Target-Oriented Classification of Triple-negative Breast Cancer.

BACKGROUND/AIM: Breast cancer that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor-2 (HER2)-negative is termed triple-negative breast cancer (TNBC). Cytotoxic chemotherapy remains the first choice of treatment against TNBC due to lack of specific therapeutic targets. TNBC is not classified based on therapeutic targets, but recently, the development of targeted therapies - including immune checkpoint inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors - has gained attention. This study aimed to examine a novel target-oriented TNBC classification to further facilitate targeted therapy by classifying TNBC based on the breast cancer 1 (BRCA1)-like as well as the protein expression of HER2, programmed death ligand 1 (PD-L1), androgen receptor (AR), cytokeratin 5/6, and epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We enrolled 17 patients with primary TNBC who did not receive preoperative chemotherapy and underwent surgery at the Kobe University Hospital, Japan, between January 1, 2018, and July 31, 2019. Immunohistochemical staining was performed on tumor specimens, while a BRCAness test was performed using multiplex ligation-dependent probe amplification (MLPA) analysis. A BRCAness score 0.5 or higher was considered BRCA1-like. RESULTS: Tumors were classified as HER2-low (immunohistochemistry score 1+ or 2+ and FISH negative), PD-L1 positive, AR positive, or BRCA1-like. HER2-low, PD-L1 positive, AR positive, and BRCA1-like were detected in 11 (64.7%), 4 (23.5%), 6 (35.3%), and 6 (35.3%) samples. The tumor of only one patient could not be classified into any of these categories. CONCLUSION: Almost all TNBC cases can be classified according to treatable targets.

No association between inactivated influenza vaccination and influenza viral load at diagnosis among young Japanese children: An observational study of the 2013/2014 through 2017/2018 influenza seasons.

BACKGROUND: The association between inactivated influenza vaccination and viral load in young children remains unclear. METHODS: During the 2013/2014 to 2017/2018 influenza seasons in Japan, children under 6 years of age with pre-defined influenza-like illness and influenza-positive status by real-time RT-PCR were recruited at pediatric clinics for this observational study. Influenza viral load was measured for the most predominant subtype/lineage in each season. Using median dichotomized viral load as an outcome, a multilevel logistic regression model was applied to estimate the multivariable adjusted odds ratio (MOR) and 95% confidence interval (CI) for higher viral load. RESULTS: A total of 1,185 influenza-positive children were analyzed. The median log10 viral load copy number (copies per milliliter) was 5.5 (interquartile range, 4.6 to 6.1) and did not differ by vaccination status: 5.5 for unvaccinated, 5.7 for one dose, and 5.5 for two doses (p = 0.67). The MOR of vaccinated (one or two doses) versus unvaccinated children was 1.19 (95% CI: 0.86-1.64). Other factors showing significant associations with higher viral load were positive results for A(H1N1)pdm09 and A(H3N2) in comparison with B/Yamagata. The respective MORs were 3.25 (95% CI: 2.28-4.64) and 1.81 (95% CI: 1.32-2.49). Significantly elevated MORs against higher viral load were also observed for higher body temperature at influenza diagnosis and shorter duration from fever onset to specimen collection. CONCLUSION: No association was observed between inactivated-influenza vaccination and viral load at influenza-positive diagnosis. Influenza subtype/lineage, body temperature, and time elapsed since fever onset were significantly associated with viral load.

Novel double staining of the stratum corneum with fluorescent ε-poly-l-lysine and anionic dextran.

OBJECTIVE: ε-Poly-l-lysine (PLL) is a cationic polymer consisting of 25-35 l-lysine residues. Our previous study revealed that fluorescently labelled PLL can stain the stratum corneum (SC) via ionic interactions between PLL and SC constituents. In this study, to further clarify the mechanisms underlying the interaction between PLL and the SC, the staining properties of fluorescent PLL were compared with that of fluorescently labelled anionic dextran (aDex), which has approximately the same molecular weight as PLL. METHODS: SC samples were collected by non-invasive tape stripping and stained with fluorescent PLL and/or fluorescent aDex. Fluorescence images were acquired using a fluorescence microscope and then analysed. RESULTS: The SC could be stained with either fluorescent PLL or aDex, both of which were inhibited by the addition of high concentrations of salt solutions. In particular, aDex staining was inhibited at a lower salt concentration than PLL staining. Moreover, PLL staining was inhibited under acidic conditions, while aDex staining was inhibited under neutral to alkaline conditions. Double staining of SC with both fluorescent polymers produced heterogeneous staining patterns: corneocytes stained with both polymers, corneocytes stained with PLL or aDex in a mutually exclusive manner, and unstained corneocytes. Staining of SC samples from the face was more extensive than staining of SC samples from the inside of the upper arm with both polymers. In addition, pretreatment of the SC with ethanol resulted in enhanced staining with both polymers. These results suggest that double staining of SC with both polymers can provide information on the damaged SC. CONCLUSION: Staining of SC with fluorescent PLL depends on its properties of a cationic and hydrophobic polymer with appropriate molecular size, which can distinguish the damaged SC. Double staining of SC with fluorescent PLL and aDex is a novel approach to obtain information for the analysis of skin conditions.

