Abstract Background Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab×mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with anti-mPEG single chain antibodies (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” PEGylated liposomal doxorubicin (PLD) to enhance the cellular internalization and anticancer activity of PLD. Results We successfully constructed the CD20 Ab×mPEG scFv and proved that CD20 Ab×mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab×mPEG scFv and PLD successfully led to a 9-fold increase in tumor cytotoxicity (LC 50 : 0.38 nM) compared to the CD20 Ab×DNS scFv and PLD (lC 50 : 3.45 nM) in vitro . Importantly, a combination of CD20 Ab×mPEG scFv and PLD had greater anti-liquid tumor efficacy ( P = 0.0005) in Raji-bearing mice than CD20 Ab×DNS scFv and PLD. Conclusion Our results indicate that this “double-attack” strategy using CD20 Ab×mPEG scFv and PLD can retain the tumor targeting ( first attack ) and confer PLD tumor-selectivity ( second attack ) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.
Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray to compare the miRNA profiles of patients with LARC who achieved pCR (pCR group, n = 5) with those who did not (non-pCR group, n = 5). The validation set confirmed that miRNA-148a was overexpressed in the pCR group (n = 11) compared with the non-pCR group (n = 40). Cell proliferation and clonogenic assays revealed that miRNA-148a overexpression radio-sensitized cancer cells and inhibited cellular proliferation, before and after irradiation (p < 0.01). Apoptosis assays demonstrated that miRNA-148a enhanced apoptosis before and after irradiation. Reporter assays revealed that c-Met was the direct target gene of miRNA-148a. An in vivo study indicated that miRNA-148a enhanced the irradiation-induced suppression of xenograft tumor growth (p < 0.01). miRNA-148a may be a biomarker of pCR following NACRT and can promote apoptosis and inhibit proliferation in CRC cells by directly targeting c-Met in vitro and enhancing tumor response to irradiation in vivo.
Technologies that screen multiple single-nucleotide polymorphisms (SNPs) could be very valuable in predicting patients' susceptibilities to diseases or responses to therapeutic interventions. In this study, we developed a chip that can accurately detect four SNPs at same time. This chip is cost-effective and user-friendly because it uses a detection protocol analogous to dot blotting and does not require sophisticated instruments. To establish this chip, we designed and blotted onto a nylon membrane SNP-specific oligonucleotide probes for human angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E. This chip detected the corresponding SNPs harbored within the angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E sequences from 20 donors. Importantly, the SNPs detected by our chip matched exactly with the direct sequencing results, thereby highlighting the accuracy of this chip. In conclusion, our chip is a robust tool for multiple SNP screening and holds the potential to future refinement in detecting diseases-associating genes in patients.
The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II-III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those in the 3DCRT group (66.7% vs 43.5%, P = 0.071). The median follow-up was 53 months (range, 18-95 months) in the 3DCRT group and 43 months (range, 17-69 months) in the IG-IMRT group. Four-year overall, disease-free, and local failure-free survival rates of the IG-IMRT and 3DCRT groups were 81.6% and 67.9% (P = 0.12), 53.8% and 51.8% (P = 0.51), and 88% and 75.1% (P = 0.031), respectively. LARC patients treated with preoperative IG-IMRT achieved lower acute gastrointestinal adverse effects and a higher local control rate than those treated with 3DCRT, but there was no prominent difference in distant metastasis rate and overall survival between two treatment modalities.
Purpose Radiation combined with natural products may improve the radiosensitivity of cancer cells. This study investigated the potential of a combined modality treatment with Ultraviolet C (UVC; wavelength range 200–280 nm) and our previously identified anti-oral cancer agent (methanolic extracts of Cryptocarya concinna roots; MECCrt) in oral cancer cells.
After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed.This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage.The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p < 0.05). The complication rate related to stoma closure was 36.0%. Patients with ileostomy had an increased risk of developing complications (p = 0.017), and early closure of the defunctioning stoma yielded a higher incidence of morbidity (p = 0.006). Multivariate analysis revealed that a time to closure of ≤109 days was an independent risk factor for developing complications (p = 0.007).The optimal timing of stoma reversal is at least 109 days after stoma construction in rectal cancer patients receiving concurrent chemoradiotherapy and low anterior resection.
Abstract 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.
Abstract: We reported a 59-year-old female who diagnosed with right breast invasive lobular carcinoma (pT2N0M0, stage IIA) and received modified radical mastectomy with adjuvant chemotherapy and radiotherapy (50 Gy) in 1999. But, she found T10-spine metastasis and received palliative radiotherapy (30 Gy in 10 fractions) 3 years later. In 2012, she had a left abdominal mass and received abdominal wall tumor resection and a metaplastic invasive lobular carcinoma [estrogen receptor (ER)(+), progesterone receptor (PR)(−), human epidermal growth factor receptor 2 (HER2)(−) with positive surgical margin] was noted by pathological reports. In spite of hormone therapy, she experienced a left abdominal painless mass at the same location underneath the previous surgical scar in 2016. After surgical excision, computed tomography showed a residual left external oblique muscle 4.8 cm × 5.0 cm mass. Under the impression of right breast cancer with left external oblique muscle metastasis [metastatic invasive lobular carcinoma, rcT0N0M1, rpT0N0M1, stage IV (AJCC 7th staging)], she received post-operative radiotherapy 60 Gy in 30 fractions. She continued to receive chemotherapy and no evidence of abdominal recurrence till now.
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