Molecular classification of cancers has been significantly improved patient outcomes through the implementation of treatment protocols tailored to the abnormalities present in each patient's cancer cells. Breast cancer represents the poster child with marked improvements in outcome occurring due to the implementation of targeted therapies for estrogen receptor or human epidermal growth factor receptor-2 positive breast cancers. Important subtypes with characteristic molecular features as potential therapeutic targets are likely to exist for all tumor lineages including hepatocellular carcinoma (HCC) but have yet to be discovered and validated as targets. Because each tumor accumulates hundreds or thousands of genomic and epigenetic alterations of critical genes, it is challenging to identify and validate candidate tumor aberrations as therapeutic targets or biomarkers that predict prognosis or response to therapy.
Therefore, there is an urgent need to devise new experimental and analytical strategies to overcome this problem. Systems biology approaches integrating multiple data sets and technologies analyzing patient tissues holds great promise for the identification of novel therapeutic targets and linked predictive biomarkers allowing implementation of personalized medicine for HCC patients.
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PURPOSE This study was designed to evaluate the efficacy of a combination treatment of S-1 plus either irinotecan or docetaxel for advanced/metastatic non-small cell lung cancer (NSCLC) patients who have already failed 3 or more lines of treatment. MATERIALS AND METHODS This was a prospective single center phase II study. The eligible patients received S-1 40 mg/m2 twice a day orally on days 1 though 14 combined with irinotecan 150 mg/m2on D1 only or docetaxel 35 mg/m2 on D1 and D8. The treatment was repeated every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The choice between the two regimens was made at the discretion of the treating physician. RESULTS A total of 14 patients participated in the study.
There were 3 patients with squamous cell carcinoma, 9 with adenocarcinoma, and 2 with NSCLC, NOS. Eight of the patients were male. There were 8 patients with an Eastern Cooperative Oncology Group (ECOG) of 1, and 6 patients with an ECOG of 2. All the patients had already been treated with platinum-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor therapy. Out of the 14 patients, 10 received irinotecan and S-1 and the other 4 received docetaxel and S-1. Twelve patients had also received pemetrexed. Disappointingly, there were no response from 2 patients with a stable disease, and therefore, as per the protocol, we stopped the study early. With a median follow-up time of 49 months, the median survival time was 5.6 months (95% confidence interval, 4.3 to 6.9 months). CONCLUSION S-1 containing doublets did not show activity in this population as a salvage treatment and further investigation cannot be recommended.
PURPOSE This study aimed to analyze the efficacy and toxicity of gemcitabine plus platinum chemotherapy for patients aged 70 years or older with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS We reviewed the records of stage IIIB, IV NSCLC patients or surgically inoperable stage II, IIIA NSCLC patients who were aged 70 years or older when treated with gemcitabine (1,250 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) chemotherapy from 2001 to 2010 at Seoul St. Mary's Hospital, Uijeongbu St. Mary's Hospital and St. Vincent's Hospital. Gemcitabine was administered on days 1 and 8, and cisplatin or carboplatin was administered on day 1. Treatments were repeated every 3 weeks for a maximum of 4 cycles. RESULTS The median age of the 62 patients was 73.5 years (range, 70 to 84 years). Forty-one (66%) patients exhibited comorbidity. The mean number of treatment cycles was 3.9.
The compared average relative dose intensity of gemcitabine plus platinum chemotherapy was 84.8%. The median progression-free survival and overall survival (OS) were 5.0 months and 9.4 months, respectively. Reduced Eastern Cooperative Oncology Group (ECOG) performance status (none vs. > or =1) and weight loss (<5% vs. > or =5%) after treatment were found to have a significant effect on OS (p=0.01). CONCLUSION Gemcitabine plus platinum chemotherapy is an effective treatment option with an acceptable level of toxicity in patients aged 70 years or older with good performance status in advanced NSCLC.
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A cross-country review of data collected on non-small cell lung cancer (NSCLC) patients in cancer registries, databases, retrospective and non-randomized prospective studies Anna De Geer, Jennifer Eriksson, Henrik W. Finnern Journal of Medical Economics.2013; 16(1): 134. CrossRef
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PURPOSE Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin. MATERIALS AND METHODS CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals. RESULTS Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously.
Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death.
Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival. CONCLUSION The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.
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Should isolated peritoneal carcinomatosis from colorectal cancer be sub-classified into stage IVB in era of modern chemotherapy? H. Ishida, K. Kumamoto, K. Ishibashi, S. Hatano, T. Matsuzawa, N. Okada, Y. Kumagai, H. Baba, N. Haga Techniques in Coloproctology.2013; 17(6): 647. CrossRef
Peritoneal carcinomatosis of colorectal origin: is it really an end-stage disease? E. Chouillard, V. Greco, N. Tsiminikakis Techniques in Coloproctology.2013; 17(6): 619. CrossRef
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PURPOSE High-risk prostate cancer patients undergoing treatment often experience biochemical recurrence. The use of bisphosphonates as an adjuvant treatment delays skeletal events, yet whether or not bisphosphonates also delay metastastic development remains to be determined. MATERIALS AND METHODS A total of 140 high-risk prostate cancer patients who were undergoing definitive treatment and who had clinically organ-confined disease and who suffered from biochemical recurrence were administered intravenous (IV) clodronate. The patients were treated with a radical retropubic prostatectomy (RP) or curative radiotherapy (RTx). Upon androgen deprivation therapy initiation, tri-monthly IV clodronate was added to the treatment to prevent bone demineralization. Twenty-six out of 60 operated cases and 45 out of 80 irradiated cases received bisphosphonate. The length of time until the first bone metastasis was recorded and analyzed. RESULTS No statistical difference was found for the type of primary treatment (RP or RTx) on the time to the first bone metastasis (95% confidence interval [CI], 0.40 to 2.43; p=0.98). However, there was a clear advantage favoring the group that received bisphosphonate (p<0.001). The addition of bisphosphonate delayed the appearance of the first bone metastasis by seven-fold (95% CI, 3.1 to 15.4; p<0.001). CONCLUSION Treatment with tri-monthly IV clodronate delayed the time to the first bone metastasis in high-risk prostate cancer patients who were experiencing an increase in the prostate specific antigen level after definitive treatment.