OBJECTIF: La ε-poly-L-lysine (PLL) est un polymère cationique constitué de résidus de 25 à 35 L-lysines. Notre précédente étude a révélé que la PLL marquée par fluorescence peut colorer le stratum corneum (SC) par des interactions ioniques entre la PLL et les constituants du SC. Dans cette étude, afin de clarifier davantage les mécanismes sous-jacents à l'interaction entre la PLL et le SC, les propriétés de coloration de la PLL fluorescent ont été comparées à celles du dextran anionique (aDex) marqué par fluorescence, qui a à peu près le même poids moléculaire que la PLL. MÉTHODES: Les échantillons SC ont été prélevés par «tape stripping¼ non invasif et colorés avec de la PLL fluorescente et/ou de l'aDex fluorescent. Les images de fluorescence ont été acquises au microscope à fluorescence puis analysées. RÉSULTATS: Le SC pouvait être coloré avec de la PLL ou de l'aDex fluorescents, tous deux inhibés par l'ajout de fortes concentrations de solutions salines. En particulier, la coloration par aDex était inhibée à une concentration en sel inférieure à la coloration par PLL. En outre, la coloration de la PLL a été inhibée dans des conditions acides, tandis que la coloration de l'aDex a été inhibée dans des conditions neutres à alcalines. La double coloration de SC avec les deux polymères fluorescents a produit des modes de coloration hétérogènes: cornéocytes colorés avec les deux polymères, cornéocytes colorés avec de la PLL ou de l'aDex d'une manière mutuellement exclusive, et cornéocytes non colorés. La coloration des échantillons de SC sur le visage était plus étendue que la coloration des échantillons de SC sur la face intérieure du haut du bras avec les deux polymères. En outre, le prétraitement du SC avec de l'éthanol a entraîné une coloration améliorée avec les deux polymères. Ces résultats indiquent qu'une double coloration du CS avec les deux polymères peut fournir des informations sur le CS endommagé. CONCLUSION: La coloration du CS avec de la PLL fluorescente dépend de ses propriétés de polymère cationique et hydrophobe de taille moléculaire appropriée, ce qui permet de distinguer le CS endommagé. La double coloration de SC avec de la PLL et de l'aDex fluorescents est une nouvelle approche pour obtenir des informations pour l'analyse des affections cutanées.

Sequence analysis of a feline- and porcine-origin G3P[9] rotavirus A strain in a child with acute gastroenteritis in Japan.

We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.

Staining of stratum corneum with fluorescent ε-poly-L-lysine and its application to evaluation of skin conditions.

BACKGROUND: ε-Poly-L-lysine (PLL) is a cationic polymer consisting of 25 to 35 L-lysine residues that adheres to the surface of skin as well as hair. However, the properties of PLL regarding its adhesion to the skin remain to be elucidated. In this study, we examined the staining of stratum corneum (SC) with fluorescence-labeled PLL and explored its relationship with skin condition. MATERIALS AND METHODS: Alexa Fluor 488-labeled PLL (AF-PLL) was reacted with tape-stripped stratum corneum (SC), and the staining properties were monitored by fluorescence microscopy. Clinical study was performed by measuring the water content of the cheek SC and transepidermal water loss (TEWL), and the tape-stripped SC was subjected to staining with AF-PLL. RESULTS: AF-PLL staining of the SC was inhibited at acidic pH or by the addition of high concentration of salt solution, suggesting the involvement of ionic interaction between PLL and the SC, at least in part. The AF-PLL staining was inhibited by unlabeled PLL or various alkyl amines, but not by L-lysine monomer. AF-PLL staining was observed inside the corneocytes as well as surrounding cornified envelope. Clinical study revealed that AF-PLL staining intensity of the SC was negatively correlated with its water content and positively correlated with its TEWL. CONCLUSION: PLL can efficiently adhere to SC and AF-PLL staining of SC can be applied to evaluate skin conditions.

