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1.
Anticancer Res ; 43(9): 4045-4053, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37648305

RESUMO

BACKGROUND/AIM: Gangliosides (acidic glycosphingolipids) have crucial regulatory roles in normal physiological processes, as well as in pathological conditions, including tumor onset and progression. GD2 is highly expressed in triple-negative breast cancer (TNBC), particularly in cancer stem cells. However, little is known on the clinical impact of GD2 expression on the prognosis of TNBC. Consequently, we aimed to investigate the association between GD2 expression in TNBC and the prognosis of TNBC. PATIENTS AND METHODS: We assessed GD2 expression in 76 patients with primary TNBC who had undergone surgery at our Institute between 2012 and 2015 using immunohistochemical analysis with a tissue microarray technique. We investigated the relationship between GD2 expression and clinicopathological factors in TNBC, recurrence-free survival (RFS), and overall survival (OS). RESULTS: Increased GD2 expression was observed in 45% of TNBC patients. There was no significant association between GD2 expression and clinicopathological factors in TNBC. The 5-year RFS rate among patients with GD2-positive TNBCs was significantly worse than that among patients with GD2-negative TNBCs (75.4% and 94.9%; HR=4.931; 95%CI=1.024-23.752; p=0.027). The OS in patients with GD2-positive TNBCs tended to be inferior to that of patients with GD2-negative TNBCs (HR=5.357; 95%CI=0.599-47.939; p=0.092). Interestingly, in patients with GD2-positive TNBCs, a higher grade of tumor-infiltrating lymphocytes (TILs) displayed a significantly better impact on OS (TILs-high vs. TILs-low; p=0.04). Both univariate and multivariate analyses showed that GD2 expression negatively affected RFS (p=0.027, p=0.021, respectively). CONCLUSION: GD2 expression is an independent unfavorable prognostic factor for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Gangliosídeos , Prognóstico , Linfócitos do Interstício Tumoral , Análise Multivariada
2.
Radiol Case Rep ; 18(9): 3212-3217, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37448598

RESUMO

Mixed epithelial and stromal tumor (MEST) of the kidney is a rare benign tumor with malignant potential, and is characterized by epithelial and stromal proliferation with a variety of cellularity and growth pattern. MEST of the kidney is often depicted as a well-defined, solid mass with a cystic component. However, due to the rarity of the disease, there are no reports of its progression in serial imaging examinations. This report presents the case of a 68-year-old woman with MEST who was followed for 13 years by computed tomography (CT). To the best of our knowledge, this is the first report of image findings of MEST of the kidney over a follow-up period longer than 10 years.

3.
Anticancer Res ; 43(7): 2923-2932, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37351990

RESUMO

BACKGROUND/AIM: Sindbis virus (SINV) is a naturally occurring oncolytic virus that kills cancer cells and is less harmful to normal cells. In this study, a recombinant SINV, which expressed green and blue fluorescent proteins, was used to precisely analyze SINV infection and replication. MATERIALS AND METHODS: Antiviral responses, including IFN-ß mRNA, protein kinase R (PKR), NF-B, and caspase 3/7, were analyzed in SINV-infected cancerous HeLa cells and normal human fibroblast TIG-1-20 cells. RESULTS: SINV could infect, replicate, and proliferate both in HeLa and TIG-1-20 cells, causing lytic infection only in HeLa cells. SINV grew preferentially in HeLa cells causing remarkable apoptosis. IFN-ß mRNA expression was suppressed in SINV-infected HeLa cells compared to that in TIG-1-20 cells. Further analyses of PKR and NF-B upstream of IFN-ß induction revealed that the compromised response in the PKR-NF-B pathway during early infection coincided with IFN induction suppression in HeLa cells. CONCLUSION: Dysregulation of PKR in HeLa cells is the determinant of SINV oncolysis.


