Relationship of CD44+CD24-/low breast cancer stem cells and axillary lymph node metastasis.

BACKGROUND: Axillary node staging plays an important role in the prognostic evaluation and planning of adjuvant treatment. Breast cancer stem cells, identified on the basis of CD44+CD24-/low expression, are associated with metastases and drug resistance. It is therefore important to investigate the proportion of CD44+CD24-/low breast cancer stem cells for the diagnosis of metastases in axillary nodes. METHODS: Thirty-two ipsilateral axillary lymph nodes were collected from patients diagnosed with invasive breast cancer. Each lymph node (LN) was divided into two equals - one was examined by H&E staining, while the other was made into a single cell suspension to study the content of CD44+CD24-/low cells by flow cytometry (FCM). The relationship was investigated between the content of CD44+CD24-/low cells and metastases in axillary nodes which were confirmed by histology. Associations were tested using the chi-square test (linear-by-linear association), and the significance level was set at a value of p < 0.05. RESULTS: In the 32 axillary nodes, the level of CD44+CD24-/low cells was determined to be between 0 and 18.4%: there was no presence of CD44+CD24-/low cells in 9 LNs, of which 2 had confirmed metastasis; there were less than 10% CD44+CD24-/low cells in 12 LNs, of which 6 had confirmed metastasis; and there were more than 10% CD44+CD24-/low cells in 11 LNs, of which 9 had confirmed metastasis. A higher percentage of detected CD44+CD24-/low cells was significantly associated with more confirmed LN metastases (p = 0.009). CONCLUSIONS: CD44+CD24-/low breast cancer stem cells might help clinicians to determine the presence of LN metastases. However, its prognostic value remains unclear, while histological diagnosis is still the gold standard.

Emodin affects ERCC1 expression in breast cancer cells.

BACKGROUND: Multi-drug resistance to chemotherapeutic agents is a major cause of treatment failure in breast cancer. In this study, we investigated the effects of emodin on reversing the multi-drug resistance, examined the ERCC1 protein expression in breast cancer cell line, and explored the relationship between reversal of multi-drug resistance and ERCC1 protein expression. METHODS: MTT assay was conducted to test the cytotoxicity of adriamycin and cisplatin to MCF-7/Adr cells with and without emodin pretreatment, and Western blot was performed to examine the ERCC1 protein expression. RESULTS: MCF-7/Adr cells had 21-fold and 11-fold baseline resistances to adriamycin and cisplatin, respectively. When emodin was added to the cell culture at the concentration of 10 µg/ml, the drug resistance was reduced from 21 folds to 2.86 folds for adriamycin, and from 11 folds to 1.79 folds for cisplatin. MCF-7/Adr cells treated with two concentrations (10 µg/mL and 20 µg/mL) of emodin, after 2, 4, 6, 10 days, the trend of ERCC1 expression was gradually decreased and the reduction was more obvious comparatively at the concentration of 20 µg/mL. CONCLUSIONS: Emodin could reverse the multi-drug resistance in MCF-7/Adr cells and down-regulate ERCC1 protein expression.

Mouse model of plasma cell mastitis.

BACKGROUND: Plasma cell mastitis is distinct from the common form of mastitis and clinically resembles breast carcinoma. The lesion occurs in non-lactating young women, and the incidence rate is rising. Surgical resection is the main treatment, but cannot prevent recurrence of the disease. Disfigurement or removal of breast after the operations can cause marked physical and psychological distress. The etiology of plasma cell mastitis is unclear up till now. It is therefore necessary to investigate further the underlying immunological changes of the disease. METHODS: The lesions of plasma cell mastitis removed from patients through aseptic operation were mixed with normal saline into homogenate tube machine (homogenate tubes were disinfected and sterilized prior to treatment). The mixture was homogenized at medium speed and grinded in ultrasonic cell disruptor. The homogenate obtained was made into oil emulsion with Freund's adjuvant. Thirty female BALB/c mice (6 weeks after sexual maturity) were divided into five groups A-E: group A was blank control; group B was normal saline control; group C was inoculated with 0.02 ml water-in-oil emulsion; group D was inoculated with 0.04 ml water-in-oil emulsion; group E was complete Freund's adjuvant control. RESULTS: Pathology results showed that mouse mammary gland acinar cells remained integral without any abnormal changes observed in control groups A and B. Experimental groups C and D showed dilation of mouse mammary ductal tissue with a large number of epithelial cells and debris in the lumen, and fibrosis around ducts accompanied by large duct cells, neutrophils, lymphocytes, and especially plasma cell infiltration. Pathological changes were observed in 3 (50%) mice and 5 (83.3%) mice in group C and D respectively. In group E, neutrophil infiltration in mammary gland was observed in 5 mice, but neither infiltration of plasma cells nor other abnormal pathological changes were observed. CONCLUSIONS: The lesions of patient with plasma cell mastitis could make the female BALB/c mice experience the similar clinical and pathological manifestation. High-dose group can successfully establish a mouse model of plasma cell mastitis.

