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1.
Mol Clin Oncol ; 16(1): 11, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34881031

ABSTRACT

Pseudocirrhosis is a rare but important complication of metastatic cancer. We herein present the case of a patient with pseudocirrhosis occurring after a complete response to chemotherapy for metastatic gastric cancer was achieved. A 72-year-old man was diagnosed with gastric adenocarcinoma with multiple liver metastases. The patient's general condition was good, with an Eastern Cooperative Oncology Group performance status of 1. Chemotherapy with oxaliplatin and S-1 was initiated and, after four cycles, the patient noticed sudden abdominal distension. Despite the marked regression of the liver metastases, massive ascites, segmental atrophy and esophageal varices developed, findings consistent with pseudocirrhosis. The patient achieved complete response for the primary and metastatic lesions. Following endoscopic ligation of the varices, he underwent subsequent chemotherapy with S-1 only and management of his ascites for 6 months. At 12 months after initial chemotherapy, the patient appeared to be disease-free. In conclusion, clinicians should be aware of the possibility of pseudocirrhosis in cases of cancer metastasis to the liver, including metastatic gastric cancer.

2.
Scand J Gastroenterol ; 57(4): 493-500, 2022 04.
Article in English | MEDLINE | ID: mdl-34951833

ABSTRACT

BACKGROUND: Expanding indications for neoadjuvant chemotherapy (NAC) for resectable pancreatic cancer prolong the period from diagnosis to surgery. In resectable pancreatic cancer with malignant biliary obstruction (MBO), the biliary drainage method without any biliary events is ideally required to safely perform NAC as planned. Plastic stents (PS) have been traditionally used for preoperative biliary drainage; however, recently, covered self-expandable metallic stents (CSEMS) have emerged as a tool for preoperative biliary drainage. AIMS: To compare CSEMS with PS for preoperative biliary drainage in the management of resectable pancreatic cancer with MBO. METHODS: In this multicenter retrospective cohort study, we compared CSEMS with PS for preoperative biliary drainage in patients with pancreatic cancer at three tertiary care centers between 2008 and 2019. RESULTS: Of the 120 enrolled patients, 45 underwent CSEMS and 75 underwent PS. No significant difference was observed in the basic characteristics between the groups. The rate of recurrent biliary obstruction (RBO) was significantly lower and the time to RBO was significantly longer in the CSEMS group. In multivariate analysis, CSEMS was an independent factor for a longer RBO. However, pancreatitis and cholecystitis were more common in the CSEMS group. The surgery-related adverse events were not significantly different between the two groups, except for longer surgery time and time to discharge in the CSEMS group. CONCLUSIONS: CSEMS for preoperative endoscopic biliary drainage in patients with pancreatic cancer reduced RBO, although the risk for pancreatitis or cholecystitis could be increased.


Subject(s)
Cholecystitis , Cholestasis , Pancreatic Neoplasms , Pancreatitis , Self Expandable Metallic Stents , Cholangiopancreatography, Endoscopic Retrograde , Cholestasis/etiology , Cholestasis/surgery , Drainage , Humans , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Plastics , Retrospective Studies , Stents , Treatment Outcome , Pancreatic Neoplasms
3.
Cell Immunol ; 369: 104437, 2021 11.
Article in English | MEDLINE | ID: mdl-34530344

ABSTRACT

Here, we investigated the effect of Th1 polarization in the tumor microenvironment (TME) on tumor-associated macrophage (TAM) maturation and activation. In our immunotherapy mouse model, with a Th1-dominant TME, tumors regressed in all cases, with complete regression in 80% of the cases. Monocyte-derived dendritic cells and activated CD4+ and CD8+T-cells increased in the tumor-draining lymph node, and correlated with each other in the therapeutic model. However, the cytotoxicity of tumor-infiltrating CD8+T-cells was slightly inhibited, whereas the number of T-cells significantly increased. Moreover, the number of TAMs increased; their maturation was inhibited; and nitrotyrosine (NT) production, as well as iNOS and arginase I expression, was increased, suggestive of the myeloid-derived suppressor cell-like immunosuppressive function of TAMs. IFN-γ knockout in the therapeutic model decreased NT production and induced macrophage maturation. Hence, Th1 polarization in the IFN-γ-dominant condition induces T-cell immune responses; however, it also enhances the immunosuppressive activity of TAMs.


