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OBJECTIVE: To retrospectively evaluate the clinical outcomes of pre-operative endovascular coil embolisation (ECE) for chronic pulmonary aspergillosis (CPA).METHODS: We evaluated surgical patients with CPA between November 2016 and April 2020. Pre-operative ECE for CPA with severe adhesions was selectively performed to reduce intra-operative blood loss. ECE procedures, operative procedures, intra-operative blood loss and complications were evaluated.RESULTS: Twenty-eight patients (21 males and 7 females; median age: 55 years) were included in the study. Of the 28 patients, 8 (28.6%) underwent pre-operative ECE. Technical success rate in pre-operative ECE was 100%. The median time required for ECE procedures was 123 min. The median number of vessels embolised per procedure was 2.5. The median period between embolisation and surgery was 5 days. Major complications were observed in three patients (10.7%). There were no significant differences between patients with and without pre-operative ECE in operative time (284 vs. 365 min, respectively, P = 0.7602) and intra-operative blood loss (294 vs. 228 mL, respectively, P = 0.8987).CONCLUSIONS: Pre-operative ECE for CPA appears to be feasible and safe; however, its role in reducing intra-operative blood loss needs further investigation.

There has been an increase in the number of Jack Russell Terriers (JRTs) diagnosed with adenomas and adenocarcinomas of the gastrointestinal tract in Japan. This study retrospectively investigated the clinical and histopathological features and prognosis of adenocarcinomas arising in the gastrointestinal tract in JRT dogs. Seven JRTs and 39 dogs of other breeds diagnosed with gastrointestinal adenocarcinoma were included in the study. The most common sites of gastrointestinal adenocarcinoma in JRTs were the pylorus and rectum. On histopathological examination, these adenocarcinomas showed a papillary or tubular growth pattern, and the lesions were confined within the mucosal epithelium and poorly invasive. Among all dogs with gastric adenocarcinoma, the median survival time (MST) for five of the JRTs could not be determined because more than half of the cases remained alive, while the MST for nine non-JRT dogs was 34 days. Among all dogs with adenocarcinoma in the large intestine, the MST for three of the JRTs could not be determined, while the MST for nine non-JRT dogs was 1,973 days. The difference in MST between JRT and non-JRT dogs with gastric adenocarcinoma was significant (P=0.0220). Since gastrointestinal adenocarcinomas in JRTs show distinct characteristics with respect to their clinical features, treatment course, and prognosis, a different surgical and medical treatment plan should be considered compared to the management of gastrointestinal adenocarcinomas in other dog breeds.

Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy. Trial registration UMIN-CTR registration identifier: UMIN000023324. Electronic supplementary material The online version of this article (10.1007/s00262-020-02619-3) contains supplementary material, which is available to authorized users.

Inflammatory colorectal polyps (ICRPs) are frequently observed in miniature dachshunds in Japan and treated by prednisolone and immunosuppressive drugs such as cyclosporine and leflunomide. The purpose of this retrospective study was to compare the treatment efficacy, such as response rate, response interval, recurrence rate, and adverse events between cyclosporine and leflunomide. While the response rates were significantly higher in dogs treated with leflunomide, no significant differences were observed in the response interval or recurrence rate. Two of the 11 dogs treated with leflunomide showed hematological or gastrointestinal adverse events, while no dog treated with cyclosporine showed any adverse events. A case-controlled prospective study to compare the treatment efficacy of leflunomide with that of cyclosporine should be conducted.

In human medicine, computed tomography (CT) is the gold standard for visceral fat measurement. Research shows that the visceral fat area (VFA) of the umbilical slice is significantly correlated with the visceral fat volume (VFV). In veterinary medicine, however, few studies have evaluated visceral fat using CT. This study aimed to evaluate the visceral fat in dogs using CT images, and determine if the slice significantly correlated with VFV to simplify visceral fat measurements. This retrospective study includes data on 90 dogs that underwent whole-body CT scans for diagnostic purposes. VFV was calculated as the product of VFA and thickness in each CT slice; the correlation between VFV and VFA was analyzed at the level of each lumbar vertebra. Visceral fat percentage (VF%) was calculated as the ratio of the product of VFV and fat density to the body weight. Visceral fat area percentage (VFA%) was calculated as the ratio of VFA to the body area, and its correlation with the VF% and the body condition score (BCS) was analyzed. VFA was highly correlated with VFV at the level of each lumbar vertebra, with the highest correlation (r=0.964) at the L3 level. VFA% was significantly correlated with VF% (r=0.930) and weakly correlated with BCS (r=0.523). This study demonstrates that it is sufficient to use only the L3 slice for visceral fat evaluation and that the evaluation can be based on VFA% of the L3 level.

X-chromosome inactivation pattern (XCIP) analysis can be used to assess the clonality of cell populations of various origin by distinguishing the methylated X chromosome from the unmethylated X chromosome. In this study, the utility of XCIP analysis was improved by incorporating the examination of AC dinucleotide repeats in SLIT and NTRK-like family member 4 (SLITRK4) gene into the previously reported CAG repeat examination of androgen receptor (AR) gene in dogs. The rate of heterozygosity when both genes were analysed (125/150, 83.3%) was higher than AR gene examination alone (86/150, 57.3%). Blood samples from heterozygous dogs in either AC-1 or AC-2 of SLITRK4 gene were examined for the corrected inactivation allele ratio (CIAR), resulting in the determination of a reference range of CIAR3.8 in non-neoplastic cell/tissue samples. Using this analytical method, 49% (21/43) of neoplastic tissue samples from dogs showed a CIAR3.8, indicating the presence of a clonal population. Through the present study, the availability of canine XCIP analysis was improved by incorporating the examination of the SLITRK4 gene, providing a highly useful laboratory examination system for the detection of the clonality of various cell/tissue samples in dogs.

