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Background Germination of mung beans increases the content of dietary fiber, vitamin C, antioxidants, and γ-aminobutyric acid (GABA). Atmospheric cold plasma is a recently developed technology that can rapidly modify the surface properties of an object. In this work, atmospheric cold plasma was utilized to promote higher moisture absorption of mung bean seeds and, thus, enhance the germination ratio and GABA level. The selected healthy seeds that were exposed to plasma generated at different ionizing powers. Result According to the experimental results, atmospheric cold plasma treatments on mung bean seeds could induce significantly more water absorption and lead to a higher rate of germination. The physical appearance of the sprout developed after plasma treatment was noticeably modified to a more desirable form, which has a short radicle and longer hypocotyls with a larger diameter. The content of the bioactive component GABA in plasma-treated beans was approximately three times higher than the untreated group due to the response of seed to the environmental stress created by the plasma treatment. Conclusion The result from this work will serve as a good reference for future investigation that is searching for a solution to enhance bioactive compound production in natural products. © 2021 Society of Chemical Industry.

BACKGROUND Post-treatment decline in serum alpha-foetoprotein (AFP) levels has been shown to predict the treatment efficacy of antiangiogenic therapy for advanced hepatocellular carcinoma (HCC). We explored whether a decline in AFP levels was also associated with treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with advanced HCC. METHODS We reviewed all patients who received ICI therapy for advanced HCC. AFP response was evaluated in patients with the pretreatment AFP level of >20 ng/mL. We defined early AFP response as a >20% decline in serum AFP levels within the first 4 weeks of treatment initiation relative to pretreatment levels. We then studied whether early AFP response was associated with treatment outcomes. RESULTS Sixty patients were enrolled in this study; 43 of them were evaluable for early AFP response. The objective response rate of early AFP responders was significantly higher than that of early AFP nonresponders (73% vs. 14%, P

Background and Aim The immune modulatory drug lenalidomide has shown promising anti-tumor activity in a clinical trial of patients with advanced hepatocellular carcinoma (HCC). The present study explored whether lenalidomide can enhance the anti-tumor activity of sorafenib, the standard molecular targeted therapy for HCC. Methods The anti-tumor efficacy of single-agent or combination treatment was measured by change in tumor volume and animal survival using an orthotopic liver cancer model. Distribution of T-cell subpopulations in tumor-infiltrating lymphocytes (TILs) and splenocytes derived from tumor-implanted mice was measured by flow cytometry. Depletion of relevant T-cell subpopulations or cytokines was done by co-administration of relevant antibodies with study drug treatment. Tumor cell apoptosis and tumor angiogenesis were measured by transferase deoxytidyl uridine end labeling assay and immunohistochemical study, respectively. Results Combination of sorafenib and lenalidomide produced significant synergistic anti-tumor efficacy in terms of tumor growth delay and animal survival. This synergistic effect was associated with a significant increase in interferon-γ expressing CD8+ lymphocytes in TILs and a significantly higher number of granzyme- or perforin-expressing CD8+ T cells, compared with vehicle- or single-agent treatment groups. Combination treatment significantly increased apoptotic tumor cells and vascular normalization in tumor tissue. The synergistic anti-tumor effect was abolished after CD8 depletion. Conclusions Lenalidomide can enhance the anti-tumor effects of sorafenib in HCC through its immune modulatory effects, and CD8+ TILs play an important role in the anti-tumor synergism.

Background and Aim Biliary tract carcinomas (BTCs) are difficult to diagnose and treat. Epidermal growth factor receptor (EGFR) represents a therapeutic target for the BTCs. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, predict the sensitivity to anti-EGFR treatment. The aims of this study were to analyze the EGFR, KRAS and BRAF mutations in BTCs and their association with clinical outcomes. Methods Paraffin-embedded specimens containing 137 BTCs resected at the National Taiwan University Hospital between 1995 and 2004 were analyzed. The exons 18–21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V600E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTCs. Results Thirteen (9.5%) BTC patients had EGFR mutations while 23 (16.8%) patients had KRAS mutations. Only one patient had BRAF mutation. Factors influencing survival on univariate analysis were tumor stage, tumor differentiation, and EGFR mutation. On multivariate analysis, EGFR mutation and tumor stage were independent prognostic factors. A correlation between KRAS or BRAF mutations and prognosis was not observed. Conclusions EGFR and KRAS mutations are not uncommon in BTCs. BRAF mutation is rare in BTCs. EGFR mutation was an independent prognostic marker in BTCs in addition to tumor stage and differentiation. No simultaneous EGFR and KRAS mutations in extrahepatic cholangiocarcinoma and gallbladder carcinoma were found. EGFR and KRAS mutations should be evaluated when tailoring molecular-targeted therapy to patients with BTCs.

