Background: Hepatocellular carcinoma (HCC) is one of the most life-threatening malignant diseases. TCTN2 protein participates in tumorigenesis and development. However, whether lncRNA TCTN2 is associated with HCC pathogenesis remains unclear.
Methods: The expression of lncRNA, TCTN2, miR-1285-3p, and ARF6 in HCC tissues and cells was detected by a quantitative Real-Time PCR (qRT-PCR) assay. lncRNA TCTN2-specific shRNA was transfected into HCC cells, and a functional investigation was performed. The direct interactions between lncRNA TCTN2 and miR-1285-3p and ARF6 were verified by dualluciferase reporter gene assay. A rescue experiment was performed to confirm the role of miR- 1285-3p/ARF6 in association with lncRNA TCTN2.
Results: LncRNA TCTN2 exhibited a high expression in HCC tumor tissues and cell lines. Knockdown of lncRNA TCTN2 suppressed cell proliferation and induced cell cycle arrest and apoptosis through regulating Cyclin D1/p21 and Bax/Bcl-2 signals. Meanwhile, the knockdown of lncRNA TCTN2 inhibited HCC cell migration and invasion through upregulating MMP2/MMP9. Mechanistic investigation revealed that lncRNA TCTN2 upregulated the expression of ARF6 via sponging miR-1285-3p. Rescue experiments indicated that miR-1285-3p inhibitor reversed the antitumor effects of lncRNA TCTN2 and ARF6 knockdown inhibited the progression of HCC.
Conclusion: Our results suggested that the knockdown of lncRNA TCTN2 inhibited HCC development by regulating the miR-1285-3p/ARF6 axis, implying that the lncRNA TCTN2 is upregulated in HCC and may serve as a diagnostic biomarker in HCC. Furthermore, it may demonstrate an important value for the clinical treatment of patients with HCC.
Background: Scientists, academicians, and researchers from academics and the pharmaceutical industries have all expressed interest in the design and production of pharmaceutical cocrystals in recent years. The development of novel drug products with enhanced physicochemical and pharmacological characteristics is aided by the cocrystallization of drug substances.
Objective: The major problem with drug candidates is their solubility and bioavailability, which may be solved with the appropriate molecular modifications. The failure of most drug candidates in earlier clinical trials is also reawakening interest. In that connection, pharmaceutical cocrystals are vital in the development of dosage forms in the field of pharmaceutical technology. The goal of this manuscript is to provide a comprehensive overview of cocrystal synthesis methods and characterization techniques.
Conclusion: In this review, it is evident that the solvent-free technique has several benefits over solvent-based approaches in the design and production of pharmaceutical cocrystals, and that these methodologies can also open opportunities for further advancement in the field of cocrystal synthesis. This manuscript provides a brief overview of each technique for manufacturing pharmaceutical cocrystals and an analysis of cocrystals. This manuscript has highlighted points on whether cocrystals comply with the requirements for intellectual property rights and how they will impact the current pharmaceutical industry. The impact of recent patents on pharmaceutical cocrystals is examined in depth with relevant examples.
Background: The RNA-binding protein Zinc Finger Protein 36 like 1(ZFP36L1) plays an important role in regulating the AU-rich elements (AREs) in the 3' untranslated region (3' UTR) of mRNAs, indicating a potential link between its expression and cancers. However, the role and mechanism of ZFP36L1 in gastric cancer (GC) are unclear.
Objectives: This study aimed to explore the role and mechanism of ZFP36L1 in gastric cancer.
Materials and methods: GC tissue samples and matched normal gastric tissues were collected, and the ZFP36L1 expression in these samples was evaluated by immunohistochemistry analysis. GC cells with different differentiation were selected for in vitro experiments. The ZFP36L1 expression in GC cells was examined by quantitative real-time polymerase chain reaction (qRTPCR) and Western blot analysis. The viability and invasiveness of GC cells were assayed by 5- Ethynyl-2-deoxyuridine (EdU) and Transwell assays, respectively. Western blot assay was used to detect the expression of epithelial-to-mesenchymal transition (EMT) related proteins and proteins of the c-Jun N-terminal kinase (JNK) and p38 Mitogen-Activated Protein Kinase (MAPK) signaling pathways.
Results: ZFP36L1 is overexpressed in GC tissues. Patients with high ZFP36L1 expression have a poor prognosis. Moreover, ZFP36L1 is overexpressed in the cell lines with a high degree of malignancy. ZFP36L1 increases cell proliferation, invasion, and migration in vitro. Furthermore, ZFP36L1 induces EMT. The JNK inhibitor and p38 inhibitor alone or in combination affect the biological function of GC cells. Furthermore, ZFP36L1 promotes GC progression by inhibiting JNK and p38 MAPK signaling pathways.
