Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with renal cell carcinoma.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of renal cell carcinoma was published in 2019 with an update planned for 2021. It was therefore decided by both the ESMO and the Singapore Society of Oncology (SSO) to convene a special, virtual guidelines meeting in May 2021 to adapt the ESMO 2019 guidelines to take into account the ethnic differences associated with the treatment of renal cell carcinomas in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with renal cell carcinoma representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate.

Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway.

OBJECTIVE: In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism. RESULTS: An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H2O drinking water; (2) mock: H2O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg-1)+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg-1)+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg-1)+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg-1)+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1ß) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation. CONCLUSION: Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake, inflammatory reaction and the formation of fatty liver by activating JAK2 signal transduction through the JAK2/STAT3 and JAK2/AMPK pathways in the high-fructose-induced fatty liver animal model. Therefore, kefir peptides may have the potential for clinical application for the prevention or treatment of clinical metabolic syndrome.

Comparison of treatment effects of guided tissue regeneration on infrabony lesions between animal and human studies: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: For ethical reasons it is becoming increasingly more difficult to obtain, from clinical studies, histological data on infrabony defects treated with guided tissue regeneration (GTR) techniques. The aim of this systematic review was to find the value of extrapolating animal data on treatment of periodontal infrabony lesions, using GTR only or GTR + bone grafts, to human clinical results. MATERIAL AND METHODS: Searches of the PubMed and Cochrane databases were combined with hand searching of articles published from 1 January 1969 to 1 August 2012. The search included any type of barrier membrane, with or without grafted materials, used to treat periodontal infrabony lesions. All studies with histological or re-entry methodology outcome parameters that evaluated bone-filling and/or new-cementum-formation ratios from a defect depth were collected. When comparing animal and human outcomes, a meta-analysis was used to evaluate the bone-filling ratio, but only a descriptive analysis of the histological studies was performed. RESULTS: In total, 22 studies were selected for the meta-analysis. In the GTR + bone graft groups the weighted-average bone-filling ratios were 52% (95% CI: 18-85%) in animals and 57% (95% CI: 30-83%) in humans, which were not statistically significantly different (p = 0.825). Similar results were found in the GTR-only groups, in which the weighted-average bone-filling ratios were 54% (95% CI: 37-72%) in animals and 59% (95% CI: 42-77%) in humans (p = 0.703). New-cementum formation of GTR only and GTR + bone grafts showed comparable ratio outcomes, and both were superior to the control group in animals only (p = 0.042). CONCLUSION: Although quality assessments differed between animal and human studies, our analysis indicated that animal models and human results showed similar bone-filling ratios in infrabony defects treated with GTR only or with GTR + bone grafting.

Application of high-frequency ultrasound for the detection of surgical anatomy in the rodent abdomen.

Rats are used extensively in abdominal disease research. To monitor disease progress in vivo, high-frequency ultrasound (HFU) can be a powerful tool for obtaining high-resolution images of biological tissues. However, there is a paucity of data regarding the correlation between rat anatomy and corresponding HFU images. Twenty-four adult male Sprague-Dawley (SD) rats underwent abdominal scans using HFU (40 MHz) surgical procedures to identify abdominal organs and major vessels as well as in situ scanning to confirm the imaging results. The results were compared with those of human abdominal organs in ultrasonographic scans. The rat liver, paired kidneys, stomach, intestines, and major blood vessels were identified by HFU and the ultrasonic morphologies of the liver and kidneys showed clear differences between rats and humans. Clinically relevant anatomical structures were identified using HFU imaging of the rat abdomen, and these structures were compared with the corresponding structures in humans. Increased knowledge with regard to identifying the anatomy of rat abdominal organs by ultrasound will allow scientists to conduct more detailed intra-abdominal research in rodents.

A case of myeloid neoplasm associated with eosinophilia and KIAA1509-PDGFRß responsive to combination treatment with imatinib mesylate and prednisolone.