Minimally invasive video-assisted thyroidectomy for the early-stage differential thyroid carcinoma.

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT), the modified Miccoli's thyroid surgery, is the most widespread minimally invasive technique and has been widely used for treatment of thyroid disease. This study aimed to verify the potential benefits of the modified Miccoli's thyroid surgery, determine the feasibility of the MIVAT for early-stage differential thyroid carcinoma and evaluate the likelihood of the surgical method as a standard operation for early malignant thyroid carcinoma. METHODS: A total of 135 patients were retrospectively compared which included two groups of patients: the first group underwent the conventional thyroidectomy; the other group underwent MIVAT. Patients with thyroid nodule smaller than 20 mm and without previous neck surgery were included while those with wide-ranging and distant metastases of cervical tissues, or any suspected thyroid nodal metastases were excluded for analysis. MIVAT and the central compartment (level VI) lymph nodes dissection (LND) were considered as a new treatment method for this retrospective study. In addition to the comparison of surgical outcomes between the new treatment and the conventional thyroid surgery, other surgical parameters including operative time, operative volume of hemorrhage, incisional length, postoperative volume of drainage, length of hospitalization, accidence of hoarse voice, accidence of bucking, accidence of hypocalcemia and peak angle of cervical axial rotation were also compared. RESULTS: Out of 135 patients, 111 patients underwent conventional thyroid surgery and 24 patients underwent MIVAT plus level VI LND for treatment of early-stage differential malignant carcinoma. Patients who received the new surgical treatment had significantly shorter incisional length (3.1 cm vs. 6.9 cm, p < 0.0001), shorter operative time (109 min vs. 139 min, p = 0.014) and fewer operative hemorrhage (29.5 ml vs. 69.7 ml, p < 0.0001) when compared to the conventional treatment. Postoperative peak angle of cervical axial rotation of patients treated with MIVAT was less than those treated with conventional surgery (L: 31.5° vs. 39.0°, p < 0.0001; R: 31.5° vs. 38.0°, p < 0.0001). Incisional wound infection, postoperative hoarse voice, bucking and hypocalcemia were not observed in all patients. Postoperative analgetica was not required as well. CONCLUSIONS: Compared with conventional thyroid surgery for early-stage differential thyroid carcinoma, the new surgical treatment could be considered as an alternative surgical method for treatment of early-stage thyroid carcinoma since it was feasible, safe and clinically effective with better surgical and cosmetic outcomes.

Application of a nanotechnology antimicrobial spray to prevent lower urinary tract infection: a multicenter urology trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a common nosocomial device-associated infection. It is now recognized that the high infection rates were caused by the formation of biofilm on the surface of the catheters that decreases the susceptibility to antibiotics and results in anti-microbial resistance.In this study, we performed an in vitro test to explore the mechanism of biofilm formation and subsequently conducted a multi-center clinical trial to investigate the efficacy of CAUTI prevention with the application of JUC, a nanotechnology antimicrobial spray. METHODS: Siliconized latex urinary catheters were cut into fragments and sterilized by autoclaving. The sterilized sample fragments were randomly divided into the therapy and control group, whereby they were sprayed with JUC and distilled water respectively and dried before use.The experimental standard strains of Escherichia coli (E. coli) were isolated from the urine samples of patients. At 16 hours and 7 days of incubation, the samples were extracted for confocal laser scanning microscopy.A total of 1,150 patients were accrued in the clinical study. Patients were randomized according to the order of surgical treatment. The odd array of patients was assigned as the therapy group (JUC), and the even array of patients was assigned as the control group (normal saline). RESULTS: After 16 hours of culture, bacterial biofilm formed on the surface of sample fragments from the control group. In the therapy group, no bacterial biofilm formation was observed on the sample fragments. No significant increase in bacterial colony count was observed in the therapy group after 7 days of incubation.On the 7th day of catheterization, urine samples were collected for bacterial culture before extubation. Significant difference was observed in the incidence of bacteriuria between the therapy group and control group (4.52% vs. 13.04%, p < 0.001). CONCLUSIONS: In this study, the effectiveness of JUC in preventing CAUTI in a hospital setting was demonstrated in both in vitro and clinical studies.

