Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer.

Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance.

Intravenous administration of manuka honey inhibits tumor growth and improves host survival when used in combination with chemotherapy in a melanoma mouse model.

Manuka honey has been recognized for its anti-bacterial and wound-healing activity but its potential antitumor effect is poorly studied despite the fact that it contains many antioxidant compounds. In this study, we investigated the antiproliferative activity of manuka honey on three different cancer cell lines, murine melanoma (B16.F1) and colorectal carcinoma (CT26) as well as human breast cancer (MCF-7) cells in vitro. The data demonstrate that manuka honey has potent anti-proliferative effect on all three cancer cell lines in a time- and dose-dependent manner, being effective at concentrations as low as 0.6% (w/v). This effect is mediated via the activation of a caspase 9-dependent apoptotic pathway, leading to the induction of caspase 3, reduced Bcl-2 expression, DNA fragmentation and cell death. Combination treatment of cancer cells with manuka and paclitaxel in vitro, however, revealed no evidence of a synergistic action on cancer cell proliferation. Furthermore, we utilized an in vivo syngeneic mouse melanoma model to assess the potential effect of intravenously-administered manuka honey, alone or in combination with paclitaxel, on the growth of established tumors. Our findings indicate that systemic administration of manuka honey was not associated with any alterations in haematological or clinical chemistry values in serum of treated mice, demonstrating its safety profile. Treatment with manuka honey alone resulted in about 33% inhibition of tumor growth, which correlated with histologically observable increase in tumor apoptosis. Although better control of tumor growth was observed in animals treated with paclitaxel alone or in combination with manuka honey (61% inhibition), a dramatic improvement in host survival was seen in the co-treatment group. This highlights a potentially novel role for manuka honey in alleviating chemotherapy-induced toxicity.

The use of a vacuum-assisted biopsy device (Mammotome) in the early detection of breast cancer in the United Arab Emirates.

Stereotactic core needle biopsy has proven to be an accurate technique for evaluation of mammographically detected microcalcification. The development of the Mammotome biopsy system has led many medical centers to use this vacuum-assisted device for the sampling of microcalcifications in mammographically detected nonpalpable breast lesions. Ninety-six women underwent 101 stereotactic Mammotome core biopsies for mammographic calcifications over a 32-month period in the Department of Surgery at Tawam Hospital, the national referral oncology center in the UAE. The stereotactic procedure was performed by surgeons using the Mammotome biopsy system. Microcalcifications were evident on specimen radiographs and microscopic sections in 96% and 87% of the cases, respectively. Excisional biopsy was recommended for diagnoses of atypical ductal hyperplasia or carcinoma. Patients with benign diagnoses underwent mammographic follow-up. Eighty-one lesions were benign, 5 atypical ductal hyperplasias and 14 carcinomas were diagnosed (2 invasive lobular carcinoma, 4 invasive ductal carcinoma, and 8 intraductal carcinomas in situ: 1 comedo, 1 cribriform, 6 mixed cribriform and micropapillary). Surgical excision in four patients with atypia on Mammotome biopsy (one was lost to follow-up) showed atypical ductal hyperplasia. Surgical excision in seven patients diagnosed with intraductal carcinoma in situ (one patient lost to follow-up) showed intraductal carcinoma with no evidence of microinvasion. Similar diagnoses were made in all the invasive ductal and lobular carcinomas in both Mammotome and excisional biopsies. A diagnosis of atypia on Mammotome biopsy warranted excision of the atypical area, yet the underestimation rate for the presence of carcinoma remained low. The likelihood of an invasive component at excision was negligible for microcalcification diagnosed as intraductal carcinoma in situ on Mammotome biopsy. Mammotome biopsy proved to be an accurate technique for the sampling, diagnosis, and early detection of breast cancer.

Validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires for Arabic-speaking Populations.

Information about quality of life in patients with cancer in Arab populations in 21 countries is inadequate. The objective of this study was to assess the psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer (EORTC) general quality of life questionnaire (QLQ-C30) and of the breast cancer-specific questionnaire (QLQ-BR23) in Arab breast cancer patients. The questionnaires were administered to 87 breast cancer patients 3 months after surgery. The mean age of patients was 48.6 years (SD: 9.9), 76% were married, all had staged disease (I, 9%; II, 46%; III, 44%; IV, 1%). The percentage of patients who underwent mastectomy and lumpectomy were 49% and 51%, respectively. Questionnaire reliability was assessed using Cronbach's alpha coefficient, in which the values were all >0.7, with the exception of cognitive function and pain in the QLQ-C30 (Cronbach's alpha 0.67 and 0.51, respectively) and breast symptoms in the QLQ-BR23 (Cronbach's alpha 0.50). The questionnaires' validity was confirmed using "known group comparisons," which showed that the QLQ-C30 discriminated between mastectomy and lumpectomy patients on the emotional and cognitive function scales (P < 0.001) and QLQ-BR23 discriminated as well on the function scales and for systemic side effects (P < 0.001). For the most part, QLQ-C30 and QLQ-BR23 distinguished clearly between subgroups of patients differing in their Hospital Anxiety and Depression Scale. In summary, the Arabic versions of the EORTC QLQ-C30 and QLQ-BR23 are reliable and valid tools for assessment of quality of life in Arab patients with cancer.