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Research Interests: Kinetics, Cancer, Apoptosis, Cell line, In Vitro, and 17 moreHumans, Sequence alignment, Female, Mechanism, Galectin, Cisplatin, Apoptose, Breast carcinoma, Biological activity, Amino Acid Sequence, Gene Family, Protein Binding, Cell Survival, Tumor Progression, DNA fragmentation, Molecular Sequence Data, and Breast Neoplasms
Stria vascularis of the mammalian cochlea transports K(+) to establish the electrochemical property in the endolymph crucial for hearing. This epithelial tissue also transports various small molecules. To clarify the profile of proteins... more
Stria vascularis of the mammalian cochlea transports K(+) to establish the electrochemical property in the endolymph crucial for hearing. This epithelial tissue also transports various small molecules. To clarify the profile of proteins participating in the transport system in the stria vascularis, membrane components purified from the stria of adult rats were analysed by liquid chromatography tandem mass spectrometry. Of the 3236 proteins detected in the analysis, 1807 were membrane proteins. Ingenuity Knowledge Base and literature data identified 513 proteins as being expressed on the 'plasma membrane', these included 25 ion channels and 79 transporters. Sixteen of the former and 62 of the latter had not yet been identified in the stria. Unexpectedly, many Cl(-) and Ca(2+) transport systems were found, suggesting that the dynamics of these ions play multiple roles. Several transporters for organic substances were also detected. Network analysis demonstrated that a few kina...
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Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown. We analyzed... more
Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown. We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16(+)CD56(+) cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells. We found that I...
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Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder. However, BPPV in children has been studied less extensively than in the adult population. This is because the observation of benign paroxysmal positional... more
Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder. However, BPPV in children has been studied less extensively than in the adult population. This is because the observation of benign paroxysmal positional nystagmus (BPPN) in children is technically very difficult and BPPV is rare in children. In this study, we present the only two cases of BPPV in children in which we successfully recorded and analyzed the BPPN. One case was an 11-year-old boy and the other was a 3-year-old girl. We analyzed their BPPN three-dimensionally. Apogeotropic positional nystagmus was observed in the first case. We analyzed it to verify the presence of cupulolithiasis in the horizontal semicircular canal (HSCC). Geotropic positional nystagmus was observed in the second case, and the analyzed data indicated the presence of canalolithiasis in HSCC. Over the last decade, we have examined 3341 patients complaining of vertigo or dizziness. Among them, there were 63 children with ...
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Renal cell carcinoma (RCC) tends to metastasize hematogenously, although metastasis to the head and neck is rare. We report 3 cases of RCC head and neck metastasis within the last 6 years. CASE 1: A 74-yearold woman presented with... more
Renal cell carcinoma (RCC) tends to metastasize hematogenously, although metastasis to the head and neck is rare. We report 3 cases of RCC head and neck metastasis within the last 6 years. CASE 1: A 74-yearold woman presented with cervical metastasis from RCC 4 years after right total nephrectomy, involving modified neck dissection. She later had additional surgery and radiation for further distant metastases, survived almost 5 years after the first neck metastasis. CASE 2: A 60-year-old man showed metastatic RCC in the right parotid gland 3 years after right total nephrectomy, involving superficial parotidectomy. CASE 3: A 54-year-old man presented with a metastasis lesion from RCC to the right maxillary sinus 7 years after left total nephrectomy, involving total maxillectomy. Distant metastasis reportedly often occurs long after initial primary RCC treatment. Physicians considering metastatic RCC in differential head and neck diagnosis and resection could conceivably promote bette...
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IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Its close relation with the tonsils is well known because tonsillitis sometimes causes aggravation of urinary findings or macrohematuria. However, the genes specific to... more
IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Its close relation with the tonsils is well known because tonsillitis sometimes causes aggravation of urinary findings or macrohematuria. However, the genes specific to the tonsils of IgAN patients are not clarified. To clarify the specific gene expression in the tonsils of IgAN patients, we performed tonsillectomy and corticosteroid IV therapy as a treatment of IgAN, analyzed the gene expression in the tonsils by microarray and compared it with that in tonsils from chronic tonsillitis patients. The upregulated genes seem to be categorized into two groups: muscle-related genes and immunerelated genes. The downregulated genes include the polymeric Ig receptor (pIgR) which was reportedly involved in single nucleotide polymorphism (SNP) of Japanese IgAN patients.
