Anesthetic management of thyroid carcinoma invading the upper tracheal segment: A case report.

INTRODUCTION AND IMPORTANCE: Intratracheal tumors account for approximately 0.2 % of respiratory tumors, including primary and secondary tumors. Secondary tumors of the upper trachea are most commonly derived from advanced thyroid cancer. Surgical resection is currently the general curative modality for thyroid cancer with tracheal invasion. Patients with tracheal tumors invading and protruding into the lumen may have reduced oxygen reserve capacity, leading to a shorter safe window for general anesthesia induction. Establishing an appropriate artificial airway is essential to ensure intraoperative safety for these patients. Here, we report a case of tracheal tumor caused by differentiated papillary thyroid carcinoma invading the upper segment of the trachea and the non-conventional approach used for intraoperative airway management without traditional endotracheal intubation. PRESENTATION OF CASE: A 59-year-old female presented with bilateral neck masses and hemoptysis. The CT scan revealed suspicious malignant thyroid nodules, and tracheoscopy showed an approximately 50 % obstruction of the tracheal lumen. The patient's physical examination and biochemical examination showed no significant abnormalities. Based on imaging studies and pre-anesthetic assessment, a multidisciplinary team decided against performing endotracheal intubation in the patient due to the risk of tumor bleeding during the procedure. Instead, they opted for a modified endotracheal tube and the insertion of a laryngeal mask airway (LMA). The anesthesia induction and maintenance proceeded smoothly, with stable intraoperative hemodynamics. The tumor was successfully resected and tracheal anastomosis was performed without any complications. CLINICAL DISCUSSION: The strategy adroitly evades the risk of bleeding and dislodgement due to tumor contact during the intubation process. In this case report, the anesthetic highlight is the employment of a reverse insertion technique for endotracheal intubation, facilitated by a sterile suction catheter and complemented by an innovative modification to the tracheal tube. CONCLUSION: For patients with thyroid cancer invading the upper segment of the trachea, and in whom rapid induction anesthesia is anticipated not to cause tumor collapse, the use of laryngeal mask airway combined with modified tracheal tube mechanical ventilation is both safe and feasible.

Radiotherapy-triggered prodrug activation: A new era in precise chemotherapy.

A major goal of cancer therapy is developing chemotherapy strategies that are accurate and efficient without being highly toxic. Recently, Bradley et al.1 and Liu et al.2 developed radioresponsive prodrugs, enabling site-directed, radiotherapy-triggered, and precise chemotherapy, which displays synergistic efficacy and avoids the serious side effects of conventional treatment approaches.

Safe and efficient 2D molybdenum disulfide platform for cooperative imaging-guided photothermal-selective chemotherapy: A preclinical study.

Introduction: The striking imbalance between the ever-increasing amount of nanomedicines and low clinical translation of products has become the focus of intense debate. For clinical translation, the critical issue is to select the appropriate agents and combination regimen for targeted diseases, not to prepare increasingly complex nanoplatforms. Objectives: A safe and efficient platform, α-tocopheryl succinate (α-TOS) married 2D molybdenum disulfide, was devised by a facile method and applied for cooperative imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Methods: A novel platform of PEGylated α-TOS and folic acid (FA) conjugated 2D MoS2 nanoflakes was fabricated  for the cooperative multimode computed tomography (CT)/photoacoustic (PA)/thermal imaging-guided photothermal-selective chemotherapy of ovarian carcinoma. Results: The photothermal efficiency (65.3%) of the platform under safe near-infrared irradiation is much higher than that of other photothermal materials reported elsewhere. Moreover, the covalently linked α-TOS renders platform with selective chemotherapy for cancer cells. Remarkably, with these excellent properties, the platform can be used to completely eliminate the solid tumor by safe photothermal therapy, and then kill the residual cancer cells by selective chemotherapy to prevent tumor recurrence. More significantly, barely side effects occur in the whole treatment process. The excellent efficacy and safety benefits in vivo lead to the prominent survival rate of 100% over 91 days. Conclusion: The safe and efficient platform might be a candidate of clinical nanomedicines for multimode theranostics. This study demonstrates an innovative thought in precise nanomedicine regarding the design of next generation of cancer theranostic protocol for potential clinical practice.