Fructus Schisandrae (Wuweizi) containing compound in modulating human lymphatic system - a Phase I minimization clinical trial.

BACKGROUND: Hepatitis B virus (HBV) infection afflicts Asia population and, in Hong Kong, about 10% was Hepatitis B surface antigen carrier. It is still one of the major issues under investigation. Herbal medicine KY88 composed of Fructus Schisandrae possessing immunomodulatory property was adopted by Chinese medicine practitioner for treatment of acute and chronic HBV infection. However, the underlying impact on host immune system is not fully understood. MATERIALS AND METHODS: Twenty-three healthy volunteers infected with HBV were taken peripheral venous blood from which the blood cells involved in simple host immunity was obtained. RESULTS: It was found that the circulating monocyte count significantly drop after 2weeks of KY88 therapy whereas the fall did not return back to baseline. Circulating white blood cell, neutrophil and lymphocyte, however, did not show obvious change upon commencement of KY88 therapy. CONCLUSION: It was postulated that reduction in circulating monocyte count may reduce the self-inflicted host immune injury to hepatocyte which may testify the hepatoprotective ability of the herb. But, the exact mechanism on how immunomodulatory properties of the herbal medicine protect chronic HBV carriers from liver injury remains a myth.

Clinical experience with docetaxel for Chinese breast cancer patients: hematological toxicity profiles.

BACKGROUND: Asians are generally regarded to tolerate cytotoxic drugs less well than their Caucasian counterpart. A substantial proportion of patients receive suboptimal doses of chemotherapy for fear of severe toxicity. This retrospective study aims to evaluate the adverse events, especially hematological, of docetaxel in Chinese patients with breast cancer. PATIENTS AND METHODS: Fifty-nine patients, age ranged from 33 to 70 (median=47) years, were assigned to receive 3 to 6 (median=4) cycles of Docetaxel 100 mg/m2 every 21 days as neoadjuvant (n=3), adjuvant (n=26), neoadjuvant plus adjuvant (n=3), or active therapy for metastatic or relapsed breast cancer (n=27). RESULTS: A total of 56 (95%) patients completed the assigned whole regimen and only 3 (5%) patients discontinued due to either poor tolerance to the drug's side effects or worsening of disease leading to death. On average, the received dose intensity (RDI) was 0.86 for docetaxel 100 mg/m2 in this study. Among all the clinical adverse events, hematological toxicities were not excessively higher. Of the total 59 patients, major adverse events of all grades were leukopenia (22%), neutropenia (20%), fever (19%), and febrile neutropenia (14%). Only 12% and 14% of patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. CONCLUSION: In view of the increasing breast cancer incidence and the acceptable toxicity profile of docetaxel among Chinese patients, a dosage of 100 mg/m2 can be recommended for use among Asians.

Acceptable cardiac safety profile of neoadjuvant 5-fluorouracil, epirubicin, cyclophosphamide and celecoxib (FEC-C) for breast cancer: a subanalysis of biomarkers for cardiac injury.

PURPOSES: This substudy aimed to examine the changes in biomarkers for cardiac injury in patients who received neoadjuvant 5-fluorouracil, epirubicin, cyclophosphamide with concurrent celecoxib (FEC-C). METHODS: Thirty-four female patients with histologically confirmed locally advanced breast cancer preoperatively received 3 cycles of FEC-C (500 mg/m2, 75 mg/m2, 500 mg/m2) with concurrent celecoxib (400 mg bid). Blood samples were drawn from patients on day (D) 0, D3, D21, D42, and D63 (end of therapy), and the serum levels of lactate dehydrogenase (LDH) and plasma levels of cardiac troponin I (cTnI) and N-terminal prohormone brain-type natriuretic peptide (NT-proBNP) were measured with commercially available test kits. RESULTS: All patients tolerated this regimen well. Neither life-threatening toxicity nor clinical symptoms of cardiac damage were observed. Serum LDH increased significantly from baseline after 3 cycles of FEC-C (p<0.0001), but the change was possibly brought about by chemotherapy-induced liver derangement. However, NT-proBNP decreased significantly (p=0.009), while cTnI increased nonsignificantly (p=0.078) after 3 cycles of FEC-C compared to baseline, although this increase was still regarded as normal. CONCLUSIONS: Short-term use of the FEC-C regimen has proven to be effective in locally advanced breast cancer, with an acceptable cardiac safety profile.

