The receptor tyrosine kinase vascular endothelial growth factor (VEGF) receptor (VEGFR) plays an important role in tumor angiogenesis of hepatocellular carcinoma (HCC). (–)‐Epigallocatechin gallate ...(EGCG), the major biologically active component of green tea, inhibits growth in a variety of human cancer cells by inhibiting the activation of several types of receptor tyrosine kinases. In this study, we examined the effects of EGCG on the activity of the VEGF–VEGFR axis in human HCC cells. The levels of total and phosphorylated (i.e. activated) form of VEGFR‐2 protein (p‐VEGFR‐2) were observed to increase in a series of human HCC cell lines in comparison to the Hc normal human hepatocytes. EGCG preferentially inhibited the growth of HuH7 HCC cells, which express constitutive activation of the VEGF–VEGFR axis, in comparison to Hc cells. Treatment of HuH7 cells with EGCG caused a time‐ and dose‐dependent decrease in the expression of VEGFR‐2 and p‐VEGFR‐2 proteins. The production of VEGF from HuH7 cells was reduced by treatment with EGCG. Drinking of EGCG significantly inhibited the growth of HuH7 xenografts in nude mice and this was associated with inhibition of the activation of VEGFR‐2 and its related downstream signaling molecules, including ERK and Akt. EGCG drinking also decreased the expression of Bcl‐xL protein and VEGF mRNA in the xenografts. These findings suggest that EGCG can exert, at least in part, its growth‐inhibitive effect on HCC cells by inhibiting the VEGF–VEGFR axis. EGCG might therefore be useful in the treatment of HCC. (Cancer Sci 2009; 100: 1957–1962)
PurposeThe increased global burden of non-communicable diseases and mental disorders is an urgent health challenge for countries around the entire world, especially those experiencing super-ageing ...societies, where over 21% of the population is age 65 years or older. Japan is the world’s most rapidly ageing society, and as a result, medical costs are also rising dramatically. With the aims of establishing a foundational framework for future research efforts, primarily focusing on the development of a personal health record (PHR) system, and creating a long-term repository for bioresources integrated with PHRs, this study investigated potential health risks and future healthcare burdens based on a longitudinal analysis of health records.ParticipantsThe Resource Center for Health Science (RECHS) project is a long-term, prospective biobank project, population and health check-up-based cohort that primarily investigates the associations between lifestyle and environmental factors and some surrogate markers of non-communicable diseases, such as diabetes, hypertension, cardiovascular disease and cancer. Starting in 2010, we initiated an annual cohort study among voluntary participants recruited from health check-up programmes and collected data from the following sources: a self-administered baseline questionnaire that included items on dietary habits and stress, a Brief Self-Administered Diet History Questionnaire, the Centre for Epidemiologic Studies Depression Scale and the General Health Questionnaire-28.Findings to dateFor this prospective cohort study, we planned to enrol approximately 10 000 participants. We collected and stored serum samples from all participants for future analyses. The study participants who still were able to participate in these health check-ups and their outcomes were then obtained from the measurements and questionnaire responses.Future plansInsights emerging from the RECHS study can provide researchers and public health policy administrators with evidence to aid in the prevention of non-communicable diseases and clarify the most malleable status to implement preventive measures.
Oral mucositis is a common and distressing complication in patients receiving high‐dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a ...single‐center retrospective analysis that zinc‐L‐carnosine (polaprezinc PZ) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi‐institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.
What's new?
Chemotherapy‐induced oral mucositis is a common, painful condition that can result in an inability to eat, affecting patient nutrition. In this multi‐institutional randomized controlled study, the authors investigated the ability of polaprezinc (PZ) lozenges to prevent oral mucositis associated with conditioning chemotherapy in patients undergoing hematopoietic stem cell transplantation (HSCT). PZ lozenges effectively prevented grade ≥2 oral mucositis associated with chemotherapy in about 22 percent of HSCT patients, with no impact on HSCT outcome. The lozenges did not prevent grade ≥3 mucositis. The findings indicate that PZ lozenges are effective against moderate oral mucositis in some patients.