Subject(s)
Macrophages/immunology , Myeloid-Derived Suppressor Cells/immunology , Neoplasms, Experimental/immunology , Th1 Cells/immunology , Tumor Microenvironment/immunology , Animals , Male , Mice , Mice, Inbred C57BL , Tumor Escape/immunology
4.
Gan To Kagaku Ryoho ; 45(10): 1549-1551, 2018 Oct.
Article in Japanese | MEDLINE | ID: mdl-30382074

ABSTRACT

From January 2016 through December 2017, 18 patients received paclitaxel plus ramucirumab combination therapy and 1 patient received ramucirumab monotherapy. Thus, a total of 19 patients were analyzed in terms of both therapeutic effect and adverse events. The response evaluation of the targeted lesion was as follows; CR: 0, PR: 1, SD: 16, PD: 2. The median of overall survival and progression-free survival of the combination therapy was 9.9 months and 4.2 months, respectively. Although more than half of the patients were enforced after tertiary therapy in our department, the therapeutic effect of paclitaxel plus ramucirumab combination therapy was considerably satisfactory. Neutropenia as an adverse event was observed in 13(68.4%)out of 19 patients, and 8 patients(42.1%)had neutropenia greater than Grade 3. Non -hematologic toxicity was observed in 17 cases(89.5%), and anorexia, nausea, diarrhea, dysgeusia, peripheral neuropathy, hair loss, and fatigue were determined to be either Grade 1 or 2. Alternatively, 1 patient developed Grade 3 interstitial pneumonia, and 3 patients(15.8%)had complicated Grade 3 high blood pressure. Only 2 patients who had severe adverse events, one was interstitial pneumonia and the other was high blood pressure, discontinued paclitaxel plus ramucirumab combination therapy.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/adverse effects , Female , Humans , Male , Middle Aged , Neutropenia/chemically induced , Recurrence , Stomach Neoplasms/pathology , Treatment Outcome , Ramucirumab
5.
Pancreatology ; 18(5): 601-607, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29753623

ABSTRACT

BACKGROUND: Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment. AIMS: To compare the efficacy and safety of GJJ and DS for GOO with APC. METHODS: Consecutive 99 patients who underwent DS or GJJ for GOO with APC were evaluated. We compared the technical and clinical success rates, the incidence of adverse event (AE), the time to start chemotherapy and discharge and survival durations between DS and GJJ. Prognostic factors for overall survival (OS) were investigated on the multivariate analysis. RESULTS: GOO was managed with GJJ in 35 and DS in 64. The technical and clinical success rates were comparable. DS was associated with shorter time to start oral intake and earlier chemotherapy start and discharge. No difference was seen in the early and late AE rates. Multivariate analyses of prognostic factors for OS showed that performance status ≧2, administration of chemotherapy, and presence of obstructive jaundice to be significant factors. There were no significant differences in survival durations between the groups, regardless of the PS. CONCLUSIONS: There were no significant differences in the technical and clinical success and AE rates and survival duration between DS and GJJ in management of GOO by APC. DS may be a preferable option over GJJ given that it will lead to an earlier return to oral intake, a shortened length of hospital stay, and finally an earlier referral for chemotherapy.

6.
Gan To Kagaku Ryoho ; 45(3): 465-467, 2018 Mar.
Article in Japanese | MEDLINE | ID: mdl-29650906

ABSTRACT

We experienced a case of curative resection as a multidisciplinary treatment for unresectable gastric cancer that attributed to peritoneal disseminations and direct invasion to other organs.Two courses of triplet chemotherapy(DCS therapy)were performed under enteral stent placement and nasoenteral nutrition for direct infiltration into the transverse colon with entire circumference stenosis.Distal gastrectomy and right hemicolectomy were performed as conversion therapy, and R0 resection was achieved.After the operation, S-1 as adjuvant chemotherapy was performed and there has been no relapse survival for 13 months since the operation.From this case, it seems that conversion therapy plays an important role in prognosis extension as a treatment strategy for Stage IV gastric cancer.


