Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Supramolecular Nanofibers Formed by Enzyme-Instructed Self-Assembly for SKBR-3 Cell Selective Inhibition.

Cell-targeted peptides are recommended for precision cancer treatment due to their comparable targeting properties, small molecular size, and good biocompatibility. However, unpredictable bioactivity, low penetration rate and poor stability greatly limit its efficacy. Supramolecular self-assembly based on synthetic peptide has great potential to solve related problems and achieve better therapeutic effects. Herein, we report and compare the effects of two different assembly pathway, heating-cooling, and enzyme instruction, on the penetrability of SKBR-3 cell targeted peptides. It was found that enzyme-instructed self-assembly (EISA) resulted in hydrogels composed of uniform supramolecular nanofibers, whereas heating-cooling resulted in solutions and precipitations composed of slightly different nanoparticles. The nanofibers formed by EISA showed enhanced cellular uptake (2.54 µM), which was significantly higher than the 1.06 µM of the nanoparticles formed by temperature regulation. Thus, EISA is a promising strategy to improve the cell penetration rate of targeted peptides and could provide a better solution for precision cancer treatment.

Parameter Estimation of Lunar Regolith from Lunar Penetrating Radar Data.

Parameter estimation of the lunar regolith not only provides important information about the composition but is also critical to quantifying potential resources for lunar exploration and engineering for human outposts. The Lunar Penetrating Radar (LPR) onboard China's Chang'E-3 (CE-3) provides a unique opportunity for mapping the near-surface stratigraphic structure and estimating the parameters of the regolith. In this paper, the electrical parameters and the iron-titanium content of regolith are estimated based on the two sets of LPR data. Firstly, it is theoretically verified that the relative dielectric constant can be estimated according to the difference of the reflected time of two receivers from a same target. Secondly, in order to verify the method, a parameter estimation flow is designed. Subsequently, a simple model and a complex model of regolith are carried out for the method verification. Finally, on the basis of the two sets of LPR data, the electrical parameters and the iron-titanium content of regolith are estimated. The relative dielectric constant of regolith at CE-3 landing site is 3.0537 and the content of TiO2 and FeO is 14.0127%. This helps us predict the reserves of resources at the CE-3 landing site and even in the entire Mare Imbrium.

FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation.

Sphingosine 1-phosphate (S1P) is an important signaling sphingolipid involved in the pathogenesis of various cardio cerebral vascular diseases such as ischemic stroke. In particular, the S1P mimetic FTY720 is protective for brain against ischemic conditions. However, whether and how FTY720 can modulate vascular tone and blood pressure remains to be determined. We showed that FTY720 (1 mg/kg) enhanced the contractile response of rat thoracic aortic rings induced by high potassium and phenylephrine, respectively. This enhancement involves the activation of extracellular signal-regulated kinase (ERK) since ERK phosphorylation was also enhanced and application of PD98059 (10 µmol/L), an inhibitor of ERK activation abrogated the aforementioned enhanced response by FTY720. In parallel, FTY720 (1 mg/kg) led to a modest elevation of blood pressure in rats, effects also being prevented by PD98059. In contrast, FTY720 decreased the high potassium-induced contractile response in basilarartery preparations from rabbits, an effect blocked by PD98059. Together, FTY720-induced an enhanced response of artery contractility in aorta and in arterial pressure involving ERK activation, with an attenuation in basilarartery contractility. This action property of FTY720 would be endowed with a potential of facilitating more blood flow perfusion to the brain and improving blood supply to the ischemic brain region and could be useful as an adjuvant in the treatment of ischemic stroke in the clinics.

Characterization of the Anticoagulant and Antithrombotic Properties of the Sphingosine 1-Phosphate Mimetic FTY720.

Sphingosine 1-phosphate (S1P) is a highly active lysophospholipid implicated in various cardiocerebrovascular events such as coagulation, myocardial infarction and stroke. However, as the functional S1P receptor antagonist, whether the S1P mimetic FTY720 can modulate coagulation and/or thrombotic formation remains largely unknown. We investigated the effects of FTY720 on adenosine diphosphate (ADP)-induced platelet aggregation, coagulation parameters and thrombus formation in rats. Pretreatment with FTY720 (2.5 mg/kg) inhibited platelet aggregation induced by ADP, elongated the thrombin time and decreased the fibrinogen levels. However, FTY720 produced no significant effects on the arteriovenous bypass thrombus formation or the FeCl3-induced thrombus formation in the inferior vena cava and the common carotid artery. Our data suggest that FTY720 can exert an inhibitory effect on platelet aggregation and coagulation-related parameters. These characteristics of FTY720 could be useful as an adjunct in the treatment of ischemic diseases such as ischemic stroke and myocardial infarction.

