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Article ; Online: Status and prognostic value of immunological biomarkers of breast cancer.

Murazawa, Chisa / Hashimoto, Nozomi / Kuraishi, Kana / Motoyama, Mutsumi / Hashimoto, Shin-Ichiro / Ikeuchi, Mayumi / Norimura, Shoko / Matsunaga, Toru / Teramoto, Koji / Haba, Reiji / Abe, Noriko / Yajima, Toshiki / Kontani, Keiichi

Oncology letters

2023 Volume 25, Issue 4, Page(s) 164

Abstract: The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of ... ...

Abstract	The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of cancer. However, the dominant subtype, luminal human epidermal growth factor receptor-2 (HER2)-negative breast cancer, is less immunogenic. To determine whether luminal HER2-negative cancer reacts to the anticancer immune response, the present study analyzed the status and prognostic value of the principal immunological biomarkers of breast cancer, including tumor-infiltrating lymphocytes (TILs), CD8
Language	English
Publishing date	2023-03-08
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2573196-8
ISSN	1792-1082 ; 1792-1074
ISSN (online)	1792-1082
ISSN	1792-1074
DOI	10.3892/ol.2023.13750
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Article: [Efficacy of TS-1 as a Late-Line Treatment for Metastatic Breast Cancer].

Murazawa, Chisa / Kontani, Keiichi / Hashimoto, Shinichiro / Hashimoto, Nozomi / Norimura, Shoko / Ohtani, Masahiro / Date, Manabu / Yokomise, Hiroyasu

Gan to kagaku ryoho. Cancer & chemotherapy

2019 Volume 46, Issue 9, Page(s) 1461–1463

Abstract: We report 4 female patients with metastatic breast cancer who were administered TS-1 as a late-line treatment and showed favorable outcomes. Their average age was 66.3. The patients, all of whom had undergone prior treatment with both anthracyclines and ... ...

Abstract	We report 4 female patients with metastatic breast cancer who were administered TS-1 as a late-line treatment and showed favorable outcomes. Their average age was 66.3. The patients, all of whom had undergone prior treatment with both anthracyclines and taxanes, showed intrinsic Luminal A or B subtypes. After administration of TS-1 in the lines of 2 to 9 in metastatic settings, all patients showed a long progression-free survival with a favorable quality of life.
MeSH term(s)	Aged ; Anthracyclines ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/drug therapy ; Female ; Humans ; Quality of Life ; Silicates/therapeutic use ; Taxoids ; Titanium/therapeutic use ; Treatment Outcome
Chemical Substances	Anthracyclines ; Silicates ; Taxoids ; titanium silicide (12067-57-1) ; Titanium (D1JT611TNE)
Language	Japanese
Publishing date	2019-09-17
Publishing country	Japan
Document type	Journal Article
ZDB-ID	604842-0
ISSN	0385-0684
ISSN	0385-0684
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Article ; Online: Clinicopathological characteristics and prognostic marker of triple-negative breast cancer in older women.

Honma, Naoko / Ogata, Hideaki / Yamada, Akimitsu / Matsuda, Yoko / Kontani, Keiichi / Miyashita, Mika / Arai, Tomio / Sasaki, Eiichi / Shibuya, Kazutoshi / Mikami, Tetuo / Sawaki, Masataka

Human pathology

2021 Volume 111, Page(s) 10–20

Abstract: Triple-negative breast cancer (TNBC) lacks an effective treatment target and is usually treated with chemotherapy. Treatment of older patients with TNBC, however, should be decided carefully because of the side effects of chemotherapy in this population. ...

