BACKGROUND Sessile serrated lesions(SSLs)are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer.Previous studies in Vietnam mainly investigated the adenoma path...BACKGROUND Sessile serrated lesions(SSLs)are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer.Previous studies in Vietnam mainly investigated the adenoma pathway,with limited data on the serrated pathway.AIM To evaluate the prevalence,risk factors,and BRAF mutations of SSLs in the Vietnamese population.METHODS This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam.SSLs were diagnosed on histopathology according to the 2019 World Health Organi-zation classification.BRAF mutation analysis was performed using the Sanger DNA sequencing method.The multivariate logistic regression model was used to determine SSL-associated factors.RESULTS There were 2489 patients,with a mean age of 52.1±13.1 and a female-to-male ratio of 1:1.1.The prevalence of SSLs was 4.2%[95%confidence interval(CI):3.5-5.1].In the multivariate analysis,factors significantly associated with SSLs were age≥40[odds ratio(OR):3.303;95%CI:1.607-6.790],male sex(OR:2.032;95%CI:1.204-3.429),diabetes mellitus(OR:2.721;95%CI:1.551-4.772),and hypertension(OR:1.650,95%CI:1.045-2.605).The rate of BRAF mutations in SSLs was 35.5%.CONCLUSION The prevalence of SSLs was 4.2%.BRAF mutations were present in one-third of SSLs.Significant risk factors for SSLs included age≥40,male sex,diabetes mellitus,and hypertension.展开更多
The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC pat...The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China.The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively.KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction(q-PCR)in 410 CRC patients,with mutation frequencies of KRAS,NRAS and BRAF of 47.56%,2.93%and 4.15%,respectively.The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed.The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes.The BRAF gene mutation was also associated with cancer thrombosis in blood vessels.Cox regression analysis showed that there was no statistically significant difference in the overall survival(OS)between patients with KRAS,NRAS mutants and wild-type CRC patients,while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients.It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.展开更多
BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic diseas...BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic disease,with a median survival<12 months.Although recurrent genomic alterations such as the BRAF V600E mutation have been reported in PC,evidence supporting the clinical effectiveness of molecularly guided targeted therapies is limited.CASE SUMMARY We report a case of a 33-year-old male who was referred to our department with weight loss of 5 kg in 2 months,anorexia and abdominal pain.Imaging showed extensive lesions involving the pancreas,liver,bones,muscles and lymph nodes accompanied by elevated carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA).Biopsy yielded a diagnosis of PC.Treatment with gemcitabine and nab-paclitaxel was initiated,but the disease progressed in<2 months even though the patient’s general condition improved.Molecular testing revealed the presence of BRAF mutation.Dabrafenib/trametinib combination therapy was introduced,and the patient was treated for 2 months with a decrease in CA19-9 and CEA levels,but he died after 2 months of treatment.CONCLUSION BRAF alterations are infrequent in PC.This case highlights the significance of molecular profiling in patients with PC,especially in patients with a high tumor burden.展开更多
Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medici...Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medicine in treating BRAF mutant mCRC has garnered increasing attention.Recent studies indicate that combining traditional Chinese and modern Western medical approaches not only extend survival but also reduces the risk of mortality in patients with BRAF V600E mutant mCRC.This approach is particularly effective for colorectal cancer patients who have right-sided colon involvement,liver metastasis,or a history of radiotherapy or chemotherapy.In this treatment combination,traditional Chinese medicine may offer symptomatic relief and improve quality of life,while Western medicine targets the disease more aggressively with advanced pharmacological agents.Ongoing research is crucial to further elucidate the mechanisms underlying these benefits and to optimize treatment protocols.展开更多
BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohor...BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.展开更多
