Intracellular Ca2+ accumulation triggered by caffeine provokes resistance against a broad range of biotic stress in rice.

Chemical pesticides are still frequently overused to diminish such crop loss caused by biotic stress despite the threat to humans and the environment. Thus, it is urgent to find safer and more effective defense strategies. In this study, we report that caffeine, implanted through a transgenic approach, enhances resistance against variable biotic stresses in rice without fitness cost. Caffeine-producing rice (CPR) was generated by introducing three N-methyltransferase genes involved in the biosynthesis of caffeine in coffee plants. The CPR plants have no differences in morphology and growth compared to their wild-type counterparts, but they show strongly enhanced resistance to both bacterial leaf blight, rice blast, and attack of white-backed planthoppers. Caffeine acts as a repellent agent against rice pathogens. Moreover, caffeine triggers a series of Ca2+ signalling-like processes to synthesize salicylic acid (SA), a hormone associated with plant resistance. In CPR, phosphodiesterase was inhibited by caffeine, cAMP and cGMP increased, intracellular Ca2+ increased, phenylalanine lyase (PAL) was activated by OsCPK1, and SA synthesis was activated. This finding is a novel strategy to improve resistance against the biotic stresses of crops with a special type of defense inducer.

[Clinical Outcomes of Five Cases of Occult Breast Cancer in Which the Primary Site Was Not Detected in the Breast-by-Breast MRI].

Occult breast cancer is rare in practice. We studied the clinical outcomes of 5 occult breast cancers, including 2 with Luminal and 3 with non-Luminal subtypes, for which the primary site was not detected in the breast-by-breast MRI. The percentage of occult breast cancers that we encountered at our hospital was 0.11%. The mean age was 54 years. The Ki-67 labeling index value was 30% or higher for all the patients except one. Four patients were administered neoadjuvant chemotherapy and all but one patient received non-mastectomy and axillary dissection plus radiotherapy. We observed recurrent cases in one example each of the Luminal and HER2 subtypes, and both patients were less than 40 years old. The estimates of the probability of 5 year recurrence-free survival and 5 year overall survival were 40.0% and 66.7%, respectively. One recurrence case was a patient negative for ER and positive for HER2 wherein a breast cancer lesion appeared in the breast during post-treatment follow-up. Intrabreast relapse, which is itself rare in occult breast cancer, was observed 4 years postoperatively after standard treatment. Although there was no deviation according to subtype rate, the Ki-67 labeling index value was high and the prognosis was poor in our 5 cases.

One-year clinical outcomes of anticoagulation therapy among Japanese patients with atrial fibrillation: The Hyogo AF Network (HAF-NET) Registry.

BACKGROUND: Although anticoagulation therapy could reduce the risk of strokes in patients with atrial fibrillation (AF), large-scale investigations in the direct oral anticoagulant (DOAC) and AF catheter ablation (CA) era are lacking. METHODS: This study was designed as a prospective, multicenter, observational study and a total of 2113 patients from 22 institutions were enrolled in the Hyogo area. RESULTS: The mean age and CHADS2 score were 70.1 ± 10.8 years old and 1.5 ± 1.1, respectively. The follow-up period was 355 ± 43 days. CA was performed in 614 (29%) and DOACs were prescribed in 1118 (53%) patients. Ischemic strokes/systemic embolisms (SEs) and major bleeding occurred in 13 (0.6%) and 17 (0.8%) patients, respectively. New onset dementia, hospitalizations for cardiac events, and all-cause death occurred in eight (0.4%), 60 (2.8%), and 29 (1.4%) patients, respectively. A multivariate analysis demonstrated that persistent AF and the body weight (BW) were associated with ischemic strokes/SEs and major bleeding, respectively (persistent AF: hazard ratio, 9.57; 95%CI, 1.2-74.0; P = .03; BW: hazard ratio, 0.94; 95%CI, 0.90-0.99; P = .02). AFCA history was associated with the cardiac events (hazard ratio, 0.44; 95%CI, 0.20-0.99; P = .04). Age was associated with new onset dementia (hazard ratio, 1.1; 95%CI, 1.0-1.2; P = .03). CONCLUSIONS: In the DOAC and CA era, the incidence of ischemic strokes/SEs, major bleeding and cardiac events could be dramatically reduced in patients with AF. However, some unsolved issues of AF management still remain especially in elderly patients with persistent AF and a low BW.

