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1.
Transl Cancer Res ; 13(4): 1773-1785, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38737680

RESUMO

Background: The recently developed anti-human epidermal growth factor receptor 2 (HER2) therapy has substantially improved the prognosis of HER2-positive breast cancer. The DESTINY-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) significantly prolonged the survival of patients with HER2-low breast cancer, thus presenting a paradigm shift in anti-HER2 therapy. This may facilitate a change in the treatment strategy for HER2-low breast cancer. However, the implication of HER2-low in hormone receptor (HR)-positive breast cancer is unclear. In this retrospective study, we aimed to reveal the association between HER2 status, namely HER2-low and HER2-zero, and prognosis in HR-positive breast cancer. Methods: We collected the data of 247 patients with estrogen receptor (ER)-positive/HER2-negative breast cancer (159 with HER2-low and 88 with HER2-zero breast cancer) who underwent surgery. Patients were divided into HER2-low and HER2-zero groups. Univariate analysis was performed to evaluate the baseline characteristics using the Wilcoxon rank sum test and Fisher's exact test. Survival analysis of the HER2-low and HER2-zero groups was performed using the Kaplan-Meier method. Results: The median observation period was 2,706 days, and the median period until recurrence was 1,380 days; 25 patients (10%) had recurrences. Age (P=0.004) and menopausal status (P=0.04) were significant variables in the univariate analysis of baseline characteristics. In the subgroup analysis of luminal A- and B-like breast cancers, there was a significant difference in overall survival (OS) only in patients with luminal A-like breast cancer, but relapse-free survival (RFS) of the HER2-low luminal B-like cancer subgroups tended to be relatively short. Conclusions: We inferred that the HER2-low and HER2-zero statuses do not affect the RFS and OS of patients with ER-positive breast cancer. The prognostic significance of HER2-low or HER2-zero status in luminal A- and B-like breast cancers might differ, and a new treatment strategy is required for the HER2-low subgroup.

2.
Geriatr Gerontol Int ; 24(6): 571-576, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38690756

RESUMO

AIM: Whether serum concentration of procalcitonin (PCT), brain natriuretic peptide (BNP) and albumin (Alb) have an association with the outcome of hospitalized older patients is unclear. We investigated clinical outcomes and any predictive factors in hospitalized Japanese older patients with a risk of infection. METHODS: In the retrospective study, 820 Japanese patients were followed up for 30 days or until death. During the observation period, 656 patients survived and 164 patients died. The predictive factors of death were analyzed according to demographic and clinical variables. RESULTS: The survival rate was decreased as the serum PCT increased from <0.5 to ≥10 ng/mL, as was also the case with BNP from <300 to ≥300 pg./mL, whereas low Alb (<2.5 g/dL) showed a lower survival rate than high Alb (≥2.5 g/dL; P < 0.01). Using the Cox regression model, the multivariable-adjusted hazard ratios (95% confidence interval) were as follows: PCT 0.5-2 versus <0.5 ng/mL: 1.61(1.04-2.49), PCT 2-10 versus <0.5 ng/mL: 1.91(1.15-3.16), PCT ≥10 versus <0.5 ng/mL: 2.90(1.84-4.59), high BNP 1.26 (0.89-1.76) and low Alb 0.68 (0.52-0.87). The mortality rate increased as the number of scores (PCT + BNP + Alb) increased. CONCLUSIONS: Concentration-dependent high PCT, high BNP and low Alb were positive risk factors associated with poor prognosis in hospitalized older patients with a risk of infection. Geriatr Gerontol Int 2024; 24: 571-576.


Assuntos
Biomarcadores , Peptídeo Natriurético Encefálico , Pró-Calcitonina , Albumina Sérica , Humanos , Masculino , Feminino , Biomarcadores/sangue , Idoso , Japão/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Prognóstico , Estudos Retrospectivos , Pró-Calcitonina/sangue , Idoso de 80 Anos ou mais , Albumina Sérica/análise , Hospitalização , Medição de Risco/métodos , Valor Preditivo dos Testes , Fatores de Risco , Taxa de Sobrevida/tendências , Infecções/sangue , Infecções/mortalidade , População do Leste Asiático
3.
J Vasc Access ; : 11297298231225808, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316617

