Gastric cancer is the fourth most common cancer,and the second-highest cause of cancer-related deaths worldwide.Despite extensive research to identify novel diagnostic and therapeutic agents,patients ...with advanced gastric cancer suffer from a poor quality of life and poor prognosis,and treatment is dependent mainly on conventional cytotoxic chemotherapy.To improve the quality of life and survival of gastric cancer patients,a better understanding of the underlying molecular pathologies,and their application towards the development of novel targeted therapies,is urgently needed.Chemokines are a group of small proteins associated with cytoskeletal rearrangements,the directional migration of several cell types during development and physiology,and the host immune response via interactions with G-protein coupled receptors.There is also growing evidence to suggest that chemokines not only play a role in the immune system,but are also involved in the development and progression of tumors.In gastric cancer,CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment.CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation,survival,growth,invasion and metastasis,as well as indirectly by regulating angiogenesis,and tumor-leukocyte interactions.In this review,we will focus on the roles of CXC chemokines and their receptors in the development,progression,and metastasis of gastric tumors,and discuss their therapeutic potential for gastric cancer.
PURPOSE We investigated the experiences of cancer patients and their family caregivers who became aware that the cancer was terminal, how they became aware, and how they felt about disclosure of the ...information. PATIENTS AND METHODS In this cohort study, we administered questionnaires to 619 consecutive patients determined by physicians to be terminally ill and to their family caregivers. RESULTS A total of 481 patients and 381 family caregivers completed the questionnaire. A majority of patients (58.0%) and caregivers (83.4%) were aware of the patient's terminal status. Approximately 28% of patients and 23% of caregivers reported that they guessed it from the patient's worsening condition. The patient group was more likely than the caregiver group (78.6% v 69.6%) to prefer that patients be informed of their terminal status. Patients informed of their terminal diagnosis had a significantly better quality of life and fewer symptoms and had a lower rate of emotional distress than patients who guessed it from their worsening condition. Younger patients and patients who paid the treatment costs themselves were significantly more likely to want to be told when their illness was terminal. If the patient paid the treatment cost and was employed at the time of the cancer diagnosis, the family caregivers were more likely to prefer disclosure of terminal illness. CONCLUSION Most patients with terminal cancer and their family caregivers preferred disclosure, and patients who knew of their terminal diagnosis had a lower rate of emotional distress and a higher health-related quality of life.
We conducted this study to evaluate the validity of the perception that awareness of their terminal prognosis and use of palliative care or nonuse of an intensive care unit (ICU) causes patients to ...die sooner than they would otherwise.
In this prospective cohort study at 11 university hospitals and the National Cancer Center in Korea, we administered questionnaires to 619 consecutive patients immediately after they were determined by physicians to be terminally ill. We followed patients during 6 months after enrollment and assessed how their survival was affected by the disclosure of terminal illness and administration of palliative care or nonuse of the ICU.
In a follow-up of 481 patients and 163.8 person-years, we identified 466 deceased patients. Nineteen percent of the patients died within 1 month, while 41.3% lived for 3 months, and 17.7% lived for 6 months. Once the cancer was judged terminal, the median survival time was 69 days. On multivariate analysis, neither patient awareness of terminal status at baseline (adjusted hazard ratio aHR, 1.20; 95% CI, 0.96 to 1.51), use of a palliative care facility (aHR, 0.96; 95% CI, 0.76 to 1.21), nor general prostration (aHR, 1.23; 95% CI, 0.96 to 1.57) was associated with reduced survival. Use of the ICU (aHR, 1.47; 95% CI, 1.06 to 2.05) and poor Eastern Cooperative Oncology Group performance status (aHR, 1.37; 95% CI, 1.10 to 1.71) were significantly associated with poor survival.
Patients' being aware that they are dying and entering a palliative care facility or ICU does not seem to influence patients' survival.
Background
Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP).
Methods
...Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen.
Results
Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS.
Conclusion
In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.
Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal ...cancer (mCRC).
Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models.
Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months 95% confidence interval (CI), 12.0 to 15.5 vs. 18.0 months 95% CI, 16.3 to 19.7 or 19.9 months 95% CI, 18.5 to 21.3, respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses.
Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Background. Scrub typhus is one of the most important endemic infections in the Asia-Pacific region. Although tetracyclines or chloramphenicol are the recommended drugs of choice for the treatment of ...scrub typhus, reports of doxycycline-resistant strains have prompted a search for alternative treatments. Methods. We conducted a prospective, open-label, randomized trial from September 2002 through November 2003 to compare azithromycin with doxycycline for the treatment of mild scrub typhus. The time to defervescence was assessed to compare the efficacy of the 2 treatment regimens. Results. A total of 93 patients were randomly assigned to receive either a single 500-mg dose of azithromycin or a 1-week course of daily oral 200-mg dose of doxycycline. Cure was achieved in 47 (100%) of 47 patients in the azithromycin-treated group and in 43 (93.5%) of 46 patients in the doxycycline-treated group (P = .117). The median time to defervescence was 21 h for the azithromycin-treated group and 29 h for the doxycycline-treated group (P = .097). There were no serious adverse events during the study. No relapses occurred in either group during a 1-month follow-up period. Conclusion. The single 500-mg dose of azithromycin was as effective as the 1-week course of daily 200-mg doses of doxycycline for the treatment of mild scrub typhus acquired in South Korea.
