Nanoformulation involving biocompatible MOFs and magnetic nanocarriers is an emerging multifunctional platform for drug delivery and tumor imaging in targeted cancer therapeutics. In this study, a nanocomposite has been developed comprising Fe/SBA-16 and ZIF-8 (Fe/S-16/ZIF-8) through ultrasonication. The drug delivery of cisplatin was studied using an automated diffusion cell system equipped with a flow type Franz cell. The anticancer activity of Fe/S-16/ZIF-8 was studied in vitro in MCF-7, HeLa cells and Human Foreskin Fibroblast (HFF-1) cells. XRD and d-spacing measurements of Fe/S-16/ZIF-8 using TEM revealed the presence of cubic-structured Fe₃O₄, γ-Fe₂O₄ (magnetite), and α-FeOOH (goethite) over an SBA-16/ZIF-8 nanocomposite. The composite showed a surface area of 365 m² g⁻¹, a pore size of 8.3 nm and a pore volume of 0.33 cm³ g⁻¹. VSM analysis of Fe/S-16/ZIF-8 showed that it possessed paramagnetic behavior with a saturated magnetization value of 2.39 emu g⁻¹. The Fe²⁺/Fe³⁺ coordination environment was characterized using diffuse reflectance spectroscopy. The cisplatin drug delivery study clearly showed the synergistic effects present in Fe/S-16/ZIF-8 with over 75% of cisplatin release as compared to that of Fe/S-16 and ZIF-8, which showed 56% and 7.5%, respectively. The morphology analysis of CP/Fe/SBA-16/ZIF-8 using TEM showed an effective transit of nanoparticles into MCF-7 cells. The lethal concentration (LC₅₀) of Fe/SBA-16/ZIF-8 for MCF-7 and HeLa cells is 0.119 mg mL⁻¹ and 0.028 mg mL⁻¹ at 24 h, respectively. For HFF-1 cells, the LC₅₀ is 0.016 mg mL⁻¹. The antibiofilm activity of Fe/SBA-16/ZIF-8 was investigated against biofilm-forming strains of drug resistant P. aeruginosa and MRSA by a microtiter tissue culture plate assay. Overall, nanosized ZIF-8 with a bioactive alkaloid imidazole inside the 3D cage type of SBA-16 pores is found to exhibit both anticancer and antibacterial properties. A Fe/S-16/ZIF-8 composite could be effectively used as a drug and drug delivery system against cancer and promote antibacterial activity.

Langerhans cell histiocytosis (LCH) is a rare clonal disease, characterized by hyperproliferation of Langerhans cells. It may rarely involve the thyroid gland. Its association with papillary thyroid carcinoma (PTC) is extremely rare; with only few case reports available in the English literature. BRAF mutations are implicated in the development of papillary thyroid carcinoma, and have also been identified in Langerhans cell histiocytosis. Here we present a rare case of a 36-year-old Indonesian female patient with dysphagia associated with neck mass which was complicated by skin sinus formation. The diagnosis of PTC was rendered on fine needle aspiration (FNA). Debulking thyroidectomy revealed co-existeence of PTC and LCH. On subsequent molecular testing, BRAF V600E and V600K mutations were detected in tissues macrodissected from both lesions, respectively. To the best of our knowledge, this case is the first case to report two different BRAF mutations in tissues of a Langerhans cell histiocytosis and a papillary thyroid carcinoma co-existing in the thyroid gland. The patient received chemotherapy of etoposide combined with prednisone. At the most recent follow-up, the patient is in a stable clinical condition. The coexistence of a PTC with LCH harboring BRAF mutation may suggest etiologic relation between the two conditions that involves the BRAF gene. Clinically, it may suggest an aggressive, locally advanced thyroid cancer, an impression that may reflect on the selected surgical management, chemotherapy and BRAF mutation-targeting therapy to these patients.

Background: Viral cause of sporadic breast cancer (SBC) has been suggested based on the experimental murine model of mammary tumor caused by mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV), and human papillomavirus (HPV). While some studies have demonstrated the presence of viral sequences of MMTV, HPV, and EBV in breast cancer cells, others failed. These contradictions may be attributed to the geographical distribution of breast cancer incidence and/or technical variations. In the current study, we aimed to investigate the correlation of MMTV, HPV, and EBV infections with the development of breast cancer in Jordanian patients. Methods: One hundred SBC tissue samples were subjected to laser capture microdissection for the selection of tumor cells populations. Fluorescence polymerase chain reaction (PCR) was used to detect the presence of the MMTV env-like sequences. Real-time PCR was used for HPV and EBV detection, and EBV was further confirmed by chromogen in situ hybridization (CISH). Results: Mouse mammary tumor virus, HPV, and EBV were detected in SBC in 11%, 21%, and 23%, respectively. Only 3 of 52 (5.7%) positive cases demonstrated multiple virus infections. However, 49 of 52 (94%) of the positive cases revealed the presence of 1 type of viral sequences. Consequently, 52% of the studied breast cancer cases were infected with at least 1 type of the aforementioned viruses. Conclusions: The current cohort suggests that MMTV, HPV, and EBV have a potential role in the development of breast cancer and adding more reasons to proceed with the quest of a possible viral origin of breast cancer.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm generated by reciprocal chromosomal translocation, t (9; 22) (q34; q11) in the transformed hematopoietic stem cell. Tyrosine kinase inhibitors (TKIs) target the mature proliferating BCR-ABL cells, the major CML driver, and increase overall and disease-free survival. However, mutant clones, pre-existing or due to therapy, develop resistance against TKIs. BCR-ABL1 oncoprotein activates various molecular pathways including the RAS/RAF/MEK/ERK pathway, JAK2/STAT pathway, and PI3K/AKT/mTOR pathway. Stimulation of these pathways in TKI resistant CML patients, make them a new target. Moreover, a small proportion of CML cells, leukemic stem cells (LSCs), persist during the TKI therapy and sustain the disease in the patient. Engraftment of LSCs in the bone marrow niche and dysregulation of miRNA participate greatly in the TKI resistance. Current efforts are needed for determining the reason behind TKI resistance, identification, and elimination of CML LSC might be of great need for cancer cure.

Hematopoietic stem cells (HSCs) are multipotent, self-renewing cells that can differentiate into myeloid or lymphoid cells. The mobilization and differentiation processes are affected by the external environment, such as extracellular matrix and soluble molecules in the niche, where the lipid rafts (LRs) of the HSCs act as the receptors and control platforms for these effectors. LRs are membrane microdomains that are enriched in cholesterol, sphingolipid, and proteins. They are involved in diverse cellular processes including morphogenesis, cytokinesis, signaling, endocytic events, and response to the environment. They are also involved in different types of diseases, such as cancer, Alzheimer’s, and prion disease. LR clustering and disruption contribute directly to the differentiation, homing, hibernation, or mobilization of HSCs. Thus, characterization of LR integrity may provide a promising approach to controlling the fate of stem cells for clinical applications. In this review, we show the critical role of LR modification (clustering, disruption, protein incorporation, and signal responding) in deciding the fate of HSCs, under the effect of soluble cytokines such as stem cell factor (SCF), transforming growth factor- β (TGF-β), hematopoietic-specific phospholipase Cβ2 (PLC-β2), and granulocyte colony-stimulating factor (G-CSF).

Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.