Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

Diffuse large B-cell lymphomas (DLBCL) express CD20. CD20 expression is described as negative, weak, or normal as determined by flow cytometry (FCM) and is an important target for the treatment of DLBCL. However, the impact of CD20 levels at onset of the disease on patient prognosis has not been fully elucidated. We analyzed 174 DLBCL cases newly diagnosed between January 1998 and April 2010. The relationship of the association between CD20 levels and patients' backgrounds and prognoses was analyzed using the Kaplan-Meier method and Cox proportional hazard regression. Of the 174 patients, three cases (1.7%) were defined as CD20 negative based on immunohistochemistry (IHC). Although the other 171 cases were positive by IHC, eight cases (4.7%) were defined as negative and 33 cases (19.3%) were defined as weak when analyzed by FCM. Of the 105 patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, those who were CD20 negative (FCM) showed significantly inferior overall (hazard ratios (HR): 6.79, 95% CI: 1.32-34.96, p = 0.04) and progression-free survival (HR: 7.3, 95% CI: 1.49-35.8, p = 0.04) compared to patients who were CD20 normal. Our findings indicate that the CD20 level (FCM) at onset is an independent predictor of the prognosis of patients with DLBCL.     

The prognosis of skin recurrence in breast carcinoma patients

In this study, we evaluated the clinical presentation of patients with skin recurrence in breast cancer patients. We treated 1, 228 cases of breast cancer patients during 2004 to 2010. The skin recurrences were recognized in 11 patients. The duration of showing skin recurrence was 1 .8 years. The muscle preserving radical mastectomy was performed in all cases. And surgical margins of all cases were negative. All cases were not performed radiation therapy. Nine cases were received chemotherapy as adjuvant therapy. Seven cases received endocrine therapy. After recurrence, they were treated by multi- disciplinary therapy. The surgical resection was useful to judge the effect of other therapies. The observation period was 2. 2 years. Two patients died, but 8 other patients are still alive.     

Clinical potential of biological response modifiers combined with chemotherapy for gastric cancer. Japanese experience

The most effective treatment for gastric cancer is complete surgical resection with lymphadenectomy. However, a number of patients experience recurrence of the cancer even after curative surgery. This review focuses on comparative trials studying the use of adjuvant therapy with chemotherapy plus immunotherapy in the treatment of patients with curatively resected gastric cancer. Preoperative and intraperitoneal therapy, and therapy for advanced or recurrent gastric cancer are also discussed. At present, some subset analyses of adjuvant trials have shown favorable results suggesting that the biological response modifiers (BRMs), PSK or OK-432, add a benefit to chemotherapy. For advanced gastric cancer, although gastric cancer cells are generally not very sensitive to most of the currently available chemotherapeutic agents, it has been reported that biochemical modulation with treatments including low-dose cisplatin + 5-FU (fluorouracil) have high response rates and exert an immunomodulatory effect especially when used in combination with BRMs. The impact of splenectomy and some of the promising newly developed drugs are discussed.     

Surgical techniques to prevent reflux esophagitis in proximal gastrectomy reconstructed by esophagogastrostomy with preservation of the lower esophageal sphincter,pyloric and celiac branches of the vagal nerve,and reconstruction of the new His angle for early proximal gastric cancer

Purpose

This article describes the surgical techniques to prevent reflux esophagitis (RE) after proximal gastrectomy reconstructed by esophagogastrostomy (PGE) preservation of the lower esophageal sphincter (LES) and both pyloric and celiac branches of the vagal nerve (PCVN), and reconstruction of the new His angle (HA) for early proximal gastric cancer (PGC).

Methods

Twenty patients after PGE were divided into 2 groups (group A: 10 patients without preserved LES and PCVN for advanced PGC; group B: 10 patients with preserved LES and PCNV and the addition of a new HA for early PGC). A postoperative interview on gastroesophageal reflux disease (GERD) and satisfaction with this procedure and the collection of endoscopic findings for RE and stasis of the remnant stomach (SRS) were conducted 1 year after PGE in groups A and B.

Results

The rates of proton pump inhibitor administration and the symptoms of GERD, RE and SRS in group A were significantly higher than those in group B (p = 0.0433, p = 0.0190, p = 0.0253, p = 0.0190, respectively). Seven out of 10 patients in group A voiced dissatisfaction. Patients in group B were significantly more satisfied with this procedure than those in group A (p = 0.0010).

Conclusion

This method is useful for preventing postoperative GERD including RE in early PGC patients.