A Rare Case of Bilateral Pectoralis Major Muscle Defect and Abnormal Muscle.

A 56-year-old female patient with left breast cancer presented at our hospital. Preoperative CT scan showed an isolated bilateral pectoralis major muscle defect and abnormal muscle originating from the entire sternum and inserting in the lower ribs and rectus sheath. Total mastectomy and axillary lymph node dissection were performed. We believe that this case is unique and that others like it have never been reported. If there is a defect in the pectoralis major muscle, reconstructive surgery with a tissue expander is contraindicated. Therefore, preoperative evaluation of the chest wall musculature on imaging is recommended.

Simplified daptomycin dosing regimen for adult patients with methicillin-resistant Staphylococcus aureus infections based on population pharmacokinetic analysis.

Daptomycin is used to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend higher daptomycin doses (8-10 mg/kg) for severe infections; however, pharmacokinetic (PK) and pharmacodynamic-based dosing strategies are still limited. Therefore, we designed a new optimal daptomycin dosing regimen for patients with MRSA infections using a population PK modeling approach. A total of 110 plasma concentrations from 47 adult patients who received daptomycin in general wards were enrolled for population PK modeling. The target area under the concentration-time curve/minimum inhibitory concentration (MIC) ratio, target peak/MIC ratio, and threshold of the trough concentration for safety were set to >666, >60, and 24.3 mg/L, respectively. Renal function was indicated as a significant covariate for daptomycin clearance. The simulated probability of target attainment was more than 90% at MIC values of 0.25 and 0.5 mg/L in all patients at the standard dose (6 mg/kg). In contrast, comprehensive simulation assessments recommended 10 mg/kg every 24 h in patients with creatinine clearance >60 mL/min for MIC values of 1.0 mg/L. We propose a new simplified daptomycin dosing regimen stratified by renal function and MIC values based on PK model-based simulation analyses. The proposed regimen is expected to maximize clinical efficacy and minimize adverse events.

Influence of Prior Influenza Vaccination on Current Influenza Vaccine Effectiveness in Children Aged 1 to 5 Years.

BACKGROUND: Although annual influenza vaccination is an important strategy used to prevent influenza-related morbidity and mortality, some studies have reported the negative influence of prior vaccination on vaccine effectiveness (VE) for current seasons. Currently, the influence of prior vaccination is not conclusive, especially in children. METHODS: We evaluated the association between current-season VE and prior season vaccination using a test-negative design in children aged 1-5 years presenting at nine outpatient clinics in Japan during the 2016/17 and 2017/18 influenza seasons. Children with influenza-like illness were enrolled prospectively and tested for influenza using real-time RT-PCR. Their recent vaccination history was categorized into six groups according to current vaccination doses (0/1/2) and prior vaccination status (unvaccinated = 0 doses/vaccinated = 1 dose or 2 doses): (1) 0 doses in the current season and unvaccinated in prior seasons (reference group); (2) 0 doses in the current season and vaccinated in a prior season; (3) 1 dose in the current season and unvaccinated in a prior season; (4) 1 dose in the current season and vaccinated in a prior season; (5) 2 doses in the current season and unvaccinated in a prior season, and (6) 2 doses in the current season and vaccinated in a prior season. RESULTS: A total of 799 cases and 1196 controls were analyzed. The median age of the subjects was 3 years, and the proportion of males was 54%. Overall, the vaccination rates (any vaccination in the current season) in the cases and controls were 36% and 53%, respectively. The VEs of the groups were: (2) 29% (95% confidence interval: -25% to 59%); (3) 53% (6% to 76%); (4) 70% (45% to 83%); (5) 56% (32% to 72%), and (6) 61% (42% to 73%). The one- and two-dose VEs of the current season were significant regardless of prior vaccination status. The results did not differ when stratified by influenza subtype/lineage. CONCLUSION: Prior vaccination did not attenuate the current-season VE in children aged 1 to 5 years, supporting the annual vaccination strategy.

Data on long-term survival of the NOD/Shi-scid IL-2Rγnull (NOG) mouse in two facilities.

The objective of this study was to investigate an appropriate observation period for an evaluation of tumorigenicity in NOD/Shi-scid IL-2 Rγnull (NOG) mice. At SNBL, 19 male and 19 female NOG mice were observed the general condition from 7 weeks old up to 68 weeks old and at FBRI, 7 male and 16 female NOG mice were observed the general condition throughout the lifespan from 7 weeks old. The survival rate started to decline rapidly around 54 to 56 weeks of age in both facilities without a facility difference. Based on these survival data, it seems reasonable to terminate a tumorigenicity study at 52 weeks of age.

