High-risk human papillomaviruses (HPVs) are etiologically implicated in human cervical cancer. Two viral genes, E6 and E7, are commonly found expressed in these cancer cells. We have previously shown that mice transgenic for the HPV-16 E6 gene or E7 gene, in which the E6 or E7 was expressed in the basal layer of epithelia, developed skin tumors. The spectrum of tumors derived from E6 and E7 mice differed, however; although most tumors derived from the E7-transgenic mice were benign, the majority of the tumors from the E6-transgenic mice were malignant. These findings led us to hypothesize that E6 and E7 play different roles in carcinogenesis. To assess at what stages in carcinogenesis E6 and E7 act, we treated the skin of K14E6- and K14E7-transgenic mice with chemical carcinogens known to contribute to distinct stages in carcinogenesis. Both E6 and E7 were found to synergize with chemical carcinogens in causing tumor formation. E6 was found to act weakly at the promotion stage of carcinogenesis in the formation of benign tumors but strongly at the progression stage which involves the malignant conversion of benign tumors. In contrast, E7 primarily affected the promotion stage of carcinogenesis. These results provide direct evidence that E6 and E7 contribute differently to carcinogenesis; E7 promotes the formation of benign tumors, and E6 acts primarily to accelerate progression of these benign tumors to the malignant stage. Consistent with this model, we found E6 and E7 to cooperate in inducing tumor formation in mice expressing both oncogenes.

In recent decades, bacteria’s therapeutic role has aroused attention in medicinal and pharmaceutical research. While bacteria are considered among the primary agents for causing cancer, recent research has shown intriguing results suggesting that bacteria can be effective agents for cancer treatment – they are the perfect vessels for targeted cancer therapy. Several bacterial strains/species have been discovered to possess inherent oncolytic potentials to invade and colonize solid tumors in vivo. The therapeutic strategy of using bacteria for treating cancer is considered to be effective; however, the severe side effects encountered during the treatment resulted in the abandonment of the therapy. State-of-the-art genetic engineering has been recently applied to bacteria therapy and resulted in a greater efficacy with minimum side effects. In addition, the anti-cancer potential of tumor-targeting bacteria through oral administration circumvents the use of the intravenous route and the associated adverse effects. This review aims to provide a comprehensive summary of the latest literature on the role of bacteria in cancer treatment.

High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy.

E6 and E7 oncoproteins from high risk human papillomaviruses (HPVs) transform cells in tissue culture and induce tumors in vivo. Both E6, which inhibits p53 functions, and E7, which inhibits pRb, can also abrogate growth arrest induced by DNA-damaging agents in cultured cells. In this study, we have used transgenic mice that express HPV-16 E6 or E7 in the epidermis to determine how these two proteins modulate DNA damage responses in vivo. Our results demonstrate that both E6 and E7 abrogate the inhibition of DNA synthesis in the epidermis after treatment with ionizing radiation. Increases in the levels of p53 and p21 proteins after irradiation were suppressed by E6 but not by E7. Through the study of p53-null mice, we found that radiation-induced growth arrest in the epidermis is mediated through both p53-dependent and p53-independent pathways. The abrogation of radiation responses in both E6 and E7 transgenic mice was more complete than was seen in the p53-null epidermis. We conclude that E6 and E7 each have the capacity to modulate p53-dependent as well as p53-independent cellular responses to radiation. Additionally, we found that the conserved region (CR) 1 and CR2 domains in E7 protein, which are involved in the inactivation of pRb function and required for E7's transforming function, were also required for E7 to modulate DNA damage responses in vivo. Thus pRb and͞or pRb-like proteins likely mediate both p53-dependent and p53-independent responses to radiation.Human papillomaviruses (HPVs) are the causative agents of warts. A subset of HPVs, referred to as high risk HPVs, are associated with human anogenital cancers such as cervical cancers in women and penile cancers in men (1). Two genes of these high risk HPVs, E6 and E7, are expressed in the cells derived from HPV-associated cancers (2, 3). E6 and E7 cooperate with each other (4, 5) and with other oncogenes (6-9) in the immortalization or transformation of cells. The transforming activities of E6 and E7 correlate, at least in part, with their inactivation of two cellular tumor suppressor gene products, p53 and pRb, which regulate the processes of division, differentiation, and͞or death in cells (10-12). E6 binds to p53 (13) and mediates degradation of p53 through the ubiquitin-proteasomal degradation pathway (14). E7 binds to pRb (15), inhibits pRb's function (16), and promotes degradation of pRb (17,18). In vivo experiments using mice transgenic for E6 and E7 have shown that E6 and E7 together can induce tumors in the targeted tissues (19-21). Our laboratory has generated transgenic mice in which the expression of HPV-16 E6 (S.S. and P.F.L. unpublished work) or E7 (22) singly was directed to mouse squamous epithelial cells by the human keratin 14 (K14) promoter. These mice develop papillomas and carcinomas in the late stage of their life, indicating that E6 and E7 each is sufficient to induce tumors. Because of the long latent period of tumor induction, it is proposed that other genetic changes must contribute to the carcinogenesis induced by E...

Red/near‐infrared (NIR) emissive carbon nanodots (CNDs) with photoluminescence (PL) quantum yield (QY) of 57% are prepared via an in situ solvent‐free carbonization strategy for the first time. 1‐Photon and 2‐photon cellular imaging is demonstrated by using the CNDs as red/NIR fluorescence agent due to the high PL QY and low biotoxicity. Further study shows that the red/NIR CNDs exhibit multiphoton excited (MPE) upconversion fluorescence under excitation of 800–2000 nm, which involves three NIR windows (NIR‐I, 650–950 nm; NIR‐II, 1100–1350; NIR‐III, 1600–1870 nm). 2‐Photon, 3‐photon, and 4‐photon excited fluorescence of the CNDs under excitation of different wavelengths is achieved. This study develops an in situ solvent‐free carbonization method for efficient red/NIR emissive CNDs with MPE upconversion fluorescence, which may push forward the application of the CNDs in bioimaging.