Synchronous colorectal cancer (sCRC) is characterized by the occurrence of more than one tumor within six months of detecting the first tumor. Evidence suggests that sCRC might be more common in the ...serrated neoplasia pathway, marked by the CpG island methylator phenotype (CIMP), than in the chromosomal instability pathway (CIN). An increasing number of studies propose that CIMP could serve as a potential epigenetic predictor or prognostic biomarker of sCRC. Therapeutic drugs already used for treating CIMP-positive colorectal cancers (CRCs) are reviewed and drug selections for sCRC patients are discussed.
Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin ...have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE
and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.
For patients with locally advanced rectal cancer (LARC), achieving a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) provides them with the optimal prognosis. However, ...no reliable prediction model is presently available. We evaluated the performance of an artificial neural network (ANN) model in pCR prediction in patients with LARC. Predictive accuracy was compared between the ANN, k-nearest neighbor (KNN), support vector machine (SVM), naïve Bayes classifier (NBC), and multiple logistic regression (MLR) models. Data from two hundred seventy patients with LARC were used to compare the efficacy of the forecasting models. We trained the model with an estimation data set and evaluated model performance with a validation data set. The ANN model significantly outperformed the KNN, SVM, NBC, and MLR models in pCR prediction. Our results revealed that the post-CRT carcinoembryonic antigen is the most influential pCR predictor, followed by intervals between CRT and surgery, chemotherapy regimens, clinical nodal stage, and clinical tumor stage. The ANN model was a more accurate pCR predictor than other conventional prediction models. The predictors of pCR can be used to identify which patients with LARC can benefit from watch-and-wait approaches.
Background
Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell ...carcinoma (ESCC) remains unclear.
Patients and Methods
Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan–Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growth, migration, and invasion were examined using TE8, CE81T, and KYSE70 cells. The mechanisms involved were also analyzed. Nude mice models were used for assessment of tumor growth.
Results
Rad51 staining was predominantly observed in ESCC patients. ESCC patients with high Rad51 expression had significantly decreased survival (
P
< 0.001) combined with increased tumor size (
P
= 0.034) and lymph node metastasis (
P
= 0.039). Rad51 overexpression promoted, while its knockdown attenuated, esophageal cancer cell viability through cell cycle entry and migration/invasion via epithelial–mesenchymal transition. Moreover, Rad51 overexpression increased colony formation in vitro and tumor growth in vivo. In addition, high Rad51 expression increased cancer progression through the p38/Akt/Snail signaling pathway.
Conclusions
This study indicates a new biological role for Rad51 in ESCC progression. Rad51 may serve as a potential prognostic biomarker and therapeutic target for ESCC patients.
Taiwan's National Health Insurance has covered targeted therapy, namely cetuximab, for locally advanced head and neck cancers (LAHNC) since July 2009. This study examines treatment trends and ...survival effects of locally advanced head and neck cancer patients before and after Taiwan's National Health Insurance covered cetuximab.
We examined treatment trends and survival effects for patients with LAHNC using Taiwan's National Health Insurance Research Database. Patients who received treatment within 6 months were categorized as either nontargeted or targeted therapy groups. We analyzed treatment trends with the Cochran-Armitage trend test and explored factors associated with treatment selection and survival effects using multivariable logistic regression and Cox proportional hazards models.
Of the 20,900 LAHNC patients included in the study, 19,696 received nontargeted therapy, while 1,204 received targeted therapy. Older patients with more comorbid conditions, advanced stages and patients with hypopharynx and oropharynx cancers were more likely to receive targeted therapy with concomitant cetuximab treatment. Patients who received targeted therapy in addition to other treatment modalities had a greater risk of one-year and long-term all-cause mortality or cancer-specific mortality than those without receiving targeted therapy (P < 0.001).
Our study found an increasing trend in cetuximab utilization among LAHNC after reimbursement in Taiwan, but overall usage rates were low. LAHNC patients receiving cetuximab with other treatments had higher mortality risk than those receiving cisplatin, suggesting cisplatin may be preferred. Further research is needed to identify subgroups that could benefit from concomitant cetuximab treatment.
Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein ...kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.
