RESUMO
An 87-year-old woman with a gradually enlarging mass in her left breast, diagnosed as having left-sided breast cancer with skin invasion by a local practitioner, was referred to our hospital. Computed tomography revealed ascending colon cancer with abdominal wall invasion and a thoracic aortic aneurysm(Stanford type B), in addition to breast cancer with skin invasion. A thoracic endovascular aortic repair and bypass surgery between the subclavian arteries were both performed for the thoracic aortic aneurysm. After 6 days, a right hemicolectomy and D2 lymphadenectomy were performed for the ascending colon cancer. A postoperative pathological diagnosis of pT3N0M0, pStage â ¡a, was made. A total left mastectomy with a full-thickness skin graft for left breast cancer was performed after 2 months following the ascending colon cancer surgery. The postoperative pathological diagnosis was pT3N0M0, pStage â ¡B. No evidence of local recurrence or distant metastasis of the ascending colon cancer has been observed at 20 months postoperatively, or of the breast cancer after 18 months following surgery.
Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Neoplasias da Mama , Neoplasias do Colo , Idoso de 80 Anos ou mais , Feminino , Humanos , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Colo Ascendente/cirurgia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Mastectomia , Stents , Resultado do TratamentoRESUMO
A 57-year-old man was diagnosed as having resectable advanced esophageal carcinoma adjacent to the trachea(Ut, cT3N0M0)and received preoperative docetaxel, cisplatin, and 5-fluorouracil therapy. Due to tracheal tumor invasion and upstaging to cT4bN0M0 after 1 course of chemotherapy, the treatment was converted to definitive chemoradiotherapy (CRT). A remarkable response with no evidence of tracheal invasion was observed on computed tomography following definitive CRT. He underwent successful curative resection with salvage esophagectomy, and the resected tumor was staged as pT1bN0M0. No adjuvant therapy was administered, and the patient was alive with no evidence of disease at the 5-year postoperative follow-up. The response to preoperative treatment should be meticulously assessed and appropriate treatment modalities used to avoid overlooking the potential for cure, even if the response to preoperative treatment with docetaxel, cisplatin, and 5-fluorouracil is poor.
Assuntos
Carcinoma , Neoplasias Esofágicas , Masculino , Humanos , Pessoa de Meia-Idade , Cisplatino , Docetaxel/uso terapêutico , Fluoruracila , Traqueia/patologia , Esofagectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Quimiorradioterapia , Carcinoma/tratamento farmacológico , Resultado do TratamentoRESUMO
Although numerous experiments revealed an essential role of a lipid mediator, sphingosine-1-phosphate (S1P), in breast cancer (BC) progression, the clinical significance of S1P remains unclear due to the difficulty of measuring lipids in patients. The aim of this study was to determine the plasma concentration of S1P in estrogen receptor (ER)-positive BC patients, as well as to investigate its clinical significance. We further explored the possibility of a treatment strategy targeting S1P in ER-positive BC patients by examining the effect of FTY720, a functional antagonist of S1P receptors, on hormone therapy-resistant cells. Plasma S1P levels were significantly higher in patients negative for progesterone receptor (PgR) expression than in those positive for expression (p = 0.003). Plasma S1P levels were also significantly higher in patients with larger tumor size (p = 0.012), lymph node metastasis (p = 0.014), and advanced cancer stage (p = 0.003), suggesting that higher levels of plasma S1P are associated with cancer progression. FTY720 suppressed the viability of not only wildtype MCF-7 cells, but also hormone therapy-resistant MCF-7 cells. Targeting S1P signaling in ER-positive BC appears to be a possible new treatment strategy, even for hormone therapy-resistant patients.
Assuntos
Neoplasias da Mama/metabolismo , Lisofosfolipídeos/análise , Esfingosina/análogos & derivados , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Cloridrato de Fingolimode/farmacologia , Expressão Gênica/genética , Humanos , Metástase Linfática , Lisofosfolipídeos/sangue , Lisofosfolipídeos/metabolismo , Células MCF-7 , Pessoa de Meia-Idade , Plasma/química , Receptores de Estrogênio/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Transdução de Sinais , Esfingosina/análise , Esfingosina/sangue , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/efeitos dos fármacos , Receptores de Esfingosina-1-Fosfato/metabolismoRESUMO
A 70-year-old female with liver metastases from gastrointestinal stromal tumor(GIST)that were found 3 months after partial gastrectomy for the primary GIST underwent Auchincloss operation for left breast cancer with ipsilateral axillary lymph node metastases. The diagnosis was microinvasive ductal cancer that was pT1miN1M0, pStage â ¡A, hormone receptor negative, and HER2 positive. Given the impact of this cancer on the prognosis of liver metastases of GIST, imatinib therapy, but not adjuvant chemotherapy, was started promptly for breast cancer after surgery. Four months after the surgery, left subclavian lymph node recurrence of breast cancer was found. Since the liver metastases of GIST had been stable, imatinib was discontinued, and paclitaxel and anti-HER2 therapy were administered. After confirming tolerability, imatinib was carefully added in combination. Because the lymph nodes shrank and liver metastases of GIST were stable, both anti-HER2 therapy and imatinib were continued. There are few reports of combined chemotherapy for synchronous double cancer, and we report our experience in which careful treatment was required.
