Serum CYFRA 21-1 Level as a Prognostic Marker for Extensive Disease Small Cell Lung Cancer.

BACKGROUND/AIM: Pretreatment serum cytokeratin 19 fragment (CYFRA21-1) level predicts outcomes in patients with non-small cell lung cancer; however, little is known about the clinical value of serum CYFRA21-1 level in patients with small cell lung cancer (SCLC). The aim of this study was to evaluate the prognostic value of pretreatment serum CYFRA21-1 level in patients with extensive disease (ED)-SCLC treated using platinum-doublet chemotherapy. PATIENTS AND METHODS: We retrospectively analyzed the pretreatment serum CYFRA21-1 levels of patients with ED-SCLC who were treated using first-line platinum-doublet chemotherapy. RESULTS: A total of 98 patients were analyzed. The patients with a high CYFRA21-1 level (≥7.0 ng/ml) (n=29) had significantly shorter progression-free survival (PFS) and overall survival (OS) than the patients with low CYFRA21-1 levels (n=67) [median PFS=118 days vs. 125 days, respectively (p=0.018); median OS=213 days vs. 295 days, respectively (p=0.046)]. In addition, high CYFRA21-1 level was associated with a high refractory relapse rate. CONCLUSION: Serum CYFRA21-1 level may be a prognostic marker for patients with ED-SCLC treated with platinum-doublet chemotherapy.

Clinical activity of crizotinib in lung adenocarcinoma harboring a HLA_A­ROS1 rearrangement: A case report.

The benefits of crizotinib therapy in patients with tyrosine receptor kinase ROS proto-oncogene 1 (ROS1)-rearranged non-small cell lung cancer (NSCLC) have been demonstrated. The present study reports a 47-year-old woman with lung adenocarcinoma harboring a rare HLA_A-ROS1 rearrangement with clinical response to crizotinib. To the best of our knowledge there have been no reports of HLA_A-ROS1-rearranged lung cancer regarding clinical course and the efficacy of treatment with crizotinib. A good response to crizotinib therapy in the present case could be a reference for the treatment and prognosis of ROS1-rearranged NSCLC with the same fusion partner. The current report will remind oncologists and pulmonologists to consider the importance of accurate multigene panel assays for detecting driver oncogenes in treating patients with NSCLC.

The levels of serum soluble CD86 are correlated with the expression of CD86 variant 3 gene and are prognostic indicators in patients with myeloma.

We previously showed that cell-surface CD86 expressed on multiple myeloma (MM) cells contributed to not only tumor growth but also antitumor cytotoxic T-lymphocyte responses mediated by induction of IL-10-producing CD4+ T cells. The soluble form of CD86 (sCD86) was also detected in serum from patients with MM. Thus, to determine whether sCD86 levels are a useful prognostic factor, we investigated the association of serum sCD86 levels with disease progression and prognosis in 103 newly diagnosed patients with MM. Serum sCD86 was detected in 71% of the patients with MM but was only rarely detected in patients with monoclonal gammopathy of undetermined significance and healthy controls, and the level was significantly increased in patients with advanced-stage MM. When we examined differences in clinical characteristics according to the level of serum sCD86, those in the high (≥2.18 ng/mL, n = 38) group exhibited more aggressive clinical characteristics, with shorter overall survival times compared with those in the low (<2.18 ng/mL, n = 65) group. On the other hand, it was difficult to stratify the patients with MM into different risk groups based on the expression levels of cell-surface CD86. The levels of serum sCD86 were significantly correlated with the expression levels of the messenger RNA (mRNA) transcripts of CD86 variant 3, which lack exon 6, resulting in a truncated transmembrane region, and its variant transcripts were upregulated in the high group. Thus, our findings suggest that sCD86 can be easily measured in peripheral blood samples and is a useful prognostic marker in patients with MM.

Precise Position Control of Holonomic Inchworm Robot Using Four Optical Encoders.

In this study, an XYθ position sensor is designed/proposed to realize the precise control of the XYθ position of a holonomic inchworm robot in the centimeter to submicrometer range using four optical encoders. The sensor was designed to be sufficiently compact for mounting on a centimeter-sized robot for closed-loop control. To simultaneously measure the XYθ displacements, we designed an integrated two-degrees-of-freedom scale for the four encoders. We also derived a calibration equation to decrease the crosstalk errors among the XYθ axes. To investigate the feasibility of this approach, we placed the scale as a measurement target for a holonomic robot. We demonstrated closed-loop sequence control of a star-shaped trajectory for multiple-step motion in the centimeter to micrometer range. We also demonstrated simultaneous three-axis proportional-integral-derivative control for one-step motion in the micrometer to sub-micrometer range. The close-up trajectories were examined to determine the detailed behavior with sub-micrometer and sub-millidegree resolutions in the MHz measurement cycle. This study is an important step toward wide-range flexible control of precise holonomic robots for various applications in which multiple tools work precisely within the limited space of instruments and microscopes.

Safety and efficacy of high-dose cytarabine MEAM therapy and other treatments for auto-peripheral blood stem cell transplantation: A retrospective comparative study.