Intelligent Molybdenum Disulfide Complexes as a Platform for Cooperative Imaging-Guided Tri-Mode Chemo-Photothermo-Immunotherapy.

Design of new nanoplatforms that integrates multiple imaging and therapeutic components for precision cancer nanomedicine remains to be challenging. Here, a facile strategy is reported to prepare polydopamine (PDA)-coated molybdenum disulfide (MoS2 ) nanoflakes as a nanocarrier to load dual drug cisplatin (Pt) and 1-methyl-tryptophan (1-MT) for precision tumor theranostics. Preformed MoS2 nanoflakes are coated with PDA, modified with methoxy-polyethylene glycol (PEG)-amine, and loaded with 1-MT and Pt. The formed functional 1-MT-Pt-PPDA@MoS2 (the second P stands for PEG) complexes exhibit good colloidal stability and photothermal conversion efficiency (47.9%), dual pH-, and photothermal-sensitive drug release profile, and multimodal thermal, computed tomography and photoacoustic imaging capability. Due to the respective components of Pt, MoS2 , and 1-MT that can block the immune checkpoint associated to tumoral indoleamine 2,3-dioxygenase-induced tryptophan metabolism, tri-mode chemo-photothermo-immunotherapy of tumors can be realized. In particular, under the near infrared laser irradiation, fast release of both drugs can be facilitated to achieve cooperative tumor therapy effect, and the combined immunogenic cell death induced by the dual-mode chemo-photothermo treatment and the 1-MT-induced immune checkpoint blockade can boost enhanced antitumor immune response to generate significant cytotoxic T cells for tumor killing. The developed 1-MT-Pt-PPDA@MoS2 complexes may be used as an intelligent nanoplatform for cooperative precision imaging-guided combinational tumor therapy.

Intelligent nanogels with self-adaptive responsiveness for improved tumor drug delivery and augmented chemotherapy.

For cancer nanomedicine, the main goal is to deliver therapeutic agents effectively to solid tumors. Here, we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels (CH-PPy NGs) for enhanced tumor delivery and augmented chemotherapy. CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method. The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs (R-NGs) with a negative charge at a physiological pH and a positive charge at a slightly acidic pH. The R-NGs display good cytocompatibility, excellent protein resistance, and high doxorubicin (DOX) loading efficiency. Encouragingly, the prepared R-NGs/DOX have prolonged blood circulation time, enhanced tumor accumulation, penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged, and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo. Notably, the tumor accumulation of R-NGs/DOX (around 4.7%) is much higher than the average tumor accumulation of other nanocarriers (less than 1%) reported elsewhere. The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma.

Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy. Here, the PAMAM dendrimer decorated PVCL-GMA nanogels (NGs) were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma. By an ingenious design, the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization. After G2 dendrimer decoration, the overall charge is changed from neutral to positive, and the NGs-G2 display the whole charge nature of positively charged corona and neutral core. Importantly, the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo. As a consequence of this alteration, the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation, enhanced tumor uptake, and promoted drug release, resulting in the significantly augmented antitumor efficacy with low side effects. Remarkably, this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake. Moreover, the NGs-G2 also displayed thermal/pH dual-responsive behaviors, excellent biocompatibility, improved cellular uptake, and stimuli-responsive drug release. Encouragingly, this work demonstrates a novel insight into the strategy for optimizing design, improving biodistribution and enhancing theranostic efficacy of nanocarriers.