Background & Aims For patients with advanced hepatocellular carcinoma (HCC) who have failed first-line anti-angiogenic therapy, there is no salvage treatment. Hepatic arterial infusion of chemotherapy (HAIC) has been reported to achieve substantial treatment responses in HCC patients. We aimed to explore the feasibility of using HAIC as second-line therapy for advanced HCC. Methods We retrospectively reviewed all consecutive patients who received HAIC for advanced HCC after failure of first-line anti-angiogenic therapy at a single institute. Patients received HAIC with 60 mg/m2 cisplatin on Day 2, and 500 mg/m2/d dose of 5-fluorouracil on Days 1–3. The treatment was repeated every 21 days and continued until disease progression or the occurrence of intolerable toxicities. Tumour assessment was performed after every 3 cycles of HAIC following RECIST criteria, version 1.0. Results A total of 23 patients were included. Eleven (48%) patients had main portal vein thrombosis. Liver reserve was classified as Child-Pugh A in 19 (83%) patients and B in 4 (17%) patients. No complete response was observed, although 6 (26%) patients showed partial responses. The median progression-free survival was 4.4 months, and the median overall survival was 7.5 months. Common toxicities included bone marrow suppression, elevated transaminase levels, neutropenia, nausea and malaise. Only 7 (30%) patients experienced grade 3 or 4 toxicities, and no patients withdrew from the therapy because of intolerable or life-threatening toxicities. Conclusion HAIC is a feasible second-line therapy for patients with advanced HCC who have failed anti-angiogenic therapy.

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents.

Aim: Radiotherapy (RT) has been used to treat hepatocellular carcinoma (HCC) in recent years. Despite its good local control, slow tumoral shrinkage and rapid recurrence compromise treatment outcomes. We evaluated the signal intensity of the hepatic parenchyma and tumours by using dynamic contrast enhanced magnetic resonance imaging (MRI) and correlated the findings with clinical outcomes. Nineteen patients with advanced HCC received 50 Gy in 25 fractions. They underwent a dynamic contrast-enhanced, turbo fast low-angle shot MR sequence at 1.5 T before therapy, at 2 weeks of therapy, and 1 month (week 9) later. Initial first-pass enhancement slopes (slope) and peak enhancement ratios (peak) were measured. Results: Initial signal intensities were not associated with RT outcomes. An increased slope and peak of the tumour at week 2 was associated with an improved local response (P

Background and Aim: The caudal-type homeodomain transcriptional factor CDX2, a member of the caudal-related homeobox gene family, plays a crucial role in the regulation of cell proliferation and differentiation in the gut. Recent studies have reported that expression of CDX2 was an independent marker of outcome in patients with resected adenocarcinoma of ampulla of Vater, gastric cancer, and colon cancer. The clinicopathological significance of CDX2 expression has hitherto remained unclear in biliary tract carcinoma (BTC). The aim of this study was to determine whether CDX2 expression in BTC indicates clinical outcome. Methods: The expression of CDX2 was investigated immunohistochemically in surgically resected specimens from 164 patients with BTC, including 74 intrahepatic cholangiocarcinomas, 49 extrahepatic cholangiocarcinomas, and 41 gallbladder carcinomas. The correlation between expression of CDX2 and clinicopathological factors, including overall survival, tumor location, tumor stage, and degree of tumor differentiation, was examined in patients with BTC. Results: In total, 27 of the 164 (16.46%) patients with BTC expressed CDX2. The frequency of CDX2 expression was much higher in the extrahepatic cholangiocarcinomas (22.45%) and gallbladder carcinomas (29.27%) than in the intrahepatic cholangiocarcinomas (5.41%), the difference being statistically significant (P = 0.002). Factors influencing survival on univariate analysis were tumor stage (P