The treatment of metastatic colorectal cancer(mCRC)harboring BRAF V600 mutations is challenging.These tumors are often refractory to standard treatment.Therefore,the patients may exhibit rapid clinical deterioration,d...The treatment of metastatic colorectal cancer(mCRC)harboring BRAF V600 mutations is challenging.These tumors are often refractory to standard treatment.Therefore,the patients may exhibit rapid clinical deterioration,depriving them of the chance to receive salvage therapy.In newly diagnosed patients with good performance status,the administration of an intensive chemotherapy regimen like FOLFOXIRI(5-fluorouracil,leucovorin,oxaliplatin,and irinotecan)along with the antiangiogenic agent bevacizumab can modify this aggressive behavior of the disease and improve patient clinical outcomes.The recently published results of the BEACON(Binimetinib,Encorafenib,and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer)study demonstrated that a combination therapy consisting of BRAF,epidermal growth factor receptor,and mitogen-activated protein kinase kinase inhibitors could be a useful second-or third-line alternative.This review summarizes the current treatment strategies for BRAF-mutant mCRC.展开更多
Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with heredita...Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers.The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer.Methods:BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer,synchronously or metachronously.Results:Mean age was 64.07 years(range:47–83 years).For the colorectal cancer,tumors were located at the sigmoid colon in eight patients(17.8%)and at the rectum in 22 patients(48.9%).Twenty-three patients(51.1%)had synchronous cancer.Four patients(8.9%)had family members with cancer.BRAF mutation was identified in three patients(6.7%).All three of these patients had metachronous cancers.The colorectal cancers were located in the sigmoid colon(1 patient)and the rectum(2 patients).Conclusions:BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer.With only BRAF gene study,it was not possible to identify any correlation with family history of colorectal cancer.Further study means considering other genes–MSI,MSH2,MLH1,MSH6.展开更多
BACKGROUND BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer(mCRC),but these data are from common BRAF V600E-mutated mCRC.Combination therapy of BRAF inhibitor and anti...BACKGROUND BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer(mCRC),but these data are from common BRAF V600E-mutated mCRC.Combination therapy of BRAF inhibitor and antiepidermal growth factor receptor(EGFR)antibody has been approved for BRAF V600E-mutated mCRC.However,BRAF non-V600 mutations are rare mutations,and their clinical behavior is not understood.Moreover,the BRAF K601E mutation is extremely rare in mCRC,and there have been no reports on its specific treatment.CASE SUMMARY Herein,we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases,which extended to whole body including mediastinal to abdominal lymph nodes,bones,pleura,and peritoneum.The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability.She received chemotherapy with mFOLFOX6(oxaliplatin plus infusional 5-fluorouracil[5-FU]and leucovorin)plus panitumumab,following FOLFIRI(irinotecan plus infusional 5-FU and leucovorin)plus ramucirumab.For the next regimen selection,a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation,which was not covered in the initial companion diagnostics.After disease progression,a combination of encorafenib,binimetinib,and cetuximab was selected as third-line chemotherapy.The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites.However,the disease progressed again,and best supportive care was done instead.CONCLUSION This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC,potentially advancing personalized therapy for rare and aggressive cases.展开更多
BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qua...BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.展开更多
Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expre...Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expression and activity thus has recently become a target for drug therapy. Several melanoma cell lines were exposed to inhibitors of Src activity despite their broad specificity. To examine the particular activity of Src in human melanoma cells, we used SU6656, the selective inhibitor of Src family protein kinases. The activity of Src and cell proliferation were suppressed in HBL human cells, wild type melanoma cells and in SK-MEL-5 human melanoma cells harboring mutant BRAF V600E, upon their treatment with SU6656. The suppression of Src kinase activity had not inhibitory effects on Akt/PKB activity in SK-MEL-5 cells, which we have previously found in HBL cells. This may indicate that changes of Src involvement in the control of Akt/PKB activity and its downstream signaling could be induced by BRAF V600E mutation in SK-MEL-5 cells.展开更多
Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<...Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<10%.V-raf murine sarcoma viral oncogene homolog B1(BRAF)and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog(KRAS)mutations are mostly studied in mCRC,as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC.Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations,given the dramatically poor prognosis conferred by these mutations in clinical trials.Thus,it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival.BRAF and KRAS mutations occur in10%and44%of patients with mCRC,respectively.Although the survival rate of patients with mCRC has improved in recent years,the response and prognosis of patients with the aforementioned mutations are still poor.There is a substantial unmet need for prospective personalized therapies for patients with BRAF-or KRAS-mutant mCRC.In this review,we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate,outcomes,and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF-and KRAS-mutant mCRC.展开更多
BACKGROUND Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon.Lymphatic and hematogenous metastases occur frequently in colon ca...BACKGROUND Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon.Lymphatic and hematogenous metastases occur frequently in colon cancer and the most common metastatic sites include the liver,lung,peritoneum,bone,and lymph nodes.As a manifestation of advanced tumor spread and metastasis,soft tissue metastasis,especially skeletal muscle metastasis with bone metaplasia caused by colon cancer,is rare,accounting for less than 1%of metastases.CASE SUMMARY A 43-year-old male patient developed skeletal muscle metastasis with bone metaplasia of the right proximal thigh 5 mo after colon cancer was diagnosed.The patient was admitted to the hospital because of pain caused by a local mass on his right thigh.Positron emission tomography-computed tomography showed many enlarged lymph nodes around the abdominal aorta but no signs of lung or liver metastases.Color ultrasound revealed a mass located in the skeletal muscle and the results of histological biopsy revealed a poorly differentiated adenocarcinoma suspected to be distant metastases from colon cancer.Immunohistochemistry showed small woven bone components that were considered to be ossified.CONCLUSION This case reminds us that for patients with advanced colorectal tumors,we should be alert to the possibility of unconventional metastasis.展开更多
Objective: To investigate the clinicopathologic features of differentiated thyroid carcinoma in children and adolescents. Methods: The clinical data of 7 children and adolescents with differentiated thyroid carcinoma ...Objective: To investigate the clinicopathologic features of differentiated thyroid carcinoma in children and adolescents. Methods: The clinical data of 7 children and adolescents with differentiated thyroid carcinoma were retrospectively analyzed, and the clinicopathologic features of differentiated thyroid carcinoma were analyzed by gender, tumor size and BRAF mutation. Results: There were 7 cases of thyroid papillary carcinoma. The mean age of patients was (18.71 ± 2.75), and the mean tumor diameter was (2.4 ± 1.04) cm. Lymph node metastasis rate was 100% (7/7). In children and adolescents, the lesion volume was larger, membrane invasion and vascular cancer thrombus were more likely to occur, BRAF mutation was less common, and the difference was statistically significant. Conclusion: Children and adolescents with differentiated thyroid carcinoma are more aggressive and prone to membrane invasion and lymph node metastasis;BRAF mutation is less common than in adults.展开更多
文摘BACKGROUND Sessile serrated lesions(SSLs)are considered precancerous colorectal lesions that should be detected and removed to prevent colorectal cancer.Previous studies in Vietnam mainly investigated the adenoma pathway,with limited data on the serrated pathway.AIM To evaluate the prevalence,risk factors,and BRAF mutations of SSLs in the Vietnamese population.METHODS This is a cross-sectional study conducted on patients with lower gastrointestinal symptoms who underwent colonoscopy at a tertiary hospital in Vietnam.SSLs were diagnosed on histopathology according to the 2019 World Health Organi-zation classification.BRAF mutation analysis was performed using the Sanger DNA sequencing method.The multivariate logistic regression model was used to determine SSL-associated factors.RESULTS There were 2489 patients,with a mean age of 52.1±13.1 and a female-to-male ratio of 1:1.1.The prevalence of SSLs was 4.2%[95%confidence interval(CI):3.5-5.1].In the multivariate analysis,factors significantly associated with SSLs were age≥40[odds ratio(OR):3.303;95%CI:1.607-6.790],male sex(OR:2.032;95%CI:1.204-3.429),diabetes mellitus(OR:2.721;95%CI:1.551-4.772),and hypertension(OR:1.650,95%CI:1.045-2.605).The rate of BRAF mutations in SSLs was 35.5%.CONCLUSION The prevalence of SSLs was 4.2%.BRAF mutations were present in one-third of SSLs.Significant risk factors for SSLs included age≥40,male sex,diabetes mellitus,and hypertension.
