Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to ...investigate effective therapies to reverse or suppress TMJOA progression.
To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model.
SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1β, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration.
Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.
We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.
Records of more ...than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.
pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.
We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.
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The fibulins are a family of secreted glycoproteins associated with basement membranes, elastic fibers, and other matrices. They are expressed in a variety of tissues. Association with these matrix ...structures is mediated by their ability to interact with many extracellular matrix constituents. The seven members of the family are defined by the presence of two structural modules, a tandem repeat of epidermal growth factor-like modules and a unique C-terminal fibulin-type module. They act not only as intermolecular bridges within the extracellular matrix to form supramolecular structures, but also as mediators for cellular processes and tissue remodeling. These important functions of fibulins in a wide range of biological processes have been shown in
in vitro
systems, gene knockout mice, and human genetic disorders. In this review, we describe the structure and function of these proteins and discuss the implication of fibulins in development and diseases.
Photo-absorption by black carbon (BC) aerosol is believed to be enhanced by the internal mixing of BC with volatile compounds. We investigate this effect quantitatively with laboratory experiments. ...Graphite particles are used as a surrogate for BC, with coatings of oleic acid and glycerol. The photo-absorption of coated graphite with known shell and core diameters are directly measured by a photo-acoustic technique. The size distribution and coating thickness are quantified using a single-particle soot photometer (SP2). The absorption is amplified by ∼30% even with a small coating thickness (shell/core diameter ratio (D
p
/D
c
) = 1.2). The amplification reaches as high as 2 at D
p
/D
c
= 2. We calculate the amplification of the absorption using a shell/core model of Mie theory. The model generally reproduces the measured amplification well.
Serratia marcescens is a nosocomial pathogen with carbapenem resistance, which limits the availability of effective treatment options. In this study, molecular characterization of GES-5 ...carbapenemase-producing S. marcescens isolated from an outbreak in Japan was undertaken. Comparative genetic analysis revealed that the blaGES-5-encoding plasmid p2020-O-9 is a unique plasmid contributing to carbapenem resistance. Furthermore, this study highlights the need for surveillance programmes to monitor both novel and commonly occurring carbapenemases in clinical settings.
Numerous studies have revealed a continuous increase in the worldwide incidence and prevalence of non-tuberculous mycobacteria (NTM) diseases, especially pulmonary
complex (MAC) diseases. Although it ...is not clear why NTM diseases have been increasing, one possibility is an increase of mycobacterial infection sources in the environment. Thus, in this review, we focused on the infection sources of pathogenic NTM, especially MAC. The environmental niches for MAC include water, soil, and dust. The formation of aerosols containing NTM arising from shower water, soil, and pool water implies that these niches can be infection sources. Furthermore, genotyping has shown that clinical isolates are identical to environmental ones from household tap water, bathrooms, potting soil, and garden soil. Therefore, to prevent and treat MAC diseases, it is essential to identify the infection sources for these organisms, because patients with these diseases often suffer from reinfections and recurrent infections with them. In the environmental sources, MAC and other NTM organisms can form biofilms, survive within amoebae, and exist in a free-living state. Mycobacterial communities are also likely to occur in these infection sources in households. Water distribution systems are a transmission route from natural water reservoirs to household tap water. Other infection sources include areas with frequent human contact, such as soil and bathrooms, indicating that individuals may carry NTM organisms that concomitantly attach to their household belongings. To explore the mechanisms associated with the global spread of infection and MAC transmission routes, an epidemiological population-wide genotyping survey would be very useful. A good example of the power of genotyping comes from
subsp.
, where close genetic relatedness was found between isolates of it from European patients and pigs in Japan and Europe, implying global transmission of this bacterium. It is anticipated that whole genome sequencing technologies will improve NTM surveys so that the mechanisms for the global spread of MAC disease will become clearer in the near future. Better understanding of the niches exploited by MAC and its ecology is essential for preventing MAC infections and developing new methods for its effective treatment and elimination.
In-line filters in peripheral and central venous catheters are used to remove bacterial cells mechanically. A recent study indicated an extension of the use of infusion sets to 7 days. There is no ...evidence regarding replacement intervals for in-line filters.
To test in-line filters that were used continuously for 7 days in order to investigate their ability to remove bacteria and assess the flow rate.
Three different in-line filters were attached to an ELNEOPA-NF No. 2 premixed infusion bag of intravenous hyperalimentation, into which Staphylococcus epidermidis ATCC12228 or Escherichia coli ATCC25922 was inoculated. These experiments were compared with a control infusion. The infusion was dropped at a flow rate of 40 mL/h and replaced at 24-h intervals for 7 days. Samples were collected 24 h after drop initiation.
