Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 22
Filter
1.
Int Cancer Conf J ; 12(3): 210-215, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37251007

ABSTRACT

A 54-year-old man was diagnosed with descending colon cancer with metastases in the liver, para-aortic lymph nodes, and penis, and chemotherapy was introduced after construction of a colostomy. The patient reported only mild penile pain at the time of diagnosis; however, the pain gradually worsened and interfered with his daily life. Opioids did not provide sufficient analgesia, and the patient developed dysuria and priapism. Through construction of a cystostomy, palliative radiotherapy with QUAD Shot regimen (14 Gy in 4 fractions twice-daily on 2 days repeated every 4 weeks) to the penile metastasis was started for pain relief and tumor shrinkage. The radiation rapidly improved the penile symptoms, enabling opioid reduction and cystostomy removal. The patient remained pain-free and able to urinate on his own until his death. Metastatic penile tumors are rare, especially those derived from colon cancer. Penile metastases occur mainly in the late stages of cancer and may impair the patient's quality of life. In such cases, palliative radiotherapy, especially with QUAD Shot regimen, is useful with short treatment time, durable symptom control, and little adverse effect, maintaining quality of life.

2.
BMC Gastroenterol ; 22(1): 313, 2022 Jun 25.
Article in English | MEDLINE | ID: mdl-35752764

ABSTRACT

BACKGROUND: Gut pathological microbial imbalance or dysbiosis is closely associated with colorectal cancer. Although there are observable differences in molecular and clinical characteristics between patients with right- and left-sided colon cancer, differences in their gut microbiomes have not been thoroughly investigated. Furthermore, subsequent changes in microbiota status after partial colectomy remain unknown. We examined the human gut microbiota composition to determine its relationship with colon cancer and partial colon resection according to location. METHODS: Stool samples from forty-one subjects (10 in the control group, 10 in the right-sided colon cancer [RCC] group, 6 in the sigmoid colon cancer [SCC] group, 9 in the right colon resection [RCR] group and 6 in the sigmoid colon resection [SCR] group) were collected, and DNA was extracted. After terminal restriction fragment length polymorphism (T-RFLP) analysis, the samples were subjected to 16S rRNA gene amplicon sequencing, and the metabolic function of the microbiota was predicted using PICRUSt2. RESULTS: T-RFLP analysis showed a reduced ratio of clostridial cluster XIVa in the SCC patients and clostridial cluster IX in the RCC patients, although these changes were not evident in the RCR or SCR patients. 16S rRNA gene amplicon sequencing demonstrated that the diversity of the gut microbiota in the RCC group was higher than that in the control group, and the diversity in the SCR group was significantly higher than that in the RCR group. Principal coordinate analysis (PCoA) revealed significant differences according to the group. Analyses of the microbiota revealed that Firmicutes was significantly dominant in the RCC group and that the SCC group had a higher abundance of Verrucomicrobia. At the genus level, linear discriminant analysis effect size (LEfSe) revealed several bacteria, such as Ruminococcaceae, Streptococcaceae, Clostridiaceae, Gemellaceae, and Desulfovibrio, in the RCC group and several oral microbiomes in the SCC group. Metabolic function prediction revealed that cholesterol transport- and metabolism-related enzymes were specifically upregulated in the RCC group and that cobalamin metabolism-related enzymes were downregulated in the SCC group. CONCLUSION: Gut microbial properties differ between RCC and SCC patients and between right hemicolectomy and sigmoidectomy patients and may contribute to clinical manifestations.


Subject(s)
Carcinoma, Renal Cell , Colonic Neoplasms , Colorectal Neoplasms , Gastrointestinal Microbiome , Kidney Neoplasms , Carcinoma, Renal Cell/genetics , Colectomy , Colonic Neoplasms/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/microbiology , Colorectal Neoplasms/surgery , Gastrointestinal Microbiome/genetics , Genes, rRNA , Humans , Kidney Neoplasms/genetics , RNA, Ribosomal, 16S/genetics
3.
Gan To Kagaku Ryoho ; 43(9): 1101-3, 2016 Sep.
Article in Japanese | MEDLINE | ID: mdl-27628552