RESUMO

BACKGROUND: Totally implantable central venous access ports, are required for various purposes, ranging from chemotherapy to nutrition. Port infection is a common complication. In many patients with port infection, the ports are removed because antibiotics are ineffective. We evaluated the risk factors associated with port removal due to port infection. METHODS: By retrospective chart review, we collected data of 223 patients who underwent port removal for any reason. Port infection was defined as infection symptoms, such as fever; elevated white blood cell counts or C-reactive protein levels; or redness at the port site, in the absence of other infections, which improved with port removal. The characteristics of patients with or without port infection were compared using univariate (chi-squared test, t-test) and multivariate logistic regression analyses. RESULTS: We compared 172 patients without port infection to 51 patients with port infection. Univariate analysis identified sex (p = 0.01), body mass index (BMI) ⩽20 kg/m2 (p = 0.00004), diabetes mellitus (p = 0.04), and purpose of use (p = 0.0000003) as significant variables. However, male sex (p = 0.03, 95% confidence interval [CI]: 0.01-0.23), BMI ⩽20 kg m2 (p = 0.002, 95% CI: 0.06-0.29), and purpose of use (total parenteral nutrition (TPN); p = 0.000005, 95% CI: 0.31-0.76) remained significant using multivariate analysis. Moreover, the patients with short bowel syndrome and difficulty in oral intake tended to be infected easily. Additionally, Staphylococcus species were the most common microbes involved in port infection. CONCLUSIONS: Male sex, BMI ⩽20 kg/m2, and purpose of use as a TPN were risk factors for port infection. Ports should not be used for long duration of TPN or used only in exceptional cases.

4.
J Evid Based Dent Pract ; 23(3): 101896, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689451

RESUMO

PURPOSE: No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer. BASIC PROCEDURES: Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2. MAIN FINDINGS: Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed. PRINCIPAL CONCLUSIONS: The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.


Assuntos
Antineoplásicos , Neoplasias da Mama , Estomatite , Humanos , Feminino , Antissépticos Bucais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Estomatite/induzido quimicamente , Estomatite/prevenção & controle , Ciclofosfamida/efeitos adversos , Antineoplásicos/efeitos adversos , Dexametasona/uso terapêutico
5.
Ann Gastroenterol Surg ; 7(2): 279-286, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36998301

RESUMO

Purpose: Anastomotic leakage (AL) is a serious postoperative complication that affects short- and long-term outcomes. The use of a trans-anal drainage tube (TDT) is reported to prevent AL in rectal cancer patients, but its value in sigmoid colon cancer patients is unknown. Methods: Admitted to the study were 379 patients who underwent surgery for sigmoid colon cancer between 2016 and 2020. Patients were divided into two groups according to the placement (n = 197) or nonplacement of a TDT (n = 182). To determine the factors affecting the association between TDT placement and AL, we estimated average treatment effects by stratifying each factor using the inverse probability of treatment weighting method. The association between prognosis and AL was evaluated in each identified factor. Results: Factors associated with postsurgical insertion of a TDT were advanced age, male sex, high body mass index (BMI), poor performance status, and presence of comorbidities. TDT placement was associated with a significantly lower AL in male patients (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.07-0.73; P = .013) and for BMI ≥ 25 kg/m2 (OR, 0.13; 95% CI, 0.02-0.65; P = .013). In addition, there was a significant association of AL with poor prognosis in patients with BMI ≥ 25 kg/m2 (P = .043), age > 75 y (P = .021), and pathological node-positive disease (P = .015). Conclusion: Sigmoid colon cancer patients with BMI ≥ 25 kg/m2 are the most appropriate candidates for postoperative TDT insertion, in terms of reduced incidence of AL and improved prognosis.

6.
Science ; 379(6636): 1023-1030, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36893254

RESUMO

Cell-cell interactions in the central nervous system play important roles in neurologic diseases. However, little is known about the specific molecular pathways involved, and methods for their systematic identification are limited. Here, we developed a forward genetic screening platform that combines CRISPR-Cas9 perturbations, cell coculture in picoliter droplets, and microfluidic-based fluorescence-activated droplet sorting to identify mechanisms of cell-cell communication. We used SPEAC-seq (systematic perturbation of encapsulated associated cells followed by sequencing), in combination with in vivo genetic perturbations, to identify microglia-produced amphiregulin as a suppressor of disease-promoting astrocyte responses in multiple sclerosis preclinical models and clinical samples. Thus, SPEAC-seq enables the high-throughput systematic identification of cell-cell communication mechanisms.