Assuntos
NF-kappa B , Sindbis virus , Humanos , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo , Células HeLa , NF-kappa B/metabolismo , Proteínas Quinases , RNA Mensageiro/metabolismo
4.
In Vivo ; 37(2): 794-800, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36881070

RESUMO

BACKGROUND/AIM: Currently, several ongoing prospective studies are investigating the safety of breast surgery omission in patients with breast cancer who are exceptional responders to neoadjuvant chemotherapy. However, there is little information about the preferences of these patients regarding omission of breast surgery. PATIENTS AND METHODS: We conducted a questionnaire survey to assess preferences regarding omission of breast surgery among patients with breast cancer who had human epidermal growth factor receptor 2-positive or estrogen receptor-negative tumors and good clinical response after neoadjuvant chemotherapy. Patients' estimation of the risk of ipsilateral breast tumor recurrence (IBTR) after definitive surgery or breast surgery omission was also assessed. RESULTS: Of 93 patients, only 22 (23.7%) said they would omit breast surgery. Under the scenario of omitting breast surgery, the 5-year IBTR rate estimated by patients who said they would omit breast surgery was significantly lower (median, 10%) than the rate estimated by patients who preferred undergoing definitive surgery (median, 30%) (p=0.017). CONCLUSION: The proportion of our surveyed patients who were willing to omit breast surgery was low. Patients who said they preferred to omit breast surgery overestimated the 5-year IBTR risk.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia Neoadjuvante , Estudos Prospectivos , Mama
5.
Surg Today ; 53(1): 52-61, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35701689

RESUMO

PURPOSE: Even if favorable cosmetic outcomes are obtained shortly after breast-conserving surgery (BCS), cosmetic changes may occur up to several years after BCS. In the present study, we evaluated cosmetic changes while focusing on changes in the nipple position after BCS. METHODS: We examined the long-term course of changes in the nipple position over time after BCS using the proportion of the distance between the sternal notch and nipple (PDSN) in 196 patients. We also evaluated risk factors for long-term nipple position changes. RESULTS: The median follow-up period was 9.9 years. Nipple position changes occurred within eight years after BCS and seemed to plateau beyond that point. The body mass index (BMI), breast size, proportion of excision volume and axillary treatment were significantly associated with the nipple position changes within one to five years after BCS. The BMI, breast size, axillary treatment, chemotherapy and hormonal therapy were significantly associated with the nipple position changes within five to eight years after BCS. CONCLUSIONS: After BCS, the nipple position changes occur within about eight years. Obesity, large breast size, large excision volume, axillary treatment, chemotherapy and hormone therapy were factors that affected the treated breast shrinkage and increase in the left-right difference after BCS.


Assuntos
Neoplasias da Mama , Mamoplastia , Humanos , Feminino , Mastectomia Segmentar , Mamilos/cirurgia , Estudos Retrospectivos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia
6.
J Plast Reconstr Aesthet Surg ; 75(7): 2035-2048, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35643598

RESUMO

BACKGROUND: Reconstructive microsurgical free flap techniques are often the treatment of choice for a variety of complex tissue defects across multiple surgical specialties. However, the practice is underdeveloped in low- and middle-income countries. The aim of this systematic review was to evaluate the clinical application and outcomes of reconstructive microsurgery performed in Africa. METHODS: Seven databases (PubMed, Web of Science, MEDLINE, CINAHL, Academic Search Complete, Embase, and Google Scholar) were searched for studies reporting microsurgical procedures performed in Africa. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Tools and quality of evidence using the GRADE approach. Meta-analysis was performed using a random effects model to estimate the pooled proportion of events with 95% confidence intervals. The primary outcome was free flap success rate, and the secondary outcomes were the complication and flap salvage rates. RESULTS: Ninety-two studies were included in the narrative synthesis and nine in the pooled meta-analysis. In total, 1376 free flaps in 1327 patients from 1976 to 2020 were analyzed. Head and neck oncologic reconstruction made up 30% of cases, while breast reconstruction comprised 2%. The pooled flap survival rate was 89% (95% CI: 0.84, 0.93), complication rate 51% (95% CI: 0.36, 0.65), and free flap salvage rate was 45% (95% CI: 0.08, 0.84). CONCLUSION: This meta-analysis showed that the free flap success rates in Africa are high and comparable to those reported in high-income countries. However, the comparatively higher complication rate and lower salvage rate suggest a need for improved perioperative care. REVIEW REGISTRATION: Registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 25th September 2020, ID: CRD42020192344.


