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1.
Anticancer Res ; 41(10): 5007-5014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593449

RESUMO

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Furanos/administração & dosagem , Humanos , Cetonas/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Retratamento , Taxa de Sobrevida
2.
Anticancer Res ; 41(9): 4447-4453, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475068

RESUMO

BACKGROUND/AIM: The tumor microenvironment plays an important role in tumor progression. Tumor-associated macrophages (TAMs) have been reported to promote proliferation, invasion, metastasis, angiogenesis, and immunosuppression. Furthermore, angiogenesis has been reported to induce chemoresistance due to the inefficient distribution of drugs to cancer cells. However, the impact of TAMs on chemoresistance via angiogenesis in colorectal cancer (CRC) remains unclear. The aim of the study was to evaluate the impact of TAMs on the chemotherapeutic outcome in CRC. PATIENTS AND METHODS: We enrolled 54 patients who underwent chemotherapy for unresectable metastatic CRC after resection of the primary tumor. We evaluated the density of TAMs and the degree of angiogenesis by immunohistochemistry and then explored the correlation between the density of TAMs and chemotherapeutic outcome. Furthermore, we assessed any correlation between the density of TAMs and that of neovascularity. RESULTS: The high-TAMs group had a significantly worse progression-free survival (p=0.0006) and a poorer response rate (p=0.0274) than the low-TAMs group. In addition, a positive correlation was observed between the density of TAMs and the degree of neovascularity (r=0.665, p=0.0004). CONCLUSION: TAMs were shown to promote chemoresistance via angiogenesis in CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/irrigação sanguínea , Resistencia a Medicamentos Antineoplásicos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Macrófagos Associados a Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Transição Epitelial-Mesenquimal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Microambiente Tumoral
3.
Anticancer Res ; 41(9): 4529-4534, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475079

RESUMO

BACKGROUND/AIM: Blood transfusion and a large amount of intraoperative blood loss (IBL) have been reported to have a negative impact on long-term survival via immunosuppression. In recent years, thanks to the spread of laparoscopic surgery and the development of surgical devices, the average amount of IBL has decreased, as has the need for perioperative blood transfusion. Under such conditions, the prognostic significance of the amount of IBL is unclear. The aim of this study was to assess the impact of the amount of IBL on long-term survival. PATIENTS AND METHODS: A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. RESULTS: The median amount of IBL was 30 ml, and 16 patients received blood transfusion. The overall survival rates were significantly better in the low-IBL (≤100 ml) group than in the high-IBL (>100 ml) group regardless of the blood transfusion. As the amount of IBL increased, the decline rate of the peripheral lymphocyte count increased. CONCLUSION: A large amount of IBL was associated with poor long-term survival, regardless of blood transfusion, in patients with colorectal cancer.


Assuntos
Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Adulto Jovem
4.
Anticancer Res ; 41(7): 3535-3542, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230149

RESUMO

BACKGROUND/AIM: No biomarkers that predict the benefit from anti-vascular endothelial growth factor (VEGF) antibodies have been identified. It is necessary to discover biomarkers that can identify patients who are more likely to benefit from bevacizumab-containing treatment, especially those who are more likely to benefit from treatment with bevacizumab beyond progression (BBP). Levels of serum lactate dehydrogenase (LDH), reported to be an indirect marker of hypoxia and angiogenesis, may be a useful marker for monitoring the efficacy of suppression of angiogenesis. PATIENTS AND METHODS: The clinical data of 91 patients with unresectable metastatic colorectal cancer who were treated with bevacizumab-containing chemotherapy as first-line treatment were collected and studied. RESULTS: In the second-line treatment, the bevacizumab plus chemotherapy group showed significantly better progression-free survival (PFS) in comparison to the chemotherapy-alone group in patients with low post-first-line-treatment serum LDH levels. On the other hand, no significant differences in the PFS rate were observed between the two groups in patients with high post-first-line-treatment serum LDH levels. CONCLUSION: The post-first-line-treatment serum LDH levels may, therefore, be useful marker for predicting the efficacy of treatment with BBP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , L-Lactato Desidrogenase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
5.
Anticancer Res ; 41(7): 3615-3624, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230158