Association between age factors and strategies for promoting participation in gastric and colorectal cancer screenings.

BACKGROUND: Despite the long history of cancer screening in Japan, the participation rates in gastric and colorectal cancer screenings have not increased. Strategies for improving the participation rates have been proposed, but differences in their effects among different age groups remain unclear. METHODS: The Japanese government conducted a national survey in all municipalities in Japan in 2010 to investigate whether the implementation of promotion strategies increased participation in cancer screening. We investigated the association between age factors and strategies for promoting participation in cancer screening based on this national survey. Multiple regression analysis with generalized linear model was performed using the participation rates in gastric and colorectal cancer screenings as dependent variables, and the following strategies for promoting participation as independent variables: 1) personal invitation letters, 2) household invitation letters, 3) home visits by community nurses, 4) screenings in medical offices, and 5) free cancer screening programs. RESULTS: One thousand six hundred thirty nine municipalities for gastric cancer screening and 1666 municipalities for colorectal cancer screening were selected for the analysis. In gastric and colorectal cancer screenings, the participation rates of individuals aged 60-69 years was higher than those of other age groups. Personal and household invitation letters were effective promotion strategies for all age groups, which encouraged even older people to participate in gastric and colorectal cancer screenings. Screening in medical offices and free screenings were not effective in all age groups. Home visits were effective, but their adoption was limited to small municipalities. CONCLUSIONS: To clarify whether promotion strategies can increase the participation rate in cancer screening among different age groups, 5 strategies were assessed on the basis of a national survey. Although personal and household invitation letters were effective strategies for promoting participation in cancer screening for all age groups, these strategies equally encouraged older people to participate in gastric and colorectal cancer screenings. If resource for sending invitation letters are limited, priority should be given to individuals who are in their 50s and 60s for gastric and colorectal cancer screening.

Knee Motion Generation Method for Transfemoral Prosthesis Based on Kinematic Synergy and Inertial Motion.

Previous research has shown that the effective use of inertial motion (i.e., less or no torque input at the knee joint) plays an important role in achieving a smooth gait of transfemoral prostheses in the swing phase. In our previous research, a method for generating a timed knee trajectory close to able-bodied individuals, which leads to sufficient clearance between the foot and the floor and the knee extension, was proposed using the inertial motion. Limb motions are known to correlate with each other during walking. This phenomenon is called kinematic synergy. In this paper, we measure gaits in level walking of able-bodied individuals with a wide range of walking velocities. We show that this kinematic synergy also exists between the motions of the intact limbs and those of the knee as determined by the inertial motion technique. We then propose a new method for generating the motion of the knee joint using its inertial motion close to the able-bodied individuals in mid-swing based on its kinematic synergy, such that the method can adapt to the changes in the motion velocity. The numerical simulation results show that the proposed method achieves prosthetic walking similar to that of able-bodied individuals with a wide range of constant walking velocities and termination of walking from steady-state walking. Further investigations have found that a kinematic synergy also exists at the start of walking. Overall, our method successfully achieves knee motion generation from the initiation of walking through steady-state walking with different velocities until termination of walking.

Does lack of resources impair access to breast and cervical cancer screening in Japan?