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Concurrent chemoradiotherapy (CCRT) is increasingly used in organ preservation for head and neck squamous cell carcinoma (HNSCC), with surgery as second-line treatment for salvaging locoregional failure. The significance of post-CCRT... more
Concurrent chemoradiotherapy (CCRT) is increasingly used in organ preservation for head and neck squamous cell carcinoma (HNSCC), with surgery as second-line treatment for salvaging locoregional failure. The significance of post-CCRT salvage surgery, however, remains to be established. We report complications and clinical outcome in 34 salvage surgeries on 30 subjects with advanced HNSCC treated by docetaxel and cisplatin concurrent with conventional radiotherapy. Postoperative complications occurred in 9 (30%) subjects and 10 (29%) surgeries. There was no significant difference in complication incidence between salvage surgeries for persistent disease (7 of 19 cases, 37%) and those for recurrent disease (3 of 15 cases, 20%). Complication incidence in isolated neck dissection (6 of 21 cases, 29%) did not differ significantly from that in primary site resection (4 of 13 cases, 31%). Most frequent complications were dysphagia and skin flap necrosis, occurring in 5 subjects each. Three...
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Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits... more
Galectin-3, a beta-galactoside-binding protein, has been shown to be involved in tumor progression and metastasis. Here, we demonstrate that expression of galectin-3 in human breast carcinoma BT549 cells inhibits cis-diamminedichloroplatinum (cisplatin)-induced poly(ADP-ribose) polymerase degradation and apoptosis, without altering Bcl-2, Bcl-X(L), or Bax expressions. Galectin-3 contains the NWGR amino acid sequence highly conserved in the BH1 domain of the bcl-2 gene family, and a substitution of glycine to alanine in this motif abrogated its antiapoptotic activity. Our findings demonstrate that galectin-3 inhibits apoptosis through a cysteine protease pathway and highlight the functional significance of the NWGR motif in apoptosis resistance of a non-Bcl-2 protein.
Research Interests: Kinetics, Cancer, Apoptosis, Cell line, In Vitro, and 17 moreHumans, Sequence alignment, Female, Mechanism, Galectin, Cisplatin, Apoptose, Breast carcinoma, Biological activity, Amino Acid Sequence, Gene Family, Protein Binding, Cell Survival, Tumor Progression, DNA fragmentation, Molecular Sequence Data, and Breast Neoplasms
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Research Interests: Neuroscience, Psychology, Animal Behavior, Behavior, real time PCR, and 22 moreTinnitus, Transient receptor potential channels, Animals, Male, Ct, Behavior Modeling, Animal Model, Capsaicin, Rats, Time Factors, Rat, Molecular Marker, Western blot, Wistar Rats, Biological markers, ABR, Sound Pressure Level, Neurosciences, Salicylates, Spiral Ganglion, Neuropsychological Tests, and False Positive
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... 1). She did not have any past history of malabsorption. There was no family history of rickets or hypophos-phatemia, either. ... Al-though urinary cAMP excretion has been studied in only a minority of such patients, Shane et al. [2]... more
... 1). She did not have any past history of malabsorption. There was no family history of rickets or hypophos-phatemia, either. ... Al-though urinary cAMP excretion has been studied in only a minority of such patients, Shane et al. [2] and Leicht et al. ...
