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  • 1
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    Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy
    Springer Science and Business Media LLC ; 2021
    In:  BMC Cancer Vol. 21, No. 1 ( 2021-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. Methods The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m 2 ]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m 2 were classified as underweight (UW), those ≥18.5 kg/m 2 and  〉  25 kg/m 2 were considered normal weight (NW), those ≥25 kg/m 2 and  〈  30 kg/m 2 were overweight (OW), and those ≥30 kg/m 2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. Results The median BMI was 21.9 kg/m 2 (range, 14.3–38.5 kg/m 2 ); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p  = 0.001; vs. OW: p  = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p  = 0.031). Conclusions Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-021-08857-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 2
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    Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment
    Springer Science and Business Media LLC ; 2020
    In:  BMC Cancer Vol. 20, No. 1 ( 2020-12)
    Details
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. Methods Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    URL: Article
    DOI: 10.1186/s12885-020-07673-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 3
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    Prediction of distant metastatic recurrence by tumor-infiltrating lymphocytes in hormone receptor-positive breast cancer
    Springer Science and Business Media LLC ; 2021
    In:  BMC Women's Health Vol. 21, No. 1 ( 2021-05-29)
    Details
    In: BMC Women's Health, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-05-29)
    Abstract: Breast cancer subtypes are known to have different metastatic recurrence sites. Distant metastases are often observed during the post-operative course in patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer and triple-negative breast cancer, but are relatively rare in those with hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer. Tumor-infiltrating lymphocytes (TILs) serve as an index to monitor tumor immune microenvironment and may possibly predict the prognosis and therapeutic effect in breast cancer. This study aimed to investigate the correlation between TIL density and recurrence site in HR+/HER2− breast cancer. Methods In stages I–II of HR+/HER2− breast cancer patients who underwent surgery as the first treatment and received adjuvant endocrine therapy (except adjuvant chemotherapy), forty-two patients relapsed after surgery. TILs were evaluated using needle biopsy specimens for the diagnosis of breast cancer. Morphological assessment was conducted using conventional hematoxylin and eosin staining. Results Six patients had no TILs density. In them, local recurrence was significantly less ( p  = 0.022), while distant metastases were significantly more ( p  = 0.015) compared to those in patients with TIL density. Therefore, for the prediction of distant metastases in HR+/HER2− breast cancer without chemotherapy, TILs could be used as predictors in univariate analysis ( p  = 0.015, odds ratio [OR] = 0.127), although not as independent factors ( p  = 0.285, OR = 0.144). Conclusions Our findings indicate that TILs may predict distant metastatic recurrence in stages I–II of HR+/HER2− breast cancer in patients who do not undergo chemotherapy.
    Type of Medium: Online Resource
    ISSN: 1472-6874
    URL: Article
    DOI: 10.1186/s12905-021-01373-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
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    Synthesis of 14.ALPHA.-methylcholesterol.
    Pharmaceutical Society of Japan ; 1987
    In:  Chemical and Pharmaceutical Bulletin Vol. 35, No. 8 ( 1987), p. 3467-3469
    Details
    In: Chemical and Pharmaceutical Bulletin, Pharmaceutical Society of Japan, Vol. 35, No. 8 ( 1987), p. 3467-3469
    Type of Medium: Online Resource
    ISSN: 0009-2363 , 1347-5223
    URL: Article
    DOI: 10.1248/cpb.35.3467
    Language: English
    Publisher: Pharmaceutical Society of Japan
    Publication Date: 1987
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  • 5
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    Development and validation of a deep learning model for detection of breast cancers in mammography from multi-institutional datasets
    Public Library of Science (PLoS) ; 2022
    In:  PLOS ONE Vol. 17, No. 3 ( 2022-3-24), p. e0265751-
    Details
    In: PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 3 ( 2022-3-24), p. e0265751-
    Abstract: The objective of this study was to develop and validate a state-of-the-art, deep learning (DL)-based model for detecting breast cancers on mammography. Methods Mammograms in a hospital development dataset, a hospital test dataset, and a clinic test dataset were retrospectively collected from January 2006 through December 2017 in Osaka City University Hospital and Medcity21 Clinic. The hospital development dataset and a publicly available digital database for screening mammography (DDSM) dataset were used to train and to validate the RetinaNet, one type of DL-based model, with five-fold cross-validation. The model’s sensitivity and mean false positive indications per image (mFPI) and partial area under the curve (AUC) with 1.0 mFPI for both test datasets were externally assessed with the test datasets. Results The hospital development dataset, hospital test dataset, clinic test dataset, and DDSM development dataset included a total of 3179 images (1448 malignant images), 491 images (225 malignant images), 2821 images (37 malignant images), and 1457 malignant images, respectively. The proposed model detected all cancers with a 0.45–0.47 mFPI and had partial AUCs of 0.93 in both test datasets. Conclusions The DL-based model developed for this study was able to detect all breast cancers with a very low mFPI. Our DL-based model achieved the highest performance to date, which might lead to improved diagnosis for breast cancer.