Role of microenvironmental periostin in pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic reaction. Pancreatic stellate cells (PSCs) are the principal effector cells responsible for stroma production. Aberrant up-regulation of periostin expression has been reported in activated PSCs. In this study, we investigated the role of periostin and the mechanisms underlying its aberrant upregulation in PDAC. We used lentiviral shRNA and human recombinant periostin protein to down and up regulate periostin expression in vitro. Specific oncogenic signaling pathways such as EGFR-Akt and EGFR-Erk-c-Myc were assessed in vitro and in vivo. Tissue microarray immunohistochemical assays including 80 pancreatic cancer tissues and paired normal tissues were used to understand the function relationship between periostin expression and PDAC pathologic stage and overall survival. We found that periostin was strongly expressed in PSCs and the stroma of PDAC tumors. We also observed a significant decrease in proliferation, metastasis, and clonality of pancreatic cancer cells when co-cultured with supernatant of periostin shRNA-transfected PSCs. Specifically, the biological behavior of periostin correlated with EGFR-Akt and EGER-Erk-c-Myc signaling pathways. Moreover, increased periostin expression significantly associated with advanced disease stage and decreased survival rate in PDAC patients. Together, our findings provide novel insights into the role of microenvironmental periostin in pancreatic cancer progression, and periostin may serve as a prognostic biomarker for PDAC.

An RGD-modified hollow silica@Au core/shell nanoplatform for tumor combination therapy.

The combination of chemotherapy and photothermal therapy (PTT) in multifunctional nanoplatforms to improve cancer therapeutic efficacy is of great significance while it still remains to be a challenging task. Herein, we report Au nanostar (NS)-coated hollow mesoporous silica nanocapsules (HMSs) with surface modified by arginine-glycine-aspartic acid (RGD) peptide as a drug delivery system to encapsulate doxorubicin (DOX) for targeted chemotherapy and PTT of tumors. Au NSs-coated HMSs core/shell nanocapsules (HMSs@Au NSs) synthesized previously were conjugated with RGD peptide via a spacer of polyethylene glycol (PEG). We show that the prepared HMSs@Au-PEG-RGD NSs are non-cytotxic in the given concentration range, and have a DOX encapsulation efficiency of 98.6±0.7%. The designed HMSs@Au-PEG-RGD NSs/DOX system can release DOX in a pH/NIR laser dual-responsive manner. Importantly, the formed HMSs@Au-PEG-RGD NSs/DOX nanoplatform can specifically target cancer cells overexpressing αvß3 intergrin and exert combination chemotherapy and PTT efficacy to the cells in vitro and a xenografted tumor model in vivo. Our results suggest that the designed HMSs@Au-PEG-RGD NSs/DOX nanoplatform may be used for combination chemotherapy and PTT of tumors. STATEMENT OF SIGNIFICANCE: We demonstrate a convenient approach to preparing a novel RGD-targeted drug delivery system of HMSs@Au-PEG-RGD NSs/DOX that possesses pH/NIR laser dual-responsive drug delivery performance for combinational chemotherapy and PTT of tumors. The developed Au NS-coated HMS capsules have both merits of HMS capsules that can be used for high payload drug loading and Au NSs that have NIR laser-induced photothermal conversion efficiency (70.8%) and can be used for PTT of tumors.

Dendrimer-Modified MoS2 Nanoflakes as a Platform for Combinational Gene Silencing and Photothermal Therapy of Tumors.

Exploitation of novel hybrid nanomaterials for combinational tumor therapy is challenging. In this work, we synthesized dendrimer-modified MoS2 nanoflakes for combinational gene silencing and photothermal therapy (PTT) of cancer cells. Hydrothermally synthesized MoS2 nanoflakes were modified with generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with lipoic acid via disulfide bond. The formed G5-MoS2 nanoflakes display good colloidal stability and superior photothermal conversion efficiency and photothermal stability. With the dendrimer surface amines on their surface, the G5-MoS2 nanoflakes are capable of delivering Bcl-2 (B-cell lymphoma-2) siRNA to cancer cells (4T1 cells, a mouse breast cancer cells) with excellent transfection efficiency, inducing 47.3% of Bcl-2 protein expression inhibition. In vitro cell viability assay data show that cells treated with the G5-MoS2/Bcl-2 siRNA polyplexes under laser irradiation have a viability of 21.0%, which is much lower than other groups of single mode PTT treatment (45.8%) or single mode of gene therapy (68.7%). Moreover, the super efficacy of combinational therapy was further demonstrated by treating a xenografted 4T1 tumor model in vivo. These results suggest that the synthesized G5-MoS2 nanoflakes may be employed as a potential nanoplatform for combinational gene silencing and PTT of tumors.