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Research Interests:
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Research Interests: Cell Division, Humans, Mice, Female, Animals, and 4 moreMale, T lymphocytes, Genotype, and B Lymphocytes
Recently, combination of tonsillectomy and steroid pulse therapy was reported to be effective as the treatment of the immunoglobulin A nephropathy (IgAN). However, the gene expression difference between the tonsils in patients with IgAN... more
Recently, combination of tonsillectomy and steroid pulse therapy was reported to be effective as the treatment of the immunoglobulin A nephropathy (IgAN). However, the gene expression difference between the tonsils in patients with IgAN and those in control patients is not established. We performed tonsillectomy combined with steroid pulse as a treatment to IgAN, analyzed the gene expression in the tonsils (N=23) using microarray, compared with those with patients suffering from chronic tonsillitis (N=22). From some candidate genes related with IgAN, we confirmed the apolipoprotein B messenger RNA-editing enzyme catalytic polypeptides 2 (APOBEC2) gene expression in the tonsil and we also analyzed its expression levels and clinical features. Up-regulated genes seem to be categorized into two groups. One group belongs to the muscle related genes which might be caused by structural differences. The other group includes the immune system-related genes, such as APOBEC2, CALB2, DUSP27, and CXCL11. APOBEC2 was positively stained in the epithelium and the peripheral region of the germinal center in both tonsils. APOBEC2 expression level was negatively related with serum igg level, but did not correlate with clinical course after tonsillectomy. We confirmed gene expression differences related with immune system and muscle structure. The APOBEC2 was confirmed to be elevated in the tonsils with IgAN patients, and the gene expression level was negatively related with serum igg level in overall patients. These results might be helpful to reveal the mechanism of IgAN.
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Research Interests:
Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital... more
Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.
Research Interests: Magnetic Resonance Imaging, Endoscopy, Head and Neck, Humans, Male, and 10 moreSquamous Cell Carcinoma, Follow-up studies, Clinical Sciences, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Malignant Lymphoma, Diffuse Large B-Cell Lymphoma, Disease Progression, Lymph Node, and X ray Computed Tomography
Endoscopic examination of the upper gastro-intestinal tract with Lugol's solution staining was performed on 150 patients with head and neck cancer treated at the Departments of Otolaryngology and Radiology, Osaka University... more
Endoscopic examination of the upper gastro-intestinal tract with Lugol's solution staining was performed on 150 patients with head and neck cancer treated at the Departments of Otolaryngology and Radiology, Osaka University Hospital, between June 1987 and December 1991. Thirteen second primary cancers (11 esophageal and 2 gastric cancers) were found endoscopically, although prior fluoroscopy had found only 4 (3 esophageal and one gastric cancer). All of the 9 second primary cancers which were not detected by fluoroscopy were in the early stage. Both Brinkman's and Alcohol indices of double primary cancer cases were significantly higher than those of single head and neck cancer cases. These results indicate that head and neck cancer patients who smoke and/or drink heavily require thorough examination of their upper gastro-intestinal tract with endoscopy, using Lugol's solution staining, as well as with fluoroscopy.
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Fine-needle aspiration cytology (FNAC) is the diagnostic modality of first choice for characterization of parotid mass lesions, while magnetic resonance imaging (MRI) should not be requested routinely. MRI can be reserved until FNAC shows... more
Fine-needle aspiration cytology (FNAC) is the diagnostic modality of first choice for characterization of parotid mass lesions, while magnetic resonance imaging (MRI) should not be requested routinely. MRI can be reserved until FNAC shows the indication for surgical intervention. Although both FNAC and MRI are useful preoperative diagnostic modalities for parotid mass lesions, it is not well established which modality is more effective. In the present study we sought to address the relative value of FNAC and MRI in relation to the differential diagnosis of benign and malignant parotid mass lesions. Eighty-one patients with parotid mass lesions (60 benign and 21 malignant) who had preoperatively undergone FNAC and MRI were reviewed retrospectively. Unsharp margin and infiltration into adjacent tissues on MRI significantly correlated with a malignant histology. The sensitivity/specificity/accuracy of FNAC and MRI were 90%/95%/94% and 81%/92%/89%, respectively. Either FNAC or MRI served equally to predict the malignant nature of parotid mass lesions. Furthermore, the combination of FNAC and MRI yielded no diagnostic advantage over either modality alone. Accurate histological typing rates by FNAC were 80% and 62% for benign and malignant lesions, respectively.
