ABSTRACT
Background: Colorectal leiomyosarcoma (LMS) is a rare colorectal malignancy accounting for approximately 1% of all colorectal malignancies with a poor prognosis and limited treatment options. Targeted therapies have been applied for breast cancer 2 (BRCA2) alterations, but their role remains to be explored in colorectal LMS. This case could provide clinical proof for the application of olaparib for LMS patients. Case Description: Here, we present a case of colorectal LMS with BRCA2 alterations who was treated with olaparib and achieved progression-free survival (PFS) for 1 year. In August 2016, a 46-year-old female patient was admitted to hospital due to a mass in the left lower abdomen and was diagnosed with LMS of the sigmoid colon. After surgical resection, chemotherapy with ifosfamide or ifosfamide combined with pirarubicin was given and achieved stable disease (SD) until the disease progressed 1.5 years later. Afterwards, a multi-target tyrosine kinase inhibitor, anlotinib, was taken. Before the observation of lung and liver metastasis, the patient's disease was stable for 1 year. BRCA2 mutation and rearrangement was revealed by next-generation sequencing (NGS), and the targeted therapy, olaparib, was given. Efficacy evaluation showed SD for 1 year, and no obvious toxic and side effects were observed. Conclusions: Our case suggested that NGS should be considered for further treatment of patients with colorectal LMS, and poly (ADP-ribose) polymerase (PARP) inhibitors could be a feasible therapy for LMS patients with BRCA2 alterations.
ABSTRACT
The crucial roles of the long noncoding RNAs (lncRNAs) in the development of ovarian cancer (OC) have been extensively studied. According to the prediction result from the Kaplan-Meier Plotter database, high expression of lncRNA proteasome subunit α type-3 antisense RNA1 (PSMA3-AS1) is associated with the poor prognosis in patients with OC. Thus, the study aimed to investigate the role of lncRNA PSMA3-AS1 in OC. Reverse transcription quantitative polymerase chain reaction analysis revealed that PSMA3-AS1 expression was significantly upregulated in OC cells and tissues. PSMA3-AS1 silencing inhibited OC cell proliferation, migration, and invasion, as shown by results of cell counting kit-8, colony formation, wound healing, and Transwell assays, respectively. Additionally, PSMA3-AS1 deficiency suppressed tumor growth in vivo. Mechanistically, luciferase reporter and RNA pulldown assays implied that PSMA3-AS1 served as a competing endogenous RNA for miR-378a-3p to upregulate the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). GALNT3 was a target gene of miR-378a-3p in OC. Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.
Subject(s)
MicroRNAs , Ovarian Neoplasms , RNA, Long Noncoding , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Ovarian Neoplasms/genetics , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proteasome Endopeptidase Complex/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Bacterial , RNA, Long Noncoding/geneticsABSTRACT
Nivolumab has been used in a variety of advanced malignant tumors. Cases of autoimmune diabetes associated with Nivolumab therapy have been reported gradually in recent years. This article reported a case of primary testicular lymphoma in an elderly patient with type 2 diabetes mellitus (T2DM). After treatment with Nivolumab, the primary disease was hyperprogressive disease but the blood glucose was relieved for a long time. Nivolumab may relieve the previous T2DM in diffuse large B-cell lymphoma patients; the potential mechanism needs to be further explored.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Nivolumab/therapeutic use , Testicular Neoplasms/surgery , Aged, 80 and over , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Glucose , Disease Progression , Humans , Male , Nivolumab/administration & dosage , Nivolumab/adverse effects , Nivolumab/pharmacology , Remission, Spontaneous , Testicular Neoplasms/therapyABSTRACT
PURPOSE: To investigate the efficacy and safety of apatinib mesylate (AM) in treating advanced non-small cell lung cancer (aNSCLC) with wild or unknown epidermal growth factor receptor (w/nEGFR). METHODS: A total of 34 w/nEGFR -aNSCLC patients who failed chemotherapy from August 2015 to April 2017 were administered orally AM (425 mg/d) as primary treatment and observed their progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR), as well as related adverse events. RESULTS: Efficacy was evaluable in 30 cases, with median PFS (mPFS) 3.75 months (95% CI 0.648-6.852), ORR 20%, and DCR 73.33%. The main adverse reactions included hypertension (52.94%), hand-foot syndrome (52.94%), proteinuria (44.12%), and fatigue (41.18%); no drug-related death occurred. The efficacy correlation analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (p=0.008) combined with chemotherapy (p=0.009) were the factors that extended PFS, and combined chemotherapy (p=0.040, HR=3.052, 95% CI 1.052- 8.858) was an independent prognostic factor. CONCLUSIONS: AM has good therapeutic efficacy in treating aNSCLC patients after chemotherapy failure. The side effects can be controlled and it is worth testing it in large-scale clinical studies.