Megaesophagus (ME) is a common esophageal disease in dogs and the prognosis is generally poor, especially with aspiration pneumonia (AP). We retrospectively investigated the clinical features and prognosis of canine ME in Japan. Twenty-eight dogs were included in this study, with the Miniature Dachshund breed being significantly overrepresented (odds ratio: 4.33). Most cases (21 of 28) were diagnosed as idiopathic ME and Myasthenia gravis was the most common cause of secondary ME. The overall median survival time (MST) was not reached and the 3-month survival rate was 85.7%. Ten dogs were diagnosed with AP, at least once during the study period, and the MST of ME dogs with AP was 114 days. The survival time overall and even with AP, was notably more prolonged compared to the previous studies. We hypothesized that treatment for canine ME could prolong the survival time, even in those with both ME and AP.

There are few reports on the comparison between teriparatide (PTH) and bisphosphonate (BP) in terms of osteoporosis pain-related behavior and immunohistochemical findings. The aims of this study were to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of PTH and BP on pain and bone loss in hind limb-unloaded (HU) mice. The mechanism of osteoporotic pain in HU mice was evaluated by examining pain-related behavior and immunohistochemical findings. The effects of PTH and alendronate (ALN), a potent osteoclast inhibitor, on these parameters were also assessed. Eight-week-old male ddY mice were tail-suspended for 2 weeks and assigned to four groups: hind limb-loaded (HL) mice with only tail suspension treated with vehicle; HU mice with tail suspension treated with vehicle; HU mice treated with PTH; and HU mice treated with ALN. Starting immediately after reloading, vehicle, PTH, or ALN was injected subcutaneously. After a 2-week treatment, mechanical sensitivity was examined using von Frey filaments. Bilateral hind limbs were removed for micro-computed tomography, immunohistochemical analysis, and messenger RNA (mRNA) expression analysis. HU mice with tail suspension developed bone loss and mechanical hyperalgesia in the hind limbs. The HU mice showed an increased osteoclasts and sclerostin-positive cells in the hind limb bone. Furthermore, PTH and ALN both prevented HU-induced bone loss and mechanical hyperalgesia in the osteoporotic animal models. Histological examination of the hind limb bone revealed that, similar to ALN, PTH inhibited the osteoclasts and sclerostin-positive cells. The mRNA levels of TNFα and IL-6 tended to decrease with ALN or PTH treatment compared with those without any treatment. Treatment with PTH as well as BP prevented bone loss, mechanical hyperalgesia, osteoclast increase, and osteocyte increase. Similar to BP, the inhibitory effect of PTH on osteoclasts might contribute to the improvement of skeletal pain.

Canine transitional cell carcinoma (cTCC) is the most common malignant tumour in the urinary bladder: it is highly invasive and exhibits metastatic characteristics. Inflammation is also strongly related to cTCC. Epithelial tumours often exhibit a mesenchymal cell phenotype during tumour invasion and metastasis owing to epithelial-mesenchymal transition (EMT), which is often induced in chronic inflammation. The aim of this retrospective study was to investigate the expression of epithelial and mesenchymal cell markers in tumour cells and to evaluate its relationship with prognosis of cTCC. In this study, 29 dogs with cTCC who underwent surgical treatment were enrolled. Clinical parameters were reviewed using medical records. Tissue expression of epithelial and mesenchymal markers was evaluated by immunohistochemical analysis. The association between the expression of mesenchymal cell markers and clinical parameters, including prognosis, was statistically examined. In five normal bladder tissues used as controls, no expression of mesenchymal markers was observed, except for one tissue that expressed fibronectin. Conversely, epithelial tumour cells expressed vimentin and fibronectin in 23/29 and 19/28 cTCC tissues, respectively. Regarding clinical parameters, vimentin score in Miniature Dachshunds was significantly higher than those in other dog breeds (P0.001). Multivariate survival analyses revealed that age12 years was related to shorter progression-free survival (P = 0.02). Higher vimentin score, lower fibronectin score, and advanced clinical T stage were significantly correlated with shorter median survival time (P0.05). The results of this study indicate that vimentin expression was associated with cTCC progression. Further studies are needed to examine the incidence and relevance of EMT in cTCC.

Purpose: The aim of this study was to examine the inhibitory effect of teriparatide (TPTD) on pain and on bone loss in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior as well as immunohistochemical examinations. Methods: Eight-week-old female ddY mice were OVX and assigned to one of three groups: (1) OVX mice treated with vehicle (OVX), (2) OVX mice treated with teriparatide (OVX-TPTD), or (3) SHAM-operated mice treated with vehicle (SHAM). Starting immediately after surgery, vehicle or TPTD was injected subcutaneously. After a 4-week treatment, mechanical sensitivity was tested using von Frey filaments. The proximal tibial metaphyses were analyzed three-dimensionally by microcomputed tomography (μCT). Calcitonin gene-related peptide (CGRP) and transient receptor potential channel vanilloid 1 (TRPV1) expressions in L3–5 dorsal root ganglion (DRG) neurons were examined using immunohistochemistry. Results: Ovariectomy induced bone loss and mechanical hyperalgesia in the hind limbs with upregulation of CGRP and TRPV1 expressions in DRG neurons innervating the hind limbs. Bone loss was prevented more effectively in the OVX-TPTD mice than in the OVX mice. Furthermore, mechanical hyperalgesia and upregulation of CGRP and TRPV1 expressions were significantly lower in the OVX-TPTD mice than in the OVX mice. Conclusion: TPTD treatment prevented ovariectomy-induced bone loss and ovariectomy-induced mechanical hyperalgesia in hind limbs, and it suppressed CGRP and TRPV1 expressions in DRG neurons. These results suggest that TPTD is useful for the treatment of osteoporotic pain in postmenopausal women.