Formation of Gold Nanostar-Coated Hollow Mesoporous Silica for Tumor Multimodality Imaging and Photothermal Therapy.

Development of multifunctional nanoplatforms for tumor multimode imaging and therapy is of great necessity. Herein, we report a new type of Au nanostar (NS)-coated, perfluorohexane (PFH)-encapsulated hollow mesoporous silica nanocapsule (HMS) modified with poly(ethylene glycol) (PEG) for tumor multimode ultrasonic (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, and photothermal therapy (PTT). HMSs were first synthesized, silanized to have thiol surface groups, and coated with gold nanoparticles via a Au-S bond. Followed by growth of Au NSs on the surface of the HMSs, encapsulation of PFH in the interior of the HMSs, and surface conjugation of thiolated PEG, multifunctional HMSs@Au-PFH-mPEG NSs (for short, HAPP) were formed and well-characterized. We show that the HAPP are stable in a colloidal manner and noncytotoxic in the studied range of concentrations, possess multimode US/CT/PA/thermal imaging ability, and can be applied for multimode US/CT/PA/thermal imaging of tumors in vivo after intravenous or intratumoral injection. Additionally, the near-infrared absorption property of the HAPP enables the use of the HAPP for photothermal ablation of cancer cells in vitro and a tumor model in vivo after intratumoral injection. The developed multifunctional HAPP may be used as a novel multifunctional theranostic nanoplatform for tumor multimode imaging and PTT.

Antifouling Manganese Oxide Nanoparticles: Synthesis, Characterization, and Applications for Enhanced MR Imaging of Tumors.

Antifouling manganese oxide (Mn3O4) nanoparticles (NPs) were synthesized by solvothermal decomposition of tris(2,4-pentanedionato) manganese(III) in the presence of trisodium citrate, followed by surface modification with polyethylene glycol and l-cysteine. The as-prepared nanoparticles have a uniform size distribution, good colloidal stability and good cytocompatibility. The modification of l-cysteine rendered the particles with much longer blood circulation time (half-decay time of 28.4 h) than those without l-cysteine modification (18.5 h), and decreased macrophage cellular uptake. Thanks to desirable antifouling property and relatively high r1 relaxivity (3.66 mM-1 s-1), the l-cysteine-modified Mn3O4 NPs can be used for enhanced tumor magnetic resonance imaging applications.

Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas. However, whether periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we focused on the role of periostin in PDAC by observing the effects of silencing this gene on gemcitabine resistance in vitro and in vivo aiming to explore the possible molecular mechanism. In this study, the pancreatic cancer cell (PCC) proliferation and apoptosis were assayed to investigate the sensitivity to gemcitabine after silencing periostin. We provide the evidence that periostin not only drives the carcinogenic process itself but also significantly associated with gemcitabine-induced apoptosis. These findings collectively indicated that periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin might offer a new opportunity to overcome the gemcitabine resistance of PDAC.

Ultrasound-Mediated Microbubble Destruction (UMMD) Facilitates the Delivery of CA19-9 Targeted and Paclitaxel Loaded mPEG-PLGA-PLL Nanoparticles in Pancreatic Cancer.

