Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

[Influence of Chinese herbal medicine Feitai Capsule on completion or delay of chemotherapy in patients with stage IIIB/IV non-small-cell lung cancer: a randomized controlled trial].

BACKGROUND: Chemotherapy completion rate can reflect the tolerance and compliance of patients to chemotherapy. Poor tolerance may result in delay or suspension of the comprehensive treatment plan, thus affect the efficacy of cancer treatment. Evaluating methods to improve the completion rate of chemotherapy and reduce the occurrence of delayed chemotherapy has gained increasing attention and is the significant area of study in the field of cancer treatment. Studies have shown that Chinese medicine combined with chemotherapy could improve the quality of life in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC). OBJECTIVE: To observe the effects of Feitai Capsule, a Chinese patent herbal drug, combined with chemotherapy in patients with stage IIIB/IV NSCLC. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 60 diagnosed stage IIIB/IV NSCLC patients from the Department of Oncology, Fuzhou General Hosipital of Najing Military Region were randomly divided into treatment group (30 cases) and control group (30 cases). Patients in the treatment group were treated with chemotherapy plus Feitai Capsule and patients in the control group only received chemotherapy. Both groups of patients were treated for 4 therapeutic cycles. MAIN OUTCOME MEASURES: The chemotherapy completion rate and the chemotherapy delay rate were observed in each cycle of treatment. The therapeutic efficacy was evaluated after 4 cycles. RESULTS: The chemotherapy completion rate was 96.42% in the treatment group, while that of the control group was 74.07%. The chemotherapy delay rate was 3.57% in the treatment group, while that of the control group was 14.8% (P=0.007 0). The disease control rate was 78.6% in the treatment group, while that of the control group was 59.3% (P=0.173 9). CONCLUSION: Feitai Capsule can increase the chemotherapy completion rate in patients with stage IIIB/IV NSCLC.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers. Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis. Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74). Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

[Effects of Feitai Capsule on quality of life in patients with advanced non-small-cell lung cancer: a randomized controlled trial].

BACKGROUND: Recently the maintenance therapy of non-small-cell lung cancer (NSCLC) patients who completed required treatment cycles has caused widespread interests in the medical field. Traditional Chinese medicine may be a useful complement in maintenance treatment of mid-to-late stage NSCLC. OBJECTIVE: To observe the effects of Feitai Capsule, a compound traditional Chinese herbal medicine for expelling blood stasis and phlegm, on the quality of life of the NSCLC patients as a maintenance treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 62 mid-to-late stage NSCLC patients from Fuzhou General Hospital of Nanjing Military Region were included and randomly divided into treatment group (31 cases) and control group (31 cases). Patients in the treatment group were treated with Feitai Capsule, and patients in the control group did not accept any intervention. Regular observations and follow-up were performed for patients in the two groups. MAIN OUTCOME MEASURES: Analysis of variance, nonparametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and quality of life. RESULTS: There were two dropouts and 60 valid cases. The baseline characteristics of the two groups were similar. In the treatment group, symptom response and physical energy level were improved by 36.6% (Z=-2.632, P=0.008) and 26.7%(Z=-2.182, P=0.029), respectively. There was a positive correlation between these two factors (r=0.917, P<0.001). The patients in treatment group had a significantly improved quality of life after treatment. No serious adverse events were observed. CONCLUSION: Feitai Capsule as maintenance treatment can improve the quality of life of the patients with mild-to-late stage NSCLC.

[Gemcitabine combined with capecitabine in the treatment for 41 patients with relapsed or metastatic biliary tract carcinoma].

OBJECTIVE: To investigate the efficacy of the combination of gemcitabine with capecitabine in the chemotherapy for patients with relapsed or metastatic biliary tract carcinoma. METHODS: Forty-one patients with unresectable relapsed or metastatic carcinoma of the biliary tract were treated from March 2000 to December 2004. The regimen consisted of intravenous administration of gemcitabine plus oral intake of capecitabine every 3 weeks for more than 2 cycles. The parameters including tumor response, clinical benefit rate,survival and safety were observed. RESULTS: Thirty-six patients were valuable and 5 patients were excluded from this series due to various reasons. Eleven patients (30.1%) had a partial response and another 11 patients (30.1%) experieced stable disease with a clinical benefit rates of 61.1%. The median overall survival time and time to progression were 10 months and 6 months, respectively. The one-year survival rate was 40.0%. The adverse events including nausea, diarrhea and hand-foot syndrome, fatigue, neutropenia, thrombocytopenia were frequently observed, which were usually in grade I or II, rarely in grade III and none in grade IV (NCI-CTC). CONCLUSION: Our results show that the regimen of gemcitabine combined with capecitabine is effective and well tolerated in patients with unresectable relapsed or metastatic carcinoma of the biliary tract.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study.

