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1.
Bioresour Technol ; 399: 130642, 2024 May.
Article in English | MEDLINE | ID: mdl-38561154

ABSTRACT

Aqueous galactose solutions containing eggshell was heated at 120 °C to produce calcium supplements containing rare sugars. Galactose was isomerized to rare sugars with improving rare sugar yields compared to those without eggshell. Organic acids were also formed as byproducts during the reaction. These acids were neutralized by dissolving eggshells with increasing the calcium ion concentration in the solution. When eggshell components (calcium carbonate, magnesium carbonate, or calcium phosphate) were used for the treatment, rare sugars were also formed. Especially, addition of magnesium carbonate improved rare sugar yield, but byproduct formation became more pronounced. Eggshells used in the treatment were used for repeated treatments. When eggshells were used three times, rare sugar yield changed only slightly but the selectivity of rare sugars improved significantly. By these processes, we obtained an aqueous solution of rare sugars containing calcium ion at 295 mg/L, which has potential as ingredients for dietary supplements.


Subject(s)
Calcium , Magnesium , Sugars , Animals , Galactose , Egg Shell , Carbohydrates , Water
2.
Cell Death Dis ; 15(1): 53, 2024 01 15.
Article in English | MEDLINE | ID: mdl-38225221

ABSTRACT

Chronic metabolic stress paradoxically elicits pro-tumorigenic signals that facilitate cancer stem cell (CSC) development. Therefore, elucidating the metabolic sensing and signaling mechanisms governing cancer cell stemness can provide insights into ameliorating cancer relapse and therapeutic resistance. Here, we provide convincing evidence that chronic metabolic stress triggered by hyaluronan production augments CSC-like traits and chemoresistance by partially impairing nucleotide sugar metabolism, dolichol lipid-linked oligosaccharide (LLO) biosynthesis and N-glycan assembly. Notably, preconditioning with either low-dose tunicamycin or 2-deoxy-D-glucose, which partially interferes with LLO biosynthesis, reproduced the promoting effects of hyaluronan production on CSCs. Multi-omics revealed characteristic changes in N-glycan profiles and Notch signaling activation in cancer cells exposed to mild glycometabolic stress. Restoration of N-glycan assembly with glucosamine and mannose supplementation and Notch signaling blockade attenuated CSC-like properties and further enhanced the therapeutic efficacy of cisplatin. Therefore, our findings uncover a novel mechanism by which tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation.


Subject(s)
Hyaluronic Acid , Resilience, Psychological , Humans , Glycosylation , Hyaluronic Acid/metabolism , Neoplasm Recurrence, Local/metabolism , Polysaccharides/metabolism , Dietary Supplements , Neoplastic Stem Cells/metabolism
3.
PLoS One ; 17(6): e0269698, 2022.
Article in English | MEDLINE | ID: mdl-35704618

ABSTRACT

Antibiotics disrupt normal gut microbiota and cause dysbiosis, leading to a reduction in intestinal epithelial barrier function. Disruption of the intestinal epithelial barrier, which is known as "leaky gut", results in increased intestinal permeability and contributes to the development or exacerbation of gastrointestinal diseases such as inflammatory bowel disease and irritable bowel syndrome. We have previously reported on a murine model of intestinal epithelial barrier dysfunction associated with dysbiosis induced by the administration of ampicillin and vancomycin. Saireito, a traditional Japanese herbal medicine, is often used to treat autoimmune disorders including ulcerative colitis; the possible mechanism of action and its efficacy, however, remains unclear. In this study, we examined the efficacy of Saireito in our animal model for leaky gut associated with dysbiosis. C57BL/6 mice were fed a Saireito diet for the entirety of the protocol (day1-28). To induce colitis, ampicillin and vancomycin were administered in drinking water for the last seven consecutive days (day22-28). As previously demonstrated, treatment with antibiotics caused fecal occult bleeding, cecum enlargement with black discoloration, colon inflammation with epithelial cell apoptosis, and upregulation of pro-inflammatory cytokines. Oral administration of Saireito significantly improved antibiotics-induced fecal occult bleeding and cecum enlargement by suppressing inflammation in the colon. Furthermore, Saireito treatment ensured the integrity of the intestinal epithelial barrier by suppressing apoptosis and inducing cell adhesion proteins including ZO-1, occludin, and E-cadherin in intestinal epithelial cells, which in turn decreased intestinal epithelial permeability. Moreover, the reduced microbial diversity seen in the gut of mice treated with antibiotics was remarkably improved with the administration of Saireito. In addition, Saireito altered the composition of gut microbiota in these mice. These results suggest that Saireito alleviates leaky gut caused by antibiotic-induced dysbiosis. Our findings provide a potentially new therapeutic strategy for antibiotic-related gastrointestinal disorders.