Concurrent celecoxib with 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel for stages II - III invasive breast cancer: the OOTR-N001 study.

OBJECTIVES: This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by docetaxel (T) in the neoadjuvant setting. PATIENTS AND METHODS: A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m(2)) followed by four cycles of T (100 mg/m(2)) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival. RESULTS: Between February 2006 and January 2010, 57 of 64 evaluable patients with luminal A (n = 35, 61.4%), luminal B (n = 12, 21.1%), HER-2 positive (n = 8, 14%) and triple-negative (n = 2, 3.5%) breast cancer completed NAT and surgery. QpCR rate was observed in 18 (31.6%) patients. Exclusive of triple-negative subtype, pCR (p = 0.761) did not differ compared to other subtypes, while npCR (p = 0.043) exhibited a difference. Patients with HER-2 overexpression had a significantly higher QpCR than those of the disease attribute (10/20 vs 8/37, p = 0.029). After NAT, 43 (75.4%) and 13 (22.8%) patients achieved cCR and cPR, respectively. Patients responding to FEC were more likely to achieve a better ORR after subsequent T (p = 0.004). Over 80% of all patients received breast-conserving therapy (BCT) after receiving NAT, and 11 of 14 (78.6%) patients with T3 tumor at diagnosis became eligible for BCT after NAT. A total of 60 patients completed ≥ 6 cycles of NAT, followed by surgery; at a median follow-up of 50 months, 80% of the patients are disease-free. Neither drug-induced life-threatening toxicity nor cardiotoxicity was observed. CONCLUSIONS: Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer. The ORR was higher, but QpCR was comparable to other studies. Most patients are still disease-free, and BCT became an option for the females. Further clinical and translational studies on the use of cyclooxygenase-2 inhibitors with neoadjuvant chemotherapy are warranted.

Status of oral ulcerative mucositis and biomarkers to monitor posttraumatic stress disorder effects in breast cancer patients.

BACKGROUND: This study was designed to assess oral ulcerative mucositis, C-reactive protein, blood pressure, heart rate and thyroid function in breast cancer patients in relation to the occurrence of posttraumatic stress disorder (PTSD). METHODS: A total of 120 female breast cancer patients and women 100 healthy subjects were enrolled in this study. PTSD status was assessed by questionnaire. Before and after treatment (modified radical mastectomy and chemotherapy), serum samples were collected and measured for levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH) and high-sensitivity C-reactive protein (hs-CRP) by ELISA. Oral ulcerative mucositis was evaluated by the number and duration of oral ulcers and the degree of pain. RESULTS: Breast cancer patients experienced long-term PTSD and had elevated serum T3 and T4 levels. Patients experienced more severe pain and longer duration of oral ulcers compared with the healthy group. Oral ulcers were significantly associated with PTSD score in terms of the number of ulcers (p=0.0025), the degree of pain (p<0.0001) and the duration of ulcers (p<0.0001). CONCLUSION: These findings support that thyroid function is altered in breast cancer patients with PTSD. Elevation of T3 and T4 and oral ulcerative mucositis might be indicative of the emotional status of breast cancer patients.

Association of cytokines, high sensitive C-reactive protein, VEGF and beta-defensin-1 gene polymorphisms and their protein expressions with chronic periodontitis in the Chinese population.

