Yan-Gao Man

Gastric cancer is one of the most severe cancers, while the relationship between Helicobacter pylori (H. pylori) and gastric cancer are still in dispute, and little work has been done to explore the microbial diversity between H. pylori positive patients and negative patients. In the present work, a total of 43 gastric cancer patients and 10 healthy 53 participants were enrolled to compare the microbial differences in community structure in gastrointestinal tract between H. pylori positive patients and negative patients with gastric cancer. Our results indicated that the abundance and diversity of gastrointestinal microbiota was slight lower in gastric cancer patients than that in healthy participants especially in intestine, while the abundance of some potential pathogens, e.g. Streptococcus, Lactobacillus, Akkermansia and Halomones were higher in H. pylori positive patients than H. pylori negative patients. Therefore, our work suggests the various microbial diversity between H. pylori positive patients and H. pylori negative patients with gastric cancer, which contribute to deepen the understanding of the role of H. pylori in gastric carcinogenesis and progression.

Various antibiotics have been used in the treatment of cancers, via their anti-proliferative, pro-apoptotic and anti-epithelial-mesenchymal-transition (EMT) capabilities. However, increasingly studies have indicated that antibiotics may also induce cancer generation by disrupting intestinal microbiota, which further promotes chronic inflammation, alters normal tissue metabolism, leads to genotoxicity and weakens the immune response to bacterial malnutrition, thereby adversely impacting cancer treatment. Despite the advent of high-throughput sequencing technology in recent years, the potential adverse effects of antibiotics on cancer treatments via causing microbial imbalance has been largely ignored. In this review, we discuss the double-edged sword of antibiotics in the field of cancer treatments, explore their potential mechanisms and provide solutions to reduce the potential negative effects of antibiotics.

As the human microbiota has been confirmed to be of great significance in maintaining health, the dominant bacteria in them have been applied as probiotics to treat various diseases. After the detection of bacteria in tumours, which had previously been considered a sterile region, these bacteria have been isolated and genetically modified for use in tumour therapy. In this review, we sum up the main types of bacteria used in tumour therapy and reveal the mechanisms of both wild type and engineered bacteria in eliminating tumour cells, providing potential possibilities for newly detected, genetically modified, tumour-associated bacteria in anti-tumour therapy.

Breast cancer is the most common cancer among American women, except for skin cancers. About 12 % women in the United States will develop invasive breast cancer during their lifetime. Currently one of the most accepted model/theories is that ductal breast cancer (most common type of breast cancer) follows a linear progression: from normal breast epithelial cells to ductal hyperplasia to atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), and finally to invasive ductal carcinoma (IDC). Distinguishing pure ADH diagnosis from DCIS and/or IDC on mammography, and even combined with follow-up core needle biopsy (CNB) is still a challenge. Therefore subsequent surgical excision cannot be avoided to make a definitive diagnosis. MicroRNAs (miRNAs) are a highly abundant class of endogenous non-coding RNAs, which contribute to cancer initiation and progression, and are differentially expressed between normal and cancer tissues. They can function as either tumor suppressors or oncogenes. With accumulating evidence of the role of miRNAs in breast cancer progression, including our own studies, we sought to summarize the nature of early breast lesions and the potential use of miRNA molecules as biomarkers in early breast cancer detection. In particular, miRNA biomarkers may potentially serve as a companion tool following mammography screening and CNB. In the long-term, a better understanding of the molecular mechanisms underlying the miRNA signatures associated with breast cancer development could potentially result in the development of novel strategies for disease prevention and therapy.