Subject(s)
Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Gastrectomy , Humans , Neoplasm Staging , Stomach Neoplasms/pathology
8.
Anticancer Res ; 38(2): 737-743, 2018 02.
Article in English | MEDLINE | ID: mdl-29374697

ABSTRACT

BACKGROUND/AIM: The aim of the present study was to further develop our previous study on c-Met expression in colorectal cancer and epithelial-mesenchymal transition (EMT) induced by hepatocyte growth factor (HGF), to investigate EMT in the process of liver metastases, and evaluate the effects of chemotherapy on EMT cells as a therapeutic strategy for colorectal liver metastasis. MATERIALS AND METHODS: CT26 colon cancer cells were treated with 5-FU and oxaliplatin with or without HGF. The signaling pathway was evaluated by western blotting analysis, and drug resistance was evaluated by the MTT (3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide) assay. RESULTS: Under pretreatment with HGF for 96 h, 5 µM and 10 µM of 5-FU mediated significant growth inhibition by 72.5±3.9% and 76.2±2.4%, respectively, compared to HGF alone, and by 105.1±2.8% and 103.5±2.9%, respectively, without HGF. The expression of E2F1 was decreased significantly to 50.5±3.8% after 24 hours by HGF with a reduction of both cyclin D1 to 52.1±7.0% and E to 73.7±3.8%. Thymidylate synthase was also decreased in a time-dependent manner to 80.6±2.0% after 24 h and to 52.7±1.5% after 96 h. CONCLUSION: The presence of HGF was found to increase the 5-FU-induced death signal, JNK pathway, and inhibition of cell growth. As its mechanism, HGF was shown to decrease E2F-1 by reducing cyclin D or E by cell-cycle activation, resulting in inactivation of thymidylate synthase. The chemotherapeutic effect of 5-FU was increased in HGF- but not TGF-ß-induced EMT.


Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effects , Liver Neoplasms/secondary , Animals , Antimetabolites, Antineoplastic/pharmacology , Cadherins/metabolism , Cell Line, Tumor , Colorectal Neoplasms/metabolism , E2F1 Transcription Factor/metabolism , Fluorouracil/pharmacology , Hepatocyte Growth Factor/pharmacology , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Mice , Organoplatinum Compounds/pharmacology , Oxaliplatin , Signal Transduction/drug effects , Thymidylate Synthase/metabolism , Time Factors , Transforming Growth Factor beta/pharmacology
9.
Mol Clin Oncol ; 7(3): 476-480, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28894583

ABSTRACT

Rectal neuroendocrine tumor (NET) is a relatively rare lesion of the gastrointestinal tract, but the prospective examination with colonofiberoscopy or endoscopic ultrasound has increased the frequency of its detection. It is often difficult to determine the optimal treatment for NETs sized <20 mm in the clinical setting. Other clinicopathological variables are not considered in the current guidelines and staging systems. Although the effects of lymphovascular invasion are not covered by the World Health Organization (WHO) 2010 guidelines or tumor-node-metastasis (TNM) staging system, this may be promising for the establishment of improved guidelines and staging systems, particularly for early-stage colorectal carcinoids. The aim of the present study was to evaluate rectal NETs sized <20 mm in comparison with the WHO 2010 guidelines. Between January 2005 and December 2013, 40 consecutive patients [26 men and 14 women; median age, 59.3 years (range, 34-81 years)] who underwent endoscopic resection of rectal NETs, and 12 patients undergoing surgical resection of rectal NETs, were enrolled in this retrospective study. The median tumor size was 7.4 mm (range, 3-15 mm). The locations of the NET were the rectosigmoid colon (n=3), the upper rectum (n=13), and the lower rectum (n=25). The NETs were classified by size as 0-5 (n=7), 6-10 (n=29) and 11-15 mm (n=4). The surgical procedures performed included low anterior resection plus esophagectomy (n=1), laparoscopic low anterior resection (n=7) and laparoscopic intersphincteric resection (n=4). Only 1 patient had lymph node metastasis (tumor sized 6-10 mm, with lymphovascular invasion). NET recurrence was not detected in any of the patients. According to the WHO guidelines, the tumors were classified as grade (G)1 (n=8), G2 (n=3) and G1/G2 (n=1). The tumor in the patient with lymph node metastasis was G1. NETs sized <10 mm may be curatively treated by endoscopic resection. However, NETs with either lymphovascular invasion or sized >1 cm carry a risk for metastasis equivalent to that of adenocarcinomas. Therefore, it is mandatory to histologically examine lymphovascular invasion in specimens retrieved via endoscopic resection to determine the necessity for further radical surgery with regional lymph node dissection. The treatment of NETs sized <20 mm as presently defined in the WHO 2010 guidelines requires further evaluation.