BACKGROUND. Chemonaive patients had higher response rates than chemotherapy-treated patients in previous analyses of East Asian patients with advanced nonsmall cell lung cancer. The survival outcome and the predictors for antitumor activity in chemonaive patients who received gefitinib as first-line treatment are unclear. METHODS. Clinicopathologic predictive factors, objective tumor responses, and the survival of consecutive patients with advanced, chemonaive nonsmall cell lung cancer who received gefitinib as first-line treatment were collected and analyzed. Multivariate analysis was conducted to determine independent predictive factors for gefitinib antitumor efficacy. RESULTS. One hundred ninety-six patients (112 males and 84 females) were analyzed. Ninety-six patients (49%) were never smokers. One hundred forty-four patients (73%) had adenocarcinoma or bronchioloalveolar carcinoma histology. One hundred twenty patients had an Eastern Cooperative Oncology Group performance status 0 to 2. Eighty-three patients (42%; 95% confidence interval, 36–49%) had an objective tumor response. An additional 35 patients had stable disease (disease control rate, 61%). The tumor response rate was 52% in patients who had a good performance status. Female gender, nonsmoking status, and adenocarcinoma histology all were independent predictors of response or disease control in multivariate analysis. The median survival was 11.1 months, and the 1-year survival rate of patients who had a good performance status was 47.5%. CONCLUSIONS. The response rate to gefitinib was high in East Asian chemonaive patients with advanced nonsmall cell lung cancer. Female gender, adenocarcinoma histology, and nonsmoking status all were independent predictors of gefitinib response. The survival outcome of these patients was similar to that of patients who initially received chemotherapy. Cancer 2006. © 2006 American Cancer Society.

BACKGROUND Both paclitaxel and cisplatin are active as second-line chemotherapy for patients with breast carcinoma. A synergistic cytotoxicity of these two drugs has been demonstrated in vitro. This study sought to determine the efficacy of combining these two drugs in the treatment of chemotherapy-naive patients with breast carcinoma. METHODS The inclusion criteria for the study were 1) women with histologically proven breast carcinoma; 2) locally advanced disease, as defined by American Joint Committee on Cancer (AJCC) Stage T4 (locally advanced breast carcinoma [LABC]) or clinically proven metastases (metastatic breast carcinoma [MBC]); and 3) no prior cytotoxic chemotherapy. The regimen consisted of paclitaxel 175 mg/m2 intravenously by 3-hour infusion immediately followed by cisplatin 50 mg/m2 intravenously by 24-hour infusion on Day 1 and repeated every 3 weeks. After a maximal response to chemotherapy was achieved, patients with LABC underwent resection of their primary tumor if the procedure was not contraindicated. RESULTS From July, 1999 to January, 2001, 46 patients were enrolled into this study (28 patients with LABC and 18 patients with MBC). Their median age was 49.5 years (range, 29.8–65.5 years). A total of 205 cycles of chemotherapy were given. All patients were evaluable for toxicity, and 45 patients were evaluable for response. There were 3 complete responses (CRs) and 24 partial responses (PRs), for an overall response rate of 58.7% (95% confidence interval, 44.5–72.9%). Grade 4 hypersensitivity (asthma) to paclitaxel occurred in one patient. Grade 3–4 nausea and emesis and Grade 3–4 myelosuppression occurred in six patients and four patients, respectively. Of the 28 patients with LABC, 2 patients achieved a CR, and 14 patients achieved a PR. Twenty-seven patients underwent mastectomy patients after chemotherapy. A pathologic CR was documented in one patient. Postoperatively, 23 patients with LABC received adjuvant chemotherapy, and 18 patients with LABC received adjuvant radiotherapy. During a median follow-up of 14.6 months, 5 of 28 patients with LABC developed recurrent disease, and 2 patients died of progressive disease, whereas 3 of 18 patients with MBC died of progressive disease. CONCLUSIONS The combination of paclitaxel by 3-hour infusion and cisplatin by 24-hour infusion appears to be an active and well-tolerated regimen for chemotherapy-naive patients with LABC or MBC. Cancer 2002;95:2044–50. © 2002 American Cancer Society. DOI 10.1002/cncr.10951

