Chueh-Chuan Yen

Stevens-Johnson syndrome after treatment with STI571: a case report.

Summary.  Between seven and 21% of patients treated with the specific tyrosine kinase inhibitor STI571 have been reported to develop mild‐to‐moderate severity of adverse cutaneous reactions. We report a patient in the blast crisis phase of chronic myeloid leukaemia who developed a life‐threatening cutaneous reaction, Stevens–Johnson syndrome, following 1 week of STI571 therapy. This report may serve to remind the clinician about the possible severe cutaneous side‐effects of STI571 before instituting more extensive clinical application of this agent in the future.

PhosphoPOINT: a comprehensive human kinase interactome and phospho-protein database

MOTIVATION To fully understand how a protein kinase regulates biological processes, it is imperative to first identify its substrate(s) and interacting protein(s). However, of the 518 known human serine/threonine/tyrosine kinases, 35% of these have known substrates, while 14% of the kinases have identified substrate recognition motifs. In contrast, 85% of the kinases have protein-protein interaction (PPI) datasets, raising the possibility that we might reveal potential kinase-substrate pairs from these PPIs. RESULTS PhosphoPOINT, a comprehensive human kinase interactome and phospho-protein database, is a collection of 4195 phospho-proteins with a total of 15 738 phosphorylation sites. PhosphoPOINT annotates the interactions among kinases, with their down-stream substrates and with interacting (phospho)-proteins to modulate the kinase-substrate pairs. PhosphoPOINT implements various gene expression profiles and Gene Ontology cellular component information to evaluate each kinase and their interacting (phospho)-proteins/substrates. Integration of cSNPs that cause amino acids change with the proteins with the phosphoprotein dataset reveals that 64 phosphorylation sites result in a disease phenotypes when changed; the linked phenotypes include schizophrenia and hypertension. PhosphoPOINT also provides a search function for all phospho-peptides using about 300 known kinase/phosphatase substrate/binding motifs. Altogether, PhosphoPOINT provides robust annotation for kinases, their downstream substrates and their interaction (phospho)-proteins and this should accelerate the functional characterization of kinomemediated signaling. AVAILABILITY PhosphoPOINT can be freely accessed in http://kinase. bioinformatics.tw/. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

High prevalence of occult hepatitis B virus infection in patients with B cell non-Hodgkin’s lymphoma

Several reports recently found that patients with B cell non-Hodgkin’s lymphoma (NHL) had a higher carrier rate of hepatitis B surface antigen (HBsAg). The current study aimed to examine the hepatitis B virus (HBV) infection status of NHL patients in Taiwan, an HBV-endemic area. Serum HBV and serum hepatitis C virus were measured in 471 NHL patients and 1,013 non-lymphoma cancer patients enrolled between February 2000 and March 2007. Furthermore, nested polymerase chain reaction of HBV-DNA was used to examine the sera from selected patients in these two populations and healthy volunteers for the presence of occult HBV infection. The infection rates (as indicated by the rates of HBsAg and occult HBV) were compared between different groups. There was a higher incidence of HBV infection in B cell NHL patients (23.5%), especially patients with diffuse large B lymphoma, than solid tumor patients (15.6%, P = 0.001). Among HbsAg-negative patients, those with B cell NHL had a higher prevalence of occult HBV infection (6%) than those with non-lymphoma solid tumors and healthy volunteers, 0% and 0.9%, respectively (P = 0.005). B cell NHL patients, even HBsAg-negative B cell NHL patients, but not T cell NHL patients, have a higher incidence of HBV infection than patients with solid tumors. Our findings support the etiologic role of HBV infection in B cell NHL.

Outcome of colorectal carcinoma in patients under 40 years of age

Aims:  Colorectal carcinoma in patients under 40 years of age usually has a poor prognosis. Controversies still exist regarding the features and the prognosis of colorectal cancer in young patients.

CIP2A is a predictor of poor prognosis in colon cancer.

PurposeThe cancerous inhibitor of protein phosphatase 2A (CIP2A) oncoprotein is overexpressed in colon cancer tissue compared to normal colon mucosa. We investigated the impact of CIP2A on colon cancer.MethodsA tissue microarray consisting of 167 colon cancer specimens was investigated. The association between CIP2A and clinicopathological parameters was analyzed using the χ2 test. Survival was analyzed using the Kaplan–Meier method. The impact of CIP2A on proliferation and drug resistance was evaluated using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide test. An anchorage-independent colony formation assay was also performed.ResultsCIP2A was an independent prognostic factor in colon cancer after controlling for other clinical confounding factors, such as stage and lymphovascular invasion, particularly in stages III and IV (hazard ratio = 2.974, P < 0.001). The knockdown of CIP2A reduced the proliferation and anchorage-independent colony formation of colon cancer cells. Knockdown of CIP2A decreased the resistance of the cells to 5-fluorouracil, oxaliplatin, and SN38 (an active metabolite of irinotecan). Treatment with 5-fluorouracil, oxaliplatin, and SN38 decreased CIP2A expression.ConclusionsCIP2A is a prognostic factor in colon cancer. The knockdown of CIP2A reduced proliferation and anchorage-independent colony formation and increased 5-fluorouracil, oxaliplatin, and SN38 efficacy in colon cancer cell lines.

