RESUMO
Nuclear plant accidents can be a risk for thyroid cancer due to iodine radioisotopes. Near the Fukushima Daiichi nuclear power plant, cattle were exposed to radiation after the accident occurred in May 2011. Here we estimated the total radiation exposure to cattle thyroid and its effects on thyroid function. Until October 2016, the estimated external exposure dose in Farm A was 1416 mGy, while internal exposure dose of 131I, 134Cs, and 137Cs were 85, 8.8, and 9.7 mGy in Farm A and 34, 0.2, and 0.3 mGy in Farm B, respectively. The exposed cattle had thyroid with relatively lower weight and lower level of stable iodine, which did not exhibit any pathological findings. Compared with the control, the plasma level of thyroid-stimulating hormone (TSH) was higher in Farm A cattle born before the accident, while the plasma thyroxine (T4) was higher in Farm A cattle born after the accident, suggesting that exposed cattle showed slight hyperactivation of the thyroid gland. In addition, Farm A cattle have higher level of cortisol, one of the anterior pituitary gland-derived hormones. However, we did not observe a causal relationship between the radiation exposure and cattle thyroid.
Assuntos
Acidente Nuclear de Fukushima , Exposição à Radiação , Bovinos , Animais , Centrais Nucleares , Glândula Tireoide/efeitos da radiação , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/análise , Exposição à Radiação/efeitos adversos , Japão/epidemiologia , Doses de RadiaçãoRESUMO
A 52-year-old male was diagnosed with cT4N3M1b, cStage â £ adenocarcinoma of the lung, and underwent 6 courses of pemetrexed(PEM), carboplatin(CBDCA), and bevacizumab(Bev)therapy, followed by 4 courses of PEM/Bev maintenance therapy. Due to the deterioration of his condition, 4 courses of pembrolizumab(Pembro)therapy were administered as second- line therapy, but the treatment was discontinued due to disease progression. Third-line therapy with docetaxel(DTX)/ ramucirumab(Rmab)was administered, resulting in a partial response, but discontinued due to adverse events. Finally, fourth-line therapy with atezolizumab(Atezo)was initiated. After 6 courses of Atezo therapy, partial response was achieved, and the tumor continued to shrink for 3 years. The aim of the treatment strategy for both PD-1 and PD-L1 antibody drugs is to suppress T-cell exhaustion, and if either drug fails, the other drug may theoretically fail. However, in this case, the PD-L1 antibody drug was effective against non-small cell lung cancer that had shown resistance to PD-1 antibody drugs, suggesting that even if a patient becomes resistant to PD-1 antibody drugs, PD-L1 antibody drugs may result in effective outcomes.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1 , Carboplatina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1RESUMO
Reports on the therapeutic drug monitoring (TDM) of second- and third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer patients are limited and are required to improve the safety of EGFR-TKI therapy. Some EGFR-TKIs have active metabolites with similar or higher potency compared with the parent compounds; thus, monitoring the parent compound as well as its active metabolites is essential for truly effective TDM. In this study, we developed and validated a method that simultaneously quantifies second- and third-generation EGFR-TKIs (afatinib, dacomitinib, and osimertinib) and the active metabolites of osimertinib, AZ5104 and AZ7550, in the human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clinical application of the method was also evaluated. The analytes were extracted from a 100 µL serum sample using a simple protein precipitation method and analyzed using LC-MS/MS. Excellent linearity of calibration curves was observed at ranges of 2.5-125.0 ng/mL for afatinib, 2.5-125.0 ng/mL for dacomitinib, 4.0-800.0 ng/mL for osimertinib, 1.0-125.0 ng/mL for AZ5104, and 2.5-125.0 ng/mL for AZ7550. The precision and accuracy were below 14.9% and within ± 14.9% of the nominal concentrations, respectively. The mean recovery was higher than 94.7% and the coefficient of variation (CV) was lower than 8.3%. The mean internal-standard normalized matrix factors ranged from 94.6 to 111.9%, and the CVs were lower than 9.7%. This analytical method met the acceptance criteria of the U.S. Food and Drug Administration guidelines. The method was also successfully applied to the analysis of 45 clinical samples; it supports the efficient and valuable analysis for TDM investigations of EGFR-TKIs.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Afatinib , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cromatografia Líquida/métodos , Receptores ErbB , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases , Quinazolinonas , Espectrometria de Massas em Tandem/métodosRESUMO
Programmed death ligand 1 (PD-L1) expression on the surface of cancer cells affects the efficacy of anti-PD-1/PD-L1 immune checkpoint therapy. However, the mechanism underlying PD-L1 expression in cancer cells is not fully understood, particularly after ionizing radiation (IR). Here, we examined the impact of high linear energy transfer (LET) carbon-ion irradiation on the expression of PD-L1 in human osteosarcoma U2OS cells. We found that the upregulation of PD-L1 expression after high LET carbon-ion irradiation was greater than that induced by X-rays at the same physical and relative biological effectiveness (RBE) dose, and that the upregulation of PD-L1 induced by high LET carbon-ion irradiation was predominantly dependent on ataxia telangiectasia and Rad3-related (ATR) kinase activity. Moreover, we showed that the downstream signaling, e.g. STAT1 phosphorylation and IRF1 expression, was upregulated to a greater extent after high LET carbon-ion irradiation than X-rays, and that IRF1 upregulation was also ATR dependent. Finally, to visualize PD-L1 molecules on the cell surface in 3D, we applied immunofluorescence-based super-resolution imaging. The three-dimensional structured illumination microscopy (3D-SIM) analyses revealed substantial increases in the number of presented PD-L1 molecules on the cell surface after high LET carbon-ion irradiation compared with X-ray irradiation.