Subject(s)
Colitis, Ulcerative , Colitis , Ampicillin/metabolism , Animals , Anti-Bacterial Agents , Colitis/metabolism , Colitis, Ulcerative/metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Dysbiosis/chemically induced , Dysbiosis/drug therapy , Dysbiosis/metabolism , Herbal Medicine , Inflammation/metabolism , Intestinal Mucosa/metabolism , Japan , Mice , Mice, Inbred C57BL , Vancomycin/adverse effects
4.
Article in English | MEDLINE | ID: mdl-35487690

ABSTRACT

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2 Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Transurethral Resection of Prostate , Antibodies, Monoclonal, Humanized , Humans , Male , Microsatellite Instability , MutS Homolog 2 Protein/genetics , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics
5.
Surg Case Rep ; 7(1): 112, 2021 May 06.
Article in English | MEDLINE | ID: mdl-33956239

ABSTRACT

BACKGROUND: The antegrade continence enema (ACE) procedure is effective for severe constipation in patients with spina bifida and can improve quality of life (QOL). The Monti-Malone procedure (MM), which is a method of creating an enema tract from the colon, has been reported as an alternative to the ACE procedure when the appendix cannot be used. We report the usefulness of MM as a reconstruction of the antegrade continence enema procedure. CASE PRESENTATION: Our patient was a 22-year-old man with congenital spina bifida and hydrocephalus. Ventriculoperitoneal (VP) shunt surgery was performed immediately after birth, and preventative appendectomy was carried out during VP shunt repair when 4 months old. At 5 years of age, the ACE procedure using a balloon-button gastrostomy tube was performed for intractable chronic constipation. Simple management was expected, but after 17 years of age, he experienced increased stool leakage around the gastrostomy tube and his QOL declined due to difficulty in managing the ACE. Therefore, reconstruction of the ACE procedure by MM was performed. After reconstruction, the ACE performed well without any complications. The patient is currently satisfied because management of the ACE is easier than before, and his QOL has markedly improved without stool leakage and dermatitis. CONCLUSIONS: MM is less likely to cause complications and is useful as a reconstruction of the ACE procedure.

6.
J Clin Biochem Nutr ; 68(2): 181-186, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33879971

ABSTRACT

Vitamin B6 is an important cofactor in fat metabolism and its deficiency has been correlated with nonalcoholic fatty liver disease. However, no study has investigated the efficacy of vitamin B6 supplementation in these patients. The aim of this open-label, single-arm, single-center study was to examine the therapeutic effect of vitamin B6 in patients with nonalcoholic fatty liver disease. Twenty-two patients with nonalcoholic fatty liver disease received vitamin B6 (90 mg/day) orally for 12 weeks. Clinical parameters were evaluated, and liver fat and fibrosis were quantified before and after treatment using magnetic resonance imaging-based proton density fat fraction and magnetic resonance elastography. Serum alanine aminotransferase levels, the primary endpoint, did not change significantly after vitamin B6 treatment (93.6 ± 46.9 to 93.9 ± 46.6, p = 0.976). On the other hand, magnetic resonance imaging-based proton density fat fraction, a parameter of hepatic lipid accumulation, was significantly reduced (18.7 ± 6.1 to 16.4 ± 6.4, p<0.001) despite no significant changes in body mass index, even in those not taking vitamin E (n = 17, 18.8 ± 6.9 to 16.7 ± 7.3, p = 0.0012). Vitamin B6 administration significantly ameliorated hepatic fat accumulation. As an inexpensive agent with few side effects, vitamin B6 could be a novel therapeutic agent for the treatment of nonalcoholic fatty liver disease.