Candidemia in cancer patients: Impact of early removal of non-tunneled central venous catheters on outcome

OBJECTIVE To explore the impact of retention of non-tunneled central venous catheters (CVCs) on survival in candidemic cancer patients, where CVCs are commonly used and essential. A second object was to determine whether early CVC removal would benefit a subset of cancer patients. METHODS We retrospectively evaluated 92 cancer patients who had a single, non-tunneled CVC in place. Patients were grouped according to CVC retention or removal; the later group was subdivided into early (CVC removed <or=72h after candidemia onset) and late removal. A Cox regression model was used for determining risk factors of adverse outcome and Kaplan-Meier analyses for comparing in-hospital 3-30 day survival among subgroups. RESULTS Baseline characteristics were comparable between CVC retention (n=20) or removal (n=72) groups. CVC retention was a significant risk factor of poor outcome, independent of other significant prognostic host factors (hazard ratio 7.15, 95% confidence interval 3.51-14.53, p<0.001). Patients of early CVC removal (n=40) had significant better survival than those of late removal (n=32) (p<0.001). CONCLUSION The results suggest that retention of CVCs has a negative impact on survival in candidemic cancer patients, and that early CVC removal should be considered in a subset of cancer patients with candidemia.

BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy

In metastatic colorectal cancer, v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a predictive biomarker for anti‐epidermal growth factor receptor (EGFR) treatment and V‐raf murine sarcoma viral oncogene homolog B1 (BRAF) is a prognostic biomarker. We aimed to determine the impact of KRAS and BRAF mutation as determined from liver metastases specimens on overall survival (OS) in patients following colorectal liver metastasectomy.

Chryseobacterium indologenes Bacteremia in a Bone Marrow Transplant Recipient with Chronic Graft-versus-Host Disease

We describe a case of Chryseobacterium indologenes bacteremia in a leukemia patient with chronic graft-versus-host disease (GVHD) 6 months after allogeneic bone marrow transplantation. Blood cultures from a vein and via Hickman catheter grew C. indologenes. The patient was successfully treated with piperacillin/tazobactam and the infection did not recur. Our case indicates that C. indologenes infection can occur in patients with GVHD after allogeneic BMT and might be treated with a single agent, piperacillin/tazobactam without the removal of intravascular catheter.1

Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation.

BACKGROUND Bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. METHODS Forty-three hepatitis B virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg+ donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS Hepatitis B virus carriers receiving a marrow graft from an HbsAg+ donor have a significantly increased risk of FH.

A Dose-Escalating Pilot Study of Sterically Stabilized, Pegylated Liposomal Doxorubicin (Lipo-Dox®) in Patients with Metastatic Breast Cancer

Doxorubicin is considered among the most active single agents used against advanced breast cancer. Recent advances in the design of liposomes as carriers of cytotoxic drugs have resulted in a new formulation of doxorubicin with improved pharmacokinetic and tumor-localizing properties. The objectives of this dose-escalating pilot study were to evaluate the efficacy and safety of the sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) for the treatment of metastatic breast cancer. Lipo-Dox was given at the dosage of 45 mg/m2 over 1 hr of intravenous infusion every 4 weeks initially and could be escalated up to a maximum of 60 mg/m2. Response was assessable in 17 of 19 intent-to-treat patients. An objective response was achieved in 41.2% (95% confidence interval: 17.8%–64.6%) of patients (5.9% complete response and 35.3% partial response), and 23.5% had stable disease. Median time to disease progression was 163 days. Major treatment-related toxicities included neutropenia, stomatitis, and skin toxicity in this dose-escalation program. Impressively, no grade 4 toxicities have ever been observed. The only grade 3 nonhematological toxicity ever to occur was reversible skin toxicity, presented as palmar-plantar erythrodysthesia. No severe nausea/vomiting, wig-necessary alopecia, or significant cardiac function change were encountered. In conclusion, Lipo-Dox is shown by this first reported pilot study to be an active agent for treatment of advanced breast cancer with a safety profile that differs markedly from free doxorubicin. The dosage of 45–60 mg/m2 every 4 weeks was well tolerated. Because myelosuppression and other nonhematological toxicities associated with Lipo-Dox were generally mild and acceptable, further assessment of this drug particularly in combination with other chemotherapeutic drugs in the management of early or advanced breast cancer is suggested.