OBJECTIVES: To assess the impact of the quantity of resources for breast and cervical cancer screening on the participation rates in screening in clinical settings in municipalities, as well as to clarify whether lack of resources impairs access to cancer screening in Japan. METHODS: Of the 1,746 municipalities in 2010, 1,443 (82.6%) and 1,469 (84.1%) were included in the analyses for breast and cervical cancer screening, respectively. In order to estimate the effects of the number of mammography units and of gynecologists on the participation rates in breast and cervical cancer screening in clinical settings, multiple regression analyses were performed using the interaction term for urban municipalities. RESULTS: The average participation rate in screening in clinical settings was 6.01% for breast cancer, and was 8.93% for cervical cancer. The marginal effect of the number of mammography units per 1,000 women was significantly positive in urban municipalities (8.20 percent point). The marginal effect of the number of gynecologists per 1,000 women was significantly positive in all municipalities (2.54 percent point) and rural municipalities (3.68 percent point). CONCLUSIONS: Lack of mammography units in urban areas and of gynecologists particularly in rural areas impaired access to breast and cervical cancer screening. Strategies are required that quickly improve access for the residents and increase their participation rates in cancer screening.

Caffeine fostering of mycoparasitic fungi against phytopathogens.

Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine.

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study.

BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80-120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8-79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469.

Japanese public long-term care insured: preferences for future long-term care facilities, including relocation, waiting times, and individualized care.

OBJECTIVES: Expenditures on long-term care insurance (LTCI) in Japan have been increasing with the aging of the population, which has led to an increase in premiums. To optimize resource allocation, we aim to clarify the priorities of the functions of long-term care facilities from the viewpoint of future beneficiaries. DESIGN: The present study was conducted using a cross-sectional study design. SETTING/PARTICIPANTS: We conducted a mail-in survey targeting 2400 adults aged 50-65 in 8 cities in Japan, and 371 persons responded. MEASUREMENTS: Conjoint analysis was applied to measure participants' preferences for long-term care facility services. Participants read 1 of 2 vignettes of an 80-year-old person with either dementia or a fracture, and were asked to envision it as a possible future scenario for themselves. Participants then completed 8 or 9 tasks to select suitable long-term care facilities for the person described. The questionnaire also contained common questions on participants' personal profiles: age, gender, family situation, education, approximate yearly family income, experience as a family caregiver, dwelling status, present health status, and possibility of requiring long-term care services in the future. RESULTS: The results focused mainly on (1) possibilities of individual choice for daily schedules/meals; (2) availability of regular care staff; (3) room; (4) main daily interactions; (5) necessity of relocation associated with medical deterioration; 6) Waiting time; 7) distance from present residence; and (8) monthly fees. Necessity of relocation associated with medical deterioration was consistently given the greatest importance. Participants with experience as a family caregiver showed significantly greater preference for individualized care and communication. CONCLUSIONS: The option of avoiding relocation was highly valued by participants compared with private rooms and individualized care. The present situation of high demand for intensive care homes for the elderly, provoked by anxiety about future residence, will not change unless a robust system is built to support residents even when their health has deteriorated. Individualized care has been promoted by long-term care insurance policies, but further advances will require efforts to obtain the understanding of the insured.

Marinibactrum halimedae gen. nov., sp. nov., a gammaproteobacterium isolated from a marine macroalga.

Phylogenetic and taxonomic characterization was performed for a bacterium, designated strain Q-192T, isolated from the surface of the green macroalga Halimeda sp., collected from the subtropical Ishigaki Island, Japan. The isolate was a polysaccharide-producing, Gram-stain-negative, aerobic, rod-shaped, motile bacterium with a polar flagellum. The isolate was slightly halophilic, required Na+, Mg2+ and Ca2+ ions for growth, but did not require growth factors. The only isoprenoid quinone was ubiquinone-8.The major cellular fatty acids were C18 : 1ω7c, C16 : 0 and C14 : 0. The main hydroxy fatty acid was C10 : 0 3-OH. The DNA G+C content was 45.9 mol%. Phylogenetic analysis of 16S rRNA gene sequences placed the isolate in the class Gammaproteobacteria. The phylogenetically closest relatives with validly published names were Pseudomaricurvus alkylphenolicus KU41GT, Teredinibacter turnerae T7902T, Pseudoteredinibacter isoporae SW-11T and Simiduia agarivorans SA1T with sequence similarities of 94.5, 94.1, 93.7 and 93.6 %, respectively. The isolate was distinguished from members of these genera by a combination of DNA G+C content, chemotaxonomic characteristics (respiratory quinone system, fatty acid profile and polar lipid composition) and other phenotypic features. Based on phylogenetic, genotypic, chemotaxonomic and phenotypic characteristics, strain Q-192T is considered to represent a novel species of a new genus, for which the name Marinibactrum halimedae gen. nov., sp. nov. is proposed. The type strain of Marinibactrum halimedae is Q-192T ( = NBRC 110095T = NCIMB 14932T).