Although antimicrobial peptides (AMPs) play an integral role in the regulation of intestinal microbiota and homeostasis, their expression in canine gastrointestinal diseases, including idiopathic inflammatory bowel disease (IBD) and intestinal lymphoma, remains unknown. The objective of this study was to investigate the intestinal expression of AMPs in dogs with IBD or intestinal lymphoma. IBD was diagnosed in 44 dogs, small cell intestinal lymphoma in 25 dogs, and large cell intestinal lymphoma in 19 dogs. Twenty healthy beagles were used as normal controls. Duodenal mRNA expression of six representative AMPs - lactoferrin, lysozyme, cathelicidin, secretory leukocyte peptidase inhibitor (SLPI), bactericidal/permeability increasing protein (BPI), and canine beta defensin (CBD103) - was quantified by real-time reverse transcription polymerase chain reaction. The relative expression of BPI, lactoferrin, and SLPI was significantly higher in dogs with IBD and intestinal lymphomas than in healthy controls. Interestingly, the expression patterns of AMPs differed between dogs with IBD and those with intestinal lymphomas, especially small cell lymphoma. Increased expression of BPI differentiated IBD from dogs with small cell intestinal lymphoma, with a sensitivity of 93.2%, a specificity of 100%, and an area under the curve of 0.955. These results suggest that the expression patterns of AMP aid in the diagnosis of canine IBD and intestinal lymphoma, although it remains uncertain whether the altered AMP expression is the cause or effect of mucosal inflammation.

Objective To evaluate the utility of the chemiluminescent enzyme immunoassay (CLEIA) method for point-of-care (POC) measurement of canine plasma thrombin-antithrombin complex (TAT) concentration. Assessment and main results Plasma TAT concentration was measured in 54 healthy dogs and in 72 dogs with various diseases. A significant correlation was found between TAT concentration measured by CLEIA and that measured by an ELISA that was previously used in dogs. The upper limit of the reference value of TAT concentrations measured by CLEIA was determined to be 0.2 ng/mL based on the TAT concentration in 54 healthy dogs. TAT concentrations exceeded the reference interval in a portion of dogs when a hypercoagulable state may be present. Conclusions Canine plasma TAT concentrations measured using CLEIA were correlated with that measured using ELISA. Hence, a POC testing instrument may be used for early detection of activation of thrombin generation in emergency and critical care settings.

The Stroop effect is one of the most famous examples of interference in human perception. The present study demonstrates that a position Stroop paradigm, comparable to the classical color-word interference paradigm, resulted in the same pattern of interference for the spatial dimension; however, the interference was significantly weaker. By exchanging the original oral response for a manual response in the spatial paradigm, we showed that the verbal component is crucial for the Stroop effect: Manual responses lead to a disappearance of the interference effect. Moreover, with manual responses word position was recognized at the same speed for the baseline condition and for words that were incongruent as well as congruent with the spatial position. The results indicate (1) that the Stoop effect depends heavily on verbal components and (2) that differing processing speeds between reading and position recognition do not serve as a proper explanation for the effect. In addition, the provided paradigm plausibly transfers the classical color-word interference to the spatial dimension.

Background Chronic back pain is one of the most important complications of postmenopausal osteoporosis. The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonates (BPs) on pain in ovariectomized (OVX) mice. The mechanism of osteoporotic pain in OVX mice was evaluated through an examination of pain-related behavior, as well as immunohistochemical findings. In addition, the effects of alendronate (ALN), a potent osteoclast inhibitor, on these parameters were assessed. Methods 8-week-old female ddY mice were ovariectomized and assigned to 3 groups: SHAM-operated mice treated with vehicle (SHAM; n = 8); OVX mice treated with vehicle (OVX-V; n = 8); and OVX mice treated with ALN (OVX-ALN; n = 8). Starting immediately after surgery, vehicle or 40 μg/kg ALN was injected subcutaneously twice a week for 4 weeks. The bilateral distal femoral metaphyses and proximal tibial metaphyses were analyzed three-dimensionally by μCT. Mechanical sensitivity was tested using von Frey filaments. Transient receptor potential channel vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP) expressions in L3-5 dorsal root ganglion (DRG) neurons were examined immunohistochemically. Results Ovariectomy induced bone loss and mechanical hyperalgesia in hindlimbs with upregulation of TRPV1 and CGRP expressions in DRG neurons innervating hindlimbs. ALN prevented bone loss and mechanical hyperalgesia in ovariectomized mouse hindlimbs, and it suppressed upregulation of pain markers. Conclusions ALN prevented ovariectomy-induced bone loss and mechanical hyperalgesia in hindlimbs, and it suppressed TRPV1 and CGRP expressions in DRG neurons. The results suggest that bone resorption with upregulation of TRPV1 and CGRP expressions is one of the causes of postmenopausal osteoporotic pain.

