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Purpose@#Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. @*Methods@#We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. @*Results@#In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. @*Conclusion@#Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.
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Purpose@#Real-time detection and intervention can be used as potential measures to markedly decrease breast cancer mortality. Assessment of circulating tumor DNA (ctDNA) may offer great benefits for the management of breast cancer over time. However, the use of ctDNA to predict the effectiveness of neoadjuvant treatment and recurrence of breast cancer has rarely been studied. @*Methods@#We prospectively recruited 31 breast cancer patients with 4 subtypes. Three time points were set in this study, including before any therapy (C1), during surgery (T), and six months after surgery (C2). We collected peripheral blood samples from all 31 patients at C1, tumor tissue from all 31 patients at T, and peripheral blood samples from 25 patients at C2. Targeted 727-gene panel sequencing was performed on ctDNA from all blood samples and tissue DNA from all tissue samples. Somatic mutations were detected and analyzed using a reference standard pipeline. Statistical analysis was performed to identify possible associations between ctDNA profiles and clinical outcomes. @*Results@#In total, we detected 159, 271, and 70 somatic mutations in 30 C1 samples, 31 T samples, and 12 C2 samples, respectively. We identified specific genes, such as PIK3CA, TP53, and KMT2C, which were highly mutated in the tissue samples. Furthermore, mutated KMT2C observed in ctDNA of the C2 samples may be an indicator of breast cancer recurrence. @*Conclusion@#Our study highlights the potential of ctDNA analysis at different timepoints for assessing tumor progression and treatment effectiveness, as well as prediction of breast cancer recurrence.
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Objective To summarize the experience ofmultidisciplinary team (MDT) in diagnosis and treatment of complicated and refractory thyroid tumors.Methods A retrospective review was performed on clinical data of 46 cases with complicated and refractory large thyroid tumors admitted to our hospital from Jan.2010 to Dec.2016.There were 23 cases in MDT group and 23 cases in the control group,respectively.The MDT group received diagnosis and treatment provided by multidisciplinary team during perioperative period whereas the control group received conventional surgery.Results Short-term complications such as trouble breathing and thyroid crisis were not observed in 46 patients after surgery.In the control group,the mean durations were (52±11.5)minutes for anesthesia,(159±38.1) minutes for surgery and (11 ±3.5) days for hospital stay,respectively.After surgery,bleeding occurred in 5 cases,hoarseness in 5 cases,irritating cough when drinking in 7 cases,transient hypocalcemia in 8 cases,permanent hypocalcemia in 6 cases,and neck tracheotomy due to tracheomalacia during surgery in 2 cases.In MDT group,the mean durations were (37±8.5) minutes for anesthesia,(134±28.5) minutes for surgery and (7±1.5) days,respectively.After surgery,bleeding occurred in 0 case,hoarseness in 0 case,irritating cough when drinking in 1 case,transient hypocalcemia in 2 cases,permanent hypocalcemia in 0 case,and neck tracheotomy due to tracheomalacia during surgery in 4 cases.Conclusion Application of multidisciplinary team in diagnosis and treatment of complicated and refractory thyroid tumors can reduce duration of preoperative endotracheal anesthesia as well as surgery,decrease postoperative complications,shorten duration of hospitalization and improve life quality after surgery.
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The poly(ADP-ribose) polymerases (PARPs) is an important group of enzymes in DNA repair pathways, especially the base excision repair (BER) for DNA single-strand breaks (SSBs) repair. Inhibition of PARP in DNA repair-defective tumors (like those with BRAC1/2 mutations) can lead to cell death and genomic instability, what is so called "synthetic lethality". Currently, PARP inhibitors combined with cytotoxic chemotherapeutic agents in the treatment of BRCA-1/2 deficient cancers are in the clinical development. In this review, we will be focused on the development of combination application of PARP inhibitors with other anticancer agents in clinical trials.
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Objective To study the effects of caffeic acid phenethyl ester (CAPE) on the expression of β-catenin, c-myc and cyclin D1 in colorectal cancer cell line SW480. Methods The changes of mRNA and protein expression of β-catenin, cyclin DI and c-myc were detected by RT-PCR and Western blot after culturing the colorectal cancer cell line SW400 with different concentrations of CAPE (2.5, 5.0, 10.0 mg/L) for 24 hours and 48 hours. Results After the treatment of CAPE, the mRNA expression of β-catenin, cyclin D1 and c-myc were decreased from 1.05±0. 26, 0.87±0.09, 0.63 ± 0. 09 to 0.67 ±0. 10, 0.51±0.14, 0.32±0.14, respectively, and the protein expression of β-catenin, cyclin D1 and c-myc were decreased from 204±52, 111±11, 87±7 to 52±16, 52±16, 32±12, respectively. There was a significant difference in the decrease of mRNA and protein expression of β-catenin, cyclin D1 and c-myc in colorectal cancer cell line SW480 with and without treatment of CAPE (F=5.724, 6.793, 7.026, 15.936, 14.889, 14.162, 31.147, 28.881, 6.322, 17.647, 9.584, P<0.05 ). The inhibition effect of CAPE was displayed in a dose- and time-dependent manner. Conclusions CAPE can obstruct the β-catenin pathway, and down-regulate the transcription and expression of β-catenin, cyclin D1 and c-myc. The anti-tumor effect of CAPE may be related to the decreased expression of β-catenin, cyclin DI and c-myc.