BACKGROUND: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. METHODS: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. RESULTS: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. CONCLUSIONS: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

[Study on the relationship between vascular endothelial growth factor and syndrome type of traditional Chinese medicine in patients with gastric carcinoma].

OBJECTIVE: By detecting the expression of vascular endothelial growth factor (VEGF) in different syndrome types of traditional Chinese medicine (TCM) in patients with gastric carcinoma (GC) to investigate the correlation of VEGF and TCM syndrome type for exploring the internal relationship between disease and syndrome. METHODS: The correlated clinical manifestations were recorded in detail and patient's syndrome type was differentiated at beside before operation. After operation, pathological examination on the resected specimen was performed routinely. The expression of VEGF in 104 GC patients of three different syndrome types, i.e. Pi-Wei asthenia type (type 1), Gan-Wei disharmony type (type 2) and phlegm-stasis-poisons stagnant type (type 3)and in 30 patients with superficial gastritis (for control) were determined by immunohistochemical method. The expressions of VEGF in different syndrome types were analyzed by combining with correlated clinical pathological characteristics. RESULTS: (1) The VEGF protein positive expression rate in GC patients was 81.7% (85/104), it was significantly higher than that in the control group with positive rate being zero (P < 0.01). (2) The intensity of VEGF expression was positively correlated with the depth of tumor infiltration, the extent of lymph node metastasis and the pathological staging of cancer (P < 0.01), and showed no evident correlation with the size of tumor and its degree of cell differentiation (P > 0.05). (3) Levels of VEGF expression in various syndrome types were significantly different (P < 0.01), the highest expression showed in the type 3, the second in the type 2, and the lowest in the type 1, comparison between them all showed significant difference (P < 0.01 for 3 vs 1, P < 0.05 for 3 vs 2 and 2 vs 1). CONCLUSION: (1) VEGF could be taken as an index for evaluating the infiltration, metastasis and prognosis of GC. (2) The different expressions of VEGF play different roles in the GC metastatic process of patients of different syndrome types, and the pathogenesis of GC metastasis may be probably various in different syndrome types. VEGF is the relevant gene of GC of type 2 and type 3. (3) High VEGF expression shows positive correlation with the GC metastasis of type 2 and 3, suggesting that the higher the intensity of evil excess, the more possibilities of tumor infiltration and metastasis and the worse the prognoses will be.

Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K/AKT/mTOR pathway.

Gefitinib is a selective inhibitor of the tyrosine kinase epidermal growth factor receptor, which inhibits tumor pathogenesis, metastasis and angiogenesis, as well as promoting apoptosis. Therefore, gefitinib presents an effective drug for the targeted therapy of lung cancer. However, the underlying mechanisms by which gefitinib induces lung cancer cell death remain unclear. To investigate the effects of gefitinib on lung cancer cells and the mechanism of such, the present study analyzed the effect of gefitinib on the autophagy, apoptosis and proliferation of the A549 and A549-gefitinib-resistant (GR) cell lines GR. The regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway was also investigated. Acridine orange staining revealed that gefitinib induced autophagy of A549 cells but not A549-GR cells. In addition, gefitinib promoted apoptosis and inhibited proliferation of A549 cells but not A549-GR cells. Furthermore, western blot analysis demonstrated that gefitinib treatment led to the downregulation of PI3K, AKT, pAKT, mTOR and phosphorylated-mTOR protein expression in A549 cells but not A549-GR cells. LY294002 blocked the PI3K/AKT/mTOR pathway and induced autophagy and apoptosis of A549 cells, however, no synergistic effect was observed following combined treatment with gefitinib and LY294002. In conclusion, the results of the present study indicate that gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway, which leads to lung cancer cell death.

Transdermal granisetron for the prevention of nausea and vomiting following moderately or highly emetogenic chemotherapy in Chinese patients: a randomized, double-blind, phase III study.