Background and Aims: The efficacy of azathioprine for Crohn’s disease under adalimumab treatment remains obscure. Methods: In an open-labelled prospective study, we evaluated the efficacy of adalimumab with and without azathioprine in patients with active Crohn’s disease, who were naive to biologics and thiopurines. The patients were randomly assigned to subcutaneous administration of adalimumab \[monotherapy group] or to exactly the same schedule of adalimumab with azathioprine [25–100mg daily\] \[combination group\] for 52 Weeks. The primary endpoint was clinical remission at WWeek 26. We also evaluated the score for simple endoscopic severity of Crohn’s disease before the therapy and at WWeeks 26 and 52. Results: A total of 176 patients were randomized to either the monotherapy group \[ n = 85] or to the combination group [ n = 91]. Eighteen patients [21.2%] from the monotherapy group and 7 patients [7.7%] from the combination group withdrew owing to active disease, and 15 patients [16.5%] from the combination group and 1 patient [1.2%] from the monotherapy group withdrew due to side effects of the medications. Non-responder imputation analysis revealed that the remission rate at WWeek 26 did not differ between the monotherapy group and the combination group [71.8% vs 68.1%; OR 0.84, p = 0.63]. The rate of endoscopic improvement at WWeek 26 was significantly higher in the combination group [84.2%, n = 57] than in the monotherapy group [63.8%, n = 58\] \[ p = 0.019\]. Conclusion: The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohn’s disease naive to both medications.

To determine the influence of the transplantation site of canine osteosarcoma (OS) cell lines on tumour growth and pulmonary metastasis, three OS cell lines were transplanted into nude mice via subcutaneous (SC), intratibial (IT) or intravenous (IV) injection. IT-xenografts exhibited greater potential for developing primary masses and pulmonary metastasis than SC-xenografts. In IT and IV xenografts, lung micrometastases along with phosphorylated ezrin-radixin-moesin (p-ERM) overexpression were found in mice xenografted with HMPOS and OOS cells after 1 week and metastasis was found with decreased p-ERM expression at later time points. The expression of ezrin and p-ERM in the primary tumours of IT-xenografted mice was higher than those in SC-xenografted mice with HMPOS and OOS cells. The results suggest that the orthotopic transplantation site plays an important role in the spontaneous metastasis of canine OS and that ezrin phosphorylation may be involved in the early metastatic mechanism of canine OS cells.

Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR–CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR–CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR–CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.

We produced 23 cloned cell lines from parental CHMp, which was previously established from a canine mammary adenocarcinoma patient in our laboratory. Two representative cloned cell lines, namely, CHMp-5b and -13a, were selected and characterized for cellular morphology, growth potential and expression of some tumour-related proteins. Subsequently, we transplanted the 2 tumour cell lines orthotopically into female nude mice to examine their tumorigenicity and metastatic potential. Interestingly, despite sharing the same origin, only CHMp-5b cells metastasized to the lung. Our results indicate that a comparison between these 2 cell lines at the molecular level will help us understand mechanisms of tumour progression, especially in the context of distant metastases originating from canine mammary gland tumours.

Background Pre-hospitalization medication such as aspirin and nitrates has been shown to affect the mode of presentation in acute coronary syndrome (ACS). However, it is not formally assessed whether other cardiovascular medications may be contributed to the differences in the mode of presentation, especially in relation to coronary risk factors. Methods and results We conducted a registration study of patients (M/F 850/323) with either ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina (UA), and examined the differences in the mode of presentation, pre-hospitalization medication, and coronary risk factors. The ratio of the incidence of STEMI and NSTEMI/UA was significantly reduced in patients having pre-hospitalization medication with aspirin, nitrates or statins, but not with other medications such as beta-blockers in multivariate analysis. Pre-hospitalization medication with aspirin and nitrates was significantly associated with the same reduction of the ratio in patients with male gender, hypertension, diabetes mellitus and a history of coronary artery disease. However, in patients who smoked, were obese and hypercholesterolemic, pre-hospitalization medication with nitrates was significantly associated with the reduced ratio. The ratio was significantly low in patients with males and hypercholesterolemia treated with statins before admission. Conclusion Depending on their coronary risk factors, pre-hospitalization medication with aspirin, nitrates or statins was associated with a different presentation and evolution of ACS.

BACKGROUND For patients with acute myocardial infarction (AMI), several studies have examined the relationship between the metabolic syndrome and prognostic outcome. However, few studies have revealed an association between the metabolic syndrome and clinical outcomes in patients with unstable angina (UA). This study compared the differences in the usefulness of recognizing metabolic disorders for the prediction of a 1-year prognosis in patients with UA and AMI. METHODS The study cohort consisted of 1173 patients with a mean age of 67 years. The focus was on general prognostic factors and five metabolic disorders (body mass index; hypertension; blood glucose/diabetes mellitus; and, serum concentrations of triglycerides and high-density lipoprotein cholesterol) at the time of admission. RESULTS According to multivariate logistic regression analysis, metabolic scores on admission positively related to 1-year mortality or major adverse cardiovascular events (MACE) for patients with UA, but not for those with AMI, with an increase in either all-causes mortality or MACE being associated with the degree of metabolic dysfunction. No other general prognostic factors were related to either 1-year mortality or MACE in patients with UA. By contrast, general prognostic factors such as age and the Killip classification had a positive effect on 1-year mortality or on MACE for the patients with AMI. CONCLUSION Accumulation of the effects of each metabolic disorder may affect mortality and MACE for patients with UA.

SummaryBackground Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A4 (LXA4) and the 15-epimer of LXA4 (15-epi-LXA4) in relation to asthma severity in AIA subjects. Objective The purpose of this study is to estimate urinary LXA4 and the 15-epimer concentrations to investigate lipoxins in AIA. Methods In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA4, 15-epi-LXA4 and leukotriene E4 (LTE4) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography. Results The urinary LXA4 concentration was significantly lower than the 15-epi-LXA4 concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA4 (P

The efficacy of the local application of recombinant human fibroblast growth factor-2 (FGF-2) in periodontal regeneration has been investigated. In this study, a randomized, double-blind, placebo-controlled clinical trial was conducted in 253 adult patients with periodontitis. Modified Widman periodontal surgery was performed, during which 200 µL of the investigational formulation containing 0% (vehicle alone), 0.2%, 0.3%, or 0.4% FGF-2 was administered to 2- or 3-walled vertical bone defects. Each dose of FGF-2 showed significant superiority over vehicle alone (p < 0.01) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the 0.3% FGF-2 group. No significant differences among groups were observed in clinical attachment regained, scoring approximately 2 mm. No clinical safety problems, including an abnormal increase in alveolar bone or ankylosis, were identified. These results strongly suggest that topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.