Covering Soybean Leaves With Cellulose Nanofiber Changes Leaf Surface Hydrophobicity and Confers Resistance Against Phakopsora pachyrhizi.

Asian soybean rust (ASR) caused by Phakopsora pachyrhizi, an obligate biotrophic fungal pathogen, is the most devastating soybean production disease worldwide. Currently, timely fungicide application is the only means to control ASR in the field. We investigated cellulose nanofiber (CNF) application on ASR disease management. CNF-treated leaves showed reduced lesion number after P. pachyrhizi inoculation compared to control leaves, indicating that covering soybean leaves with CNF confers P. pachyrhizi resistance. We also demonstrated that formation of P. pachyrhizi appressoria, and also gene expression related to these formations, such as chitin synthases (CHSs), were significantly suppressed in CNF-treated soybean leaves compared to control leaves. Moreover, contact angle measurement revealed that CNF converts soybean leaf surface properties from hydrophobic to hydrophilic. These results suggest that CNF can change soybean leaf surface hydrophobicity, conferring resistance against P. pachyrhizi, based on the reduced expression of CHSs, as well as reduced formation of pre-infection structures. This is the first study to investigate CNF application to control field disease.

Long-Term Oncologic Safety of Nipple-Sparing Mastectomy With Immediate Reconstruction.

BACKGROUND: We assessed the long-term oncologic safety of nipple-sparing mastectomy (NSM) compared to skin-sparing mastectomy (SSM) for primary breast cancer patients with immediate reconstruction. PATIENTS AND METHODS: Data of stage 0-III primary breast cancer patients undergoing NSM (n = 190) or SSM (n = 729) from June 2006 to December 2012 were retrospectively collected. Nipple-tumor distance (NTD) was measured on pretreatment mammography, magnetic resonance imaging, or ultrasonography findings. NSM patients with NTD < 1 cm were excluded. Locoregional recurrence (LRR) rates were compared between groups. Disease-free survival (DFS) and overall survival (OS) according to surgical procedure were assessed. RESULTS: The median (range) follow-up period for NSM and SSM was 71 (10-131) months and 79 (9-140) months, respectively. LRR developed in 11 patients with invasive ductal carcinoma (5.8%) for NSM and 44 (42 in patients with invasive ductal carcinoma and 2 in patients with ductal carcinoma-in-situ) (6.0%) for SSM. Hormone receptor and HER2 status were not associated with LRR in either group. DFS and OS rates did not differ between groups (DFS: 89.3% for NSM, 89.3% for SSM, P = .87; OS: 98.4% for NSM, 94.5% for SSM, P = .43). CONCLUSION: NSM with immediate reconstruction was as safe as SSM for primary breast cancer with respect to prognosis and local control, regardless of the presence of invasive carcinoma or breast cancer subtype.

Evaluation of Axillary Lymph Nodes in Breast Cancer Patients with Atopic Dermatitis.

This study assessed the diagnostic accuracy of ultrasound in detecting axillary lymph node metastases in women with breast cancer and atopic dermatitis. We retrospectively reviewed the records of 91 breast cancer patients with a history of atopic dermatitis and compared the dimensions of the lymph nodes on ultrasonographic images of women with and without lymph node metastases diagnosed using histology. Using a major-axis length of ≥5 mm, a short-axis length of ≥5 mm and a cortical thickness of ≥2.3 mm as the criteria for diagnosing axillary lymph node metastases, the specificity was 12.7%, 41.3% and 58.7%, respectively. The low specificity of the ultrasound criteria makes ultrasound unsuitable for diagnosing axillary lymph nodes metastases in breast cancer patients with atopic dermatitis.

Effect of Vesicle Size on the Cytolysis of Cell-Penetrating Peptides (CPPs).