PURPOSES: This study aimed at investigating the association between interleukin-6 (IL-6), interleukin-12 (IL-12), C-reactive protein (CRP), vascular endothelial growth factor (VEGF) and ß-defensin-1 polymorphisms and the susceptibility to periodontitis in the Chinese population. METHODS: DNA was extracted from the blood samples of 532 healthy individuals and 122 chronic periodontitis (CP) patients enrolled in the study. The genes encoding IL-6, IL-12, CRP, VEGF and ß-defensin-1 were amplified using PCR and digested with restriction enzymes. The protein expression of the abovementioned genes was determined by ELISA. Differences in the allele/genotype frequencies were assessed with the chi-square test. RESULTS: The frequencies of the C/C genotypes of IL-6, IL-12, and VEGF were higher in CP patients than healthy controls (66.3% vs 25.9%; 27.8% vs 19.9%; and 64.8% vs 52.1%, respectively). In the patients' group we also recorded frequencies of the A/A genotypes of CRP and VEGF higher than in healthy controls (63.1% vs 58.1% and 64.8% vs 35.2%, respectively). Protein production evaluated by ELISA demonstrated significant differences between CP patients and healthy controls for IL-6, IL-12, CRP, VEGF and ß-defensin-1. CONCLUSIONS: The genotypes of IL-6, IL-12, VEGF and ß-defensin-1 and their protein productions were associated with CP in a Chinese population. Genotypes and serum levels of CRP were associated with CP, but alleles frequency showed no difference between CP patients and healthy controls.

Application of interleukin-1 genes and proteins to monitor the status of chronic periodontitis.

It has been widely reported that periodontitis may lead to bone tissue and teeth loss and result in failure of prosthodontics or implants. Interleukin-1 (IL-1) is a potent proinflammatory cytokine that plays an essential role during the pathogenesis of periodontitis. However, the gene polymorphisms of IL-1α, IL-1ß and IL-1RN and the relationship between these protein expressions in healthy people and patients with chronic periodontitis (CP) in China have not been fully elucidated. We investigated the gene polymorphisms and protein expression of IL-1α, IL-1ß and IL-1RN in healthy subjects and CP patients, and our data suggest that these gene polymorphisms are associated with CP. The frequency of the C/C genotype of IL-1α was 55% in CP patients, while in the control group it was 20% (p<0.0001). The C/C genotype of IL-1ß was also higher in CP patients (51%) than in controls (21%) (p<0.0001). For the 2/2 genotype of IL-1RN, CP patients showed a 30% frequency, while in controls this was 15% (p<0.0001). Protein levels evaluated by enzyme-linked immunosorbent assay demonstrated a significant difference in secretion between patients and controls for IL-1α and IL-1ß. These results indicate that genotype and protein production of IL-1α, IL-1ß and IL-1RN are associated with CP in a Chinese population, and might be putative risk indicators for chronic periodontitis.

Comparative evaluation of cytokines in gingival crevicular fluid and saliva of patients with aggressive periodontitis.

OBJECTIVES: This study aims to evaluate and compare cytokines in gingival crevicular fluid (GCF) and saliva of patients with aggressive periodontitis (AP) before and after treatment. METHODS: Forty AP patients and 40 healthy volunteers were enrolled in this study. Clinical parameters included probing depth and sulcus bleeding index. GCF and saliva were collected from both groups. The levels of IL-1ß, IL-2, IL-4, IL-6, IFN-γ and TNF-α were measured using ELISA. RESULTS: The probing depth in AP patients was significantly deeper before treatment than after treatment. The concentrations of cytokines in GCF and saliva were significantly higher in AP patients than in the control group and decreased after periodontal treatment. Positive relationships were found between cytokine levels in GCF and clinical parameters. The reliability of cytokines in GCF and saliva was assessed by Cronbach's alpha analysis, which could be considered satisfactory. CONCLUSION: Cytokine levels in GCF and saliva correlated well with clinical parameters and AP. Measurements of cytokines in saliva may be regarded as a noninvasive and quick method for monitoring periodontal disease activity.

Translational research to realize the full potential of novel agents--an opportunity for vinflunine?

In the past few years, innumerable novel anti-cancer agents have been developed. Some of them have successfully entered into clinical practice while some of them have failed for different reasons. Although, nowadays, cancer treatment still relies heavily on conventional chemotherapy and surgery, with increasing evidence of novel biologic agents which demonstrate its higher anti-cancer activity and fewer side effects, more and more efforts have been spent on development of different types of novel agents. Vinflunine, a novel fluorinated vinca alkaloid, carries mitotic-arresting and tubulin-interacting properties and was just approved for treating transitional cell carcinoma of the urothelial tract (TCCU) in Europe. It, however, took quite a long time to get an approval. Needless to say, TCCU, similar to other types of cancer, is a very complex and heterogeneous disease and therefore, a single drug can hardly eradicate a cancer. Translational research, a new scientific research method, creates a link between clinical and laboratory studies. The link helps us to investigate the change in tumor environment in response to treatment, select patients who are more responsive to a particular treatment and predict prognosis of a group of patients with similar tumor characteristics. It can not only improve the success of a treatment, but also maximize the potential of novel anti-cancer agents.