Our study examined the effects of performing a pointing movement with the left hand on the kinematics of a simultaneous grasping movement executed with the right hand. We were especially interested in the question of whether both movements can be controlled independently or whether interference effects occur. Since previous studies suggested that eye movements may play a crucial role in bimanual movement control, the effects of different fixation strategies were also studied. Human participants were either free to move their eyes (Experiment 1) or they had to fixate (Experiment 2) while doing the task. The results show that bimanual movement control differed fundamentally depending on the fixation condition: if free viewing was allowed, participants tended to perform the task sequentially, as reflected in grasping kinematics by a delayed grip opening and a poor adaptation of the grip to the object properties for the duration of the pointing movement. This behavior was accompanied by a serial fixation of the targets for the pointing and grasping movements. In contrast, when central fixation was required, both movements were performed fast and with no obvious interference effects. The results support the notion that bimanual movement control is moderated by fixation strategies. By default, participants seem to prefer a sequential behavior in which the eyes monitor what the hands are doing. However, when forced to fixate, they do surprisingly well in performing both movements in parallel.

A genome-wide scan for QTL affecting economically important traits in beef production was performed using an F(2) resource family from a Japanese Black x Limousin cross, where 186 F(2) animals were measured for growth, carcass, and meat-quality traits. All family members were genotyped for 313 informative microsatellite markers that spanned 2,382 cM of bovine autosomes. The centromeric region of BTA2 contained significant QTL (i.e., exceeding the genome-wide 5% threshold) for 5 carcass grading traits [LM area, beef marbling standards (BMS) number, luster, quality grade, and firmness), 8 computer image analysis (CIA) traits [LM lean area, ratio of fat area (RFA) to LM area, LM area, RFA to musculus (M.) trapezius area, M. trapezius lean area, M. semispinalis lean area, RFA to M. semispinalis area, and RFA to M. semispinalis capitis area], and 5 meat quality traits (contents of CP, crude fat, moisture, C16:1, and C18:2 of LM). A significant QTL for withers height was detected at 80.3 cM on BTA5. We detected significant QTL for the C14:0 content in backfat and C14:0 and C14:1 content in intermuscular fat around the 62.3 to 71.0 cM region on BTA19 and for C14:0, C14:1, C18:1, and C16:0 content and ratio of total unsaturated fatty acid content to total SFA content in intramuscular fat at 2 different regions on BTA19 (41.1 cM for C14:1 and 62.3 cM for the other 4 traits). Overall, we identified 9 significant QTL regions controlling 27 traits with genome-wide significance of 5%; of these, 22 traits exceeded the 1% genome-wide threshold. Some of the QTL affecting meat quality traits detected in this study might be the same QTL as previously reported. The QTL we identified need to be validated in commercial Japanese Black cattle populations.

Background Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. Methods In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score

Background The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis. Objective The aim was to identify the allergen components useful to diagnose sesame-allergic children with the goal to reduce the number of OFCs needed. Methods Ninety-two sesame-sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application). Results Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826-0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589-0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut-off (3.96 kUA /L) were 86.1% and 85.7%, respectively. Conclusion and clinical relevance Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.

A free-prefabricated auricular composite graft was applied in two patients who underwent extended hemilaryngectomy. Good phonatory and respiratory functions were obtained without any significant aspiration. Although this reconstructive method is a two-staged procedure involving microsurgical techniques, we believe that it provides a good physiologic reconstruction of the larynx and trachea.

The epithelial-mesenchymal transition (EMT) is a crucial event that occurs during cancer metastasis and can be induced by transforming growth factor-β (TGF-β) in various tumor cells in vitro. However, little is known about the effects of TGF-β in canine mammary gland tumors (CMGTs). Here, we investigated the role of TGF-β in CMGT. We observed that treatment of the CMGT cell line CHMp13a with TGF-β1 leads to transient induction of the mesenchymal marker vimentin. Real-time measurements of cellular electrical impedance also showed that CMGT invasiveness is transiently increased by TGF-β1 treatment, but is reversed after prolonged stimulation. This phenomenon is similar to the mesenchymal-epithelial transition (MET, the reverse phenomenon of EMT), and a process that is implicated in the establishment of secondary metastatic lesions.

Stromal cell-derived factor-1 (SDF-1) acts as a chemoattractant for leukocytes and can induce neovascularisation. To examine the role of SDF-1 in the development of angiogenesis, immunohistochemical studies were performed on bronchial biopsy specimens from asthmatic and control subjects. Bronchial biopsy specimens were obtained from 13 asthmatic and eight control subjects. The number of vessels and the percentage area they occupied were estimated after staining for type-IV collagen. In addition the number of SDF-1-positive cells was determined. There was a significant increase in the number of vessels and the percentage vascularity in the submucosa of asthmatic subjects compared with control subjects. Asthmatic subjects exhibited a greater number of SDF-1-positive cells in the airway mucosa than control subjects. The degree of vascularity was associated with the number of SDF-1-positive cells. Furthermore, the number of SDF-1-positive cells was inversely correlated with airway calibre and airway hyperresponsiveness. Colocalisation studies revealed that endothelial cells, macrophages and T-lymphocytes were the major sources of SDF-1. These findings suggest that increased vascularity of bronchial mucosa in asthmatic subjects is closely related to the expression of stromal cell-derived factor-1 positive cells, which may play a role in remodelling of airways via angiogenesis.

