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Noriyuki Katsumata

Publications and source records attributed to Noriyuki Katsumata.

At least 19 recordsLinked to original sources

Current trends and controversies over pre-operative chemotherapy for women with operable breast cancer.

The multi-disciplinary approach, including surgery, chemotherapy, endocrine therapy and radiation therapy, has become the standard treatment for primary breast cancer patients. The indication of pre-operative chemotherapy has been extended to women with potentially operable breast cancer based on the results of large randomized studies and has become an attractive option that extends the chance of breast conservation. The clinical and pathological responses to pre-operative chemotherapy correlates with long-term outcome. The anthracycline-containing regimen is now considered the standard. Sequential administration of non-cross-resistant drugs, namely taxanes, improves local tumor response but its long-term benefit has been controversial. Prediction of response to pre-operative chemotherapy still remains a challenge. Identification of useful predictive markers and development of molecular-targeted drugs is the key to individualized therapy in the future.

Antineoplastic Agents↗

Sibling cases of Addison's disease caused by DAX-1 gene mutations.

We report two sibling cases of Addison's disease without any evidence of sexual precocity, adrenal hyperplasia, or autoimmune disease. The diagnosis of primary adrenocortical insufficiency was made at the age of 5 in the younger brother and at the age of 18 in the elder brother. The younger brother had been inactive during infancy and had diffuse skin pigmentation without abnormal external genitalia, while the elder brother had been healthy until the age of 17 when he noticed skin pigmentation and small testes. Both boys had delayed puberty due to hypogonadotropic hypogonadism. The diagnosis of adrenal hypoplasia congenita (AHC) was established by genetic analysis of DAX-1 gene (dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene 1) with the same single frameshift mutation (305delG). However, yet-uncharacterized epigenetic, nongenetic and/or genetic factors other than the DAX-1 gene may be responsible for the differential onset of AHC in these sibling cases.

Addison Disease↗

[Palliative chemotherapy in cancer patients].

Palliative chemotherapy is applied for incurable cancer patients to prolong their survival, decrease their cancer-related symptoms, and improve their quality of life. These are important end points in clinical trials of palliative chemotherapy. A lot of clinical studies have demonstrated the palliative effect of chemotherapy for incurable cancers such as advanced pancreatic cancer, non-small cell lung cancer and so on. On the other hand, treatment with anti-cancer drugs can be harmful, and sometimes the toxicities may be very severe leading to worsened quality of life and shortened survival. So, we must carefully consider the application of palliative chemotherapy and discuss it with patients.

Humans↗

Cancer of unknown primary site: review of consecutive cases at the National Cancer Center Hospital of Japan.

BACKGROUND: Cancer of unknown primary (CUP) is not a rare clinical entity, accounting for 3%-5% of all solid malignancies. METHODS: We retrospectively reviewed 86 (38 male/48 female) patients with a diagnosis of CUP (exclusive of female patients with adenocarcinoma involving the axillary lymph nodes alone and patients with squamous cell carcinoma of the cervical lymph nodes) who were referred to the National Cancer Center Hospital between April 1996 and October 2002. RESULTS: The median interval between the first visit to a local community hospital and referral to our hospital was 1 month (range, 1 to 45 months). The histological diagnosis was adenocarcinoma in 61 patients (71%), poorly differentiated carcinoma in 18 patients (21%), and squamous cell carcinoma in 4 patients (5%). Twenty-three female patients had peritoneal carcinomatosis of adenocarcinoma. Seventy-eight patients (91%) received platinum-containing chemotherapy. Sixty-one of the 86 patients (71%) were categorized as a subgroup of CUP without a specific therapy, and 55 of these 61 patients (90%) received platinum-containing regimens. The median survivals of all 86 patients and the 61 patients in the subgroup without a specific therapy in this series were 13 months and 11 months, respectively. CONCLUSION: In this series, the survival of the patients in the CUP subgroup without a specific therapy did not seem worse than that in previous reports. Empirical chemotherapy with platinum-containing regimens may benefit some CUP patients in a subgroup without a specific chemotherapy.

