PubMed | Kariya Toyota General Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Nishimino Kosei Hospital, Kasukabe Municipal Hospital and 9 more.
Type: Journal Article | Journal: Oncology reports | Year: 2014
Although 5-fluorouracil (5-FU) is an important drug for colorectal cancer (CRC) treatment, no useful biomarker is currently available to predict treatment response. Since 5-FU is converted into active or inactive forms by orotate phosphoribosyltransferase (OPRT) or dihydropyrimidine dehydrogenase (DPD), a correlation between these enzymes and response to 5-FU has been suggested. However, such a correlation has not been investigated prospectively. Therefore, in the present study, we aimed to prospectively evaluate whether OPRT and DPD were predictive factors of the response to 5-FU treatment in patients with resectable CRC. The present investigation was designed as a multicenter prospective cohort study. OPRT and DPD activities were assessed in biopsy samples, obtained surgically from patients with resectable CRC. The OPRT/DPD ratio was calculated and the cut-off values for this ratio were determined for 5-year disease-free survival (DFS) and overall survival (OS). Patients were treated with 5-FU/leucovorin(LV) regimens and oral 5-FU. The endpoint of this study was the correlation between the OPRT/DPD ratio and 5-year DFS and OS. The cut-off value for the OPRT/DPD ratio was determined by using the maximum 2 statistic method against 5-year DFS and OS. Sixty-eight patients were enrolled from July 2003 to May 2005. The median follow-up period was 1925 days. The OPRT/DPD ratio cut-off values for 5-year DFS and OS were 0.015 and 0.013, respectively. During the 5-year DFS and OS periods, patients with higher cut-off values had a better prognosis than those with lower ratios (P=0.03 and 0.02, respectively). In conclusion, our results suggest that the OPRT/DPD ratio could be a predictive factor for response to 5-FU/LV adjuvant chemotherapy.
Inoue K.,Saitama Cancer Center |
Saito T.,Red Cross |
Okubo K.,Toda Central General Hospital |
Kimizuka K.,Kasukabe Municipal Hospital |
And 6 more authors.
Breast Cancer Research and Treatment | Year: 2016
No clinical evidence on the efficacy and safety of eribulin monotherapy has been obtained by a prospective clinical study in patients with metastatic breast cancer (MBC) who had well-defined taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to obtain the evidence. Japanese female patients, aged 33–74 years who had the metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) ≥24 weeks]. A total of 51 patients underwent chemotherapy cycles (median 4; range 1–42 cycles). The CBR was 39.2 % (CR 2.0 %; PR 23.5 %; and LSD 13.7 %), and the rate of progressive disease was 49.0 %. The median progression-free survival and the median overall survival were 3.6 months [95 % confidence interval (CI) 2.6–4.6 months] and 11.7 months (95 % CI 9.2–14.2 months), respectively. Grade 3 or greater adverse events were leukopenia (23.5 %), neutropenia (35.3 %), anemia (5.9 %), and febrile neutropenia (7.8 %). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0 and 0 %, respectively. Eribulin showed a clinically manageable tolerability profile by dose adjustments or symptomatic treatment. Eribulin was effective and well tolerated in heavily pretreated patients with MBC who had well-defined taxane resistance, thus providing a potential therapeutic option in the clinical settings. © 2016 The Author(s)
PubMed | Red Cross, Shintoshin Ladies Mammo Clinic, Saitama Medical Center, Kasukabe Municipal Hospital and 5 more.
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016
No clinical evidence on the efficacy and safety of eribulin monotherapy has been obtained by a prospective clinical study in patients with metastatic breast cancer (MBC) who had well-defined taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to obtain the evidence. Japanese female patients, aged 33-74years who had the metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4mg/m(2) (equivalent to eribulin 1.23mg/m(2) [expressed as free base]) as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) 24weeks]. A total of 51 patients underwent chemotherapy cycles (median 4; range 1-42 cycles). The CBR was 39.2% (CR 2.0%; PR 23.5%; and LSD 13.7%), and the rate of progressive disease was 49.0%. The median progression-free survival and the median overall survival were 3.6months [95% confidence interval (CI) 2.6-4.6months] and 11.7months (95% CI 9.2-14.2months), respectively. Grade 3 or greater adverse events were leukopenia (23.5%), neutropenia (35.3%), anemia (5.9%), and febrile neutropenia (7.8%). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0 and 0%, respectively. Eribulin showed a clinically manageable tolerability profile by dose adjustments or symptomatic treatment. Eribulin was effective and well tolerated in heavily pretreated patients with MBC who had well-defined taxane resistance, thus providing a potential therapeutic option in the clinical settings.