Hyaluronic acid-tagged silica nanoparticles in colon cancer therapy: therapeutic efficacy evaluation.

Colon cancer is one of the leading causes of cancer-related death worldwide, and the therapeutic application of 5-fluorouracil (5-FU) is limited due to its nonspecificity, low bioavailability, and overdose. The present study is an attempt to improve the chemotherapeutic efficacy of 5-FU in colon cancers. Therefore, we have prepared 5-FU-loaded hyaluronic acid (HA)-conjugated silica nanoparticles (SiNPs) to target to colon cancer cells. In this study, we have showed the specific binding and intracellular accumulation of targeted nanoparticles based on HA surface modifications in colon carcinoma cells. The particles had spherical shapes with sizes of approximately 130 nm. HA-conjugated nanoparticles showed a sustained release pattern for 5-FU and continuously released for 120 hours. We have further investigated the cytotoxicity potential of targeted and nontargeted nanoparticles in colo-205 cancer cells. IC50 value of 5-FU/hyaluronic acid-conjugated silica nanoparticles (HSNP) was 0.65 µg/mL compared with ~2.8 µg/mL for 5-FU/SNP after 24 hours of incubation. The result clearly showed that HA-conjugated NP was more effective in inducing apoptosis in cancer cells than nontargeted NP. The 5-FU/HSNP showed ~45% of cell apoptosis (early and late apoptosis stage) compared with only 20% for 5-FU/silica nanoparticles (SNP)-treated group. The HA-conjugated nanoparticles provide the possibility of efficient drug transport into tumors that could effectively reduce the side effects in the normal tissues. 5-FU/HSNP was highly efficient in suppressing the tumor growth in xenograft tumor model. The proportion of Ki67 in 5-FU/HSNP-treated group was significantly lower than that of either free drug or nontargeted SiNPs. Altogether, we have showed that conjugation of HA to SiNPs could result in enhanced uptake of 5-FU through CD44-mediated endocytosis uptake and could result in significant antitumor efficacy. Thus, 5-FU/HSNP could be a promising drug delivery system for colon cancer therapy.

A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy.

BACKGROUND: Oral squamous cell carcinoma (OSCC) or cancers of oral cavity is one of the most common cancers worldwide with high rate of mortality and morbidity. At present, chemotherapy is one of the most effective treatments; however it often fails to meet the requirements in the clinical therapy. In the present study, we have successfully formulated ligand-decorated cancer-targeted CDDP-loaded PLGA-PEG/NR7 nanoparticles and demonstrated the feasibility of using NR7 peptide for targeted delivery, rapid intracellular uptake, and enhanced cytotoxic effect in receptor-overexpressed OSCC cancer cells. RESULTS: Nanosized particles were formed and sustained release patterns were observed for PLGA/NR7 nanoparticles. Significantly higher cellular uptake was observed in HN6 OSCC cancer cells and superior anticancer effects are observed from the optimized targeted nanoparticles. Furthermore, Live/Dead assay showed a higher extent of red fluorescence was observed for the cells exposed with PLGA/NR7 than compared with non-targeted PLGA NP. The presence of the NR7-targeting moiety on the surface of PLGA carriers could allow the specific receptor-mediated internalization, enhanced cellular uptake, and higher cell killing potency. Especially, PLGA/NR7 NP exhibited a superior apoptosis effect in HN6 cancer cells with around ~45 % (early and late apoptotic stage) and ~59 % after 24 and 48 h incubation, respectively. It is apparent that the actively targeted micelles will deliver more anticancer agent to cancer cell than non-targeted one. CONCLUSION: Altogether, our results show the feasibility and promise of a cell-targeted anticancer nanomedicine strategy that can be effective for the treatment of oral squamous cell carcinoma. The present work might be of great importance to the further exploration of the potential application of PLGA/NR7 in the clinically relevant animal models.

Metastases of basal-like breast invasive ductal carcinoma to the endometrium: A case report and review of the literature.