Adenocarcinoma↗

An alternative medicine, Agaricus blazei, may have induced severe hepatic dysfunction in cancer patients.

We report three cases of patients with advanced cancer who showed severe hepatic damage, and two of whom died of fulminant hepatitis. All the patients were taking Agaricus blazei (Himematsutake) extract, one of the most popular complementary and alternative medicines among Japanese cancer patients. In one patient, liver functions recovered gradually after she stopped taking the Agaricus blazei, but she restarted taking it, which resulted in deterioration of the liver function again. The other patients who were admitted for severe liver damage had started taking the Agaricus blazei several days before admission. Although several other factors cannot be completely ruled out as the causes of liver damage, a strong causal relationship between the Agaricus blazei extract and liver damage was suggested and, at least, taking the Agaricus blazei extract made the clinical decision-making process much more complicated. Doctors who are aware of their patients taking the extract may accept it probably because they believe there is no harm in a complementary and alternative medicine. When unexpected liver damage is documented, however, doctors should consider the use of the Agaricus blazei extract as one of its causal factors. It is necessary to evaluate many modes of complementary and alternative medicines, including the Agaricus blazei extract, in rigorous, scientifically designed and peer-reviewed clinical trials.

Agaricus↗

Prediction of response to repeat utilization of anthracycline in recurrent breast cancer patients previously administered anthracycline-containing chemotherapeutic regimens as neoadjuvant or adjuvant chemotherapy.

PURPOSE: The aim of this study was to identify the predictors of the response to doxorubicin plus cyclophosphamide in patients with recurrent breast cancer (RBC) previously treated with anthracycline-containing regimens in a neoadjuvant or adjuvant setting. METHOD: Between December 1993 and October 2005, 664 patients had received combined doxorubicin plus cyclophosphamide chemotherapy (doxorubicin, 40 mg/m(2), iv on day 1; cyclophosphamide, 500 mg/m(2), iv on day 1, every 21 days) for RBC at our institution. In this study, we retrospectively analyzed the efficacy of doxorubicin plus cyclophosphamide in 99 of these 664 RBC patients who had also previously been administered an anthracycline-based chemotherapy in a neoadjuvant or adjuvant setting. RESULTS: The median cumulative dose of the previously administered anthracycline was 156 mg/m(2). The median disease-free interval (DFI) and median anthracycline-free interval were 33.8 and 43.7 months, respectively. The overall response rate to doxorubicin plus cyclophosphamide therapy was 38.4% (95% CI; range, 28.8-48.0%). The median time to progression and overall survival were 6.2 and 17.5 months, respectively. The results of a multivariate logistic regression analysis revealed a significant association of the response to doxorubicin plus cyclophosphamide therapy with the DFI (P = 0.02); human epidermal receptor type 2 (HER2) status also tended to affect the response rate, however the association was not statistically significant (P = 0.06). CONCLUSION: DFI and HER2 status may be associated with the response to repeat utilization of anthracycline-containing regimens in RBC patients also treated previously with anthracycline-containing chemotherapeutic regimens in a neoadjuvant or adjuvant setting.

Adult↗

The outpatient management of low-risk febrile patients with neutropenia: risk assessment over the telephone.

OBJECTIVE: The purpose of this retrospective study is to evaluate the feasibility of the risk assessment over the telephone in the outpatient management of low-risk febrile patients with neutropenia. MATERIALS AND METHODS: Febrile patients with neutropenia were eligible for outpatient management with oral ciprofloxacin if they demonstrated the following characteristics: resolution of neutropenia expected in <10 days, good performance status, controlled cancer, no symptoms or signs suggesting systemic infection other than fever, and no comorbidity requiring hospitalization. Eligible patients received oral ciprofloxacin (400 mg, three times daily) and were monitored as far as possible by telephone. Risk assessment concerning general condition was carried out over the telephone. RESULTS: Of the 60 consecutive patients who received neoadjuvant chemotherapy as a phase II trial of docetaxel (60 mg/m(2)) and doxorubicin (50 mg/m(2)) for primary breast cancer, 30 low-risk febrile patients received oral ciprofloxacin. Twenty-seven of these patients (90%) recovered uneventfully without hospitalization and the use of granulocyte colony-stimulating factor. Treatment was considered to have failed in the remaining three (10%) on the account of the need to modify or change their regimens. CONCLUSIONS: For carefully selected low-risk febrile patients with neutropenia, risk assessment over the telephone may be convenient, and close daily medical scrutiny may be not routinely required in the outpatient.

