| 1. |
- Bjersand, Kathrine, et al.
(författare)
-
Ex vivo assessment of cancer drug sensitivity in epithelial ovarian cancer and its association with histopathological type, treatment history and clinical outcome
- 2022
-
Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 61:4
-
Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian cancer (EOC) is divided into type I and type II based on histopathological features. Type I is clinically more indolent, but also less sensitive to chemotherapy, compared with type II. The basis for this difference is not fully clarified. The present study investigated the pattern of drug activity in type I and type II EOC for standard cytotoxic drugs and recently introduced tyrosine kinase inhibitors (TKIs), and assessed the association with treatment history and clinical outcome. Isolated EOC tumor cells obtained at surgery were investigated for their sensitivity to seven standard cytotoxic drugs and nine TKIs using a short-term fluorescent microculture cytotoxicity assay (FMCA). Drug activity was compared with respect to EOC subtype, preoperative chemotherapy, cross-resistance and association with progression-free survival (PFS). Out of 128 EOC samples, 120 samples, including 21 type I and 99 type II, were successfully analyzed using FMCA. Patients with EOC type I had a significantly longer PFS time than patients with EOC type II (P=0.01). In line with clinical experience, EOC type I samples were generally more resistant than type II samples to both standard cytotoxic drugs and the TKIs, reaching statistical significance for cisplatin (P=0.03) and dasatinib (P=0.002). A similar pattern was noted in samples from patients treated with chemotherapy prior to surgery compared with treatment-naive samples, reaching statistical significance for fluorouracil, irinotecan, dasatinib and nintedanib (all P<0.05). PFS time gradually shortened with increasing degree of drug resistance. Cross-resistance between drugs was in most cases statistically significant yet moderate in degree (r<0.5). The clinically observed relative drug resistance of EOC type I, as well as in patients previously treated, is at least partly due to mechanisms in the tumor cells. These mechanisms seemingly also encompass kinase inhibitors. Ex vivo assessment of drug activity is suggested to have a role in the optimization of drug therapy in EOC.
|
|
| 2. |
|
|
| 3. |
- Martinez-Monleon, Angela, et al.
(författare)
-
Identification of recurrent 3q13.31 chromosomal rearrangement indicates LSAMP as a tumor suppressor gene in neuroblastoma
- 2023
-
Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 62:2
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system. NB is mainly driven by copy number alterations, such asMYCN amplification, large deletions of chromosome arm 11q and gain of chromosome arm 17q, which are all markers of high-risk disease. Genes targeted by recurrent, smaller, focal alterations include CDKN2A/B, TERT, PTPRD and ATRX. Our previous study on relapsed NB detected recurrent structural alterations centered at limbic system-associated membrane protein (LSAMP; HUGO Gene Nomenclature Committee: 6705; chromosomal location 3q13.31), which is a gene frequently reported to be deleted or downregulated in other types of cancer. Notably, in cancer, LSAMP has been shown to have tumor-suppressing functions. The present study performed an expanded investigation using whole genome sequencing of tumors from 35 patients, mainly with high-risk NB. Focal duplications or deletions targeting LSAMP were detected in six cases (17%), whereas single nucleotide polymorphism-microarray analysis of 16 NB cell lines detected segmental alterations at 3q13.31 in seven out of the 16 NB cell lines (44%). Furthermore, low expression of LSAMP in NB tumors was significantly associated with poor overall and event-free survival. In vitro, knockdown of LSAMP in NB cell lines increased cell proliferation, whereas overexpression decreased proliferation and viability. These findings supported a tumor suppressor role for LSAMP in NB. However, the higher incidence of LSAMP aberrations in cell lines and in relapsed NB tumors suggested that these alterations were a late event predominantly in advanced NB with a poor prognosis, indicating a role of LSAMP in tumor progression rather than in tumor initiation. In conclusion, the present study demonstrated recurrent genomic aberrations of chromosomal region 3q13.31 that targeted the LSAMP gene, which encodes a membrane protein involved in cell adhesion, central nervous system development and neurite outgrowth. The frequent aberrations affecting LSAMP, together with functional evidence, suggested an anti-proliferative role of LSAMP in NB.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Yang, Wen-Jing, et al.
(författare)
-
Heparanase from triple-negative breast cancer and platelets acts as an enhancer of metastasis
- 2020
-
Ingår i: International Journal of Oncology. - : SPANDIDOS PUBL LTD. - 1019-6439 .- 1791-2423. ; 57:4, s. 890-904
-
Tidskriftsartikel (refereegranskat)abstract
- Triple-negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia-inducible factor-1a (HIF-1a)/vascular endothelial growth factor-a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti-Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
