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1.
Gastroenterol Nurs ; 41(6): 491-496, 2018.
Article in English | MEDLINE | ID: mdl-30489406

ABSTRACT

The multidisciplinary team (MDT) model involves multiple medical professionals providing integrated medical care. Colorectal cancer (CRC) has the highest prevalence of cancer in Taiwan. This study examines and evaluates the survival rates of CRC patients treated under the MDT model. In this retrospective and prospective study, 651 CRC patients were recruited. They were divided into 2 groups: the MDT group and the traditional care (TC) group. The MDT group comprised 326 patients who received care from a MDT. The TC group comprised 325 patients who received care from a TC. The outcome variables were survival rates, follow-up appointment compliance, and 14-day readmission rates. Adopting the MDT model for CRC care increased patient follow-up appointment compliance rates at the first week, first month, and third month (p = .032, p = .007, p = .001, respectively). The model also effectively reduced patients' 14-day readmission rates. The results indicated that the survival rates of the MDT care were superior to those of TC. The adoption of the MDT model to treat CRC effectively enhanced clinical treatment adherence, increased survival rates, and reduced the 14-day readmission rate.


Subject(s)
Colorectal Neoplasms/therapy , Delivery of Health Care, Integrated/organization & administration , Patient Care Team/organization & administration , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/mortality , Female , Humans , Male , Middle Aged , Survival Rate , Taiwan
2.
J Clin Lab Anal ; 28(4): 261-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24577940

ABSTRACT

BACKGROUND: Iron overload is a major complication in patients with hemoglobin H (Hb H) disease and causes damage of tissues. METHODS: We investigated 26 Hb H patients and 75 controls to evaluate their oxidative stress and antioxidant statuses. RESULTS: There were significantly increased levels of superoxide anion in leucocytes, nitrite (NO2-), and malondialdehyde (MDA) in plasma, and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx) and oxidized glutathione (GSSG) in erythrocytes, decreased levels of nitrate (NO3-) and vitamin C in plasma, and reduced glutathione (GSH) in erythrocytes, in addition to the abnormal iron status in the patients when compared with those in the controls. Meanwhile, levels of serum ferritin were positively correlated with serum iron, plasma MDA, and erythrocyte SOD in the patients. In addition, the activities of SOD were positively correlated with those of GPx and GRx, and the levels of GSSG and MDA, but negatively correlated with those of GSH. Furthermore, the levels of MDA were negatively correlated those of vitamin C. CONCLUSIONS: These results demonstrate the presence of oxidative stress and decreased levels of antioxidants; moreover, the related metabolic antioxidant pathway is active in Hb H patients with iron overload.


Subject(s)
Iron Overload/metabolism , Iron Overload/pathology , Metabolic Networks and Pathways , Oxidative Stress , alpha-Thalassemia/metabolism , alpha-Thalassemia/pathology , Adolescent , Alanine Transaminase/blood , Antioxidants/metabolism , Case-Control Studies , Creatine Kinase/blood , Erythrocytes/enzymology , Female , Ferritins/blood , Humans , Iron/blood , Iron Overload/blood , Iron Overload/complications , Male , Malondialdehyde/blood , Superoxide Dismutase/metabolism , Young Adult , alpha-Thalassemia/blood , alpha-Thalassemia/complications
3.
Oncology ; 84(5): 299-304, 2013.
Article in English | MEDLINE | ID: mdl-23548831

ABSTRACT

OBJECTIVE: An increased risk of serious adverse effects related to bevacizumab has been observed in many Western studies for metastatic colorectal cancer. To evaluate the safety of bevacizumab in Chinese patients, a safety study was conducted in Taiwan. METHODS: Bevacizumab was provided by the Expanded Access Program in combination with first-line chemotherapy per investigator's choice. The primary objective is the safety profile, particularly the targeted adverse events such as proteinuria, bowel perforation, hypertension, wound healing complication, thromboembolism and bleeding. The second objectives include time to disease progression and overall survival time. Patients with major surgical procedure performed within the 28 days of bevacizumab were excluded from this study. RESULTS: Forty patients were eligible for intent-to-treat analysis. The overall rate of objective response and disease control was 55.2 and 81.6%. The median time to disease progression and overall survival were 11.9 and 22.9 months. The actuarial 2-year survival was 46.6%. Regarding toxicity, 7 subjects (17.5%) had serious adverse effects related to study treatment. None of the patients in this cohort had arterial thrombotic events and bowel perforation. CONCLUSIONS: Bevacizumab demonstrates a similar activity and safety profile in Chinese patients. Life-threatening bowel complications were avoided in this study by excluding patients with major surgery within the first 28 days.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents/administration & dosage , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Asian People , Bevacizumab , Cohort Studies , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/pathology , Disease Progression , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Neoplasm Metastasis , Patient Safety , Taiwan , Time Factors , Treatment Outcome , Wound Healing
4.
In Vivo ; 37(1): 454-460, 2023.
Article in English | MEDLINE | ID: mdl-36593061