Assuntos
Antígeno B7-H1/biossíntese , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Radioterapia com Íons Pesados , Proteínas de Neoplasias/biossíntese , Osteossarcoma/patologia , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/fisiologia , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Humanos , Imageamento Tridimensional , Fator Regulador 1 de Interferon/biossíntese , Fator Regulador 1 de Interferon/genética , Transferência Linear de Energia , Morfolinas/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Fosforilação/efeitos da radiação , Processamento de Proteína Pós-Traducional/efeitos da radiação , Pirazinas/farmacologia , Pironas/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Fator de Transcrição STAT1/metabolismo , Sulfonas/farmacologia , Regulação para Cima/efeitos da radiação , Raios XRESUMO
Chemotherapy for patients with poor performance status(PS)is not recommended because it increases the risk of death and shortens their survival. We report on 3 cases in which palliative care improved PS and enabled chemotherapy, resulting in a prolonged prognosis. Case 1 involves a 57âyearâold woman with multiple lung, liver, and bone metastases from breast cancer who was administered celecoxib and oxycodone. She received Mohs paste therapy. Her PS improved from 3 to 2, and paclitaxel and trastuzumab were started; however, the patient died on day 861. Case 2 involves a 53âyearâold woman with multiple lymph node metastases from carcinoma of an unknown primary cause. She was administered oxycodone, loxoprofen, and dexamethasone. Her PS improved from 4 to 3. The biopsy of her bone marrow showed diffuse large Bâcell lymphoma. The patient is still alive, 6 years and 10 months after the introduction of RâCHOP. In case 3, a 57âyearâold man with multiple bone metastases from small cell lung cancer was administered loxoprofen and betamethasone. His PS improved from 4 to 3. Etoposide and carboplatin were administered to him, but the patient died on day 692. Palliative care may enable the introduction of chemotherapy and consequently improve prognosis.
Assuntos
Neoplasias da Mama , Cuidados Paliativos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carboplatina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Trastuzumab/uso terapêuticoRESUMO
Drinking water is one of the major exposure routes to Perfluoroalkyl substances (PFASs). These chemicals are scarcely removed by the conventional process in water purification plants. In the present study, four models of pitcher-type water purifiers (A-D) were tested to evaluate their removal effect on six PFASs including PFOS and PFOA. All of the water purifiers removed PFASs, but the efficiency was dependent on the models. Model C was most effective; more than 90% of all PFASs were removed through the recommended life of the filter cartridge. Model D was least effective; its removal efficiency declined below 50% by the end of the cartridge's life. When compared by the carbon chain length of PFASs, the removal efficiency was "C12 > C10 > C8 > C6" in all models. This study clearly demonstrates that household water purifiers are effective in decreasing the exposure to PFASs through drinking water.