S. epidermidis was not detected in droplets between Days 1 and 6, but In-line filters 1 and 2 showed droplets containing 6–10 colony-forming units/mL on Day 7. E. coli was not detected in any of the filters after 7 days of continuous use. Flow rates <40 mL/h were observed on Day 7 for In-line filter 3 in studies of S. epidermidis, and on Days 4 and 3 for In-line filters 2 and 3, respectively, in studies of E. coli.
This study revealed differences in bacterial removal and flow rates under high inoculation between the three in-line filters tested. It is suggested that in-line filters can be used continuously for a maximum of 6 days, and reductions in flow rate after 48 h of continuous use should be noted carefully.
Although 1% has been used as cut-off for estrogen receptor (ER) positivity, several studies have reported that tumors with ER < 1% have characteristics similar to those with 1% ≤ ER < 10%. We ...hypothesized that in patients with human epidermal growth factor 2 (HER2)-negative breast cancer, a cut-off of 10% is more useful than one of 1% in discriminating for both a better pathological complete response (pCR) rate to neoadjuvant chemotherapy and a better long-term outcome with adjuvant hormonal therapy. Our objectives were to identify a percentage of ER expression below which pCR was likely and to determine whether this cut-off value can identify patients who would benefit from adjuvant hormonal therapy.
Patients with stage II or III HER2-negative primary breast cancer who received neoadjuvant chemotherapy followed by definitive surgery between June 1982 and June 2013 were included. Logistic regression models were used to assess the association between each variable and pCR. Cox models were used to analyze time to recurrence and overall survival. The recursive partitioning and regression trees method was used to calculate the cut-off value of ER expression.
A total of 3055 patients were analyzed. Low percentage of ER was significantly associated with high pCR rate (OR = 0.99, 95% CI = 0.986–0.994,P<0.001). The recommended cut-off of ER expression below which pCR was likely was 9.5%. Among patients with ER ≥ 10% tumors, but not those with 1%≤ER < 10% tumors, adjuvant hormonal therapy was significantly associated with long time to recurrence (HR = 0.24, 95% CI = 0.16–0.36,P<0.001) and overall survival (HR = 0.32, 95% CI = 0.2–0.5,P<0.001).
Stage II or III HER2-negative primary breast cancer with ER < 10% behaves clinically like triple-negative breast cancer in terms of pCR and survival outcomes and patients with such tumors may have a limited benefit from adjuvant hormonal therapy. It may be more clinically relevant to define triple-negative breast cancer as HER2-negative breast cancer with <10%, rather than <1%, of ER and/or progesterone receptor expression.
Subtypes defined by hormonal receptor (HR) and HER2 status have not been well studied in inflammatory breast cancer (IBC). We characterized clinical parameters and long-term outcomes, and compared ...pathological complete response (pCR) rates by HR/HER2 subtype in a large IBC patient population. We also compared disease-free survival (DFS) and overall survival (OS) between IBC patients who received targeted therapies (anti-hormonal, anti-HER2) and those who did not.
We retrospectively reviewed the records of patients diagnosed with IBC and treated at MD Anderson Cancer Center from January 1989 to January 2011. Of those, 527 patients had received neoadjuvant chemotherapy and had available information on estrogen receptor (ER), progesterone receptor (PR), and HER2 status. HR status was considered positive if either ER or PR status was positive. Using the Kaplan–Meier method, we estimated median DFS and OS durations from the time of definitive surgery. Using the Cox proportional hazards regression model, we determined the effect of prognostic factors on DFS and OS. Results were compared by subtype.
The overall pCR rate in stage III IBC was 15.2%, with the HR-positive/HER2-negative subtype showing the lowest rate (7.5%) and the HR-negative/HER2-positive subtype, the highest (30.6%). The HR-negative, HER2-negative subtype (triple-negative breast cancer, TNBC) had the worst survival rate. HR-positive disease, irrespective of HER2 status, had poor prognosis that did not differ from that of the HR-negative/HER2-positive subtype with regard to OS or DFS. Achieving pCR, no evidence of vascular invasion, non-TNBC, adjuvant hormonal therapy, and radiotherapy were associated with longer DFS and OS.
Hormone receptor and HER2 molecular subtypes had limited predictive and prognostic power in our IBC population. All molecular subtypes of IBC had a poor prognosis. HR-positive status did not necessarily confer a good prognosis. For all IBC subtypes, novel, specific treatment strategies are needed in the neoadjuvant and adjuvant settings.
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