Assuntos
Anfirregulina , Astrócitos , Comunicação Autócrina , Testes Genéticos , Técnicas Analíticas Microfluídicas , Microglia , Astrócitos/fisiologia , Testes Genéticos/métodos , Ensaios de Triagem em Larga Escala , Técnicas Analíticas Microfluídicas/métodos , Microglia/fisiologia , Anfirregulina/genética , Comunicação Autócrina/genética , Expressão Gênica , Humanos
7.
J Cancer Educ ; 38(2): 406-411, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-34989978

RESUMO

The aim of this study was to evaluate the knowledge and educational needs with regard to hereditary breast and ovarian cancer among nurses working in breast cancer care in the Nagasaki Prefecture. In breast cancer care, the identification of patients at risk for hereditary breast and ovarian cancer is necessary for the implementation of genetic testing and counseling. Nurses should be involved in this process, since they play a crucial role in the care of patients with breast cancer. However, the knowledge regarding hereditary breast and ovarian cancer among nurses working in oncology care in Japan has not been assessed. The design of this study is cross-sectional design. We distributed 597 surveys to nurses working in breast cancer care. The surveys assessed the nurses' demographic data, their current knowledge and practices regarding cancer genetics and hereditary breast and ovarian cancer, and their attitude and preferences regarding learning about the condition. We received 317 valid replies. Nurses had limited knowledge about hereditary breast and ovarian cancer characteristics: 41.6% reported that they do not know about the condition, whereas less than 10% knew its characteristics. However, nurses were aware of hereditary breast and ovarian cancer significance and were willing to learn about it: 91% wished to learn about the condition, and 88.6% wanted to participate in study group meetings. Further, nurses' preferences regarding educational programs were clarified. Overall, our results show that educational programs should be implemented to advance nurses' knowledge of hereditary breast and ovarian cancer characteristics.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Competência Clínica , Estudos Transversais , Neoplasias Ovarianas/genética , Neoplasias da Mama/genética , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
8.
Int J Surg Pathol ; 31(4): 460-463, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35635208

RESUMO

We present a rare tumor of adenoid cystic carcinoma, solid-basaloid subtype of the breast. Solid-basaloid adenoid cystic carcinoma may have a worse prognosis than classical adenoid cystic carcinoma. A 70-year-old woman presented with a mass in her left breast. Malignancy was suspected on imaging and confirmed via core needle biopsy. Left breast partial mastectomy and sentinel lymph node biopsy were performed. Histologically, the tumor was composed of basaloid cells with hyperchromatic nuclei and frequent mitotic figures, as are small-cell neuroendocrine carcinomas. Immunohistochemical analysis of the tumor cells showed high expression of KIT and CD10 and focal expression of keratin 7. Synaptophysin, chromogranin A, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were not expressed. This patient should be followed up carefully for distant metastases and recurrences.


Assuntos
Neoplasias da Mama , Carcinoma Adenoide Cístico , Carcinoma de Células Pequenas , Feminino , Humanos , Idoso , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/cirurgia , Mastectomia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Carcinoma de Células Pequenas/patologia , Mastectomia Segmentar
9.
Clin Case Rep ; 10(12): e6762, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36545558

RESUMO

Breast cancer patients with bone marrow metastasis (BMM) having profound thrombocytopenia and anemia are rare and there is no definitive treatment guideline. We present a case of successful initial treatment with anti-disseminated intravascular coagulation therapy and endocrine therapy, followed by chemotherapy to avoid deterioration of severe thrombocytopenia and anemia.

10.
Acta Med Okayama ; 76(6): 689-694, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36549771

RESUMO

Taxanes are key drugs for patients with breast cancer. A major adverse effect of taxanes is peripheral neuropathy (PN). To investigate the ability of compression therapy using sleeves and stockings to prevent PN due to the taxane docetaxel, we conducted a single-center historical control trial. Patients receiving docetaxel at 75 mg/m2 every 3 weeks for 4 cycles as first-line chemotherapy for breast cancer were eligible. PN was evaluated using the common terminology criteria for adverse events version 4.0. The primary endpoint was the incidence of allgrade PN until 3 weeks after the fourth docetaxel administration. We evaluated 26 patients in the intervention group and compared their data to those collected retrospectively from 52 patients treated with docetaxel without compression. Neither the incidence of all-grade PN until 3 weeks after the fourth docetaxel administration (63.5% in the control group vs. 76.9% in the intervention group, p=0.31) nor that of PN grade ≥ 2 (13.5% vs. 15.4%, p=0.99) differed between the groups. In this study, the efficacy of compression therapy using sleeves and stockings to prevent PN induced by docetaxel was not demonstrated. Further clinical studies including medications or intervention are needed to reduce the incidence and severity of PN induced by chemotherapy.