Optical imaging for monitoring tumor oxygenation response after initiation of single-agent bevacizumab followed by cytotoxic chemotherapy in breast cancer patients.

PURPOSE: Optical imaging techniques for measuring tissue hemoglobin concentration have been recently accepted as a way to assess tumor vascularity and oxygenation. We investigated the correlation between early optical response to single-agent bevacizumab and treatment outcome. METHODS: Seven patients with advanced or metastatic breast cancer were treated with single-agent bevacizumab followed by addition of weekly paclitaxel. Optical imaging of patient's breasts was performed to measure tumor total hemoglobin concentration (tHb) and oxygen saturation (stO2) at baseline and on days 1, 3, 6, 8, and 13 after the first infusion of bevacizumab. To assess early metabolic response, 2-deoxy-2-(18F)-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), 18F-fluoromisonidazole (FMISO)-PET/CT, and magnetic resonance imaging were performed at baseline and after two cycles of the regimen. RESULTS: Seven patients were grouped as responders (n = 4) and nonresponders (n = 3) on the basis of metabolic response measured by FDG-PET/CT. The responders showed remarkable tumor shrinkage and low accumulations of FMISO tracer relative to those of the nonresponders at the completion of two cycles of chemotherapy. Tumors of both groups showed remarkable attenuation of mean tHb as early as day 1 after therapy initiation. The nonresponders had lower baseline stO2 levels compared with adjacent breast tissue stO2 levels along with a pattern of steadily low stO2 levels during the observation window. On the other hand, the responders appeared to sustain high stO2 levels with temporal fluctuation. CONCLUSIONS: Low tumor stO2 level after single-agent bevacizumab treatment was characteristic of the nonresponders. Tumor stO2 level could be a predictor of an additional benefit of bevacizumab over that provided by paclitaxel.

Clinicopathological and prognostic impact of imaging of breast cancer angiogenesis and hypoxia using diffuse optical spectroscopy.

Near-infrared diffuse optical spectroscopy (DOS) imaging can non-invasively measure tumor hemoglobin concentration using high contrast to normal tissue, thus providing vascularity and oxygenation status. We assessed the clinical usefulness of DOS imaging in primary breast cancer. In all, 118 women with a histologically confirmed diagnosis of primary malignant tumor were enrolled. All participants underwent testing using time-resolved DOS before treatment initiation. Visual assessment of DOS imaging for detecting tumors was carried out by two readers blinded to the clinical data. Relative total hemoglobin (rtHb) and oxygen saturation (stO2 ) of the tumors was compared with clinicopathological variables and 10-year prognosis was calculated. Sensitivity for detecting a tumor based on the rtHb breast map was 62.7% (74/118). The sensitivity depended on T stage: 100% (7/7) for T3, 78.9% (45/57) for T2, 44.7% (17/38) for T1, and 31.3% (5/16) for Tis . Tumors showed unique features of higher rtHb with a wider range of stO2 than normal breast tissue, depending on histological type. There was a significant correlation of rtHb with tumor size, lymphatic vascular invasion, and histological grade, and of stO2 with age and tumor size. Neither rtHb nor stO2 correlated with intrinsic biomarkers such as estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2; rtHb inversely correlated with 10-year relapse-free survival and overall survival, with statistical significance. Diffuse optical spectroscopy imaging has limited utility for the early detection of breast cancer; nonetheless, the findings suggest that the degree of tumor angiogenesis and hypoxia may be associated with tumor aggressiveness and poor prognosis.