Prevention of oncological diseases: primary and secondary prevention.

Cancer is the leading cause of death worldwide. Because there is presently no cure for cancer, the best strategy to combat oncological diseases is through early detection and prevention. The methods currently available are vaccines to target specific viruses (primary prevention), in combination with screening (secondary prevention), use of biomarkers, and administration of adjuvant therapy (tertiary prevention). Modifiable lifestyle-related risk factors are also important in cancer prevention. Vaccination has been proven to be highly effective against targeted diseases leading to the development of cancer, particularly if the vaccination is given in the early years of life. The need for regular screening (for breast cancer, cervical cancer, etc.) should not be neglected and should be followed to detect unusual changes or abnormalities in the body. With discoveries as targeted therapies, adjuvant treatment becomes a secure component of tertiary prevention in the betterment of disease management. The discovery of biomarkers and subsequent targeted therapies has led to personalized medicine as the current trend in cancer care.

Evaluation of the psychological and biological changes of patients diagnosed with benign and malignant breast tumors.

PURPOSE: Posttraumatic stress disorder (PTSD) is a severe anxiety disorder developed by exposure to any incident or circumstance that results in psychological trauma. In this study we compared the psychological and physiological changes between patients with malignant and benign breast tumors. METHODS: We selected 150 Chinese women with a breast mass, aged 20 to 45 years, from the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital between 2009 and 2011 for this study; 30 healthy participants were enrolled into the control group. All subjects were examined and had their tumor mass aspirated for diagnosis. Equal numbers of patients with benign and malignant tumors were recruited. Patients with malignant tumors presented with low grade, minimal tumor invasion and non-involved lymph nodes. Questionnaires regarding anxiety, depression and PTSD were conducted 2 hours before getting the diagnostic result and 1 month after the diagnosis. Serum levels of IL-6, TNF-α, cortisol and high-sensitivity C-reactive protein before and after diagnosis were investigated and compared. The number of occurrences of oral ulcerative mucositis was also recorded. RESULTS: All patients experienced a certain degree of anxiety and their biomarkers were elevated compared with the normal reference range before the pathological report was disclosed. However, 1 month after the operation, the benign tumor group showed significantly lower levels of biomarkers and anxiety scores than patients with a malignant breast tumor. The results were consistent throughout 12 months of study. CONCLUSION: Study subjects with a benign tumor returned to their normal condition after being diagnosed, while patients with a malignant tumor suffered from a certain degree of PTSD or depression.

Correlation of epigenetic change and identification of risk factors for oral submucous fibrosis.

BACKGROUND: DNA methylation of certain genes is an epigenetic change that is essential for tumorigenesis. Oral submucous fibrosis (OSF) is a precancerous condition of oral mucosa with inflammation and progressive fibrosis of the lamina propria and deeper connective tissue. The hypermethylation of E-cadherin and cyclooxygenase 2 (COX-2) in chronic inflammation may demonstrate a mild lesion/mutation at epigenetic levels. This study compares the hypermethylation status of E-cadherin and COX-2 genes in patients with oral cancer and patients with OSF and also aims to identify risk factors for the development of OSF. METHODS: DNA was extracted from blood samples of 50 healthy subjects, 50 patients with OSF and 60 patients with oral cancer. Methylation-specific polymerase chain reaction for E-cadherin and COX-2 was performed on these samples and the products were analyzed on 2% agarose gel. Surveys about oral health habits and clinical periodontal examinations in patients with OSF and healthy subjects were also conducted by well-trained dentists, and logistic regression was performed to identify risk factors for OSF. RESULTS: Hypermethylation of E-cadherin and COX-2 was observed in 36% and 22% of oral cancer samples, respectively. In patients with OSF, the rates were 52% and 30%, and in healthy controls the rates were 4% and 6%. Hypermethylation was shown to be correlated between the 3 groups with statistical significance (p<0.01). Methylation of CpG islands in E-cadherin and COX-2 occurred more frequently in patients with OSF than in the control group, but less frequently than in patients with oral cancer. In the logistic regression analysis, smoking, brushing more than twice daily, periodontal probing depth and plaque index were identified as 4 major risk factors for OSF. CONCLUSIONS: These data confirm that E-cadherin and COX-2 expressions are related to OSF. The epigenetic changes presented in patients with chronic inflammation might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic OSF was significantly associated with hypermethylation, a cancer risk factor.