A 41-year-old woman presented with dyspnoea, persistent leucocytosis and eosinophilia for 8 months. High-resolution computed tomography scan and pathology of bronchoalveolar lavage confirmed the diagnosis of hypereosinophilic pneumonitis. The patient was treated with prednisolone (0·5-1 mg/kg/day) for more than 20 weeks under the impression of hypereosinophilic syndrome, but without improvement of leucocytosis and eosinophilia. The bone marrow aspiration smear disclosed hypercellular marrow with myeloid hyperplasia and eosinophilia. The fusion gene detection was positive for KIAA1509-PDGFRß. Myeloid neoplasm associated with eosinophilia and abnormality of PDGFRß was then diagnosed (Tefferi A, Vardiman JW, Leukemia, 22, 2008, 14). The tyrosine kinase inhibitor, imatinib mesylate (Glivec; 200 mg/day), was administered along with prednisolone (0·25-1 mg/kg/day). White blood cell (WBC) count decreased from 49,500/µL to 17,200/µL, and eosinophil count decreased from 1932/µL to 35/µL, which represent percentage dropped from 7·7%> to 0·2%. Withdrawal of prednisolone was done to avoid adverse events. However, absolute eosinophil count increased progressively despite the continue administration of imatinib and negative detection PDGFRß fusion gene. The patient then received combination therapy of imatinib and prednisolone again. WBC and absolute eosinophil were normalized subsequently. We had discontinued the prednisolone one more time, and rebound of eosinophilia was seen again. The phenomenon of rebounding of eosinophilia was observed in two subsequent withdrawals of prednisolone. Either steroid or imatinib mesylate alone failed to achieve complete haematological response. A synergistic effect of imatinib and steroid is postulated.

Haematopoietic stem cell transplantation in Taiwan: past, present, and future.

In Taiwan, haematopoietic stem cell transplantation (HSCT) has been used to treat patients with haematological diseases since 1983. Thereafter till 2007, there were 2537 patients who had undergone HSCT in more than 15 hospitals. Their diseases included acute myeloid leukaemia in 27.8% of cases, non-Hodgkin's lymphoma 23.3%, acute lymphoblastic leukaemia 12.8%, chronic myeloid leukaemia 11.9%, severe aplastic anaemia 8.7%, and multiple myeloma 4.1%. Most of the cases received myeloablative conditioning regimens. More than 15% of cases received non-myeloablative regimens, and the mean age of these cases was at least 10 years older than those who received myeloablative regimens. The types of graft included peripheral blood (60.4%) and bone marrow (32.0%). A total of 35% of patients received autologous grafts. Of 1557 allogeneic HSCT patients, 338 (21.7%) received grafts from unrelated donors. Cord blood transplantation has been successfully performed in paediatric patients with thalassaemia major and with a large body size, and adult patients. The incidence of acute graft-versus-host disease was relatively low in Taiwan. On the contrary, a relatively higher proportion of hepatitis B carrier in the recipients had led to a higher incidence of reactivation hepatitis, which was markedly decreased following lamivudine prophylaxis. In conclusion, HSCT has become a routine therapy for major medical centres in Taiwan. Our unique experiences in the past decades also contributed to the progress of HSCT. With the establishment of professional association and patient supportive groups, we hope we can fully improve our daily practice and clinical as well as basic research in HSCT.

Simulating sharp gradients for short-term, Ca(2+) transients and long-term chemotaxis in cancer cells.

Rapid progress in the elucidation of candidate genes and proteins that play a role in disease processes such as cancer has been possible with widespread use of genomics and proteomics in the last ten years. It is becoming important to adapt the knowledge gained from mass analytical techniques to visual techniques that enable spatial-temporal discernment of molecular events. This is significant, particularly for the study of pathways that regulate dynamic processes such as cell migration or early events associated with differentiation such as Ca(2+) signaling. This paper describes the use of techniques that create sharp growth factor gradients suitable for local activation of cell surface receptors. The methods involve retardation of the direct flow to create steep gradients at the surface plane where cells are grown. These methods are shown to be suitable for rapid biological assays such as Ca(2+) transients that occur within 1 min of receptor activation, demonstrating that the speed and level of Ca(2+) transients are related to gradient strength. A microfabricated chamber is also determined to be suitable for longer-term analyses such as cancer cell chemotaxis.

