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Biomedical subjects

Hiroko Bando

Publications and source records attributed to Hiroko Bando.

At least 19 recordsLinked to original sources
PubMed2025

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer.

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for postmenopausal and tamoxifen plus ovarian function suppression for pre-/perimenopausal patients) plus palbociclib or placebo. The co-primary endpoints included preoperative endocrine prognostic index (PEPI) score and EndoPredict (EPclin) risk score according to the gatekeeping procedure. Of 141 randomized patients, 130 completed the treatment with surgical samples evaluable for endpoints in 126 patients. The proportion of patients with a low, moderate, and high PEPI score was 15.2, 50.0, and 34.8% in the palbociclib arm and 13.3, 55.0, and 31.7% in the placebo arm, respectively, with no statistical difference (one-sided P = 0.563). Statistical analysis was not performed on EPclin risk score. No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in the palbociclib and placebo arms, respectively. In conclusion, the addition of palbociclib to NET did not improve the efficacy. ClinicalTrials.gov NCT03969121.

Humans↗
PubMed2007

Overexpression of soluble vascular endothelial growth factor receptor 1 in colorectal cancer: Association with progression and prognosis.

We examined the expression of sVEGFR1 in colorectal cancer tissue and corresponding normal colorectal mucosa to assess the clinical significance of sVEGFR1 in colorectal cancer. We also assessed the relationship between sVEGFR1 levels and various clinicopathologic factors and prognoses. sVEGFR1 and VEGF levels were measured in fresh-frozen tumor extracts from 84 primary colorectal cancer tissues and 27 corresponding normal mucosa using ELISA. Mean of sVEGFR1 levels were 3.17 ng/mg protein. sVEGFR1 levels increased significantly in cancer tissue compared with normal mucosa. Although VEGF levels increased in cancer tissues, the ratio of sVEGFR1/VEGF in cancer tissue was significantly lower than that in normal tissue. No significant correlation between sVEGFR1 or VEGF levels and any clinicopathologic parameter was found. Overexpression of sVEGFR1 was significantly associated with a favorable prognosis. Based on sVEGFR1 levels in colorectal cancer without distant metastases, patients with higher sVEGFR1 levels (>=1.5 ng/mg protein) demonstrated significant longer recurrence-free survival than patients with lower sVEGFR1 levels (<1.5 ng/mg protein) (P = 0.0017). Multivariate analysis showed that the sVEGFR1 levels in cancer tissue were an independent prognostic indicator of disease progression. sVEGFR1 expression was significantly elevated in colorectal cancer tissue compared with normal mucosa and the intratumoral balance between sVEGFR1 and VEGF was significantly different between tumor tissue and normal controls. Furthermore, sVEGFR1 levels showed a significant prognostic value. Further studies concerning the biologic and therapeutic significance of sVEGFR1 in colorectal cancer are warranted.

Adult↗
PubMed2006

The association between vascular endothelial growth factor-C, its corresponding receptor, VEGFR-3, and prognosis in primary breast cancer: a study with 193 cases.

Lymphangiogenesis plays an important role in several normal and pathological conditions, such as wound healing, pathogen infection, inflammation or the metastasis formation of endothelial malignancies. Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are important and specific regulatory factors for lymphatic endothelial proliferation and lymphangiogenesis. Both growth factors mediate their biological activity mainly by VEGF receptor-3 (VEGFR-3, Flt-4). In this study, we measured intratumoral levels of VEGF-C and VEGFR-3 through enzyme-linked immunosorbent assay (ELISA) in 193 primary breast cancer tissues and examined their prognostic values. A significant correlation was found between the VEGF-C and VEGFR-3 protein levels. High VEGF-C levels were associated with low-grade tumors and a smaller size. Univariate analysis showed that high VEGF-C was significantly associated with a favourable prognosis for disease-free survival (DFS) and overall survival (OS). No significant prognostic value of VEGFR-3 was detected. Multivariate analysis confirmed the independent prognostic value of VEGF-C. The intratumoral VEGF-C level is a significant prognostic indicator of primary breast cancer. An investigation of the mechanisms of VEGF-C protein processing in human cancer tissue should be carried out in the future.

Adult↗
PubMed2005

Targeting of nuclear factor kappaB Pathways by dehydroxymethylepoxyquinomicin, a novel inhibitor of breast carcinomas: antitumor and antiangiogenic potential in vivo.