BACKGROUND: The granisetron transdermal delivery system (GTDS) has been demonstrated effectiveness in the control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of GTDS in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in China. METHODS: A total of 313 patients were randomized into the GTDS group (one transdermal granisetron patch, 7 days) or the oral granisetron group (granisetron oral 2 mg/day, ≥2 days). The primary endpoint was the percentage of patients achieving complete control (CC) from chemotherapy initiation until 24 h after final administration (PEEP). Chi-square test and Fisher's exact test were used for statistical analysis. RESULTS: Two hundred eighty-one patients were included in the per protocol analysis. During PEEP, CC was achieved by 67 (47.52%) patients in the GTDS group and 83 (59.29%) patients in the oral granisetron group. There was no statistical significance between the groups (P=0.0559). However, the difference of the CC percentage mainly occurred on the first day of chemotherapy between the groups. The CC was 70.13% on day 1 in the GTDS group, which was significantly lower than that of 91.03% in the oral granisetron group in the full analysis set. In the following days of chemotherapy, the CC was similar between the groups. In terms of cisplatin-contained regimen and female, there was statistical significance between the groups. Both treatments were well tolerated and safe. The most common adverse event was constipation. CONCLUSIONS: GTDS provided effective and well-tolerated control of CINV in Chinese patients, especially to non-cisplatin-contained regimen.

Clinical study on treatment of primary hepatocellular carcinoma by Shenqi mixture combined with microwave coagulation.

OBJECTIVE: To observe the short-term efficacy and safety of Shenqi mixture (SQM) combined with microwave coagulation in treating primary hepatocellular carcinoma (HCC). METHODS: Seventy-two patients with primary HCC of stage II-III, Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and randomly assigned into two groups, the treated group and the control group, 36 in each. Microwave therapy was applied to both groups by double leads, 60 W, 800 sec once a week for two weeks. To the treated group, SQM was given additionally through oral intake of 20 ml, three times a day for 1 month. The changes in tumor size, main symptoms, serum level of alpha-fetoprotein (AFP), immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group. RESULTS: (1) In the SQM treated group, after treatment 3 patients got completely remitted (CR), 24 partial remitted (PR), 4 unchanged (NC) and 5 progressively deteriorated (PD), the effective rate being 75.00%; while in the control group, 1 got CR, 19 PR, 9 NC and 7 PD, the effective rate being 55.56%. Comparison of the effective rate between the two groups showed significant difference (P < 0.05). (2) AFP level decreased after treatment in both groups, but the decrement in the treated group was significantly higher than that in the control group (P < 0.01). (3) After treatment, in the treated group, CD3(+), CD4(+), CD4(+)/CD8(+) and NK activity were improved, Karnofsky scores increased and liver function bettered, with these improvements significantly superior to those in the control group (P < 0.01). (4) The improvement in symptoms such as hepatic region pain, fever, weakness, poor appetite and jaundice in the treated group after treatment was also superior to that in the control group (P < 0.01). (5) The 12-month, 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group, showing significant difference (P < 0.05). CONCLUSION: Combined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence, but also enhance the cellular immunity of organism. It is one of the effective therapies for patients with middle-advanced hepatocarcinoma, who have lost the chance of surgical operation. It could improve clinical symptoms, elevate the quality of life, prolong the survival period of patients, but shows no evident adverse reaction.

[Effects of tumor suppressing gene TIP30/CC3 on the growth of tumor cells].