7.
J Food Sci ; 86(3): 867-873, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33580513

ABSTRACT

The solubility of oxygen and its transfer rate to the lipid phase play important roles in lipid oxidation, which affects the taste and safety of lipid-containing foods. In this study, we measured the Henry's constants (solubility) of oxygen for fatty acids, fatty acid esters, and triacylglycerols (TAGs; vegetable oils), as well as the mass transfer coefficients of oxygen at the gas- and water-lipid interfaces. The constants and coefficients were estimated by analyzing the change over time in the oxygen partial pressure or concentration in the closed container based on the mass balance equations of oxygen in the gas and liquid phases. The constant for water obtained by the method used in this study was in agreement with the previously reported value to confirm the validity of the method. The constants for lipids depended on the lipid type, and were higher in the order of fatty acid ester, fatty acid, and TAG. That is, the solubility of oxygen decreased in this order. For all lipids, the constant increased as the number of carbon atoms in the fatty acid chain increased. The constants for fatty acids and their esters were linearly correlated with the enthalpies of evaporation of the lipids. The mass transfer coefficients of oxygen at the gas-liquid interface were on the order of 10-5 m/s for water and methyl dodecanoate and of 10-6 m/s for TAG (rapeseed oil). The coefficient at the water-lipid interface was on the order of 10-6 m/s. PRACTICAL APPLICATION: The Henry's constants (solubility) and transfer rate of oxygen to the lipid phase, fatty acids, fatty acid esters, and triacylglycerols (TAG) were measured. The lipids solubilized three to five times more oxygen than water, and mass transfer rate of oxygen at gas- and water-lipid interfaces were almost same. The constants for fatty acids and fatty acid esters were linearly correlated to their enthalpies of evaporation, and this correlation is expected to be useful for estimating the Henry's constants for other fatty acids and their esters.


Subject(s)
Lipids/chemistry , Oxygen/chemistry , Water/chemistry , Esters/chemistry , Fatty Acids/chemistry , Laurates/chemistry , Lipid Peroxidation , Rapeseed Oil/chemistry , Solubility , Thermodynamics , Triglycerides/chemistry
8.
Urol Oncol ; 39(2): 131.e9-131.e15, 2021 02.
Article in English | MEDLINE | ID: mdl-33127301

ABSTRACT

BACKGROUND: The aim of this study was to investigate the clinical significance of the effect of age on disease control in men who received high-dose intensity-modulated radiation therapy (IMRT) for nonmetastatic prostate cancer (NMPCa). METHODS: NMPCa patients with favorable intermediate to very high-risk features (National Comprehensive Cancer Network risk classification) treated with IMRT at our institution between September 2000 and May 2011 were analyzed retrospectively. Treatment consisted of high-dose IMRT (74-78 Gy/37-39 fractions) combined with 6 months of neoadjuvant hormonal therapy. Multivariable analysis using Fine and Gray's regression model was performed to evaluate whether age at initiation of IMRT was associated with biochemical failure (BF) and castration-resistant prostate cancer (CRPC) progression. RESULTS: A total of 367 patients were analyzed. The median follow-up period was 8.8 years after IMRT. The 5- and 10-year BF rates were 22.1 and 31.7%, and those of CRPC rates were 4.5 and 12.6%, respectively. Multivariable analysis revealed that a younger age (cut-off: 70 years old) at the initiation of IMRT was significantly correlated with both a higher BF rate (hazard ratio: 1.691, P= 0.0064) and higher CRPC rate (hazard ratio: 2.579, P = 0.0079). CONCLUSIONS: Younger men with NMPCa had increased risks of BF and CRPC after high-dose IMRT, and may benefit from more intensive treatments. Our findings should be further tested in prospective studies.