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To establish a system of differential diagnosis for vertigo/dizziness at the Emergency Department (ED), careful history-taking of complications and examinations of nystagmus should be helpful and therefore prepared by ED staff.... more
To establish a system of differential diagnosis for vertigo/dizziness at the Emergency Department (ED), careful history-taking of complications and examinations of nystagmus should be helpful and therefore prepared by ED staff. Vertigo/dizziness could come from various kinds of organs for equilibrium, sometimes resulting in an emergency due to the central origin. In the present study, we checked patients' background data at the ED in advance of a definitive diagnosis at the Department of Otolaryngology and examined the significance of the correlation between the data and the diagnosis. We studied a series of 120 patients with vertigo/dizziness, who visited the Departments of Emergency and Otolaryngology between April 2011 and March 2012. At the ED, we first checked patients' backgrounds and carried out neurologic and neuro-otologic examinations. At the Department of Otolaryngology, we finally diagnosed all the patients according to the criteria and classified the origins of vertigo/dizziness into central and non-central diseases. The ratio of patients with disease of central origin was 12.5% and that for non-central origin was 87.5%. The risk factors for cerebrovascular disease such as hypertension, heart disease, and diabetes were also the risk factors for central vertigo/dizziness by the chi-squared test. To predict a central origin for vertigo/dizziness, only gaze nystagmus was the significant factor by multivariate regression analysis.
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Research Interests:
Galectin-3, a beta-galactoside-binding protein, is highly expressed in thyroid papillary carcinomas, while functional relevance of galectin-3 overexpression to the malignant phenotype remains elusive. In the present study we transfected... more
Galectin-3, a beta-galactoside-binding protein, is highly expressed in thyroid papillary carcinomas, while functional relevance of galectin-3 overexpression to the malignant phenotype remains elusive. In the present study we transfected galectin-3 antisense cDNA into the human thyroid papillary carcinoma cell line NPA which expresses an innately high level of galectin-3, and examined the effect of antisense inhibition of galectin-3 expression on the transformed phenotype. There was no difference in anchorage-dependent growth between the antisense clones and either the control or parental clones. In contrast, anchorage-independent growth and saturation density of the antisense clones were significantly suppressed compared to those of either the control or parental clones. These results demonstrate that overexpression of galectin-3 in thyroid papillary carcinoma cells is necessary for the maintenance of transformed phenotype, and suggest galectin-3 as a potential target for therapeutic interventions in the future.
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Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and... more
Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor-κB ligand (RANKL) which, in some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro co-culture system composed of keratinocytes, fibroblasts and osteoclast precursors was used to demon...
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When a participant is rotated while displaced from the axis of rotation (eccentric rotation, ER), both rotational stimulation and linear acceleration are applied to the participant. As linear acceleration stimulates the otolith, the... more
When a participant is rotated while displaced from the axis of rotation (eccentric rotation, ER), both rotational stimulation and linear acceleration are applied to the participant. As linear acceleration stimulates the otolith, the vestibulo-ocular reflex (VOR) caused by the otolith (linear VOR; lVOR) would be induced during ER. Ten participants were rotated sinusoidally at a maximum angular velocity of 50°/s and at frequencies of 0.1, 0.3, 0.5, and 0.7Hz. The radius of rotation during ER was 90cm. The participants sat on a chair at three different positions: on the axis (center rotation, CR), at 90cm backward from the axis (nose-in ER, NI-ER) and at 90cm forward from the axis (nose-out ER, NO-ER). Their eye movements during rotation were recorded and analyzed three-dimensionally. The VOR gain during NI-ER was lower at 0.5 and 0.7Hz, and that during NO-ER was higher at 0.3, 0.5, and 0.7Hz than during CR. These results indicate that lVOR actually worked at 0.5 and 0.7Hz during ER an...
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Research Interests:
Leucine-rich α2-glycoprotein (LRG) is an approximately 50-kDa glycoprotein that has been found to be elevated in the sera of patients with several types of cancer. LRG directly binds to transforming growth factor beta 1 (TGFβ1) and... more
Leucine-rich α2-glycoprotein (LRG) is an approximately 50-kDa glycoprotein that has been found to be elevated in the sera of patients with several types of cancer. LRG directly binds to transforming growth factor beta 1 (TGFβ1) and modulates TGFβ1 signaling in endothelial cells; however, the precise function of LRG in cancer remains unclear. This study aimed to investigate the role of LRG in cancer. Lewis lung carcinoma (LLC) cells hardly expressed LRG. The growth of LLC tumors allografted in the LRG knockout (KO) mice was significantly increased compared with wild-type (WT) mice. Conversely, overexpression of LRG significantly inhibited the growth of LLC tumors in WT mice. In the presence of LRG, TGFβ1 significantly inhibited the proliferation of LLC cells and human hepatocellular carcinoma Hep3B cells in vitro by inducing apoptosis via the potent activation of smad2 and its downstream signaling pathway. Furthermore, administration of a TGFβR1 inhibitor (SB431542) significantly enhanced the growth of LLC tumors in WT mice compared with LRG KO mice via inhibition of apoptosis. We propose that LRG potentiates the effect of TGFβ1 in cancer cells whose growth is suppressed in the presence of TGFβ1.
