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1.
Mol Clin Oncol ; 11(4): 416-424, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31497299

ABSTRACT

Liquid biomarkers for the early detection of resistance to chemotherapy are important for improving prognosis. This study investigated the usefulness of plasma exosomal microRNA-125b (ex-miRNA-125b) for the early detection of resistance to modified fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)-based first-line chemotherapy in patients with advanced or recurrent (advanced/recurrent) colorectal cancer (CRC). First, ex-miRNAs associated with resistance to mFOLFOX6-based chemotherapy were profiled via miRNA microarray analysis. In this analysis, ex-miR-125b exhibited the greatest upregulation in patients with progressive disease (PD) compared with the findings for patients with stable disease (SD) and healthy controls. Next, another 55 patients with advanced/recurrent CRC who received mFOLFOX6-based first-line chemotherapy underwent a validation study of ex-miR-125b. Blood samples were collected before and during treatment until tumor progression. Ex-miRNA levels were measured via TaqMan microRNA assays. Patients with CRC had significantly higher ex-miR-125b levels than healthy controls. In patients with partial responses, ex-miR-125b levels at the Response Evaluation Criteria in Solid Tumors (RECIST) judgment point were significantly lower than those measured before treatment. In patients with SD, ex-miR-125b levels did not differ before and during treatment. In patients with PD, ex-miR-125b levels at the RECIST judgment point were significantly higher than those measured before treatment. These changes in ex-miR-125b levels were significantly different between groups even 1 month after the initiation of chemotherapy. Progression-free survival (PFS) was significantly worse in patients with high baseline ex-miR-125b levels than in those with low levels. In the Cox analysis, baseline ex-miR-125b levels and KRAS mutation were indicated to be independent prognostic factors for PFS. The present results suggest that plasma ex-miR-125b levels may be useful for the early detection of resistance to mFOLFOX6-based first-line chemotherapy. Furthermore, ex-miR-125b before chemotherapy is a predictive biomarker for PFS in patients with advanced/recurrent CRC.

2.
Int Surg ; 96(2): 139-43, 2011.
Article in English | MEDLINE | ID: mdl-22026305

ABSTRACT

A 67-year-old man had rectal cancer with para-aortic lymph node metastasis. Prior to surgical resection, tegafur-uracil and leucovorin had been administered orally as chemotherapy, and radiotherapy (50.4 Gy) was applied for the rectum and para-aortic lymph nodes. Low anterior resection was then performed, followed by 45 cycles of chemotherapy in total. Enlargement of the left axillary lymph nodes was noted during treatment, but nodes shrank in response to treatment with bevacizumab + FOLFIRI (i.e., irinotecan + 5-fluorouracil/leucovorin). As of the time of writing, 36 months after diagnosis, no swelling of the para-aortic lymph nodes was evident and chemotherapy was being continued. This patient was alive after achieving response to neoadjuvant therapy comprising chemotherapy and irradiation of the para-aortic lymph nodes, along with postoperative chemotherapy. This therapeutic approach of preoperative chemotherapy plus irradiation of the primary lesion and para-aortic lymph nodes has potential as an effective treatment.


Subject(s)
Neoadjuvant Therapy , Preoperative Care , Rectal Neoplasms/surgery , Aged , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Carcinoembryonic Antigen/blood , Colonoscopy , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Lymphatic Metastasis , Male , Radiotherapy Dosage , Rectal Neoplasms/diagnosis , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy , Tegafur/therapeutic use , Tomography, X-Ray Computed
3.
Int Surg ; 96(2): 176-81, 2011.
Article in English | MEDLINE | ID: mdl-22026313

ABSTRACT

Gastrointestinal metastasis of lung cancer is fairly rare, and metastasis to the duodenum is very uncommon. We report a case of duodenum and small intestine metastases of lung squamous cell carcinoma. The patient was a 66-year-old man. He was diagnosed with lung squamous cell carcinoma (T4N3M1 [mediastinum, cervical lymph node, and duodenum metastases], stage IV). He noted a sense of abdominal fullness on the evening of the day chemoradiotherapy was given, and emergency surgery was performed for suspected perforation of the digestive tract. Intraoperative findings included a tumor in the small intestine with a perforation at the tumor site; partial resection of the small intestine, including the tumor, was performed. Small intestine metastasis of lung cancer was diagnosed following histopathologic examination. When lung cancer patients complain of abdominal symptoms, it is important to consider gastrointestinal metastases in diagnosis and treatment.


Subject(s)
Carcinoma, Squamous Cell/secondary , Duodenal Neoplasms/secondary , Intestinal Neoplasms/secondary , Lung Neoplasms/pathology , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Duodenal Neoplasms/drug therapy , Duodenal Neoplasms/radiotherapy , Humans , Intestinal Neoplasms/surgery , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Lung Neoplasms/diagnostic imaging , Male , Tomography, X-Ray Computed
4.
Gan To Kagaku Ryoho ; 38(9): 1396-402, 2011 Sep.
Article in Japanese | MEDLINE | ID: mdl-21918334

ABSTRACT

The purpose of postoperative adjuvant chemotherapy is to achieve a higher or rate of surgical radical cure and to eliminate recurrence of cancer. There are many differences between colon cancer and rectal cancer. Recurrence of colon cancer almost always metastasizes to liver and lung Adjuvant chemotherapy is indicated for stage III and high risk stage II. Standard adjuvant chemotherapy is a combination of Leucovorin and 5-FU, or a combination of oxaliplatin, 5-FU and Leucovorin. Combination treatment with VEGF antibody and EGFR antibody has shown no evidence of effectiveness in adjuvant chemotherapy. In rectal cancer, radiation is the standard form of neoadjuvant therapy. In the future, treatment of colorectal cancer may make remarkable improvement with the introduction of new drugs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Chemotherapy, Adjuvant , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Neoplasm Staging
5.
Gan To Kagaku Ryoho ; 37(5): 791-4, 2010 May.
Article in Japanese | MEDLINE | ID: mdl-20495308

ABSTRACT

For the patient in whom the Kras gene variation appears, cancer cell grow and continue to multiply even if blocked by EGFR inhibitor. A topping the offered figure effect of cetuximab is not accepted. The addition of cetuximab for treatment of metastatic colorectal cancer with Kras wild-type tumors is effective.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , ErbB Receptors/metabolism , Mutation , Proto-Oncogene Proteins/genetics , Signal Transduction/drug effects , ras Proteins/genetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/immunology , Antineoplastic Agents/therapeutic use , Cetuximab , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , ErbB Receptors/immunology , Humans , Neoplasm Metastasis , Proto-Oncogene Proteins p21(ras)
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