Bone metabolism and quality-of-life of postmenopausal women with invasive breast cancer receiving neoadjuvant hormonal therapy: sub-analyses from celecoxib anti-aromatase neoadjuvant (CAAN) trial.

OBJECTIVE: Anti-aromatase therapy is important in the treatment of breast cancer in postmenopausal women but they have effects on the bone mineral density (BMD) and osteoporosis. Cyclooxygenase-2 (COX-2) inhibitors have been shown to be effective in chemoprevention in animal and clinical studies. A proof of principle study was performed to investigate the efficacy of combing anti-aromatase therapy (exemestane) and COX-2 inhibitors neoadjuvantly. The changes in the BMD, bone turnover proteins and quality-of-life (QoL) were analyzed and presented here. METHOD: 82 postmenopausal patients with histologically confirmed invasive hormone-sensitive breast cancers were included for the neoadjuvant therapy (NHT). 30 patients received exemestane (EXE) 25 mg daily and celecoxib (CXB) 400 mg twice daily (group A), 24 patients received EXE 25 mg daily (group B) and 28 patients received letrozole (LET) 2.5 mg daily (group C). The same assigned treatment was intended to continue for 2 years to study the changes in the bone metabolism. BMD of 48 patients were analyzed; 23 belongs to group A, 10 to group B and 15 to group C. The serum bone turnover proteins bone-specific alkaline phosphatase (BAP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP), were measured with commercially available test kits before treatment, 3 months and 15 months after treatment. Functional Assessment of Cancer Therapy core questionnaire (FACT-G) with its additional breast cancer subscale were performed at baseline, 4, 8, and 12 weeks after NHT. RESULT: Difference between groups (p=0.007) for BMD at femur was significant. The changes of BMD in group B patients were significantly greater than patients in group A (p=0.011, CI=0.063-0.437), and group C (p=0.003, CI=0.146-0.620). The mean BAP increased from baseline in group B patients but decreased from baseline in group C patients at 3 months and 15 months. No statistical significance was found in the FACT-G scores and FACT-B scores among different groups at baseline, week 4, week 8 and week 12 after NHT. The Breast Cancer Subscale scores in group A patients were significantly higher than that of group C patients (p=0.021). After 4 weeks of NHT, negative changes of FACT-B and FACT-G scores were found in group B and C patients, but there were positive changes in group A patients. Significant differences of FACT-B score (p=0.008) and FACT-G score (p=0.019) were observed at that time point. Article from the Special issue on Targeted Inhibitors.

Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer.

BACKGROUND: Racial disparities in breast cancer outcomes are attributed to differences in baseline tumour characteristics and biology, stage, age, ethnic background and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesised that racial/ethnic differences result in differential tolerance to chemotherapy potentially, leading to compromised dose intensity/density of chemotherapy in patients with early-stage breast cancer. METHODS: Data were collected from patients treated at five international centers for early breast cancer with the same adjuvant/neoadjuvant chemotherapy (FEC 100: fluorouracil 500mg/m(2), epirubicin 100mg/m(2), and cyclophosphamide 500mg/m(2),every 21d for 3-6 cycles). Toxicities were assessed by first episode of ⩾grade 2 toxicity. RESULTS: Toxicities were compared according to four race/ethnicity groups (103 Caucasian, 30 African American, 164 Asian, and 34 Hispanic patients). Tumour characteristics across four race/ethnicity groups were similar. Asians had a significantly higher rate of grade 3 haematologic toxicity than Caucasians, African Americans or Hispanic women (32%, 16%, 10%, and 15%, respectively; p<0.05). In multivariate analysis, only lower BMI was associated with a higher incidence of ⩾grade 3 toxicities. However, no significant differences in chemotherapy dose intensity/density were shown across the four race/ethnicity groups. CONCLUSION: Racial differences in acute toxicity were noted in women with breast cancer who were treated with FEC 100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy across ethnicities is not possible and emphasising the need to validate safety of chemotherapeutic regimens in patients of different ethnicities by enhancing the participation of minorities in clinical trials.