Assuntos
Neoplasias da Mama , Doenças do Sistema Nervoso Periférico , Humanos , Feminino , Docetaxel/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Taxoides/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
11.
Nature ; 611(7937): 787-793, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36323781

RESUMO

Emerging studies indicate that cooperation between neurons and immune cells regulates antimicrobial immunity, inflammation and tissue homeostasis. For example, a neuronal rheostat provides excitatory or inhibitory signals that control the functions of tissue-resident group 2 innate lymphoid cells (ILC2s) at mucosal barrier surfaces1-4. ILC2s express NMUR1, a receptor for neuromedin U (NMU), which is a prominent cholinergic neuropeptide that promotes ILC2 responses5-7. However, many functions of ILC2s are shared with adaptive lymphocytes, including the production of type 2 cytokines8,9 and the release of tissue-protective amphiregulin (AREG)10-12. Consequently, there is controversy regarding whether innate lymphoid cells and adaptive lymphocytes perform redundant or non-redundant functions13-15. Here we generate a new genetic tool to target ILC2s for depletion or gene deletion in the presence of an intact adaptive immune system. Transgenic expression of iCre recombinase under the control of the mouse Nmur1 promoter enabled ILC2-specific deletion of AREG. This revealed that ILC2-derived AREG promotes non-redundant functions in the context of antiparasite immunity and tissue protection following intestinal damage and inflammation. Notably, NMU expression levels increased in inflamed intestinal tissues from both mice and humans, and NMU induced AREG production in mouse and human ILC2s. These results indicate that neuropeptide-mediated regulation of non-redundant functions of ILC2s is an evolutionarily conserved mechanism that integrates immunity and tissue protection.


Assuntos
Imunidade Inata , Mucosa Intestinal , Linfócitos , Neuropeptídeos , Animais , Humanos , Camundongos , Citocinas/imunologia , Citocinas/metabolismo , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/parasitologia , Inflamação/patologia , Linfócitos/imunologia , Neuropeptídeos/metabolismo , Neuropeptídeos/fisiologia , Anfirregulina , Mucosa Intestinal/imunologia , Mucosa Intestinal/parasitologia , Mucosa Intestinal/patologia
12.
Cell ; 185(22): 4170-4189.e20, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36240781

RESUMO

Nociceptive pain is a hallmark of many chronic inflammatory conditions including inflammatory bowel diseases (IBDs); however, whether pain-sensing neurons influence intestinal inflammation remains poorly defined. Employing chemogenetic silencing, adenoviral-mediated colon-specific silencing, and pharmacological ablation of TRPV1+ nociceptors, we observed more severe inflammation and defective tissue-protective reparative processes in a murine model of intestinal damage and inflammation. Disrupted nociception led to significant alterations in the intestinal microbiota and a transmissible dysbiosis, while mono-colonization of germ-free mice with Gram+Clostridium spp. promoted intestinal tissue protection through a nociceptor-dependent pathway. Mechanistically, disruption of nociception resulted in decreased levels of substance P, and therapeutic delivery of substance P promoted tissue-protective effects exerted by TRPV1+ nociceptors in a microbiota-dependent manner. Finally, dysregulated nociceptor gene expression was observed in intestinal biopsies from IBD patients. Collectively, these findings indicate an evolutionarily conserved functional link between nociception, the intestinal microbiota, and the restoration of intestinal homeostasis.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , Nociceptores/fisiologia , Substância P , Disbiose , Inflamação
13.
Sci Rep ; 12(1): 14059, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982150

RESUMO

In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
14.
Lymphat Res Biol ; 20(6): 600-606, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35357959

RESUMO

Background: Lymphedema may develop when axillary lymph node dissection (ALND) injures and obstructs the lymph ducts in the upper limb. In patients with breast cancer, lymphedema is difficult to treat and can cause arm swelling, heaviness, and restricted movement. We aimed to identify the prevalence and risk factors for lymphedema after ALND in patients with breast cancer. Methods and Results: This retrospective study included 175 patients with breast cancer who underwent ALND in the Nagasaki University Hospital, Japan, between 2005 and 2018. Lymphedema was defined as symptomatic arm swelling with a >2-cm difference in the arm circumference between the affected and contralateral arms. Patients were divided into two groups according to the presence or absence of lymphedema. Surgical and pathological findings were compared between the two groups. Univariate and multivariate analyses were performed, including the chi-square test, Student's t-test, and logistic regression analysis. Lymphedema was prevalent in 20% of the study participants, and the mean time interval from surgery to development of lymphedema was 479 days. In the univariate analysis, a body mass index of >26 kg/m2, smoking, radiotherapy (RT), and dissection of >18 axillary lymph nodes (ALNs) significantly increased the risk of lymphedema. In the multivariate analysis, smoking, RT, and dissection of >18 ALNs significantly increased the risk of lymphedema. Conclusions: The prevalence of lymphedema in our study was 20%. Our findings suggest that smoking, RT, and dissection of >18 ALNs are risk factors for lymphedema. Aggressive and empiric ALND might be associated with axillary lymph duct damage.