ABSTRACT

A 52-year-old woman presented with redness and swelling with a peau d'orange appearance in the whole right breast. Ultrasound revealed elevated subcutaneus fat density and a diffuse hypoechoic area. She was diagnosed with inflammatory breast cancer(T4dN2M0, Stage III B of the HER2 subtype). After 4 courses of EC treatment as primary systemic therapy, the hypoechoic area was still present. Subsequent chemotherapy with pertuzumab, trastuzumab, and docetaxel was effective, as hypoechoic area was not observed on ultrasound. She underwent mastectomy and axillary dissection, and pathological examination revealed pCR. At present, 2 years after surgery, the patient is alive with no reccurence.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Inflammatory Breast Neoplasms/drug therapy , Neoadjuvant Therapy , Biopsy , Female , Humans , Inflammatory Breast Neoplasms/chemistry , Inflammatory Breast Neoplasms/pathology , Inflammatory Breast Neoplasms/surgery , Mastectomy , Middle Aged , Neoplasm Staging , Receptor, ErbB-2/analysis , Receptor, ErbB-2/metabolism , Treatment Outcome
4.
Surg Laparosc Endosc Percutan Tech ; 24(2): e41-2, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24686359

ABSTRACT

BACKGROUND: The double-stapling technique (DST) is frequently used in laparoscopic sigmoidectomy. Unfortunately, anastomotic leakage after laparoscopic intracorporeal colorectal anastomosis with DST is seen with some frequency. METHODS: We performed DST on 40 patients (June 2007 to August 2008) and hemi-DST on 50 patients (September 2008 to December 2011) undergoing laparoscopic sigmoidectomy. RESULTS: There were no occurrences of anastomotic leakage in the hemi-DST group, and 2 instances of anastomotic leakage in the DST group were observed. In these patients, the leakage appeared at the lateral intersecting anastomotic margins. CONCLUSIONS: Using the hemi-DST for laparoscopic intracorporeal colorectal anastomosis will make laparoscopic sigmoidectomy a safer procedure.


Subject(s)
Colon, Sigmoid/surgery , Laparoscopy/methods , Anastomosis, Surgical/instrumentation , Anastomotic Leak/etiology , Colonic Neoplasms/surgery , Humans , Lymph Node Excision , Rectum/surgery , Sutures
5.
Oncol Rep ; 19(3): 755-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18288412

ABSTRACT

Chemotherapy remains the main choice of treatment for the management of unresectable or metastatic colorectal cancer. However, drug resistance is a major problem, limiting the effectiveness of the chemotherapies presently used to treat cancer. During treatment, drug resistance can also be acquired by tumors that are initially sensitive to chemotherapy. We present a case of metachronous splenic recurrence after a curative resection of appendical cancer with ovarian metastasis, although the patient had been treated with 5-FU/LV followed by mFOLFOX6 after surgery. Molecular analyses by RT-PCR also showed that the residual tumor after chemotherapy has cancer cells overexpressing 5-FU/l-OHP based chemotherapy-resistant genes. Therefore, it was suggested that a careful assessment of the disease status be undertaken during chemotherapy to ensure that the possibility of surgical resection, especially of the re-growth or partial response tumors, was not missed, since several genes, chemoresistant to the agents used, can be induced in residual tumors during chemotherapy.


Subject(s)
Colonic Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Aged , Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Combined Modality Therapy , Enzymes/genetics , Enzymes/metabolism , Female , Humans , RNA, Messenger/metabolism , Splenic Neoplasms/pathology , Splenic Neoplasms/secondary
6.
J Surg Oncol ; 97(5): 404-8, 2008 Apr 01.
Article in English | MEDLINE | ID: mdl-18181167

ABSTRACT

AIMS: Immunosuppressive acidic protein (IAP) is a potent biological marker for immunological surveillance in patients with malignant tumors. This study aimed to investigate the significance of serum IAP as an index of disease status, clinicopathological findings and prognosis in colorectal cancer. METHODS: A total of 101 patients with colorectal cancer and 80 normal volunteers were included in this retrospective trial. Preoperative serum IAP was assayed using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: The serum IAP level in the patients, which was not associated with clinicopathological features except for tumor size, was significantly higher than that in controls. The serum IAP level was closely correlated with percent body weight loss, serum albumin and cholinesterase, and percentage of circulating lymphocytes reflecting the host's nutritional and immunological conditions. Interestingly, these parameters were not associated with factors reflecting disease progression except for tumor size. The prognosis of patients with higher IAP levels was significantly worse than that of patients with lower IAP levels. Furthermore, an elevated serum IAP level was an independent prognostic marker in all patients. CONCLUSION: The preoperative serum IAP level may reflect the general condition of colorectal cancer patients, and thus may predict long-term survival independently of stage progression.