ABSTRACT

BACKGROUND/AIM: The combination of bevacizumab and atezolizumab (Bev-Ate) has been established as a standard first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC) since 2020. This study examined the outcomes of HCC patients who received the combination in southern Taiwan. PATIENTS AND METHODS: All patients were enrolled from four hospitals in Taiwan. They received Bev-Ate therapy for unresectable HCC. RESULTS: Thirty-five patients were included; 28 (80%) had Barcelona Clinic Liver Cancer stage C disease. Hepatitis etiology was chronic hepatitis B and C in 63% and 17% of patients, respectively. Eleven (31%) patients had received prior systemic treatment for unresectable HCC. The response rate was 51%, and the disease control rate was 72% for all patients. The median progression-free survival (PFS) and overall survival (OS) was 5.2 and 22.2 months, respectively. For patients who received prior systemic treatment, the efficacy of Bev-Ate in terms of response rates was similar compared with those without prior systemic treatment. Patients who received lower doses of bevacizumab (<15 mg/kg per dose) had non-inferior PFS and OS compared with those receiving a standard dose of bevacizumab. The incidence of proteinuria of all grades (15.8%) was less common when lower doses of bevacizumab were used. CONCLUSION: Real world data from HCC patients in southern Taiwan disclosed that the efficacy outcomes of Bev-Ate treatment were generally consistent with those of clinical trials in other countries. In patients who were exposed to prior systemic treatment or who received lower doses of bevacizumab, the Bev-Ate regimen retained its clinical efficacy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Taiwan/epidemiology
5.
Front Oncol ; 12: 1047684, 2022.
Article in English | MEDLINE | ID: mdl-36698421

ABSTRACT

Introduction: Breast cancer (BC) is the most common cancer in women worldwide. Because of the extended survival of patients with BC, the occurrence of second primary malignancies (SPMs) after BC is an important issue. Methods: We identified female patients with BC in the Breast Cancer Health Database of Taiwan, which includes four cancer registry datasets between 2002 and 2014 from Taiwan Cancer Registry. We compared the incidence of SPM between patients who received chemotherapy and/or radiotherapy with those who did not. Stratified analyses were performed according to the American Joint Committee on Cancer (AJCC) stage. The Cox regression model was used to identify the risk factors for SPM and evaluate their effects. Results: We enrolled 85,947 eligible patients with BC, and 2,656 (3.09%) patients developed SPM. The median duration of SPM was 2.70 (1.14-5.14) years. Radiotherapy was administered in 40,946 (47.64%) patients, and chemotherapy was administered in 52,120 (60.64%). The most common SPMs were digestive tract cancers (876, 31.89%). The risk factors for SPM included the AJCC stage, chemotherapy, radiotherapy, age, and underlying comorbidities. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in any stage. In contrast, after adjusting for other risk factors, patients at stage III/IV who received both therapies had lower risks of SPM compared with those who did not (p = 0.047). Conclusion: The risk of SPM was different across BC stages. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in women with BC.