Abstract	Triple-negative breast cancer (TNBC) lacks an effective treatment target and is usually treated with chemotherapy. Treatment of older patients with TNBC, however, should be decided carefully because of the side effects of chemotherapy in this population. Some forms of TNBC are associated with a favorable prognosis and do not require chemotherapy. To optimize the treatment of older patients with TNBC, it is important to know the clinicopathological characteristics and a prognostic marker. In this study, classic clinicopathological factors, immunohistochemical characteristics (androgen receptor [AR], cytokeratin 5/6 [CK5/6], epidermal growth factor receptor), tumor-infiltrating lymphocytes (TILs), and the clinical outcome based on the status of each biomarker were compared among a consecutive series of female patients with TNBC aged ≥75 years (n = 75) and among those aged 55-64 years matched for the pathological stage (n = 47) who underwent surgery without neoadjuvant therapy. TNBC with special histology (particularly apocrine carcinoma, pleomorphic invasive lobular carcinoma, and metaplastic carcinoma) was more frequent in the older group than in the younger group (35/75, 57% versus 11/47, 23%, P = 0.010). The AR positivity rate was higher in older patients than in younger patients, whereas TILs and CK5/6 exhibited the opposite results. In multivariate analyses, AR positivity was an independent predictor of a favorable outcome in older patients (lower recurrence rate), whereas the high level of TILs was favorable in younger patients (lower recurrence and mortality rates). AR positivity or apocrine morphology was frequent and predicts a favorable clinical outcome in older patients with TNBC, suggesting the importance of AR examination in this population.
MeSH term(s)	Aged ; Aged, 80 and over ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Middle Aged ; Prognosis ; Receptors, Androgen/metabolism ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	AR protein, human ; Biomarkers, Tumor ; Receptors, Androgen
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2021.01.005
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Article: [Utility of Prophylactic Administration of Pegfilgrastim in Breast Cancer Chemotherapy].

Norimura, Shoko / Kontani, Keiichi / Morishita, Atsushi / Kubo, Takako / Murazawa, Chisa / Hashimoto, Shinichiro / Hashimoto, Nozomi / Kenzaki, Koichiro / Miura, Kazumasa / Yokomise, Hiroyasu

Gan to kagaku ryoho. Cancer & chemotherapy

2018 Volume 45, Issue 12, Page(s) 1729–1732

Abstract: Febrile neutropenia(FN)is a frequent adverse event observed in cancer patients undergoing chemotherapy that may cause life-threatening infections. However, reducing the dose of anti-cancer drugs for breast cancer in adjuvant settings to prevent FN has ... ...

Abstract	Febrile neutropenia(FN)is a frequent adverse event observed in cancer patients undergoing chemotherapy that may cause life-threatening infections. However, reducing the dose of anti-cancer drugs for breast cancer in adjuvant settings to prevent FN has been reported to adversely affect patient survival. Therefore, it is important to administer therapeutic agents as per their prescheduled regimens without delays or reductions in the dosage. From April 2015 to September 2017, pegfilgrastim was administered to 24 patients with breast cancer(primary prevention in 11 patients and secondary prevention in 13 patients)to prevent FN during chemotherapy in either adjuvant or metastatic settings. We were able to reduce the incidence of FN through prophylactic administration of pegfilgrastim without encountering serious adverse events. The inclusion of pegfilgrastim is considered essential for the safe administration of chemotherapy according to a preplanned schedule. Here, we discuss the indications, efficacy, and safety of the drug.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast Neoplasms/drug therapy ; Filgrastim/therapeutic use ; Granulocyte Colony-Stimulating Factor ; Humans ; Neutropenia/chemically induced ; Neutropenia/prevention & control ; Polyethylene Glycols/therapeutic use ; Recombinant Proteins
Chemical Substances	Recombinant Proteins ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; pegfilgrastim (3A58010674) ; Polyethylene Glycols (3WJQ0SDW1A) ; Filgrastim (PVI5M0M1GW)
Language	Japanese
Publishing date	2018-12-23
Publishing country	Japan
Document type	Journal Article
ZDB-ID	604842-0
ISSN	0385-0684
ISSN	0385-0684
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Article ; Online: Hypertension and Proteinuria as Predictive Factors of Effects of Bevacizumab on Advanced Breast Cancer in Japan.

