Treatment of head and neck cancer with photodynamic therapy: results after one year

Photodynamic therapy (PDT) is a new and promising treatment modality for the treatment of malignant disease. This paper reports the preliminary experience of our group in the use of this therapy for the treatment of tumours arising in the head and neck. The majority of treatments in these cases have used a second generation systemic photosensitizer, meta-tetrahydroxyphenylchlorin (m-THPC). Two other cases were treated with either Photofrin 2 (a first generation systemic sensitizer) or with the topical photosensitizer, delta-aminolaevulinic acid (delta-ALA).The initial results have been encouraging with good clinical responses evident in patients presenting with a variety of differing tumour types. We feel there is now sufficient evidence of the efficacy of this treatment to warrant a multicentre prospective study into the treatment of early head and neck cancer with PDT

Bilateral parotid secondaries from primary bronchial carcinoid tumour

Three years following a right lower lobectomy for primary carcinoid tumour of the bronchus, a patient presented with bilateral parotid masses. On investigation, both these were shown to be carcinoid tumours, consistent with metastatic spread from the primary bronchial tumour. This unique case is presented together with a discussion of the diagnostic methods employed

Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results

Foscan® (mTHPC) photosensitized macrophage activation: enhancement of phagocytosis, nitric oxide release and tumour necrosis factor-α-mediated cytolytic activity

Photodynamic activation of macrophage-like cells contributes to an effective outcome of photodynamic therapy (PDT) treatment. The possibility for an enhancement of macrophage activity by photosensitization with meta-tetra(hydroxyphenyl)chlorin (mTHPC) (1 μg ml−1) was studied in U937, monocyte cell line differentiated into macrophages (U937Φ cells). Phagocytic activity of U937Φ cells was evaluated by flow-cytometry monitoring of ingestion of fluorescein-labelled Escherichia coli particles. Increase in irradiation fluence up to 3.45 mJ cm−2 (corresponding irradiation time 15 s) resulted in significant increase in fluorescence signal (145%), while at higher light fluences the signal lowered down to the untreated control values. A light energy-dependent production of tumour necrosis factor-alpha (TNF-α) by photosensitized macrophages was further demonstrated using the L929 assay. The maximum TNF-α mediated cytolysis was observed at 28 mJ cm−2 and was 1.7-fold greater than that in control. In addition, we demonstrated a fluence-dependent increase in nitric oxide (NO) production by mTHPC-photosensitized macrophages. NO release increased gradually and reached a plateau after irradiation fluence of 6.9 mJ cm−2. Cytotoxicity measurements indicated that the observed manifestations of mTHPC-photosensitized macrophage activation took place under the sublethal light doses. The relevance of the present findings to clinical mTHPC-PDT is discussed. © 1999 Cancer Research Campaig

Genes in S and T Subgenomes Are Responsible for Hybrid Lethality in Interspecific Hybrids between Nicotiana tabacum and Nicotiana occidentalis

Many species of Nicotiana section Suaveolentes produce inviable F(1) hybrids after crossing with Nicotiana tabacum (genome constitution SSTT), a phenomenon that is often called hybrid lethality. Through crosses with monosomic lines of N. tabacum lacking a Q chromosome, we previously determined that hybrid lethality is caused by interaction between gene(s) on the Q chromosome belonging to the S subgenome of N. tabacum and gene(s) in Suaveolentes species. Here, we examined if hybrid seedlings from the cross N. occidentalis (section Suaveolentes)×N. tabacum are inviable despite a lack of the Q chromosome.Hybrid lethality in the cross of N. occidentalis×N. tabacum was characterized by shoots with fading color. This symptom differed from what has been previously observed in lethal crosses between many species in section Suaveolentes and N. tabacum. In crosses of monosomic N. tabacum plants lacking the Q chromosome with N. occidentalis, hybrid lethality was observed in hybrid seedlings either lacking or possessing the Q chromosome. N. occidentalis was then crossed with two progenitors of N. tabacum, N. sylvestris (SS) and N. tomentosiformis (TT), to reveal which subgenome of N. tabacum contains gene(s) responsible for hybrid lethality. Hybrid seedlings from the crosses N. occidentalis×N. tomentosiformis and N. occidentalis×N. sylvestris were inviable.Although the specific symptoms of hybrid lethality in the cross N. occidentalis×N. tabacum were similar to those appearing in hybrids from the cross N. occidentalis×N. tomentosiformis, genes in both the S and T subgenomes of N. tabacum appear responsible for hybrid lethality in crosses with N. occidentalis

The OSU1/QUA2/TSD2-Encoded Putative Methyltransferase Is a Critical Modulator of Carbon and Nitrogen Nutrient Balance Response in Arabidopsis

The balance between carbon (C) and nitrogen (N) nutrients must be tightly coordinated so that cells can optimize their opportunity for metabolism, growth and development. However, the C and N nutrient balance perception and signaling mechanism remains poorly understood. Here, we report the isolation and characterization of two allelic oversensitive to sugar1 mutants (osu1-1, osu1-2) in Arabidopsis thaliana. Using the cotyledon anthocyanin accumulation and root growth inhibition assays, we show that the osu1 mutants are more sensitive than wild-type to both of the imbalanced C/N conditions, high C/low N and low C/high N. However, under the balanced C/N conditions (low C/low N or high C/high N), the osu1 mutants have similar anthocyanin levels and root lengths as wild-type. Consistently, the genes encoding two MYB transcription factors (MYB75 and MYB90) and an Asn synthetase isoform (ASN1) are strongly up-regulated by the OSU1 mutation in response to high C/low N and low C/high N, respectively. Furthermore, the enhanced sensitivity of osu1-1 to high C/low N with respect to anthocyanin accumulation but not root growth inhibition can be suppressed by co-suppression of MYB75, indicating that MYB75 acts downstream of OSU1 in the high C/low N imbalance response. Map-based cloning reveals that OSU1 encodes a member of a large family of putative methyltransferases and is allelic to the recently reported QUA2/TSD2 locus identified in genetic screens for cell-adhesion-defective mutants. Accumulation of OSU1/QUA2/TSD2 transcript was not regulated by C and N balance, but the OSU1 promoter was slightly more active in the vascular system. Taken together, our results show that the OSU1/QUA2/TSD2-encoded putative methyltransferase is required for normal C/N nutrient balance response in plants