基金the National Natural Science Foundation of China(No.81472707)Chinese South Western Oncology Group(CSWOG-CCET005).
文摘The incidence of colorectal cancer(CRC)is increasing in China,with high mortality.Here,we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China.The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital,Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively.KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction(q-PCR)in 410 CRC patients,with mutation frequencies of KRAS,NRAS and BRAF of 47.56%,2.93%and 4.15%,respectively.The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed.The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes.The BRAF gene mutation was also associated with cancer thrombosis in blood vessels.Cox regression analysis showed that there was no statistically significant difference in the overall survival(OS)between patients with KRAS,NRAS mutants and wild-type CRC patients,while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients.It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.
基金Supported by Clinical Research Center for Precision Medicine of Abdominal Tumor of Fujian Province.
文摘BACKGROUND Pancreatic cancer(PC)is a highly malignant tumor that is resistant to chemotherapy,radiotherapy and immunotherapy.Combination chemotherapy regimens are the standard first-line regimens for metastatic disease,with a median survival<12 months.Although recurrent genomic alterations such as the BRAF V600E mutation have been reported in PC,evidence supporting the clinical effectiveness of molecularly guided targeted therapies is limited.CASE SUMMARY We report a case of a 33-year-old male who was referred to our department with weight loss of 5 kg in 2 months,anorexia and abdominal pain.Imaging showed extensive lesions involving the pancreas,liver,bones,muscles and lymph nodes accompanied by elevated carbohydrate antigen 19-9(CA19-9)and carcinoembryonic antigen(CEA).Biopsy yielded a diagnosis of PC.Treatment with gemcitabine and nab-paclitaxel was initiated,but the disease progressed in<2 months even though the patient’s general condition improved.Molecular testing revealed the presence of BRAF mutation.Dabrafenib/trametinib combination therapy was introduced,and the patient was treated for 2 months with a decrease in CA19-9 and CEA levels,but he died after 2 months of treatment.CONCLUSION BRAF alterations are infrequent in PC.This case highlights the significance of molecular profiling in patients with PC,especially in patients with a high tumor burden.
基金Supported by the Natural Science Foundation of Hubei Province,No.2019CFC929.
文摘Metastatic colorectal cancer(mCRC)patients with BRAF V600E mutation have a poor prognosis despite the implementation of multiple treatment strategies.The integration of traditional Chinese medicine with Western medicine in treating BRAF mutant mCRC has garnered increasing attention.Recent studies indicate that combining traditional Chinese and modern Western medical approaches not only extend survival but also reduces the risk of mortality in patients with BRAF V600E mutant mCRC.This approach is particularly effective for colorectal cancer patients who have right-sided colon involvement,liver metastasis,or a history of radiotherapy or chemotherapy.In this treatment combination,traditional Chinese medicine may offer symptomatic relief and improve quality of life,while Western medicine targets the disease more aggressively with advanced pharmacological agents.Ongoing research is crucial to further elucidate the mechanisms underlying these benefits and to optimize treatment protocols.
基金Supported by National Natural Science Foundation of China,No.82174461Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0201-22Technology Innovation Project of China Academy of Chinese Medical Sciences,No.CI2021A01811.