What is the most effective strategy for improving the cancer screening rate in Japan?

BACKGROUND: Cancer screening rates in Japan are much lower than those in Western countries. This study evaluated the relationship between cancer screening rates and strategies used to improve screening rates, and determined which strategy is the most effective. MATERIALS AND METHODS: All municipalities are responsible for conducting gastric, lung, colorectal, cervical, and breast cancer screenings in Japan. Of the 1,746 municipalities in total, 92-99% were included in the analyses for each cancer screening. Using national data in 2009, the correlations between cancer screening rates and strategies for improving screening rates of all municipalities, both large (populations of over 30,000) and small (populations of under 30,000), were determined. The strategies used were as follows: sending personal invitation letters, personal visits by community health workers, use of a clinical setting for screening, and free screening. RESULTS: Of all four strategies used to improve cancer screening rates, sending personal invitation letters had the highest correlations with all screening rates, with the exception of breast cancer screening. The partial correlation coefficients linking this strategy with the screening rates in all municipalities were 0.28, 0.32, 0.30, and 0.26 for gastric, lung, colorectal, and cervical cancer screening, respectively. In large municipalities, the correlations between the number of examinees in a clinical setting and the screening rates were also relatively high, particularly for cervical cancer screening (r=0.41). CONCLUSIONS: Sending personal invitation letters appears to be particularly effective in improving cancer screening rates in all municipalities. All municipalities should implement a system that sends personal invitation letters for cancer screening. In large municipalities, increasing the availability of screening in a clinical setting is also effective in improving cancer screening rates.

Contribution of bone marrow-derived mesenchymal stem cells to the morphological changes in the bladder after partial outlet obstruction: a preliminary study.

OBJECTIVES: To investigate the contribution of bone marrow-derived mesenchymal stem cells to the changes in bladder morphology in response to partial bladder outlet obstruction. METHODS: Allogenic bone marrow cells were transplanted from transgenic rats expressing green fluorescent protein into female Sprague-Dawley rats 1 day after their bone marrow-derived mesenchymal stem cells had been destroyed by irradiation. This generated chimeric rats in which green fluorescent protein labeled bone marrow-derived mesenchymal stem cells replaced host bone marrow-derived mesenchymal stem cells. The animals received partial bladder outlet obstruction or sham surgery 6 weeks later. The animals were killed 6 weeks after the surgery, and bladder tissue was prepared for immunofluorescence with antibodies against a urothelium marker (AE1/AE3), a myofibroblast marker (vimentin), a smooth muscle marker and green fluorescent protein. RESULTS: More labeled bone marrow-derived mesenchymal stem cells were found in the partial bladder outlet obstruction group than in the in the sham group. Most bone marrow-derived mesenchymal stem cells were present around the basement membrane (laminin) and lamina propria below the urothelium. Bone marrow-derived mesenchymal stem cells were also found in the urothelium layer, and some of them were double-stained with green fluorescent protein and AE1/AE3. Some bone marrow-derived mesenchymal stem cells, which were located in the interstitial tissue, were double-stained with green fluorescent protein and vimentin. Bone marrow-derived mesenchymal stem cells, which migrated into the smooth muscle layer, showed fusiform morphology, and some were double-stained with green fluorescent protein and smooth muscle marker. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells home to the partial bladder outlet obstruction bladder, and these cells have the potential to differentiate into the several components of bladder tissue including the urothelium, myofibroblasts and smooth muscle cells. Thus, bone marrow-derived mesenchymal stem cells contribute to the morphological changes of the bladder in response to partial bladder outlet obstruction.

Optical imaging of tumor vascularity associated with proliferation and glucose metabolism in early breast cancer: clinical application of total hemoglobin measurements in the breast.