Few studies have addressed whether there are differences in clinical efficacy between intravenous methylprednisolone (methyl-Pd) and intravenous immunoglobulin (IVIg) use.
We retrospectively compared ...platelet responses and toxicities associated with these two treatments in adult patients with immune thrombocytopenia. Patients received intravenous methyl-Pd therapy followed by oral prednisolone (Pd) from 1993 to 2002 and IVIg together with oral Pd from 2003 to 2008.
Early response and maintenance of the response were assessed at 7 days and 6 months after treatment, respectively. Of the 87 patients enrolled, 77 (88.5%) were eligible for analysis. Early responses occurred in 30 of 39 patients (76.9%) receiving methyl-Pd versus 33 of 38 patients (86.6%) receiving IVIg (p = 0.187). The response was maintained in 28 patients (71.8%) in the methyl-Pd arm and in 23 patients (60.5%) in the IVIg arm (p = 0.187). The time to a complete response in the IVIg arm (6 days; range, 1 to 35) was shorter than that in the methyl-Pd arm (13.5 days; range, 2 to 29) (p = 0.002). Side effects were mild and tolerable in both arms. Five years after initiating treatment, 7 of 18 patients (38.9%) and five of 14 patients (35.7%) were still maintaining a response in the methyl-Pd and IVIg arms, respectively.
These results indicate that neither the early response rate nor the long-term outcome differed between the methyl-Pd and IVIg treatments. However, IVIg induced a complete response more rapidly than did methyl-Pd.
The C-X-C chemokine receptor 7 (CXCR7) has been shown to be a decoy receptor for CXCR4 in certain cell types. We investigated the expression status and functional roles of CXCR7 in acute myeloid ...leukemia (AML) cells in vitro.
CXCR7 mRNA was knocked down in AML cells by using small interfering RNA (siRNA) technology, and subsequent biological alterations in the cells were evaluated in vitro.
All AML cell lines examined in this study (U937, K562, KG1a, HL-60, and MO7e) and primary CD34(+) cells obtained from patients with AML expressed CXCR7 mRNA at various levels. Western blotting showed that all AML cells produced CXCR7. Furthermore, all AML cells expressed CXCR7 in both the cytoplasm and on the cell surface at various levels. Stromal cell-derived factor-1 (SDF-1; C-X-C motif ligand 12 (CXCL12)) induced internalization of cell surface CXCR7. However, neither hypoxia nor the examined hematopoietic growth factors (interleukin-1β (IL-1β), IL-3, IL-6, granulocyte-colony-stimulating factor, granulocyte, macrophage-colony-stimulating factor, and stem cell factor) and proinflammatory cytokines (interferon-γ, transforming growth factor-β, and tumor necrosis factor-α) were found to alter cell surface CXCR7 expression. The transfection of AML cells with CXCR4 siRNA, but not CXCR7 siRNA, significantly impaired the CXCL12-induced transmigration of the cells. The transfection of AML cells with CXCR7 siRNA did not affect the survival or proliferation of these cells. Knockdown of CXCR7, but not CXCR4, induced the upregulation of CXCL12 mRNA expression and CXCL12 production in AML cells.
CXCR7 is involved in the regulation of autocrine CXCL12 in AML cells.
Objective Iron-deficiency anemia (IDA) is the most common nutritional deficiency worldwide. However, the information concerning various causes of IDA in adult men is still insufficient. The aim of ...our study was to evaluate adult men with IDA. Methods We prospectively studied 206 adult men with IDA. All subjects had a direct history taken and underwent a physical examination. Esophagogastroduodenoscopy was performed in most patients, and colonoscopy was conducted if no lesion causing IDA was found or the fecal occult blood test was positive. Results The history of prior gastrectomy and blood-letting cupping therapy that probably had caused IDA were reported in 24 (11.7%) and 11 (5.3%) patients, respectively. In terms of potential causes of IDA, 68 (33.0%) patients were found to have upper gastrointestinal disorders (34 peptic ulcers, 17 erosive gastritis, 16 gastric cancers, and one gastrointestinal stromal tumor). Colonoscopy showed 42 (20.4%) clinically relevant lesions that probably caused IDA: colon cancer (five patients), colon polyps (14 patients), ulcerative colitis (one patient), and hemorrhoids (22 patients). One small bowel tumor was detected at small bowel series. Concerning malignant lesions that were responsible for IDA, 22 malignant lesions were found in patients of 50 years or older, accounting for 16.8% (22 of 131 patients), while only one (1.3%) early gastric cancer was found in the younger patients. Conclusion This study demonstrated that gastrointestinal blood loss is the main cause of IDA in adult men, and that there is a high rate of malignancy in men older than 50 years, emphasizing the need for a complete, rigorous gastrointestinal examination in this group of patients. Considering blood-letting cupping therapy, there is a need to consider culture-specific procedures as a possible cause of IDA.
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