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ABSTRACTmechanism or have tumor suppressive functions, depending on the context. In addition, autophagy is involved in other important aspects of blood cancers as it promotes immune competence and anticancer immunity, and may even help to enhance patients' tolerance to standard treatments.

Abstract. Krukenberg tumor is a rare metastastic tumor of the ovary, characterized by poor prognosis. In order to analyze the clinical characteristics and prognostic factors, we retrospectively investigated 128 patients who were diagnosed with Krukenberg tumor between January, 1990 and December, 2010. The median patient age was 48 years. The median overall survival (OS) of Krukenberg tumor for all patients was 16 months (95% CI: 15-19 months). The median OS among patients with Krukenberg tumors of gastric, colorectal, breast and other origins (including appendix, gallbladder, small intestine and unknown primary) was 11, 21.5, 31 and 19.5 months, respectively (P<0.0001). In the univariate analysis, synchronous metastasis, no chemotherapy, ovarian metastasis beyond the pelvis, ascites and no metastasectomy were identified as significant poor prognostic factors. The multivariate analysis suggested that synchronous metastasis (P=0.0080), pelvic invasion (P=0.0138), ascites (P<0.0001) and no metastasectomy (P=0.0060) were independent factors for predicting unfavorable OS. It was suggested that the prognosis of Krukenberg tumor is dismal and ovarian metastasectomy may prove beneficial. Adequate treatment planning is required for this group of patients. IntroductionKrukenberg tumor is a rare metastatic signet ring cell tumor of the ovary, accounting for 1-2% of all ovarian tumors. The stomach is the primary site in the majority of Krukenberg tumor cases, followed by carcinomas of the colon, appendix and breast, particularly invasive lobular carcinoma (1). The eponym was attributed to this tumor following the description of 5 cases by Friedrich Krukenberg (1871-1946) in 1896, who described it as being common among young women, presenting with ascites, an uneven knobby ovarian surface and lymphatic involvement (2). These tumors are characterised by uncertain pathogenesis, challenging etiological diagnosis and poorer prognosis compared with their primaries. Previously, any metastatic ovarian cancer was referred to as Krukenberg tumor; however, Novak and Gray (3) created new diagnostic criteria to eliminate any confusion. Accordingly, a mucin-secreting signet ring cell carcinoma in the dense fibroblastic stroma of the ovary is referred to as Krukenberg tumor. The diagnosis of Krukenberg tumor is currently based on the diagnostic criteria of the World Health Organization based on the pathological description by Serov and Scully (4). The presence of the following characteristics is required for diagnosis: Stromal involvement, mucin-producing neoplastic signet ring cells and ovarian stromal sarcomatoid proliferation.Krukenberg tumor is considered as a late-stage disease with poor prognosis and may account for 30-40% of metastatic cancers to the ovaries (5). The treatment approach to these metastatic ovarian tumors remains controversial. To date, treatment mainly consists of ovarian metastasectomy, chemotherapy or radiotherapy; however, the optimal treatment has not yet been established. As the biological behavior and clinical...

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Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.

Abstract. It is well-established that triple-negative breast cancer (TNBC) is a subtype of breast cancer, characterized by a poor prognosis and aggressive biological behavior. However, the available relevant data on TNBC in non-Western populations are limited. In order to analyze the clinicopathological and molecular biological characteristics and observe survival and prognostic factors, 972 breast cancer patients (156 of whom had TNBC) who received treatment at the First Affiliated Hospital of Medical School of Xi'an Jiaotong University and the First Hospital of China Medical University, between January, 2004 and January, 2007 were retrospectively evaluated. In the univariate analysis, tumor size, TNM stage, axillary lymph node status and recurrence or metastasis were identified as prognostic factors for 7-year disease-free survival (DFS) and overall survival (OS). Our multivariate Cox's regression analysis demonstrated that tumor size and axillary lymph node status were significant prognostic factors for 7-year DFS and OS. Notably, tumor subgroup (TNBC vs. non-TNBC) was a significant prognostic factor associated with 7-year DFS and OS in breast cancer. It was suggested that TNBC exhibited a worse 7-year survival compared with that in non-TNBC patients, most likely due to its more aggressive behavior and insensitivity to specific therapy. IntroductionBreast cancer is the most common malignancy among females (1) and the second most common cause of cancer-related mortality behind lung cancer (2). Due to changes in lifestyle, the incidence of breast cancer, which is currently on the increase in developing countries, including China, has increased significantly. Based on DNA microarray techniques, breast cancer is classified into five subtypes: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2 (HER2/neu)-overexpressing and basal-like (3). The basal-like and normal breast-like subtypes, which are immunohistochemically characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PgR) and HER2, are defined as triple-negative breast cancer (TNBC) (4).TNBC is a distinct breast cancer subtype, which accounts for ~10-17% of all breast carcinomas (5). TNBC, usually occurring in young females, is generally considered to exhibit an aggressive clinical behavior and poor prognosis, due to the fact that it is insensitive to endocrine and targeted therapy (6). Furthermore, the TNBC subgroup is associated with a higher risk of distant recurrence and mortality compared to its non-triple-negative counterparts, particularly during the first 3-5 years of follow-up (6). However, few studies have been conducted among non-Western populations (7) and the information on the Asian TNBC subtype remains confusing and limited (8). Kurebayashi et al (9) reported that Japanese patients with TNBC are mostly superimposable for disease-free survival (DFS) and overall survival (OS). Lin et al (10) indicated that Taiwanese TNBC patients exhibited a better 5-year OS compared with HER2...

Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR). Overexpressing Beclin 1 improved the repair of IR-induced DSB, but did not restore an autophagy response in cells lacking autophagy gene Atg7, suggesting that Beclin 1 may regulate DSB repair independent of autophagy in the cells exposed to IR. Indeed, we found that Beclin 1 could directly interact with DNA topoisomerase IIβ and was recruited to the DSB sites by the interaction. These findings reveal a novel function of Beclin 1 in regulation of DNA damage repair independent of its role in autophagy particularly when the cells are under radiation insult.

Background: Autophagy is required in hematopoiesis and protects against leukemogenesis. Results: When ATG7-dependent canonical autophagy is impaired, ATG7-independent alternative autophagy engages in myeloid cells but not in hematopoietic stem cells. Conclusion:The integrity of hematopoietic stem cells is jeopardized by a lack of alternative autophagy. Significance: Learning autophagy organization in hematopoietic system is crucial for understanding hematopoietic stem cell transformation.