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

Effect of a periodized exercise training and active recovery program on antitumor activity and development of dendritic cells.

AIM: Dendritic cells (DCs) are potent antigen-presenting cells that promote antitumor immunity in vivo when pulsed with tumor antigen. No studies have indicated that exercise training affects DC function. The purpose of this study was to investigate the effect of a 5-week periodized exercise training and active recovery program on the development of DCs, and to test their effect on the antitumor immunity of mononuclear cells (MNC) from blood and spleen against human leukemic U937 and murine lymphoma Yac-1 cells, respectively. METHODS: Male Fisher 344 rats were divided into 2 groups: exercise and non-exercise group. The training protocol consisted of running on a motor-driven treadmill 6 days a week for consecutive 5 weeks, during which the running time, treadmill speed, and incline gradient were increased weekly. Active recovery parameters were set at 30% of the intensity of the previous day. RESULTS: DC numbers increased significantly (P<0.05) in the exercise group compared to controls, but there were no significant changes in the expression of surface antigens CD80 and CD86. In exercise group MNC-conditioned medium (CM) prepared with 50 microg/mL phytohemagglutinin (PHA) significantly inhibited proliferation of U937 cells, and splenocyte-CM with PHA at 20 and 40 microg/mL significantly inhibited proliferation of YAC-1 cells greater than control group. CONCLUSIONS: The 5-week periodized exercise training with active recovery promotes the number of DCs and enhances the activity of DCs against tumor cells.

Stem cells in the lung parenchyma and prospects for lung injury therapy.

Until recently, it was thought that only embryonic stem cells were pluripotent and that adult stem cells were restricted in their differentiative and regenerative potential to become the tissues in which they reside. However, the discovery that adult stem cells in one tissue can contribute to the formation of other tissues, especially after injury or cell damage, implies that stem cells have developmental plasticity. For example, haematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) from bone marrow can be used to regenerate diverse tissues at distant sites, including the lung. This article reviews the character of stem cells in the lung parenchyma and focuses on the potential uses of adult stem cells in research of lung injury and lung disease therapies.

Relatively favorable outcomes of post-transplant pulmonary function in patients with chronic myeloid leukemia receiving non-myeloablative allogeneic hematopoietic stem cell transplantation.

Pulmonary function tests were performed in 20 patients with chronic myeloid leukemia before and after human leukocyte antigen-matched allogeneic sibling hematopoietic stem cell transplantation (HSCT) to identify any conditioning treatment effects on post-transplant function from January 1995 to December 2002. Of 20 patients, eight received non-myeloablative conditioning treatment and 12 received conventional myeloablative conditioning treatment. Pulmonary function tests including forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and diffusion capacity for carbon monoxide (DLCO) were performed pretransplant, 6 and 12 months post-transplant. Possible pre-HSCT and post-HSCT risk factors were evaluated for association with pulmonary function. The results showed that myeloablative conditioning treatment had greater negative impact on FEV1, FVC, and DLCO than non-myeloablative conditioning therapy. We conclude that non-myeloablative allogeneic HSCT may apply a better transplant choice in patients who need special concern with post-transplant pulmonary function changes.

Hematopoietic stem cell transplantation for severe aplastic anemia--experience of an institute in Taiwan.