6.
Oncol Lett ; 23(6): 194, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35572494

ABSTRACT

The incidence of nasopharyngeal carcinoma (NPC) in Southeast Asia and Taiwan is high due to epidemiological factors. Cisplatin-based chemoradiotherapy is an important treatment strategy with excellent outcomes for patients with NPC. However, the outcomes for patients who are refractory to cisplatin-based therapy are poor. Methods for risk stratification of patients with NPC undergoing cisplatin-based chemoradiotherapy require to be investigated. A previous study indicated that ubiquitin-conjugating enzyme E2 B (UBE2B) was able to regulate alkylating drug sensitivity in NPC cells. In the present study, the clinical significance of UBE2B expression in patients with NPC was analyzed. Analysis of the two available NPC datasets containing the UBE2B expression profile (GSE12452 and GSE68799) was performed to evaluate the UBE2B expression levels in NPC tissues compared with nasopharyngeal mucosal epithelial tissues. Furthermore, immunohistochemical staining was performed using anti-UBE2B antibodies on samples from 124 patients with NPC who underwent cisplatin-based chemoradiotherapy. Disease-specific survival (DSS), distant metastatic-free survival (DMeFS) and local recurrence-free survival (LRFS) of patients with high and low UBE2B expression was analyzed. Furthermore, the associations between UBE2B expression and the biological behavior of NPC cells were investigated in vitro. Using public NPC datasets and in vitro studies, it was identified that UBE2B expression levels were increased in NPC tumor tissues compared with those in mucosal epithelial tissues. The cell proliferation ability was decreased in UBE2B-deficient NPC cells as compared with that in UBE2B-proficient cells. Immunohistochemical analysis of 124 NPC tissues from patients who underwent cisplatin-based chemoradiotherapy indicated that high UBE2B expression levels were associated with poor DSS, DMeFS and LRFS. Multivariate regression analysis of factors influencing survival also confirmed that high UBE2B expression levels were a statistically significant independent risk factor for poor clinical outcomes in terms of DSS [hazard ratio (HR), 1.955; 95% CI 1.164-3.282], DMeFS (HR, 2.141; 95% CI 1.206-3.801) and LRFS (HR, 2.557; 95 CI 1.313-4.981). In vitro analysis indicated that O6-methylguanine-DNA methyltransferase attenuated cisplatin sensitivity induced by knockdown of UBE2B in NPC cells. In conclusion, the present study demonstrated that high UBE2B expression is associated with poor clinical outcomes for patients with NPC treated with cisplatin-based chemoradiotherapy.

7.
Case Rep Oncol ; 14(1): 232-238, 2021.
Article in English | MEDLINE | ID: mdl-33776709

ABSTRACT

Anti-epithelial growth factor receptor or anti-vascular endothelial growth factor agents combined with chemotherapy were the standard of treatment for metastatic colorectal cancer (CRC). However, increasing evidence of molecularly stratified treatment makes the complexity of treatment. Anaplastic lymphoma kinase (ALK) gene alternation is one of potential target for biomarker-guided therapy for CRC. We present a case of a 56-year-old man who suffered from advanced ascending colon cancer, harboring echinoderm microtubule associated protein-like 4 (EML4)-ALK fusion gene E21; A20 variant, a rare variant in EML4-ALK fusion gene in lung cancer. We also detected this fusion gene from different tissue types including circulating tumor DNA (ctDNA) and ascites fluid. The patient was offered alectinib, an ALK inhibitor, with partial response in lung, liver, and peritoneal metastasis for 8 months. Tumor heterogeneity, especially in gastrointestinal tract cancer, raise our interest in comprehensive genetic profiling in clinical practice. Convenience and reliability of next-generation sequencing, including using ctDNA, help physicians deal with clinical dilemma. ALK-positive CRC is rare. However, advanced CRC with ALK gene alteration responds to ALK inhibitor. It is reasonable to check ALK gene alteration in clinical practice for CRC.

8.
Aging (Albany NY) ; 13(13): 17337-17348, 2021 07 05.
Article in English | MEDLINE | ID: mdl-34226296

ABSTRACT

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.


Subject(s)
Aging , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/therapeutic use , Chemoradiotherapy, Adjuvant/methods , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Stomach Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Chemoradiotherapy, Adjuvant/adverse effects , Disease-Free Survival , Female , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Lymph Node Excision/methods , Male , Middle Aged , Prognosis , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Survival Analysis , Taiwan , Treatment Outcome
9.
Cancer Sci ; 101(9): 2033-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20624167

