Two new sesquiterpene glycosides from Dendrobium findleyanum.

One new ylangene-type sesquiterpene glycoside, findlayanoside C (1), and one new picrotoxane-type sesquiterpene glycoside, findlayanoside D (3), together with five known sesquiterpene glycosides, dendrofindlayanoside C (2), dendronobiloside B (4), dendronobiloside A (5), dendroside F (6) and dendromoniliside D (7), have been isolated from the stems of Dendrobium findleyanum. The structures of compounds 1 and 3 were elucidated by means of extensive spectroscopic analyses, and their absolute configuration were confirmed by electronic circular dichroism (ECD) calculations. Cytotoxic activity assays against SMMC-7721, A-549 and MCF-7 human cancer cell lines revealed IC50 values of 10.12, 12.32 and 14.13 µM for compound 1, and of 9.25, 13.16 and 16.26 µM for compound 2. This study enriches the anti-tumour sesquiterpenoids composition of D. findleyanum.

Glucose-Regulated Protein 78 Targeting ICG and DOX Loaded Hollow Fe3O4 Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy.

Purpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC. Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety. Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells. Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy.

Molecular imaging-guided extracellular vesicle-based drug delivery for precise cancer management: Current status and future perspectives.

Extracellular vesicles (EVs), the mediators of intercellular communication, have attracted the attention of researchers for the important roles they play in cancer treatment. Compared with other inorganic nano-materials, EVs possess the advantages of higher biocompatibility, better physiochemical stability, easier surface modification, and excellent biosafety. They can be used as an advanced drug delivery system with an improved therapeutic index for various therapeutic agents. Engineered EV-based imaging and therapeutic agents (engineered EVs) have emerged as useful tools in targeted cancer diagnosis and therapy. Non-invasive tracing of engineered EVs contributes to a better evaluation of their functions in cancer progression, in vivo dynamic biodistribution, therapeutic response, and drug-loading efficiency. Recent advances in real-time molecular imaging (MI), and innovative EV labeling strategies have led to the development of novel tools that can evaluate the pharmacokinetics of engineered EVs in cancer management, which may accelerate further clinical translation of novel EV-based drug delivery platforms. Herein, we review the latest advances in EVs, their characteristics, and current examples of EV-based targeted drug delivery for cancer. Then, we discuss the prominent applications of MI for tracing both natural and engineered EVs. Finally, we discuss the current challenges and considerations of EVs in targeted cancer treatment and the limitations of different MI modalities. In the coming decades, EV-based therapeutic applications for cancer with improved drug loading and targeting abilities will be developed, and better anti-cancer effects of drug delivery nanoplatform will be achieved.

Using immunohistochemistry to classify the molecular subtypes of Paget's disease of the breast.

PURPOSE: To classify the molecular subtypes of Paget's disease of the breast, and then compare them with general breast cancer to get deeper understanding of this disease and offer better management of associate patients in clinical decisions. METHODS: We used immunohistochemistry to examine 42 cases of this disease by antibodies against estrogen and progesterone receptors, Ki-67, as well as human epidermal growth factor receptor 2 (HER-2). Due to damage and loss of specimens, etc., we obtained 36 pathological specimens from the 42 patients. For 30 of 36 pathological specimens (83.3%), we obtained a complete molecular subtype. Cause the other 6 pathological specimens have missing immunohistochemistry items. For patients with bilateral breast cancer, only information on the side with PDB is listed. For patients with recurrence, only information on the first onset was included. We finally compared and studied the molecular subtype of 26 samples. We calculated the relative frequencies of molecular subtypes including luminal A, luminal B, HER-2-enriched, and basal-like and compared them between PDB and general breast carcinomas in other studies. RESULTS: The luminal A and B subtype were found, respectively, in 3 (11.5%) and 6 (23.1%) of all patients, and 15 cases of HER-2-enriched subtype was detected (57.7%). In addition, 2 (7.7%) showed a basal-like subtype. CONCLUSION: The molecular subtypes of common breast cancer and PDB-associated breast cancer differ. Luminal subtypes are the most common in the former, while within our samples HER-2 positive subtype was the highest in PDB-associated breast carcinoma. With further understanding of this disease, rational therapies will be applied in different patients and cures for PDB and PDB-associated carcinoma will be achieved.

Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer.

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.

Non-invasive molecular imaging for precision diagnosis of metastatic lymph nodes: opportunities from preclinical to clinical applications.