Introduction: Triple-negative breast cancer (TNBC) represents 15 to 20% of all types of breast cancer; however, it accounts for a large number of metastatic cases and deaths, and there is still no effective treatment. The deregulation of microRNAs (miRNAs) in breast cancer has been widely reported. We previously identified that miR-638 was one of the most deregulated miRNAs in breast cancer progression. Bioinformatics analysis revealed that miR-638 directly targetsBRCA1. The aim of this study was to investigate the role of miR-638 in breast cancer prognosis and treatment.Methods: Formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were microdissected into normal epithelial and invasive ductal carcinoma (IDC) cells, and total RNA was isolated. Several breast cancer cell lines were used for the functional analysis. miR-638 target genes were identified by TARGETSCAN-VERT 6.2 and miRanda. The expression of miR-638 and its target genes was analyzed by real-time qRT-PCR and Western blotting. Dual-luciferase reporter assay was employed to confirm the specificity of miR-638 target genes. The biological function of miR-638 was analyzed by MTT chemosensitivity, matrigel invasion and host cell reactivation assays.Results: The expression of miR-638 was decreased in IDC tissue samples compared to their adjacent normal controls. The decreased miR-638 expression was more prevalent in non-TNBC compared with TNBC cases. miR-638 expression was significantly downregulated in breast cancer cell lines compared to the immortalized MCF-10A epithelial cells.BRCA1was predicted as one of the direct targets of miR-638, which was subsequently confirmed by dual-luciferase reporter assay. Forced expression of miR-638 resulted in a significantly reduced proliferation rate as well as decreased invasive ability in TNBC cells. Furthermore, miR-638 overexpression increased sensitivity to DNA-damaging agents, ultraviolet (UV) and cisplatin, but not to 5-fluorouracil (5-FU) and epirubicin exposure in TNBC cells. Host cell reactivation assays showed that miR-638 reduced DNA repair capability in post UV/cisplatin-exposed TNBC cells. The reduced proliferation, invasive ability, and DNA repair capabilities are associated with downregulatedBRCA1expression.Conclusions: Our findings suggest that miR-638 plays an important role in TNBC progression viaBRCA1deregulation. Therefore, miR-638 might serve as a potential prognostic biomarker and therapeutic target for breast cancer.

It is a commonly held belief that adult stem cells represent the "seeds" for normal cellular replenishment and also for carcinogenesis. The identification and characterization of stem cells for clinical therapeutic applications, however, is extremely challenging for a number of reasons. Recently, our group and others have attempted to isolate stem cells using spheroids from fresh surgical specimens and utilize them for in vitro and in vivo studies. This mini-review summarizes the major technical steps of these methods along with the primary findings. Besides, it critically analyzes the advantages and limitations of the concept and technical approaches. Finally, this mini-review presents our thoughts on the potential future directions of stem cell isolation and cancer stem cell-related research and clinical applications.

Because billions of cells die every day in their bodies, animals have evolutionarily developed apoptosis to preserve the tissue environment from adverse effects of dead cells, a process achieved via phagocytosis of the cell corpses by professional or amateur phagocytes that are collectively referred to as scavengers. Hence, apoptosis is a merger of two procedures separately occurring inside the dying and the scavenger cells, respectively. The task of apoptosis research is to study how these death procedures occur without hurting the host tissues, and recruitment of in vitro system into the study must be justified for this purpose. Cells in culture have no motivation to preserve the environment, and their death does not involve corpse clearance by scavengers. Therefore, programmed cell death in culture should be redefined, for example as stress-induced cell death, to avoid many sources of confusions, since the word “apoptosis” had already been defined, prior to the era of cell culture, as a silent and beneficial cell suicide with corpse clearance as a distinctive hallmark. We should start over again on apoptosis research by determining whether different physiological apoptotic procedures in animals involve the cytochrome c-caspase pathway, since it has been established from cultured cells as a central mechanism of “apoptosis” but whether it overarches any physiological apoptotic procedure in animals is still unclear. Probably, cells in living animals are programmed to use scavengers to assist their apoptosis but cells in culture have no scavengers to help and thus need to go mainly through the cytochrome c-caspase pathway.

Isolating high-affinity antibodies against native tumor antigens on the cell surface is not straightforward using standard hybridoma procedures. Here, we describe a combination method of synthetic peptide immunization and high-throughput flow cytometry screening to efficiently isolate hybridomas for cell binding. Using this method, we identified high-affinity monoclonal antibodies specific for the native form of glypcian-3 (GPC3), a target heterogeneously expressed in hepatocellular carcinoma (HCC) and other cancers. We isolated a panel of monoclonal antibodies (YP6, YP7, YP8, YP9 and YP9.1) for cell surface binding. The antibodies were used to characterize GPC3 protein expression in human liver cancer cell lines and tissues by flow cytometry, immunoblotting and immunohistochemistry. The best antibody (YP7) bound cell surface-associated GPC3 with equilibrium dissociation constant, KD = 0.3 nmol/L and was highly specific for HCC, not normal tissues or other forms of primary liver cancers (such as cholangiocarcinoma). Interestingly, the new antibody was highly sensitive in that it detected GPC3 in low expression ovarian clear cell carcinoma and melanoma cells. The YP7 antibody exhibited significant HCC xenograft tumor growth inhibition in nude mice. These results describe an improved method for producing high-affinity monoclonal antibodies to cell surface tumor antigens and represent a general approach to isolate therapeutic antibodies against cancer. The new high-affinity antibodies described here have significant potential for GPC3-expressing cancer diagnostics and therapy.