A specific series of peptides, called a cell-penetrating peptide (CPP), is known to be free to directly permeate through cell membranes into the cytosol (cytolysis); hence, this CPP would be a potent carrier for a drug delivery system (DDS). Previously, we proposed the mechanism of cytolysis as a temporal and local phase transfer of membrane lipid caused by positive membrane curvature generation. Moreover, we showed how to control the CPP cytolysis. Here, we investigate the phospholipid vesicle's size effect on CPP cytolysis because this is the most straightforward way to control membrane curvature. Contrary to our expectation, we found that the smaller the vesicle diameter (meaning a higher membrane curvature), the more cytolysis was suppressed. Such controversial findings led us to seek the reason for the unexpected results, and we ended up finding out that the mobility of membrane lipids as a liquid crystal is the key to cytolysis. As a result, we could explain the cause of cytolysis suppression by reducing the vesicle size (because of the restriction of lipid mobility); osmotic pressure reduction to enhance positive curvature generation works as long as the membrane is mobile enough to modulate the local structure. Taking all the revealed vital factors and their effects as a tool, we will further explore how to control CPP cytolysis for developing a DDS system combined with appropriate cargo selection to be tagged with CPPs.

Self-Assembled Fullerene Crystals as Excellent Aromatic Vapor Sensors.

Here we report the aromatic vapor sensing performance of bitter melon shaped nanoporous fullerene C60 crystals that are self-assembled at a liquid-liquid interface between isopropyl alcohol and C60 solution in dodecylbenzene at 25 °C. Average length and center diameter of the crystals were ca. 10 µm and ~2 µm, respectively. Powder X-ray diffraction pattern (pXRD) confirmed a face-centered cubic (fcc) structure with cell dimension ca. a = 1.4272 nm, and V = 2.907 nm³, which is similar to that of the pristine fullerene C60. Transmission electron microscopy (TEM) confirmed the presence of a nanoporous structure. Quartz crystal microbalance (QCM) results showed that the bitter melon shaped nanoporous C60 performs as an excellent sensing system, particularly for aromatic vapors, due to their easy diffusion through the porous architecture and strong π⁻π interactions with the sp²-carbon.

Prior vaccinations improve immunogenicity of inactivated influenza vaccine in young children aged 6 months to 3 years: A cohort study.

In young children, infrequent antigen exposure, which is partly characterized by fewer vaccinations, may be a factor impairing the immunogenicity of inactivated influenza vaccine.We assessed the effects of prior vaccinations on age-specific immune responses in Japanese children aged 6 months to 3 years, using data from a cohort study with 266 children who had received 2 doses (0.25 mL/dose for < 3 years old, 0.5 mL/dose for 3 years old) in the 2006/2007 season. Serological measures, primarily seroprotection rates, between previously vaccinated and vaccine-naïve children were compared within 1-year age strata. The seroprotection rate was defined in 2 ways as the proportion of subjects who achieved an antibody titer of 1:40 or 1:160. Multivariate logistic regression was also performed to estimate the independent effect of prior vaccination on seroprotection rate.After the first dose, seroprotection rates with the threshold of 1:40 in vaccine-naïve 1-year-olds remained low (28% for AH1, 26% for AH3, 2% for B), similar to those of 0-year-olds. In contrast, seroprotection rates in previously vaccinated 1-year-olds (77% for AH1, 86% for AH3, 18% for B) were significantly higher than those in vaccine-naïve 1-year-olds. These seroprotection rates for AH1 and AH3 were comparable with those in previously vaccinated 2- and 3-year-olds. Although seroprotection rates for B remained low in every age stratum even after the second dose, seroprotection rate in previously vaccinated 1-year-olds (50%) was similar to that in 3-year-olds. After adjustment for age, baseline antibody titer and experience of acute febrile respiratory illness in the preceding season, odds ratios showed a significant independent positive effect of prior vaccination on seroprotection rate for every strain. After the seroprotection threshold was changed from 1:40 to 1:160, the results of the effects of prior vaccinations on immunogenicity were similar or became more evident, which demonstrate the robustness of our findings.Our study found that prior vaccinations improved poor immunogenicity among young children, especially in 1-year-olds.

Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer.

BACKGROUND: Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. METHODS: We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. RESULTS: We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. CONCLUSIONS: Marked differences in fatty acid metabolism pathways, including those related to ELOVL1 and 6, were detected between TN and EP+H-, and it was suggested that ELOVL1 and 6-related fatty acid metabolism pathways may be targets for therapies against TN.

Effectiveness of Pertuzumab, Trastuzumab, and Docetaxel Combination Neoadjuvant Chemotherapy for HER2-Positive Inflammatory Breast Cancer: A Case Report.