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. PATIENTS AND METHODS: A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. RESULTS: Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. CONCLUSION: Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Taxa de Sobrevida
6.
PLoS One ; 16(7): e0255049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34293030

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status. However, recent investigations have demonstrated that intratumoral fibrosis is important as a factor affecting the infiltration of TILs. This study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis. METHODS: Patients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with CD3&CD8 and intratumoral fibrosis by immunohistochemical staining with α-SMA positive cancer-associated fibroblasts and Masson's trichrome staining against collagen fibers. The "ImageJ" was used to evaluate fibrosis, and the density of TILs in the dense and sparse areas of fibrosis was calculated. The Immunoscore (IS) was obtained based on the density of CD3+/CD8+TILs in the tumor center and invasive margin of the primary tumor. RESULTS: The degree of CD3+/CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver and lung metastases. The area ratio of α-SMA positive cancer-associated fibroblasts and collagen fibers in peritoneal metastases was significantly higher than that of liver and lung metastases. Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area. In the high-IS group of primary tumors, the degree of TIL infiltration in distant metastases was significantly higher than that in the low-IS group. CONCLUSION: The infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.

7.
Anticancer Res ; 41(5): 2605-2610, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952490

RESUMO

BACKGROUND/AIM: Recently, elevated levels of postoperative inflammatory markers have been reported to be associated with poorer long-term survival outcomes, regardless of the occurrence of infectious complications, in gastroenterological malignancies. The aim of this study was to evaluate the association between postoperative inflammation and shorter long-term survival after resection of colorectal liver metastases. PATIENTS AND METHODS: A total of 104 patients who underwent R0 resection for colorectal liver metastases were enrolled. The CRPmax levels were defined as the highest postoperative serum C-reactive protein levels during hospital stay. RESULTS: The high-CRPmax group had a significantly lower relapse-free survival rate than the low-CRPmax group, regardless of the occurrence of infectious complications. CONCLUSION: In colorectal liver metastasis as well as other malignancies, elevated postoperative levels of serum C-reactive protein are associated with shorter long-term survival, regardless of the occurrence of infectious complications.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Colorretais/cirurgia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/sangue , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Inflamação/sangue , Inflamação/microbiologia , Inflamação/patologia , Inflamação/cirurgia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/cirurgia
8.
BMC Womens Health ; 21(1): 225, 2021 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051785

RESUMO

BACKGROUND: 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.


Assuntos
Linfócitos do Interstício Tumoral , Recidiva Local de Neoplasia , Quimioterapia Adjuvante , Hormônios , Humanos , Prognóstico , Microambiente Tumoral
9.
Anticancer Res ; 41(3): 1593-1598, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788754

RESUMO

BACKGROUND/AIM: We previously showed that an elevated postoperative serum C-reactive protein (CRP) level has a negative impact on long-term survival outcomes, regardless of the occurrence of infectious complications in colorectal cancer. However, the cause of postoperative inflammation could not be properly evaluated, because patient background factors, such as the surgical approach (open/laparoscopic), were not unified. PATIENTS AND METHODS: A total of 277 patients who underwent laparoscopic surgery for stage II/III colorectal cancer were enrolled. RESULTS: The high-CRP group had lower relapse-free and overall survival rates in comparison to the low-CRP group. A high postoperative serum CRP level was significantly associated with a larger tumor diameter and longer operation time, and tended to be associated with a higher T stage and larger amount of bleeding. CONCLUSION: Larger tumor volume, longer operation time and larger amount of bleeding were associated with the promotion of postoperative inflammation, which worsened long-term survival outcomes in colorectal cancer.


Assuntos
Infecções Bacterianas/sangue , Proteína C-Reativa/análise , Neoplasias Colorretais/cirurgia , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/mortalidade , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/mortalidade , Adulto Jovem
10.
In Vivo ; 35(2): 1091-1100, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622906

