肺移植後慢性拒絶反応に対するアンチセンスMTI-MMP遺伝子導入の効果

金沢大学附属病院【目的】癌の浸潤,進展だけでなく,慢性肺気腫や肺線維症にもマトリックスメタロプロテアーゼ(MMPs)が関与していることが報告されている.我々は,肺移植慢性拒絶反応の代表的な病態である,閉塞性細気管支症候群におけるMMPsとの関連性を,ラット肺移植モデルを用いて検討した.【方法】Brown Norway種(BN)をdonor, Lewis種(LW)をrecipientとして異所性気管移植(異系群)を行い,4週後にgraftを採取した.対象として,LWおよびLWによる同系移植モデル(同系群)を用いた.1.ゼラチンザイモグラフィー:採取した移植片をゼラチンザイモグラフィーによりゼラチナーゼ活性を測定し,その分子量により,MMP-9(92kDa),MMP-2(68-72kDa)の発現を検索した.2.in situ zymography:移植片の薄切をFilm in situ Zymography(FIZ)フイルムRを用いて,ゼラチナーゼ活性の局在を検索した.3.RT-PCR:移植片より抽出した全RNAを用いてRT-PCRを行い,MMPsならびにMT1-MMPのm-RNAの発現を定量した.【結果】1.ゼラチンザイモグラフイー:異系群のみにMMP-9(92kDa)の発現を認めた.MMP-2(68-72kDa)は,同系,異系群ともに発現を認めた.活性型MMP-2(62kDa)の発現の割合を検索すると,異系群は同系群に比べ有意に多く発現していた.2.In situ zymography:気管支断面における内腔閉塞率は異系群が有意に高く,肥厚閉塞しているのは上皮下〜粘膜下組織であった.同部位にに一致して,ゼラチナーゼ活性の局在を認めた.同系群では内腔閉塞をほとんど認めず,ゼラチナーゼ活性部位は極わずかであった.3.Northern Blotting:MMP-9は異系群にのみ認められた.MMP-2およびMT1-MMPのm-RNAの発現は異系群において有意に高かった.【総括】ラット気管支移植モデルにおいて,MMP-9, MMP-2およびMT1-MMPの発現を認めた.これにより,閉塞性細気管支症候群のメカニズムにおいて,MMPs, MT1-MMPsが寄与していることが示唆された.研究課題/領域番号:13770733, 研究期間(年度):2001-2002出典：「肺移植後慢性拒絶反応に対するアンチセンスMTI-MMP遺伝子導入の効果」研究成果報告書　課題番号13770733（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-13770733/)を加工して作

膜型マトリックスメタロプロテアーゼ-1(MT-MMP-1)CDNA導入による癌細胞の転移,浸潤の促進

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1217号, 学位授与年月日：平成8年3月25日,学位授与年：199

A Pulmonary Nodule due to Pulmonary Infarction Diagnosed by Video-Assisted Thoracoscopy

We report a pulmonary infarction in 68-year-old man who was referred for an asymptomatic pulmonary nodule in chest radiography. Computed tomography (CT), positron emission tomography (PET), and transthoracic needle aspiration suggested suspicion for malignancy. Video-assisted thoracoscopic surgery (VATS) was performed for histologic diagnosis. Our case is a pulmonary nodule due to pulmonary infarction diagnosed by VATS in Korea

Subcutaneous emphysema in a case of infective sinusitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Subcutaneous emphysema with pneumomediastinum is a rare phenomenon with a high morbidity and may occur spontaneously.</p> <p>Case presentation</p> <p>A 30-year-old Caucasian man presented with sudden onset of a painful, swollen neck and was found, via clinical and radiological examination to have subcutaneous emphysema. A swallow study showed no oesophageal perforation. Computed tomography of his neck and thorax demonstrated pneumomediastinum but no other pathology. Management was conservative with intravenous antibiotics, fluids and no oral intake. He had a history of a productive cough and a flexible nasoendoscopy found purulent sinusitis which was treated with topical nasal washes. The patient was discharged after 72 hours and will be followed up by the otolaryngology-head and neck service.</p> <p>Conclusions</p> <p>Infective sinusitis is a rare cause of subcutaneous emphysema and pneumomediastinum. It may be managed conservatively provided there is early recognition and exclusion of more serious pathology, such as a ruptured trachea or oesophagus.</p

Recurrence in skeletal muscle from squamous cell carcinoma of the uterine cervix: a case report and review of the literature

BACKGROUND: The occurrence of skeletal muscle metastases is a very rare event. Only two cases of late skeletal muscle recurrence from cervical cancer have been documented until now. CASE PRESENTATION: A 38-year old patient, submitted to radical hysterectomy and pelvic lymphadenectomy for a squamous FIGO stage IB1 cervical carcinoma, presented after 76 months with a palpable, and painless swelling on the left hemithorax. MRI showed a nodule located in the context of the intercostal muscles. Pathology revealed the presence of metastasis of squamous cell carcinoma of similar morphology as the primary. On the basis of FDG-PET findings, which excluded other sites of disease, surgical excision of the lesion was performed. The patient was triaged to chemotherapy plus external radiotherapy. CONCLUSION: A case of skeletal muscle recurrence from cervical cancer after a very long interval from primary diagnosis is reported. Muscular pain or weakness, or just a palpable mass in a patient with a history of cancer has always to raise the suspicion of muscle metastasis

