1 protein expression. The relationships between clinical characteristics, survival data, and immunophenotype (IHC) were studied. The 5-year overall survival (OS) in the CHOP and R-CHOP groups was 50.4% and 66.6% (P=0.031), respectively. GCB patients had a better 5-year OS than non-GCB patients whether treated with CHOP or not (65.0% versus 40.9%;P=0.011). In contrast, there is no difference in the 5-year OS for the GCB and non-GCB with R-CHOP (76.5% versus 61.3%;P=0.141). In non-GCB subtype, additional rituximab improved survival better than CHOP (61.3% versus 40.9%;P=0.0303). These results indicated that addition of rituximab to standard chemotherapy eliminates the prognostic value of IHC-defined GCB and non-GCB phenotypes in DLBCL by improving the prognostic value of non-GCB subtype of DLBCL.


2010 ◽  
Vol 6 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Celso Arrais Rodrigues ◽  
Poliana Alves Patah ◽  
Yana A. S. Novis ◽  
Chitra Hosing ◽  
Marcos de Lima

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wilfred Delacruz ◽  
Robert Setlik ◽  
Arash Hassantoufighi ◽  
Shyam Daya ◽  
Susannah Cooper ◽  
...  

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted.


2021 ◽  
Vol 5 (01) ◽  
pp. 03-09
Author(s):  
Zulfia Zinat Chowdhury ◽  
Tamanna Bahar ◽  
Shaila Rahman ◽  
Salina Haque ◽  
A K M Mynul Islam ◽  
...  

Background: Diffuse Large B-Cell Lymphoma (DLBCL), most common Non-Hodgkin Lymphoma (NHL) variety, is an aggressive, fast-growing form comprising up to 40% of all cases globally. Objective: To observe the treatment outcome of different subtypes of Diffuse Large B-Cell Lymphoma (DLBCL) after first-line chemotherapy and also the association with IHC, presenting age, sex, and IPI score with outcome. Methodology: This is a retrospective data analysis included all DLBCL patients registered in the department of Haematology of National Institute of Cancer Research and Hospital (NICRH) between July 2016 to June 2019. Results: Total 188 cases were included in this study and mean age was 48 years with a Standard deviation of 15 years with Male (69.1%) predominance. We divide the cases into three different entities of DLBCL [Germinal Centre B-cell like (GCB), Non-GCB and others (NOS) among them Non-GCB variety was the prevalent (47.3%) one. After first line   chemotherapy 52.1% complete remission with 7% death was observed in overall outcome. There was no significant difference in outcome among different types of DLBCL after chemotherapy based on Han’s algorithm. Rituximab with CHOP has significantly better outcome than CHOP alone arm (p: 0.021). Conclusion: This limited database study of NICRH will help to ascertain the outcome of DLBCL after first-line chemotherapy in Bangladesh.


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