RESUMO

BACKGROUND/AIM: The neutrophil-to-lymphocyte ratio (NLR) and the density of tumor-infiltrating lymphocytes (TILs) have been reported as immunological prognostic factors for various cancers. We evaluated the association between the prognosis and the immunological status in patients who underwent complete resection of pulmonary metastases of colorectal cancer (CRC). PATIENTS AND METHODS: We evaluated the associations between the NLR before the resection of pulmonary metastases and the relapse-free survival (RFS) or overall survival (OS), or between the density of TILs in the pulmonary metastasis and the RFS or OS. RESULTS: The RFS and OS were significantly worse in the NLR-High group than in the NLR-Low group. The RFS was significantly longer in the CD3+TILs-High group than in the CD3+TILs-Low group. CONCLUSION: The NLR and the density of TILs may have prognostic significance in patients who undergo complete resection of pulmonary metastases of CRC.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Linfócitos , Linfócitos do Interstício Tumoral , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
11.
Gan To Kagaku Ryoho ; 48(1): 136-138, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468746

RESUMO

Case 1: A 73-year-old man underwent total gastrectomy for residual gastric cancer, and final pathological diagnosis was pStage ⅠB. Adjuvant chemotherapy was not performed. CT findings showed multiple liver metastasis 16 months after procedure. S-1 and CDDP were administered for 28 months. Although chemotherapy regimen was changed to S-1, paclitaxel plus ramucirumab, nivolumab, irinotecan and S-1 plus oxaliplatin(SOX)after progression, he died 73 months after operation, and 57 months after recurrence. Case 2: A 72-year-old man was pointed out swelling of gastric lymph nodes in CT imaging. He was diagnosed as advanced gastric cancer with para-aortic lymph node metastasis by followed examination. S- 1 plus CDDP was administrated for 30 months. S-1 and SOX were administered after progressive findings, but he died 48 months after diagnosis. We report 2 cases of recurrent and advanced gastric cancer with long-term survival because of successful chemotherapy.


Assuntos
Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Humanos , Metástase Linfática , Masculino , Recidiva Local de Neoplasia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
12.
Gan To Kagaku Ryoho ; 48(1): 148-150, 2021 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-33468750

RESUMO

An 82-year-old woman who underwent total thyroidectomy and left cervical lymph node dissection 21 years ago admitted our hospital because of left cervical pain. Neck CT scan showed a 6 cm tumor on the left clavicle. Pathological diagnosis by needle biopsy revealed poorly differentiated to undifferentiated carcinoma, positive for TTF-1, and diagnosed as thyroid cancer lymph node metastasis anaplastic transformation. Administration of lenvatinib was started after radiation therapy. Since thrombocytopenia was observed, lenvatinib was gradually reduced from 14 mg and the dose was continued at 4 mg. The tumor shrinked and the effect of chemotherapy was partial response. She survived for 3 years while continuing lenvatinib. We reported long-term survival due to radiation therapy and lenvatinib of anaplastic transformation of thyroid cancer in lymph node metastasis due to radiation therapy and lenvatinib.


Assuntos
Quinolinas , Neoplasias da Glândula Tireoide , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Compostos de Fenilureia , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
13.
BMC Cancer ; 20(1): 1215, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302911

RESUMO

BACKGROUND: 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.


Assuntos
Deferasirox/farmacologia , Desferroxamina/farmacologia , Furanos/farmacologia , Quelantes de Ferro/farmacologia , Ferro/deficiência , Cetonas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia , Moduladores de Tubulina/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Antígeno B7-H1/biossíntese , Antígeno B7-H1/genética , Caderinas/biossíntese , Caderinas/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Ferro/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Oncol Lett ; 20(5): 180, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32934747

RESUMO

Currently, when determining treatment regimens, there is an emphasis on the quality of life (QOL), in addition to treatment efficacy. Especially in hormone receptor-positive breast cancer with distant metastases, unless death is imminent, a common first-line treatment is endocrine therapy, which has fewer side effects. In the present study, the differences in QOL were evaluated based on the age and prognostic indicators of 46 patients with hormone receptor-positive breast cancer with distant metastases (stage IV), who received first-line endocrine therapy at the Osaka City University Hospital (Osaka, Japan) between November 2007 and November 2016. QOL score before and after endocrine therapy was retrospectively analyzed, using the Quality of Life Questionnaire for Cancer Patients Treated with Anti-Cancer Drugs-Breast (QOL-ACD-B). There was no significant association between age and any of the clinicopathological features investigated. However, the QOL score of the elderly patient group was significantly higher compared with that of the younger group in the 'Satisfaction with treatment and coping with disease' subcategory (P=0.008). The QOL score of the younger age group in the same subcategory was significantly improved by the treatment (P=0.013). The patients that had an increased overall QOL score 3 months after treatment initiation had a significant extension of progression-free survival (PFS) rate compared to the patients with decreased or no change in QOL (P=0.032). In conclusion, psychological stress was more prominent in younger patients with stage IV breast cancer treated with hormonal therapy compared with elderly patients. Importantly, improving QOL within the 3 months after treatment initiation could lead to longer PFS rate.