Subject(s)
Prostatic Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Age Factors , Aged , Disease Progression , Humans , Male , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/epidemiology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms, Castration-Resistant/epidemiology , Retrospective Studies , Risk Assessment
9.
Thorac Cancer ; 10(7): 1648-1653, 2019 07.
Article in English | MEDLINE | ID: mdl-31187563

ABSTRACT

A 32-year-old woman was referred to our hospital because of severe psychosis and was found to have an ectopic ACTH-producing thymic neuroendocrine tumor. Laboratory data revealed an elevated serum cortisol and plasma ACTH level, hypokalemia, and metabolic alkalosis. Chest computed tomography (CT) revealed an anterior mediastinal mass and multiple pulmonary nodules. As the patient was unable to communicate because of her consciousness disturbance, she was managed with artificial ventilation and deep sedation. Metyrapone and potassium supplementation were administered, and steroid psychosis gradually improved. Thoracic surgery was performed and the histopathological diagnosis was thymic neuroendocrine tumor with positive anti-ACTH immunohistochemical staining. Here we present details of the case and review the literature.


Subject(s)
Adrenocorticotropic Hormone/blood , Neuroendocrine Tumors/diagnosis , Psychotic Disorders/etiology , Thymus Neoplasms/diagnosis , Adult , Female , Humans , Metyrapone/therapeutic use , Multiple Pulmonary Nodules/diagnostic imaging , Neuroendocrine Tumors/blood , Potassium/therapeutic use , Psychotic Disorders/blood , Psychotic Disorders/drug therapy , Thymus Neoplasms/blood , Tomography, X-Ray Computed
10.
Acta Med Okayama ; 72(5): 535-538, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30369613

ABSTRACT

Some patients with chronic kidney disease (CKD) receiving hemodialysis develop erythropoietin-resistant anemia, possibly due to zinc deficiency. The frequency of zinc deficiency in CKD (stages 1-5 and 5D) and CKD improvement via zinc supplementation are not completely verified. Here 500 CKD patients (Stage 1/2, n=100; Stage 3, n=100; Stage 4, n=100, Stage n=5, 100; Stage 5D, n=100) will be recruited to determine the frequency of serum zinc deficiency at each CKD stage. Patients with serum zinc concentrations <80 µg/dL will be treated with zinc acetate dihydrate (NobelzinR) to evaluate its effects on hypozincemia, taste disturbances, and anemia.


Subject(s)
Anemia/drug therapy , Renal Insufficiency, Chronic/complications , Taste Disorders/drug therapy , Zinc Acetate/therapeutic use , Zinc/deficiency , Adult , Aged , Cross-Sectional Studies , Humans , Middle Aged , Renal Insufficiency, Chronic/blood , Young Adult , Zinc/blood
11.
Genes Cells ; 23(12): 1043-1055, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30353943

ABSTRACT

Antibiotics sometimes exert adverse effects on the pathogenesis of colitis due to the dysbiosis resulting from the disruption of gut homeostasis. However, the precise mechanisms underlying colitogenic effects of antibiotic-induced colitis are largely unknown. Here, we show a novel murine fecal occult bleeding model induced by the combinatorial treatment of ampicillin and vancomycin, which is accompanied by an enlarged cecum, upregulation of pro-inflammatory cytokines IL-6 and IL-12, a reduction in Ki-67-positive epithelial cell number and an increase in the apoptotic cell number in the colon. Moreover, gas chromatography-tandem mass analysis showed that various kinds of metabolites, including glutamic acid and butyric acid, were significantly decreased in the cecal contents. In addition, abundance of butyric acid producer Clostridiales was dramatically reduced in the enlarged cecum. Interestingly, supplementation of monosodium glutamate or its precursor glutamine suppressed colonic IL-6 and IL-12, protected from cell apoptosis and prevented fecal occult blood indicating that the reduced level of glutamic acid is a possible mechanism of antibiotic-induced fecal occult bleeding. Our data showed a novel mechanism of antibiotic-induced fecal occult bleeding providing a new insight into the clinical application of glutamic acid for the treatment of antibiotic-induced colitis.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Colon/pathology , Epithelial Cells/pathology , Metabolic Diseases/complications , Occult Blood , Administration, Oral , Ampicillin/administration & dosage , Ampicillin/pharmacology , Animals , Antimicrobial Cationic Peptides/metabolism , Butyric Acid/pharmacology , Carbohydrate Metabolism/drug effects , Cecum/microbiology , Cell Line, Tumor , Cell Proliferation/drug effects , Colonic Neoplasms/pathology , Cytokines/metabolism , Glutamine/administration & dosage , Lipid Metabolism/drug effects , Macrophages/drug effects , Macrophages/metabolism , Metabolome/drug effects , Metagenomics , Mice , Microbiota/drug effects , Microbiota/genetics , RAW 264.7 Cells , Regeneration/drug effects , Sodium Glutamate/administration & dosage , Species Specificity , Vancomycin/administration & dosage , Vancomycin/pharmacology
12.
Ann Palliat Med ; 6(Suppl 1): S52-S57, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28866892