Objective For patients with Gaucher disease (GD), a rare, inherited lysosomal storage disease, obtaining a definitive diagnosis is currently time-consuming and costly. A simplified screening method ...to measure the glucocerebrosidase (GBA) activity using dried blood spots (DBS) on filter paper has recently been developed. Using this newly developed screening method, we evaluated real-world GD screening in patients suspected of having GD. Methods This multicenter, cross-sectional, observational study with a diagnostic intervention component evaluated real-world screening in patients suspected of having GD based on their clinical symptoms and a platelet count <120,000/μL. The endpoint was the number of patients with low GBA activity determined using DBS. Results In 994 patients who underwent initial DBS screening, 77 had low GBA activity. The assay was not repeated in 1 patient who was diagnosed as having a high possibility of GD due to clinical symptoms, and a further 21 patients completed the study without undergoing the second assay. Of the remaining 55 patients who had 2 DBS assays performed, 11 had a low GBA activity in both assays. Overall, DBS screening identified 12 (1.2%) patients with a low GBA activity, a proportion consistent with prior screening studies. Conclusion These results suggest that the simplified DBS method was less burdensome to patients, was easily utilized by many physicians, and could be a useful first-tier screening assay for GD prior to initiating burdensome genetic testing.
Obesity and related metabolic abnormalities are risk factors for colorectal cancer. A state of chronic inflammation and adipocytokine imbalance may play a role in colorectal carcinogenesis. Statins, ...which are commonly used for the treatment of hyperlipidemia, are known to possess anti‐inflammatory effects. Statins also exert chemopreventive properties against various cancers. The present study examined the effects of pitavastatin, a recently developed lipophilic statin, on the development of azoxymethane (AOM)‐initiated colonic premalignant lesions in C57BL/KsJ‐db/db (db/db) obese mice. Male db/db mice were administrated weekly subcutaneous injections of AOM (15 mg/kg body weight) for 4 weeks and then were subsequently fed a diet containing 1 ppm or 10 ppm pitavastatin for 8 weeks. Feeding with either dose of pitavastatin significantly reduced the number of colonic premalignant lesions, β‐catenin accumulated crypts, by inhibiting proliferation and the surrounding inflammation. Pitavastatin increased the serum levels of adiponectin while conversely decreasing the serum levels of total cholesterol, tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, IL‐18, and leptin. Pitavastatin also caused a significant increase in the expression of phosphorylated form of the AMP‐activated kinase (AMPK) protein on the colonic mucosa of AOM‐treated mice. In addition, the expression levels of TNF‐α, IL‐6, IL‐18, and COX‐2 mRNAs on the colonic mucosa of AOM‐treated mice were decreased by treatment with this agent. These findings suggest that pitavastatin attenuates chronic inflammation and improves the imbalance of adipocytokines, both of which are caused by the presence of excess adipose tissues, thereby preventing the development of colonic premalignancies in an obesity‐related colon cancer model. Therefore, some types of statins, including pitavastatin, may be a useful chemoprevention modality for colon cancer in obese individuals. (Cancer Sci 2010)
Follicular lymphoma (FL) is an indolent lymphoma that often transforms into a high-grade lymphoma, mostly diffuse large B-cell lymphoma. A case of FL suggested to transform into plasmablastic ...lymphoma is presented. A 59-year-old man was admitted to our hospital because of right lower abdominal pain and vomiting. Computed tomography showed a mass in the ileocecum. Colonoscopy showed a mass with an ulcer in the ascending colon, and surgery was performed. Immunohistochemical staining of the biopsied mass showed infiltrated lymphocytes that were positive for CD38, CD45, CD138, and λ chain, and negative for CD4, CD5, CD8, CD10, CD20, CD56, and κ chain. Flow cytometric analysis of the ascites showed similar results. FISH analyses performed using lymph node biopsy specimens, ascite fluid and pleural effusion fluid identified the presence of an IGH/BCL2 translocation. FL was suggested to transform into PBL. Although the patient received three courses of R-CHOP chemotherapy and salvage chemotherapy, the patient died because of lymphoma progression less than 6 months after the diagnosis of PBL. Transformation of FL to PBL is highly unusual. The lack of a standard treatment for PBL results in the poor outcome of this entity. Novel therapeutic approaches are needed.
Aim
Current guidelines recommended adequate nutritional support for patients with liver cirrhosis to improve clinical outcome and quality of life (QOL). However, these evidences were obtained more ...than 10 years ago when malnutrition prevailed. In recent years, the impact of obesity on liver damage and carcinogenesis has grown. We attempted to elucidate the nutritional state and QOL in present cirrhotics.