A marked depression of swallowing reflex has been found in patients with aspiration pneumonia. We have examined the effects of Banxia Houpo Tang (BHT, Hange Koboku-To in Japanese), on swallowing reflex among the elderly. Thirty-two patients, mean age 74.2 +/- 1.7 years who had at least one episode of aspiration pneumonia, were divided into two groups. Twenty patients took BHT extracts of 7.5 g per day for four weeks, and the other 12 patients took a placebo. The swallowing reflex was measured by a bolus injection of 1 ml of distilled water into the pharynx through a nasal catheter. The reflex was evaluated by the latency time of response, which was the time from the injection to the onset of swallowing. The latency of response decreased significantly from 11.6 +/- 3.0 sec to 2.6 +/- 0.4 sec in the group treated with BHT (p0.01), while in the other group with placebo it was from 11.0 +/- 4.0 to 10.8 +/- 3.6 (p0.5). Depletion of substance P in the pharynx causes impairments of the swallowing reflex. Substance P in the saliva of treated patients increased from 9.2 +/- 2.5 fmol/ml to 15.0 +/- 2.2 fmol/ml after BHT treatment (p0.01), while levels were 8.0 +/- 4.0 fmol/ml before and 7.1 +/- 3.1 fmol/ml after among the placebo group (no significant difference). We suggest that BHT improves the impaired swallowing reflex and may help to prevent aspiration pneumonia in the elderly.

We developed a computer program to perform three-dimensional analysis of the acetabular coverage of the femoral head using two anteroposterior (supine and erect) radiographs of the hip. The center of radiation was marked, and an additional vertical line was placed on radiographs in the neutral standing position, permitting estimation of change in pelvic tilt and its effect on acetabular coverage. We studied 64 normal hip joints, 82 acetabular dysplastic hip joints, and 15 hip joints that had undergone rotational acetabular osteotomy (RAO). In normal hips, the pelvis tilted posteriorly on standing, and the anterior acetabular coverage decreased, but the extent of reduction was not significant. However, in dysplastic hip joints, the pelvic tilt changed from the posterior to anterior direction and from the painful side to the nonpainful side with progression of osteoarthritis. While RAO provided sufficient correction of anterior coverage for acetabular dysplasia, lack of posterior coverage was sometimes observed.

The purpose of this study was to characterize regional blood flow (BF) in untreated cerebral gliomas (CG) using stable Xe-enhanced computed tomography (XeCT). XeCT of 38 patients with untreated CG were analyzed and compared with CT and magnetic resonance images (MRI) and histopathological findings. Individual averaged BF values for tumour in 29 high grade gliomas (HGGs) and 9 low grade gliomas (LGGs) were intermediate between averaged BF values for cortex and white matter in the non-tumour bearing hemisphere. All averaged BF values for cyst and central necrosis were very low. In 27 HGGs, BF in tumour was relatively high in ring-enhancement lesions on CT and MRI, but was low even in viable tumour centers showing no contrast enhancement. In the other 2 HGGs, BF was low in tumour center and relatively high in tumour periphery regardless of homogeneous enhancement. In 5 HGGs, averaged BF value of the cortex outside surrounding oedema was higher than that of cortex in the non-tumour bearing hemisphere. In LGGs, BF distribution in tumour was homogeneously low in 3 small-sized and heterogeneous in 6 large-sized lesions including moderately high and low BF regions. These differences in BF pattern between HGGs and LGGs on XeCT might be helpful in considering to some extent the histopathology of untreated cerebral glioma pre-operatively.

Thrombotic microangiopathy is a well-known heterogeneous disorder that occurs as a complication of allogenic bone marrow transplantation (BMT). We evaluated 12 consecutive patients receiving HLA-matched unrelated BMT and 12 consecutive recipients of HLA-identical related BMT for the development of bone marrow transplantation-associated thrombotic microangiopathy (BMT-TM) on days 30 and 60 following BMT. A diagnosis was made in four of 12 (33.3%) unrelated compared to none of 12 (0%) HLA-identical cases. Levels of serum lactic dehydrogenase (LDH), fibrin degraded products (FDP) and de novo thrombocytopenia were elevated in eight of 12 patients (66.7%) receiving unrelated donor BMT, and none of the patients receiving related donor BMT. Our findings suggest clinical or subclinical microangiopathic changes may occur frequently in unrelated donor BMT. FDP elevation is possibly an important marker of microangiopathic changes as early complications of BMT.

Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma.

In recent years the study of the intrinsic brain dynamics in a relaxed awake state in the absence of any specific/ntask has gained increasing attention, as spontaneous neural activity has been found to be highly structured at a/nlarge scale. This so called resting-state activity has been found to be comprised by nonrandom spatiotemporal/npatterns and fluctuations, and several Resting-State Networks (RSN) have been found in BOLD-fMRI as well as/nin MEG signal power envelope correlations. The underlying anatomical connectivity structure between areas of/nthe brain has been identified as being a key to the observed functional network connectivity, but the mechanisms/nbehind this are still underdetermined. Theoretical large-scale brain models for fMRI data have corroborated the/nimportance of the connectome in shaping network dynamics,while the importance of delays and noise differ between/nstudies and depend on the models' specific dynamics. In the current study, we present a spiking neuron/nnetworkmodel that is able to produce noisy, distributed alpha-oscillations, matching the power peak in the spectrumof/ngroup resting-stateMEG recordings.We studied howwell the model captured the inter-node correlation/nstructure of the alpha-band power envelopes for different delays between brain areas, and found that the model/nperforms best for propagation delays inside the physiological range (5–10 m/s). Delays also shift the transition/nfrom noisy to bursting oscillations to higher global coupling values in the model. Thus, in contrast to the/nasynchronous fMRI state, delays are important to consider in the presence of oscillation. TTN was supported by the SUR of the DEC of the Catalan Government/nand by the FSE. GD was supported by the ERC Advanced Grant:/nDYSTRUCTURE (n. 295129), by the Spanish Research Project SAF2010-/n16085 and by the CONSOLIDER-INGENIO 2010 Programme CSD2007-/n00012, and the FP7-ICT BrainScales. The research reported herein was/nsupported by the Brain Network Recovery Group through the James S./nMcDonnell Foundation.