Assuntos
Retalhos de Tecido Biológico , Mamoplastia , Procedimentos de Cirurgia Plástica , Retalhos de Tecido Biológico/cirurgia , Cabeça/cirurgia , Humanos , Microcirurgia/métodos , Pescoço/cirurgia , Complicações Pós-Operatórias/cirurgia , Procedimentos de Cirurgia Plástica/métodos
7.
Am J Case Rep ; 23: e935035, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35017459

RESUMO

BACKGROUND Primary squamous cell carcinoma of the breast is a rare type of metaplastic breast carcinoma, characterized by resistance to conventional chemotherapy agents. We report a case of metaplastic squamous cell carcinoma of the breast in which a pathological complete response was achieved after neoadjuvant chemotherapy with weekly paclitaxel and in which the patient remained disease free for 15 years and 7 months. CASE REPORT A 40-year-old woman had a palpable 5-cm-diameter tumor in the right breast that was diagnosed as metaplastic squamous cell carcinoma of the breast based on core needle biopsy. The patient was initially treated with an adjuvant chemotherapy (AC) regimen consisting of doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) as neoadjuvant chemotherapy. Because the tumor grew rapidly and the skin redness increased after 1 cycle of the AC regimen, 12 cycles of weekly paclitaxel 80 mg/m² were subsequently administered. The tumor responded dramatically to paclitaxel. The patient underwent mastectomy with level II axillary lymph node dissection. No residual tumor cells were found, which indicated pathological complete response. The patient is currently disease free at 15 years and 7 months after the operation. CONCLUSIONS To our knowledge, there are no previous reports of metaplastic squamous cell carcinoma of the breast in which pathological complete response was achieved by treatment with neoadjuvant chemotherapy with weekly paclitaxel (80 mg/m²).


Assuntos
Neoplasias da Mama , Carcinoma de Células Escamosas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma de Células Escamosas/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Mastectomia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico
8.
Asian J Surg ; 45(11): 2268-2272, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35000855

RESUMO

BACKGROUND: There is little information on the risk factors for fat necrosis after breast-conserving surgery using an inframammary adipofascial flap (IAF). METHODS: We conducted a retrospective cohort study from a single institution evaluating the risk factors for fat necrosis after breast-conserving surgery using an IAF (n = 41) performed from 2005 to 2020 for newly diagnosed stage 0-2 breast cancer or phyllodes tumor. RESULTS: Age (≥50 years of age vs. <50 years of age), mammographic density (fatty vs. other) and operation period (before vs. after revision of surgical procedure and patient indication) were significantly associated with fat necrosis (p = 0.006, p = 0.04 and p = 0.02, respectively). CONCLUSION: Our study suggested that the use of an IAF with crescent dermis and selection of appropriate cases for IAF after breast-conserving surgery may be useful for the purpose of reducing fat necrosis. Further study is needed.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Necrose Gordurosa , Mamoplastia , Neoplasias da Mama/patologia , Carcinoma in Situ/cirurgia , Necrose Gordurosa/etiologia , Necrose Gordurosa/prevenção & controle , Necrose Gordurosa/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Retalhos Cirúrgicos
9.
Commun Biol ; 4(1): 1320, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811492

RESUMO

Although transcriptome alteration is an essential driver of carcinogenesis, the effects of chromosomal structural alterations on the cancer transcriptome are not yet fully understood. Short-read transcript sequencing has prevented researchers from directly exploring full-length transcripts, forcing them to focus on individual splice sites. Here, we develop a pipeline for Multi-Sample long-read Transcriptome Assembly (MuSTA), which enables construction of a transcriptome from long-read sequence data. Using the constructed transcriptome as a reference, we analyze RNA extracted from 22 clinical breast cancer specimens. We identify a comprehensive set of subtype-specific and differentially used isoforms, which extended our knowledge of isoform regulation to unannotated isoforms including a short form TNS3. We also find that the exon-intron structure of fusion transcripts depends on their genomic context, and we identify double-hop fusion transcripts that are transcribed from complex structural rearrangements. For example, a double-hop fusion results in aberrant expression of an endogenous retroviral gene, ERVFRD-1, which is normally expressed exclusively in placenta and is thought to protect fetus from maternal rejection; expression is elevated in several TCGA samples with ERVFRD-1 fusions. Our analyses provide direct evidence that full-length transcript sequencing of clinical samples can add to our understanding of cancer biology and genomics in general.