Methods
A research group supported by the Ministry of Health, Labor and Welfare of Japan recruited 294 cirrhotics between 2007 and 2011. Subjects comprised 171 males and 123 females, 158 of whom had hepatocellular carcinoma (HCC) and Child–Pugh grades A : B : C were 154:91:49. Anthropometry, blood biochemistry and indirect calorimetry were conducted, and QOL was measured using Short Form‐8.
Results
The mean body mass index (BMI) of all patients was 23.1 ± 3.4 kg/m2, and 31% showed obesity (BMI ≥ 25.0). In subjects without ascites, edema or HCC, mean BMI was 23.6 ± 3.6, and 34% had obesity. Protein malnutrition defined as serum albumin of less than 3.5 g/dL and energy malnutrition as respiratory quotient of less than 0.85 appeared in 61% and 43%, respectively, and protein‐energy malnutrition (PEM) in 27% of all subjects. Among subjects without HCC, each proportion was 67%, 48% and 30%, respectively. QOL was significantly lower on all subscales than Japanese national standard values, but was similar regardless the presence or absence of HCC.
Conclusion
While PEM is still present in liver cirrhosis, an equal proportion has obesity in recent patients. Thus, in addition to guidelines for PEM, establishment of nutrition and exercise guidelines seems essential for obese patients with liver cirrhosis.
Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. ...We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkin’s lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.
Obesity and related metabolic abnormalities, including insulin resistance, are risk factors for hepatocellular carcinoma in non‐alcoholic steatohepatitis as well as in chronic viral hepatitis. ...Branched‐chain amino acids (BCAA), which improve insulin resistance, inhibited obesity‐related colon carcinogenesis in a rodent model, and also reduced the incidence of hepatocellular carcinoma in obese patients with liver cirrhosis. In the present study, we determined the effects of BCAA on the development of diethylnitrosamine (DEN)‐induced liver tumorigenesis in obese C57BL/KsJ‐db/db (db/db) mice with diabetes mellitus. Male db/db mice were given tap water containing 40 ppm DEN for an initial 2 weeks and thereafter they received a basal diet containing 3.0% of BCAA or casein, which served as a nitrogen content‐matched control of BCAA, throughout the experiment. Supplementation with BCAA significantly reduced the total number of foci of cellular alteration, a premalignant lesion of the liver, and the expression of insulin‐like growth factor (IGF)‐1, IGF‐2, and IGF‐1 receptor in the liver when compared to the casein supplementation. BCAA supplementation for 34 weeks also significantly inhibited both the development of hepatocellular neoplasms and the proliferation of hepatocytes in comparison to the basal diet or casein‐fed groups. Supplementation with BCAA improved liver steatosis and fibrosis and inhibited the expression of α‐smooth muscle actin in the DEN‐treated db/db mice. The serum levels of glucose and leptin decreased by dietary BCAA, whereas the value of the quantitative insulin sensitivity check index increased by this agent, indicating the improvement of insulin resistance and hyperleptinemia. In conclusion, oral BCAA supplementation improves insulin resistance and prevents the development of liver tumorigenesis in obese and diabetic mice. (Cancer Sci 2009)
Abstract
We compared the predictive ability of the International Prognostic Index (IPI), a frequently used prognostic model for peripheral T-cell lymphoma (PTCL), with that of a type-specific ...prognostic model, the Prognostic Index for PTCL-U (PIT). We retrospectively analyzed 113 patients diagnosed with PTCL. The median age was 67 years (range, 16–88 years), 75 patients (66%) were male, and the most common disease type was PTCL, not otherwise specified (69%). With a median follow-up of 6.8 years (interquartile range, 2.7–9.9 years), 5-year survival rates for the four groups in IPI were 85%, 62%, 49%, and 13%, respectively. Similarly, 5-year survival rates for the four groups in PIT were 83%, 64%, 49%, and 19%, respectively. The area under the receiving operating characteristic curve for predicting mortality from PIT (0.725) was not significantly different from that from the IPI (0.685,
P
= 0.134). Multivariable analysis showed that performance status ≥ 2 (
P
< 0.0001) and extranodal lesions ≥ 2 (
P
= 0.029) were significantly associated with lower overall survival. The present study found no significant difference in prognostic ability between the IPI and PIT for PTCL, and both models appear useful as predictive models.
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