BACKGROUND The overexpression of HER-2/neu oncogene has been implicated in the development and modulation of many types of cancer. However, whether HER-2/neu overexpression plays a similar role in hepatocellular carcinoma (HCC) has not been determined. METHODS Tissue specimens from 36 HCC patients who had been enrolled in 3 separate prospective clinical trials of systemic chemotherapy were studied by immunohistochemical staining. A polyclonal antibody (A0485; DAKO, Copenhagen, Denmark) against HER-2/neu and a horseradish peroxidase-based visualization system (Envision+, DAKO) was used. Scoring criteria was in accordance with the manufacturer's guidelines. Twelve HCC cell lines were examined for HER-2/neu overexpression by Western blotting. Single-agent growth regulatory activity of the anti–HER-2/neu antibody, trastuzumab (Herceptin; Genentech, South San Francisco, CA), and its combinative cytotoxicity with chemotherapeutic agents (doxorubicin, gemcitabine, cisplatin, irinotecan) were determined by a tetrazolium-based colorimetric assay (MTT test). RESULTS All but one of the HCC tumor tissues were negative for HER-2/neu expression. The only patient with positive HER-2/neu expression was a 57-year-old male patient who achieved stabilization of disease for 2 months after chemotherapy. Eight of the 35 patients with negative HER-2/neu expression had had partial remission after chemotherapy (P = 0.78). Only one (Tong cells) of the 12 HCC cell lines had a significant level of HER-2/neu expression. However, trastuzumab up to 10 μg/mL had no discernible growth inhibitory or chemosensitizing effect on Tong cells or any other cell lines. CONCLUSIONS HER-2/neu overexpression is rare in human HCC tissues, and anti–HER-2/neu regulation appears to play little role in the treatment of this tumor. Cancer 2002;94:415–20. © 2002 American Cancer Society.

BACKGROUND Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy. METHODS The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988–December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 (range, 1–21). RESULTS Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17–124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary. Cancer 2001;91:49–56. © 2001 American Cancer Society.

Division of Cancer Research, National Health Research Institutes, Taipei, TaiwanThe optimal treatment of localized large-cell lymphoma of the stomach remains contro-versial. In particular, the role of surgical resection of the primary tumor needs to beclearly defined. We have reviewed all patients with a diagnosis of gastric lymphoma andtreated in our institutions between 1988 and 1998. Patients fulfilling the following criteriawere included in this study: (1) histologically proven large-cell lymphoma of the stomach;(2) adequate pathological materials and complete clinical information for analysis; (3)clinical stage I/II disease according to the Musshoff modification of Ann Arbor system;and (4) received primary chemotherapy alone with anthracycline- or anthracenedione-containing regimens (group A) or curative surgery followed by adjuvant chemotherapy(group B). There were 38 and 21 patients in group A and group B, respectively. Allpertinent clinicopathologic features were similar between the two groups of patients,except that patients of group A had significantly more stage II-2 disease (P= 0.004). Ofgroup A, among 36 patients who could be evaluated for response to chemotherapy, therewere 29 complete and 1 partial responses, with an overall response rate of 83.3% (95% CI,71.1–95.5%). The projected 5-year relapse-free survival (RFS) and overall survival (OS)were 86.0% (95% CI, 73.3–98.7%) and 72.6% (95% CI, 57.0–88.2%), respectively. On theother hand, the projected 5-year RFS and OS of group B were 77.9% (95% CI, 58.0–97.8%)and 77.8% (95% CI, 57.9–97.7%), respectively, not significantly different from that ofgroup A. Our data suggest that systemic chemotherapy alone may be a reasonablealternative treatment for stage I/II large-cell lymphoma of the stomach. Resection of theprimary tumor before systemic chemotherapy does not appear to improve the cure rateof this group of patients. Am. J. Hematol. 64:175–179, 2000.