Pancreatic cancer, one of the most lethal human malignancies with dismal prognosis, is refractory to existing radio-chemotherapeutic treatment modalities. There is a critical unmet need to develop effective approaches, especially for targeted pancreatic cancer drug delivery. Targeted and drug-loaded nanoparticles (NPs) combined with ultrasound-mediated microbubble destruction (UMMD) have been shown to significantly increase the cellular uptake in vitro and drug retention in vivo, suggesting a promising strategy for cancer therapy. In this study, we synthesized pancreatic cancer-targeting organic NPs that were modified with anti CA19-9 antibody and encapsulated paclitaxol (PTX). The three-block copolymer methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) constituted the skeleton of the NPs. We speculated that the PTX-NPs-anti CA19-9 would circulate long-term in vivo, "actively target" pancreatic cancer cells, and sustainably release the loaded PTX while UMMD would "passively target" the irradiated tumor and effectively increase the permeability of cell membrane and capillary gaps. Our results demonstrated that the combination of PTX-NPs-anti CA19-9 with UMMD achieved a low IC50, significant cell cycle arrest, and cell apoptosis in vitro. In mouse pancreatic tumor xenografts, the combined application of PTX-NP-anti CA19-9 NPs with UMMD attained the highest tumor inhibition rate, promoted the pharmacokinetic profile by increasing AUC, t1/2, and mean residence time (MRT), and decreased clearance. Consequently, the survival of the tumor-bearing nude mice was prolonged without obvious toxicity. The dynamic change in cellular uptake, targeted real-time imaging, and the concentration of PTX in the plasma and tumor were all closely associated with the treatment efficacy both in vitro and in vivo. Our study suggests that PTX-NP-anti CA19-9 NPs combined with UMMD is a promising strategy for the treatment of pancreatic cancer.

Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling.

Pancreatic cancer (PaC) consists of a bulk of stroma cells which contribute to tumor progression by releasing angiogenic factors. Recent studies have found that periostin (POSTN) is closely associate with the metastatic potential and prognosis of PaC. The purpose of this study is to determine the role of POSTN in tumor angiogenesis and explore the precise mechanisms. In this study, we used lentiviral shRNA and human recombinant POSTN protein (rPOSTN) to negatively and positively regulate POSTN expression in vitro. We found that increased POSTN expression promoted the tubule formation dependent on human umbilical vein endothelial cells (HUVECs). Moreover, knockdown of POSTN in PaC cells reduced tumor growth and VEGF expression in vivo. In accordance with these observations, we found that Erk phosphorylation and its downstream VEGF expression were upregulated achieved in rPOSTN-treated groups, opposing results were obversed in POSTN-slienced group. Meanwhile, Erk inhibitor SCH772984 significantly decreased VEGF expression as well as tubule formation of HUVECs in rPOSTN-treated PaC cells. Taken together, these findings suggest that POSTN promotes tumor angiogenesis via Erk/VEGF signaling in PaC and POSTN may be a new target for cancer anti-vascular treatment.

Imaging findings of bile duct hamartomas: a case report and literature review.

Bile duct hamartomas (BHs), also called von Meyenburg complex (VMC), are benign biliary malformations that originate from disorganization of the small intrahepatic bile ducts. This disorganization is often associated with the abnormal involution of embryonic ductal end plates in the liver. This is clinically significant, as the development of BHs can cause diagnostic confusion with liver metastases and small hepatocellular carcinoma (SHCC). Currently, we report a specific case of BHs and review the literature to better define and diagnose BHs. In the following case, a 37 year-old male bearing a lesion in his liver is presented and undergoes both radiological and pathological diagnosis. The lesion is preliminarily suspected to be a hepatic hemangioma by examination of conventional ultrasound (US), contrast enhanced ultrasound (CEUS), computerized tomographic scanning (CT) and magnetic resonance imaging (MRI). However, SHCC is suspected by follow-up analysis of US and CEUS, due to the patient's background history of hepatitis B and growth of the lesion and a tumor-feeding vessel in BHs via CEUS. However, BHs are finally diagnosed by biopsy pathology under the guidance of ultrasound. Therefore, we believe pathology is imperative for correct diagnosis of BHs over other similar diseases when the imaging findings are atypical. Here we report the novel and unique detection of a tumor-feeding vessel, which mimicked SHCC strongly, during the course of CEUS. We also present a comprehensive review of the previous reported radiological examination related to BHs.