ABSTRACT

Sprouty2 (Spry2) is known to increase the expression of epidermal growth factor receptors (EGFR) by conjugating with c-Casitas B-lineage lymphoma (C-Cbl) to decrease protein degradation. The effect of Spry2 on the treatment of gefitinib, a tyrosine kinase inhibitor of EGFR, with regards to colon cancer is still unclear. The half maximal inhibitory concentration (IC50) values of gefitinib in six colon cancer cell lines were assessed. HCT116 and C2BBel cells expressed lower levels of Spry2 protein and were less sensitive to gefitinib, whereas HT29 cells that expressed high levels of Spry2 protein were more sensitive to gefitinib. The sensitivity to gefitinib was increased after overexpression of Spry2 in HCT116 cells, whereas it was decreased after Spry2 knockdown in HT29 cells. The levels of both phosphorylated and total EGFR were increased when HCT116 cells ectopically overexpressed Spry2, with concomitant increase in phosphatase and tensin homolog (PTEN) expression. Inhibition of EGFR by cetuximab reduced sensitivity to gefitinib in HCT116 cells overexpressing Spry2. However, knockdown of PTEN or K-ras failed to diminish the effect of Spry2 on gefitinib sensitivity. Of note, Spry2 enhanced the antitumor effect of gefitinib in a xenograft model of HCT116 tumors, which harbored K-ras codon 13 mutation. In conclusion, Spry2 can enhance the response of colon cancer cells to gefitinib by increasing the expression of phosphorylated and total EGFR. These results suggest that Spry2 may be a potential biomarker in predicting the response to anti-EGFR treatment in colon cancer and that it is necessary to conduct clinical studies to incorporate Spry2 into the network of cancer treatment.


Subject(s)
Colonic Neoplasms/drug therapy , ErbB Receptors/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Quinazolines/pharmacology , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Cetuximab , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , ErbB Receptors/genetics , Female , Gefitinib , HCT116 Cells , HT29 Cells , Humans , Immunoblotting , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins , Mice , Mice, Inbred BALB C , Mice, Nude , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Xenograft Model Antitumor Assays
10.
Lancet Oncol ; 10(1): 25-34, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19095497

ABSTRACT

BACKGROUND: Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. METHODS: Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00492752. FINDINGS: 271 patients from 23 centres in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6.5 months (95% CI 5.56-7.56) in patients treated with sorafenib, compared with 4.2 months (3.75-5.46) in those who received placebo (hazard ratio [HR] 0.68 [95% CI 0.50-0.93]; p=0.014). Median TTP was 2.8 months (2.63-3.58) in the sorafenib group compared with 1.4 months (1.35-1.55) in the placebo group (HR 0.57 [0.42-0.79]; p=0.0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10.7%]), diarrhoea (nine patients [6.0%]), and fatigue (five patients [3.4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11.4%]) and diarrhoea (11 patients [7.4%]); these adverse events rarely led to discontinuation. INTERPRETATION: Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma.


Subject(s)
Antineoplastic Agents/therapeutic use , Benzenesulfonates/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyridines/therapeutic use , Adult , Aged , Aged, 80 and over , Benzenesulfonates/adverse effects , Cost-Benefit Analysis , Double-Blind Method , Female , Humans , Male , Middle Aged , Niacinamide/analogs & derivatives , Phenylurea Compounds , Pyridines/adverse effects , Sorafenib
11.
Ann Surg Oncol ; 16(3): 729-34, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19101767

ABSTRACT

BACKGROUND: The implantation of a Port-A-Cath (PAC) is a common surgical procedure usually done under guidance with techniques such as fluoroscopy, ultrasound, or intravenous electrocardiography. PAC implantation without guidance avoids radiation exposure and decreases time, expense, and complexity. The purpose of this study was to analyze the success rate, and operation-related and postoperative complications of PAC implantation without intraoperative guidance. METHODS: Between July 2004 and June 2007, 1,070 PACs were implanted in 1,025 patients receiving chemotherapy. All PACs were placed via the subclavian vein by percutaneous puncture. The catheter length was precalculated for each patient. Postoperative chest radiography was immediately performed to check the catheter position. All data on outcome of the implantations were reviewed retrospectively. RESULTS: The catheter tip was correctly placed at the cavoatrial junction without complications in 1,055/1,070 (98.6%) of the implants. Surgery-related complications occurred in 15 (1.4%) implantations: 9 malposition, 3 pneumothorax, 2 hematoma, and 1 catheter kinking. Two patients underwent PAC removal due to hematoma with subsequent wound infection in one and catheter occlusion by kinking in the other. There were 86 (8.0%) postoperative complications that resulted in PAC removal: catheter occlusion in 24 (2.2%), pocket infection in 22 (2.1%), catheter rupture in 11 (1.0%), venous thrombosis in 9 (0.8%), port exposure in 9 (0.8%), catheter fracture in 6 (0.6%), infraclavicular pain in 3 (0.3%), catheter migration in 1 (0.1%), and extraportal injection in 1 (0.1%). CONCLUSIONS: PACs can be safely and accurately placed using percutaneous puncture of the subclavian vein without intraoperative guidance.


