The Wilms' tumor gene WT1 is overexpressed in leukemias and various types of solid tumors, and the WT1 protein was demonstrated to be an attractive target antigen for immunotherapy against these ...malignancies. Here, we report the outcome of a phase I clinical study of WT1 peptide-based immunotherapy for patients with breast or lung cancer, myelodysplastic syndrome, or acute myeloid leukemia. Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints. Twenty-six patients received one or more WT1 vaccinations, and 18 of the 26 patients completed WT1 vaccination protocol with three or more injections of WT1 peptides. Toxicity consisted only of local erythema at the WT1 vaccine injection sites in patients with breast or lung cancer or acute myeloid leukemia with adequate normal hematopoiesis, whereas severe leukocytopenia occurred in patients with myelodysplastic syndrome with abnormal hematopoiesis derived from WT1-expressing, transformed hematopoietic stem cells. Twelve of the 20 patients for whom the efficacy of WT1 vaccination could be assessed showed clinical responses such as reduction in leukemic blast cells or tumor sizes and/or tumor markers. A clear correlation was observed between an increase in the frequencies of WT1-specific cytotoxic T lymphocytes after WT1 vaccination and clinical responses. It was therefore demonstrated that WT1 vaccination could induce WT1-specific cytotoxic T lymphocytes and result in cancer regression without damage to normal tissues.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objective: The prognosis of patients with advanced gastric cancer (GC) with multiple lymph-node metastasis is poor. The present study evaluated a neoadjuvant S-1 and oxaliplatin regimen (SOX) ...followed by D2 gastrectomy for advanced GC with lymph-node metastasis. Patients and Methods: Ten patients with resectable clinical advanced gastric cancer with multiple lymph-node metastasis who received preoperative SOX therapy were included in this study from 2015 to 2021. Results: A clinical evaluation by RECIST version 1.1 criteria after SOX therapy showed 8 cases of partial response (PR), 2 cases of stable disease (SD), and no progress disease (PD). The histopathological stages were IB in 3 patients, IIA in 2, IIB in 2, IIIA in 2, and IIIB in 1, and downstaging was observed in 8 of 10 patients (80%). Histopathological effects were Grade 1a in 4 patients, Grade 1b in 3 patients, Grade 2a in 2 patients, and Grade 2b in 1 patient; there were no Grade 3 patients. Adverse events of neoadjuvant chemotherapy (NAC) according to the CTCAE criteria were Grade 1 anemia, nausea, dysgeusia, and peripheral neuropathy in one patient each; Grade 2 anemia in two patients; and diarrhea in one patient. No grade ≧3 adverse events were observed. The surgical techniques were distal gastrectomy in four cases, total gastrectomy in five cases, and total gastrectomy and caudal pancreatectomy in one case; all patients underwent D2 dissection, and all received R0 surgery. One patient had local recurrence, and one patient had peritoneal recurrence and is on chemotherapy. The remaining eight patients are alive without recurrence. Conclusions: In the future, neoadjuvant chemotherapy with SOX therapy may become a treatment option for advanced resectable GC with multiple lymph-node metastasis.
Objective: Gastrointestinal stromal tumors (GISTs) present with different clinical and immunohistochemical characteristics depending on the anatomic site. The present study clarified the ...clinicopathological characteristics of small bowel (SB) GISTs, which are relatively infrequent. Patients and Methods: The clinicopathological characteristics of 15 cases of small intestinal GISTs resected at our hospital were reviewed. SBGISTs were divided into duodenal (d) GISTs and jejunal/ ileal (ji) GISTs for the comparison. Results: The tumors included six cases in the duodenum, six in the jejunum, and three in ileum. All patients underwent duodenal wedge resection for dGIST and partial SB resection for jiGIST. The stage was I in seven patients, II in two patients, IIIB in five patients, and IV in one patient. The median postoperative observation period was 67 (11-175) months. Ten patients had no recurrence, two had hepatic and peritoneal recurrence, one had multiple hepatic recurrence, one had peritoneal recurrence, and one had lymph node recurrence. On comparing dGISTs and jiGISTs, recurrence was significantly more frequent in jiGISTs than in dGISTs. Conclusions: In five cases of recurrence, chemotherapy and surgery at the appropriate time seemed effective for achieving a long-term survival. Recurrence was significantly more frequent in jiGISTs than in dGISTs.
CHD7 gene mutations were identified in 17 (71%) of 24 children clinically diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart defects; A, atresia of the choanae; R, ...retardation of growth and/or development; G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss, laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing for
CHD7 enables an accurate diagnosis and provides health anticipatory guidance and genetic counseling to families with CHARGE syndrome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
No method for the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) has been established except for pathologic examination.
To identify a reliable marker for the clinical ...diagnosis of MM2-type sCJD.