We previously designed and synthesized the new nuclear factor kappaB (NF-kappaB) inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) derived from the structure of the antibiotic epoxyquinomicin C. We looked into the effect of DHMEQ on cellular phenotypes and tumor growth in mice injected with human breast carcinoma cell line MDA-MB-231 or MCF-7. In estrogen-independent breast adenocarcinoma cell line MDA-MB-231, NF-kappaB is constitutively activated. The addition of DHMEQ (10 microg/mL) completely inhibited the activated NF-kappaB for at least 8 hours. On the other hand, NF-kappaB is not activated in estrogen-dependent MCF-7 cells. In this cell line, DHMEQ completely inhibited the tumor necrosis factor-alpha-induced activation of NF-kappaB. DHMEQ did not inhibit the degradation of IkappaB but inhibited the nuclear translocation of NF-kappaB by both p65/p50 and RelB/p52 pathways. MDA-MB-231 cells secrete interleukin (IL)-6 and IL-8 without stimulation, and DHMEQ decreased the secretion levels of both cytokines. When MDA-MB-231 or MCF-7 cells were stimulated by tumor necrosis factor-alpha, the inhibitory effects of DHMEQ were still maintained. I.p. administration of DHMEQ (thrice a week) significantly inhibited the tumor growth of MDA-MB-231 (12 mg/kg) or MCF-7 (4 mg/kg) in severe combined immunodeficiency mice. No toxicity was observed during the experiment, including the loss of body weight. An immunohistological study on resected MCF-7 tumors showed that DHMEQ inhibited angiogenesis and promoted apoptosis. Furthermore, in Adriamycin-resistant MCF-7 cells highly expressing multidrug resistance gene-1, DHMEQ also exhibited the above capability, including down-regulation of IL-8. Thus, DHMEQ might be a potent drug for the treatment of various breast carcinomas by inhibiting the NF-kappaB activity.

Angiogenesis Inhibitors↗
PubMed2005

Trastuzumab: updates and future issues.

Trastuzumab has had an enormous impact on the clinical management of breast cancer: the survival of Her-2-positive metastatic breast cancer patients has improved significantly and tumor Her-2 status has been built into the decision-making tree for primary breast cancer patients. Several pioneering studies have shown that trastuzumab-combined chemotherapy elicits high levels of pathological complete response in the neoadjuvant setting. Currently, therefore, a more precise understanding of the mechanisms of therapeutic response is needed so that trastuzumab-based therapies can be optimized more individually. It might also be important to investigate, with greater depth, the interaction between the Her-axis and the hormone-axis. This short review describes and discusses these topics.

Antibodies, Monoclonal↗
PubMed2005

Thymidine phosphorylase (platelet-derived endothelial-cell growth factor) in cancer biology and treatment.

Thymidine phosphorylase (TP) is often induced in the tumour microenvironment by physiological and chemical stress. Its induction protects cells from apoptosis and helps cell survival by stimulating nucleoside metabolism and angiogenesis. Chemotherapy often upregulates TP, which acts in cell rescue; this result indicates that TP is a crucial therapeutic target. Clinical trials for metastatic diseases have shown that TP-targeting chemotherapy with fluorouracil derivatives greatly improves the effectiveness of conventional chemotherapy for not only response but also prognosis. This new idea, the improvement of TP-inducible therapy with TP-targeting therapy, should be further investigated for early disease states, and inhibitors of TP warrant extensive investigation.

Apoptosis↗
PubMed2004

Immunodetection and quantification of vascular endothelial growth factor receptor-3 in human malignant tumor tissues.

Vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligands, vascular endothelial growth factor-C (VEGF-C) and -D (VEGF-D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme-linked immunosorbent assay (ELISA) for the quantification of VEGFR-3 in different human cell and tissue lysates. A combination of the goat polyclonal anti-VEGFR-3 antibody and the mouse monoclonal anti-human VEGFR-3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2-25 ng/ml. The assay was specific for VEGFR-3, with no cross-reactivity to VEGFR-1 or VEGFR-2. Complex formation with VEGF-C and VEGF-D had no effect on the sensitivity of the assay. The VEGFR-3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14-fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR-3 were in the range of 0.6-16.7 ng/mg protein. Importantly, the level of VEGFR-3 protein detected in the ELISA correlated significantly with the number of VEGFR-3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR-3-positive vessel density. The protein levels of VEGFR-3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF-C (p<0.001), or biological active, free VEGF-A (p<0.0001), but not with VEGFR-1 or total VEGF-A. This assay provides a useful tool for the investigations of the expression levels of VEGFR-3 in physiological and pathological processes, particular in cancer and in lymphangiogenesis-related disease.

Animals↗
PubMed2004

Quantification of vascular endothelial growth factor-C (VEGF-C) by a novel ELISA.