Subject(s)
Catheterization, Central Venous , Infusion Pumps, Implantable , Neoplasms/surgery , Postoperative Complications/diagnosis , Punctures/methods , Subclavian Vein , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Perioperative Care , Punctures/instrumentation , Young Adult
12.
Lung Cancer ; 63(1): 151-3, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18571759

ABSTRACT

A 46-year-old nonsmoking female was diagnosed with pulmonary lymphoepithelioma-like carcinoma (LELC). She simultaneously had a rare skin manifestation, erythema elevatum diutinum (EED), which did not respond to topical treatment. The patient underwent platinum-based chemotherapy and thoracic radiotherapy and had shown complete remission in both LELC and EED. EED is therefore considered as a paraneoplastic syndrome of pulmonary LELC in this case. Literature on LELC and EED were also reviewed.


Subject(s)
Carcinoma/diagnosis , Erythema/diagnosis , Lung Neoplasms/diagnosis , Paraneoplastic Syndromes/diagnosis , Antineoplastic Agents/pharmacology , Biopsy , Carcinoma/complications , Erythema/complications , Female , Humans , Lung/pathology , Lung Neoplasms/complications , Lung Neoplasms/pathology , Middle Aged , Platinum/pharmacology , Remission Induction , Skin/pathology , Tomography, X-Ray Computed/methods , Treatment Outcome
13.
Kaohsiung J Med Sci ; 25(7): 389-94, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19605331

ABSTRACT

Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with frequent involvement of the gastrointestinal tract and peripheral blood (PB). In addition to the B cell markers, the neoplastic cells express CD5 and CD43. In patients with a prior history of MCL with PB involvement, the appearance of leukemic cells after chemotherapy usually heralds a relapse, particularly if the leukemic cells express B cell markers and CD43. We report a patient with MCL who presented with multiple lymphomatous polyposis of the intestine. The staging procedures revealed the involvement of lymph nodes, bone marrow and PB. Three years after chemotherapy, thrombocytopenia with the appearance of rare leukemic cells in the PB was noted. Leukemic cells obtained from bone marrow aspirate expressed CD19 and CD43, suggesting a relapse. Detailed cytomorphological and immunophenotypic studies unveiled the myeloid nature of these leukemic cells, and a diagnosis of therapy-related acute myeloid leukemia was made. This case illustrates the importance of morphologic examination and performing a complete antibody panel in the diagnosis of a suspected relapse in patients with a prior history of lymphoma.


Subject(s)
Antigens, CD19/immunology , Gene Expression Regulation, Neoplastic , Leukemia, Myeloid, Acute/etiology , Leukemia, Myeloid, Acute/immunology , Leukosialin/immunology , Lymphoma, Mantle-Cell/immunology , Flow Cytometry , Humans , Leukemia, Myeloid, Acute/pathology , Lymphoma, Mantle-Cell/pathology , Male , Middle Aged
14.
Cancer Genomics Proteomics ; 16(6): 569-576, 2019.
Article in English | MEDLINE | ID: mdl-31659110

ABSTRACT

BACKGROUND/AIM: The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been reported. MATERIALS AND METHODS: We exploited two-dimensional gel electrophoresis coupled with mass spectrometry to find de-regulated proteins by using conditioning of a sorafenib-resistant HCC cell line, Huh7. Tumor samples from 60 patients with HCC treated with sorafenib were analyzed and correlated with survival outcome. RESULTS: Comparative proteomics indicated three proteins including, 78 kDa glucose related protein (GRP78), 14-3-3ƎĀµ, and heat shock protein 90Ɵ (HSP90Ɵ). The three proteins were over-expressed in sorafenib-resistant Huh7 cells. In HCC tumor samples from patients treated with sorafenib, 73% of tumor samples had a high expression of GRP78, 18% had high 14-3-3ƎĀµ expression and 85% had high HSP90Ɵ expression. Among these, GRP78 was associated with the shortest progression-free survival of HCC patients treated with sorafenib. CONCLUSION: GRP78 can be a predictive biomarker in HCC patients treated with sorafenib. Strategies designed to inhibit the GRP78-related pathway may overcome sorafenib resistance.