Assuntos
Neoplasias da Mama , Linfedema , Humanos , Feminino , Neoplasias da Mama/complicações , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/efeitos adversos , Prevalência , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Linfedema/patologia , Fatores de Risco , Axila/patologia
15.
Nat Immunol ; 23(2): 251-261, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35102343

RESUMO

Tumor necrosis factor (TNF) drives chronic inflammation and cell death in the intestine, and blocking TNF is a therapeutic approach in inflammatory bowel disease (IBD). Despite this knowledge, the pathways that protect the intestine from TNF are incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3s) protect the intestinal epithelium from TNF-induced cell death. This occurs independent of interleukin-22 (IL-22), and we identify that ILC3s are a dominant source of heparin-binding epidermal growth factor-like growth factor (HB-EGF). ILC3s produce HB-EGF in response to prostaglandin E2 (PGE2) and engagement of the EP2 receptor. Mice lacking ILC3-derived HB-EGF exhibit increased susceptibility to TNF-mediated epithelial cell death and experimental intestinal inflammation. Finally, human ILC3s produce HB-EGF and are reduced from the inflamed intestine. These results define an essential role for ILC3-derived HB-EGF in protecting the intestine from TNF and indicate that disruption of this pathway contributes to IBD.


Assuntos
Fator de Crescimento Semelhante a EGF de Ligação à Heparina/imunologia , Imunidade Inata/imunologia , Inflamação/imunologia , Intestinos/imunologia , Linfócitos/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Células Epiteliais/imunologia , Mucosa Intestinal/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/imunologia
16.
J Interferon Cytokine Res ; 41(11): 391-406, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34788131

RESUMO

The balance between inflammatory and anti-inflammatory immune responses is maintained through immunoregulatory cell populations and immunosuppressive cytokines. Interleukin-35 (IL-35), an inhibitory cytokine that belongs to the IL-12 family, is capable of potently suppressing T cell proliferation and inducing IL-35-producing induced regulatory T cells (iTr35) to limit inflammatory responses. Over the past decade, a growing number of studies have indicated that IL-35 plays an important role in controlling immune-related disorders, including autoimmune diseases, infectious diseases, and cancer. In this review, we summarize the current knowledge about the biology of IL-35 and its contribution in different diseases, and we discuss the potential of and barriers to harnessing IL-35 as a clinical biomarker or immunotherapy.


Assuntos
Inflamação/metabolismo , Interleucinas/química , Interleucinas/fisiologia , Animais , Artrite Reumatoide/metabolismo , Aterosclerose/metabolismo , Doenças Autoimunes/imunologia , Autoimunidade , Biomarcadores/metabolismo , Proliferação de Células , Doenças Transmissíveis/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Regulação da Expressão Gênica , Humanos , Doenças do Sistema Imunitário , Imunoterapia , Doenças Inflamatórias Intestinais/metabolismo , Subunidade p35 da Interleucina-12/sangue , Interleucinas/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Ativação Linfocitária , Esclerose Múltipla/metabolismo , Neoplasias/metabolismo , Transdução de Sinais , Linfócitos T/química , Linfócitos T Reguladores/imunologia , Microambiente Tumoral
17.
Int J Surg Case Rep ; 89: 106544, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34775327