We present a case of single endometrial metastasis from breast invasive ductal cancer. This case was unique because the immunohistochemical staining was negative for human epidermal growth factor receptor 2/neu and estrogen and progesterone receptors, and positive for cytokeratin 5/6 and epidermal growth factor receptor in the primary and metastatic tumor cells. No gross evidence of tumor was observed in other sites. We identified 12 cases of metastases to the endometrium from breast carcinoma from series and case reports in the literature between 1985 and 2014. This review indicated that hormone receptor-positive invasive lobular breast cancer cells are more likely to metastasize to the endometrium than other cell types in patients over 50 years of age.

Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation.

The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA-TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.

Metastasis of breast cancer to renal cancer: report of a rare case.

Tumor-to-tumor metastasis (TTM) is a rare phenomenon. We present a case of an invasive ductal carcinoma (IDC) of the breast metastasizing to a clear cell renal cell carcinoma (RCC). Breast cancer (BC) metastasis to the RCC is rarely reported, especially in resected kidney tumor. In several cases reported, IDC was the exclusively histologic type of BC metastasized to RCC. It seems that the different molecular type of IDC doesn't affect the metastatic tendencies to RCC. TTM was an indicator of diffuse disease. For any patient with a history of breast cancer, especially with multi-organs metastasis, resection of kidney tumor should be carefully considered.

Conventional craniospinal irradiation with patient supine and source-skin distance (SSD) 100 cm for spinal field.

We describe a method of craniospinal irradiation (CSI) in the supine position and at a source-skin distance (SSD) of 100 cm for the spinal fields. The procedure is carried out with a 100-cm isocenter linear accelerator and conventional simulator, and the treatment is delivered with 2 opposed lateral cranial fields at source-axis distance (SAD) of 100 cm and 1 or 2 direct posterior spinal fields at SSD, 100 cm. The half beam-blocked cranial fields with a collimator rotation is used to match the superior border of the spinal field at the level of C2 vertebral body. The length of the spinal field is fixed, and is the same if 2 spinal fields are used. The position of the isocenter of the spine field is defined by longitudinally moving the couch a distance from the isocenter of the cranial fields and adjusting the SSD = 100 cm to the surface of the couch with the gantry rotated to the angle of 180° (posteroanterior position), and the distance can be calculated easily according to a few parameters. It only needs a simple calculation without couch rotation, extended SSD, or markers. The inferior and superior borders of the spinal field do not require visualization under fluoroscopy when it is beyond the visual field of the simulator. The entire simulation takes no more than 20 minutes. Supine craniospinal treatment using this technique may substitute the traditional prone position as a potentially beneficial alternative to CSI.

Comparison of (18)F-fluorothymidine and (18)F-fluorodeoxyglucose PET/CT in delineating gross tumor volume by optimal threshold in patients with squamous cell carcinoma of thoracic esophagus.

PURPOSE: To determine the optimal method of using (18)F-fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) simulation to delineate the gross tumor volume (GTV) in esophageal squamous cell carcinoma verified by pathologic examination and compare the results with those using (18)F-fluorodeoxyglucose (FDG) PET/CT. METHODS AND MATERIALS: A total of 22 patients were enrolled and underwent both FLT and FDG PET/CT. The GTVs with biologic information were delineated using seven different methods in FLT PET/CT and three different methods in FDG PET/CT. The results were compared with the pathologic gross tumor length, and the optimal threshold was obtained. Next, we compared the simulation plans using the optimal threshold of FLT and FDG PET/CT. The radiation dose was prescribed as 60 Gy in 30 fractions with a precise radiotherapy technique. RESULTS: The mean +/- standard deviation pathologic gross tumor length was 4.94 +/- 2.21 cm. On FLT PET/CT, the length of the standardized uptake value 1.4 was 4.91 +/- 2.43 cm. On FDG PET/CT, the length of the standardized uptake value 2.5 was 5.10 +/- 2.18 cm, both of which seemed more approximate to the pathologic gross tumor length. The differences in the bilateral lung volume receiving > or =20 Gy, heart volume receiving > or =40 Gy, and the maximal dose received by spinal cord between FLT and FDG were not significant. However, the values for mean lung dose, bilateral lung volume receiving > or =5, > or =10, > or =30, > or =40, and > or =50 Gy, mean heart dose, and heart volume receiving > or =30 Gy using FLT PET/CT-based planning were significant lower than those using FDG PET/CT. CONCLUSION: A standardized uptake value cutoff of 1.4 on FLT PET/CT and one of 2.5 on FDG PET/CT provided the closest estimation of GTV length. Finally, FLT PET/CT-based treatment planning provided potential benefits to the lungs and heart.