CAR T-cell therapy: Blessing of 21st century

More than twenty years of research on cellular immunotherapy has recently resulted in the development of genetically-modified T cell products that express synthetic chimeric antigen receptor (CAR) with specificity toward the cell-surface tumor antigens. Recent studies have demonstrated promising response rates after infusion of these cells in patients with B-cell precursor and mature B-cell neoplasms, including acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and plasma cell myeloma. Given the satisfactory evidence of their outstanding therapeutic benefit, CD19-targeted CAR T cells have become the first genetic engineering element approved by the United States Food and Drug Administration to treat patients for whom other promising options are unavailable. While clinicians are widely using CAR T-cell therapies, the two most common toxicities are cytokine-release syndrome and CAR T cell-related neurotoxicity/encephalopathy syndrome. Moreover, some studies have explained that the relapse after receiving CAR T-cell therapy is caused by acquired resistance due to genetic mutation or splicing variants, leading to the loss or diminished surface expression of the target molecule in neoplastic cells. To overcome these caveats and achieve therapeutic success, restless efforts are ongoing toward the development of next-generation CAR T cells with more sophisticated design.This study was supported in part by Grants-in-Aid from the Japan Agency for Medical Research and Development (AMED) (19pc0101041s0101, 20ek0510027h0002, 21ek0510032h0002 to TI) and the Program of the network-type Joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University, Nagasaki University, and Fukushima Medical University (to TI)

Current status of Japanese detectors

Current status of TAMA and CLIO detectors in Japan is reported in this article. These two interferometric gravitational-wave detectors are being developed for the large cryogenic gravitational wave telescope (LCGT) which is a future plan for detecting gravitational wave signals at least once per year. TAMA300 is being upgraded to improve the sensitivity in low frequency region after the last observation experiment in 2004. To reduce the seismic noises, we are installing new seismic isolation system, which is called TAMA Seismic Attenuation System, for the four test masses. We confirmed stable mass locks of a cavity and improvements of length and angular fluctuations by using two SASs. We are currently optimizing the performance of the third and fourth SASs. We continue TAMA300 operation and R&D studies for LCGT. Next data taking in the summer of 2007 is planned. CLIO is a 100-m baseline length prototype detector for LCGT to investigate interferometer performance in cryogenic condition. The key features of CLIO are that it locates Kamioka underground site for low seismic noise level, and adopts cryogenic Sapphire mirrors for low thermal noise level. The first operation of the cryogenic interferometer was successfully demonstrated in February of 2006. Current sensitivity at room temperature is close to the target sensitivity within a factor of 4. Several observation experiments at room temperature have been done. Once the displacement noise reaches at thermal noise level of room temperature, its improvement by cooling test mass mirrors should be demonstrated.Comment: 6 pages, 5 figures, Proceedings of GWDAW-1

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

Streptococcus gallolyticus ssp. pasteurianus bacteremia during chemotherapy-induced neutropenia in a patient with malignant lymphoma

Background: Streptococcus gallolyticus ssp. pasteurianus is a commensal bacterium of the alimentary tract in humans and animals. This microorganism not only causes sepsis, endocarditis, and meningitis but is also associated with colorectal tumors. We report herein a rare case of S. gallolyticus ssp. pasteurianus bacteremia in a patient with concomitant colon cancer and aggressive malignant lymphoma during the neutropenic period after chemotherapy against lymphoma. Case presentation: A 79-year-old man was found to have an adenoma in the ascending colon, and endoscopic mucosal resection (EMR) was planned to remove the lesion. However, he was diagnosed with diffuse large B-cell lymphoma during the pre-operation examination. The EMR was postponed, and he received rituximab, cyclophosphamide, etoposide, vincristine, and prednisolone (R-CEOP). He had a neutropenic fever with positive blood cultures for S. gallolyticus ssp. pasteurianus during the first course of R-CEOP. He improved as soon as cefepime was administered. Bacteremia did not recur thereafter, and he underwent EMR after completing six cycles of R-CEOP. The histological diagnosis of the colon tumor was well-differentiated adenocarcinoma in adenoma. Streptococcus gallolyticus ssp. pasteurianus was not detected in the culture of the resected tissue. Conclusion: Although there have been few reports of bloodstream infection due to S. gallolyticus ssp. pasteurianus in patients with hematological malignancies undergoing cytotoxic chemotherapy, physicians should investigate the presence of coexisting colorectal tumors when this bacterium is isolated from blood cultures

Sudden Hearing Loss in a Young Patient with Chronic Myelogenous Leukemia

Hyperleukocytosis is a typical presentation of chronic myelogenous leukemia (CML). It sometimes induces leukostasis, the symptoms of which include visual change, headache, tinnitus, dizziness, and occasional disturbance of consciousness. In the present study, a 26-year-old male patient visited a general physician, who observed marked hyperleukocytosis and referred the patient to our hospital. The patient was diagnosed with CML and treated with a tyrosine kinase inhibitor and hydroxycarbamide. On the fourth day after admission, the patient suddenly complained of left-sided hearing loss. An audiogram revealed profound left sensorineural hearing loss. Magnetic resonance imaging of the head showed no lesions in the inner ear, cerebellum, or brain stem; therefore, we diagnosed sudden hearing loss due to leukostasis. Subsequently, his hearing did not improve, despite a decrease in leukocytes. The pathophysiology of leukocytosis involves increased leukocytes and thrombi, which induce high blood viscosity in the microcirculation. Leukostasis-related infarction and hemorrhage can lead to occlusion of the labyrinthine artery, causing deafness. Physicians should be aware that deafness can develop when diagnosing marked leukocytosis because such deafness is irreversible in most cases

Successful combination treatment with azacitidine and venetoclax as a bridging therapy for third allogenic stem cell transplantation in a patient with 11q23/MLL‐rearranged complex karyotype acute myeloid leukemia

Abstract Translocation t(6;11) occurs in approximately 5% of patients with acute myeloid leukemia (AML) corresponding to 11q23/mixed lineage leukemia (MLL) rearrangement. The AF6 gene on chromosome 6q27 is the fusion partner of the MLL gene on 11q23 in t(6;11), which results in a poor prognosis. The case of a patient with 11q23/MLL‐rearranged AML who successfully underwent a third allogeneic stem cell transplantation after treatment with azacitidine (AZA) and venetoclax (VEN) is presented in this article. This report suggests that a combination of AZA and VEN is an effective therapeutic approach for relapsed and refractory MLL‐rearranged AML