Controlled targeting of different subcellular sites by porphyrins in tumour-bearing mice.

Unilamellar liposomes of dipalmitoyl-phosphatidylcholine can incorporate various porphyrins in either the phospholipid bilayer or the internal aqueous compartment depending on the water-/lipo-solubility of the drug. Intraperitoneal injection of the liposome-bound porphyrins to mice bearing a MS-2 fibrosarcoma results in remarkably more efficient tumour targeting than that obtained by administration of the same porphyrins dissolved in homogeneous aqueous solution. Moreover, also water-insoluble porphyrins can be transported to the tumour via liposomes. Fractionation of liver and neoplastic cells indicates that the subcellular distribution of liposome-delivered porphyrins is also dependent on their solubility properties: thus, relatively polar porphyrins, such as tetra(4-sulfonatophenyl)porphine and uroporphyrin, are mainly recovered from the soluble fraction, whereas hydrophobic porphyrins, such as haematoporphyrin or porphyrin esters, preferentially partition in the cytoplasmic membrane. As a consequence, different subcellular sites can be targeted by porphyrins and possibly photodamaged through a suitable choice of the drug-carrier system

Noise Removal in Microarray Images Using Variational Mode Decomposition Technique

Microarray technology allows the simultaneous monitoring of thousands of genes in parallel. Based on the gene expression measurements, microarray technology have proven powerful in gene expression profiling for discovering new types of diseases and for predicting the type of a disease. Enhancement, Gridding, Segmentation and Intensity extraction are important steps in microarray image analysis. This paper presents a noise removal method in microarray images based on Variational Mode Decomposition (VMD). VMD is a signal processing method which decomposes any input signal into discrete number of sub-signals (called Variational Mode Functions) with each mode chosen to be its band width in spectral domain. First the noisy image is processed using 2-D VMD to produce 2-D VMFs. Then Discrete Wavelet Transform (DWT) thresholding technique is applied to each VMF for denoising.  The denoised microarray image is reconstructed by the summation of VMFs.  This method is named as 2-D VMD and DWT thresholding method. The proposed method is compared with DWT thresholding and BEMD and DWT thresholding methods. The qualitative and quantitative analysis shows that 2-D VMD and DWT thresholding method produces better noise removal than other two methods

Low doses of cisplatin or gemcitabine plus Photofrin/photodynamic therapy: Disjointed cell cycle phase-related activity accounts for synergistic outcome in metastatic non-small cell lung cancer cells (H1299).

We compared the effects of monotherapy (photodynamic therapy or chemotherapy) versus combination therapy (photodynamic therapy plus a specific drug) on the non-small cell lung cancer cell line H1299. Our aim was to evaluate whether the additive/synergistic effects of combination treatment were such that the cytostatic dose could be reduced without affecting treatment efficacy. Photodynamic therapy was done by irradiating Photofrin-preloaded H1299 p53/p16-null cells with a halogen lamp equipped with a bandpass filter. The cytotoxic drugs used were cis-diammine-dichloroplatinum [II] (CDDP or cisplatin) and 2',2'-difluoro-2'-deoxycytidine (gemcitabine). Various treatment combinations yielded therapeutic effects (trypan blue dye exclusion test) ranging from additive to clearly synergistic, the most effective being a combination of photodynamic therapy and CDDP. To gain insight into the cellular response mechanisms underlying favorable outcomes, we analyzed the H1299 cell cycle profiles and the expression patterns of several key proteins after monotherapy. In our conditions, we found that photodynamic therapy with Photofrin targeted G0-G1 cells, thereby causing cells to accumulate in S phase. In contrast, low-dose CDDP killed cells in S phase, thereby causing an accumulation of G0-G1 cells (and increased p21 expression). Like photodynamic therapy, low-dose gemcitabine targeted G0-G1 cells, which caused a massive accumulation of cells in S phase (and increased cyclin A expression). Although we observed therapeutic reinforcement with both drugs and photodynamic therapy, reinforcement was more pronounced when the drug (CDDP) and photodynamic therapy exert disjointed phase-related cytotoxic activity. Thus, if photodynamic therapy is appropriately tuned, the dose of the cytostatic drug can be reduced without compromising the therapeutic response

Liposome- or LDL-administered Zn (II)-phthalocyanine as a photodynamic agent for tumours. I. Pharmacokinetic properties and phototherapeutic efficiency.

The pharmacokinetics of Zn-phthalocyanine (Zn-Pc) in mice bearing a transplanted MS-2 fibrosarcoma has been studied using dipalmitoyl-phosphatidylcholine (DPPC) liposomes and low density lipoproteins (LDL) as drug delivery systems. LDL induce a higher Zn-Pc uptake by the tumour and improve the selectivity of tumour targeting as compared to DPPC liposomes. Experimental photodynamic therapy (PDT) of the MS-2 fibrosarcoma has been performed using liposome-delivered Zn-Pc and the efficiency of tumour necrosis has been measured following four different irradiation protocols. We found that Zn-Pc doses as low as 0.07-0.35 mg kg-1 are sufficient for inducing an efficient tumour response that is linearly dependent on the injected dose. The amount of Zn-Pc in the tumour decreases very slowly as a function of time, hence PDT gives satisfactory results even if performed at relatively long time intervals after administration

Initial performance of ten oil palm cross combinations under three agro-climatic conditions in India