The obturator hernia sac may follow the anterior or posterior branch of the obturator nerve, and thus, it can be classified anatomically. The relationship between the symptoms and the anatomical classification of obturator hernia has not yet been clearly described in the literature. Multidetector-row computed tomography (MDCT) examinations of 35 consecutive cases of new-onset obturator hernia admitted from March 2005 to April 2012 were reviewed retrospectively. Obturator hernia was classified anatomically using MDCT. Patient characteristics and clinical presentations were compared among the anatomical classifications. Fifteen cases were classified as type I (anterior branch type) and 20 cases as type II (posterior branch type). There were no significant differences regarding time from onset of symptoms to diagnosis, presence of small bowel obstruction, and need for bowel resection. The Howship–Romberg sign was seen in 6 cases (30 %) of type II and 10 cases (67 %) of type I (p = 0.044). The Howship–Romberg sign was present significantly more often with the anterior than the posterior branch type of obturator hernia.

To evaluate the efficacy and complications of transportal ethanol injection (TPEI) combined with transcatheter arterial chemoembolization to achieve complete tumor necrosis and prevent intrahepatic metastases in patients with hepatocellular carcinoma (HCC).In 13 patients with HCC, chemoembolization was performed with injection of a mixture of iodized oil and doxorubicin hydrochloride followed by administration of gelatin sponge; 1-4 weeks later, TPEI was performed with percutaneous transhepatic portography. Ethanol (15-65 mL) was injected in the portal veins around the tumor until occlusion.TPEI was successfully performed in all patients. Two patients subsequently underwent surgery; their tumors were resected completely. Two died of hepatic failure. Seven of the nine other patients showed no recurrence or intrahepatic metastasis during follow-up (7-42 months). Histologic examination, performed in nine patients, showed complete necrosis of tumor and scattered or severe necrosis of surrounding tissues.This treatment has a strong anticancerous effect and is expected to be used in treatment of properly selected patients with HCC.

To assess the accuracy of three-dimensional, Fourier transform, time-of-flight magnetic resonance (MR) angiography in the identification of intracranial aneurysms.MR angiograms of 126 patients (59 male and 67 female patients, aged 12-77 years) with various intracranial vascular lesions were evaluated. Seventy-eight aneurysms, including 60 less than 5 mm in diameter, in 61 patients were depicted at conventional angiography. Eight projection images, as well as one axial collapsed MR angiogram obtained with a maximum-intensity projection algorithm, were used for evaluation.Sensitivity for the five observers ranged from 58% to 68% (mean, 63%). Higher sensitivity was achieved for anterior communicating and middle cerebral artery aneurysms, while that for internal carotid artery aneurysms was poor. Sensitivities for small and medium aneurysms ranged from 50% to 60% (mean, 56%) and from 77% to 94% (mean, 86%), respectively.MR angiography can depict intracranial aneurysms 5 mm or larger with good accuracy but is less useful for the identification of smaller aneurysms.

We report 26 cases of hyperextension injury of the MP joint of the thumb. These were classified into the following three categories; dorsal dislocation of the MP joint or volar plate avulsion; locking of the MP joint and fracture of the sesamoid bone. We report the pathomechanics and clinical features of these injuries.

A clinicopathological study of senile dementia of Alzheimer's type (SDAT) accompanied by the white matter lesions of Binswanger's type was carried out. Fifty-seven patients, who were diagnosed as suffering from SDAT based on clinical and pathological criteria, were classified into two groups based on the white matter lesions of Binswanger's type. Namely, group 1 consisted of the SDAT patients without any subcortical or white matter lesions (30 cases); group 2 consisted of those with white matter lesions of Binswanger's type (11 cases). The other 9 cases included those with vascular lesions and 4 with some of the same pathological changes found in Parkinson's disease. Clinically, group 2 patients showed subcortical symptoms such as urinary incontinence, Parkinsonian gait, being accompanied by hypertension and arrhythmias. Periventricular lucency (CT) were common in group 2. Macroscopically, both groups showed moderately to severe atrophy, and the width of the corpus callosum of group 2 was narrower than that of group 1. There was no difference in cerebral arteriosclerosis between the groups. In microscopic findings, patients in group 2 showed diffuse distribution of cortical changes such as senile plaques as well as Alzheimer's senile plaques as well as Alzheimer's neurofibrillary tangles while those in group 1 showed various types of diffuse or local distribution. Arteriolosclerosis of the white matter were found in both groups. There was no difference in aortic atherosclerosis and/or heart disease. The complication of white matter lesions of Binswanger's type was not a rare finding in SDAT.