Assuntos
Ácidos Alcanossulfônicos , Água Potável , Fluorocarbonos , Poluentes Químicos da Água , Purificação da Água , Fluorocarbonos/análise , Poluentes Químicos da Água/análiseRESUMO
The patient was a 65-year-old man with advanced gastric cancer, cT4bN3aM1, cStage â £. The SOX therapy was administered as the primary treatment but discontinued after 9 courses because of disease progression. The PTX plus RAM therapy was then administered for 1 courses as the secondary treatment but discontinued because of the development of peritoneal dissemination, increased number of ascites, and increased number of lymph node metastases. The nivolumab(NIV)therapy was initiated as the tertiary treatment, but the patient complained of fatigue and diplopia after 2 courses. Ptosis was observed, and transaminase and creatine kinase levels were elevated. Electrocardiography showed complete right bundle branch block. The patient showed immune-related adverse events and was diagnosed with myocarditis and myasthenia gravis due to NIV. Consequently, systemic steroids were administered. Although 2 course of CPT-11 was administered as the fourth-line treatment, the treatment was discontinued upon the patient's request. Ten months after the discontinuation of chemotherapy, the disease showed no progression. The patient is being followed-up as an outpatient. Here, we reported a case of gastric cancer with tumor shrinkage after the discontinuation of NIV.
Assuntos
Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gastrectomia , Humanos , Metástase Linfática , Masculino , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , TiazóisRESUMO
Since the Fukushima nuclear accident in 2011, various abnormalities have been reported in animals living in the contaminated area. In the present study, we examined DNA damage in cattle living in the "difficult-to-return zone" by 8-hydroxy-2'-deoxyguanosine, comet, and micronucleus assays using their peripheral blood. The radiation exposure dose rate at the sampling time was approximately 0.25 or 0.38 mGy/day and the cumulative dose was estimated at approximately 1000 mGy. Significant increase in DNA damage was not detected by any of the three methods. As DNA damage is a stochastic effect of radiation, it might be occurring in animals living in the contaminated area. However, the present results suggest that radiation-induced DNA damage in the cattle did not increase to the level detectable by the assays we used due to the low dose rate in this area.
Assuntos
Doses de Radiação , Exposição à Radiação/análise , Monitoramento de Radiação , Animais , Bioensaio , Bovinos , Dano ao DNA , Acidente Nuclear de Fukushima , JapãoRESUMO
La2O3-Ga2O3 binary glass exhibits unusual optical properties owing to its high oxygen polarizability and low vibration energy. These optical properties include high refractive indices and a wide transmittance range. In this study, we performed classical molecular dynamics simulations on La2O3-Ga2O3 glass synthesized by an aerodynamic levitation technique. We have obtained structural models that reproduce experimental results, such as NMR, high-energy X-ray diffraction, and neutron diffraction. Based on our analysis, the structural features were clarified: 5-, 6-coordinated Ga, edge-sharing GaOx-GaOx polyhedral linkages, and oxygen triclusters. Additionally, the vibrational density of states was calculated by diagonalization of the dynamical matrix derived from the structural models and the results were compared with Raman scattering spectra. The mode analysis of the Raman spectra revealed that the principal bands at 650 cm-1 were mainly attributed to the stretching modes of the bridging and nonbridging oxygens. Meanwhile, the shoulder bands at the highest frequency of 750 cm-1 were mainly attributed to the stretching modes of the bridging oxygens and oxygen triclusters. The structural models obtained in this study well describe the characteristic local structures and vibrational properties of the La2O3-Ga2O3 glass.
RESUMO
To study the effect of ionizing radiation on thyroid glands, 66 Japanese Black cattle residing in the restricted area of the Fukushima Daiichi Nuclear Power Plant in 2013-2017 were pathologically examined. There were no clinical symptoms of thyroid disease in these cattle. Three cases of goiter and seven of atrophy were found in two among the four farms examined. Cases of goiter exhibited normal morphological structure without mass or nodule formation in thyroid glands. Cellular atypia or capsular invasion of the follicular epithelium was absent. The estimated integrated dose of external radiation in goiter cases ranged from maximum 797 mSv to minimum 24 mSv. All lobules in the seven atrophic thyroid glands were affected, but pathological findings, such as inflammatory cell infiltration or stromal fibrosis, were not observed. The estimated integrated dose of external radiation in atrophic thyroids ranged from maximum 589 mSv to minimum 8 mSv. Immunohistochemical analysis of anti-nitroguanosine and the TUNEL method in goiter and atrophic thyroid glands did not reveal any positive findings. The present study indicates that there was no significant relationship between a radiation effect and pathological findings in any thyroid glands.