Subject(s)
Drug Resistance, Neoplasm/drug effects , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Heat-Shock Proteins/biosynthesis , Hematoma/metabolism , Liver Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Proteomics , Sorafenib/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Endoplasmic Reticulum Chaperone BiP , Heat-Shock Proteins/genetics , Hematoma/drug therapy , Hematoma/genetics , Hematoma/pathology , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Neoplasm Proteins/genetics
15.
J Exp Clin Cancer Res ; 38(1): 282, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-31262325

ABSTRACT

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide despite diagnostic improvements and the development of targeted therapies, notably including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling has been shown to contribute to tumorigenesis, tumor progression, and resistance to therapy in most human cancer types, including lung cancer. Here, we explored the therapeutic effects of co-inhibition of PI3K and mTOR in non-small-cell lung cancer (NSCLC) cells with different EGFR status. METHODS: The antiproliferative activity of a dual PI3K/mTOR inhibitor BEZ235 was examined by the WST-1 assay and the soft agar colony-formation assay in 2 normal cell lines and 12 NSCLC cell lines: 6 expressing wild-type EGFR and 6 expressing EGFR with activating mutations, including exon 19 deletions, and L858R and T790 M point mutations. The combination indexes of BEZ235 with cisplatin or an EGFR-TKI, BIBW2992 (afatinib), were calculated. The mechanisms triggered by BEZ235 were explored by western blotting analysis. The anti-tumor effect of BEZ235 alone or combined with cisplatin or BIBW2992 were also studied in vivo. RESULTS: BEZ235 suppressed tumor growth in vitro and in vivo by inducing cell-cycle arrest at G1 phase, but without causing cell death. It also reduced the expression of cyclin D1/D3 by regulating both its transcription and protein stability. Moreover, BEZ235 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells by enhancing or prolonging DNA damage and BIBW2992-induced apoptosis in EGFR-TKI-resistant NSCLC cells containing a second TKI-resistant EGFR mutant. CONCLUSIONS: The dual PI3K/mTOR inhibition by BEZ235 is an effective antitumor strategy for enhancing the efficacy of chemotherapy or targeted therapy, even as a monotherapy, to restrict tumor growth in lung cancer treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Imidazoles/therapeutic use , Lung Neoplasms/drug therapy , Phosphoinositide-3 Kinase Inhibitors , Quinolines/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , A549 Cells , Afatinib/therapeutic use , Animals , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Cycle Checkpoints/drug effects , Cisplatin/therapeutic use , Cyclin D1/genetics , Cyclin D1/metabolism , Cyclin D3/genetics , Cyclin D3/metabolism , Drug Resistance, Neoplasm/drug effects , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Imidazoles/pharmacology , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Phosphatidylinositol 3-Kinases/metabolism , Quinolines/pharmacology , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolism
16.
Oncol Lett ; 17(6): 5740-5746, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31105795

ABSTRACT

Prothymosin α (ProTα) is a nuclear protein that serves a role in oncogenesis, by promoting proliferation and inhibiting apoptosis in various malignancies. The present study was designed to investigate ProTα expression in resected human non-small cell lung cancer to define the clinicopathological associations of ProTα-positive lung cancer. Immunohistochemical staining of ProTα was performed using tumor sample slides from 149 patients with non-small cell lung cancer, who underwent surgical resection. Association between the expression of ProTα and the following clinicopathological parameters was accessed: Age, sex, stage, lymph node involvement, pathological subtype, recurrence and cigarette smoking. A total of 85 tumors (57%) were classified as ProTα-positive lung cancer by staining intensity and 73 tumors (49%) were regarded as ProTα-positive by scoring index. The majority of patients with ProTα-positive tumors were younger (P=0.05) and had squamous cell carcinoma (P<0.01) compared with older and adenocarcinoma. Positive expression of ProTα by staining intensity was associated with a higher incidence rate of cancer recurrence (P=0.05) compared with negative ProTα expression. ProTα was also associated with cigarette smoking, particularly in the group with squamous cell carcinoma. Therefore, the present data suggested that ProTα-positive non-small cell lung cancer was associated with younger patients, squamous cell carcinoma, cigarette smoking and a higher incidence recurrence rate, subsequently indicating a subtype consisting of patients with smoking-associated inferior outcomes.