Tokumaru A.,Kasukabe Municipal Hospital |
Tsutsumi T.,Dokkyo Medical University
Equilibrium Research | Year: 2010
The effect on the vestibulo-ocular reflex (VOR) is evaluated by using a caloric stimulation in which the ears of subjects in the supine position are irrigated with water or air. Studies on the clinical application of caloric stimulation have shown that the stimulation results in a gentle rise of VOR response, which does not precisely reveal the time course of VOR onset. In our study, 14 healthy subjects were evaluated with a step stimulus technique, which showed the onset and offset of caloric stimulation with a rapid change of the position of the subject's head during continuous irrigation of his or her ear. The technique showed a rapid rise (indicating an activation) and consequent gentle attenuation (indicating a compensation) of VOR response. On-step (from sitting to supine position) and off-step (the opposing maneuver) stimulation delivered the same characteristics of this rise and attenuation with opposing direction, through the ampulo-petal and ampulo-fugal convection along their lateral semi-circular canals respectively. Repeated ipsi-lateral stimulation with an interval of 4 minutes caused an increased adaptation of VOR during the on-step response. Some possible reasons for these results might be the occurrence of a central adaptation of VOR or a mechanism involving the peripheral vestibular apparatus such as depletion of the synaptic transmitting substance. Step stimulus of one side did not demonstrate any contribution to subsequent contra-lateral stimulation with the same 4-minute interval. This finding supports the idea that the peripheral vestibular system contributes to the adaptation of VOR. Introducing this step stimulus technique into the clinical examination setting would facilitate the elucidation of the pathophysiological basis of vestibular deficits.
Ishizawa M.,Nihon University |
Ogura M.,Nihon University |
Ogura M.,Kasukabe Municipal Hospital |
Kato S.,University of Tokyo |
Makishima M.,Nihon University
PLoS ONE | Year: 2012
The vitamin D receptor (VDR) mediates the physiological and pharmacological actions of 1α,25-dihydroxyvitamin D3 in bone and calcium metabolism, cellular growth and differentiation, and immunity. VDR also responds to secondary bile acids and belongs to the NR1I subfamily of the nuclear receptor superfamily, which regulates expression of xenobiotic metabolism genes. When compared to knockout mouse investigations of the other NR1I nuclear receptors, pregnane X receptor and constitutive androstane receptor, an understanding of the role of VDR in xenobiotic metabolism remains limited. We examined the effect of VDR deletion in a mouse model of cholestasis. We performed bile duct ligation (BDL) on VDR-null mice and compared blood biochemistry, mRNA expression of genes involved in bile acid and bilirubin metabolism, cytokine production, and expression of inflammatory regulators with those of wild-type mice. VDR-null mice had elevated plasma conjugated bilirubin levels three days after BDL compared with wild-type mice. Urine bilirubin levels and renal mRNA and/or protein expression of multidrug resistance-associated proteins 2 and 4 were decreased in VDR-null mice, suggesting impaired excretion of conjugated bilirubin into urine. While VDR-null kidney showed mRNA expression of interleukin-6 (IL-6) after BDL and VDR-null macrophages had higher IL-6 protein levels after lipopolysaccharide stimulation, the induction of intestinal Il6 mRNA expression and plasma IL-6 protein levels after BDL was impaired in VDR-null mice. Immunoblotting analysis showed that expression of an immune regulator, IκBα, was elevated in the jejunum of VDR-null mice, a possible mechanism for the attenuated induction of Il6 expression in the intestine after BDL. Increased expression of IκBα may be a consequence of compensatory mechanisms for VDR deletion. These results reveal a role of VDR in bilirubin clearance during cholestasis. VDR is also suggested to contribute to tissue-selective immune regulation. © 2012 Ishizawa et al.
Fukushima M.,Kasukabe Municipal Hospital |
Fukushima M.,Nihon University |
Katagiri A.,Nihon University |
Mori T.,Nihon University |
And 2 more authors.
Neurological Surgery | Year: 2010
It has occasionally been reported that mechanical trauma and posttraumatic inflammation may promote metastasis from a primary tumor to the site of the trauma. However, the etiologies that contribute to the metastasis formation at the trauma site remain unknown. We describe here the first case of skull metastasis from hepatocellular carcinoma (HCC) revealing a growing subcutaneous mass at the site of skull fracture. A 58-year-old man had undergone surgical resection of a primary tumor in the liver 2 years previously and was in clinical remission. The patient fell head first off his bicycle and suffered a skull fracture in the squamous portion of the left temporal bone without ostelysis. Three months after the head trauma, he presented at our department with a growing lump on the left side of his head, and magnetic resonance (MR) imaging revealed an osteolytic tumor extending into the adjacent subcutaneous and epidural space. The tumor was at the same location as the skull fracture sustained in the bicycle accident. The mass lesion was radically resected with surrounding normal bone. The tumor formed a well-demarcated mass with osteolysis of the inner and outer skull tables, and the inner layer of the dura mater was intact. The histological diagnosis for the surgical specimen from the skull tumor was a HCC identical to the primary tumor. Immunohistochemically, the tumor cells were diffusely and strongly positive for vascular endothelial growth factor (VEGB and basic fibrous growth factor (bFGF). It is well known that the extracellular matrix and cytokines are involved in the processes of not only bone healing but also metastasis formation. The present case suggests that several processes involved in bone healing modified the microenvironment and represent a possible cause of skull metastasis from primary tumor.