RESUMO

INTRODUCTION AND IMPORTANCE: A lactating adenoma is a benign breast tumor occurring in young women during pregnancy or lactation. Its growth is usually slow but, occasionally, can become rapid, resulting in a giant mass. This case report outlines an example of the rapid growth of a lactating adenoma, which was surgically excised. In this case, malignancy could not be ruled out, and biopsy and surgical excision were considered. CASE PRESENTATION: We present the case of a 28-year-old woman referred to us owing to the presence of a left breast mass with progressive enlargement. She initially presented with a left breast mass of approximately 20-mm in size, which increased to an approximate size of 70 mm during pregnancy. The patient's mammogram showed an equal-density lobular mass in the left breast. Ultrasonography and magnetic resonance imaging revealed a circumscribed lobular mass with cystic regions in the upper lateral quadrant. The patient was diagnosed with adenosis using core needle biopsy. However, it did not shrink during follow-up, and resection was performed. Histologically, the proliferation of the cystic ducts containing eosinophilic secretions and dilated tubules consisting of cuboidal or hobnail-shaped cells were observed. CLINICAL DISCUSSION: Lactating adenoma, phyllodes tumor, and breast cancer are essential differential diagnoses when the size of breast masses increases rapidly. Ultrasonography is the first choice to examine lactating adenomas. Echogenic bands and pseudocapsules are characteristics of lactating adenomas. CONCLUSION: Surgical excision is a notable treatment option when a lactating adenoma exhibits rapid growth or increase in mass, as it could be malignant.

18.
J Bone Miner Metab ; 39(6): 1031-1040, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34191126

RESUMO

INTRODUCTION: Although aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer. MATERIALS AND METHODS: This prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia. RESULTS: Twenty women were included (median age 57.5 years; range 55-72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius - 5.3%, p < 0.01; distal tibia - 3.2%, p < 0.01), Tb.vBMD (- 3.2%, p < 0.01; - 1.0%, p < 0.05, respectively), and Ct.vBMD (- 3.2%, p < 0.01; - 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  - 0.53, r =  - 0.47, respectively) CONCLUSION: Postmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.


Assuntos
Densidade Óssea , Neoplasias da Mama , Absorciometria de Fóton , Idoso , Neoplasias da Mama/tratamento farmacológico , Feminino , Colo do Fêmur , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
19.
J Clin Med Res ; 13(4): 222-229, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34007360

RESUMO

BACKGROUND: Endoscopic ultrasonography (EUS) is one of the helpful tools to diagnose depth of early gastric cancer (EGC). In this study, we examined efficiencies of EUS for EGC such as overall accuracy, risk factors of over/under-staging, and accuracies of each invasive distance. METHODS: A total of 403 EGC lesions that could be investigated by EUS during pre-operation and histological diagnosis after endoscopic submucosal dissection (ESD) or surgery were enrolled in this study. For the 403 cases, we analyzed the accuracies of depth by conventional endoscopy (CE) and EUS retrospectively. We evaluated the clinical survey items of CE and EUS which will be described later to compare the differences between "accuracy group" and "over-staging group", and between "accuracy group" and "under-staging group", retrospectively. Additionally, 78 EGC lesions which were confined to the submucosa and for which it was possible to measure accurate invasive distance from the muscularis mucosae were examined for the relationship between preoperative diagnosis of depth by CE and EUS and invasive distance retrospectively. RESULTS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were 87.3%. For CE staging, histological classification was the factor which influenced over-staging. Gastric regions and tumor area were the factors which influenced under-staging of CE. For EUS staging, tumor area was the factor which influenced over-staging, and gastric regions were the factors which influenced under-staging. Both CE and EUS were not sufficient for predicting the lesions confined to < 500 µm from the muscularis mucosae because the accuracies of both in predicting depth were less than 50%. However, EUS has a higher accuracy than CE for the lesions confined to 500 - 2,000 µm. CONCLUSIONS: The overall accuracies of both CE and EUS in predicting EGC invasion depth were equal, but the contributing factors for over/under-staging were different. Both CE and EUS are not sufficient at present to predict the lesions confined to < 500 µm from the muscularis mucosae. However, the accuracy of EUS in predicting them may increase if high-performance EUS systems are developed in the future.

20.
World J Oncol ; 12(2-3): 67-72, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34046101

RESUMO

A 77-year-old man who underwent radiotherapy for hepatocellular carcinoma 6 months prior consulted for esophageal obstruction. Esophagogastroduodenoscopy revealed an esophageal ulcer caused by radiotherapy for hepatocellular carcinoma. He was treated with dietary counseling and vonoprazan. After 9 months, the ulcer improved but a moderate stenosis remained. Several factors such as high fraction size, history of chemotherapy, and stress associated with food intake might involve in the development of a radiation-associated ulcer. Opportunities to choose radiotherapy for hepatocellular carcinoma may increase, so we hypothesize that esophageal ulcers might be a complication that should be noted associated with this therapy.

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