CSF, EEG, and neuroimaging studies were performed in eight patients with MM2-type sCJD confirmed by neuropathologic, genetic, and western blot analyses.
The eight cases were pathologically classified into the cortical (n = 2), thalamic (n = 5), and combined (corticothalamic) (n = 1) forms. The cortical form was characterized by late-onset, slowly progressive dementia, cortical hyperintensity signals on diffusion-weighted imaging (DWI) of brain, and elevated levels of CSF 14-3-3 protein. The thalamic form showed various neurologic manifestations including dementia, ataxia, and pyramidal and extrapyramidal signs with onset at various ages and relatively long disease duration. Characteristic EEG and MRI abnormalities were almost absent. However, all four patients examined with cerebral blood flow (CBF) study using SPECT showed reduction of the CBF in the thalamus as well as the cerebral cortex. The combined form had features of both the cortical and the thalamic forms, showing cortical hyperintensity signals on DWI and hypometabolism of the thalamus on 18F2-fluoro-2-deoxy-d-glucose PET.
For the clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease, cortical hyperintensity signals on diffusion-weighted MRI are useful for the cortical form and thalamic hypoperfusion or hypometabolism on cerebral blood flow SPECT or 18F2-fluoro-2-deoxy-d-glucose PET for the thalamic form.
The number of airborne methicillin-resistant Staphylococcus aureus (MRSA) before, during and after bedmaking was investigated. Air was sampled with an Andersen air sampler in the rooms of 13 ...inpatients with MRSA infection or colonization. Sampling of surfaces, including floors and bedsheets, was performed by stamp methods. MRSA-containing particles were isolated on all the sampler stages—stage 1 (>7μm diameter) to stage 6 (0.65–1.1μm). The MRSA-containing particles were mostly 2–3μm diameter before bedmaking and >5μm during bedmaking. The number was significantly higher 15min after bedmaking than during the resting period, but the differences in counts after 30 and 60min were not significant. MRSA was detected on many surfaces. The results suggest that MRSA was recirculated in the air, especially after movement. To prevent airborne transmission, healthcare staff should exercise great care to disinfect inanimate environments. Further studies will be needed to confirm the level of MRSA contamination of air during bedmaking and establish measures for prevention of airborne transmission.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Wilms tumor gene, WT1, is overexpressed not only in leukemias and myelodysplastic syndrome (MDS) but also in various types of solid tumors, including lung and breast cancer, and the WT1 protein ...is a tumor antigen for these malignancies. In clinical trials of WT1 peptide-based cancer immunotherapy, patients with overt leukemia from MDS or MDS with myelofibrosis were injected intradermally with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant. Only a single dose of WT1 vaccination resulted in an increase in WT1-specific cytotoxic T-lymphocytes, which was followed by a rapid reduction in leukemic blast cells. Severe leukopenia and local erythema at the injection sites of WT1 peptide were observed as adverse effects. These results have provided us with the first clinical evidence suggesting that WT1 peptide-based immunotherapy is an attractive treatment for patients with leukemias or MDS.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Atypical Teratoid Rhabdoid Tumor (ATRT) is a rare malignant intracranial neoplasm more commonly diagnosed in young children. The authors report the case of an 11-year-old boy with a long standing ...history of slowly progressive weight loss, fatigue, and weakness over 1.5 years whose magnetic resonance imaging revealed a large heterogeneous enhancing dorsally exophytic lower brainstem mass. Examination revealed extreme cachexia, gaze-evoked nystagmus, dysphagia, dysarthria, bilateral dysmetria, and global weakness without ambulation. The protracted history and neuroimaging features were most suggestive of a low grade glioma. However, pathology revealed a hypercellular tumor with large hyperchromatic nucleoli and loss of INI-1 staining on immunohistochemistry consistent with a diagnosis of an ATRT. The child died shortly after surgery due to complications from his brainstem infiltrative disease. This case illustrates the diverse presentation of ATRT in childhood that can clinically and radiographically mimic that of low grade glioma.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
We previously isolated from mouse spleen an octapeptide (LSPFPFDL) that in association with the class I major histocompatibility complex protein Ld is recognized by the antigen-specific receptor of ...an alloreactive CD8+ T-cell clone (2C). Guided by an assay dependent upon the same 2C T-cell receptor, we have now isolated from the same source another naturally occurring peptide. The second peptide (VAITRIEQLSPFPFDL) includes the entire octapeptide sequence and preliminary evidence suggests that it may be a natural precursor of the octapeptide. On finding extensive sequence homology between the 16-mer and part of human 2-oxoglutarate dehydrogenase, we determined the cDNA sequence of mouse 2-oxoglutarate dehydrogenase and found that the deduced amino acid sequence matches precisely the two naturally occurring peptides, indicating their origin by cellular processing of this ubiquitous self protein.
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