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment strategy for patients with severe aplastic anemia (SAA). We report our experience in a general hospital in Taiwan. From March 1985 to July 2001, 79 consecutive SAA patients, 46 male and 33 female, with a median age of 22 (4-43) years, received 80 courses of transplantation. Cyclophosphamide and total body radiation were used for the conditioning regimen, and cyclosporine-A and methotrexate for graft-versus-host disease (GVHD) prevention. Patients were followed for a median of 39 months (from 8 days to 194 months). Myeloid and platelet engraftment occurred in a median of 15 (8-27) days and 18 (8-77) days, respectively. Three patients had primary and three patients secondary graft failure. Five patients (6.8%) had grade II-IV acute GVHD in 73 evaluable patients. Chronic GVHD occurred in 23 (34.8%) patients, with extensive stage in six. Only two patients had CMV disease. The projected 3- and 5-year overall survival rates estimated by the Kaplan-Meier method were 76.08 and 74.13%, respectively. Age at transplant, non-sibling donor, mononuclear cell dose, grade II-IV acute GVHD, interval from diagnosis to transplant, and red blood cell and platelet transfusion before transplant were poor prognostic factors for overall survival by univariate analysis. Grade II-IV acute GVHD was the only prognostic factor affecting overall survival after multivariate Cox regression analysis (P=0.040). In conclusion, SAA patients receiving HSCT have good long-term survival. The low incidence of acute GVHD in our patients may be related to ethnicity.

Plasma protein regulation by thyroid hormone.

Thyroid hormones (THs) regulate growth, development, differentiation and metabolic processes by interacting and activating thyroid hormone receptors (TRs). Although much progress has been made in our understanding of the transcriptional regulation of many TR target genes, little is known of the regulation of plasma protein gene expression by TRs. To investigate the role of TRs in plasma protein expression we used human hepatocellular carcinoma cell lines and carried out cDNA microarray analysis. Our results indicate that several plasma proteins including transferrin, prothrombin, angiotensinogen, haptoglobin, alpha-2-HS-glycoprotein alpha and beta chain, complement, lipoproteins and fibrinogen are up-regulated by THs. Furthermore, clusterin, alpha-2-macroglobulin precursor, prothymosin alpha and alpha-fetoprotein were found to be down-regulated by THs.Transferrin, an iron-binding protein expressed in all mammals, and mainly synthesized in the liver, was investigated further. Immunoblot and Northern blot analyses revealed that exposure of HepG2-TRalpha1 sub-lines and HepG2-Neo cells to tri-iodothyronine (T(3)) induced time- and dose-dependent increases in the abundance of transferrin mRNA and protein, with the extent of these effects correlating with the level of expression of TRalpha1. Nuclear run-on experiments indicate that this induction is functioning at the transcriptional level. Moreover, cyclohexamide treatment did not eliminate the induction of transferrin by TH. Thus, our results suggest that the induction of transferrin by TH is direct and may in fact be mediated by an as yet unidentified response element in the promoter region.

Case report: Unusual peritoneal spreading by metastatic osteosarcoma of the tibia.

We report a 17-year-old boy with chondroblastic osteosarcoma initially found in left proximal tibia. He received surgical resection and chemotherapy. However, a lung metastasis was found 4 years later. Despite intensive chemotherapy, the metastatic osteosarcoma of lung continued to invade the ribs and later into retroperitoneum and liver. The metastatic pattern of chondroblastic osteosarcoma of tibia directly to the chest and then into the abdomen is unusual.

Myelodysplastic syndrome complicated by autoimmune hemolytic anemia: remission of refractory anemia following mycophenolate mofetil.

Autoimmune hemolytic anemia (AIHA) rarely occurs in myelodysplastic syndrome (MDS). A 36-year-old Asian female was diagnosed with MDS (refractory cytopenia with multilineage dysplasia, RCMD) and complicated by AIHA 7 months later. Secondary myelofibrosis developed at the same time. Steroid therapy was ineffective and cyclosporin A (CsA) was discontinued due to its neurotoxicity with the development of leukoencephalopathy. However, the patient achieved a good hematological response after the use of mycophenolate mofetil (MMF, CellCept) with a dose of 1 g/day and prednisolone (15 mg/day). Prednisolone was tapered off over the next 3 weeks. The patient did not require any blood support 4 weeks after the use of MMF and has been hematologically stable for 4 months. To our knowledge, this is the first report of using MMF in treating MDS complicated by AIHA. MMF might be considered as a salvage therapy for patients with refractory anemia complicated by AIHA.

Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis.

BACKGROUND: Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood. METHODS: Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically. RESULTS: In total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12-q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis. CONCLUSIONS: CGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging.

Molecular analysis of mucosa-associated lymphoid tissue (MALT) lymphoma of ocular adnexa.

Lymphomas of mucosa-associated lymphoid tissue (MALT) are a distinct subgroup of extranodal B-cell non-Hodgkin's lymphomas. Most studies have failed to demonstrate the clonal rearrangement of BCL-1, BCL-2 or c-MYC genes for MALT lymphomas. Further, alteration of the p53 gene is rarely demonstrated in low-grade MALT lymphomas, but can be detected in high-grade disease. Lymphomas of the ocular adnexa represent approximately eight percent of all extranodal lymphomas, most of which are MALT lymphomas, but few studies had explored the alterations of BCL-1, BCL-2, c-MYC and p53 genes specifically for ocular MALT lymphomas. We investigated the changes to BCL-1, BCL-2, c-MYC and p53 genes in these lymphomas for Taiwanese patients. Clonal rearrangement for immunoglobulin heavy-chain (IgH), BCL-1, BCL-2, c-MYC and p53 genes was examined for 16 cases of ocular MALT lymphoma. Restriction-length polymorphism and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) of the DNA, corresponding to exons 5 through 9, followed by DNA sequencing, were utilized to analyze the possible mutations of the p53 gene for these tumors. Thirteen of the cases revealed rearranged IgH genes using Southern blotting or PCR. No rearrangement of BCL-1, BCL-2, c-MYC or p53 genes was discovered, with point mutation of the p53 gene in one case. As for other types of MALT lymphomas, BCL-1, BCL-2 and c-MYC genes are not implicated in the pathogenesis of the ocular sub-group. Although alteration of the p53 gene is rare for low-grade ocular MALT lymphoma, its role in disease progression merits further research.

Salvage therapy with single-agent paclitaxel by three-hour infusion in metastatic breast cancer: an experience in Taipei Veterans General Hospital.

BACKGROUND: Paclitaxel is an active agent in the treatment of breast, ovarian, lung and head and neck cancers. In previous phase I and II trials, it exerted novel cytotoxic effect on several malignancies. Various doses and regimens of paclitaxel have been assessed in metastatic breast cancer, with responses between 20 and 62%. However, combination therapy with other anti-cancer drugs leads to a high incidence of side effects. Our aim was to evaluate the efficacy of paclitaxel given by 3 h infusion as salvage chemotherapy for patients with metastatic breast cancer. METHODS: Between May 1999 and April 2000, 14 women with metastatic breast cancer were enrolled in this study and all the patients had to have measurable lesions. The median age of the patients was 48.7 years (range 39-56 years). All of them were definitely evidenced as having metastatic breast cancer and received complete courses of anthracycline-containing agents before applying paclitaxel. The protocol was single-agent paclitaxel (Anzatax, Faulding, Australia) at a moderate dosage of 175 mg/m(2) by 3 h intravenous infusion every 3 weeks. RESULTS: A total of 75 cycles were administered to these 14 patients with a median of four delivered cycles (range 3-14) and the response rate was 28.6% (95% CI: 21-40%), including four partial remission, three stable disease and seven progressive disease. The median time to progression was 3 (range 3-7) months. Hematological toxicities were minimal with no evidence of severe (grade 3 or 4) leukopenia and thrombocytopenia. Hepatic toxicities were observed in 12 cycles with five in grade 3. CONCLUSIONS: Our study indicates that utilizing single-agent paclitaxel exerts moderate activity on anthracycline-refractory metastatic breast cancer patients without excessive toxicities.