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Objective To study the expression and significance of proliferating cell nuclear antigen (PCNA) and argyrophilia nucleolar organizer regions (AgNORs) in colorectal carcinoma (CRC) and carcinoma adjacent mucosa (CAM).Methods The expression of PCNA in 48 cases of colorectal carcinoma tissue, CAM and 10 cases of normal mucosa was detected by immunohistochemistry techniques. AgNORs was determined with argyrophilia stain. Results The PCNA labeling index (PCNA LI) and AgNORs count in CRC were higher than that in CAM and normal mucosa( P
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Objectives To study the relationship between gastrin expression and proliferating cell nuclear antigen (PCNA),argyrophilia nucleolar organizer regions(AgNORs) in colorectal cancer (CC) tissue. Methods Gastrin and PCNA expression in 48 cases of CC tissue and cancer adjacent mucosa was detected by immunohistochemistry techniques. AgNORs was determined with argyrophilia stain. Results The positive rate of gastrin in CC tissue was 39 58%, that of well differentiated adenocarcinoma was higher than the poorly differentiated and mucinous adenocarcinoma( P
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Objective To study the relationship between gastrin and c-myc, c-fos expression in colorectal cancerous tissue and the mechanism of gastrin effect on colorectal cancer.Methods The gastrin and c-myc, c-fos expression in 48 cases of colorectal cancerous tissue and cancer-adjacent mucosa were detected with immunohistochemistry techniques. Results The positive rate of gastrin in colorectal cancerous tissue was 39.58%. The rate of the well differentiated adenocarcinoma was higher than that of the poorly differentiated and mucinous adenocarcinoma(P＜0.05). The positive rates of c-myc and c-fos in colorectal cancerous tissue were higher than those in cancer-adjacent and normal mucosa. The positive rate of c-myc and c-fos in the group with gastrin positive expression were 78.94% and 73.68%, higher than those in the group with negative gastrin expression(37.93% and 31.04%). Conclusion Some of colorectal cancer cells formed and secreted gastrin through autocrine. The increase of c-myc, c-fos etc oncogene expression probably stimulate the cancer cells proliferation.
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Objective To observe the effect of caffeic acid phenethyl ester (CAPE) on proliferation, cell cycle and apoptosis of human colorectal cancer cell line SW480.MethodsSW480 cells were treated with CAPE .The proliferative status of cells was measured by methabenzthiazuron (MTT) assay. Cell cycle was analyzed by flow cytometry (FCM) . Apoptosis was detected by FCM. The apoptosis cells were detected by TUNEL staining.ResultsCAPE inhibited growth of SW480 cells in a dose-dependent and time-dependent manner. Cell G_0/G_1 phase rate increased, S phase rate decreased and cell apoptosis rate increased after exposed to CAPE in a dose dependent manner (2.5, 5.0 and 10mg/L). Apoptosis cells increased after the treatment of CAPE.ConclusionsCAPE inhibits the proliferation and induces apoptosis in human colon cancer cell line SW480.The effect mechanism is related to arrest the cell cycle G_1 and induce cell apoptosis.
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Objective To investigate the relationship between ? catenin expression and colorectal adenoma with canceration. Methods The expression levels of ? catenin in 25 cases of normal colorectal mucosa (NCM), 42 cases of colorectal adenoma (CA), and 19 cases of colorectal adenoma with canceration (CAC) were detected by immunohistochemistry. Results ? catenin expression was detected on the cell membrane in normal colorectal mucosa. Reduced membrane expression, cytoplasmic and nuclear expression were detected in the colorectal adenoma and adenoma with canceration. The cytoplasmic and nuclear expression rate of ? catenin was 89.5% in colorectal adenoma with canceration, significantly higher than that in colorectal adenoma(42 9%, P
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0.05) Conclusion Subtotal colectomy and intraoperative colonic irrigation are effective methods for management of obstructing carcinoma in the left colon To select an effective technique depends on the analysis of the practical situations and evaluation of the idiographic complexions.
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Objective To study the effect of caffeic acid phenethyl ester (CAPE) on the expression of ?-catenin in the cultured colorectal cancer cell lines. Methods HCT116 and W480 cells were treated with CAPE at serial concentrations of 2.5, 5, and 10 mg/L. ?-catenin protein expression was assayed by Western blot analysis. ?-catenin localization was detected by indirect immunofluorescence. Results CAPE treatment was associated with decreased total ?-catenin protein expression. The expression of ?-catenin at the cell nucleus and cytoplasm was downregulated, but at the cell-cell linked site the ?-catenin protein expression was upregulated. Conclusion CAPE can downregulate the expression of ?-catenin and inhibit the translocation of ?-catenin to nucleus, which may play an important role in the anticancer activity of CAPE.