Tanaka, Hiroaki / Takahashi, Koichi / Yamaguchi, Kazunori / Kontani, Keiichi / Motoki, Takahiro / Asakura, Masato / Kosaka, Shinji / Yokomise, Hiroyasu / Houchi, Hitoshi

Biological & pharmaceutical bulletin

2018 Volume 41, Issue 4, Page(s) 644–648

Abstract: Bevacizumab (BV), an inhibitor of vascular endothelial growth factor, is used in combination with paclitaxel (PTX) to treat advanced breast cancer. Hypertension and proteinuria are characteristic adverse events of BV therapy. We assessed the potential of ...

Abstract	Bevacizumab (BV), an inhibitor of vascular endothelial growth factor, is used in combination with paclitaxel (PTX) to treat advanced breast cancer. Hypertension and proteinuria are characteristic adverse events of BV therapy. We assessed the potential of these adverse events as predictors of BV treatment responses. Our results revealed that groups that developed hypertension and proteinuria early (by day 56) had a stronger antitumor response (Fisher's exact test p<0.05). However, no significant difference was observed in progression-free survival (the Kaplan-Meier method and Log-rank test). As a reference, age, the treatment line, subtypes, liver and renal function, diabetes mellitus and hyperlipidemia history, body mass index, influencing concomitant medicine, average relative dose intensity and hematotoxicity did not significantly differ between groups with or without hypertension and with or without proteinuria. These results indicate the potential of the development of hypertension and proteinuria as predictors of improved outcomes with PTX plus BV therapy in patients with breast cancer. However, since both adverse events may preclude the continuation of treatment, their earlier management may be required.
MeSH term(s)	Adult ; Aged ; Angiogenesis Inhibitors/adverse effects ; Angiogenesis Inhibitors/therapeutic use ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; Bevacizumab/adverse effects ; Bevacizumab/therapeutic use ; Breast Neoplasms/drug therapy ; Female ; Humans ; Hypertension/chemically induced ; Middle Aged ; Neoadjuvant Therapy ; Paclitaxel/therapeutic use ; Proteinuria/chemically induced ; Treatment Outcome
Chemical Substances	Angiogenesis Inhibitors ; Antineoplastic Agents, Immunological ; Bevacizumab (2S9ZZM9Q9V) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2018-04-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b17-00605
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Article ; Online: Simultaneous activation of T helper function can augment the potency of dendritic cell-based cancer immunotherapy.

Teramoto, Koji / Ohshio, Yasuhiko / Fujita, Takuya / Hanaoka, Jun / Kontani, Keiichi

Journal of cancer research and clinical oncology

2013 Volume 139, Issue 5, Page(s) 861–870

Abstract: Purpose: Simultaneous activation of T helper 1 (Th1) cell function has crucial roles in induction of potent cytotoxic T lymphocyte (CTL) responses in cancer immunotherapy. Here, we investigated whether dendritic cell (DC)-based vaccines loaded with both ...

Abstract	Purpose: Simultaneous activation of T helper 1 (Th1) cell function has crucial roles in induction of potent cytotoxic T lymphocyte (CTL) responses in cancer immunotherapy. Here, we investigated whether dendritic cell (DC)-based vaccines loaded with both tumor-associated antigen (TAA)-derived MHC class I and pan-MHC class II peptides could elicit more potent CTL responses through simultaneous activation of Th1 function and reduction in CD4(+) regulatory T (Treg) cell proliferation. Methods: C57BL/6 mice bearing LLC1, a mouse Lewis lung cancer cell line, were subcutaneously administered DCs loaded with both LLC-derived MHC class I (MUT1&2) and LLC-unrelated pan-MHC class II (PADRE) peptides (DC-MUT1&2-PADRE). In assays using samples from advanced lung cancer patients, peripheral blood mononuclear cells were stimulated with autologous DCs loaded with both MUC1 MHC class I and PADRE peptides (DC-MUC1-PADRE) in vitro. Subsequently, TAA-specific CTL responses and the population of CD4(+) Treg cells were analyzed. Results: The population of spleen CD4(+) PADRE-specific cells producing interferon-gamma (IFNγ) was significantly increased by DC-MUT1&2-PADRE administration. Vaccinations with DC-MUT1&2-PADRE decreased the population of CD4(+) Treg cells in spleen and augmented CTL responses, effectively leading to suppression of tumor growth. In assays with human samples, CD4(+) Treg cells were induced less frequently, and MUC1-specific cytotoxicity was enhanced by stimulation with DC-MUC1-PADRE compared with that by stimulation with DC-MUC1 alone. Conclusions: Simultaneous activation of Th1 function by DCs loaded with both TAA-derived MHC class I and PADRE peptides augments TAA-specific CTL responses while reducing Treg cell proliferation.
MeSH term(s)	Animals ; Cancer Vaccines/immunology ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Disease Models, Animal ; Female ; Histocompatibility Antigens Class II/chemistry ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunotherapy ; Interferon-gamma/biosynthesis ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Activation/immunology ; Mice ; Neoplasms/immunology ; Neoplasms/therapy ; Peptides/immunology ; Peptides/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology
Chemical Substances	Cancer Vaccines ; Histocompatibility Antigens Class II ; Peptides ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2013-02-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-013-1394-4
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Article ; Online: Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis.