Lymph node metastasis is an indicator of the invasiveness and aggressiveness of cancer. It is a vital prognostic factor in clinical staging of the disease and therapeutic decision-making. Patients with positive metastatic lymph nodes are likely to develop recurrent disease, distant metastasis, and succumb to death in the coming few years. Lymph node dissection and histological analysis are needed to detect whether regional lymph nodes have been infiltrated by cancer cells and determine the likely outcome of treatment and the patient's chances of survival. However, these procedures are invasive, and tissue biopsies are prone to sampling error. In recent years, advanced molecular imaging with novel imaging probes has provided new technologies that are contributing to comprehensive management of cancer, including non-invasive investigation of lymphatic drainage from tumors, identifying metastatic lymph nodes, and guiding surgeons to operate efficiently in patients with complex lesions. In this review, first, we outline the current status of different molecular imaging modalities applied for lymph node metastasis management. Second, we summarize the multi-functional imaging probes applied with the different imaging modalities as well as applications of cancer lymph node metastasis from preclinical studies to clinical translations. Third, we describe the limitations that must be considered in the field of molecular imaging for improved detection of lymph node metastasis. Finally, we propose future directions for molecular imaging technology that will allow more personalized treatment plans for patients with lymph node metastasis.

Two new cadinene-type sesquiterpene glycosides from Dendrobium findlayanum.

Two new and one known cadinene-type sesquiterpene glycosides, findlayanosides A-B (1-2) and dendronobiloside D (3), were isolated from the stems of Dendrobium findlayanum. This is the first report that cadinene-type sesquiterpene glycosides were isolated from D. findlayanum. The structures of compounds 1 and 2 were elucidated by extensive spectroscopic analyses, and their absolute configurations were confirmed by electronic circular dichroism (ECD) calculations. The obtained compounds were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549 and MCF-7 human cancer cells, and no obvious cytotoxic activity was observed at the concentration of 25 µΜ.

Invasive micropapillary breast carcinoma: A retrospective study on the clinical imaging features and pathologic findings.

Purpose: To describe the clinical imaging and pathological features of invasive micropapillary breast carcinoma (IMPC), including breast mammography, sonography, magnetic resonance imaging (MRI), and molecular imaging findings. Patients and methods: We retrospectively reviewed our institution's surgical pathology database and identified 65 patients with pathologically proven IMBC; 63/65 patients had available imaging results. Two radiologists retrospectively reviewed all imaging evaluations according to the Breast Imaging Reporting / Data System (BI-RADS) Lexicon. Clinical and histopathologic features, receptor statuses, and clinical follow-up data were recorded. Results: Sixty-three patients were admitted with palpable abnormalities; one patient's mammogram revealed no abnormality (3.3%, 1/32), whereas 31 had abnormal mammograms (31/32, 96.8%) demonstrating 37 lesions. Twenty-four had irregular, spiculated masses, 12 had microcalcifications, and 19 had architectural distortion. Sonography detected 69 masses (54 patients), characterized by irregular shapes (61/69, 88.4%), hypoechoic structures (50/69, 72.4%), angular or spiculated margins (38/69, 55.1%; 30/69, 43.4%), echogenic halo (8/69, 11.5%), and abnormal vascularity (52/69, 75.3%). MRI detected 68 lesions (52 patients); 59/68 (86.8%) appeared as masses with angular or spiculated margins (32/68, 47.1%; 35/68, 51.4%), 58 exhibited irregular or lobulated shapes (58/68, 89.7%), 29 displayed heterogeneous internal enhancement (29/68, 42.5%), and 64 demonstrated type II or III washout kinetic curves (37/68, 55%; 27/68, 40%). Breast molecular imaging showed mild-to-moderate radiotracer uptake in 15 focal areas among 13 patients. Thirty-two, 38, and 43 patients had abnormal lymph nodes identified mammographically, by breast sonography, and by MRI, respectively. Immunohistochemistry revealed high estrogen receptor (90.5%), high progesterone receptor (71.6%), and low HER-2 (26.4%) positivity. Conclusion: IMPC mammography, sonography, and MRI clinical imaging features highly suggest malignancy. Breast molecular imaging also contributed to the diagnosis. IMPC's invasiveness correlated well with regional lymph node metastasis. Radiologists and surgeons should be more attentive to these imaging findings and additional clinical and pathological IMPC features.

Application of Noninvasive Imaging to Combined Immune Checkpoint Inhibitors for Breast Cancer: Facts and Future.