Adult↗

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast.

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.

Adult↗

Determination of specific activities and kinetic constants of biotinidase and lipoamidase in LEW rat and Lactobacillus casei (Shirota).

Enzyme kinetic parameters, such as K(m), V(max) (or V), k(cat)/K(m), and K(i) (by biotin or lipoic acid) for biotinidase and lipoamidase were determined in Lewis (LEW) rat and Lactobacillus casei (Shirota) using fluorimetric high-performance liquid chromatography (HPLC). It was found that the final protein concentration below 0.1mg/ml is sufficient to obtain linear hydrolytic reaction and to determine the Michaelis-Menten type kinetic parameters (K(m), V, K(i)). We applied this HPLC enzyme assay method onto the rat and some bacteria. The highest specific activities (Vs) for biotinidase were found in Lactobacillus casei (Shirota) and rat kidney. It was also found that the largest K(i) by product for biotinidase and lipoamidase were present in the Lactobacillus casei (Shirota). There has been found specie (between rat and mouse) differences and tissue (organ) differences, together with tissue region differences and sex differences in some tissues. Summary of the distributions of both enzymes in LEW rat was also presented. Therefore, this HPLC determination method for the enzyme kinetic parameters in tissues is expected to be an indispensable tool for the investigation of the various diseases in humans.

Amidohydrolases↗

[Turner syndrome].

Explore the source record for details and available documents.

Chromosomes, Human, X↗

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Adult↗

Gene expression profiling of ATP-binding cassette (ABC) transporters as a predictor of the pathologic response to neoadjuvant chemotherapy in breast cancer patients.

Drug resistance is a major obstacle to the successful chemotherapy. Several ATP-binding cassette (ABC) transporters including ABCB1, ABCC1 and ABCG2 have been known to be important mediators of chemoresistance. Using oligonucleotide microarrays (HG-U133 Plus 2.0; Affymetrix), we analyzed the ABC transporter gene expression profiles in breast cancer patients who underwent sequential weekly paclitaxel/FEC (5-fluorouracil, epirubicin and cyclophosphamide) neoadjuvant chemotherapy. We compared the ABC transporter expression profile between two classes of pretreatment tumor samples divided by the patients' pathological response to neoadjuvant chemotherapy (residual disease [RD] versus pathologic complete response [pCR]) ABCB3, ABCC7 and ABCF2 showed significantly high expression in the pCR. Several ABC transporters including ABCC5, ABCA12, ABCA1 ABCC13, ABCB6 and ABCC11 showed significantly increased expression in the RD (p<0.05). We evaluated the feasibility of developing a multigene predictor model of pathologic response to neoadjuvant chemotherapy using gene expression profiles of ABC transporters. The prediction error was evaluated by leave-one-out cross-validation (LOOCV). A multigene predictor model with the ABC transporters differentially expressed between the two classes (p<or=0.003) showed an average 92.8% of predictive accuracy (95% CI, 88.0-97.4%) with a 93.2% (95% CI, 85.2-100%) positive predictive value for pCR, a 93.6% (95% CI, 87.8-99.4%) negative predictive value, a sensitivity of 88.1%(95% CI, 76.8-99.4%), and a specificity of 95.9% (91.1% CI, 87.8-100%). Our results suggest that several ABC transporters in human breast cancer cells may affect the clinical response to neoadjuvant chemotherapy, and transcriptional profiling of these genes may be useful to predict the pathologic response to sequential weekly paclitaxel/FEC in breast cancer patients.