Matsuda, Yoko / Ye, Juanjuan / Yamakawa, Keiko / Mukai, Yuri / Azuma, Kazuki / Wu, Linxuan / Masutomi, Kenkichi / Yamashita, Taro / Daigo, Yataro / Miyagi, Yohei / Yokose, Tomoyuki / Oshima, Takashi / Ito, Hiroyuki / Morinaga, Soichiro / Kishida, Takeshi / Minamoto, Toshinari / Kojima, Motohiro / Kaneko, Shuichi / Haba, Reiji /

Kontani, Keiichi / Kanaji, Nobuhiro / Okano, Keiichi / Muto-Ishizuka, Mariko / Yokohira, Masanao / Saoo, Kousuke / Imaida, Katsumi / Suizu, Futoshi

Journal of the National Cancer Institute

2022 Volume 115, Issue 2, Page(s) 208–218

Abstract: Background: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that ... ...

Abstract	Background: Telomere dysfunction has been reported to be directly involved in carcinogenesis owing to chromosomal instability and immortalization; however, the clinicopathological significance of telomeres remains controversial. We have shown that telomere shortening occurs in normal-appearing duct cells at initiation and then continues during the progression of pancreatic cancer. In this study, we determined the clinicopathological and prognostic value of telomere length (TL) in cancer progression. Methods: TL in both cancer cells and cancer-associated fibroblasts (CAFs) was analyzed by high-throughput quantitative fluorescence in situ hybridization using a previously reported cohort comprising 1434 cases of adenocarcinoma (ADC), squamous cell carcinoma (SCC), adenosquamous carcinoma, hepatocellular carcinoma, and renal cell carcinoma (RCC), which are known cancers with a statistically significantly low incidence of alternative lengthening of telomeres. Cases were divided into 2 groups as follows: longer and shorter telomeres, according to the median TL of cancer cells and CAFs. The statistical significance of TL in cancer cells and CAFs on clinicopathological characteristics and prognosis was analyzed. Results: There was a close association between TL in cancer cells and CAFs. Longer telomeres in cancer cells and CAFs were associated with aggressive features such as advanced stage, high mitosis score and nuclear score, poorly differentiated cancer, and desmoplastic stroma in ADC. Furthermore, a longer TL was an independent prognostic factor for ADC, SCC, and RCC. Conclusions: Longer telomeres are associated with worse prognosis in ADC, SCC, and RCC. Thus, TL is a novel biomarker for the diagnosis of aggressive cancers with poor prognoses.
MeSH term(s)	Humans ; Carcinoma, Renal Cell ; Cancer-Associated Fibroblasts/pathology ; In Situ Hybridization, Fluorescence ; Prognosis ; Telomere Shortening ; Telomere ; Carcinoma, Squamous Cell/pathology ; Liver Neoplasms/pathology ; Kidney Neoplasms ; Telomere Homeostasis
Language	English
Publishing date	2022-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2992-0
ISSN	1460-2105 ; 0027-8874 ; 0198-0157
ISSN (online)	1460-2105
ISSN	0027-8874 ; 0198-0157
DOI	10.1093/jnci/djac226
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Article: Study of the measurement of serum extracellular domain of HER-2/neu protein with CLIA method.