Assuntos
Neoplasias da Mama/genética , Fusão Gênica , Transcriptoma , Neoplasias da Mama/metabolismo , Humanos , Isoformas de Proteínas/metabolismo , RNA/análise , Tensinas/genética , Tensinas/metabolismo
10.
Surg Today ; 51(2): 309-321, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32901376

RESUMO

PURPOSE: To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan. METHODS: The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment. RESULTS: The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child. CONCLUSIONS: Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.


Assuntos
Escolha da Profissão , Cirurgia Geral/organização & administração , Saúde Ocupacional , Estresse Ocupacional/psicologia , Parto/psicologia , Médicas/psicologia , Gravidez/psicologia , Gravidez/estatística & dados numéricos , Sociedades Médicas/organização & administração , Cirurgiões/psicologia , Inquéritos e Questionários , Local de Trabalho/psicologia , Adulto , Feminino , Humanos , Japão , Assédio Sexual/psicologia
11.
Oncol Lett ; 21(1): 36, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33262828

RESUMO

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3+, CD8+, FOXP3+, CD20+, CD68+ and CD204+ cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TIL+PD-L1+, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TIL-PD-L1-, of which 77% (37/48) were HR+ and HER2- types. The number of CD204+ M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68+ macrophages were not associated with these factors. Furthermore, CD204+ macrophages and FOXP3+ Tregs accumulated in 88% (14/16) and 63% (10/16) of TIL+PD-L1+ tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TIL-PD-L1- tumors. In conclusion, 22% of BC tumors were classified as TIL+PD-L1+ (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.

12.
Toxicol Appl Pharmacol ; 412: 115353, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33301752

RESUMO

Chronic exposure to arsenic causes cancers in various organs including the skin, liver, lung, and bladder in humans, but the mechanisms of the multi-organ carcinogenicity of arsenic remain unknown. Natural killer (NK) cells play important roles in the immune surveillance and elimination of tumor cells. Although accumulating evidence has indicated that arsenic has immunosuppressive properties, little is known about the effects of arsenic on the tumoricidal functions of NK cells. We examined the effects of arsenite on the cytotoxic activities of human and mouse NK cells toward target tumor cells. Exposure of human NK-92 cells and primary mouse NK cells to sublethal doses of arsenite reduced the IL-2-activated cytotoxic activities toward human K562 cells and murine YAC-1 cells, respectively. NK cells recognize target cells via integrated signals from both activating and inhibitory receptors and induce apoptosis of target cells via a granzyme/perforin system. We found that exposure of NK-92 cells to arsenite diminished the IL-2-activated down-regulation of the inhibitory receptors, KIR2DL2 and KIR2DL3, and the up-regulation of granzyme B and lymphotoxin-α. The IL-2-activated increases in secretion of interferon-γ and IL-10 were also slightly reduced by arsenite. Thus, arsenite suppressed the IL-2-activated cytotoxic activity of NK cells by disrupting multiple pathways required for the recognition and killing of target tumor cells. Our findings provide new insights into the roles of NK cell-mediated tumor immunity in cancer development by arsenic.


Assuntos
Arsenitos/toxicidade , Citotoxicidade Imunológica/efeitos dos fármacos , Interleucina-2/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Compostos de Sódio/toxicidade , Evasão Tumoral/efeitos dos fármacos , Animais , Técnicas de Cocultura , Granzimas/genética , Granzimas/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/metabolismo , Células K562 , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Linfotoxina-alfa/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptores KIR2DL2/genética , Receptores KIR2DL2/metabolismo , Receptores KIR2DL3/genética , Receptores KIR2DL3/metabolismo
13.
Ann Surg Oncol ; 28(5): 2545-2552, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33021710

RESUMO

BACKGROUND: Attention has been focused on attempts to eliminate breast surgery for breast cancer patients who achieve a pathologic complete response after neoadjuvant chemotherapy (NAC). However, there are few data on ipsilateral breast tumor recurrence (IBTR) among patients with triple-negative or epidermal growth factor receptor 2-positive (HER2+) tumors who achieve a pathologic complete response after NAC and breast-conserving treatment. METHODS: Using a multi-institutional retrospective database, this study evaluated the risk factors for IBTR among patients with newly diagnosed stages 1 to 3 breast cancer involving triple-negative or HER2+ tumors who achieved ypT0 after NAC and breast-conserving treatment. RESULTS: During a median follow-up period of 4.8 years (range, 0.1-15.5 years), the 5-year IBTR-free survival rate was 95.5%. The breast cancer subtype was not associated with IBTR-free survival. Patients younger than 40 years at diagnosis had significantly worse IBTR-free survival than those who were 40 years of age or older (5-year IBTR-free survival, 87.7 vs 96.9%; p = 0.002). CONCLUSIONS: This retrospective study demonstrated that age at diagnosis was independently associated with IBTR-free survival. Special caution is needed when clinical trials analyzing omission of breast surgery after NAC are enrolling younger patients (UMIN-CTR No. UMIN000037067).


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Humanos , Mastectomia Segmentar , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
14.
JMA J ; 3(1): 29-40, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33324773

RESUMO

Spinal epidural abscess (SEA) is still an uncommon but devastating infection of the spine. In recent years, a number of reported cases have risen. The most important prognostic factor for a favorable outcome is early diagnosis and appropriate treatment. However, a diagnosis of SEA is often delayed, particularly in the early stages of the disease before patients present with neurological symptoms. With enough knowledge of risk factors, clinical features, and appropriate diagnostic procedures, it may be possible to reduce diagnostic delay in the early stages of the disease. This review focuses on early diagnosis of SEA based on risk factors, presenting symptoms, and characteristic findings on magnetic resonance imaging (MRI), and also discusses the timing of surgical interventions. Traditionally, the symptoms of SEA are characterized by fever, back pain, and neurological symptoms, which are described as a classical triad of symptoms for this type of infection; but this collection of symptoms is seen in only about 10% of cases. However, most patients complain of severe localized lower back pain. Gadolinium-enhanced MRI is the most sensitive, specific, and beneficial imaging modality for establishing a diagnosis of SEA. Patients diagnosed prior to neurological deficits with a known causative microbial organism can be safely treated with antimicrobial therapy alone. However, about 30%-40% of the patients fail in conservative management without surgery. The best management and timing for surgical decompression in patients with or without mild neurological deficits should be established in the near future. Early diagnosis and management, before the occurrence of serious neurological symptoms, are the most important prognostic factors for good outcomes in patients with SEA. We proposed a simple algorithm for early diagnosis of SEA by selecting patients with severe back pain, leading to emergent MRI.

15.
Cancer Chemother Pharmacol ; 86(4): 559-566, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32949266

RESUMO

PURPOSE: The pharmacokinetics (PKs) of cisplatin have not been investigated in patients with renal dysfunction, characterized by creatinine clearance (Ccr) < 60 mL/min. In this study, we performed a population pharmacokinetic (PPK) analysis of unchanged cisplatin in patients with renal dysfunction. We investigated the effects of renal dysfunction on the PKs and nephrotoxicity of unchanged cisplatin. METHODS: We enrolled 23 patients with moderate renal dysfunction (Ccr calculated to be 30-60 mL/min using the Cockcroft-Gault formula) treated with cisplatin. PPK analysis was performed by nonlinear mixed effect modeling using NONMEM (Version 7.2). We evaluated gender, age, body surface area (BSA), weight, baseline Ccr, baseline serum creatinine (Scr), and baseline urea nitrogen as potential covariates. The final model was evaluated using bootstrap analysis. Renal toxicity was evaluated using Common Terminology Criteria for Adverse Events ver. 4.0. The frequency of severe renal dysfunction (Grade 3/4 Scr elevation) was measured in the population. RESULTS: A one-compartment model adequately described the unchanged cisplatin data. The population mean values for clearance (CLtot) and volume of distribution (Vd) were 19.1 L/h [coefficient of variation (CV) 19.4%] and 13.8 L (CV 41.0%), respectively. The final model identified BSA as a significant covariate for CLtot. There were no significant covariates for Vd. No patients suffered from severe nephrotoxicity to the point that hemodialysis was required. CONCLUSION: Moderate renal dysfunction does not affect the PKs of unchanged cisplatin. The increased serum concentration of cisplatin may not lead to increased toxicity in patients with renal dysfunction. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: UMIN000007091 (January 17, 2012).


Assuntos
Injúria Renal Aguda/epidemiologia , Cisplatino/farmacocinética , Neoplasias/tratamento farmacológico , Eliminação Renal/fisiologia , Insuficiência Renal/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/fisiopatologia , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Creatinina/sangue , Creatinina/metabolismo , Creatinina/urina , Conjuntos de Dados como Assunto , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias/sangue , Neoplasias/complicações , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Insuficiência Renal/fisiopatologia , Índice de Gravidade de Doença , Fatores de Tempo
16.
Am J Pathol ; 190(10): 2123-2135, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32650003

RESUMO

Tenascin-C (TNC) is strongly expressed by fibroblasts and cancer cells in breast cancer. To assess the effects of TNC on stromal formation, we examined phenotypic changes in human mammary fibroblasts treated with TNC. The addition of TNC significantly up-regulated α-smooth muscle actin (α-SMA) and calponin. TNC increased the number of α-SMA- and/or calponin-positive cells with well-developed stress fibers in immunofluorescence, which enhanced contractile ability in collagen gel contraction. The treatment with TNC also significantly up-regulated its own synthesis. Double immunofluorescence of human breast cancer tissues showed α-SMA- and/or calponin-positive myofibroblasts in the TNC-deposited stroma. Among several receptors for TNC, the protein levels of the αv and ß1 integrin subunits were significantly increased after the treatment. Immunofluorescence showed the augmented colocalization of αv and ß1 at focal adhesions. Immunoprecipitation using an anti-αv antibody revealed a significant increase in coprecipitated ß1 with TNC in lysates. The knockdown of αv and ß1 suppressed the up-regulation of α-SMA and calponin. The addition of TNC induced the phosphorylation of SMAD2/3, whereas SB-505124 and SIS3 blocked myofibroblast differentiation. Therefore, TNC enhances its own synthesis by forming a positive feedback loop and increases integrin αvß1 heterodimer levels to activate transforming growth factor-ß signaling, which is followed by a change to highly contractile myofibroblasts. TNC may essentially contribute to the stiffer stromal formation characteristic of breast cancer tissues.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos/patologia , Miofibroblastos/patologia , Tenascina/farmacologia , Neoplasias da Mama/metabolismo , Diferenciação Celular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/farmacologia , Fibroblastos/metabolismo , Humanos , Miofibroblastos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Fosforilação/efeitos dos fármacos , Receptores de Vitronectina/metabolismo , Transdução de Sinais/fisiologia , Tenascina/metabolismo , Fator de Crescimento Transformador beta/metabolismo
17.
Intern Med ; 59(13): 1643-1647, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238719

RESUMO

Varicella-zoster virus (VZV) encephalitis in the absence of vasculopathy may rarely occur in association with herpes zoster. We herein report the case of a 67-year-old woman with non-Hodgkin's lymphoma undergoing chemotherapy who presented with an acute alteration in consciousness. Magnetic resonance imaging of the brain revealed multiple and nonspecific lesions of hyperintensity with mild edema in the cortex and subcortex. She was treated with intravenous acyclovir. However, two days after admission, the patient died and was diagnosed with VZV encephalitis. This case highlights the risk of VZV reactivation with severe neurological complications in patients undergoing immunosuppressive therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encefalite por Varicela Zoster/etiologia , Linfoma não Hodgkin/tratamento farmacológico , Aciclovir/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Autopsia , Encéfalo/patologia , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Encefalite por Varicela Zoster/tratamento farmacológico , Feminino , Herpesvirus Humano 3 , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico
18.
J Anesth ; 34(3): 397-403, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32222907

RESUMO

PURPOSE: Propofol clearance can be reduced when cardiac output (CO) is decreased. This clearance reduction may alter the pharmacokinetics of propofol and worsen the predictive performance of target-controlled infusion (TCI) of propofol. The head-down position (HDP) and CO2 pneumoperitoneum, which are required for robotic-assisted laparoscopic prostatectomy (RALP), may cause changes in CO. We investigated the predictive performance of propofol TCI during CO2 pneumoperitoneum in patients who underwent RALP in the HDP. METHODS: Fifteen male patients received propofol TCI using the Diprifusor model. Propofol concentrations were measured at seven time points: (T1) 15 min after anesthesia induction; (T2) before the insufflation; (T3, T4, and T5) 15, 60, and 90 min, respectively, after insufflation in the HDP; (T6) before the release of pneumoperitoneum in the HDP; and (T7) 15 min after the release of pneumoperitoneum in the supine position. Cardiac index (CI) was assessed using an arterial pulse contour CO monitor. The predictive performance of propofol TCI was evaluated by calculating the performance errors (PE) in propofol concentrations for each data point. The relationship between CI and PE was examined. Median PE (MDPE) and median absolute PE (MDAPE) were calculated as measures of bias and accuracy, respectively. RESULTS: A total of 104 blood samples were analyzed. There was significantly negative correlation between CI and PE. The predictive performance of propofol TCI during pneumoperitoneum in the HDP was acceptable (MDPE = - 1.5% and MDAPE = 18.8%). CONCLUSION: The predictive performance of propofol TCI during RALP with CO2 pneumoperitoneum in the HDP was acceptable.


Assuntos
Insuflação , Laparoscopia , Pneumoperitônio , Propofol , Procedimentos Cirúrgicos Robóticos , Anestésicos Intravenosos , Dióxido de Carbono , Débito Cardíaco , Humanos , Masculino , Prostatectomia/métodos
19.
Case Rep Neurol Med ; 2019: 2929782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061739

RESUMO

We presented a case of a 19-year-old woman who suffered from anti-N-methyl-D-aspartate (NMDA) receptor encephalitis associated with ovarian teratoma. The patient showed a variety of higher visual symptoms which changed over the recovery phase of the disease. In chronological order, she experienced cortical blindness, amblyopia, dyschromatopsia, static form agnosia, and prosopagnosia. Among these symptoms, the most intriguing was the static form agnosia. Although she could recognize the forms of moving objects, she could not make out those of stationary ones. All of these visual symptoms were transient, implying that she might have incidentally regained the function of the distinct cortical visual areas in the time course of follow-up. This case further suggests that visual functions concerned with the perceptions of static form and form-from-motion could be dissociable and may rely on distinct brain regions.

20.
Asian J Surg ; 42(1): 228-234, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29661546

RESUMO

BACKGROUND: After the ACOSOG Z0011 trial, it became important to evaluate the number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of this paper is to confirm whether the number of metastases can be accurately diagnosed by preoperative computed tomography (CT), ultrasound sonography (US), and US-guided fine-needle aspiration cytology (FNAC). METHODS: We retrospectively analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer patients. Metastasis was suspected based on the following findings: LNs with a long-axis diameter of ≥10 mm or a short-axis diameter of ≥5 mm on CT, and LNs with the absence of a fatty hilum, focal cortical thickness or a cortical thickness ≥2 mm on US. We also examined the results of FNAC making a rapid bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic based on the US findings. RESULTS: On CT, all cases with ≥3 LNs with a long-axis diameter of ≥10 mm and a short-axis diameter of ≥5 mm had metastasis. However, there was no relationship between the number of detected LNs and the number of metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs with cortical thickness ≥6 mm had metastasis. The accuracy of bedside-FNAC for suspicious LNs was 100%. CONCLUSIONS: Although we can pick up LNs that are likely to have metastasis on CT/US, it was impossible to accurately predict the number of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately predict the number of metastases.


Assuntos
Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Humanos , Biópsia Guiada por Imagem , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia
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