ABSTRACT

BACKGROUND: Several studies indicated that plasma L-carnitine (LC) levels are significantly decreased during chemotherapy or chemoradiation and that LC supplementation can improve the fatigue score in some cancer patients. However, the LC levels in end-stage cancer patients treated only with palliative care remained unclear. The present study was performed to examine the plasma LC levels of terminally ill and hospitalized patients. METHODS: Twenty-one terminally ill cancer patients in our hospital, with expected survival of several months, were enrolled in the present study. Blood samples were taken for measurement of total, free, and acyl-LC. These values were compared with those in 22 chemo-naive cancer patients scheduled to receive cisplatin-containing chemotherapy as first-line therapy. We examined the relationships with body mass index, albumin and CRP levels, the presence of general fatigue, and body weight loss. RESULTS: Median survival in terminally ill cancer patients after enrollment was 38.5 days. Plasma concentrations of total, free, and acyl-LC in terminally ill cancer patients were 59.5±16.0, 46.1±14.2, and 13.4±5.9 µmol/L, respectively. These values were not significantly different from those in chemo-naive patients (58.3±18.1, 48.7±16.3, and 9.6±3.3 µmol/L, respectively). In addition, plasma LC levels in terminally ill patients showed no correlations with albumin or CRP values nor with other clinical parameters, such as fatigue or body weight loss. CONCLUSIONS: The present study suggested that plasma LC levels remain normal and its deficiency is not always common even in terminally ill and hospitalized palliative cancer patients.


Subject(s)
Carnitine/blood , Hospitalization , Neoplasms/blood , Terminally Ill , Case-Control Studies , Female , Humans , Japan , Male , Middle Aged , Neoplasms/mortality , Palliative Care , Prognosis , Prospective Studies
13.
Jpn J Clin Oncol ; 47(4): 313-320, 2017 Apr 01.
Article in English | MEDLINE | ID: mdl-28100684

ABSTRACT

OBJECTIVE: Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer. METHODS: This retrospective study enrolled 131 patients with stage III colorectal cancer who underwent curative resection: 72 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 59 did not (surgery-alone group). Poorly differentiated cluster was defined as a cancer cluster of ≥5 cancer cells without gland-like structure, and was classified into poorly differentiated cluster G1, G2 and G3 according to the number of clusters. The benefit of 5-fluorouracil-based adjuvant chemotherapy was evaluated based on poorly differentiated cluster grade. RESULTS: Thirty-nine, 40 and 52 patients were classified as poorly differentiated cluster G1, G2 and G3, respectively. Significant differences in the 5-year cumulative recurrence rate and relapse-free survival were observed between poorly differentiated cluster G1/G2 and G3 (26.7% vs. 47.5%, P = 0.010; 66.0% vs. 43.9%, P = 0.004). A comparison of cumulative recurrence rate and relapse-free survival between the chemotherapy and surgery-alone groups showed a significant benefit of adjuvant chemotherapy in poorly differentiated cluster G1/G2 patients (cumulative recurrence rate: 17.4% vs. 37.3%, P = 0.035; relapse-free survival: 79.5% vs. 51.9%, P = 0.002), but not in poorly differentiated cluster G3 patients (cumulative recurrence rate: 48.6% vs. 44.8%, P = 0.885; relapse-free survival: 51.4% vs. 32.7%, P = 0.068). CONCLUSIONS: In stage III colorectal cancer, poorly differentiated cluster G1/G2 predicts a significant benefit from 5-fluorouracil-based adjuvant chemotherapy, whereas poorly differentiated cluster G3 predicts a poor response to it.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Chemotherapy, Adjuvant/methods , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Staging , Prognosis , Retrospective Studies
14.
Acute Med Surg ; 3(1): 36-38, 2016 01.
Article in English | MEDLINE | ID: mdl-29123746