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Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer Nicole M Reusser, Heather J Dalton, Sunila Pradeep, Vianey Gonzalez-Villasana, Nicholas B Jennings, Hernan G Vasquez, Yunfei Wen, Rajesh Rupaimoole, Archana S Nagaraja, Kshipra Gharpure, Takahito Miyake, Jie Huang, Wei Hu, Gabriel Lopez-Berestein, Anil K Cancer Biology & Therapy.2014; 15(8): 1061. CrossRef
Ibandronate increases the expression of the pro-apoptotic gene FAS by epigenetic mechanisms in tumor cells R. Thaler, S. Spitzer, H. Karlic, C. Berger, K. Klaushofer, F. Varga Biochemical Pharmacology.2013; 85(2): 173. CrossRef
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PURPOSE The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response. MATERIALS AND METHODS Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study.
Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI. RESULTS The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy. CONCLUSION It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles.
Development of individualized chemotherapy regimens based on gene expression profiles is warranted.
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PURPOSE The prognosis of gastric cancer patients with bone marrow metastases is extremely poor. The current study was conducted to evaluate the clinical outcomes of advanced gastric cancer patients with bone marrow metastases. MATERIALS AND METHODS We retrospectively reviewed the medical records of 26 advanced gastric cancer patients with bone marrow metastases who were treated at Soonchunhyang University Hospital between September 1986 and February 2009. RESULTS The median age was 46 years (range, 24 to 61 years). All patients had poorly differentiated adenocarcinoma, including 17 signet ring cell carcinomas.
The majority of the patients had thrombocytopenia, anemia, and elevated lactate dehydrogenase levels. Sixteen patients (61.5%) received palliative chemotherapy (median, 4 cycles; range, 1 to 13 cycles). The median overall survival after detection of bone marrow metastases for the cohort of patients was 37 days (95% confidence interval, 12.5 to 61.5 days). The median overall survival after detection of bone marrow involvement was 11 days in the best supportive care group (range, 2 to 34 days) and 121 days (range, 3 to 383 days) in the palliative chemotherapy group (p<0.001). The causes of death were tumor progression (11 patients, 45%), brain hemorrhage (6 patients, 25%), infection (5 patients, 21%), and disseminated intravascular coagulation (1 patient, 4%). There were no chemotherapy-related deaths. CONCLUSION Palliative chemotherapy could be considered in advanced gastric cancer patients with bone marrow metastases as a treatment option.
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Methylated TIMP-3 DNA in Body Fluids Is an Independent Prognostic Factor for Gastric Cancer Jiang-Liu Yu, Ping Lv, Jing Han, Xin Zhu, Lian-Lian Hong, Wang-Yu Zhu, Xin-Bao Wang, Yi-Chen Wu, Pei Li, Zhi-Qiang Ling Archives of Pathology & Laboratory Medicine.2014; 138(11): 1466. CrossRef
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PURPOSE About 10% of all gastric cancers (GCs) are Epstein-Barr virus (EBV)-associated. However, the oncogene of EBV in gastric carcinogenesis has not yet been established. In the present study, we investigated the virus-derived transcripts in the EBV-infected GC cell line to explore the viral oncogene of EBV-positive GCs. MATERIALS AND METHODS We used the SNU719 cell line, a naturally derived EBV-infected GC cell line. The individual expressed sequence tags from the cDNA libraries of SNU719 were searched against the mRNA subset extracted from the GenBank data base. Sequence reaction was carried out for the EBV-associated clones. Reverse transcription-polymerase chain reaction was performed after cells were partitioned into nuclear and cytoplasmic fractions. RESULTS Using bioinformatic tools, we selected 13 EBV-associated clones from cDNA libraries of SNU719. By sequencing analysis, we revealed that they were all associated with RPMS1, one of the BamHI-A rightward transcripts (BART) of EBV. Some BART cDNAs such as RPMS1 and A73 are known to be translated into protein in vitro, and have been shown to have some biochemical functions relevant to tumorigenesis. But, presently, the BART transcripts were expressed only in the nucleus and not in the cytoplasm, arguing against their role as messenger RNAs. Some other BART transcripts expressed in GCs (BARF0, CST, vIL, BARF1, BLLF1, and BcLF1) were also extensively detected in the nucleus. CONCLUSION BART transcripts are the predominant viral transcripts expressed in EBV-associated GCs, and they are located only in the nucleus. Therefore, it seems less likely that BART transcripts produce functional proteins to play a role in carcinogenesis of EBV-associated GCs.
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