Subject(s)
Colorectal Neoplasms/mortality , Neoplasm Proteins/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Cholinesterases/blood , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lymphocyte Count , Male , Middle Aged , Neoplasm Metastasis , Preoperative Care , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Serum Albumin/analysis , Weight Loss
7.
J Gastroenterol ; 42(9): 730-6, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17876542

ABSTRACT

BACKGROUND: Our aim was to determine whether the expression levels of specific genes could predict clinical radiosensitivity in human colorectal cancer. METHODS: Radioresistant colorectal cancer cell lines were established by repeated X-ray exposure (total, 100 Gy), and the gene expressions of the parent and radioresistant cell lines were compared in a microarray analysis. To verify the microarray data, we carried out a reverse transcriptase-polymerase chain reaction analysis of identified genes in clinical samples from 30 irradiated rectal cancer patients. RESULTS: A comparison of the intensity data for the parent and three radioresistant cell lines revealed 17 upregulated and 142 downregulated genes in all radioresistant cell lines. Next, we focused on two upregulated genes, PTMA (prothymosin alpha) and EIF5a2 (eukaryotic translation initiation factor 5A), in the radioresistant cell lines. In clinical samples, the expression of PTMA was significantly higher in the minor effect group than in the major effect group (P = 0.004), but there were no significant differences in EIF5a2 expression between the two groups. CONCLUSIONS: We identified radiation-related genes in colorectal cancer and demonstrated that PTMA may play an important role in radiosensitivity. Our findings suggest that PTMA may be a novel marker for predicting the effectiveness of radiotherapy in clinical cases.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , Gene Expression Regulation, Neoplastic , Peptide Initiation Factors/genetics , Preoperative Care/methods , Protein Precursors/genetics , RNA, Neoplasm/genetics , RNA-Binding Proteins/genetics , Thymosin/analogs & derivatives , Aged , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/radiation effects , Biopsy , Colectomy , Colonoscopy , Colorectal Neoplasms/pathology , Female , Humans , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Peptide Initiation Factors/biosynthesis , Peptide Initiation Factors/radiation effects , Prognosis , Protein Precursors/biosynthesis , Protein Precursors/radiation effects , RNA, Neoplasm/biosynthesis , RNA, Neoplasm/radiation effects , RNA-Binding Proteins/biosynthesis , RNA-Binding Proteins/radiation effects , Radiotherapy, Adjuvant , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Thymosin/biosynthesis , Thymosin/genetics , Thymosin/radiation effects , Tumor Cells, Cultured , Eukaryotic Translation Initiation Factor 5A
8.
Oncol Rep ; 18(2): 369-75, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17611658

ABSTRACT

To assess whether preoperative chemo-radiotherapy enhances the expression of vascular endothelial growth factor (VEGF) in patients with colorectal cancer, we investigated in vivo and in vitro the interactions between chemo-radiotherapy and the expression of VEGF, and their possible impact on distant metastasis. Cellular cytotoxicity in the colon cancer cell lines, LoVo, SW480 and Caco2, was determined using a WST-8 colorimetric assay after cells were exposed to 5-fluorouracil combined with radiation. In addition, the VEGF levels in cultured cells were measured by ELISA. Preoperative serum samples and tumor specimens were prospectively collected from 32 rectal cancer patients who received preoperative chemo-radiotherapy. Both local and circulating VEGF expression levels were measured perioperatively by ELISA, and assessed in relation to the clinicopathological findings. Perioperative circulating VEGF levels from irradiated patients were also compared with a non-irradiated control group. There were significant increases in local VEGF levels, both in vivo and in vitro, after chemo-radiotherapy, especially in viable cancer cells. The circulating VEGF levels in the irradiated patients were significantly lower after surgery compared with those in the control group. Although preoperative chemo-radiotherapy enhanced tumor-specific VEGF expression, especially in individual cancer cells both in vitro and in vivo, it did not necessarily enhance systemic VEGF expression, possibly because of tumor volume reduction induced by the chemo-radiotherapy.