OBJECTIVE: To introduce the newly found gene TIP30/CC3 into a hepatoma cell line PLC/PRF/5 and select the stable expression clones. The growth and cell cycles were studied with the clones stably expressing TIP30/CC3 or anti-TIP30/CC3, and the effects of TIP30/CC3 gene on hepatoma cells were analyzed. METHODS: The internal expression of TIP30/CC3 protein was detected with Western blot, then TIP30/CC3 or anti-TIP30/CC3 cDNA was subcloned into a constitutive vector pcDNA3 followed by transfection into PLC/PRF/5. Stable expression clones were selected. The cell growth curve was made and cell cycles detected using flow cytometry. To confirm the results in vitro, stable-expressing cells were implanted subcutaneously into nude mice and time of tumor formation recorded and tumor volume measured. RESULTS: PLC-anti-TIP30 grew faster than the others. Three days after transfection, live cells of PLC-anti-TIP30 were 14.0*10(4), in comparison with the control PLC-DNA3 and PLC/PRF/5, the differences were statistically significant. Live cells of PLC-TIP30 were 4.9*10(4), significantly less than the two control groups. Six days after transfection, live cells of PLC-anti-TIP30 were 25.0*10(4), significantly more than the controls PLC-DNA3 and PLC/PRF/5. Live cells of PLC-TIP30 were 12.4*10(4), significantly less than the two control groups. Cell cycle analysis showed that PLC-anti-TIP30 proliferated faster, 22.4% cells were in G0/G1 (gap) phases and 58.6% cells in S (DNA synthesis) phase. The growth of the PLC-anti-TIP30 cell was retarded and many cells were arrested from G1 to S phases. Cells in G0/G1 and S phase were 44.2% and 33.3% respectively. Furthermore, the average time of tumor formation was shorter in anti-TIP30 group and longer in TIP30/CC3 group, and times were 6.0 d (with control groups) and 15.6 d (with control groups) respectively. Tumors in the nude mice grew faster in PLC-anti-TIP30 group and slower in PLC-TIP30 group. CONCLUSION: Tumor suppressor gene TIP30/CC3 can inhibit the proliferation of tumor cells and interfere in its cell cycles. It can be used as a valuable tool for hepatoma biotherapy including gene therapy.

[Relationship between sCD44v6 expression and TCM differentiation type of gastric carcinoma patients and influence of weitai capsule on the expression].

OBJECTIVE: To explore the relationship of TCM type with serum level of soluble CD44v6 (sCD44v6) and different histologic parameters in gastric carcinoma patients and to observe the influence of Weitai capsule (WTC) on the sCD44v6 expression. METHODS: TCM typing and sCD44v6 expression were determined in all the enrolled patients (30 in the control and 32 in the trial group) before operation, and 3-4 courses of chemotherapy was applied to them from 3-4 weeks after operation. To the patients of trial group, oral administration of WTC was given additionally with 4 capsules, 3 times a day for consecutive 3 months. RESULTS: sCD44v6 was significantly positive correlated with the degree of cancer cell differentiation, infiltration and lymph node metastasis; (2) Level of sCD44v6 was the highest in patients of blood stasis type, as compared with that in the patients of Pi-deficiency type or of damp-heat type, the difference was significant; (3) After ending treatment, level of sCD44v6 in the trial group was significantly lower than that in the control group. CONCLUSION: (1) Serum level of sCD44v6 could be taken as the criterion for evaluating the development and prognosis of gastric cancer, as well as the therapeutic target for anti-metastasis treatment; (2) Serum level of sCD44v6 is related to some extent with TCM type of blood stasis and Pi-deficiency; (3) WTC combined with chemotherapy could further inhibit the expression of serum sCD44v6 in gastric carcinoma patients.

Misdiagnosed male breast cancer with an unknown primary tumor: A case report.

Compared with female breast cancer, male breast cancer (MBC) has an extremely low morbidity, later staging and fewer breast tissues. The lumps are easier to invade in the center and the majority of the cases are positive for metastatic lymph node, with the typical clinical manifestation as a painless mass in partial breast. MBC with an unknown primary tumor is rare and is often prone to misdiagnosis, resulting in a delay in correct treatment. Such a case is extremely significant for clinical reference. The current study presents a 58-year-old male who developed a painless mass in the left armpit and received armpit mass biopsy and pathological examination which showed glandular cancer, with a high possibility of mammary primary tumor. The patient was administered four cycles of paclitaxel plus oxaliplatin chemotherapy. However, three months later, the patient identified novel disseminated lymph nodes in the left armpit. The initial pathological section and paraffin blocks were re-examined and the patient was finally diagnosed with breast invasive ductal carcinoma based on the metastases pathology and immunohistochemical examination. No breast mass was found on physical examination of the patient and the tumor markers, including cancer antigen 125 and carcinoembryonic antigen, were normal. No primary tumors were observed in the mammography and PET-CT and the primary tumor was not found following the left breast modified radical mastectomy.

Influence of UGT1A1 gene methylation level in colorectal cancer cells on the sensitivity of the chemotherapy drug CPT-11.