ABSTRACT

Case: We report a case with concurrent ingestion of carbamazepine (CBZ) overdose and grapefruit juice. A 23-year-old man, with a history of epilepsy, was admitted to our emergency department 2 h after ingesting 10 g CBZ with 1 L grapefruit juice. On arrival, the patient's Glasgow Coma Scale score was 9 and he showed signs of restlessness. Grapefruit juice-like gastric fluid, with tablet residue, was observed in his stomach after we inserted a gastric tube. Our initial test detected a blood CBZ level of 41.5 mg/L. Outcome: We treated the patient with gastric lavage, activated charcoal, and charcoal hemoperfusion. His blood CBZ level began to decrease after gastrointestinal decontamination, and he was discharged without any sequelae on day 9. Conclusion: Gastric lavage or aspiration may be considered in cases where drug residue is found in the stomach, especially if materials are involved that might exacerbate the drug's toxicity.

15.
Gan To Kagaku Ryoho ; 42(12): 2184-6, 2015 Nov.
Article in Japanese | MEDLINE | ID: mdl-26805305

ABSTRACT

A 58-year-old woman was diagnosed with a sigmoid colon cancer and synchronous liver metastasis. Because an obstruction of the sigmoid colon was identified, the patient underwent sigmoidectomy. Computed tomography(CT)findings suggested possible vena cava and hepatic vein invasion. Therefore, the decision was made to offer systemic chemotherapy. The patient underwent 6 courses of chemotherapy with 5-fluorouracil, Leucovorin, and oxaliplatin (mFOLFOX6). After 4 courses of chemotherapy, CT scans showed a significant reduction of the liver metastasis (reduction rate of 5 0%; a partial response) and demonstrated improved exclusion of the inferior vena cava and hepatic vein. After 6 courses of chemotherapy, we performed right trisegmentectomy of the liver and resection of the inferior vena cava and diaphragm. Postoperative pathological findings revealed negative margins, and no invasion of the inferior vena cava. The pathological response grade of the tumor after chemotherapy was determined to be Grade 2. Adjuvant chemotherapy was not performed because of the patient 's poor performance status. The patient was alive with no recurrence 8 years after resection of the liver metastasis.


Subject(s)
Liver Neoplasms/secondary , Sigmoid Neoplasms/pathology , Vena Cava, Inferior/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Middle Aged , Neoplasm Invasiveness , Organoplatinum Compounds/therapeutic use , Sigmoid Neoplasms/drug therapy , Sigmoid Neoplasms/surgery , Time Factors , Vena Cava, Inferior/surgery
16.
J Chromatogr A ; 1370: 246-54, 2014 Nov 28.
Article in English | MEDLINE | ID: mdl-25454149