Assuntos
Doenças dos Bovinos/patologia , Acidente Nuclear de Fukushima , Bócio/veterinária , Neoplasias Induzidas por Radiação/veterinária , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/veterinária , Animais , Bovinos , Doenças dos Bovinos/etiologia , Bócio/patologia , Humanos , Japão , Centrais Nucleares , Doses de Radiação , Glândula Tireoide/patologia , Glândula Tireoide/fisiopatologiaRESUMO
Blood and urine were compared to clarify which is a better sample for estimating the concentration of radioactive cesium in muscles of live cattle. The most probable concentration of 137 Cs in muscles was 21.0 times that in blood, and the error of this estimation was 28%. The concentration of 137 Cs in blood was estimated accurately using urine samples. The estimation error did not increase so much (33%), even when the concentration of 137 Cs in muscles was estimated using urine samples. On the other hand, the maximum volume of blood that can be collected with one syringe is 50 ml, whereas it is easy to collect 1,000 ml of urine. It took at least 360 min to confirm that a cow meets the legal standard by inspecting 50 ml of blood. However, with 1,000 ml of urine, a 20 min measurement time was sufficient for this purpose. This difference in the required measurement time is critically important for practical use. In addition, urine can be collected by farmers themselves, whereas the blood collection requires a veterinarian. Therefore, urine is a more convenient and practical sample for estimating the contamination level of live cattle with radioactive cesium.
Assuntos
Bovinos/sangue , Bovinos/urina , Radioisótopos de Césio/sangue , Radioisótopos de Césio/urina , Exposição à Radiação/efeitos adversos , Exposição à Radiação/análise , Animais , Biomarcadores/sangue , Biomarcadores/urina , Radioisótopos de Césio/efeitos adversos , Acidente Nuclear de FukushimaRESUMO
HIGHLIGHTS: Boiling effectively decreased radioactive cesium concentrations in beef. Water extraction was also effective but not as effective as boiling. The decontamination effect increased with treatment time. The decontamination effect was inversely proportion to the square of the thickness of the beef slice.
Assuntos
Radioatividade , Carne Vermelha , Animais , Bovinos , Césio , Radioisótopos de Césio , ÁguaRESUMO
White blood cells, especially lymphocytes, are susceptible to radiation exposure. In the present study, red blood cell, total white blood cell, and lymphocyte counts were repeatedly measured in cattle living on three farms located in the "difficult-to-return zone" of the Fukushima nuclear accident, and compared with two control groups from unaffected areas. Blood cell counts differed significantly between the two control groups, although almost all the values fell within the normal range. The blood cell counts of the cattle in the "difficult-to-return zone" varied across sampling times even on the same farms, being sometimes higher or lower than either of the two control groups. However, neither a statistically significant decrease in blood cell counts nor an increase in the rate of cattle with extremely low blood cell counts was observed overall. The estimated cumulative exposure dose for the cattle on the most contaminated farm was within a range of 500-1000 mSv, exceeding the threshold for the lymphopenia. Because of the low dose rate on these farms, potential radiation damages would have been repaired and have not accumulated enough to cause deterministic effects.
Assuntos
Bovinos/sangue , Exposição Ambiental/efeitos adversos , Contagem de Eritrócitos , Acidente Nuclear de Fukushima , Contagem de Leucócitos , Contagem de Linfócitos , Poluentes Radioativos/efeitos adversos , Animais , Fazendas , Japão , Doses de RadiaçãoRESUMO
We previously identified a novel nanomagnetic particle, N,N'-bis(salicylidene)ethylenediamine iron [Fe(Salen)]. Fe(Salen) not only shows antitumor effects but also magnetic properties. We found that Fe(Salen) can be used for magnet-guided drug delivery and visualization of accumulated drug by magnetic resonance imaging (MRI) because of its magnetism. In addition, Fe(Salen) can generate heat by itself when exposed to an alternating current magnetic field (AMF), resulting in a hyperthermia effect. Herein, we partly elucidated the antitumor mechanism of Fe(Salen) and carried out an i.v. repeated dose toxicity study to decide the therapeutic amount. Furthermore, we evaluated the antitumor effect of selective intra-arterial injection or i.v. injection of Fe(Salen) by catheter and the hyperthermia effect of Fe(Salen) when exposed to AMF in vivo. We used a rabbit model grafted with VX2 cells (rabbit squamous cell carcinoma) on the right leg. Intra-arterial injection of Fe(Salen) showed a greater antitumor effect than did i.v. injection. The combination of Fe(Salen) intra-arterial injection and AMF exposure showed a greater antitumor effect than did either Fe(Salen) or methotrexate (MTX) without AMF exposure, suggesting that AMF exposure greatly enhanced the antitumor effect of Fe(Salen) by arterial injection by catheter. This is the first report that the effectiveness of Fe(Salen) was evaluated in the point of administration route; that is, selective intra-arterial injection by catheter. Taken together, these results indicate a new administration route; that is, selective arterial injection of Fe(Salen) by catheter, and the development of a new strategy of simultaneous hyperthermia-chemotherapy in the future.