With the application of mono-immunotherapy in cancer, particularly immune checkpoint inhibitors, improved outcomes have been achieved. However, there are several limitations to immunotherapy, such as a poor response to the drugs, immune resistance, and immune-related adverse events. In recent years, studies of preclinical animal models and clinical trials have demonstrated that immune checkpoint inhibitors for breast cancer can significantly prolong the overall survival and quality of patients' lives. Meanwhile, combined immune checkpoint inhibitor treatment has attracted researchers' attention and showed great potential in the comprehensive treatment of breast cancer patients. Additionally, noninvasive imaging enables physicians to predict response to combined immunotherapeutic drugs, achieve treatment efficacy, and lead to better clinical management. Herein, we review the background of combined immune checkpoint inhibitor therapy and summarize its targeted imaging as well as progress in noninvasive imaging aimed at evaluating therapeutic outcomes. Finally, we describe several factors that may influence the outcome of this combined immunotherapy, the future direction of medical imaging, and the potential application of artificial intelligence in breast cancer. With further development of noninvasive imaging for the guidance of combined immune checkpoint inhibitors, cures for this disease may be achieved.

Ten picrotoxane-type sesquiterpenoids from the stems of Dendrobium wardianum Warner.

Ten undescribed picrotoxane-type sesquiterpenoids, dendrowardins A-J, together with two known ones, were isolated from the stems of Dendrobium wardianum Warner (Orchidaceae). Dendrowardins A-D feature the unusual 5,2-δ-lactone and additionally dendrowardins C-D are the first examples containing the 11,10-γ-lactone moiety. The structures were established using spectroscopic methods and by comparison with literature data. Further, dendrowardin E, amotin, and aduncin exhibited significant effects of promoting the proliferation on human lens epithelial cells (HLECs) induced by D-galactose.

Two unusual dendrobine-type alkaloids from Dendrobium findlayanum.

Two unusual dendrobine-type alkaloids, findlayines E and F (1, 2), along with five known dendrobine-type alkaloids (3-7), were isolated from the stems of Dendrobium findlayanum Par. et Rchb. f. Compound 1 is the first example of dendrobine-type alkaloids with a 2-ethoxy-2-oxoethyl group attaching to the C-2, and compound 2 is a nor-dendrobine-type alkaloid, featuring a 5-decarboxylated structure. The structures of compounds 1 and 2 were elucidated by means of extensive spectroscopic analyses, and their absolute configuration were confirmed by electronic circular dichroism (ECD) calculations. All isolates were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549 and MCF-7 human cancer cells.

Four new sesquiterpene derivatives from Dendrobium findlayanum.

Three new sesquiterpene glycosides with alloaromadendrane and ylangene-derived type aglycones, named dendrofindlayanosides A-C (1-3), one new cyclopacamphane type sesquiterpene named dendrofindlayanobilin A (4), together with five known compounds have been isolated from stems of Dendrobium findlayanum. Their structures were determined on the basis of spectroscopic and chemical methods.

Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium findlayanum.

Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines, dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds, dendrofindlaphenols A-C (7, 9, and 10) and 6″-de-O-methyldendrofindlaphenol A (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3 bond of dendrobine. The structures were established using spectroscopic methods and by comparison with literature data. The absolute configurations of 1-4 were confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines revealed IC50 values ranging from 2.3 to 5.3 µM for compound 7, from 19.4 to 34.4 µM for 8, and from 49.4 to 96.8 µg/mL for the EtOAc extract. An assay of the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50 value of 21.4 µM, and the EtOAc extract, 10.5 µg/mL. The EtOAc extract possessed DPPH radical scavenging activity of 69.93% at 100 µg/mL.

Five new phenolic compounds from Dendrobium aphyllum.

One new phenanthrene, aphyllone A (1) and four new bibenzyl derivatives, aphyllone B (2) and aphyllals C-D (3-5), together with nine known compounds (6-14), were isolated from the stems of Dendrobium aphyllum (Roxb.) C. E. Fischer. The structures of these new compounds were elucidated by means of extensive spectroscopic analyses, and the absolute configuration of compound 1 was determined by single crystal X-ray diffraction and quantum calculations. Compounds 6, 8 and 14 inhibited NO production at the concentration of 25 µM in LPS-stimulated RAW264.7 cells with the inhibition (%) of 32.48, 35.68, and 38.50. Compound 2 possessed significant DPPH radical scavenging activity with scavenging percentage of 87.97% at the concentration of 100 µg/mL.

Three new sesquiterpenes with cytotoxic activity from Dobinea delavayi.

Three new sesquiterpenes dobinins A-C (1-3), together with five known compounds, were isolated from the root of Dobinea delavayi. The structures of the three new compounds were determined on the basis of spectroscopic analysis including 1D-, 2D-NMR and MS techniques as well as by comparison of the spectral data with those of analogous compounds reported in the literatures. Compounds 1-3 were screened for antitumor activity in vitro and exhibited definite cytotoxic activity against the human tumor cell line HL-60 with IC50 levels of 8.0 × 10-5, 4.7 × 10-5, and 5.1 × 10-5 M, respectively.