     

In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes

We constructed a reproducible, simple, and small-scale determination method of the psychoactive drugs that acted directly on the monoamine receptor by measuring the activation of [(35)S]guanosine-5'-O-(3-thio)-triphosphate binding to guanine nucleotide-binding proteins (G proteins). This method can simultaneously measure the effects of three monoamines, namely dopamine (DA), serotonin (5-HT), and norepinephrine (NE), in rat brain membranes using a 96-well microplate. Activation of D(1) and D(2) receptors in striatal membranes by DA as well as 5-HT and NEalpha(2) receptors in cortical membranes could be measured. Of 12 tested phenethylamines, 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,5-dimethoxy-4-ethylphenethylamine (2C-E), and 2,5-dimethoxy-4-iodophenethylamine (2C-I) stimulated G protein binding. The other phenethylamines did not affect G protein binding. All 7 tryptamines tested stimulated G protein binding with the following rank order of potency; 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)>5-methoxy-N,N-diallyltryptamine (5-MeO-DALT)>5-methoxy-alpha-methyltryptamine (5-MeO-AMT)>or=5-methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT)>5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT)>N,N-dipropyltryptamine (DPT)>or=alpha-methyltryptamine (AMT). This assay system was able to designate psychoactive drugs as prohibited substances in accordance with criteria set forth by the Tokyo Metropolitan government.     

JunB induced by constitutive CD30-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling activates the CD30 promoter in anaplastic large cell lymphoma and reed-sternberg cells of Hodgkin lymphoma

High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). Possible interactions of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)-positive and NPM-ALK-negative ALCL and HL is regulated by a constitutively active CD30-extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylation of ERK1/2 MAPK was confirmed in nuclei of tumor cells in both ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression, which maintains high activity of the CD30 promoter. JunB induction seems to be largely independent of nuclear factor kappaB in ALCL and HL. These results show a common mechanism of CD30 overexpression in ALCL and HL, although the outcome of CD30 signaling differs between NPM-ALK-positive ALCL and NPM-ALK-negative ALCL, cutaneous ALCL, and HL as we recently reported.     

A case of advanced gastric cancer with obstructive jaundice that responded to TS-1/CPT-11 combination therapy after percutaneous transhepatic cholangio drainage

TS-1/CPT-11 combination therapy was carried out in a case of advanced gastric cancer with liver and lymph node metastases and obstructive jaundice after percutaneous transhepatic cholangio drainage (PTCD). Regression of the primary carcinoma and reduction in size of metastases were observed. Grade 1 fatigue and grade 2 neutropenia were noted as adverse reactions to the treatment. TS-1/CPT-11 combination therapy was useful in this case of advanced gastric cancer with liver and lymph node metastases.     

Dehydroxymethylepoxyquinomicin (DHMEQ) therapy reduces tumor formation in mice inoculated with tax-deficient adult T-cell leukemia-derived cell lines

Adult T-cell leukemia (ATL) is an aggressive neoplasm caused by human T-cell leukemia virus type I (HTLV-I), which induces nuclear factor-kappaB (NF-kappaB), a molecule central to the ensuing neoplasia. The NF-kappaB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) has been shown to inhibit NF-kappaB activation in Tax-expressing HTLV-I-infected cells. In this study, we used NOD/SCID beta2-microglobulin(null) mice to show that intraperitoneal inoculation with Tax-deficient ATL cell lines caused rapid death, whereas DHMEQ-treated mice survived. Furthermore, DHMEQ treatment after subcutaneous inoculation inhibited the growth of transplanted ATL cells. These results demonstrate that DHMEQ has therapeutic efficacy on ATL cells, regardless of Tax expression.     

A case of resection of esophageal cancer infiltrating the left main bronchus following preoperative chemo-radiotherapy and resection of metachronous lung metastasis

We herein report a case of T4 esophageal carcinoma, which was resected after chemo-radiation therapy. In addition, the metachronous lung metastasis was also resected. A 59-year-old female with esophageal carcinoma, which invaded the left main bronchus, underwent chemo-radiation therapy (the combination of systemic chemotherapy of 5-FU/CDDP and external radiation therapy) from January 2004. After the therapy, although the imaging showed a downstaging of esophageal carcinoma, a severe esophageal stricture appeared with ingestion defective. So hyper-alimentation was performed. After the state of nutrition was improved, esophagectomy was performed on March 2004 without a complication. Histopathological study revealed that no viable cells remained. Nine months after esophagectomy, chest CT scan revealed that a solitary pulmonary tumor appeared in S6 of the right. The solitary tumor enlarged gradually. On August 2005, a surgical resection for the solitary pulmonary tumor was performed. Histopathologically, the lesion was compatible for metastasis from esophageal carcinoma. The patient is alive without recurrence more than 23 months after the last surgery.