15.
Mol Clin Oncol ; 13(2): 195-202, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32714546

RESUMO

The tumor immune environment not only modulates the effects of immunotherapy, but also the effects of other anticancer drugs and treatment outcomes. These immune responses may be evaluated by measuring tumor-infiltrating lymphocytes (TILs), which has been frequently verified clinically. In the present study, the prediction of the therapeutic effect of endocrine therapy by TILs on stage IV breast cancer was clinically analyzed. Data from 40 patients who underwent endocrine therapy as the initial drug therapy for stage IV breast cancer were used. The correlation between TILs, evaluated according to standard methods, and prognosis, including the efficacy of endocrine therapy, was investigated retrospectively. Patients with ≥50% lymphocytic infiltration were considered to have lymphocyte-predominant breast cancer (LPBC). An analysis of outcomes revealed no difference in progression-free survival (PFS; P=0.171), time to treatment failure (TTF; P=0.054), or overall survival (OS; P=0.641) between the high TIL (>10%) and low TIL (≤10%) groups. Patients with LPBC (≥50%) exhibited a significant prolongation of PFS (P=0.005, log-rank), TTF (P=0.001) and OS (P=0.027) compared with non-LPBC patients. On receiver operating characteristics (ROC) curve analysis, better results were obtained with LPBCs [area under the curve (AUC)=0.700] than with TILs (AUC=0.606). The present findings suggest that a high level of lymphocytic infiltration in the tumor stroma may serve as a predictor of the therapeutic efficacy of endocrine therapy in patients with stage IV estrogen receptor-positive breast cancer.

16.
Anticancer Res ; 40(7): 4157-4163, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620665

RESUMO

BACKGROUND/AIM: The efficacy of trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) plus bevacizumab as later-line treatment for metastatic colorectal cancer (mCRC) has been demonstrated. However, little is known about the impact of a usage history of bevacizumab in front-line treatment on the clinical benefit of combining bevacizumab with FTD/TPI. PATIENTS AND METHODS: A total of 62 patients with mCRC treated with FTD/TPI±bevacizumab was enrolled and assessed for chemotherapeutic efficacy and adverse events. RESULTS: Regardless of the usage history of bevacizumab in front-line treatment, the FTD/TPI plus bevacizumab group had a significantly better progression-free survival rate than the FTD/TPI monotherapy group, and no significant differences in the safety profile were observed between the two groups. CONCLUSION: Combining bevacizumab with FTD/TPI improves the survival outcomes with manageable toxicity, regardless of the usage history of bevacizumab in front-line treatment, in patients with mCRC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Pirrolidinas/uso terapêutico , Timidina Fosforilase/antagonistas & inibidores , Trifluridina/uso terapêutico , Uracila/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Timina , Uracila/uso terapêutico , Adulto Jovem
17.
Anticancer Res ; 40(6): 3535-3542, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487655

RESUMO

BACKGROUND/AIM: Inflammation is known to promote the progression of cancer, and there is increasing evidence that inflammation caused by the antitumor response of the host and post-operative infectious complications worsens the prognosis for colorectal cancer. However, the impact of post-operative inflammation caused by surgical stress on long-term survival is unclear. PATIENTS AND METHODS: A total of 274 patients who underwent curative operation for stage II/III colorectal cancer were enrolled and assessed for the serum C-reactive protein (CRP) levels on postoperative day (POD) 1 and 7 and postoperative infectious complications. RESULTS: The high POD-1 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-1 CRP group. Similarly, the high POD-7 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-7 CRP group. Sub-group analysis limited to patients without postoperative infectious complications indicated that the high POD-7 CRP group tended to have a lower relapse-free survival rate and a significantly lower overall survival rate than the low POD-7 CRP group. CONCLUSION: Inflammation caused by postoperative infectious complications and by surgical stress worsens long-term survival outcomes after a curative operation for colorectal cancer.