Subject(s)
Preoperative Care , Rectal Neoplasms/pathology , Vascular Endothelial Growth Factor A/biosynthesis , Aged , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/therapeutic use , Caco-2 Cells , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Combined Modality Therapy , Enzyme-Linked Immunosorbent Assay , Female , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Humans , Immunohistochemistry , Male , Middle Aged , Radiation Dosage , Rectal Neoplasms/metabolism , Rectal Neoplasms/therapy , Time Factors , Vascular Endothelial Growth Factor A/blood
9.
Int J Cancer ; 121(1): 33-8, 2007 Jul 01.
Article in English | MEDLINE | ID: mdl-17354233

ABSTRACT

This study consisted of 2 aims: (i) to determine genes associated with hepatocellular carcinoma (HCC) by microarray analysis; and (ii) to evaluate the clinicopathological significance of human ubiquitin-conjugating enzyme E2C (Ube2c) found to be overexpressed in HCC from microarray analysis. Laser microdissection and cDNA-microarray were performed to identify genes associated with HCC. We then focused on the Ube2c gene. Using real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR), Ube2c expression status and clinicopathological significance were studied in 65 clinical HCC samples. A number of genes upregulated in HCC cells compared to noncancerous liver cells were identified, one of which was the Ube2c gene. Ube2c gene expression in the cancer tissue was higher than in the corresponding noncancerous tissue in 62 of the 65 cases (95.4%, p < 0.01). Tumors with high Ube2c expression showed higher frequencies of tumor invasion to capsular formation (fc-inf), invasion to portal vein (vp) and tumor de-differentiation (p < 0.05). Patients with high Ube2c expression also showed significantly worse disease-free survival rates than those with low Ube2c expression (p < 0.01). In addition, Ube2c expression was found to be an independent prognostic factor for disease-free survival rate in multivariate analysis. We identified differentially expressed genes between HCC and normal liver tissues. Of those, the Ube2c gene appeared to be associated with HCC progression, and may be useful as a prognostic indicator for HCC patients.


Subject(s)
Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Gene Expression Regulation, Neoplastic/genetics , Ubiquitin-Conjugating Enzymes/genetics , Aged , Carcinoma, Hepatocellular/pathology , Cell Line , Female , Humans , Male , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Survival Rate , Ubiquitin-Conjugating Enzymes/metabolism
10.
J Pediatr Surg ; 42(1): 259-60, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17208578

ABSTRACT

This is a first pediatric case about the efficacy of octreotide for improving symptoms of malignant bowel obstruction. A 12-year-old boy was referred to our hospital for treatment of transverse colon cancer with peritoneal dissemination. A transverse colectomy was undertaken with postoperative adjuvant chemotherapy. Seven months later, severe abdominal symptoms occurred caused by incomplete bowel obstruction owing to tumor progression. The patient's quality of life decreased with a resultant disturbed mental condition. His parents sought to stop chemotherapy and for him to receive palliative care at home. We suggested nasogastric tube placement, but this was rejected. After obtaining informed consent, octreotide was administered intravenously. After 1 week, abdominal symptoms improved and the boy's complaints stopped. He had a good appetite and was able to eat small amounts of food. He was able to spend his final 2 months at home without nausea and in his family surroundings.


Subject(s)
Adenocarcinoma/complications , Colonic Neoplasms/complications , Gastrointestinal Agents/therapeutic use , Intestinal Obstruction/drug therapy , Octreotide/therapeutic use , Peritoneal Neoplasms/complications , Adenocarcinoma/secondary , Child , Colon, Transverse , Colonic Neoplasms/pathology , Colonic Neoplasms/surgery , Fatal Outcome , Humans , Intestinal Obstruction/etiology , Male , Palliative Care , Peritoneal Neoplasms/secondary , Quality of Life
11.
Cancer Chemother Pharmacol ; 59(6): 733-42, 2007 May.
Article in English | MEDLINE | ID: mdl-16957932