BACKGROUND: Near-infrared optical imaging targeting the intrinsic contrast of tissue hemoglobin has emerged as a promising approach for visualization of vascularity in cancer research. We evaluated the usefulness of diffuse optical spectroscopy using time-resolved spectroscopic (TRS) measurements for functional imaging of primary breast cancer. METHODS: Fifty-five consecutive TNM stage I/II patients with histologically proven invasive ductal carcinoma and operable breast tumors (<5 cm) who underwent TRS measurements were enrolled. Thirty (54.5%) patients underwent 18F-fluoro-deoxy-glucose (FDG) positron emission tomography with measurement of maximum tumor uptake. TRS was used to obtain oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (tHb) levels from the lesions, surrounding normal tissue, and contralateral normal tissue. Lesions with tHb levels 20% higher than those present in normal tissue were defined as "hotspots," while others were considered "uniform." The findings in either tumor type were compared with clinicopathological factors. RESULTS: "Hotspot" tumors were significantly larger (P= 0.002) and exhibited significantly more advanced TNM stage (P=0.01), higher mitotic counts (P=0.01) and higher levels of FDG uptake (P=0.0004) compared with "uniform" tumors; however, other pathological variables were not significantly different between the two groups. CONCLUSIONS: Optical imaging for determination of tHb levels allowed for measurement of tumor vascularity as a function of proliferation and glucose metabolism, which may be useful for prediction of patient prognosis and potential response to treatment.

Genomic profiling shows increased glucose metabolism in luminal B breast cancer.

We had previously reported a close association between pathological response and the maximum tumor standardized uptake value (SUVmax) measured by (18)F-fluorodeoxyglucose positron emission tomography prior to chemotherapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that glucose hypermetabolism by luminal B tumors may result in chemotherapy responsiveness. Using a single-gene expression assay, TargetPrint® (Agendia) and a 70-gene expression classifier, MammaPrint® (Agendia), we divided 20 patients with ER-positive primary breast cancer into luminal A and luminal B subtypes and compared the tumor SUVmax value between the two groups. A significantly higher SUVmax was measured for luminal B tumors (n=10; mean±SD, 7.6±5.6) than for luminal A tumors (n=10; mean±SD, 2.6±1.2; p=0.01). Glucose hypermetabolism could help predict intrinsic subtyping and chemotherapy responsiveness as a supplement to ER, progesterone receptor, HER2, and Ki-67 histochemical scores.

Pulmonary tumor thrombotic microangiopathy showing aggressive course after transurethral resection of urinary bladder: an autopsy case report.

A 77-year-old man developed pulmonary tumor thrombotic microangiopathy (PTTM) 2 days after undergoing transurethral resection for urothelial carcinoma (G3) of the urinary bladder and died of respiratory failure 6 days later. Histological findings demonstrated marked intimal fibrocellular proliferation, fibrin thrombi, and both cancer cells and fibrin thrombi in the arteries of the lungs, findings consistent with PTTM. Prominent stenosis in arteries smaller than 300 µm was also seen. The Ki-67 labeling index of primary and metastasized cancer cells was 62.4 % and 70.2 %, respectively. The membranes of metastasized cancer cells expressed E-cadherin, similar to membranes in the urinary bladder. An aggressive PTTM course is affected by intimal fibrocellular proliferation and the high cell proliferation of cancer cells. Furthermore, prominent stenosis in small arteries and membranous staining of E-cadherin of metastasized cells suggest that cancer cells formed clusters by maintaining adhesion molecules and migrated into the arteries of the lungs, where they easily caused damage to the endothelium of small arteries, in contrast to dispersed cancer cells.

Axillary ultrasound examination is useful for selecting patients optimally suited for sentinel lymph node biopsy after primary systemic chemotherapy.