    Type of Medium: Online Resource
    ISSN: 1932-6203
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    DOI: 10.1371/journal.pone.0265751
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    Language: English
    Publisher: Public Library of Science (PLoS)
    Publication Date: 2022
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  • 6
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    Obesity and hiatal hernia may be non-allergic risk factors for esophageal eosinophilia in Japanese adults
    Springer Science and Business Media LLC ; 2019
    In:  Esophagus Vol. 16, No. 3 ( 2019-7), p. 309-315
    Details
    In: Esophagus, Springer Science and Business Media LLC, Vol. 16, No. 3 ( 2019-7), p. 309-315
    Type of Medium: Online Resource
    ISSN: 1612-9059 , 1612-9067
    URL: Article
    DOI: 10.1007/s10388-019-00662-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 7
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    Abstract 2343: The novel potential of palbociclib (CDK4/6 inhibitor) in the treatment of triple-negative breast cancer
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Research Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2343-2343
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 2343-2343
    Abstract: Background: The effectiveness of palbociclib (CDK4/6 inhibitor) for estrogen receptor positive breast cancer has been demonstrated by large-scale clinical studies, with the drug garnering attention as a key drug for breast cancer subtypes with endocrine sensitivity in the future. According to PALOMA-3 trial, palbociclib has been demonstrated to contribute to the extension of progression-free survival in patients with advanced hormone receptor-positive and HER2-negative metastatic breast cancer after endocrine therapy. On the other hand, in the case of triple-negative breast cancer (TNBC), luminal AR (LAR) related to androgen signaling is believed to have endocrine activity. Previous clinical data revealed that palbociclib shows high sensitivity in luminal breast cancer cell lines with endocrine activity, with effectiveness also expected in LAR. In this study, we created TNBC cell lines that forcibly express AR and examined the effectiveness of palbociclib for TNBC. Materials and Methods: MCF-7 and T-47D were used as luminal breast cancer cell lines, while MDA-MB-231 and BT-549 were used as TNBC cell lines. In addition, we created TNBC cell lines that forcibly express AR, called AR-MDA-MB-231, by the transfection of pEGFP-C1-AR Plasmid Vector using Lipofectamine® 3000 Reagent. We confirmed the expression of AR by qRT-PCR as well as Western blotting and examined the impact of palbociclib on proliferation as well as apoptosis of breast cancer cell lines. Results: AR was found to have been expressed only in luminal breast cancer cell lines but not TNBC cell lines. It was confirmed that AR was expressed in AR-MDA-MB-231 which are stable cell lines with the properties of LAR. In a CCK assay, palbociclib showed high sensitivity in AR-MDA-MB-231 as in luminal breast cancer cell lines. Furthermore, in an apoptosis assay using FACS and cell cycle assay, apoptosis was induced in AR-MDA-MB-231 and cell cycle arrest at the G1S check point was confirmed. Conclusion: palbociclib (CDK4/6 inhibitor) showed effectiveness for TNBC cell lines that compulsively express AR, suggesting it may be one treatment option for TNBC in the future. Citation Format: Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Tsutomu Takashima, Tamami Morisaki, Satoru Noda, Naoyoshi Onoda, Kosei Hirakawa, Masaichi Ohira. The novel potential of palbociclib (CDK4/6 inhibitor) in the treatment of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2343. doi:10.1158/1538-7445.AM2017-2343
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2017-2343
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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  • 8
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    Abstract 1980: Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Research Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1980-1980
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 1980-1980