Kimura S.,Kasukabe Municipal Hospital |
Kimura S.,Nihon University |
Igarashi T.,Nihon University |
Kotani A.,Kasukabe Municipal Hospital |
Katayama Y.,Nihon University
Neurological Surgery | Year: 2010
We encountered a case of nontraumatic arterial dissection of the anterior cerebral artery (ACA) which exhibited cerebral infarction and subarachnoid hemorrhage (SAH) simultaneously, and whose symptoms were improved by conservative treatment. A 55-year-old female presenting with headache and weakness in her left leg was admitted to our hospital. CT scans on admission revealed SAH in the interhemispheric fissure and surface of the right frontal lobe, but CT scans at 3 days after onset demonstrated cerebral infarction in the medial part of the right frontal lobe. Cerebral angiography on day 6 disclosed an aneurysmal dilatation and narrowing at the right A2-A3 segment. We continued conservative therapy including blood pressure control, since there was no symptomatic deterioration. The aneurysmal dilatation disappeared and the weakness of the left leg also improved. This case indicates that conservative treatment could be an option for the management of nontraumatic arterial dissection of the ACA with simultaneous cerebral infarction and SAH.
Kimura S.,Nihon University |
Kimura S.,Kasukabe Municipal Hospital |
Kotani A.,Kasukabe Municipal Hospital |
Takimoto T.,Kasukabe Municipal Hospital |
And 2 more authors.
Brain Tumor Pathology | Year: 2014
A 63-year-old woman was admitted to our hospital with serious headache and vomiting. Five months before admission, she had undergone surgery for a primary advanced gastric cancer. Neuroradiological examinations revealed subdural fluid collection. We twice performed evacuation of the subdural fluid collection. However, aggravation of her state of consciousness progressed and she passed away. Histological examinations demonstrated that the dural veins were infiltrated by numerous tumor cells that produced mucus; however, ruptured vessels were not found. Furthermore, the subdural fluid collection increased shortly after the initial operation. We infer that the cause of the collection, which was associated with the dural metastasis of malignant tumors, was not only mucin secretion by tumor cells but also a rapid increase in perfusion pressure in the vessels of the dura mater, resulting in extravasation of plasma components into the subdural space. Our case demonstrates that the pathogenetic mechanism that is specific for subdural fluid collection caused by dural metastasis of malignant tumors differs from the mechanism of production of subdural hematoma associated with dural metastasis. © 2013, The Author(s).
PubMed | Kasukabe Municipal Hospital, Jichi Medical University and Nihon University
Type: Case Reports | Journal: Cancer genetics | Year: 2016
The Philadelphia chromosome (Ph) is the most frequent chromosomal abnormality detected in adult acute lymphoblastic leukemia (ALL). This chromosome forms the BCR/ABL1 fusion gene; thus, ABL1 exon a2 is generally used as a primer-binding region for the detection of the fusion transcript via reverse transcription polymerase chain reaction (RT-PCR). We observed a rare case of adult Ph-positive (Ph(+)) ALL, in which the BCR/ABL1 fusion transcript was not detected using the ABL1 exon a2 region primer. However, we were able to isolate a PCR product by RT-PCR with the BCR exon 13 (b2) and ABL1 exon a3 primers. Analysis of the sequence of the RT-PCR product revealed that the fusion point was between BCR exon 14 (b3) and ABL1 exon a3, and that the transcript lacked ABL1 exon a2. The patient achieved cytogenetic remission through combination chemotherapies, but relapse occurred before hematopoietic stem cell transplantation and the patient died 11 months after the initialization of chemotherapies. If the BCR/ABL1 fusion transcript is undetected with the ABL1 exon a2 region primer in Ph(+) ALL cases, an RT-PCR analysis that can detect the b3a3 type BCR/ABL1 fusion transcript should be considered to improve diagnosis.
PubMed | Kasukabe Municipal Hospital
Type: Journal Article | Journal: Neurologia medico-chirurgica | Year: 2012
A 64-year-old male presented with an extremely unusual case of solitary clivus metastasis from gastric cancer manifesting as mild headache and diplopia 10 years after radical excision of the primary tumor. The patient underwent surgical resection using an endoscopic transsphenoidal approach. Histological examination revealed typical signet ring cell carcinoma (SRC) which was identical to that of the previous gastric cancer. Why the late recurrence occurred such a long time after the first surgery and how it spread to the clivus remain unclear. The characteristics of SRC and the process of tumor dormancy may have been involved in the mechanism underlying late metastasis.