文摘BACKGROUND Patients with BRAF V600E mutant metastatic colorectal cancer(mCRC)have a low incidence rate,poor biological activity,suboptimal response to conventional treatments,and a poor prognosis.In the previous cohort study on mCRC conducted by our team,it was observed that integrated Chinese and Western medicine treatment could significantly prolong the overall survival(OS)of patients with colorectal cancer.Therefore,we further explored the survival benefits in the population with BRAF V600E mutant mCRC.AIM To evaluate the efficacy of integrated Chinese and Western medicine in the treatment of BRAF V600E mutant metastatic colorectal cancer.METHODS A cohort study was conducted on patients with BRAF V600E mutant metastatic colorectal cancer admitted to Xiyuan Hospital of China Academy of Chinese Medical Sciences and Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region from January 2016 to December 2022.The patients were divided into two cohorts.RESULTS A total of 34 cases were included,with 23 in Chinese-Western medicine cohort(cohort A)and 11 in Western medicine cohort(cohort B).The median overall survival was 19.9 months in cohort A and 14.2 months in cohort B,with a statistically significant difference(P=0.038,hazard ratio=0.46).The 1-3-year survival rates were 95.65%(22/23),39.13%(9/23),and 26.09%(6/23)in cohort A,and 63.64%(7/11),18.18%(2/11),and 9.09%(1/11)in cohort B,respectively.Subgroup analysis showed statistically significant differences in median OS between the two cohorts in the right colon,liver metastasis,chemotherapy,and first-line treatment subgroups(P<0.05).CONCLUSION Integrated Chinese and Western medicine can prolong the survival and reduce the risk of death in patients with BRAF V600E mutant metastatic colorectal cancer,with more pronounced benefits observed in patients with right colon involvement,liver metastasis,combined chemotherapy,and first-line treatment.
文摘The treatment of metastatic colorectal cancer(mCRC)harboring BRAF V600 mutations is challenging.These tumors are often refractory to standard treatment.Therefore,the patients may exhibit rapid clinical deterioration,depriving them of the chance to receive salvage therapy.In newly diagnosed patients with good performance status,the administration of an intensive chemotherapy regimen like FOLFOXIRI(5-fluorouracil,leucovorin,oxaliplatin,and irinotecan)along with the antiangiogenic agent bevacizumab can modify this aggressive behavior of the disease and improve patient clinical outcomes.The recently published results of the BEACON(Binimetinib,Encorafenib,and Cetuximab Combined to Treat BRAF-Mutant Colorectal Cancer)study demonstrated that a combination therapy consisting of BRAF,epidermal growth factor receptor,and mitogen-activated protein kinase kinase inhibitors could be a useful second-or third-line alternative.This review summarizes the current treatment strategies for BRAF-mutant mCRC.
基金supported by a grant from Kosin University College of Medicine(2010).
文摘Aims:Recently,BRAF mutation testing has been introduced as a marker in differentiating Lynch syndrome from sporadic colorectal cancers or in predicting colorectal cancers with worse prognosis.Individuals with hereditary predisposition to cancer development are at an increased risk of developing multiple primary cancers.The purpose of this study is to identify mutation in the BRAF gene in multiple primary cancers with colorectal cancer and stomach cancer.Methods:BRAF mutation was analysed in 45 patients with colorectal cancer and stomach cancer,synchronously or metachronously.Results:Mean age was 64.07 years(range:47–83 years).For the colorectal cancer,tumors were located at the sigmoid colon in eight patients(17.8%)and at the rectum in 22 patients(48.9%).Twenty-three patients(51.1%)had synchronous cancer.Four patients(8.9%)had family members with cancer.BRAF mutation was identified in three patients(6.7%).All three of these patients had metachronous cancers.The colorectal cancers were located in the sigmoid colon(1 patient)and the rectum(2 patients).Conclusions:BRAF mutation rate was low in the multiple primary cancer with colorectal cancer and stomach cancer.With only BRAF gene study,it was not possible to identify any correlation with family history of colorectal cancer.Further study means considering other genes–MSI,MSH2,MLH1,MSH6.