Assuntos
Neoplasias da Mama , Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND: Although previous experiments have implicated sphingosine-1-phosphate (S1P) as a links between immune reactions and cancer progression, the exact mechanism of this interaction has not comprehensively studied in clinical human samples. This study sought to evaluate the S1P regulation by sphingosine kinase 1 (SPHK1), an S1P-producing enzyme, in the immunity/immuno-reactivity of clinical human breast cancer surgical specimens. METHODS: S1P levels were examined in tumor, peritumoral, and normal human breast samples using mass spectrometry. Genomics Data Commons data portal of The Cancer Genome Atlas cohort was used to assess the expression of S1P-related and immune-related genes. RESULTS: S1P levels were significantly higher in tumor samples compared to peritumoral (P < 0.05) or normal human breast samples (P < 0.001). SPHK1 gene expression was elevated in tumoral samples compared to normal breast samples (P < 0.01). Furthermore, the elevated expression of SPHK1 in breast cancer tissue was associated with an increased expression of the different kinds of immune-related genes, such as CD68, CD163, CD4, and FOXP3 (forkhead box P3), in HER2-negative breast cancer. Network analysis showed the central role of SPHK1 in the interaction of S1P signaling and expression of immune cell-related proteins. CONCLUSIONS: We demonstrated that S1P is mainly produced by tumor tissue, rather than peritumoral tissue, in breast cancer patients. Our data revealed the involvement of S1P signaling in the regulation of immune-related genes, suggesting the links between S1P and complicated immune-cancer interactions in breast cancer patients.
Assuntos
Neoplasias da Mama/imunologia , Mama/patologia , Regulação Neoplásica da Expressão Gênica/imunologia , Lisofosfolipídeos/análise , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Esfingosina/análogos & derivados , Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Conjuntos de Dados como Assunto , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Lisofosfolipídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/análise , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Espectrometria de Massas por Ionização por Electrospray , Esfingosina/análise , Esfingosina/metabolismo , Espectrometria de Massas em TandemRESUMO
We report the case of an elderly male patient with ductal carcinoma in situ(DCIS) of the nipple. A 93-year-old man visited the hospital because of pain and bleeding in and swelling of the right nipple. A benign tumor was suspected, but a definite diagnosis could not be made before surgery based on echo and cytology findings; thus, a malignant tumor could not be ruled out. He underwent partial mastectomy combined with the areola and nipple for diagnosis and treatment. Histologic examination confirmed the diagnosis of DCIS of the nipple. The surgical margin was negative. At 6 months after the surgery, he was doing well with no evidence of disease in the absence of postoperative adjuvant therapy. Thus, clinicians should consider breast carcinoma of the nipple as a differential diagnosis when an elderly man presents with swelling of the nipple.
Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Humanos , Mastectomia , Mastectomia Segmentar , Mamilos/cirurgiaRESUMO
A 48-year-old female discovered a mass in her left axilla. A thorough examination resulted in a diagnosis of left invasive lobular carcinoma(ILC)of the accessory mammary gland with wide ductal spread. Considering the wide ductal spread, massive resection of the left axilla mass, left lymph node dissection, and a latissimus dorsi musculocutaneous flap procedure were performed. However, histological analysis revealed ILC measuring 80×50 mm with lymph node metastases(5/23)and extensive cancer spread, resulting in a positive surgical margin. It is important to recognize the characteristics of ILC, axillary accessory breast cancer, and the axilla in a treatment strategy.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Glândulas Mamárias Humanas , Axila , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Pessoa de Meia-IdadeRESUMO
Here, we report about a woman in her 30s who had peritoneal dissemination and multiple colon cancer with high-frequency microsatellite instability(MSI-H). Her father, paternal grandfather, and maternal grandmother had a history of colorectal cancer treatment. Thus, Lynch syndrome was suspected. We performed R0 resection for peritoneal dissemination and subsequent peritoneal dissemination. A 435-gene panel testing using a next-generation sequencer identified MSH2 and other mutations in the tumor. Hence, we speculated that she could have a germline mutation of MSH2, which causes Lynch syndrome. In the future, if she wishes to receive genetic counseling and undergo germline testing for variants to confirm the diagnosis of Lynch syndrome, we will perform them after receiving informed consent.