10.
Oncol Lett ; 14(4): 4142-4150, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28943921

ABSTRACT

The aim of the present study was to evaluate the short-term surgical outcomes of laparoscopic intersphincteric resection (ISR) for a lower rectal tumor in comparison with a case-control series of patients undergoing open ISR. Quality of life factors and anal function were also evaluated. Between July 2008 and April 2013, 103 patients with lower rectal cancer underwent laparoscopic surgery at the Surgical Oncology Department of Gifu University School of Medicine. A total of 25 patients with lower rectal cancer underwent ISR, and 19/25 patients who underwent laparoscopic ISR were compared with the control group of 6 patients who underwent open ISR. The technical feasibility and safety of ISR, and the short- and long-term outcomes following laparoscopic ISR were evaluated. Additional data associated with fecal incontinence conditions of the postoperative patients were evaluated using the Modified Fecal Incontinence Quality of Life scale. There was no recorded perioperative mortality, three complications were observed to occur in three patients and the morbidity rate was 15.8%. The postoperative complications detected included bleeding in one patient and ileus in two patients of the laparoscopic ISR group. The rate of severe complications of grade ≥3a was 15.8% and that of grade ≥3b was 5.3%. In the matched case-control study, blood loss was significantly lower in the laparoscopic ISR group. The median postoperative hospital stay was 14.1 days in the laparoscopic ISR group, which was significantly shorter compared with in the open ISR group (18.7 days). Cancer recurrence was detected in one (5%) patient in a single inguinal lymph node. No significant differences between the ISR and ultra-low anterior resection (ULAR) groups were observed in the maximum resting and maximum squeeze pressures; the outcomes for anal function and fecal incontinence were the same for ISR and ULAR. Thus, laparoscopic ISR for lower rectal cancer may provide a benefit in the early postoperative period without increasing morbidity or mortality.

11.
Surg Endosc ; 31(3): 1257-1263, 2017 03.
Article in English | MEDLINE | ID: mdl-27444837

ABSTRACT

BACKGROUND: The indications for laparoscopic gastrectomy for early stomach cancer have spread worldwide, and the short-term outcomes have been favorable. Intraabdominal delta-shaped gastroduodenostomy using endoscopic linear staplers, a technique which was developed by Kanaya et al. is one of the feasible reconstructive procedures. Pure laparoscopic surgery is reported to be associated with several intraoperative and postoperative advantages in comparison with laparoscopy-assisted surgery. However, the clinical results remain uncertain. The present study aimed to evaluate both the technical feasibility and safety of delta-shaped anastomosis with LDG according to the short-term outcomes. METHODS: The study group was composed of 229 patients who underwent delta-shaped anastomosis with LDG at Gifu University School of Medicine from December 2004 to December 2014. RESULTS: The median total operative blood loss and operative time were 20 ml and 277 min, respectively. Postoperative complications were detected in 20 (8.7 %) patients. The complications included: anastomotic stenosis, n = 3 (1.3 %); anastomotic leakage, n = 3 (1.3 %); pancreatic injury, n = 8 (3.5 %); anastomotic ulcer, n = 1 (0.4 %); bowel obstruction, n = 1 (0.4 %); abdominal abscess, n = 1 (0.4 %); lymphorrhea, n = 1 (0.4 %); cardiac failure, n = 1 (0.4 %); and infection, n = 1 (0.4 %). The complications were classified as grade 2, n = 4 (1.7 %); grade 3a, n = 12 (5.2 %); grade 3b, n = 4 (1.7 %); and grade 4 and 5, n = 0 (0 %). CONCLUSION: The findings of the present study indicate the safety of Kanaya's procedure and that it should provide better outcomes in patients who undergo intracorporeal gastroduodenostomy after laparoscopic distal gastrectomy.