ABSTRACT

To assess food safety emergencies caused by highly hazardous chemical-tainted foods, simultaneous analysis of organophosphorus insecticides in fatty foods such as precooked foods was conducted using thin-layer chromatography/direct analysis in real time time-of-flight mass spectrometry (TLC/DART-TOFMS) and isotope dilution technique. Polar (methamidophos and acephate) and nonpolar organophosphorus insecticides (fenitrothion, diazinon, and EPN) were studied. Experiments to ascertain chromatographic patterns using TLC/DART-TOFMS reveal that it was more useful than GC/MS or GC/MS/MS for the simultaneous analyses of polar and nonpolar pesticides, while obviating the addition of a protective agent for tailing effects of polar pesticides. Lower helium gas temperature (260°C) for DART-TOFMS was suitable for the simultaneous analysis of target pesticides. Linearities were achieved respectively at a lower standard concentration range (0.05-5 µg) for diazinon and EPN and at a higher standard concentration range (2.5-25 µg) for methamidophos, acephate, and fenitrothion. Their respective coefficients of determination were ≥ 0.9989 and ≥ 0.9959. A few higher repeatabilities (RSDs) for diazinon and EPN were found (>20%), although isotope dilution technique was used. Application to the HPTLC plate without an automatic TLC sampler might be inferred as a cause of their higher RSDs. Detection limits were estimated in the higher picogram range for diazinon and EPN, and in the lower nanogram range for methamidophos, acephate, and fenitrothion. Aside from methamidophos, recovery results (n=3) obtained using a highly insecticide-tainted fatty food (dumpling) and raw food (grapefruit) samples (10mg/kg) using TLC/DART-TOFMS with both complex and simpler cleanups were not as susceptible to matrix effects (95-121%; RSD, 1.3-14%) as those using GC/MS/MS (102-117%; RSD, 0.4-8.5%), although dumpling samples using GC/MS were remarkably susceptible to matrix effects. The coupled method of TLC with simpler cleanup and DART-TOFMS can be regarded as the same analytical tool as GC/MS/MS, which is useful to assess food safety emergencies caused by highly hazardous chemical-tainted foods.


Subject(s)
Chromatography, Thin Layer/methods , Fats/chemistry , Food Analysis/methods , Insecticides/analysis , Mass Spectrometry/methods , Phosphorus/analysis , Chromatography, High Pressure Liquid , Indicator Dilution Techniques , Isotopes , Time Factors
17.
Int J Clin Exp Pathol ; 7(4): 1299-313, 2014.
Article in English | MEDLINE | ID: mdl-24817927

ABSTRACT

Sorafenib is a multi-kinase inhibitor approved for hepatocellular carcinoma, but rarely causes tumor regression in patients with chronic liver diseases. To investigate whether growth factor-mediated signaling is involved in sorafenib resistance, HepG2 and PLC/PRF/5 hepatoma cells were exposed to epidermal growth factor (EGF), hepatocyte growth factor (HGF) or transforming growth factor-ß (TGF-ß) prior to treatment with sorafenib. Furthermore, to identify an effective combination treatment with sorafenib, growth factor-sensitized cells were treated with sorafenib alone or in combination with celecoxib, lovastatin or valproic acid (VPA). Trypan blue staining and Annexin V assays showed that the cytotoxic effect of sorafenib was inhibited by 15-54% in cells sensitized to TGF-ß (P<0.05). Western blotting analysis showed that TGF-ß significantly activated extracellular signal-regulated kinase (ERK)-mediated AKT signaling, and sorafenib failed to suppress both ERK and AKT in TGF-ß-sensitized cells. The decreased anti-tumor effect of sorafenib was rescued by chemical inhibition of ERK and AKT. When TGF-ß-sensitized cells were treated with sorafenib plus VPA, the levels of phosphorylated ERK and AKT were considerably suppressed and the numbers of dead cells were increased by 3.7-5.7-fold compared with those exposed to sorafenib alone (P<0.05). Moreover, low dose sorafenib-induced cell migration was effectively suppressed by combination treatment with sorafenib and VPA. Collectively, TGF-ß/ERK/AKT signaling might play a critical role in sorafenib resistance in hepatoma cells, and combination treatment with VPA may be effective against this drug resistance.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Drug Resistance, Neoplasm , Enzyme Inhibitors/therapeutic use , Liver Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Transforming Growth Factor beta/physiology , Valproic Acid/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/drug effects , Drug Resistance, Neoplasm/drug effects , Enzyme Inhibitors/pharmacology , Humans , Liver Neoplasms/pathology , MAP Kinase Signaling System/drug effects , Niacinamide/therapeutic use , Proto-Oncogene Proteins c-akt/drug effects , Signal Transduction/drug effects , Sorafenib , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/drug effects , Treatment Failure , Treatment Outcome , Valproic Acid/pharmacology
18.
Gan To Kagaku Ryoho ; 41(12): 1677-9, 2014 Nov.
Article in Japanese | MEDLINE | ID: mdl-25731293