文摘BACKGROUND BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer(mCRC),but these data are from common BRAF V600E-mutated mCRC.Combination therapy of BRAF inhibitor and antiepidermal growth factor receptor(EGFR)antibody has been approved for BRAF V600E-mutated mCRC.However,BRAF non-V600 mutations are rare mutations,and their clinical behavior is not understood.Moreover,the BRAF K601E mutation is extremely rare in mCRC,and there have been no reports on its specific treatment.CASE SUMMARY Herein,we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases,which extended to whole body including mediastinal to abdominal lymph nodes,bones,pleura,and peritoneum.The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability.She received chemotherapy with mFOLFOX6(oxaliplatin plus infusional 5-fluorouracil[5-FU]and leucovorin)plus panitumumab,following FOLFIRI(irinotecan plus infusional 5-FU and leucovorin)plus ramucirumab.For the next regimen selection,a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation,which was not covered in the initial companion diagnostics.After disease progression,a combination of encorafenib,binimetinib,and cetuximab was selected as third-line chemotherapy.The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites.However,the disease progressed again,and best supportive care was done instead.CONCLUSION This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC,potentially advancing personalized therapy for rare and aggressive cases.
文摘BACKGROUND Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma RAS viral oncogene homolog(NRAS),and v-raf murine sarcoma viral oncogene homolog B1(BRAF)nucleotide variants may generate quantitatively or qualitatively various protein activities,which may be reflected in their differential association with tumor characteristics.AIM To examine the association between these mutations and colorectal cancer(CRC)progression stages.METHODS A retrospective analysis was conducted on 799 patients with CRC,whose tumor samples were examined for mutations in the hot-spots of the KRAS,NRAS,and BRAF genes at the University of Texas Medical Branch,spanning from January 2016 to July 2023.Statistical analyses were performed to assess the association of spe-cific nucleotide changes with tumor,nodes,and metastasis stages.RESULTS KRAS mutations were found in 39.5%of cases,NRAS mutations in 4.4%,and BRAF mutations in 6.0%.The KRAS p.Gly12Val and p.Gly13Asp mutations were positively associated with pathological stage 4 tumors.Additionally,the KRAS p.Gly12Asp and p.Gly12Val mutations were linked to an increased risk of distant metastasis.Meanwhile,the BRAF Val600Glu mutation was associated with a higher likelihood of lymph node involvement.CONCLUSION Our findings support the potential prognostic utility of specific KRAS(p.Gly12Val,p.Gly12Asp,and p.Gly13Asp)and BRAF p.Val600Glu mutations in CRC.These results are preliminary and require validation through larger,multi-center studies before they can be considered reliable in clinical practice.
基金supported by grant NT11231-3/2010 from the Ministry of Health of the Czech Republic
文摘Src regulates cell adhesion, invasiveness, motility and growth in cancer cells. In melanoma, accumulating data show that Src inhibition can be effective and may enhance the effects of other agents. Increased Src expression and activity thus has recently become a target for drug therapy. Several melanoma cell lines were exposed to inhibitors of Src activity despite their broad specificity. To examine the particular activity of Src in human melanoma cells, we used SU6656, the selective inhibitor of Src family protein kinases. The activity of Src and cell proliferation were suppressed in HBL human cells, wild type melanoma cells and in SK-MEL-5 human melanoma cells harboring mutant BRAF V600E, upon their treatment with SU6656. The suppression of Src kinase activity had not inhibitory effects on Akt/PKB activity in SK-MEL-5 cells, which we have previously found in HBL cells. This may indicate that changes of Src involvement in the control of Akt/PKB activity and its downstream signaling could be induced by BRAF V600E mutation in SK-MEL-5 cells.
基金supported by National Natural Science Foundation of China[No.U1608281]National Natural Science Foundation of China[81903658]+2 种基金Liaoning Province Scientific Research Foundation[JC2019032]Liaoning Revitalization Talents Program[No.XLYC1807201]Shenyang S&T Projects[19-109-4-09].