Subject(s)
Gastrectomy/methods , Gastroenterostomy/methods , Laparoscopy , Blood Loss, Surgical , Feasibility Studies , Female , Humans , Male , Middle Aged , Operative Time , Postoperative Complications
12.
Anticancer Res ; 36(10): 5215-5226, 2016 10.
Article in English | MEDLINE | ID: mdl-27798882

ABSTRACT

BACKGROUND: 5-Fluorouracil (5-FU) has been a mainstay of chemotherapy for gastric cancer. Vandetanib is a tyrosine kinase inhibitor with inhibitory activity against vascular endothelial growth factor receptor and epidermal growth factor receptor (EGFR). We investigated the combination effect of vandetanib with 5-FU on gastric cancer cells. MATERIALS AND METHODS: Anticancer efficacy was assessed by 3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide assay of five gastric cancer cell lines, MKN1, MKN7, MKN45, MKN74, and TMK1. Signal expression was examined by western blot, and the cell-cycle distribution was assessed by flow cytometry. In vivo anticancer activity of vandetanib with/without 5-FU was tested in MKN74 cells on nude mice. RESULTS: Vandetanib inhibited the growth of all cell lines. In MKN7 and MKN74 cells, the combination of 5-FU and vandetanib had synergistic effects, but effects were only additional against the other cell lines in vitro. Combination chemotherapy in vivo also significantly inhibited tumor growth compared to single use of each drug. Flow cytometry showed vandetanib increased the proportion in the G1 phase, and in MKN74, combination therapy increased the early S phase and caused bimodal peaks in the G1 phase. The level of expression of cyclin D1 was clearly strong in MKN7 and MKN74 in the natural state, and the expression of cyclin D1, E2 promoter binding factor 1 and thymidylate synthase (TYMS) was inhibited by vandetanib, but not in MKN1 cells. The synergistic effect disappeared in MKN7 and MKN74 cells in vitro when cyclin D1 was knocked-down by siRNA. CONCLUSION: The synergistic effect of vandetanib with 5-FU is related to vandetanib-induced reduction of TYMS via down-regulation of cyclin D1. Hyperexpression of cyclin D1 might be a biomarker of the synergistic effect.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclin D1/metabolism , Fluorouracil/therapeutic use , Piperidines/therapeutic use , Quinazolines/therapeutic use , Stomach Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin D1/genetics , Drug Synergism , E2F1 Transcription Factor/metabolism , ErbB Receptors/metabolism , Female , Humans , Mice , Mice, Nude , Stomach Neoplasms/metabolism , Thymidylate Synthase/metabolism , Tumor Burden/drug effects
15.
J Magn Reson Imaging ; 43(3): 680-7, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26201823

ABSTRACT

PURPOSE: To evaluate the diagnostic performance of noncontrast-enhanced magnetic resonance imaging (MRI) to grade pancreatic fibrosis and to assess hemoglobin (Hb) A1c values. MATERIALS AND METHODS: Twenty-nine consecutive patients with pancreatic or biliary malignancy who underwent pancreatectomy were evaluated. Patients were classified into three groups: HbA1c < 5.7 (group 1), 5.7 ≤ HbA1c < 6.5 (group 2), and HbA1c ≥ 6.5 (group 3). MRI of the pancreas was performed using a 1.5T MR system. The pancreas-to-muscle signal intensity ratio (SIR) on in- and opposed-phase T1 -, T2 -, and diffusion-weighted images, as well as the apparent diffusion coefficient were calculated. MRI measurements, degrees of pancreatic fibrosis, and HbA1c values were compared using multiple regression analysis and Kruskal-Wallis test. RESULTS: The pancreatic fibrosis grade was negatively correlated with the SIR on in-phase T1 -weighted images (r = -0.67, P = 0.0002). The pancreatic fibrosis grade and HbA1c value were negatively correlated with the SIR on opposed-phase T1 -weighted images (r = -0.47, P = 0.019 and r = -0.51, P = 0.0089, respectively). SIRs on in- and opposed-phase T1 -weighted images were significantly lower in group 3 than in groups 1 and 2 (P < 0.05). CONCLUSION: The pancreas-to-muscle SIRs on in- and opposed-phase T1 -weighted images could be a potential biomarker for pancreatic fibrosis and elevated HbA1c values.