AIM: The MEAM regimen consisting of ranimustine (MCNU), etoposide (ETP), cytarabine (Ara-C), and melphalan (MEL) is widely used before auto-peripheral blood stem cell transplantation (auto-PBSCT) for malignant lymphoma in Japan. The MEAM regimen generally consists of 200-400 mg/m2 for 4 days, but we decided to increase the dosage of Ara-C from the standard to 2 g/m2 for 2 days with the aim of increasing drug transferability to the central nervous system. We evaluate the safety and therapeutic efficacy of high-dose Ara-C MEAM therapy. METHODS: The high-dose Ara-C MEAM protocol consisted of MCNU 300 mg/m2 on day -7, ETP 200 mg/m2 on days -6, -5, -4, -3 and Ara-C 2 g/m2 on day -4 -3, and MEL 140 mg/m2 on day -2. We retrospectively analyzed 37 cases of malignant lymphoma at our institution between May 2014 and July 2020. RESULTS: All patients got engraftment and there were no cases of treatment-related mortality. In all cases, the 3-year overall survival (OS) and progression-free survival (PFS) after transplantation were 80.6% and 65.7%, respectively. Twenty-one cases of diffuse large B-cell lymphoma recurrence, for which there is proven usefulness of auto-PBSCT, showed good results after transplantation, with the 3-year OS and PFS after transplantation being 100% and 74.3%, respectively. CONCLUSION: The safety and efficacy of high-dose Ara-C MEAM therapy were demonstrated, but the expected therapeutic effect on central nervous system lesions could not be fully evaluated owing to the small number of cases.

Epstein-Barr Virus-Related Hemophagocytic Lymphohistiocytosis with Central Nervous System Symptoms.

Hemophagocytic lymphohistiocytosis (HLH) involves pathological histiocytes and phagocytosis of normal blood cells through activation of inflammatory cytokines. We report a case of Epstein-Barr virus-HLH in a 75-year-old woman who presented with fever, thrombocytopenia, and loss of consciousness. Epstein-Barr virus-HLH was diagnosed after we identified massive hemophagocytosis in bone marrow and Epstein-Barr virus DNA in cerebrospinal fluid. The HLH-2004 protocol was applied, and lactate dehydrogenase levels-which reflect HLH disease status-decreased. However, persistent loss of consciousness and multiple organ failure led to the patient's death on day 18. Most cases of primary and secondary HLH involve pediatric patients; adult cases are rare. Few cases of central nervous system involvement in older adults have been reported. Therefore, accumulation of more data will help in developing better treatment strategies.

[A Case of Second Primary Small Cell Lung Carcinoma after Radiotherapy for Breast Cancer].

We report the case of a 72-year-old woman who underwent partial mastectomy due to left breast cancer(invasive ductal carcinoma)in March 20XX-4. This was followed by radiotherapy(50 Gy/25 Fr)and hormone therapy. In July 20XX, she was referred to our department because a chest computed tomography(CT)scan performed at the postoperative follow-up revealed a band-like consolidation adjacent to the pleura in the lingular segment, with enlarged ipsilateral hilar and mediastinal lymph nodes. CT-guided lung tumor biopsy was performed, and she was diagnosed with limited-stage small cell lung cancer. Chemotherapy with carboplatin, etoposide, and atezolizumab was initiated. Radiotherapy was not performed due to the overlap between the distribution of the lung tumor and the postoperative irradiation field of breast cancer. Due to the difference in the histopathological findings of the first and second primary tumors, and the location of the tumor in the postoperative irradiation field, the second cancer was considered to be radiation-induced cancer despite the short latency period.

Central Nervous System-related Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.

The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma.

The signaling lymphocytic activation molecule family 3 (SLAMF3) is highly expressed on plasma cells from patients with multiple myeloma (MM) and induces high malignant potential by ERK signaling mediated via the interaction with adaptor proteins SHP2 and GRB2. This study focused on the single-nucleotide polymorphism (SNP) of the SLAMF3 gene (rs509749, 1804A>G, M602V) in MM. The SNP G allele was a major type, and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, in patients with MM, which was almost the same as in healthy the control group in the Japanese population. Interestingly, patients with GG genotypes had significantly shorter overall survival times than patients with GA/AA genotypes. Consistent with those results, SLAMF3-overexpressing KMS-34 cells with the G allele (V602) had higher cell proliferation potential and were more resistant to anti-MM agents than those with the A allele (M602). When those cells were subcutaneously inoculated into NOG mice, tumor sizes in mice receiving V602 cells rapidly increased, and survival was significantly shorter than in mice injected with M602 cells. Furthermore, SLAMF3 V602 molecules bound more tightly to SHP2 and GRB2, with increased SHP2 and ERK phosphorylation compared with M602 cells. The mRNA expression of cell cycle-related genes (CCND1 and CCNE1) and anti-apoptotic genes (BCL2L and p21) was increased in V602 cells compared with M602 cells. The results thus suggested that the G allele of SLAMF3 SNP rs509749 may be associated with MM disease progression.

Clinical impact of serum soluble SLAMF7 in multiple myeloma.

The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab. The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.