ABSTRACT

AIM: This study was performed to investigate the range of optimal concentration and mechanisms of paclitaxel (PXL) radio-enhancement in gastrointestinal cancer cell lines HT29 and MKN45. METHODS: Cell growth inhibition by PXL pretreatment at various concentrations (0-10 microM) followed by irradiation was investigated using a modified MTT assay. To investigate the mechanisms of the observed radio-enhancement, flow cytometry was conducted to define the cell cycle distributions. Furthermore, the alterations in expression of a DNA repair molecule [excision repair cross-complementation group1 (ERCC1)] and an angiogenesis factor [vascular endothelial growth factor (VEGF)] induced by PXL were investigated. RESULTS: Cytotoxic concentrations of PXL (0.1-10 microM) that cause accumulation of cells in the G2/M phase have strong radio-enhancing effects and inhibit total cell growth. The maximal non-cytotoxic concentration of PXL (0.01 microM) also had a radio-enhancing effect. The expression of the genes of ERCC1 and VEGF induced by radiation was suppressed by PXL pretreatment. The protein secretion of VEGF induced by radiation was suppressed at cytotoxic doses of PXL, and the induced protein secretion of ERCC1 was also suppressed even at maximal non-cytotoxic doses of PXL. CONCLUSION: The range of optimal concentration for PXL pretreatment was 0.01-0.1 microM in these cells. Two major mechanisms of radio-enhancement are suggested: (1) PXL induces G2/M arrest leading to increased DNA damage after radiation, which results in mitotic death, and (2) PXL suppresses the expression of radiation-induced DNA repair molecules and angiogenesis factors, resulting in inhibition of cell growth and cell death.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/administration & dosage , Gastrointestinal Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adenocarcinoma/radiotherapy , Antineoplastic Agents, Phytogenic/pharmacology , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , DNA Repair , Gastrointestinal Neoplasms/radiotherapy , HT29 Cells , Humans , Paclitaxel/pharmacology , Radiation Dosage , Radiation-Sensitizing Agents , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A/metabolism
12.
Oncol Rep ; 16(5): 971-4, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17016579

ABSTRACT

We have previously demonstrated that the combined use of doxifluridine and irinotecan shows a different molecular mechanism than that of the protracted venous infusion of 5-FU and irinotecan. In this analysis, there is a suggestion that doxifluridine may enhance irinotecan and enable us to decrease the dose of irinotecan without losing the strong effect by using doxifluridine instead of 5-FU. We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28) as a known high risk for irinotecan, who was treated with a combination of doxifluridine and irinotecan for peritoneal dissemination resulting in stable disease for 2 years without adverse reactions, although the patient initially developed severe adverse effects to the combination of the protracted venous infusion of 5-FU and irinotecan. Even with the same ratios of fluoropyrimidine and irinotecan combinations, replacing 5-FU with doxifluridine or capecitabine could provide new strategies to obtain not only convenience but also better efficacy and safety at the molecular level.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Glucuronosyltransferase/genetics , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Colonic Neoplasms/enzymology , Female , Floxuridine/administration & dosage , Floxuridine/adverse effects , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Glucuronosyltransferase/metabolism , Humans , Irinotecan , Polymorphism, Genetic
13.
Oncol Rep ; 16(5): 1085-91, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17016597

ABSTRACT

To evaluate the optimal schedule of 5-fluorouracil (5-FU) radiosensitization in rectal cancer, we investigated the interaction between radiation and several doses of 5-FU on colon cancer cell lines based on pharmacokinetics of oral fluoropyrimidine. Cellular cytotoxicity in colon cancer cell lines, LoVo, WiDr and Caco-2 was determined, using a WST-8 colorimetric assay, after 24 h exposure to several concentrations of 5-FU and a radiation dose of 5 Gy. Cells were exposed to 5-FU 24 and 0 h before radiation. 5-FU doses were classified into three groups: uracil-tegafur (0.01-0.1 microM), S-1 (0.1-1.0 microM) and pharmacokinetic modulating chemotherapy (0.1-10 microM). In addition, the effect of 5-FU on the steady-state levels of a human excision repair cross-complementing 1 gene and cell cycle distribution were examined. Regardless of time of 5-FU exposure, all cell growth was significantly inhibited in a dose-dependent manner. In Caco-2 cells, the cytotoxicity of radiation followed by 5-FU was significantly greater than that of 5-FU followed by radiation, unlike in the other cell lines. The growth inhibitory effect of radiation followed by 5-FU increased in a dose-dependent manner to reach a plateau at S-1 doses in all cell lines. In cell cycle distribution, 5-FU exposure for 24 h increased the S phase fraction in a dose-dependent manner. RT-PCR showed that 5-FU post-treatment graduallly inhibited mRNA expression of ERCC1, which may affect recombination repair efficiency, accounting for the higher tumor sensitivity. Oral fluoropyrimidines, like S-1, that can maintain a constant level of 5-FU may be an acceptable alternative radiosensitizer to protracted 5-FU infusion, when the aim of neoadjuvant chemoradiotherapy for rectal cancer is locoregional control.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/radiotherapy , Fluorouracil/administration & dosage , Radiation-Sensitizing Agents/administration & dosage , Caco-2 Cells , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Growth Processes/drug effects , Cell Growth Processes/radiation effects , Cell Line, Tumor , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Dose-Response Relationship, Drug , Endonucleases/biosynthesis , Endonucleases/genetics , Humans , Reverse Transcriptase Polymerase Chain Reaction/methods
14.
Dis Colon Rectum ; 49(11): 1710-8, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16990975