Subject(s)
Diffusion Magnetic Resonance Imaging , Glycated Hemoglobin/metabolism , Pancreas/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Adult , Aged , Aged, 80 and over , Contrast Media , Female , Fibrosis , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatectomy , Pancreatic Diseases/pathology , Pancreatic Neoplasms/pathology , Radiology , Regression Analysis , Retrospective Studies , Young Adult
16.
Support Care Cancer ; 24(2): 933-941, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26266659

ABSTRACT

PURPOSE: We investigated the effect of glutamine (Gln) and an elemental diet (ED) on chemotherapy-induced oral mucositis in esophageal cancer patients. METHODS: Thirty patients were randomized to the control group (no treatment: n = 10), Gln group (oral intake of 8910 mg Gln/day: n = 10), or Gln plus ED group (total oral intake of 8862 mg Gln/day, including the Gln in ED: n = 10). Oral administration of Gln and ED began 1 week before chemotherapy and continued during treatment. Oral mucositis was evaluated during 2 cycles of chemotherapy using Common Terminology Criteria for Adverse Events v3.0. RESULTS: The incidence of grade ≥2 oral mucositis was 60 % in the control group, 70 % in the Gln group, and 10 % in the Gln plus ED group. Gln plus ED showed a significant preventive effect on the development and severity of oral mucositis. By multivariate analysis, Gln plus ED and cancer stage were independent factors affecting chemotherapy-induced oral mucositis. The percentage of change in body weight and diamine oxidase activity from before chemotherapy was higher in the Gln plus ED group than in the control group. CONCLUSIONS: Oral administration of Gln plus ED may prevent chemotherapy-induced oral mucositis in esophageal cancer patients.


Subject(s)
Food, Formulated , Glutamine/administration & dosage , Mucositis/diet therapy , Stomatitis/prevention & control , Administration, Oral , Aged , Aged, 80 and over , Amine Oxidase (Copper-Containing)/metabolism , Body Weight , Esophageal Neoplasms/drug therapy , Feasibility Studies , Female , Humans , Induction Chemotherapy/adverse effects , Male , Middle Aged , Mucositis/chemically induced , Mucositis/prevention & control , Stomatitis/chemically induced , Stomatitis/diet therapy
17.
Mol Clin Oncol ; 5(6): 807-810, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28105361

ABSTRACT

Pathological response to preoperative chemotherapy was recently found to be correlated with improved survival and has been proposed as a new outcome end-point following resection of liver metastases from colorectal cancer (CRC). It was demonstrated that, particularly after therapy with bevacizumab, CRC liver metastases decreased in size and underwent distinct morphological changes on computed tomography (CT). However, morphological changes in response to treatment with regorafenib have not yet been reported. A 73-year-old male patient with synchronous multiple liver and lung metastases from colon cancer was treated with regorafenib as a fifth-line therapy. CT imaging revealed a decrease in the tumor size and distinct morphological changes, namely homogeneous attenuation and sharp tumor-liver interface. The patient continued to take regorafenib for 8 months. Thus, regorafenib appeared to be effective as a last-line chemotherapy. In particular, the unique morphological changes of the metastases on CT imaging of may represent a method for evaluating the effects of CRC cancer therapy.