Kuroda, Noriyuki / Kontani, Keiichi / Kajikawa, Tatsushi / Taminato, Tomohiko

Rinsho byori. The Japanese journal of clinical pathology

2010 Volume 58, Issue 6, Page(s) 541–552

Abstract: Objective: Immunohistochemistry (IHC) and Fluorescent In Situ Hybridization (FISH) are important technologies to examine the protein expression and gene amplification of human epidermal growth factor receptor type 2/neu (HER-2/neu), respectively, in ... ...

Abstract	Objective: Immunohistochemistry (IHC) and Fluorescent In Situ Hybridization (FISH) are important technologies to examine the protein expression and gene amplification of human epidermal growth factor receptor type 2/neu (HER-2/neu), respectively, in breast cancer tumors; however, tumor samples are not always available for examination. Therefore, an easy and sensitive examination to detect HER2-overexpressed tumors should be developed. The extracellular domain of HER-2/neu protein (HER2ECD) has been reported to be observed in the serum of many patients with metastatic breast cancer. In this study we assessed the clinical usefulness of serum HER2ECD (sHER2ECD) as a biological marker in breast cancer. Method: We measured sHER2ECD levels in 108 patients with breast cancer using the ADVIA Centaur assay system, and conventional tumor markers, i.e. CEA and CA15-3, using enzyme or chemiluminescent immunoassay. The sHER2ECD levels were compared with the levels of tumor markers and clinical characteristics. Results: Patients with primary breast cancer who had four or more lymph nodes involved (n=6) showed significantly higher sHER2ECD values than those with no nodes involved (n=57, p<0.05) and those with 1 to 3 nodes involved (n=15, p<0.01). In the IHC-positive group, the positive rate of sHER2ECD was higher than those of CA15-3 or CEA. In metastatic breast cancer, the combination of sHER2ECD and CA15-3 showed the highest positive rate (81.5%). In all 3 patients with HER2-overexpressed cancer showing a partial response (PR) or complete response (CR) to trastuzumab therapy, sHER2ECD levels declined after treatment (39.9 to 58.7%). Conclusion: The sHER2ECD assay by the CLIA method may be useful for the diagnosis and monitoring of metastatic/recurrent breast cancer.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/blood ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Female ; Humans ; Immunoassay/methods ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/diagnosis ; Reagent Kits, Diagnostic ; Receptor, ErbB-2/blood ; Sensitivity and Specificity ; Trastuzumab
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Biomarkers, Tumor ; Reagent Kits, Diagnostic ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
Language	English
Publishing date	2010-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	604196-6
ISSN	0047-1860 ; 0485-1404
ISSN	0047-1860 ; 0485-1404
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Article: Predictive biomarkers and effectiveness of MUC1-targeted dendritic-cell-based vaccine in patients with refractory non-small cell lung cancer.

Teramoto, Koji / Ozaki, Yoshitomo / Hanaoka, Jun / Sawai, Satoru / Tezuka, Noriaki / Fujino, Shozo / Daigo, Yataro / Kontani, Keiichi

Therapeutic advances in medical oncology

2016 Volume 9, Issue 3, Page(s) 147–157

Abstract: Background: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be ... ...