Conclusion: RNA-binding protein ZFP36L1 exerts a role in the occurrence of gastric cancer by the regulation of the JNK and p38 MAPK signaling pathways. The combination of inhibitors of the JNK and p38 MAPK signaling pathways could be a novel treatment strategy for gastric cancer.
Background: Chemotherapeutic drugs are principally intended to treat breast cancer. However, sooner or later, tumor drug resistance developed. These chemo drugs are effective but with numerous side effects. Breast cancer care may be extremely difficult since recurring cancer is frequently pre-treated with powerful agents. Cancer cells acquire high resistance to earlier therapies, necessitating alternative and more powerful drugs. Nanoparticles (NPs) as a medication delivery technology can overcome medication resistance in breast cancer and significantly reduce the effective dose. The off-targeted nature of chemo drugs can be resolved by encapsulating or attaching chemo drugs in nanocarriers, specifically targeting breast cancer cells.
Objectives: This review highlights various chemo drugs for breast cancer and their encapsulation or bioconjugation with nanoparticles for its targeted delivery.
Conclusion: Nanoparticles may subsist valuable abet in breast cancer management in this regard. Given that traditional chemotherapy approaches have been demonstrated to have several side effects and defects during treatment, the NPs-mediated drug delivery mechanism is a possible contender for replacement as a new technique.
Even today, cancer is one of the prominent leading causes of death worldwide. However, there are a couple of treatment options available for management, but the adverse effects are more prominent as compared to therapeutic effects. Therefore, there is a need to design some midway that may help to bypass the negative effects or lower their severity. Nanotechnology has addressed many issues, still many miles are needed to cover before reaching the center stage. The developed nanoformulations can target distant organs owing to their multifunctionality and targeting potential. Stimuli-responsive nanomedicine is one of the most exploited formulations. They can encapsulate and release the drugs for a higher period. However, they release a burst mechanism. The other nanoformulations contain dendrimers, micelles, and lipid-based nano-formulations that have been developed and evaluated for their efficacy in cancer treatment. This review paper highlights some significant patents granted/applied in various patent offices around the globe to treat cancer using the nanotechnology. The Google Patent, United States Patent and Trademark Office (USPTO), Escapenet, and many others were used as the search engine for patent search, and data were collected and analyzed. They used these patented technologies for diagnostic and treatment options, enhancing the absorption, distribution, metabolism, and excretion (ADME) profile of therapeutic molecules.
Background: Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics.
Objective: The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia.
Methods: A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms "acute myeloid leukemia" and "venetoclax" and the new patents published in this field.
Results: BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed.
Conclusion: The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.
Background: Thymic epithelial tumors (TETs) are rare thoracic malignancies with no standard second-line treatment. Tumor angiogenesis is closely associated with the pathogenesis and invasiveness of TETs. Anlotinib is a small-molecule multitarget tyrosine kinase inhibitor (TKI) which inhibits tumor angiogenesis and tumor cell proliferation. Published studies have demonstrated the promising clinical effect of multitarget TKIs sunitinib and lenvatinib in previously treated TETs. However, TKIs have a high incidence of adverse events (AEs).
Objective: In this study, we investigated the clinical efficacy and safety of anlotinib in previously treated TET patients.
Methods: We collected clinical data of 22 patients from Shandong Cancer Hospital and Institute between October 2018 and March 2022. These patients were diagnosed with advanced TETs and received at least the first-line (1st-line) treatment. We analyzed the clinical effects between anlotinib monotherapy and anlotinib combination therapy in the second-line (2nd-line) or anlotinib treatment in different lines.
Results: These 22 patients included 18 cases of thymic carcinoma (TC) and 4 cases of thymoma (T). 68.2% of patients were males, and the median age was 53 years. Fourteen patients (63.6%) received anlotinib monotherapy and 8 patients (36.4%) received anlotinib combination therapy. The objective response rate (ORR) was 9.1% in the overall patients. The median progression-free survival (PFS) in the overall population was 12 months (14 months for T and 9 months for TC), and the median overall survival (OS) was 24 months (survival was not reached for T and was 24 months for TC). The incidence of AEs was 50%, most of them were grades I and II, and the incidence of grades III and IV AEs was 9%.
Conclusion: This is the first study reporting the clinical effect of anlotinib in previously treated TETs patients. The survival data indicate that the efficacy of anlotinib is superior to sunitinib and lenvatinib. Our results suggest that anlotinib is a promising treatment option for previously treated TET patients and its toxicity is tolerable. More research and patents are needed in the future to explore better options for the diagnosis and treatment of TETs.