Assuntos
Carcinoma de Células Escamosas/terapia , Neoplasias Femorais/terapia , Hipertermia Induzida/métodos , Compostos de Ferro/administração & dosagem , Nanopartículas/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Injeções Intra-Arteriais , Injeções Intravenosas , Compostos de Ferro/farmacologia , Campos Magnéticos , Masculino , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Coelhos , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
N,N'-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.
RESUMO
Prolinate salt is an efficient catalyst in the Mannich reaction of alkynyl imine and aldehyde, to afford synthetically useful chiral propargyl amine derivatives with excellent syn-selectivity and nearly perfect control of the absolute configuration. The counterion of the prolinate salt does not affect the enantioselectivity. This is a rare example, in which proline alkali metals, alkaline-earth metals, or ammonium salt show higher reactivity and better stereoselectivity than the parent proline.
RESUMO
A two-pot synthetic method to construct the chiral syn-1,3-diol unit has been developed from three aldehydes and either Wittig or Horner-Wadsworth-Emmons reagents. In the first pot, chiral δ-hydroxy α,ß-unsaturated ketones are synthesized with excellent enantioselectivity by the organocatalyst-mediated asymmetric direct aldol reaction of two different aldehydes, followed by either Wittig or Horner-Wadsworth-Emmons reactions. In the second pot, domino acetalization with an aldehyde and subsequent oxy-Michael reaction proceeds in the presence of NaClO4 and a catalytic amount of Bi(OTf)3 (OTf=trifluoromethanesulfonate) to provide the chiral 1,3-syn-diol derivative with excellent diastereoselectivity. Diosponginâ C and yashabushidiolâ A have been synthesized efficiently by using the present method as a key step.
RESUMO
In the region contaminated by the Fukushima nuclear accident, radioactive contamination of live cattle should be checked before slaughter. In this study, we establish a precise method for estimating radioactive cesium concentrations in cattle blood using urine samples. Blood and urine samples were collected from a total of 71 cattle on two farms in the 'difficult-to-return zone'. Urine 137 Cs, specific gravity, electrical conductivity, pH, sodium, potassium, calcium, and creatinine were measured and various estimation methods for blood 137 Cs were tested. The average error rate of the estimation was 54.2% without correction. Correcting for urine creatinine, specific gravity, electrical conductivity, or potassium improved the precision of the estimation. Correcting for specific gravity using the following formula gave the most precise estimate (average error rate = 16.9%): [blood 137 Cs] = [urinary 137 Cs]/([specific gravity] - 1)/329. Urine samples are faster to measure than blood samples because urine can be obtained in larger quantities and has a higher 137 Cs concentration than blood. These advantages of urine and the estimation precision demonstrated in our study, indicate that estimation of blood 137 Cs using urine samples is a practical means of monitoring radioactive contamination in live cattle.
Assuntos
Bovinos/sangue , Bovinos/urina , Radioisótopos de Césio/sangue , Radioisótopos de Césio/urina , Monitoramento Ambiental/métodos , Contaminação Radioativa de Alimentos/prevenção & controle , Urinálise/métodos , Animais , Acidente Nuclear de Fukushima , Sensibilidade e EspecificidadeRESUMO
Fifty-one Japanese black cattle from four farms in the evacuation zone of the Fukushima nuclear accident were examined pathologically during the period, 2013-2016. We found no evidence of a radiation effect on pathological findings in any of these autopsy cases, although nine cases (3.7%) of enzootic bovine leukosis (EBL) and three cases (1.2%) of goiter were diagnosed. Estimated integrating dose of external exposure in EBL cases ranged from a maximum of 1200 mSv to a minimum of 72 mSv. Clinically, five cases showed wobble, dysstasia or paralysis. Exophthalmos was observed in three cases. Macroscopically, enlarged lymph nodes, multiple irregular masses of intra-abdominal and intrapelvic adipose tissue, diffuse thickening of the abomasal submucosa with ulceration, and numerous white nodules of myocardium were observed. Histologically, neoplastic lymphoid cells were extensively proliferated and infiltrated in the lesions. Lymphoid tumor cells showed mature or large lymphoblastic appearance. Immunohistochemically, tumor cells were positive for BLA-36, CD20 and CD5, and negative for CD3. Three cases showed diffuse enlargement of the thyroid gland with no mass or nodule lesion. Histologically, diffuse proliferation of follicular epithelium was observed with preservation of normal structures. There were no malignant findings such as cellular atypia or invasion to capsule.