High yielding hybrids can play an important role in increasing the productivity of oil in the oil palm. With a view to evaluate high yielding new oil palm cross combinations, a field experiment was conducted in different agro-climatic regions of India viz., Zone No-10 Southern Plateau and Hills (Gangavathi, Karnataka), Zone No-12 Western Coastal Plains and Ghats (Mulde, Maharashtra) and Zone No-11 Eastern Coastal Plains and Hills (Vijayarai, Andhra Pradesh) involving ten cross combinations of tenera oil palm (NRCOP 1-10). The data from three locations over two years indicated that, significantly higher annual rate of leaf production per palm was recorded in NRCOP-6 (21.7) compared to NRCOP-3 and it was on par with other hybrid combinations. Significantly higher sex ratio was recorded with NRCOP-4 (63.1%) compared to NRCOP-1 (54.6%) and NRCOP-6 (54.8%) and was on par with other hybrid combinations.The hybrid cross combination, NRCOP-4 recorded significantly higher fresh fruit bunches (FFBs) yield 12.5 t ha-1 compared to NRCOP-1, NRCOP-3, NRCOP-7 and NRCOP-9 and it was on par with remaining hybrids and a similar result in bunch weight and number of bunches per palm was recorded. Pooled data on FFB yield for 2013-15 indicated that the hybrid combination NRCOP-4 which recorded higher FFB yield (12.6 t ha-1) at Gangavathi and at Vijayarai (22.6 t ha-1) have better prospects for adaptation under Tungabhadra command area and coastal region of Andhra Pradesh. For Konkan region of Maharashtra, the hybrid NRCOP-8 recorded the highest FFB yield

Evaluation of African oil palm germplasm for drought tolerance

A field experiment was conducted at ARS Campus, Gangavati, University of Horticultural Sciences, Bagalkot to evaluate the oil palm genotypes for drought tolerance under medium black soils of Tungabhadra Command area of Karnataka. Nine oil palm genotypes were collected from Zambia and Tanzania for drought tolerance studies under rainfed conditions. The genotype ZS-3 recorded significantly higher fresh fruit bunch (FFB) yield 7.0 t ha-1 over Z-6, ZS-8, ZS-8, ZS-9, TS-5 and TS-7. Number of bunches were significantly higher in the genotypes ZS-3 (4.4) followed by ZS-1 (4.1) and ZS-9 (4.0). Bunch weight was significantly higher in the genotype ZS-3 (11.2 kg bunch-1) followed by ZS-5 (10.8 kg bunch-1) and ZS-6 (9.4 kg bunch-1). The number of fruits per bunch was significantly higher in the genotype ZS-8 (3031) over all other genotypes. The number of male inflorescence was lower with the genotype ZS-5 and TS-5 (7.8 and 8.0 respectively). The number of female inflorescence was higher with the genotypes ZS-3 and TS-5 (7.0 and 7.0, respectively). Per cent sex ratio was higher with the genotype TS-5 and ZS-5 (46.2 and 44.8, respectively). The genotype ZS-1 and ZS-5 recorded higher annual leaf production of 21.4 and 20.3, respectively. The genotype ZS-1 recorded significantly lower number of leaf scorched per palm of 2.2 over other genotypes but it was on par with genotype ZS-3 (3.6). The data on various physiological and biochemical parameters revealed that the genotype ZS-1 and ZS-3 recorded higher relative water content, lower electrolyte leaching and significantly lower peroxidase activity indicating relatively more stress tolerant than other tested genotypes

The Role of the PAX8/PPARγ Fusion Oncogene in Thyroid Cancer

Thyroid cancer is uncommon and exhibits relatively low mortality rates. However, a subset of patients experience inexorable growth, metastatic spread, and mortality. Unfortunately, for these patients, there have been few significant advances in treatment during the last 50 years. While substantial advances have been made in recent years about the molecular genetic events underlying papillary thyroid cancer, the more aggressive follicular thyroid cancer remains poorly understood. The recent discovery of the PAX8/PPARγ translocation in follicular thyroid carcinoma has promoted progress in the role of PPARγ as a tumor suppressor and potential therapeutic target. The PAX8/PPARγ fusion gene appears to be an oncogene. It is most often expressed in follicular carcinomas and exerts a dominant-negative effect on wild-type PPARγ, and stimulates transcription of PAX8-responsive promoters. PPARγ agonists have shown promising results in vitro, although very few studies have been conducted to assess the clinical impact of these agents

Carotenoporphyrins as selective photodiagnostic agents for tumours.

The covalent binding of a carotene moiety to one phenyl ring and meso-tetraphenyl-substituted porphyrins (see Figure 1) efficiently quenches the photosensitising activity of the porphyrin while a relatively large yield of fluorescence emission around 650 nm is retained. Pharmacokinetic studies performed with two carotenoporphyrins (CPs) and the corresponding porphyrins (Ps) in Balb/c mice bearing an MS-2 fibrosarcoma show that the two Ps give a high selectivity of tumour localisation (tumour/peritumoral tissue ratios of dye concentration ranging between c. 30 and 90 at 24 h after injection of 4.2-8.4 mumol kg-1 in a Cremophor emulsion) and photosensitive tumour necrosis upon red light irradiation. For the same injected doses, the two CPs show no tumour-photosensitising activity even though they localise in the tumour in concentrations of the order of 10-40 micrograms g-1 at 24 h with tumour/peritumoral ratios larger than 10. Thus, the fluorescence emitted by these CPs in the tumour can be used for photodiagnostic purposes with no risk of skin photosensitisation. However, this approach is presently limited by the large accumulation and prolonged retention of the CPs in the liver and spleen