文摘Colorectal cancer(CRC)is one of the most commonly diagnosed cancers worldwide and 30%of patients with CRC experience metastasis.Patients with metastatic colorectal cancer(mCRC)have a 5-year overall survival rate of<10%.V-raf murine sarcoma viral oncogene homolog B1(BRAF)and V-Ki-ras2 Kirsten ratsarcoma viral oncogene homolog(KRAS)mutations are mostly studied in mCRC,as clinical trials found that first-line chemotherapy with anti-epidermal growth factor receptor agent confers limited efficacy for mCRC.Treatment decisions for early-stage mCRC do not consider BRAF or KRAS mutations,given the dramatically poor prognosis conferred by these mutations in clinical trials.Thus,it is necessary to identify patients with mCRC harboring BRAF or KRAS mutations to formulate rational therapeutic strategies to improve prognosis and survival.BRAF and KRAS mutations occur in10%and44%of patients with mCRC,respectively.Although the survival rate of patients with mCRC has improved in recent years,the response and prognosis of patients with the aforementioned mutations are still poor.There is a substantial unmet need for prospective personalized therapies for patients with BRAF-or KRAS-mutant mCRC.In this review,we focus on BRAF and KRAS mutations to understand the mechanisms underlying resistance and improving the response rate,outcomes,and prognosis of patients with mCRC bearing these mutations and to discuss prospective personalized therapies for BRAF-and KRAS-mutant mCRC.
基金Supported by the Science and Technology Development Project of Jilin Province,No.3D5197434429the Youth Program of the National Natural Science Foundation of China,No.3A4205367429+1 种基金the Education Project of Jilin UniversityNo.419070600046。
文摘BACKGROUND Colon cancer is a common malignant disease of the gastrointestinal tract and usually occurs at the junction of the rectum and sigmoid colon.Lymphatic and hematogenous metastases occur frequently in colon cancer and the most common metastatic sites include the liver,lung,peritoneum,bone,and lymph nodes.As a manifestation of advanced tumor spread and metastasis,soft tissue metastasis,especially skeletal muscle metastasis with bone metaplasia caused by colon cancer,is rare,accounting for less than 1%of metastases.CASE SUMMARY A 43-year-old male patient developed skeletal muscle metastasis with bone metaplasia of the right proximal thigh 5 mo after colon cancer was diagnosed.The patient was admitted to the hospital because of pain caused by a local mass on his right thigh.Positron emission tomography-computed tomography showed many enlarged lymph nodes around the abdominal aorta but no signs of lung or liver metastases.Color ultrasound revealed a mass located in the skeletal muscle and the results of histological biopsy revealed a poorly differentiated adenocarcinoma suspected to be distant metastases from colon cancer.Immunohistochemistry showed small woven bone components that were considered to be ossified.CONCLUSION This case reminds us that for patients with advanced colorectal tumors,we should be alert to the possibility of unconventional metastasis.
文摘Objective: To investigate the clinicopathologic features of differentiated thyroid carcinoma in children and adolescents. Methods: The clinical data of 7 children and adolescents with differentiated thyroid carcinoma were retrospectively analyzed, and the clinicopathologic features of differentiated thyroid carcinoma were analyzed by gender, tumor size and BRAF mutation. Results: There were 7 cases of thyroid papillary carcinoma. The mean age of patients was (18.71 ± 2.75), and the mean tumor diameter was (2.4 ± 1.04) cm. Lymph node metastasis rate was 100% (7/7). In children and adolescents, the lesion volume was larger, membrane invasion and vascular cancer thrombus were more likely to occur, BRAF mutation was less common, and the difference was statistically significant. Conclusion: Children and adolescents with differentiated thyroid carcinoma are more aggressive and prone to membrane invasion and lymph node metastasis;BRAF mutation is less common than in adults.