ABSTRACT

PURPOSE: There is no marker capable of differentiating patients with Dukes A and B colorectal cancer with aggressive diseases from those with indolent diseases. We evaluated the results of five years of actuarial survival data to determine whether serial monitoring of serum hepatocyte growth factor could provide prognostic information on these patients. METHODS: Blood samples of 147 colorectal cancer patients were obtained and the serum concentration of hepatocyte growth factor was measured. RESULTS: Elevated serum hepatocyte growth factor levels were associated with stage progression. Although the overall positive rate of hepatocyte growth factor in the patients was the same as that of the carcinoembryonic antigen, the positive rate of hepatocyte growth factor in the Dukes A patients was two times higher than that of the carcinoembryonic antigen, and nearly 40 percent of the carcinoembryonic antigen-negative patients had a positive serum hepatocyte growth factor in the Dukes A and B classification. In this subgroup, patients with positive serum hepatocyte growth factor or carcinoembryonic antigen levels had a poorer prognosis, whereas positive serum hepatocyte growth factor level after surgery could predict disease recurrence. CONCLUSIONS: A combination of serum hepatocyte growth factor and carcinoembryonic antigen tests might be useful for selecting patients with aggressive diseases in Dukes A and B classification.


Subject(s)
Carcinoembryonic Antigen/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/mortality , Hepatocyte Growth Factor/blood , Adenocarcinoma/blood , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Biomarkers/blood , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Humans , Japan/epidemiology , Liver Neoplasms/secondary , Lymphatic Metastasis , Male , Neoplasm Invasiveness , Neoplasm Recurrence, Local/blood , Prognosis , Survival Analysis
15.
Surgery ; 139(3): 305-11, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16546493

ABSTRACT

BACKGROUND: Chromosomal instability evidenced by a loss of heterozygosity (LOH) is implicated as a predictor of poor survival in patients with colorectal cancer, whereas microsatellite instability (MSI) is associated with improved survival rates. We investigated the relationship between tumor expression of angiogenic growth factors and genomic alterations in colorectal cancer. METHODS: Two genotypes, LOH and MSI, determined by microsatellite markers in the 4 cancer-related chromosomes 2p, 3p, 17p, and 18q, were analyzed in 73 patients with colorectal cancer. The tumor-specific expression of vascular endothelial growth factor and hepatocyte growth factor (HGF) were quantified, and the interleukin-6 network also was evaluated. RESULTS: MSI-positive neoplasms showed a lesser expression of both tumor growth factors and interleukin-6. In contrast, LOH-positive neoplasms showed a greater expression of HGF and a lesser expression of interleukin-1-receptor antagonist. MSI neoplasms were correlated with favorable prognosis in agreement with previous findings. CONCLUSIONS: The suppressed production of angiogenic growth factors in MSI cancers partly might explain the better prognosis in MSI-positive patients. The interleukin-6 network, which upregulates production of vascular endothelial growth factor and HGF, might be involved in this mechanism.


Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/physiopathology , Genetic Predisposition to Disease , Genomic Instability , Hepatocyte Growth Factor/biosynthesis , Neovascularization, Pathologic , Vascular Endothelial Growth Factor A/biosynthesis , Adult , Aged , Aged, 80 and over , Female , Gene Expression Profiling , Humans , Interleukin-6/biosynthesis , Interleukin-6/physiology , Loss of Heterozygosity , Male , Microsatellite Repeats , Middle Aged , Prognosis
16.
J Gastroenterol ; 41(12): 1149-57, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17287894

