OncoTargets and therapy最新文献

Introduction: Erythrina subumbrans, a medical plant found in sub-Saharan Africa and the Western Ghats of India, shows promise as a potential source of bioactive compounds to treat cancer. In our ongoing research on folk medical plants, we report the isolation of flavonoid compound from the stem bark of E. subumbrans along with its cytotoxic activity against breast cancer (MCF-7 and T47D), and cervical cancer (HeLa) cell lines.

Purpose: This study aimed to isolate secondary metabolite from the stem bark of E. subumbrans and evaluate its cytotoxic activity to support the use of folk medicinal plants as alternative therapy against cancer.

Methods: Isolupalbigenin was isolated from the stem bark of E. subumbrans by column chromatography. Cytotoxic activity against breast cancer (MCF-7 and T47D) and cervical cancer (HeLa) cell lines was evaluated using the MTT assay, whereas the in silico study was evaluated using molecular docking and molecular dynamics against estrogen receptor alpha (ERα).

Results: The cytotoxic assay showed that isolupalbigenin inhibited the growth of MCF-7 cell with an IC₅₀ of 31.62 µg∙mL^-1, while showing no toxicity against normal human cells (Vero cell line). The molecular docking results suggested that isolupalbigenin can bind to ERα with a lower binding affinity than estradiol, whereas the stability of the isolupalbigenin-ERα complex was confirmed by molecular dynamic simulation with a median Root Mean Square Deviation (RMSD) of 2.80 Å. Toxicity prediction suggested that isolupalbigenin was less likely to cause hepatotoxicity or carcinogenicity, whereas pharmacokinetic prediction suggested that isolupalbigenin has high intestinal absorption with medium Caco2 permeability. In addition, isolupalbigenin was predicted to have a medium volume of distribution (Vd).

Conclusion: Isolupalbigenin isolated from the stem bark of E. subumbrans with cytotoxic activity supports further development of plants from the genus Erythrina as a medicinal plant for alternative therapy against cancer.

Purpose: The diagnosis of breast cancer during pregnancy is a rare event, but it is more frequent in our daily clinical practice due to the progressing aging of pregnant women. The management of a woman affected by pregnancy-associated breast cancer (PABC) remains a challenge for the clinician as it is related to ethical and psychological decisions.

Patients and methods: Here, we retrospectively described 10 cases of PABC in women treated at our Institution. All cases were discussed in the multidisciplinary team. We reviewed available literature data on the topic.

Results: Nine out 10 patients were diagnosed with localized breast cancer. The remaining patients were presented with metastatic de novo disease. Median age was 37.5 years (range 26-42). Seven patients presented with grade 3 tumor and 9 patients had Ki-67 value higher than 30%. All but 2 patients received neoadjuvant chemotherapy consisting of sequential anthracyclines and cyclophosphamide followed by weekly paclitaxel during pregnancy. No safety concerns or complications during delivery for both the mothers and the babies were reported.

Conclusion: Breast cancer during pregnancy is a challenging clinical situation and all the decisions need to consider both the patients and the fetus safety. Data from our series and from literature confirm the safety of standard chemotherapy approach starting from the second trimester of gestation. More research and effort are needed to offer these patients excellent outcomes and it is mandatory that cases should be closely followed up by a multidisciplinary team.

Background: Overwhelming evidence has suggested that dysregulated long noncoding RNAs (lncRNAs) play a critical modulating effect in the evolution of breast cancer (BRCA). Nevertheless, the roles of lncRNA PTPRG antisense RNA 1 (PTPRG-AS1) in BRCA and the underlying mechanisms have not been experimentally validated and functionally annotated.

Methods: The expression of lncRNA PTPRG-AS1 in BRCA tissues and cell lines was evaluated by reverse transcription-quantitative PCR (RT-qPCR), and by using public databases. The proliferation of BRCA cells was detected using Cell Counting Kit-8 and colony formation assays. Wound healing assay, and Transwell migration and invasion assays were carried out to explore the migratory and invasive abilities of BRCA cells. The interaction between lncRNA PTPRG-AS1, microRNA (miR)-4659a-3p and glutaminyl-peptide cyclotransferase (QPCT) was verified using RT-qPCR, dual-luciferase reporter assay and Western blotting.

Results: The results showed that LncRNA PTPRG-AS1 was markedly upregulated in BRCA tissues and cell lines. Knocking down lncRNA PTPRG-AS1 significantly inhibited the proliferation, migration and invasion of BRCA cells, while overexpression of lncRNA PTPRG-AS1 enhanced the aforementioned properties of BRCA cells. Further analyses revealed that PTPRG-AS1 may act as a molecular sponge for miR-4659a-3p, thus regulating QPCT expression, therefore, acting as an oncogene in BRCA.

Conclusion: Collectively, the study demonstrates that lncRNA PTPRG-AS1 may act as a competing endogenous RNA by regulating the miR-4659a-3p/QPCT axis in BRCA progression. This lncRNA could potentially be a biomarker and therapeutic target for BRCA.

[This corrects the article DOI: 10.2147/OTT.S57126.].

Cervical cancer is ranked the fourth most common cause of cancer related deaths amongst women. The situation is particularly dire in low to lower middle-income countries. It continues to affect these countries due to poor vaccine coverage and screening. Cervical cancer is mostly detected in the advanced stages leading to poor outcomes. This review focuses on the progress made to date to improve early detection and targeted therapy using both circulating RNA. Vaccine has played a major role in cervical cancer control in vaccinated young woman in mainly developed countries yet in low-income countries with challenges of 3 dose vaccination affordability, cervical cancer continues to be the second most deadly amongst women. In this review, we show the progress made in reducing cervical cancer using vaccination that in combination with other treatments that might improve survival in cervical cancer. We further show with both miRNA and siRNA that targeted therapy and specific markers might be ideal for early detection of cervical cancer in low-income countries. These markers are either upregulated or down regulated in cancer providing clue to the stage of the cancer.

The EML4-ALK oncogene is a fusion of the EML4 and ALK genes and is found in approximately 5-6% of the cases of non-small cell lung cancer (NSCLC). Herein, we present a unique case of lung adenocarcinoma with metastases to the bilateral ovaries harboring a rare EML4-ALK fusion gene variant in a 52-year-old patient. The patient had initially received a diagnosis of ovarian cancer, then had undergone neo-adjuvant chemotherapy followed by a surgical resection. Despite two cycles of adjuvant chemotherapy consisting of carboplatin and gemcitabine, CT revealed that the pleural effusion had increased from it before chemotherapy, and the shortness of breath worsened. Molecular profiling revealed an EML4-ALK rearrangement containing ALK -EML4 and ALK -NPR2 fusion genes. The diagnosis was changed to primary lung adenocarcinoma with metastases to the bilateral ovaries based on a pathological reevaluation. Treatment with alectinib, a second-generation ALK-tyrosine kinase inhibitor, led to a partial response of 18 months' duration, and the shortness of breath improved. No adverse events related to the alectinib therapy occurred. To assess the unique structure of the fusion genes, RNA sequencing was performed. An intronic sequence from both ALK and EML4 was found between ALK and EML4 exon, possibly because of an unusual insertion of a gene fragment derived from NRP2, indicated by the panel sequencing results. Variations in the drug response among EML4-ALK fusion variants highlight the importance of understanding their molecular structure. Further investigation is warranted to refine fusion gene detection methods and assess the therapeutic implications of rare fusion variants.