Colorectal cancer is a major public health problem worldwide, and locally advanced rectal cancer (LARC) is known for its poor prognosis. A multimodal treatment approach is the only method to achieve ...satisfactory local recurrence and survival rates in LARC. Determining which therapeutic modality for LARC has the most satisfactory influence on quality of life and disease outcome is still controversial. LARC treatment is subject to continuous advancement due to the development of new and better diagnostic tools, radiotherapy techniques, and chemotherapeutic agents. Herein, we review various therapeutic modalities for LARC from several aspects. In addition to radiotherapy techniques such as neoadjuvant chemoradiotherapy (NCRT), we discuss the progress of chemotherapy, appropriate time interval between NCRT and surgery, relationship between tumor location and NCRT efficacy/safety, wait‐and‐watch policy, and predictors of treatment response following NCRT. Because of the controversies and unanswered questions regarding NCRT treatments for LARC, additional investigations are required to determine which therapeutic approach is the most feasible for LARC patients.
Ovarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and ...cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2
tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2
ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2
ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2
ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P < 0.05) with minimal obvious toxicity in a tumor-bearing mouse model. We believe that the mPEG × HER2 can significantly improve the therapeutic efficacy, potentially reduce the relapse freqency and thereby achieve good prognosis in ovarian cancer patients.
Background
Platinum resistance enhances DNA damage repair through nucleotide excision repair mechanisms involving the excision repair cross-complementing group 1 (
ERCC1
), X-ray cross-complementing ...group 1 (
XRCC1
), and excision repair cross-complementing group 2 (
ERCC2
). We evaluated the correlation between the expression of these three DNA repair genes and clinical outcomes in patients with rectal cancer receiving FOLFOX-based preoperative chemoradiotherapy (CRT).
Methods
Using immunohistochemistry, we examined the expression of ERCC1, ERCC2, and XRCC1 in pre-CRT cancer tissues from 86 patients with rectal cancer who had undergone curative resection and preoperative CRT with FOLFOX-4 to identify potential predictors of clinical outcomes.
Results
Following CRT, 57 and 29 patients were classified as responders (pathological tumor regression grade TRG 0 and TRG 1) and poor responders (TRG 2 and TRG 3), respectively. The multivariate analysis revealed that ERCC1 overexpression was correlated with a poor CRT response
p
< 0.0001; odds ratio (OR), 9.397; 95% confidence interval (CI) 2.721–32.457. Furthermore, a poor response to CRT (pathological TRG of 2–3) (
p
= 0.18; OR 5.685; 95% CI 1.349–23.954) and abnormal pre-CRT serum carcinoembryonic antigen levels (>5 ng/mL) (
p
= 0.03; OR 6.288; 95% CI 1.198–33.006) were independent predictors of postoperative relapse. By contrast, ERCC2 and XRCC1 expression did not play predictive roles in the analyzed patients.
Conclusions
ERCC1 overexpression is associated with a poor preoperative CRT response in patients with rectal cancer receiving FOLFOX-based preoperative CRT. ERCC1 is a potential biomarker for identifying patients who can benefit from customized treatment programs.
Intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) reduces overall treatment duration and results in less radiotherapy (RT)-induced dermatitis. However, the use of ...traditional sequential approach or IMRT-SIB is still under debate since there is not enough evidence of long-term clinical outcomes. The present study investigated 216 patients who underwent breast conserving surgery (BCS) between 2010 and 2013. The median age was 51 years (range, 21-81 years). All patients received IMRT-SIB, 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Among 216 patients, 175 patients received post-operative RT with forward IMRT and 41 patients had Tomotherapy. The median follow-up was 6.4 years. Forty patients (97.6%) in the Tomotherapy arm and 147 patients (84%) in the IMRT arm developed grade 0-1 skin toxicity (P = 0.021). For the entire cohort, the 5-year and 7-year overall survival (OS) rates were 94.4% and 93.1% respectively. The 7-year distant metastasis-free survival rates were 100% vs 89.1% in the Tomotherapy and IMRT arm respectively (P = 0.028). In conclusion, Tomotherapy improved acute skin toxicity compared with forward IMRT-SIB. Chronic skin complication was 1.9%. IMRT-SIB resulted in good long-term survival.
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