ABSTRACT

BACKGROUND: Our aim was to clarify the significance of widely accepted irinotecan (CPT-11)/5-fluorouracil (5-FU) combinations in colon cancer by investigating their sequential effect. METHODS: The sequential effect of CPT-11/5-FU in two colon cancer cell lines, LoVo and SW480, was evaluated by WST-8 colorimetric assay. The cell cycle distributions of each drug were analyzed by flow cytometry, and then the chemoresistant mechanisms and expression of a drug transporter (MDR1), the bcl-2 apoptotic pathway, metabolizing enzymes [carboxylesterase (CE), dihydropyrimidine dehydrogenase], and target enzymes (topoisomerase I, thymidine synthase) associated with sequence-dependent cytotoxicity were examined. RESULTS: The cytotoxicity of 5-FU (10, 100, 1000 microM) followed by CPT-11 (1 microM) was significantly greater than that of CPT-11 (1 microM) followed by 5-FU (10, 100, 1000 microM) (P < 0.05). Reverse transcription-polymerase chain reaction analysis revealed that exposure to 5-FU downregulated both MDR1 and bcl-2 mRNA and simultaneously upregulated CE2 mRNA expression, suggesting enhancement of subsequent CPT-11 cytotoxicity. CONCLUSIONS: The cytotoxic effects of the CPT-11/5-FU combinations were shown to be schedule-dependent in human colon cancer cells. The findings suggest that 5-FU followed by CPT-11 administration might be the optimal sequence for CPT-11/5-FU treatment of advanced colon cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/analogs & derivatives , Colonic Neoplasms/drug therapy , Fluorouracil/administration & dosage , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Drug Administration Schedule , Flow Cytometry , Fluorouracil/adverse effects , Humans , Irinotecan , Tumor Cells, Cultured
17.
Oncol Rep ; 14(6): 1571-6, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16273258

ABSTRACT

This retrospective study was conducted to assess the safety, efficacy, and long-term results of multi-modality therapy including radio-frequency thermal ablation (RFA) and radiotherapy as an additional cytoreductive method for eliciting the marked effects of chemotherapy in treating unresectable lung metastases from colorectal cancer. Total of 21 patients with lung metastasis from colorectal cancer were included. They were treated with modified pharmacokinetic modulating chemotherapy (PMC). Eleven were also treated with RFA and/or radiotherapy (multi-modality group), and 10 were treated with chemotherapy alone (chemotherapy group). Characteristics and survival of patients in the multi-modality group were compared with those of the chemotherapy group. The median survival of all patients was 38.6 months after the initial PMC. The cumulative 3-year survival rate of patients in the multi-modality group was 87.5% compared with 33.3% in the chemotherapy group (p=0.0041). The course of multi-modality therapy was uneventful except for pneumothorax in those who received RFA. Although pneumothorax developed in 4 of 11 patients (36.4%) treated with RFA, all were able to receive chemotherapy within 2 weeks after RFA. In conclusion, multi-modality therapy combined with modified PMC, radiation and RFA is a feasible choice of treatment associated with reasonable morbidity and mortality in patients with inoperable lung metastases from colorectal cancer.


Subject(s)
Colorectal Neoplasms/therapy , Lung Neoplasms/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , CA-19-9 Antigen/analysis , Carcinoembryonic Antigen/analysis , Catheter Ablation/adverse effects , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Combined Modality Therapy , Disease Progression , Female , Humans , Leukopenia/etiology , Lung Neoplasms/mortality , Lung Neoplasms/secondary , Male , Middle Aged , Nausea/etiology , Neoplasm Recurrence, Local , Radiotherapy/adverse effects , Retrospective Studies , Survival Analysis , Survival Rate , Treatment Outcome , Vomiting/etiology
18.
Crit Care Med ; 33(1): 177-80, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15644666

