BODIPY dyes tend to be highly fluorescent, but their emissions can be attenuated by adding substituents with appropriate oxidation potentials. Substituents like these have electrons to feed into photoexcited BODIPYs, quenching their fluorescence, thereby generating relatively long-lived triplet states. Singlet oxygen is formed when these triplet states interact with 3O2. In tissues, this causes cell damage in regions that are illuminated, and this is the basis of photodynamic therapy (PDT). The PDT agents that are currently approved for clinical use do not feature BODIPYs, but there are many reasons to believe that this situation will change. This review summarizes the attributes of BODIPY dyes for PDT, and in some related areas.

/pdf/bodipy-dyes-in-photodynamic-therapy-4fs3p30tk8.pdf

BODIPY dyes in photodynamic therapy.

Epstein-Barr virus (EBV) is a herpesvirus associated with nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and other malignancies. EBV is the first human virus found to express microRNAs (miRNAs), the functions of which remain largely unknown. We report on the regulation of a cellular protein named p53 up-regulated modulator of apoptosis (PUMA) by an EBV miRNA known as miR-BART5, which is abundantly expressed in NPC and EBV-GC cells. Modulation of PUMA expression by miR-BART5 and anti–miR-BART5 oligonucleotide was demonstrated in EBV-positive cells. In addition, PUMA was found to be significantly underexpressed in ∼60% of human NPC tissues. Although expression of miR-BART5 rendered NPC and EBV-GC cells less sensitive to proapoptotic agents, apoptosis can be triggered by depleting miR-BART5 or inducing the expression of PUMA. Collectively, our findings suggest that EBV encodes an miRNA to facilitate the establishment of latent infection by promoting host cell survival.

/pdf/an-epstein-barr-virus-encoded-microrna-targets-puma-to-o598101z7k.pdf

An Epstein-Barr virus–encoded microRNA targets PUMA to promote host cell survival

The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5′,5‴-P1,P3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase “dead” Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5′,5‴-P1,P3-triphosphate hydrolysis is not required for tumor suppression.

https://www.pnas.org/content/pnas/94/25/13771.full.pdf

Replacement of Fhit in cancer cells suppresses tumorigenicity

We have established a cell line (C666-1) from undifferentiated nasopharyngeal carcinoma (NPC). This cell line consistently carries the Epstein-Barr virus (EBV) in long-term cultures. C666-1 is a subclone of its parental cell line, C666, derived from an NPC xenograft of southern Chinese origin. It grows as an adherent culture and lacks contact inhibition. In addition, it is tumorigenic in athymic nude mice. The cells consistently express EBV-encoded RNAs and are positively stained for cytokeratin, an epithelial marker. In addition, they express EBNA1 protein, LMP1 and LMP2 transcripts and thus resemble the EBV latency II pattern. The virus genotype is EBV-1 with the latent membrane protein 1 gene showing a 30-bp deletion at the carboxyl terminus, both consistent with findings in southern Chinese NPC tumours. Cytogenetic analysis revealed a sub-diploid status with a chromosomal modal number of 45. C666-1 is unique among NPC cell lines in that it carries EBV. These cells may serve as a good investigative tool as the viral latency pattern and genotype are observed in the majority of primary NPC biopsies from Chinese patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0215%2819990924%2983%3A1%3C121%3A%3AAID-IJC21%3E3.0.CO%3B2-F

Nasopharyngeal carcinoma cell line (C666‐1) consistently harbouring Epstein‐Barr virus

We have investigated the genetic and epigenetic changes of a newly isolated tumor suppressor gene on 3p213, RASSF1A, in nasopharyngeal carcinoma (NPC) Four xenografts, four cell lines and 21 primary tumors were examined Promoter hypermethylation of the 5'CpG island of RASSF1A was detected in 4 of 4 (100%) xenografts, in 3 of 4 (75%) cell lines, and in 14 of 21 (667%) primary tumors but not in the normal nasopharyngeal epithelia Mutations were found in 2 of 21 (95%) primary tumors In the cell lines and xenografts with extensive methylation, no RASSF1A gene expression was found After treatment with 5'-aza-2'deoxycytidine, reexpression and demethylation of the RASSF1A gene were detected in a NPC cell line These findings suggest that promoter hypermethylation may participate in the transcriptional inactivation of the RASSF1A gene in NPC The high incidence of RASSF1A alterations suggest that it is the critical target gene on chromosome 3p213 involved in the development of NPC

/pdf/high-frequency-of-promoter-hypermethylation-of-rassf1a-in-3uf39ryc3r.pdf

High Frequency of Promoter Hypermethylation of RASSF1A in Nasopharyngeal Carcinoma

A long-term cell culture epithelioid cell line was established from a recurrent squamous carcinoma of the nasopharynx of a Chinese male 17 1/2 years after radiation therapy. The cell line, designated NPC/HK1, has been passed 72 times over a period 1 year. The cells have been shown by light and electron microscopies to be of the squamous epithelial type. When they were transplanted subcutaneously into the back of athymic nude BALB/c (nu/nu) mice, tumors developed at the sites of inoculation, which on histological examination were shown to be well-differentiated squamous carcinomas, similar in morphology to the recurrent human tumor from which they were derived. Karyotypic analysis of cells from the cell line demonstrates an aneuploid human type with a modal chromosome number of 74 with both numerical and structural aberrations. Viral particles or Epstein-Barr viral nuclear antigen (EBNA) has not been demonstrated in the cells from the primary culture or several of the subcultures tested. The presence of EBNA in touch smears prepared from the biopsy tissue was inconclusive. Infection of the subcultured cells with EBV from P3HR1 and B95-8 cells was unsuccessful.

D. Saw

Papers

Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx.