RESUMO
The thymus is where T cells, among the most important immune cells involved in biological defense and homeostasis, are produced and developed. The thymus plays an important role in the defense against infection and cancer as well as the prevention of autoimmune diseases. However, the thymus gland atrophies with age, which might have pathological functions, and in some circumstances, there is a congenital defect in the thymus. These can be the cause of many diseases related to the dysregulation of T cell functions. Thus, the enhancement and/or normalization of thymic function may lead to protection against and treatment of a wide variety of diseases. Therefore, thymus transplantation is considered a strong candidate for permanent treatment. The status and issues related to thymus transplantation for possible immunotherapy are discussed although it is still at an early stage of development.
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A 67-year-old man underwent renal transplantation in his twenties. He developed refractory pleural effusion, with many large lymphocytes with severe atypia and mitosis in the effusion, indicating malignant lymphoma. He finally died of respiratory failure. An autopsy revealed atypical lymphocytes positive for CD3, CD4, and CD30 and negative for CD8, CD20, PAX5, human herpesvirus (HHV) 8, and Epstein-Barr virus-encoded small RNAs by immunohistochemistry and in situ hybridization. Atypical lymphocytes also had T-cell receptor gene rearrangements Jß2, Jγ2, and Jδ1 and chromosomal aberrations der(8)t(1;8)(q21;p21), add(13)(q12), add(14)(q32), and add(16)(q12-13). A few atypical lymphocytes were present at other sites. We finally diagnosed this case as monomorphic T-cell post-transplant lymphoproliferative disorder with features of HHV8-negative primary effusion lymphoma. A literature review only identified six cases (four HHV8-negative, two HHV8-positive) of effusion lymphoma of T-cell type, including the present case. Interestingly, about half of HHV8-negative and HHV8-positive cases had a history of renal transplantation in their twenties. All cases showed tumor CD30 expression, whereas CD4 and CD8 expressions were inconsistent. These findings indicated that this lymphoma may be associated with post-transplant lymphoproliferative disorder by renal transplantation at a young age, although further cases need to be analyzed.
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A 68-year-old male patient underwent laparoscopic pyloric gastrectomy(D2)in October 2015 for gastric cancer, pStage â B. In August 2017, a 3 cm large abdominal wall metastasis in the left lateral abdomen was removed. In September 2019, a 2 cm tumor was found in the left inguinal region. The left inguinal area was repaired using mesh with the TAPP technique because of a large abdominal wall defect centered on the inner inguinal ring. Three and a half years after the resection, he is continuing complete response(CR)with nivolumab therapy.
Assuntos
Gastrectomia , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Masculino , Idoso , LaparoscopiaAssuntos
Leucemia Neutrofílica Crônica , Gamopatia Monoclonal de Significância Indeterminada , Humanos , Ascite , Proteínas de Transporte/genética , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/genética , Mutação , Proteínas Nucleares/genética , Receptores de Fator Estimulador de Colônias/genética , Proteínas Repressoras/genética , Transdução de Sinais , Fatores de TranscriçãoRESUMO
Although knee extensor muscle strength is strongly associated with postoperative walking ability (PWA) in patients undergoing total knee arthroplasty (TKA), few studies have considered the impact of both knee extensor and flexor muscle strength. This study aimed to determine whether operative side knee flexor and extensor muscle strength before surgery affects the PWA of patients who undergo TKA while accounting for potential covariates. This multicenter retrospective cohort study involved four university hospitals, and patients who underwent unilateral primary TKA were included. The outcome measure was the 5-m maximum walking speed test (MWS), which was completed 12 weeks postoperatively. Muscle strength was measured as the maximum isometric muscle strength required for knee flexor and extensor. Three multiple regression models with a progressively larger number of variables were developed to determine the predictors of 5-m MWS at 12 weeks post-TKA surgery. One hundred thirty-one patients who underwent TKA were enrolled in the study (men, 23.7%; mean age, 73.4 ± 6.9 years). Age, sex, operative side knee flexor muscle strength before surgery, Japanese Orthopaedic Association knee score, and preoperative walking ability were significantly associated with PWA in the final model of the multiple regression analysis ( R2 = 0.35). The current findings suggest that the operative side knee flexor muscle strength before surgery is a robust modifiable predictor of improved PWA. We believe that further validation is needed to determine the causal relationship between preoperative muscle strength and PWA.
Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Força Muscular/fisiologia , Osteoartrite do Joelho/cirurgia , Caminhada/fisiologiaRESUMO
T cells bearing γδ antigen receptors have been investigated as potential treatments for several diseases, including malignant tumours. However, the clinical application of γδT cells has been hampered by their relatively low abundance in vivo and the technical difficulty of inducing their differentiation from hematopoietic stem cells (HSCs) in vitro. Here, we describe a novel method for generating mouse γδT cells by co-culturing HSC-enriched bone marrow cells (HSC-eBMCs) with induced thymic epithelial cells (iTECs) derived from induced pluripotent stem cells (iPSCs). We used BMCs from CD45.1 congenic C57BL/6 mice to distinguish them from iPSCs, which expressed CD45.2. We showed that HSC-eBMCs and iTECs cultured with IL-2 + IL-7 for up to 21 days induced CD45.1+ γδT cells that expressed a broad repertoire of Vγ and Vδ T-cell receptors. Notably, the induced lymphocytes contained few or no αßT cells, NK1.1+ natural killer cells, or B220+ B cells. Adoptive transfer of the induced γδT cells to leukemia-bearing mice significantly reduced tumour growth and prolonged mouse survival with no obvious side effects, such as tumorigenesis and autoimmune diseases. This new method suggests that it could also be used to produce human γδT cells for clinical applications.
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Células da Medula Óssea/metabolismo , Diferenciação Celular , Células Epiteliais/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Linfócitos Intraepiteliais/metabolismo , Transferência Adotiva , Animais , Biomarcadores , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Técnicas de Cocultura , Células Epiteliais/citologia , Células-Tronco Hematopoéticas/citologia , Imunofenotipagem , Células-Tronco Pluripotentes Induzidas/citologia , Linfócitos Intraepiteliais/citologia , Camundongos , Camundongos Transgênicos , Transplante AutólogoRESUMO
Amyloidosis is known as a group of diseases that causes various disorders because of deposition of amyloid protein in various organs. Amyloidosis occurring in the retroperitoneum is a rare disease. We report a 75-year-old male patient presented to our hospital because he was identified with a retroperitoneal mass incidentally by CT. Laparoscopic surgery was performed to resect the tumor. In the histopathological specimen, amyloid was found in the fibrous soft tissue by Congo red staining. This is the first report to document a primary solitary amyloidosis of the retroperitoneum without systemic amyloidosis, which was resected using the laparoscopic approach.
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BACKGROUND: Colonic volvulus, a condition in which a colonic segment partially twists around its base, is the third leading cause of large bowel obstruction after colonic neoplasms and diverticular disease. However, volvulus of the transverse colon is the rarest type of large intestinal volvulus. Moreover, the occurrence of transverse colonic volvulus secondary to a benign tumor originating from outside the intestine has never been reported. We hereby report a case of transverse colonic volvulus caused by mesenteric fibromatosis. CASE PRESENTATION: A 53-year-old female with a history of rheumatoid arthritis and thyroid tumor presented with abdominal pain for 1 day. Abdominal computed tomography revealed intestinal torsion at the hepatic flexure. Twisted and obstructed mucosa of the transverse colon was observed during colonoscopy, but no tumor invasion of the mucosal surface was detected. A solid mass of a mesenteric origin with involvement of the transverse colon was observed during surgery. The mass was diagnosed surgically as transverse colonic volvulus induced by a mesenteric tumor. Hence, the patient underwent a right hemicolectomy. Histopathological results indicated mesenteric desmoid-type fibromatosis. The postoperative recovery was uneventful, and the patient was discharged 8 days after surgery. CONCLUSIONS: Although mesenteric fibromatosis is rare, this disease should be considered when managing transverse colonic volvulus resulting from nonmucosal tumors.
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Colo Transverso , Doenças do Colo , Fibroma , Obstrução Intestinal , Volvo Intestinal , Colo Transverso/diagnóstico por imagem , Colo Transverso/cirurgia , Feminino , Humanos , Volvo Intestinal/diagnóstico por imagem , Volvo Intestinal/etiologia , Volvo Intestinal/cirurgia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory upper airway disease, accompanied mainly by eosinophilia and/or asthma. In addition, the disease correlates with a high rate of hyposmia, following a marked infiltration of eosinophils into the inflamed site, the paranasal sinus. Although eosinophils are known to contribute to the development of hyposmia and CRSwNP pathology, the underlying mechanisms remain unclear. This study aimed to investigate whether eosinophilic upper airway inflammation induces hyposmia and CRSwNP in a murine model using an adoptive transfer system. METHODS: To induce eosinophilic rhinosinusitis, splenocytes, including a high proportion (over 50%) of activated eosinophils (SPLhEos), were collected from interleukin-5 transgenic mice following double intraperitoneal injections of antigens, such as ovalbumin, house dust mite, or fungus. Activated SPLhEos with corresponding antigens were then transferred into the nasal cavity of recipient mice, which were sensitized and challenged by the corresponding antigen four times per week. Olfactory function, histopathological, and computed tomography (CT) analyses were performed 2 days after the final transfer of eosinophils. RESULTS: Hyposmia was induced significantly in mice that received SPLhEos transfer compared with healthy and allergic mice, but it did not promote morphological alteration of the paranasal sinus. Pathological analysis revealed that epithelial layer injury and metaplasia similar to polyps, with prominent eosinophil infiltration, was induced in recipient tissue. However, there was no nasal polyp development with interstitial edema that was similar to those recognized in human chronic rhinosinusitis. CONCLUSIONS: This study supports the previously unsuspected contribution of eosinophils to CRS development in the murine model and suggests that murine-activated eosinophilic splenocytes contribute to the development of hyposmia due to more mucosal inflammation than physical airway obstruction and epithelial layer injury with convex lesions.
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We recently developed a new allogeneic hematopoietic stem cell transplantation method (allo-HSCT) combined with thymus transplantation (TT) from the same donor (allo-HSCT + TT). This method induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (DLI). This new method is effective against several intractable diseases, including malignant tumors, for which conventional treatments are ineffective. Regulatory T (Treg) cells play an important role in the enhanced graft-versus-tumor (GVT) effect and reduction of GVHD, thus leading to longer survival. Replacement and reduction of elevated Treg cells by donor-derived allo-Treg cells from the transplanted thymus may play one of crucial roles in the effect. This review discusses the role of Treg cells in a tumor-bearing mouse model treated with allo-HSCT + TT.
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Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Transplante de Órgãos , Linfócitos T Reguladores/imunologia , Timo/transplante , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Transplante HomólogoRESUMO
BACKGROUND: In general, splenic metastasis of epithelial ovarian cancer is considered a terminal stage resulting in widespread metastasis. Solitary splenic metastasis of epithelial ovarian cancer is rare in patients with post-treatment ovarian cancer with long disease-free intervals. CASE PRESENTATION: We report a case of a 62-year-old Japanese woman who presented with elevated serum cancer antigen 125 due to a solitary splenic metastasis of ovarian cancer. She underwent primary open cytoreduction including resection of the right ovarian cancer and postoperative chemotherapy, followed by secondary open cytoreduction and additional postoperative chemotherapy. The disease-free interval was more than 5 years after the additional postoperative chemotherapy. She did not complain of any symptoms and there were no abnormal findings except for elevated cancer antigen 125. However, computed tomography and magnetic resonance imaging revealed a tumor of 6.5 × 4.5 cm in her spleen, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography showed no other metastatic lesions. Laparoscopic splenectomy was performed as tertiary cytoreduction with a diagnosis of a solitary splenic metastasis. Her elevated cancer antigen 125 immediately decreased to within the normal range after the splenectomy. On microscopic examination, the tumor was grade 3 endometrioid adenocarcinoma localized in the spleen, consistent with the previous grade 3 endometrioid adenocarcinoma ovarian cancer. CONCLUSIONS: Elevated cancer antigen 125 is useful for early detection of metastasis of ovarian cancer. Computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography are useful to evaluate whether splenic metastasis of ovarian cancer is solitary, and laparoscopic splenectomy is safe and feasible for a solitary splenic metastasis.
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Laparoscopia , Neoplasias Ovarianas/patologia , Esplenectomia , Neoplasias Esplênicas/secundário , Neoplasias Esplênicas/cirurgia , Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/secundário , Carcinoma Endometrioide/cirurgia , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Esplênicas/sangue , Resultado do TratamentoRESUMO
AIMS: Most thymic carcinomas express the lymphocyte marker CD5 aberrantly. This study was performed to examine the role of the self-reactive CD5 antigen in thymic carcinoma. METHODS AND RESULTS: We examined CD5 expression in thymic carcinoma in relation to the lymphoid stroma. All cases of thymic carcinoma examined expressed CD5. A number of CD5(+) lymphocytes were also present in the stroma of thymic carcinoma. The CD5(+) tumour areas were predominantly in contact with the lymphoid stroma, and the expression level was significantly lower in tumour cells than lymphocytes. Although p53 and Bcl-2 expression levels were significantly higher in thymic carcinoma than normal thymic epithelial cells (TECs), they did not differ between CD5(+) and CD5(-) areas. E-cadherin expression in thymic carcinoma was comparable with that of normal TECs, and it also did not differ between these areas. In contrast, both Ki-67 index and mitotic activity were significantly higher in thymic carcinoma than normal TECs, and they were significantly higher in CD5(+) than CD5(-) areas. CONCLUSIONS: CD5 may be induced by interaction with CD5(+) lymphoid stroma, and may be related to tumour proliferation. CD5 induction may also be a significant and/or specific effect of the tumour microenvironment of the thymus.
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Antígenos CD5/metabolismo , Timoma/metabolismo , Neoplasias do Timo/metabolismo , Caderinas/metabolismo , Humanos , Linfócitos/metabolismo , Linfócitos/patologia , Timoma/patologia , Neoplasias do Timo/patologiaRESUMO
PURPOSE: This study aimed to clarify the role of complement activation in fibrogenesis in BA. METHODS: In total, 27 paraffin-embedded liver biopsy samples were immunohistochemically analyzed using C4d polyclonal antibody, vascular cell adhesion molecule-1 (VCAM-1), and CD45. The liver samples were obtained from 25 patients during Kasai operation, and two additional specimens were obtained from 2 patients by needle biopsy later at the time of liver function deterioration. The degree of liver fibrosis was histologically graded 1-3. RESULTS: Among the 25 samples, 9 showed C4d-positive immunostaining localized on the endothelia of a few portal veins in the portal tract. The degree of fibrosis was correlated with C4d staining (p = 0.025). The age at Kasai operation correlated with the degree of fibrosis and the C4d positivity. Two needle biopsy samples were positive for C4d. Among 13 samples submitted for VCAM-1 staining, 2 negative samples were C4d negative and all positive C4d samples were VCAM-1 positive with CD45 mononuclear cell infiltration. CONCLUSION: These findings suggest that ongoing cirrhosis could be a result of progressive "vasculopathy" of the portal vein caused by humoral and cell-mediated immune interaction.
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Atresia Biliar/imunologia , Complemento C4b/imunologia , Imunidade Humoral/imunologia , Cirrose Hepática/imunologia , Fígado/imunologia , Fragmentos de Peptídeos/imunologia , Veia Porta/imunologia , Fatores Etários , Atresia Biliar/complicações , Atresia Biliar/patologia , Biópsia , Endotélio/patologia , Endotélio/ultraestrutura , Feminino , Imunofluorescência/métodos , Seguimentos , Humanos , Lactente , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Variações Dependentes do Observador , Veia Porta/patologia , Veia Porta/ultraestrutura , Índice de Gravidade de DoençaRESUMO
Allogeneic Hematopoietic stem cell transplantation (allo-HSCT) is effective for several diseases, including leukemia, solid tumors, and immunodeficiency. However, there are still some intractable diseases that cannot be treated with HSCT alone. We have developed a new HSCT method, allo-HSCT + thymus transplantation (TT) from the same donor, which induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (HSCT + DLI). This method leads to improvement of immune function and the ability of engraftment, and is effective for treatment of autoimmune chronic pancreatitis and sialoadenitis in aging, lupus nephritis in hosts with radioresistance, and supralethal irradiation, in which conventional HSCT alone is ineffective. This method may become a valuable form of clinical therapy for intractable diseases.
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Transplante de Células-Tronco Hematopoéticas/métodos , Timo/transplante , Animais , Doenças Autoimunes/terapia , Nefrite Lúpica , Camundongos , Lesões por Radiação/terapia , Linfócitos T/fisiologia , Doadores de Tecidos , Transplante HomólogoRESUMO
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a valuable strategy for some intractable diseases, a number of problems remain to be resolved. We have developed a new HSCT method, HSCT + thymus transplantation (TT) from the same donor, which induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (HSCT + DLI). This new method is effective in the treatment of several intractable diseases and conditions, such as autoimmune diseases in aging, advanced malignant tumors, exposure to supralethal irradiation, multiple organ transplantation from different donors, and type 2 diabetes mellitus, for which conventional methods are ineffective. Our findings suggest that allo-HSCT + TT is preferable to conventional allo-HSCT alone or allo-HSCT + DLI. This method may become a valuable next-generation HSCT technique.
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Doenças Autoimunes/terapia , Diabetes Mellitus Tipo 2/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Lesões por Radiação/terapia , Timo/transplante , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Transfusão de Linfócitos , Camundongos , Lesões por Radiação/imunologia , Lesões por Radiação/patologia , Timo/imunologia , Transplante HomólogoRESUMO
PURPOSE: We describe cases presenting with progressive thoracic myelopathy after lumbopelvic fusion attributed to proximal junctional vertebral compression fracture (PJF) followed by spinal calcium pyrophosphate dehydrate (CPPD) crystal deposition. METHODS: The study included six patients, ranging from 62 to 75 years. All patients had been treated previously with lumbopelvic fusion. The mean period from the detection of PJF to the onset of myelopathy was 4.8 months. Notably, five patients demonstrated upper-instrumented vertebra (UIV) collapse. RESULTS: After revision surgery involving decompressive laminectomy and extension of the spinal fusion, all patients experienced significant improvement. Photomicrographs of the resected ligamentum flavum showed CPPD crystals and multinucleated giant cells. CONCLUSIONS: The combination of mechanical stress plus PJF and CPPD crystal deposition followed by a foreign body reaction to the deposited crystals caused myelopathy. Patients with radiographic evidence of PJF, especially UIV collapse, after lumbopelvic fusion should be followed carefully for the emergence of myelopathy.
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Pirofosfato de Cálcio/metabolismo , Fraturas por Compressão/etiologia , Doenças da Medula Espinal/etiologia , Fraturas da Coluna Vertebral/etiologia , Fusão Vertebral/efeitos adversos , Coluna Vertebral/metabolismo , Idoso , Feminino , Humanos , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Pelve , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Reoperação , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/cirurgia , Vértebras TorácicasRESUMO
We recently found that allogeneic intrabone marrow-bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor is effective in mice bearing solid tumors. In the current study, we examined the effects of this strategy on the survival of mice with leukemia. One week after intravenous injection of 1×10(6) leukemic cells (EL-4, H-2(b)) into 8-week-old B6 (H-2(b)) mice, the mice were 8 Gy irradiated and transplanted with 1×10(7) bone marrow cells (BMCs) from 8-week-old BALB/c mice (H-2(d)) by IBM-BMT with or without donor lymphocyte infusion (DLI) or ATT. All the mice without treatment died within 70 days after injection of EL-4. About 40% of those treated with IBM-BMT alone died within 100 days due to tumor relapse. In contrast, those treated with IBM-BMT+DLI or ATT showed the longest survival rate without relapse of leukemia. In addition, the former showed less graft versus host disease (GVHD) than the latter. The mice treated with IBM-BMT+ATT also showed an intermediate percentage of effector memory (EM) and central memory (CM) cells between those treated with BMT alone and those treated with IBM-BMT+DLI. The numbers and functions of T cells increased in those treated with IBM-BMT+ATT with interleukin-2 and interferon-γ production. These results suggest that IBM-BMT+ATT is effective in the treatment of leukemia with strong graft versus leukemia without increased risk of GVHD.
Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Timo/transplante , Animais , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Memória Imunológica , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-2/imunologia , Interleucina-2/metabolismo , Leucemia/imunologia , Leucemia/metabolismo , Leucemia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais , Timo/imunologia , Timo/metabolismo , Timo/patologia , Transplante HomólogoRESUMO
A 73-year-old woman showed marked exophytic growth of a tumor (25 × 23 × 14 mm) of the nipple over a period of 2 months. Histologically, numerous tumor nodules with no apparent keratinization were observed in the exophytic lesion. The tumor cells also showed little invasion to the dermis and no metastasis to the axillary lymph nodes (LN). The tumor cells were immunohistochemically positive for cytokeratins (CKs; AE1/AE3 and 34ßE12), epithelial membrane antigen (EMA), and p53, but negative for Ber-EP4 and human papilloma virus (HPV). The MIB-1 index was 56%. Some tumor cells were also positive for some neuroendocrine markers, and showed some tonofilaments and neurosecretory granules in the cytoplasm under electron microscopy. We made the differential diagnosis of mammary ductal carcinoma, basal cell carcinoma (BCC), Paget's disease, and neuroendocrine carcinoma including Merkel cell carcinoma. The final diagnosis was poorly differentiated squamous cell carcinoma (SCC) showing exophytic growth with neuroendocrine differentiation (ND) in the nipple. To our knowledge, although only five cases of Bowen's disease have been reported in the nipple, such a unique SCC has not been reported previously.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Mamilos/patologia , Idoso , Neoplasias da Mama/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Invasividade Neoplásica , Tumores Neuroendócrinos/diagnóstico , Mamilos/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Tomografia Computadorizada por Raios X , Carga Tumoral , UltrassonografiaRESUMO
We have recently shown that allogeneic intrabone marrow-bone marrow transplantation + adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2(b)) into BALB/c mice (H-2(d)) bearing Meth-A sarcoma (H-2(d)). The mice treated with all types of HSCT + TT showed more pronounced regression and longer survival than those treated with HSCT alone in all age groups. Those treated with HSCT + TT showed increased numbers of CD4(+) and CD8(+) T cells but decreased numbers of Gr-1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in CD4(+) T cells, compared with those treated with HSCT alone. In all mice, those treated with fetal liver cell (as fetal HSCs) transplantation + fetal TT or with newborn liver cell (as newborn HSCs) transplantation (NLT) + newborn TT (NTT) showed the most regression, and the latter showed the longest survival. The number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L(-)CD44(+) effector memory T cells and the production of interferon γ (IFN-γ) were highest in the mice treated with NLT + NTT. These findings indicate that, at any age, HSCT + TT is more effective against cancer than HSCT alone and that NLT + NTT is most effective.
Assuntos
Células-Tronco Embrionárias/transplante , Transplante de Células-Tronco Hematopoéticas , Neoplasias Experimentais/terapia , Timo/transplante , Fatores Etários , Animais , Animais Recém-Nascidos , Antígenos de Diferenciação de Linfócitos T/metabolismo , Antígeno CD11b/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fígado/citologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Receptores de Quimiocinas/metabolismo , Baço/citologia , Análise de Sobrevida , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia , Transplante Heterólogo , Transplante Homólogo , Carga TumoralRESUMO
There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM-BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT + TT) could be used to treat T2 DM by normalizing the T cell imbalance. Hence we addressed this issue by using such dual transplantation and demonstrate herein that seven weeks later, recipient db/db mice manifested improved body weight, reduced levels of blood glucose, and a reduction of plasma IL-6 and IL-1ß. More importantly, this treatment regimen showed normal CD4/CD8 ratios, and increased plasma adiponectin levels, insulin sensitivity, and the number of insulin-producing cells. Furthermore, the expression of pancreatic pAKT, pLKB1, pAMPK and HO-1 was increased in the mice treated with IBM-BMT + TT. Our data show that IBM-BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM-BMT + TT is a viable therapeutic option in the treatment of T2 DM.