Assuntos
Neoplasias do Colo , Proteína 2 Homóloga a MutS/genética , Adulto , Neoplasias do Colo/genética , Feminino , Mutação em Linhagem Germinativa , Humanos , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutLRESUMO
Precision medicine can be defined as the customization of medical treatment based on the individual genetic profile, which enables one to identify patients who respond to therapies while sparing side effects for those who do not. Breast cancer patients have been treated based on subtyping, which is considered a prototype of precision medicine. Furthermore, the development of multigene panel testing has resulted in a paradigm shift in the treatment of breast cancer. The knowledge generated from the Human Genome Project, and subsequently The Cancer Genome Atlas, has provided the concept of precision medicine, in which cancer patients can be sub-classified based on actionable driver mutations that can be selectively targeted by molecular targeted drugs and treated by appropriate molecular targeted therapies. Development of next-generation sequencing has both dramatically advanced genomic sequencing technology and revealed actionable driver mutations for individual cancer patients when applied to a clinical setting. Clinical target sequencing by next-generation sequencing enables one to formulate treatment strategies, not only by selecting a subgroup of patients who are expected to experience more effectiveness of each drug, but also by revealing patients with drug resistance based on their actionable driver mutations.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Terapia de Alvo Molecular , Mutação , Medicina de Precisão , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Feminino , HumanosRESUMO
BACKGROUND: Pancreatic cancer is a disease with poor prognosis, and development of new treatments is necessary. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays a critical role in progression of many types of cancer. However, little is known about the role of sphingosine kinases in pancreatic cancer. This study investigated the roles of sphingosine kinases in pancreatic cancer progression. MATERIALS AND METHODS: S1P levels in pancreatic cancer and noncancerous pancreatic tissue were measured in 10 patients. We generated PAN02 murine pancreatic cancer cell lines with a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system genes 9 (Cas9)-mediated deletion of SphK1 or SphK2 and assessed cell growth and migration. In an animal model, we assessed the survival of mice injected with PAN02 cells intraperitoneally. RESULTS: S1P levels in the pancreatic cancer tissue were significantly higher than those in noncancerous tissue. SphK1 knockout (KO) cells showed greater proliferation and migration than wild type (WT) cells, and SphK2 KO cells showed less proliferation and migration than WT cells. Animal experiments showed that the survival of mice injected with SphK1 KO cells was significantly shorter than those injected with WT cells, and the survival of mice injected with SphK2 KO cells was longer than those injected with WT cells. Surprisingly, cytotoxic assay using gemcitabine showed that SphK1 KO cells survived less than WT cells, and SphK2 KO cells survived more than WT cells. CONCLUSIONS: S1P produced by SphK1 and SphK2 may have different functions in pancreatic cancer cells. Targeting both SphK1 and SphK2 may be a potential strategy for pancreatic cancer treatment.
Assuntos
Neoplasias Pancreáticas/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/fisiologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Lisofosfolipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/enzimologia , Neoplasias Pancreáticas/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/análise , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Esfingosina/análogos & derivados , Esfingosina/fisiologiaRESUMO
A 33-year-old woman underwent resection of a right breast mass, which was diagnosed as a fibroadenoma 15 years ago. Ten years later, a right breast mass appeared again, and it was diagnosed as a fibroadenoma based on core needle biopsy. After observation for a while, the mass increased in size, and she underwent resection of the tumor, which was diagnosed as a borderline-malignant phyllodes tumor. A mass appeared again in the right breast and rapidly expanded. A malignant phyllodes tumor was suspected, and right mastectomy was performed. The pathological diagnosis revealed a benign phyllodes tumor. Four years ago, a left breast mass was also detected. Because the mass was suspected to be a fibroadenoma, it has been observed for a few years. The mass has increased in size since 1 year ago, and another mass emerged 2 months ago. Core needle biopsy of the 2 masses revealed that both were phyllodes tumors. She underwent left mastectomy, and the pathological examination revealed that both masses were benign phyllodes tumors. We report this rare case of metachronal phyllodes tumors that presented bilaterally.