Assuntos
Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Inflamação/etiologia , Complicações Pós-Operatórias , Estresse Fisiológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Proteína C-Reativa , Colectomia/efeitos adversos , Colectomia/métodos , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Inflamação/diagnóstico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
18.
PLoS One ; 15(6): e0234613, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555715

RESUMO

Cancer-associated fibroblasts (CAFs) are activated fibroblasts and are the major stromal component in various types of malignancies. CAFs often undergo metabolic reprogramming to create an appropriate microenvironment for cancer progression. However, it remains unclear whether the metastatic properties of cancer cells affect aerobic glycolysis in stromal cells. Here, we show that gastric cancer (GC) cells with high metastatic potential strongly promote the metabolic switch from oxidative phosphorylation to aerobic glycolysis in fibroblasts. Transcriptome analysis showed that the expression of glycolysis-related genes, such as LDHA and ENO2, significantly changed in fibroblasts when they were cocultured with cancer cells with high metastatic potential compared to fibroblasts incubated with cancer cells with low metastatic potential. Glucose uptake, lactate production and oxygen consumption in fibroblasts were changed by coculture with GC cells with high metastatic potential. Thus, metabolic reprogramming in CAFs may reflect the metastatic properties of GC cells.


Assuntos
Fibroblastos Associados a Câncer/patologia , Fibroblastos/metabolismo , Glicólise , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Glicólise/genética , Humanos , Metástase Neoplásica , Fosforilação Oxidativa , Neoplasias Gástricas/patologia
19.
BMC Cancer ; 20(1): 598, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590956

RESUMO

BACKGROUND: Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer. METHODS: We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter > 2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted. RESULTS: For SLN biopsy (SLNB), a median of 2 (range, 1-8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter > 10 mm than in those with diameter ≤ 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p < 0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p = 0.017, lymphatic invasion; p = 0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p = 0.008, odds ratio [OR] = 2.522) and TILs (p < 0.001, OR = 0.137) as independent factors. CONCLUSIONS: Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Metástase Linfática/diagnóstico , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Mama/citologia , Mama/imunologia , Mama/cirurgia , Neoplasias da Mama/imunologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática/imunologia , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Prognóstico , Fatores de Risco , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Tomografia Computadorizada por Raios X , Microambiente Tumoral/imunologia
20.
BMC Cancer ; 20(1): 513, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493410

RESUMO

BACKGROUND: Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperatively diagnosed by CNB as DCIS. Risk factors for invasion have been studied by postoperative examination, but no factors have been found that could be obtained preoperatively from blood tests. In this study, we investigated factors predictive of invasion based on preoperative blood tests in patients diagnosed with DCIS by preoperative biopsy. METHODS: In this study, 118 patients who were diagnosed with DCIS by preoperative biopsy were included. Biopsies were performed with 16-gauge CNB or VAB. Peripheral blood was obtained at the time of diagnosis. This study evaluated absolute platelet count, absolute lymphocyte count, lactate dehydrogenase, carcinoembryonic antigen, and cancer antigen 15-3 (CA15-3). The platelet-lymphocyte ratio (PLR) was calculated by dividing the absolute platelet count by the absolute lymphocyte count, and patients were grouped into high PLR (≥160.0) and low PLR (< 160.0) groups. RESULTS: Invasion was found more frequently after surgery in pathologically high-grade cases than in pathologically not-high-grade cases (p = 0.015). The median PLR was 138.9 and 48 patients (40.7%) were classified into the high PLR group. The high PLR group was significantly more likely to have invasion detected by the postoperative pathology than the low PLR group (p = 0.018). In multivariate analysis of factors predictive of invasion in postoperative pathology, a high PLR (p = 0.006, odds ratio [OR] = 3.526) and biopsy method (VAB vs. CNB, p = 0.001, OR = 0.201) was an independent risk factor. CONCLUSIONS: The PLR may be a predictor of invasion in the postoperative pathology for patients diagnosed with DCIS by preoperative biopsy.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Mama/cirurgia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/sangue , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Metástase Linfática , Contagem de Linfócitos , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Contagem de Plaquetas , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
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