Expansion of functional human mucosal-associated invariant T cells via reprogramming to pluripotency and redifferentiation.

Mucosal-associated invariant T (MAIT) cells play an important physiological role in host pathogen defense and may also be involved in inflammatory disorders and multiple sclerosis. The rarity and inefficient expansion of these cells have hampered detailed analysis and application. Here, we report an induced pluripotent stem cell (iPSC)-based reprogramming approach for the expansion of functional MAIT cells. We found that human MAIT cells can be reprogrammed into iPSCs using a Sendai virus harboring standard reprogramming factors. Under T cell-permissive conditions, these iPSCs efficiently redifferentiate into MAIT-like lymphocytes expressing the T cell receptor Vα7.2, CD161, and interleukin-18 receptor chain α. Upon incubation with bacteria-fed monocytes, the derived MAIT cells show enhanced production of a broad range of cytokines. Following adoptive transfer into immunocompromised mice, these cells migrate to the bone marrow, liver, spleen, and intestine and protect against Mycobacterium abscessus. Our findings pave the way for further functional analysis of MAIT cells and determination of their therapeutic potential.

[Gastrojejunostomy for irresectable gastric cancer with pyloric stenosis-new role of surgery in the era of S-1].

We report a patient with an advanced gastric cancer complicated by pyloric stenosis who was effectively treated by S-1 mono-therapy after gastrojejunostomy. A 62-year-old man consulted a general practitioner for abdominal pain and anorexia. Gastric roentgenography and upper gastrointestinal endoscopy showed gastric cancer(Borrmann Type 3) with pyloric stenosis. He was referred to our department. He underwent laparotomy, which revealed a T4 tumor invading the pancreas head, but neither liver nor peritoneal metastasis. A gastrojejunostomy was made. After the operation, chemotherapy of S-1(120 mg/day, day 1-21)+cisplatin(100 mg/day, day 8)was administered. After 2 courses, level of tumor marker decreased remarkably and abdominal enhanced computed tomography showed a significant size reduction of lymph nodes and that direct invasion to the pancreas was not clear any more. Second laparotomy was carried out and curative surgery was performed. After 4 courses of S-1(120 mg/day, day 1 approximately 28)mono-therapy as adjuvant chemotherapy, bone metastasis was confirmed by scintigram. Then methotrexate+5-FU, irinotecan+cisplatin and cisplatin+paclitaxel were chosen as second-, third-and fourth-line chemotherapy, which were not effective for long. He died 572 a days after the initial surgery. In the past, gastrojejunostomy was regarded as useful palliative treatment for those with gastric outlet stenosis to ameliorate the QOL. As S-1 is taking major role in the chemotherapy for advanced gastric cancer recently, usefulness of bypass surgery for such patients is highlighted even for longer survival time.

[The diagnostic imagings of liver metastases].

The liver is an organ susceptible metastases. Malignant neoplasms of many organs frequently metastasize to the liver, particularly colon malignancies. Most metastases enter the liver via the blood circulation, but metastases through lymphatic vessels and the peritoneum are also common. The morphologies of liver metastases and findings on diagnostic images vary considerably. Numerous modalities are available for diagnostic imaging of liver metastases: ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), angiography, nuclear medicine, and others. Ultrasonography is the simplest, most non-invasive, and cheapest, but relies on the skill of the operator. CT and MRI are also non-invasive, and the sensitivities of these techniques have recently been improved with the development of multidetector CT, contrast agents for MRI that specifically accumulate in the liver, and other advances. Moreover, positron emission CT using fluorine-18-deoxyglucose (FDG-PET) displays a high sensitivity. Angiography is an invasive modality, but is adopted with CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA), or for the purpose of interventional radiology. Rational selection of appropriate modalities for a given purpose requires familiarity with the characteristics of each modality. In the present paper, we describe the morphologic characters of liver metastases and investigate the associated characteristics and usefulness of each modality.