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive form of primary breast cancer. CASE REPORT: A 40-year-old woman was referred to our hospital for evaluation of an induration in the right breast, suspected to be breast cancer. The tumor was diagnosed as estrogen receptor-negative, progesterone receptor-negative, HER2-positive, T4dN3cM0 stage IIIc IBC with axillary lymph node metastasis. Rather than surgical intervention, we chose a systemic treatment approach with pertuzumab, trastuzumab, and docetaxel (PTD) combination therapy which was shown to be effective for HER2-positive IBC in the NeoSphere trial. After 4 cycles of treatment, the patient had a partial response, allowing mastectomy of the right breast and axillary lymph node dissection to achieve local control. We review this case because of the success of PTD combination neoadjuvant chemotherapy for HER2-positive IBC. CONCLUSION: To improve the poor prognosis of IBC, combined modality therapy is required, including chemotherapy and local treatment such as surgery and/or radiation therapy. In this case, combination neoadjuvant chemotherapy with PTD for HER2-positive IBC was effective, and this regimen may contribute to further improvements in the cure rate for this malignancy.

Immunogenicity study to investigate the interchangeability among three different types of polio vaccine: A cohort study in Japan.

In Japan, the routine immunization program with oral polio vaccine (OPV) has been suspended since September 2012, when a program with 4 doses of inactivated monovalent polio vaccine (IPV) or quadrivalent vaccine against diphtheria, pertussis, and tetanus with IPV (DTaP-IPV) was introduced. The aim of this study was to examine the interchangeability among these 3 types of polio vaccines.We conducted a prospective cohort study at 5 pediatric clinics in Japan. A total of 153 infants were assigned to 1 of the 4 groups by considering the vaccination history of OPV and trivalent vaccine against DTaP. Eleven infants with a history of OPV received 3 doses of DTaP-IPV; 49 infants with a history of OPV and DTaP received 3 doses of IPV; 50 polio vaccine-naïve infants received 2 doses of IPV followed by 2 doses of DTaP-IPV; and 43 polio vaccine-naive infants received 2 doses of DTaP-IPV followed by IPV. The immunogenicity after polio vaccination was evaluated among these 4 groups.After 2 doses of polio vaccination, more than 80% of the infants exhibited a neutralization antibody titer ≥1:8 for all Sabin strains and wild strains in all groups. After the third dose, the seroprotection proportion (i.e., a neutralization antibody titer ≥1:8) reached about 100%. After the fourth dose, a neutralization antibody titer exceeded the required protective levels (i.e., a neutralization antibody titer ≥1:8) considerably in all groups.Four doses of polio vaccines induced a sufficient level of immunity in Japanese infants, irrespective of vaccine combinations or order.

[Evaluation of a new immunochromatographic kit for enhanced detection of influenza B virus].

We have evaluated a new immunochromatographic kit, "KBM LineCheck Flu AB", which had been developed for enhanced detection of influenza B viruses. Five strains of influenza A and B viruses were tested for reactivity and detection limits of the kit. Compared with the detection limits of commercially available kit of QuickNavi-Flu, "KBM LineCheck Flu AB" showed a nearly equal reactivity to influenza A viruses, but quadruple reactivity to 2 influenza B viruses. Also, "KBM LineCheck Flu AB" exhibited high specificity when tested in 130 influenza-negative culture specimens derived from 24 adult volunteers. Furthermore, "KBM LineCheck Flu AB" was clinically evaluated by using 866 specimens, including 190 nasal swabs, 201 nasal aspirations, 262 self-blown nasal discharges, and 213 pharyngeal swabs. Compared with the results of QuickNavi-Flu for influenza A, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 92.0%, 95.0%, and 94.8%, respectively. Whereas, as to influenza B, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 96.3%, 98.5%, 96.2%, and 93.4%, respectively. Similarly, compared with the results of influenza A viral culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 95.3%, 91.0%, 93.9%, and 92.5%, respectively. Regarding influenza B culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 97.5%, 95.1%, 91.5%, respectively. Overall, we concluded that the "KBM LineCheck Flu AB" is useful and suitable for diagnosis of influenza A and especially influenza B.

Novel pegylated interferon-ß as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer.

Malignant ascites manifests as an end-stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon-ß (IFN-ß) has been used to treat several cancer indications; however, little is known about the efficacy of IFN-ß on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN-ß, each conjugated with a polyethylene glycol molecule (PEG-hIFN-ß and PEG-mIFN-ß, respectively). We provide evidence that these IFN-ß molecules retain anti-viral potency comparable to unmodified IFN-ß in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG-mIFN-ß significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG-hIFN-ß directly suppresses VEGF165 -induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG-mIFN-ß enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN-ß in maintaining vascular integrity, and provide proof-of-mechanism for a novel and long-acting pegylated hIFN-ß for the therapeutic treatment of malignant ascites.