ABSTRACT

A 71 -year-old man was referred to our hospital because of repeated bowel obstruction. He had previously undergone cystectomy with ileal conduit urinary diversion for the treatment of bladder cancer at the age of 28 years. Computed tomography revealed a mass in the ascending colon. Ileostomy was initially performed because of poor general condition that improved with postoperative nutrition management. Enema findings revealed ascending colon cancer and we therefore decided to perform curative surgery. Intraoperative findings revealed that the ascending colon cancer had invaded the ileal conduit. However, it was confirmed that the ureter-ileal conduit anastomosis and the mesentery of the ileal conduit could be preserved. We performed right colectomy and partial resection of the ileal conduit with curative intent. The pathological stage was pT4bpN0cM0, pStage II. There were no signs of recurrence 15 months after curative surgery.


Subject(s)
Colon, Ascending/pathology , Colonic Neoplasms/pathology , Aged , Colon, Ascending/surgery , Colonic Neoplasms/surgery , Humans , Male , Neoplasm Invasiveness , Neoplasm Staging , Tomography, X-Ray Computed , Urinary Diversion
19.
Gan To Kagaku Ryoho ; 41(12): 2364-6, 2014 Nov.
Article in Japanese | MEDLINE | ID: mdl-25731524

ABSTRACT

A 70-year-old man was referred to our hospital with ascending colon cancer (cT3N1M0, Stage IIIa), which was found during examinations following a positive fecal occult blood test. The patient was also diagnosed with early gastric cancer (cT1a, N0, M0, Stage IA)during a preoperative gastroscopy examination. A laparoscopically assisted right colectomy and D3 lymphadenectomy was performed for the ascending colon cancer. The postoperative pathological diagnosis was Stage IIIb (pT3N2), he was administered in combination with capecitabine plus oxaliplatin (CapeOX) as adjuvant chemotherapy before the treatment for the colon cancer. After 6 months of adjuvant chemotherapy, we were unable to detect any gastric lesions at the same location using gastroscopy, and so diagnosed a clinical complete response. A follow-up gastroscopy 6 months later showed the same findings. The patient has had no recurrence of gastric cancer for 18 months after the initial operation. He will continue to be followed up closely using gastroscopy. In this case, CapeOX as adjuvant chemotherapy for advanced colon cancer was also effective for early gastric cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colon, Ascending/pathology , Colonic Neoplasms/drug therapy , Neoplasms, Multiple Primary/drug therapy , Stomach Neoplasms/drug therapy , Aged , Capecitabine , Chemotherapy, Adjuvant , Colectomy , Colon, Ascending/surgery , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Male , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Stomach Neoplasms/pathology
20.
Biosci Biotechnol Biochem ; 77(10): 2112-6, 2013.
Article in English | MEDLINE | ID: mdl-24096678

ABSTRACT

Rice stems were subjected to a subcritical fluid treatment at 230 °C, using ethanol or acetone at a dilution of 0-100% in water. The obtained extracts were determined for their yield, carbohydrate content, phenolic content, DPPH radical scavenging ability, and color. The highest yield and carbohydrate content were achieved with the subcritical 20% (v/v) organic solvent, while the highest phenolic content was obtained with subcritical 80% (v/v) acetone. The highest radical scavenging ability was achieved with subcritical 60% (v/v) ethanol and 80% (v/v) acetone. The lightness of the extracts obtained with subcritical ethanol and acetone was negatively correlation with their radical scavenging ability (R=-0.85). The relationship between the lightness and phenolic content of the extracts was not significant, suggesting that other substances in the extract could also possess radical scavenging ability.


Subject(s)
Free Radical Scavengers/chemistry , Free Radical Scavengers/isolation & purification , Oryza/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Stems/chemistry , Biphenyl Compounds/chemistry , Carbohydrates/analysis , Phenol/analysis , Picrates/chemistry , Pigmentation
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