Lymphangiogenesis plays an important role in several normal and pathological conditions such as wound healing, inflammation or metastasis formation in several malignancies. VEGF-C and VEGF-D are important and specific regulatory factors for lymphatic endothelial proliferation and lymphangiogenesis. In order to develop a highly sensitive and specific detection system for VEGF-C, we produced soluble binding proteins and antibodies for a microtiterplate-based assay. Here we describe a specific enzyme-linked immunosorbent assay (ELISA) for the measurement of human, rat and murine VEGF-C. The different antibodies developed against human and rat VEGF-C could be combined to detect processed and partially processed VEGF-C in a specific way. The ELISA was able to detect human and rat VEGF-C with a minimum detection limit of 100 pg/ml. The assay did not show any cross-reactivity with the related protein VEGF-D. Furthermore, complex formation with its soluble receptors VEGFR-2 and VEGFR-3 did not restricted the sensitivity of the assay. Using this assay, VEGF-C was measured in supernatants and lysates of different cell types and in tumour tissue samples of murine, rat and human origin. Cell lines secrete VEGF-C in very low amounts (<1 ng/ml) whereas VEGF-C transfected cells can secrete up to 50 ng/ml VEGF-C into the supernatant. In human tumour tissue samples VEGF-C was detected in some carcinomas in the low protein range. This ELISA will be a useful tool for investigations concerning the physiological function of VEGF-C in lymphangiogenesis under normal and pathophysiological conditions.

Animals↗
PubMed2004

Current status of antibody therapy for breast cancer.

Antibody therapy with trastuzumab has greatly impacted breast cancer treatment. Combination treatment with trastuzumab is regarded currently as a first-line therapy for metastatic breast cancers that overexpress Her-2. It has become routine practice to examine the status of Her-2 expression in primary tumors. The impact of this therapy might be as great as that of endocrine therapy from a historical point of view. A number of new approaches using trastuzumab for seeking individualized treatment are being tested in current clinical trials. We reviewed recent advances in trastuzumab treatment and discuss the future of antibody therapy for breast cancer.

Antibodies, Monoclonal↗
PubMed2004

DFU, a selective COX-2 inhibitor, suppresses MCF-7 xenograft tumor growth in mice.

Cyclooxygenase-2 (COX-2) inhibitors are regarded as potentially important in strategies for cancer treatment. however, the precise mechanisms of these anti-inflammatory drugs as anti-cancer therapy are still unknown. In this study, we examined the effect of DFU both in vitro on MCF-7 cell growth, as well as in vivo on tumor growth produced by MCF-7 cell injection in mice. DFU has growth inhibitory effects on tumor growth in mice compared to the control group. We examined the tumor tissues for apoptosis and angiogenesis by immunostaining. Apoptosis was detected only in the treatment group. DFU treatment also resulted in the inhibition of angiogenesis, as well as decreased COX-2 expression. Results of this study suggest that inhibitory effects of DFU might be COX-2 dependent.

Animals↗
PubMed2004

A close association between alteration in growth kinetics by neoadjuvant chemotherapy and survival outcome in primary breast cancer.

Few surrogate markers are available for predicting the survival benefit from chemotherapy in primary breast cancer. We examined tumor growth kinetics by assessing cytokeratin 18 neo-epitope (CK18NE), an apoptosis marker detected by M30 antibody and Ki-67 antigen, a proliferation marker detected by MIB-1 antibody in 72 primary breast cancer patients who underwent pre-operative anthracycline-based chemotherapy. Increase in M30 index and decrease in MIB-1 index after the exposure of 2 to 4 cycles of chemotherapy correlated significantly with pathological tumor response. Univariate survival analysis, conducted in the subgroup of 42 patients who underwent CAF (cyclophosphamide, adriamycin and 5-FU) therapy alone, showed that the patients with the high levels of M30 index (>35 counts/1000 tumor cells) and the low levels of MIB-1 index (<140 counts/1000 tumor cells) after chemotherapy had a remarkably favorable prognosis as compared with patients in other categories. In addition, the alteration in growth kinetics by the treatment showed a significant prognostic value. Multivariate analysis also confirmed that the post-treatment growth kinetics was an independent prognostic indicator. These findings suggest that the alteration in growth kinetics revealed by CK18NE and MIB-1 might be a surrogate marker for predicting the survival benefit from chemotherapy in primary breast cancer.

Adult↗
PubMed2004

[Trastuzumab treatment for breast cancer].

Trastuzumab is a recombinant humanized monoclonal antibody directed against the HER-2. HER-2 is overexpressed in 20-25% of invasive breast cancer and known as poor prognostic factor and its status of a tumor is related to response to trastuzumab. Combination therapy with trastuzumab and chemotherapy increases response rate, time to progression, and survival thus trastuzumab is perceived to be the first line treatment for HER-2 overexpressed metastatic breast cancer. The optimal duration and period of trastuzumab treatment are still unknown and result of large scale randomized trial will be expected.