    Abstract: Object: Lysyl oxidase (LOX) family is the extracellular matrix-modifying enzymes comprising of LOX and LOX-like (LOXL) 1-4. These enzymes have intracellular functions involved in the regulation of motility, migration, differentiation, and transcription in various types of cells. LOX is associated with mesenchymal reconstruction that is essential for cancer invasion and metastasis. LOX overexpression is crucial to promoting tumor growth and metastasis in several cancers such as breast cancer and colorectal cancer, however, role of LOX in gastric cancer remain unknown. Here, we investigated the clinicopathological significance of LOX and LOXL2 in gastric cancer. Materials and Methods: A total of 549 patients who had undergone surgery for gastric cancer at Osaka-City University were enrolled. LOX and LOXL2 expressions were evaluated by intensity of staining and percentage of stained tumor cells at the invading tumor front. This study was approved by the Osaka City University ethics committee. Informed consent was obtained from all patients. Results: LOX and LOXL2 expression were positive in 265 (48.3%) and 342 (58.5%) of the 549 gastric tumors. Both LOX and LOXL2 expression in cancer cells were significantly associated with macroscopic type (p & lt;0.01), histological type (p & lt;0.01), depth of invasion (p & lt;0.01), lymph node status (p & lt;0.01), vessel invasion (p & lt;0.01). The prognosis of patients with LOX-positive tumors or LOXL2-positive tumors was significantly (p & lt;0.001 or p & lt;0.001, log-rank) worse than that of patients with LOX-negative or LOXL2-negative tumors, respectively. A multivariate analysis indicated LOX and LOXL2 expression in cancer cells to be an independent prognostic factor (p=0.016 or p & lt;0.001). Conclusions: LOX and LOXL2 expression might be associated with metastatic activity of gastric cancer cells. LOX and LOXL2 might be useful predictive prognostic factors for patients with gastric cancer. Citation Format: Hiroaki Kasashima, Masakazu Yashiro, Yukie Go, Go Masuda, Haruhito Kinoshita, Mao Tokumoto, Tamami Morisaki, Tatsunari Fukuoka, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Hirakawa. Role of lysyl oxidase and lysyl oxidase-like 2 in gastric carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1980. doi:10.1158/1538-7445.AM2014-1980
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2014-1980
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
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  • 9
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    Abstract 3939: Clinical significance of expression of androgen-receptor splice variant-7 (AR-V7) in neoadjuvant chemotherapy for breast cancer
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3939-3939
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3939-3939
    Abstract: Background: Triple-negative (TN) breast cancer (BC) patients testing positive for androgen receptor (AR) expression are thought to be chemotherapy resistant, similar to other hormone receptor-positive (HR) BCs. On the other hand, prostate cancer is a hormone-dependent malignant tumor like breast cancer, it has been reported that chemotherapy is more likely to be effective if there is an abnormality in androgen-receptor splice variant-7 (AR-V7). In an immunohistochemical study, as well, AR-V7 expression was reportedly a poor prognostic factor in castration-resistant prostate cancer (CRPC). In this study, we investigated the association between chemotherapy sensitivity and AR-V7 expression in patients treated with neoadjuvant chemotherapy (NAC) using standardized chemotherapy criteria and regimens. Materials and Methods: A total of 177 patients with resectable early-stage breast cancer were treated with NAC. ER, PgR, HER2, Ki67 and AR-V7 status were assessed immunohistochemically. Results: In the 43 AR-V7 expression positive group, compared to the 133 negative group, TNBC (p & lt;0.001) and non-HRBC (p = 0.001) were significantly more frequent, and the pCR rate were significantly higher (p & lt;0.001). Among the 61 TNBC and the 80 HRBC patients, the pathological complete response (pCR) rate was significantly higher in AR-V7 expression positive group than in the negative group (p = 0.008) (p = 0.018). Analysis of all 177 patients receiving NAC revealed that no significant difference in disease-free survival (DFS) was associated with AR-V7 expression (p = 0.080, log-rank). However, a significantly extended non-recurrence period was observed in patients with AR-V7-expressing tumors