ABSTRACT

OBJECTIVE: Aging and tumor-related malnutrition are associated with increased inflammatory cytokine levels. However, it is unclear whether this influences the outcomes of surgery. We explored the relationships between cytokines and surgical complications among patients undergoing surgery for colorectal cancer. DESIGN: Laboratory experiment. SETTING: Surgery department of school of medicine. PATIENTS: One hundred patients with colorectal cancer. INTERVENTIONS: The perioperative circulating levels of interleukin (IL)-1beta, IL-6, and IL-1 receptor antagonist (Ra) were determined, and the numbers of circulating lymphocytes and neutrophils were counted. MEASUREMENTS AND MAIN RESULTS: Trends toward increasing postoperative infection were observed among patients who were older and had lower body mass index. Preoperative IL-1Ra and intraoperative blood loss, however, remained the only two independent predictors of postoperative infection. Clinically, patients with low preoperative IL-1Ra most frequently were the elderly with low body mass index. Postoperatively, elderly patients with low body mass index showed an exaggerated IL-6 response, followed by an exaggerated postoperative inflammatory response and increased postoperative loss of body weight. In contrast, normal immunoreactivity was preserved in well-nourished elderly patients. CONCLUSIONS: In colorectal cancer patients undergoing surgery, low preoperative IL-1Ra is associated with postoperative infection. In our patient population, lower IL-1Ra level is commonly observed in the elderly with low body mass index. These findings suggest that postoperative infection, frequently seen in the nutritionally deficient elderly, may be the result of defective immunoinflammatory adaptation system.


Subject(s)
Colorectal Neoplasms/immunology , Postoperative Complications/immunology , Protein-Energy Malnutrition/immunology , Sialoglycoproteins/deficiency , Age Factors , Aged , Body Mass Index , Colectomy , Colon, Sigmoid/surgery , Female , Humans , Immune Tolerance/immunology , Interleukin 1 Receptor Antagonist Protein , Lymphocytes/immunology , Male , Middle Aged , Neutrophils/immunology , Predictive Value of Tests , Receptors, Interleukin-6/blood , Risk Factors , Surgical Wound Infection/immunology , Systemic Inflammatory Response Syndrome/immunology
19.
Dig Dis Sci ; 49(6): 970-6, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15309885

ABSTRACT

Up-regulation of the IL-1-IL-6 network stimulates systemic expression of C-reactive protein (CRP). This cytokine network system plays a pivotal role in inducing angiogenic growth factors in intestinal mucosa. Serum CRP level and tissue concentrations of cytokines in colorectal cancer patients were determined and an in vitro model was employed to determine the time course of induction of IL-6 in Caco-2 cells. Increased serum CRP was associated with recurrent disease and shorter survival time. Intense surgical stress and the presence of an acute phase reactant were independently associated with overexpression of IL-6 in the tumor. Enhanced IL-6 protein expression in Caco-2 cells induced by the initial treatment with IL-1beta or lipopolysaccharide could be abrogated by additional presupplementation of IL-1ra. The presence of an acute phase reactant reflects uncontrolled up-regulation of the local IL-1-IL-6 network system in the tumor, which may enhance the survival and proliferation of remnant cancer cells after tumor resection.


Subject(s)
C-Reactive Protein/metabolism , Colorectal Neoplasms/metabolism , Interleukin-1/metabolism , Interleukin-6/metabolism , Up-Regulation/physiology , Aged , Caco-2 Cells , Cell Culture Techniques , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
20.
Int J Clin Oncol ; 8(5): 336-9, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14586762

ABSTRACT

Insufficiency fractures of the pelvic bones are rare complications of radiotherapy, but they can cause significant morbidity. We report a patient who developed pelvic insufficiency fractures because of preoperative hypofractionated radiotherapy with chemotherapy for rectal carcinoma. She was treated with a four-field box technique, receiving 20 Gy in four fractions, and she underwent concurrent pharmacokinetic modulating chemotherapy (PMC; intravenous infusion of 5-fluorouracil [FU], 750 mg/body per 24 h and oral administration of uracil and futrafur [UFT] 400 mg/day) over a 1-week period. She developed severe buttock and femoral pain 10 months after this preoperative therapy. Physical examination at this time was unremarkable, with an absence of neurological signs, and radiographic examination was also normal, resulting in the patient initially being undiagnosed. However, 2 months after the onset of her initial pain, she was diagnosed as having pelvic insufficiency fractures on conventional radiographs. Although preoperative chemoradiotherapy has been widely accepted for improving local control and survival in patients with primary rectal carcinoma, surgeons need to be aware of this rare complication that can arise even 10 months after preoperative chemoradiotherapy.


Subject(s)
Fractures, Spontaneous/etiology , Pelvic Bones/injuries , Radiation Injuries , Rectal Neoplasms/radiotherapy , Aged , Female , Fractures, Spontaneous/diagnostic imaging , Humans , Pelvic Bones/radiation effects , Radiation Injuries/diagnostic imaging , Radiography
SELECTION OF CITATIONS
SEARCH DETAIL
...