Antibodies, Monoclonal↗
PubMed2003

Expression of thymidylate synthase and thymidine phosphorylase in human breast carcinoma: implication for method to detect expression of these molecules in clinic.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor, and has an angiogenic activity in experimental models and human solid tumors. A critical step in the de novo pathway of DNA synthesis is the production of the pyrimidine nucleotide dTMP from dump and this reaction is catalyzed by thymidylate synthase (TS). Both dThdPase and TS levels seemed to be related to response to 5-fluorouracil (5-FU) therapy in different types of human solid tumors. The present study evaluated dThdPase and TS expression levels by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), using a same set of 39 breast carcinoma tissues for both methods. An inverted-relationship in the expression levels of TS and dThdPase was observed. Further, immunohistochemical analysis may be a better tool than analysis by RT-PCR in detection of dThdPase and TS, because of both dThdPase and TS expression in cells besides carcinoma cells. These imply that immunohistochemical analysis of dThdPase and TS is available for selection of patients who will be received 5-FU based chemotherapy.

Adult↗
PubMed2003

Weekly schedule of docetaxel in breast cancer: evaluation of response and toxicity.

Several recent studies have investigated the administration of docetaxel on a weekly basis. Here, we review the weekly use of docetaxel in breast cancer. To identify articles published on this topic we performed a computer-assisted MEDLINE search; additional references were found in the bibliographies of these articles. Several phase Tstudies of weekly docetaxel have provided encouraging data indicating that there is generally less myelosuppression than with the three week schedule in patients with a variety of advanced malignancies. Dose-limiting toxicities are reached at 43 to 50 mg/m(2), and the recommended dose ranges from 36 to 42 mg/m(2). Furthermore, five studies of weekly docetaxel in patients with metastatic breast cancer achieved 32 to 41% response rates using 25 to 40 mg/m(2) of docetaxel. Myelosuppression was mild, but fatigue was common and was the most common reason for dose reduction. In general, the planned dose intensity was equivalent to those used in standard three week schedules, and fatigue, asthenia, nail changes, excessive lacrimation (tearing), and fluid retention became more common with prolonged administration of docetaxel. Thus, weekly scheduling of docetaxel maintains efficacy and alters the toxicity profile, and the use of weekly docetaxel will become a promising alternative to three week dosing in the treatment of advanced breast cancer once randomized controlled studies confirm these results. However, there is still much to learn about the role of weekly docetaxel in adjuvant and neoadjuvant therapy.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Genes commonly upregulated by hypoxia in human breast cancer cells MCF-7 and MDA-MB-231.

Hypoxia is a stress that causes alterations in signal transduction and gene instability. In the cancer microenvironment, hypoxia plays a significant role in forming a tumor phenotype and tumor progression. We aimed to identify the genes upregulated by hypoxia in human breast cancer cell lines, a hormone-dependent MCF-7 and a hormone-independent MDA-MB-231, using microarray analysis. These cells were exposed to two oxygen concentrations such as 21% and 1% in a time-course. Out of 12625 genes, 26 genes were identified as commonly upregulated in both MCF-7 and MDA-MB-231 cells. Some of these genes were already reported as hypoxia-related, but some of those were identified newly. These commonly upregulated genes between hormone-dependent and hormone-independent cells would be a clue to study hypoxia-related events and to explore the novel therapeutic targets in human breast cancer.

Breast Neoplasms↗
PubMed2003

Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo.

We previously showed pomegranate seed oil and fermented juice polyphenols to retard oxidation and prostaglandin synthesis, to inhibit breast cancer cell proliferation and invasion, and to promote breast cancer cell apoptosis. Here we evaluated the anti-angiogenic potential of these materials in several ways. We checked a possible effect on angiogenic regulation by measuring vascular endothelial growth factor (VEGF), interleukin-4 (IL-4) and migration inhibitory factor (MIF) in the conditioned media of estrogen sensitive (MCF-7) or estrogen resistant (MDA-MB-231) human breast cancer cells, or immortalized normal human breast epithelial cells (MCF-10A), grown in the presence or absence of pomegranate seed oil (SESCO) or fermented juice polyphenols (W). VEGF was strongly downregulated in MCF-10A and MCF-7, and MIF upregulated in MDA-MB-231, overall showing significant potential for downregulation of angiogenesis by pomegranate fractions. An anti-proliferative effect on angiogenic cells was shown in human umbilical vein endothelial cell (HUVEC) and in myometrial and amniotic fluid fibroblasts, and inhibition of HUVEC tubule formation demonstrated in an in vitro model employing glass carrier beads. Finally, we showed a significant decrease in new blood vessel formation using the chicken chorioallantoic membrane (CAM) model in vivo. 'In sum, these varied studies employing different models in different laboratories overall demonstrate for the first time an anti-angiogenic potential of pomegranate fractions, suggesting further in vivo and clinical investigations (for updates: info@rimonest.com).

Angiogenesis Inhibitors↗