17.
J Clin Med ; 8(6)2019 Jun 19.
Article in English | MEDLINE | ID: mdl-31248135

ABSTRACT

The oncologic merits of the laparoscopic technique for colorectal cancer surgery remain debatable. Eligible patients with non-metastatic colorectal cancer who were scheduled for an elective resection by one surgeon in a medical institution were randomized to either laparoscopic or open surgery. During this period, a total of 188 patients received laparoscopic surgery and the other 163 patients received the open approach. The primary endpoint was cancer-free five-year survival after operative treatment, and the secondary endpoint was the tumor recurrence incidence. Besides, surgical complications were also compared. There was no statistically significant difference between open and laparoscopic groups regarding the average number of lymph nodes dissected, ileus, anastomosis leakage, overall mortality rate, cancer recurrence rate, or cancer-free five-year survival. Even though performing a laparoscopic approach used a significantly longer operation time, this technique was more effective for colorectal cancer treatment in terms of shorter hospital stay and less blood loss. Meanwhile, fewer patients receiving the laparoscopic approach developed postoperative urinary tract infection, wound infection, or pneumonia, which reached statistical significance. For non-metastatic colorectal cancer patients, laparoscopic surgery resulted in better short-term outcomes, whether in several surgical complications and intra-operative blood loss. Though there was no significant statistical difference in terms of cancer-free five-year survival and tumor recurrence, it is strongly recommended that patients undergo laparoscopic surgery if not contraindicated.

18.
Head Neck ; 41(6): 1703-1712, 2019 06.
Article in English | MEDLINE | ID: mdl-30636183

ABSTRACT

BACKGROUND: The prognosis of advanced oral squamous cell carcinoma is poor. We investigated the effect of cetuximab-based sequential therapy as a primary treatment. METHODS: Forty-seven treatment-naive patients with advanced tumors originating from the oral cavity or oropharynx were enrolled. Neoadjuvant cetuximab, paclitaxel, and cisplatin were administered, followed by cetuximab-based radiotherapy. Immunohistochemical staining was applied to study the tissues. RESULTS: The best overall response rate was 70.2%, including 4 patients with a complete response and 29 with a partial response. The median progression-free and overall survival rates were 10.3 and 15.2 months, respectively. Patients with more than 50% tumor reduction with neoadjuvant therapy had better survival outcomes. Twenty-two patients had severe adverse events with mostly dermatological complications. Of the 16 patients who received operations, 9 had increased PD-L1 staining compared to pretreatment biopsy in the post hoc study. CONCLUSION: The regimen was effective in selected patients. Increased PD-L1 suggested altered tumor features.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/therapy , Cetuximab/administration & dosage , Cisplatin/administration & dosage , Mouth Neoplasms/therapy , Paclitaxel/administration & dosage , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy , Female , Humans , Male , Middle Aged , Mouth Neoplasms/mortality , Mouth Neoplasms/pathology , Neoadjuvant Therapy , Neoplasm Staging , Survival Rate
19.
Lung Cancer ; 62(1): 78-84, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18423781

ABSTRACT

PURPOSE: Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. METHODS: Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150mg/day till disease progression. RESULTS: From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p=0.033), adenocarcinoma/BAC (p=0.0027), female (p=0.0013), aged less than 65 years (p=0.0115), stage IV (p=0.0492), patients with skin rash (p=0.0216), and a higher grade of skin rash (p=0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3-4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. CONCLUSIONS: This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Adult , Age Factors , Aged , Aged, 80 and over , Asian People , Carcinoma, Non-Small-Cell Lung/mortality , Erlotinib Hydrochloride , Exanthema/chemically induced , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Sex Factors , Smoking , Taiwan
20.
Int J Hematol ; 88(2): 237-239, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18470598

ABSTRACT

Thyroid dysfunction after hematopoietic stem cell transplantation has been investigated in many studies. Most post-transplant thyroid disorders such as hypothyroidism are recognized as a late complication whilst hyperthyroidism is infrequent and transient, and usually happens early at the onset after transplant. Here, we report two rare hyperthyroid cases, developing more than 2 years after autologous stem cell transplant. We suggest that hyperthyroidism be alerted in the post-transplant care, and special attention be paid to any latent events.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Hyperthyroidism/etiology , Leukemia, Myeloid, Acute/therapy , Adult , Female , Humans , Time Factors , Transplantation, Autologous
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