Intracranial plasma cell granuloma with genetic analysis

Summary.  Background: Plasma cell granuloma of the central nervous system is rare and less than 30 cases have been reported in literature.  Method/findings: A 64-year-old woman complained of headache, and computed tomography (CT) and magnetic resonance (MR) imaging of the brain revealed a tumour at the right anterior-third parasagittal region which led us to diagnose a parasagittal meningioma. We performed total resection of the tumour and the pathological diagnosis was plasma cell granuloma. Polymerase chain reaction (PCR) analysis of immunoglobulin heavy chain (IgH) gene rearrangements produced no monoclonal band. This patient underwent no supplementary treatment and no recurrent tumour was observed for 3 years.  Interpretation: A case of plasma cell granuloma which is diagnosed with genetic analysis is presented. An analysis of the clonality using the PCR procedure would play an important role in supporting the pathological and clinical diagnosis. Published online March 3, 2003  Correspondence: Mamoru Murakami, M.D., Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.     

Temporal changes in posterior laxity after isolated posterior cruciate ligament injury: 35 patients examined by stress radiography and MRI

We examined the temporal changes in posterior laxity and MRI findings in acute isolated posterior cruciate ligament (PCL)-injured knees. 35 patients with acute isolated PCL injuries who attended our clinic within 10 weeks of an injury underwent nonoperative treatment, and were chronologically evaluated for posterior laxity and MRI. We divided them in 3 groups, as regards the evolution of laxity and MRI findings. In 20 patients, the degree of posterior laxity was slight throughout the observation periods. In 9 patients, who had severe posterior laxity on their initial visit, the laxity had improved markedly 6 months after injury and did not deteriorate. In 6 patients the severe posterior laxity did not improve during the study. 4 patients whose PCL on MRI was seen as a continuous swollen band having high signal intensity and showed consistently good stability or even an improvement. We conclude that acute isolated PCL injuries with a continuous swollen band on MRI should be treated conservatively for at least 6 months after injury, even if the posterior laxity is severe initially.     

Malignant fibrous histiocytoma of the lung

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.     

A case of advanced gastric cancer with abdominal paraaortic lymph node swelling successfully resected following neoadjuvant chemotherapy of TS-1 and low-dose cisplatin

A 63-year-old man who had suffered from anorexia and body weight loss was admitted to the hospital. Upper GI series and an endoscopic examination revealed type 3 cancer in the posterior wall of the cardia. Abdominal CT scan showed enlargement of No. 16 lymph nodes. Preoperative diagnosis was stage IV gastric cancer (T3 (SE) H0 P0 N3), and we considered a curative operation impossible. Therefore, neoadjuvant chemotherapy with TS-1 and low-dose cisplatin (CDDP) was planned. After 4 weeks of administration, the primary lesion was reduced in size and the No. 16 lymph nodes were shrunken remarkably. Therefore, a total gastrectomy with a splenectomy, a distal pancreatectomy, and D3 lymph node dissection was performed. Histological findings demonstrated the degeneration of cancer cells and fibrosis in the primary tumor and metastatic regional lymph nodes. There were no viable cancer cells in the No. 16 lymph nodes. The histological changes against neoadjuvant chemotherapy were judged to be Grade 1b for the main tumor and Grade 3 for the No. 16 lymph nodes. Neoadjuvant chemotherapy with TS-1 and low-dose cisplatin is so effective in a short period that can be adapted to advanced gastric cancer for downstaging.     

Successful treatment of postoperative multiple hepatic recurrence with hepatic arterial infusion of cisplatin and degrable starch microspheres

A 38-year-old man had multiple recurrence of hepatocellular carcinoma (HCC) with portal vein thrombosis after hepatectomy and postoperative transcatheter arterial chemotherapy with 5-fluorouracil (5-FU). He was treated by trans hepatic arterial embolization (TAE) with 100 mg of cisplatin (CDDP) and degrable starch microspheres (DSM). After 3 courses were administered, the recurrent lesions almost disappeared on CT, and the postoperative rise in PIVKA-II level and AFP level normalized. There were no side effects except slight fever and general fatigue. We recognized a partial response, and the patient is still alive 14 months after hepatectomy. This case suggests that TAE with CDDP and DSM might be useful for prolonging the survival of advanced HCC patients.     

Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site

The immune response is modulated by genetic adjuvants using plasmid vectors expressing cytokines. Skeletal muscle can express a foreign gene intramuscularly administered via a needle injection, and the potential of muscle as a target tissue for somatic gene therapy in treating cancer has been explored. In the present study, we investigated the efficacy of particle-mediated intramuscular transfection modified with a local anesthetic agent, bupivacaine, on luciferase and green fluorescent protein. The results indicate that these proteins are more efficiently expressed and persist longer in muscle modified in this way compared with the needle-injection method. Using an established rat sarcoma model, particle-mediated intramuscular gene-gun therapy with a combination of IL-12 and IL-18 cDNA was conducted. Growth of the distant sarcoma was significantly inhibited by particle-mediated intramuscular combination gene therapy, and the survival rate was also improved. Furthermore, the combination gene-gun therapy maintained significant levels of interferon-gamma and induced a high activity of tumor-specific cytotoxic T lymphocytes. These results suggest that the sustained local delivery of IL-12 and IL-18 cDNA using intramuscular gene-gun therapy modified with bupivacaine can induce long-term antitumor immunity, and can provide the great advantage of inhibiting the disseminated tumor.     

A case of pulmonary aspergilloma molecular biological identification and typing of the isolates from antemortem sputa and autopsy fungus ball

Filamentous fungi were isolated from antemortem sputum and an autopsy fungus ball of the lung in a case of aspergilloma. Both of the isolates were analyzed for the sequences of species or strain-specific nuclear ribosomal DNA (partial 28S and ITS1 regions), and were identified as Aspergillus fumigatus. The molecular biological technique saved time and is thought to be a powerful tool in the accurate diagnosis of pulmonary fungal infection to assure effective treatment.     

Presenilin-dependent gamma-secretase activity mediates the intramembranous cleavage of CD44

CD44 is the major adhesion molecule for the extracellular matrix components and is implicated in a wide variety of physiological and pathological processes including the regulation of tumor cell growth and metastasis. Our previous studies have shown that CD44 undergoes sequential proteolytic cleavages in the extracellular and transmembrane domains and the cleavage product derived from CD44 intramembranous cleavage acts as a signal transduction molecule. However, the underlying mechanism of the intramembranous cleavage of CD44 remains to be elucidated. In the present study, we report for the first time that CD44 is a substrate of the presenilin (PS)-dependent gamma-secretase. We demonstrate that the intramembranous cleavage of CD44 induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) treatment or mechanical scraping is blocked by gamma-secretase inhibitors in U251MG cells and that this cleavage is also inhibited in PS-deficient mouse embryonic fibroblasts. Furthermore, we showed that PS1 is redistributed to ruffling areas of the plasma membrane similarly to CD44 after TPA treatment, supporting our biochemical observation that PS1 is involved in the intramembranous cleavage of CD44. Our present findings suggest important implications for understanding CD44-dependent signal transduction and a potential role of PS/gamma-secretase activity in the functional regulation of adhesion molecules.     

Promoter methylation of the TSLC1 gene in advanced lung tumors and various cancer cell lines

We previously identified TSLC1, a tumor suppressor gene in human nonsmall cell lung cancer (NSCLC). TSLC1 belongs to immunoglobulin superfamily molecules and is involved in cell adhesion. Loss of TSLC1 expression was strongly correlated with the promoter hypermethylation in several NSCLC cell lines. Here, we examined the methylation status of the TSLC1 gene promoter in 48 primary NSCLC tumors by bisulfite SSCP in combination with bisulfite sequencing. Six CpG sites around the promoter regions were significantly methylated in 21 of 48 primary NSCLC tumors (44%). Promoter methylation was more likely to be observed in relatively advanced tumors with TNM classification of pT2, pT3 or pT4 (19 of 33, 58%) than in those with pT1 (2 of 15, 13%), suggesting that alteration of TSLC1 would be involved in the progression of human NSCLC. Loss of TSLC1 expression was also observed in 20 of 46 (43%) human cancer cell lines, including those from esophageal (3 of 3), gastric (8 of 9), ovarian (2 of 5), endometrial (2 of 2), breast (1 of 3), colorectal (2 of 8) and small cell lung cancers (2 of 10). Combined analysis of promoter methylation and the allelic state in these cell lines indicated that the TSLC1 gene was often silenced not only by mono-allelic methylation associated with loss of the other allele but also through bi-allelic methylation. These results suggest that alteration of TSLC1 would be involved in advanced NSCLC as well as in many other human cancers.