The case of double primary lung adenocarcinomas with an EGFR mutation and ALK translocation successfully treated with alectinib at the post-surgicalrecurrence

A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence

Metabolic responses to salt stress of barley (Hordeum vulgare L.) cultivars, Sahara and Clipper, which differ in salinity tolerance

Plants show varied cellular responses to salinity that are partly associated with maintaining low cytosolic Na+ levels and a high K+/Na+ ratio. Plant metabolites change with elevated Na+, some changes are likely to help restore osmotic balance while others protect Na+-sensitive proteins. Metabolic responses to salt stress are described for two barley (Hordeum vulgare L.) cultivars, Sahara and Clipper, which differed in salinity tolerance under the experimental conditions used. After 3 weeks of salt treatment, Clipper ceased growing whereas Sahara resumed growth similar to the control plants. Compared with Clipper, Sahara had significantly higher leaf Na+ levels and less leaf necrosis, suggesting they are more tolerant to accumulated Na+. Metabolite changes in response to the salt treatment also differed between the two cultivars. Clipper plants had elevated levels of amino acids, including proline and GABA, and the polyamine putrescine, consistent with earlier suggestions that such accumulation may be correlated with slower growth and/or leaf necrosis rather than being an adaptive response to salinity. It is suggested that these metabolites may be an indicator of general cellular damage in plants. By contrast, in the more tolerant Sahara plants, the levels of the hexose phosphates, TCA cycle intermediates, and metabolites involved in cellular protection increased in response to salt. These solutes remain unchanged in the more sensitive Clipper plants. It is proposed that these responses in the more tolerant Sahara are involved in cellular protection in the leaves and are involved in the tolerance of Sahara leaves to high Na+

肺非結核性抗酸菌 (MOTT) 合併肺癌

金沢大学医薬保健研究域医学系From January 1997 to June 1999, we performed surgery in 17 patients with mycobacteria other than tuberculosis (MOTT), and 2 patients with lung cancer among them. Both patients had the diagnosis of MOTT by sputa bacterial cultures preoperatively, but no diagnosis of lung cancer. By computed tomography (CT) scanning, lung cancer was suspected in both patients, therefore they were performed video-assisted thoracoscopic resection of the lung. The diagnosis of malignancy was made by intraoperative frozen section of resected tissue, the patients were performed lobectomy with systematic mediiastinal lymph nodes dissection. According to increment of detection of the small peripheral lesion, infectious disease such as MOTT can be detected as small abnormal shadow by CT. However, it is difficult to distinguish malignancy from infectious disease preoperatively. Even if a preoperative diagnosis, of MOTT was made like present cases, diagnostic video-assisted thoracoscopic surgery must be performed, considering that lung cancer could combined with MOTT

Patient, tumor, and healthcare factors associated with regional variability in lung cancer survival: a Spanish high‑resolution population‑based study

Purpose The third most frequently diagnosed cancer in Europe in 2018 was lung cancer; it is also the leading cause of cancer death in Europe. We studied patient and tumor characteristics, and patterns of healthcare provision explaining regional variability in lung cancer survival in southern Spain. Methods A population-based cohort study included all 1196 incident first invasive primary lung cancer (C33–C34 according to ICD-10) cases diagnosed between 2010 and 2011 with follow-up until April 2015. Data were drawn from local population-based cancer registries and patients’ hospital medical records from all public and private hospitals from two regions in southern Spain. Results There was evidence of regional differences in lung cancer late diagnosis (58% stage IV in Granada vs. 65% in Huelva, p value < 0.001). Among patients with stage I, only 67% received surgery compared with 0.6% of patients with stage IV. Patients treated with a combination of radiotherapy, chemotherapy, and surgery had a 2-year mortality risk reduction of 94% compared with patients who did not receive any treatment (excess mortality risk 0.06; 95% CI 0.02–0.16). Geographical differences in survival were observed between the two regions: 35% vs. 26% at 1-year since diagnosis. Conclusions The observed geographic differences in survival between regions are due in part to the late cancer diagnosis which determines the use of less effective therapeutic options. Results from our study justify the need for promoting lung cancer early detection strategies and the harmonization of the best practice in lung cancer management and treatment.Maria Jose Sanchez Perez is supported by the Andalusian Department of Health: Research, Development, and Innovation Office project grant PI-0152/2017. Miguel Angel Luque-Fernandez is supported by the Spanish National Institute of Health, Carlos III Miguel Servet I Investigator Award (CP17/00206)