OBJECTIVE: To study the influence of the methylation level of UGT1A1 gene related to CPT-11 metabolic enzymes in colorectal cancer cells on the sensitivity of chemotherapy drugs. METHODS: Test the changes in sensitivity of seven colorectal cancer cell strains that have been/not been subject to DAC treatment to CPT-11, analyze its correlation with CES2, UGT1A1 and GUSB mRNA expression according to IC50; screen the effective interference sequence of UGT1A1 siRNA, test the changes in cytotoxicity of CPT-11 after UGT1A1 siRNA is transfected, select RK0 cells and make them transfected with the chemosynthetic UGT1A1 siRNA after their UGT1A1 expression is restored with or without demethylation treatment. RESULTS: The sensitivity of different colorectal cancer cell strains to CPT-11 showed difference (P<0.05), UGT1A1 expression in colorectal cell lines had a negative correlation with the IC50 (r=0.790648, P<0.05), the interference efficiency of the screened UGT1A1 siRNA was up to 78%. The IC50 value of siRNA decreased by nearly one time after transfected with HT-29 (P<0.01); which of methylated RK0 cells of UGT1A1 gene increased instead after the demethylation treatment. However, the IC50 value of the demethylation treatment group increased compared with the non-demethylation treatment group after UGT1A1 siRNA was transfected. CONCLUSIONS: The cytotoxicity of CPT-11 to colorectal cancer cells has a negative correlation with UGT1A1 expression, and positive correlation with CES2 and GUSB. The specific silencing UGT1A1 gene of siRNA could significantly increase the sensitivity of CPT-11 to the chemotherapy of colorectal cancer cells. UGT1A1 methylation was an important factor affecting the chemosensitivity of CPT-11.

Regulation and expression of aberrant methylation on irinotecan metabolic genes CES2, UGT1A1 and GUSB in the in-vitro cultured colorectal cancer cells.

OBJECTIVE: To evaluate the aberrant methylation gene expression related to the irinotecan (CPT-11) metabolic enzymes in different colorectal cancer cell strains; provide new thoughts and measures for reverse of tumor drug resistance. METHODS: Studied the aberrant methylation state of CES2, UGT1A1 and GUSB in eight colorectal cancer cell strains through MSP method; and analyze the expression of the target gene after being dealt with DAC. RESULTS: UGT1A1 showed methylation in five cell strains, while CES2 and GUSB respectively showed consistent unmethylation or hemimethylation. After being dealt with DAC, CES2 and GUSB mRNA showed different expressions but not significant. The expression quantity of UGT1A1mRNA in the low-expression cell strains increased significantly. The expression of UGT1A1 protein where POSITIVE presented low expression was up-regulated to different degrees. Negative tropism was found in CES2 and UGT1A1. CONCLUSION: Methylation in UGT1A1 gene expression silencing as an important mechanism; methylation could provide an effective target for methylation regulation intervening in the treatment of CPT-11. Meanwhile, studies found that the changes in expressions of CES2 and GUSB might be resulted from some unknown target that still existed during the regulation, or from the influence of methylation in the non-core zone of promoters on the gene transcription.

Expression of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa co-determines the prognosis of colon cancer patients.

Provirus integration site for Moloney murine leukemia virus (pim-1) is a proto-oncogene that is linked to the development and progression of several cancers. In this study, we evaluated pim-1 expression in tumors, tumor stroma and tumor-adjacent mucosa together as an independent prognostic factor for colon cancer patients. The study included 343 colon cancer patients. Immunohistochemical staining was used to detect pim-1. Multivariate cox regression for disease-free survival (DFS) were used to identify independent prognostic factors. Analytic hierarchy process (AHP) was used to calculate the weight of pim-1 in tumors, tumor stroma and tumor-adjacent mucosa in order to obtain a Pim-1 total score (PTS) for recurrence and survival. Kaplan-Meier DFS curves and OS curves for patients with different pim-1 expression levels were compared using the log-rank test. In this study, four independent prognostic factors were identified for colon cancer patients: pim-1 expression in tumors, tumor stroma, tumor-adjacent mucosa, as well as tumor stage. It has been established that clinical stage is an important prognostic factor for colon cancer patients. However, PTS can identify the patients who are likely to recur not only in the whole radical excision group but also within each stage of this group. Based on the results of this study we can conclude that the PTS combined with clinical staging system may be a better predictor of colon cancer patients' prognosis than using the clinical stage system alone. ClinicalTrials.gov Number: ChiCTR-PRCH-12002842.

Effect of Feitai Capsule () on quality of life and progression-free survival of patients with unresectable non-small cell lung cancer.

OBJECTIVE: To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC). METHODS: Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS. RESULTS: Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048). CONCLUSION: Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.