Abstract	Background: The dendritic cell (DC)-based vaccine targeting the highly immunogenic tumor antigen, MUC1, has been promising for a cancer immunotherapy; however, predictive biomarkers for beneficial clinical responses of the vaccine remain to be determined. Methods: DCs loaded with MUC1-derived peptide were subcutaneously administered to patients with MUC1-positive non-small cell lung cancer (NSCLC) that was refractory to standard anticancer therapies, every 2 weeks. The effectiveness and tolerability of the vaccine were evaluated, and predictive biomarkers of clinical responses were explored. Results: Between August 2005 and May 2015, 40 patients received the vaccines. The median survival time (MST) after the initial vaccination was 7.4 months, and the 1-year survival rate was 25.0%. The MST for patients who received more than six vaccinations was 9.5 months, and the 1-year survival rate was 39.3%. In this cohort, patients who experienced immune-related adverse events, including skin reactions at the vaccination site and fever, had significantly longer survival times compared with patients without those immune-related adverse events (12.6 Conclusion: The MUC1-targeted DC-based vaccine induced an antitumor immune response that promoted prolonged survival of patients with refractory NSCLC. The occurrence of immune-related adverse events and having a higher percentage of peripheral lymphocytes were predictive biomarkers of a beneficial clinical response during cancer immunotherapy for NSCLC.
Language	English
Publishing date	2016-11-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/1758834016678375
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Article ; Online: Inhibition of transforming growth factor-β release from tumor cells reduces their motility associated with epithelial-mesenchymal transition.

Ohshio, Yasuhiko / Teramoto, Koji / Hashimoto, Masayuki / Kitamura, Shoji / Hanaoka, Jun / Kontani, Keiichi

Oncology reports

2013 Volume 30, Issue 2, Page(s) 1000–1006

Abstract: The high level of transforming growth factor‑β (TGF‑β) in tumor tissue, which is primarily released from tumor cells, helps maintain their metastatic nature and exacerbates the creation of a pro-tumor microenvironment. Although the strategy of targeting ... ...

Abstract	The high level of transforming growth factor‑β (TGF‑β) in tumor tissue, which is primarily released from tumor cells, helps maintain their metastatic nature and exacerbates the creation of a pro-tumor microenvironment. Although the strategy of targeting TGF‑β in cancer therapy has shown promise, its effects remain limited. In the present study, we focused on tumor cells as sources of TGF‑β release, and hypothesized that inhibition of their TGF‑β release could suppress their epithelial-mesenchymal transition (EMT)-associated metastatic nature and inactivate the induction of suppressor immune cells. To investigate this hypothesis, LLC1 cells, a mouse lung cancer cell line, were cultured with the TGF‑β release inhibitor tranilast and the motility of LLC1 cells was examined. Furthermore, to examine whether inhibition of TGF‑β release influences the induction of regulatory T (Treg) cells, spleen cells from normal mice were cultured in medium in which LLC1 cells had been cultured with tranilast. The results showed that tranilast inhibited the release of TGF‑β1 from LLC1 cells without affecting their proliferation. Inhibition of TGF‑β1 release suppressed the invasive activity of LLC1 cells, but enhanced their activity to adhere. mRNA levels of Slug and Twist were decreased in LLC1 cells, whereas levels of E‑cadherin were recovered. Treg cells were less frequently induced by medium in which LLC1 cells had been cultured with tranilast. Taken together, inhibition of TGF‑β1 release dampens the metastatic nature of LLC1 cells through the downregulation of EMT and possesses the possibility to improve antitumor immune responses through suppression of Treg cell induction. These findings provide a new rationale for development of TGF‑β‑targeted molecular immunotherapy against cancer.
MeSH term(s)	Animals ; Cadherins/genetics ; Cadherins/metabolism ; Cell Growth Processes/physiology ; Cell Line ; Cell Line, Tumor ; Cell Movement/physiology ; Down-Regulation ; Epithelial-Mesenchymal Transition/genetics ; Epithelial-Mesenchymal Transition/physiology ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Mice ; RNA, Messenger/genetics ; Snail Family Transcription Factors ; Spleen/metabolism ; Spleen/physiology ; T-Lymphocytes, Regulatory/metabolism ; T-Lymphocytes, Regulatory/pathology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transforming Growth Factor beta1/antagonists & inhibitors ; Transforming Growth Factor beta1/metabolism ; Twist-Related Protein 1/genetics ; Twist-Related Protein 1/metabolism
Chemical Substances	Cadherins ; RNA, Messenger ; Snai2 protein, mouse ; Snail Family Transcription Factors ; Transcription Factors ; Transforming Growth Factor beta1 ; Twist-Related Protein 1
Language	English
Publishing date	2013-08
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2013.2505
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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