Crigler-Najjar syndrome (CN) type II is characterized by severe chronic nonhemolytic unconjugated hyperbilirubinemia due to reduced hepatic bilirubin UDP-glucuronosyl-transferase (UGT) activity. Two bilirubin UGT isozymes, UGT1A and UGT1D, have been identified. We analyzed the DNA sequence of the bilirubin UGT genes in a 5-year-old Japanese male patient with CN type II, who had consanguineous parents. Point mutations were found on exons 1 of the UGT1A and UGT1D genes. The abnormalities were single nucleotide substitutions of G by A and of T by C at base position 211 of UGT1A cDNA and at base position 395 of the UGT1D, respectively. We found another single nucleotide substitution of T by G on exon 5 common to both genes at base position 1456 of the UGT1A cDNA or 1459 of the UGT1D cDNA. These three mutations result in changes of glycine to arginine and of tyrosine to aspartic acid at amino acid positions 71 and 486 of the UGT1A protein, and of leucine to proline and of tyrosine to aspartic acid at amino acid positions 132 and 487 of the UGT1D protein, respectively. Our patient was homozygous for all defects and his parents and elder brother were heterozygous for all defective alleles. The findings suggest that the CN Type II is inherited as an autosomal recessive trait.

One way of obtaining an enhanced production of specific antibodies against given antigens is to maximize the level of antigen presentation through artificially augmented antigen uptake by antigen presenting cells (APCs). In this respect, it has been shown that the receptor mediated endocytosis of antigens can be a very effective way to achieve this purpose. Such a process should also enhance the weak immunogenicity of synthetic peptides produced as artificial vaccines with amino acid sequences resembling those of epitopic sites of pathogens. In this report we used alpha 2 -macroglobulin (a 2 M) which has specific receptors on macrophages (MFs) as a delivery protein and were able to induce high concentrations of antibodies against an HIV-1 derived synthetic peptide in mice. a 2 M enhanced immunogenicity of the peptide better than Freund′s adjuvant did. We should be able to develop effective peptide vaccines by further improving this system.

Gasless laparoscopic surgery using the abdominal wall lifting (AWL) method was first developed in Japan and has been used in various surgical fields. The AWL method allows the use of conventional reusable surgical instruments. The purpose of this study was to compare the cost-effectiveness of laparoscopic cholecystectomy (LSC) using the AWL method in relation to that using pneumoperitoneum (P) method.Retrospective analysis of 431 LSC procedures between 1991 and 2004 was performed. The two surgical groups consisted of consecutively operated patients with a diagnosis of cholecystolithiasis or gallbladder polyps. One group consisted of 224 LSC procedures performed using the P method from 1992 to 1998 and the other group comprised 207 LSC performed using the AWL method from 1998 to 2004. All instruments used in the P method were disposable, whereas trocars, scissors, dissectors, graspers and L-hook electrodes (excluding clips) used in the AWL method were reusable. Hospital expenses, length of hospital admission and complication rates were analyzed.Mean hospital cost per case for LSC using the AWL method (dollars 6743) was 7% less expensive than that using the P method (dolars 7215). Costs of operative equipment contributed to the difference (mean dollars 912 per case) in total cost. Conversion to open cholecystectomy occurred in 6 cases (2.9%) using the AWL method and 7 cases (3.1%) using the P method. There were no significant differences in length of hospital admission or complication rates between the two groups.LSC using AWL method was less expensive than that using P method. This is mainly due to the use of reusable instruments in the AWL method. If LSC is performed using the AWL method instead of using disposable equipment, considerable savings can be achieved without compromising patient safety.

A 65-year-old female with a heart murmur developed progressive symptom of chest oppression. She was diagnosed severe aortic valve stenosis with echocardiogram. Antibody screening revealed anti-Jr(a) antibody. Preoperatively, erythropoietin was administered. Over 14 days, a total 1,000 ml of her blood was drawn and stored for autologous transfusion. The aortic valve was replaced with ATS mechanical valve [18 mm advanced performance (AP)]. Following surgery, her stored blood was administered to him. But her HCT was 17% on the 1st postoperative day. Frozen thawed red cells were transferred 7th postoperative day.

We compared the efficacy of ACD-CPR and STD-CPR based on 64 multi-institutional reports. No significant differences were observed in the rate of restoration of spontaneous circulation (ROSC) and in cardiopulmonary parameters during CPR using the two methods. There were 5 cases in which cardiopulmonary parameters improved after switching from STD-CPR to ACD-CPR and, eventually, in two of them spontaneous circulation was restored. In the ROSC cases of both groups, ETCO2 and values of SpO2, PaO2, and systolic BP at 30 minutes were higher than those of non-ROSC cases. ETCO2 never exceeded 20 mmHg in the non-ROSC cases, but it was higher in the ROSC cases. ACD-CPR is a good choice when trained persons are present or when extra hands are available to continue the CPR.

A 56-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT2N2M0, stage III A). She received one course of a combination of etoposide and cisplatin as adjuvant therapy, followed by oral intake of UFT. In November 1999, a left para-aortic lymph node recurrence was found. She received radiation therapy (total 60 Gy) to the mediastinum. In April 2000, new lung and left supraclavicular lymph node recurrences were found. She received three courses of vinorelbine 20 mg/m2 (days 1, 8) and cisplatin 80 mg/m2 (day 1) followed by radiation therapy (total 50.4 Gy) to the left supraclavicular lesion. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved. Adverse reactions were grade 1 alopecia, grade 2 nausea/vomiting, grade 3 neutropenia, hypochromia, and injection site reaction. The combination of vinorelbine and cisplatin is a useful regimen in non-small-cell lung cancer.

A 50-year-old female underwent mastectomy for left breast cancer in June, 1991. She received tamoxifen for 36 months and tegafur for 30 months as adjuvant therapy. In November 1997, liver, lung and para-aortic lymph node recurrences were found, and we treated her six times with docetaxel 60 mg. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved and her serum CA15-3 level was decreased. Adverse reactions were grade 4 neutropenia, grade 2 alopecia, fever, and grade 1 edema. She received medroxyprogesterone acetate after the chemotherapy and has been well without re-growth of any metastases for over eight months.