ATP-Binding Cassette Transporters↗

Replacement of alanine with asparagic acid at position 203 in human steroidogenic acute regulatory protein impairs the ability to enhance steroidogenesis in vitro.

Steroidogenic acute regulatory protein (StAR) is a 30-kDa phosphorylated protein that rapidly appears in mitochondria of steroidogenic cells following tropic stimulation, and is required in the acute regulation of steroidogenesis. It was reported that mutations in the STAR gene encoding StAR cause congenital lipoid adrenal hyperplasia (CLAH), an autosomal recessive disorder characterized by impaired synthesis of all adrenal and gonadal steroid hormones. We previously reported a D203A polymorphism in the STAR gene in Japanese patients with CLAH as well as in normal Japanese subjects. In the present study, we analyzed the ability of the A203 StAR and D203 StAR to stimulate steroidogenesis using the in vitro functional expression system. The A203 StAR caused a twelve-fold increase in pregnenolone secretion over COS-1 cells transfected with an NH2-cholesterol side-chain cleavage enzyme (P450scc)-adrenodoxin reductase-adrenodoxin-COOH fusion protein expressing plasmid (F2) and an empty vector, whereas the D203 StAR increased pregnenolone production no more than threefold. Western blot analysis detected mainly two species of StAR consisting of the 37-kDa precursor and the 30-kDa mature form. Together, these results indicate that the alanine at position 203 in human StAR is functionally important and that the D203 StAR is extremely unlikely to be a polymorphism.

Alanine↗

Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum.

CONTEXT: The cholesterol side-chain cleavage enzyme catalyzes the conversion of cholesterol to pregnanalone in the first step of steroidogenic pathways. Defective enzyme activity leads to the deficiency of all steroid hormones, including progesterone, which is essential to sustain term pregnancy. RESULTS: We report a homozygous point mutation in the CYP11A1 gene in a 46, XY phenotypic female born at term to healthy heterozygous parents, presenting relatively late at the age of 1 yr 9 months with life-threatening adrenal insufficiency and complete sex reversal. She was found to have complete agenesis of corpus callosum. The mutation resulted in a single amino acid substitution: valine for alanine at position 359. The functional analysis of the mutant enzyme revealed markedly reduced enzyme activity, but about 11% residual activity was demonstrated. We explained the completion of pregnancy to term and the late presentation by a possible difference in the mutant enzyme activity in vivo and in vitro or by the residual mutant activity, which would have been enough to maintain pregnancy and viability of the patient. The clinical findings of nearly undetectable levels of steroid hormones at presentation are explained by the total disruption of steroidogenic cells later on, with recurrent ACTH stimulation leading to intramitochondrial cholesterol accumulation and cell death (a two-hit mechanism). CONCLUSION: This report of a homozygous mutation in CYP11A1 gene in a child with agenesis of corpus callosum shows that homozygous mutations in CYP11A1 gene can be compatible with term pregnancy and delayed presentation.

Adrenal Insufficiency↗

Molecular genetic analysis of MODY candidate genes in Japanese patients with non-obese juvenile onset diabetes mellitus.

We analyzed 84 Japanese patients with juvenile-onset (before 18 years of age) non-obese diabetes mellitus (DM) for mutations in the genes for HNF-1alpha, HNF-4alpha and HNF-1beta. In HNF-1alpha, previously reported mutations (R271W and R272C) and one novel sequence variant (at nucleotide -129/-130 insTTGGGG of the promoter region) were identified in three different patients. In vitro functional study of the new promoter variant demonstrated that the transcriptional activity was 1.6-2.0 times higher than that of the wild-type. This may lead to overexpression of HNF-1alpha and subsequent negative regulation of the target genes of HNF-1alpha. No mutation was identified in the HNF-4alpha and HNF-1beta genes. In this study on a small series of non-obese Japanese patients with juvenile-onset DM, the prevalence of MODY3 was 3.5%. The significance of the new promoter variant in the development of DM is unclear; however, a promoter mutation in the HNF-1alpha gene could be diabetogenic.

Adolescent↗