compared to AR-V7 negative tumors, when the analysis was limited to patients with TNBC (p = 0.016, log-rank). In univariate analysis, AR-V7 expression made a significant contribution to extending disease-free survival in patients with TNBC (p = 0.044, hazard ratio = 0.121). However, multivariate analysis indicated that AR-V7 expression was not an independent factor (p = 0.083, hazard ratio = 0.158). Conclusion: These findings show that AR-V7 expression is a therapeutic effect predictive marker in BCNAC, and indicates particularly high chemotherapy sensitivity in TNBC. Citation Format: Yuka Asano, Shinichiro Kashiwagi, Wataru Goto, Kento Kurata, Tamami Morisaki, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Sayaka Tanaka, Masahiko Ohsawa, Masaichi Ohira, Kosei Hirakawa. Clinical significance of expression of androgen-receptor splice variant-7 (AR-V7) in neoadjuvant chemotherapy for breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3939.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2016-3939
    RVK:
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    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 10
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    Abstract 1405: Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1405-1405
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 1405-1405
    Abstract: Purpose: Cancer stem cells (CSCs) are responsible for cancer progression, metastasis, and recurrence. The identification of CSC markers may open a new therapeutic perspective on the basis of selectively targeting this small population of cancer cells, however, the specific markers of CSCs remain undiscovered. The aim of this study was to identify novel biomarkers of gastric CSCs for clinical diagnosis using proteomics technology. Materials and Methods: Since the side population (SP) cells of gastric cancer possess CSC-like properties, we used CSC-like SP cells, OCUM-12/SP cells and OCUM-2MD3/SP cells in this study. Their parent OCUM-12 cells and OCUM-2MD3 cells were also used. Protein lysates from each cell line were analyzed using QSTAR Elite Liquid Chromatography with Tandem Mass Spectrometry, coupled with isobaric tags for relative and absolute quantitation technology. Proteins overexpressed in SP cells were determined by comparing the proteomes among parent cells and CSC-like SP cells. Candidate proteins detected by proteomics technology were validated by RT-PCR, western blot, invasion assay, and immunohistochemical analysis of 300 gastric cancers. Results: Based on the results of LC-MS/MS, eight proteins, including RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, were up-regulated in both OCUM-12/SP cells and OCUM-2MD3/SP cells when compared to their corresponding parent cells. RT-PCR analysis indicated that the expression level of RBBP6, HSPA4, DCTPP1, HSPA9, VPS13A, ALDOA, GLG1, and CK18 was high in OCUM-12/SP and OCUM-2MD3/SP, in compared with the control of parent OCUM-12 and OCUM-2MD3. These proteins were significantly associated with advanced invasion depth, lymph node metastasis, distant metastasis, or advanced clinical stage. RBBP6, DCTPP1, HSPA4, and ALDOA expression in particular were significantly associated with a poor prognosis in the 300 gastric cancer patients. RBBP6 was determined to be an independent prognostic factor. The motility-stimulating ability of OCUM-12/SP cells and OCUM-2MD3/SP cells was inhibited by RBBP6 siRNA. Conclusion: The eight proteins, RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, utilizing comparative proteomics analysis, were perceived to be potential CSC markers of gastric cancer. Of the eight candidate proteins, RBBP6 was suggested to be a promising prognostic biomarker and a therapeutic target for gastric cancer. Citation Format: Masakazu Yashiro, Tamami Morisaki, Tsuyoshi Hasegawa, Anna Kakehashi, Haruhito Kinoshita, Tatsunari Fukuoka, Hiroaki Kasashima, Go Masuda, Katsunobu Sakurai, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Hideki Wanibuchi, Kosei Hirakawa. Novel biomarkers for gastric cancer stem cells utilizing comparative proteomics analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1405. doi:10.1158/1538-7445.AM2015-1405
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2015-1405
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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