BACKGROUND: Controversy surrounds the reliability of sentinel lymph node biopsy after primary systemic chemotherapy. In this study, we assessed axillary ultrasound for selecting patients most likely to optimally benefit from biopsy. METHODS: The study included 87 patients who received primary systemic chemotherapy and underwent a sentinel lymph node biopsy followed by axillary lymph node dissection. Lymph nodes >10 mm in diameter, irregularly swollen, round, and homogeneously hypoechoic without an echo-rich center were considered axillary ultrasound positive. RESULTS: In axillary ultrasound-negative patients before and after primary systemic chemotherapy, identification, sensitivity, and false-negative rates were 81%, 100%, and 0%, respectively. However, in patients whose lymph nodes converted from positive to negative after primary systemic chemotherapy, these values were 83%, 70.8%, and 29.2%, respectively. CONCLUSIONS: Axillary ultrasound-negative patients before and after primary systemic chemotherapy were suitable for sentinel lymph node biopsy. Axillary ultrasound should be used during primary systemic chemotherapy and before surgery.

Quantitative prediction of tumor response to neoadjuvant chemotherapy in breast cancer: novel marker genes and prediction model using the expression levels.

BACKGROUND: In breast cancer, the identification of accurate predictors of tumor response to neoadjuvant chemotherapy is of key importance, but none of the critical markers have been validated to date. We attempted to identify potent marker genes genome-wide, and we developed a prediction model for individual response to epirubicin (EPI)/cyclophosphamide (CPM) combination chemotherapy (EC). METHODS: From 10 human breast cancer cell lines, genes whose expression levels correlated with cytotoxicities of EPI and CPM were chosen through comprehensive gene expression analysis followed by correlation-confirmation study of the quantified expression levels analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: We finally selected a total of 4 genes (ANXA1 and PRKCA for EPI; DUSP2 and SERPINA3 for CPM) as reliable prediction markers. Using quantified expression data of genes in 18 tumor samples, we performed multiple linear regression analysis to establish the best linear model that could convert the quantified expression data to show tumor response to the EC therapy (the ratio of tumor size to the baseline, %). Outliers were identified by referring to the value of AIC (Akaike's information criterion) for each sample (AIC/sample) or checking residuals graphically. The multiple linear regression analysis of the selected genes yielded 2 highly predictive formulae for the tumor response: one used all of the genes except SERPINA3 (R = 0.8348, AIC/sample = 4.9182) and the other used all of the 4 genes (R = 0.8224, AIC/sample = 5.0730). CONCLUSIONS: A study to validate the predictive values of the selected 4 genes is now planned, along with research to determine their functional roles.

Stromal Cell-Derived Factor 1α Induces Accumulation of Intraveneously Administered Marrow-Derived Stromal Cells in the Partially Obstructed Rat Bladder.

OBJECTIVES: We investigated the time course of the stromal cell-derived factor 1α (SDF1α) expression and behavior of intravenously administered bone marrow-derived stromal (BMS) cells in the urinary bladder of partial bladder outlet obstruction (PBOO) rats. METHODS: Study 1: Recombinant SDF1α or saline was directly injected into the bladder wall of female rats followed by intravenous administration of BMS cells isolated from green fluorescent protein (GFP) transgenic rats. The bladder was examined with immunohistochemistry to determine whether SDF1α would enhance migration of BMS cells to the bladder. Study 2: Following surgery of PBOO or sham in female rats, bladders were removed on days 1-14, and expression of hypoxia inducible factor 1α (HIF1α) and SDF1α were examined with real-time polymerase chain reaction (PCR) to determine if PBOO preferentially increased their expression. Study 3: Female rats underwent PBOO or sham surgery followed by intravenous administration of GFP-positive BMS cells. Bladders were examined with immunohistochemistry on days 1-14 to determine whether BMS cells preferentially accumulated in the bladder. RESULTS: BMS cells were accumulated in the injection site of SDF1α but not saline in the bladder. SDF1α and HIF1α increased at day 1 after PBOO compared to sham. More BMS cells accumulated in the bladder of PBOO on day 1, and some BMS cells expressed smooth muscle phenotypes by day 14. CONCLUSION: SDF1α induced with ischemia/hypoxia due to PBOO is implicated in the accumulation of BMS cells in the bladder and regeneration of the bladder for PBOO.