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A 62-year-old male with cT4bN2cM0 hypopharyngeal carcinoma with ipsilateral vocal cord fixation was initially treated with concurrent chemoradiotherapy. Since the patient complained of dysphagia caused by mucositis, a nasogastric tube was... more
A 62-year-old male with cT4bN2cM0 hypopharyngeal carcinoma with ipsilateral vocal cord fixation was initially treated with concurrent chemoradiotherapy. Since the patient complained of dysphagia caused by mucositis, a nasogastric tube was placed on the day of irradiation with a dose of 20 Gy. Bilateral vocal cord fixation and laryngeal necrosis became evident 3 weeks after the concurrent chemoradiotherapy. He underwent a total pharyngolaryngectomy (neck dissection, and reconstruction with a free jejunal graft) followed by adjuvant chemotherapy. It is highly suspected that the nasogastric tube compressed the mucosa of the post cricoid region, resulting in laryngeal necrosis.
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Research Interests:
Selective inbreeding of C.B17-scid/scid mouse pairs showing undetectable IgG and IgM has been carried out in order to reduce the mortality of mice by early occurrence of thymic lymphocytic leukemia and abnormal lymphocyte clones producing... more
Selective inbreeding of C.B17-scid/scid mouse pairs showing undetectable IgG and IgM has been carried out in order to reduce the mortality of mice by early occurrence of thymic lymphocytic leukemia and abnormal lymphocyte clones producing immunoglobulins, both of which inhibit the successful heterotransplantation of normal and neoplastic human tissues. Although the majority of C.B17-scid/scid mice showed undetectable (< 1 microgram/ml) or low level (< or = 25 micrograms/ml) of serum IgG and IgM, some produced abnormally high concentrations of IgG and IgM (> 25 micrograms/ml). The incidence of such mice showing higher levels of IgG was very high at F1 and F2 generation (10/55, 18.2%), but significantly low after the F3 generation (18/446, 4.0%, p < 0.001). Although leukemia incidence was very high at F4 to F5 generations (8/40, 20.0%), death from leukemia was not observed early in life (4-6 months after birth) at F7 to F10 generations (0/36, 0%, p < 0.01) and was very low during the age of 6-10 months after the F8 generation (11/66, 16.7% at F4 and F5 vs 4/93, 4.3% at F8-10), p < 0.01). Scid mice improved by the selective inbreeding will provide an invaluable experimental system for the heterotransplantation of normal and neoplastic human tissues.
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Chemotherapy-related death can occur, but is rarely experienced in the case of head and neck cancer. In this report, we present the case of a 55-year-old male who died of a severe febrile neutropenia during adjuvant chemotherapy. He was... more
Chemotherapy-related death can occur, but is rarely experienced in the case of head and neck cancer. In this report, we present the case of a 55-year-old male who died of a severe febrile neutropenia during adjuvant chemotherapy. He was initially diagnosed as having nasopharyngeal carcinoma (cT2N0M0), and concurrent chemoradiotherapy was used as a primary treatment. He did not show any critical side effects during that therapy. After residual disease was proven by biopsy, docetaxel, cisplatin and 5-fluorouracil (TPF) therapy was introduced as adjuvant chemotherapy. The patient developed a high fever with a decreased neutrophil count on day 8, and went into a state of shock on day 9. He underwent immediate systemic management, but methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and enteritis were uncontrolled, resulting in death on day 43. The autopsy findings suggested that the main cause of death was acute respiratory distress syndrome (ARDS), but cytomegalovirus (CMV)...