Assuntos
Neoplasias da Mama , Fibroadenoma , Tumor Filoide , Adulto , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Feminino , Fibroadenoma/diagnóstico , Fibroadenoma/cirurgia , Humanos , Mastectomia , Tumor Filoide/diagnóstico , Tumor Filoide/cirurgiaRESUMO
A 68-year-old woman who had leftbreastcancer (cT2N0M0, cStage â ¡A)underwentbreast -conserving therapy and sentinel lymph node biopsy. Pathological diagnosis of the resected specimen revealed a 60mm cancer lesion including a 50 mm invasive ductal carcinoma with surrounding ductal carcinoma in situ, although the pre-operative MRI suggested a 30mm invasive cancer. The surgical margin was positive with the exposure of ductal carcinoma in situ. Additional resection was performed with a resection margin of 20mm from the head-side stump of the previous surgery. Pathological diagnosis of the additionally resected specimen revealed a 6mm invasive carcinoma with its exposure on the surface of the specimen around the new surgical stump distant from the initial surgical margin, where no remnant cancer was noted. She underwent left mastectomy. Pathological diagnosis further revealed 7mm and 2mm invasive carcinomas in the remnant breast. The preoperative imaging was reviewed retrospectively, and it was found that identifying the nodules in the remnant breast was quite difficult based on the images, including MRI. We report a case of breast cancer with metastatic nodules in additionally resected specimens.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mastectomia , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses. S1P is formed in cells by sphingosine kinases and released from them, which acts in an autocrine, paracrine, and/or endocrine manner. S1P in extracellular space, such as interstitial fluid, interacts with components in the tumor microenvironment, which may be important for metastasis. Importantly, recent translational research has demonstrated an association between S1P levels in breast cancer patients and clinical outcomes, highlighting the clinical importance of S1P in breast cancer. We suggest that S1P is one of the key molecules to overcome the resistance to the drug therapies, such as hormonal therapy, anti-HER2 therapy, or chemotherapy, all of which are crucial aspects of a breast cancer treatment.
Assuntos
Neoplasias da Mama/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Animais , Humanos , Linfangiogênese/genética , Linfangiogênese/fisiologia , Modelos Biológicos , Metástase Neoplásica , Esfingosina/metabolismoRESUMO
A 59-year-old woman attended a previous hospital complaining of a nodule of the right axilla. Although ultrasonography had shown no evidenceof malignancy, a growth of thenodulewas found on follow-up. Excisional biopsy revealed a primary accessory breast cancer. Because the resected margins were involved, she was referred to our hospital for additional treatment. Based on imaging, both bilateral mammary glands and axillary lymph nodes were reported normal, and distant metastasis was not observed. We performed additional resection of the right axillary tissue around the biopsy site and the right axillary lymph nodedisse ction. Histo-pathological examination revealed the residual invasive ductal carcinoma in the resected specimen. Both the new surgical margins and the lymph nodes were free of disease. Accessory breast cancer is relatively rare, with the incidence being less than 1% of all breast cancers. It is most frequent in the axillary region. Local extensive resection with sufficient surgical margin and axillary lymph node dissection are generally required. This case report presents our clinical experience of accessory breast cancer with some discussion of the literature.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama , Axila , Biópsia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.
Assuntos
Neoplasias da Mama/metabolismo , Mama/metabolismo , Líquido Extracelular/metabolismo , Lisofosfolipídeos/metabolismo , Glândulas Mamárias Animais/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Esfingosina/análogos & derivados , Microambiente Tumoral , Ativação Metabólica , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Líquido Extracelular/efeitos dos fármacos , Feminino , Cloridrato de Fingolimode/farmacocinética , Cloridrato de Fingolimode/uso terapêutico , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Lisofosfolipídeos/sangue , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos Endogâmicos BALB C , Camundongos Knockout , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêutico , Distribuição Aleatória , Esfingosina/sangue , Esfingosina/metabolismo , Microambiente Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Sphingosine-1-phosphate (S1P), a pleiotropic bioactive lipid mediator, has been implicated as a key regulatory molecule in cancer through its ability to promote cell proliferation, migration, angiogenesis, and lymphangiogenesis. Previous studies suggested that S1P produced by sphingosine kinase 1 (SphK1) in breast cancer plays important roles in progression of disease and metastasis. However, the associations between S1P and clinical parameters in human breast cancer have not been well investigated to date. MATERIALS AND METHODS: We determined levels of S1P and other sphingolipids in breast cancer tissue by electrospray ionization-tandem mass spectrometry. Associations between S1P levels and clinicopathologic features of the tumors were analyzed. Expression of phospho-SphK1 (pSphK1) in breast cancer tissues was determined by immunohistochemical scoring. RESULTS: Levels of S1P in breast cancer tissues were significantly higher in patients with high white blood cell count in the blood than those patients without. S1P levels were lower in patients with human epidermal growth factor receptor 2 overexpression and/or amplification than those patients without. Furthermore, cancer tissues with high pSphK1 expression showed significantly higher levels of S1P than cancer tissues without. Finally, patients with lymph node metastasis showed significantly higher levels of S1P in tumor tissues than the patients with negative nodes. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that high expression of pSphK1 is associated with higher levels of S1P, which in turn is associated with lymphatic metastasis in breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Lisofosfolipídeos/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Esfingosina/análogos & derivados , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Genes erbB-2 , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Esfingosina/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
BACKGROUND: Sphingolipids, including sphingosine-1-phosphate (S1P) and ceramide, have emerged as key regulatory molecules that control various aspects of cell growth and proliferation in cancer. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients have yet to be determined. The aims of this study were to determine the levels of sphingolipids including S1P, ceramides, and other sphingolipids, in breast cancer and normal breast tissue and to compare the difference in levels of each sphingolipid between the two tissues. MATERIALS AND METHODS: Tumor and noncancerous breast tissue were obtained from 12 patients with breast cancer. Sphingolipids including S1P, ceramides, and their metabolites of sphingosine, sphingomyelin, and monohexosylceramide were measured by liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS: The levels of S1P, ceramides, and other sphingolipids in the tumor were significantly higher than those in normal breast tissue. There was a relatively strong correlation in the levels of S1P between the tumor and those of normal breast tissue from the same person. On the other hand, there was no correlation in the levels of most of the ceramide species between the tumor and those of normal breast tissue from the same person. CONCLUSIONS: To our knowledge, this is the first study to reveal that levels of sphingolipids in cancer tissue are generally higher than those of normal breast tissue in patients with breast cancer. The correlation of S1P levels in these tissues implicates the role of S1P in interaction between cancer and the tumor microenvironment.
Assuntos
Neoplasias da Mama/metabolismo , Lisofosfolipídeos/metabolismo , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Feminino , Humanos , Esfingosina/metabolismoRESUMO
Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.
Assuntos
Carcinoma Hepatocelular/etiologia , Dano ao DNA/genética , Neoplasias Hepáticas/etiologia , Lisofosfolipídeos/fisiologia , Transdução de Sinais/fisiologia , Esfingosina/análogos & derivados , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Carcinoma Hepatocelular/terapia , Dano ao DNA/fisiologia , Hepatite B/complicações , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/terapia , Liases/fisiologia , Lisofosfolipídeos/metabolismo , Terapia de Alvo Molecular , Hepatopatia Gordurosa não Alcoólica/complicações , Monoéster Fosfórico Hidrolases/fisiologia , Fosfotransferases (Aceptor do Grupo Álcool)/fisiologia , Esfingosina/metabolismo , Esfingosina/fisiologiaRESUMO
A 63-year-old woman was found to have a mass in her right breast and visited our hospital to undergo a detailed examination. A histopathological examination by using ultrasound-guided core needle biopsy revealed ductal carcinoma in situ. A partial mastectomy with sentinel lymph node biopsy was performed for the cancer of the right breast. The postoperative histopathological examination indicated apocrine carcinoma with a predominantly intraductal component without lymph node metastasis. The discrimination between ductal adenoma and apocrine carcinoma sometimes becomes a problem in making decisions about treatment. We need to take care when making a diagnosis.
Assuntos
Glândulas Apócrinas/patologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Biópsia de Linfonodo Sentinela , Resultado do TratamentoRESUMO
Although ductal carcinoma in situ(DCIS)is generally cured by surgical resection, it has been suggested that resection is over-treatment for some patients with DCIS. The aim of this study was to reconsider operative indications for patients with DCIS by examining clinicopathological features of 23 patients who underwent surgical resection for DCIS in our institute over a single year. Postoperative histological examination revealed that there were Luminal and HER2-positive subtypes, but no triple negative cancers. We found coincidental invasive ductal carcinoma(IDC)in 5 patients, and in all 5 the tumor size exceeded 60 mm. There was no coincidence of IDC in patients with a Ki-67 index ≤5%. Positive surgical margins were observed in 7 patients, all of which were histologically diagnosed as DCIS. Only 1 of the 7 patients underwent additional surgical resection; the 6 remaining patients, including 2 patients who received no treatment, did not undergo additional resection. All patients including those with positive surgical margins have had a 5-year relapse-free survival. Our findings imply that the subgroup of DCIS patients without IDC could be followed up without surgery.