18.
Anticancer Res ; 35(10): 5485-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26408713

ABSTRACT

AIM: The benefit of preoperative chemotherapy is evaluated in order to clarify the relationship of tumor site with hepatic vessels for hepatectomy. Tumor location in relation to intrahepatic vessels is critical in the decision to operate, but the argument for this concept remains insufficient. Currently, the response rate is evaluated by the decrease in size or number of tumors but not by hepatic resection range. PATIENTS AND METHODS: We evaluated 32 patients who underwent hepatectomy after chemotherapy for liver metastases from colorectal cancer (CLM). Tumor diameter was defined by contrast computed tomographic imaging before both chemotherapy and surgery. The targeted vessels were those in the main Glisson capsule and hepatic vein and were indicated to change in the resected area by their treatment. RESULTS: Tumor size decreased, increased or remained unchanged in 62 (68.9%), 27 (30.0%) and one (1.1%) tumor, respectively. Out of the 29 tumors, reduced resection volume was achieved in 12 (37.9%), and the difference in volume was 17.4±4.15 ml. A significant positive correlation was found between tumor shrinkage rate and final distance from the attached vessels (p=0.017), and a shrinkage rate of 63.6±12.4% was necessary for a tumor to be separated from an attached vessel. The final distance was significantly positively correlated with tumor shrinkage speed (p=0.0027), and a shrinkage speed of 0.64±0.12%/day was expected to enable a a tumor to be separated from its attached vessel. CONCLUSION: Chemotherapy, especially by favorable combination with molecular targeting agents, even for resectable CLM appears to be acceptable and may lead to increased performance of radical surgical resection.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Staging , Preoperative Care , Prognosis
19.
Int J Oncol ; 47(4): 1266-72, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26252842

ABSTRACT

To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3-25.1 µM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC.


Subject(s)
Antineoplastic Agents/pharmacology , Cell Proliferation/drug effects , Mammary Neoplasms, Experimental/drug therapy , Triple Negative Breast Neoplasms , Vitamin K 3/pharmacology , Animals , Blotting, Western , Cell Line, Tumor , Extracellular Signal-Regulated MAP Kinases/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Phosphorylation , Xenograft Model Antitumor Assays
20.
Oncotarget ; 6(28): 24722-32, 2015 Sep 22.
Article in English | MEDLINE | ID: mdl-26160842

ABSTRACT

Aldehyde dehydrogenase 1A1 (ALDH1A1) is considered to be a cancer stem cell marker in several human malignancies. However, the role of ALDH1A1 in hepatocellular carcinoma (HCC) has not been well elucidated. In this study, we investigated the relationship between ALDH1A1 and clinicopathological findings and examined whether ALDH1A1 deserves to be a cancer stem cell marker in HCC. Sixty HCC samples obtained from surgical resection were collected for immunohistochemical (IHC) staining. Of these 60 samples, 47 samples of HCC tumorous and non-tumorous tissues were evaluated with qRT-PCR. There was no significant difference in the ALDH1A1-mRNA level between tumorous and non-tumorous tissues. Tumorous ALDH1A1-mRNA level had no relationship with the clinicopathological features. Immunoreactivity of ALDH1A1 was classified into two groups based on the percentage of ALDH1A1-overexpressing cells. The ALDH1A1-high group was significantly associated with low serum levels of α-fetoprotein, small tumor diameter, very little lymphovascular invasion, more differentiated pathology and good stage. The ALDH1A1-high group showed more favorable prognosis for recurrence-free survival. In double-staining IHC, ALDH1A1 was not co-expressed with BMI1, EpCAM, CD13, CD24, CD90 and CD133, which reported as cancer stem cell markers in HCC. In conclusion, ALDH1A1-overexpressing cells could appear to be differentiated cells rather than cancer stem cells in HCC.


Subject(s)
Aldehyde Dehydrogenase/analysis , Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/enzymology , Cell Differentiation , Liver Neoplasms/enzymology , Neoplastic Stem Cells/enzymology , Adult , Aged , Aged, 80 and over , Aldehyde Dehydrogenase/genetics , Aldehyde Dehydrogenase 1 Family , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Disease-Free Survival , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Middle Aged , Multivariate Analysis , Neoplastic Stem Cells/pathology , Phenotype , Proportional Hazards Models , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Retinal Dehydrogenase , Risk Factors , Up-Regulation
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