Sirtuin family members are characterized by either mono-ADP-ribosyltransferase or deacylase activity and are linked to various cancer-related biological pathways as regulators of transcriptional progression. Sirtuins play fundamental roles in carcinogenesis and maintenance of the malignant phenotype, mainly participating in cancer cell viability, apoptosis, metastasis, and tumorigenesis. Although sirtuin family members have a high degree of homology, they may play different roles in various kinds of cancer. This review highlights their fundamental roles in tumorigenesis and cancer development and provides a critical discussion of their dual roles in cancer, namely, as tumor promoters or tumor suppressors.

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A monitoring study was carried out with the aim to assess the level of toxic metals i.e., lead (Pb), cadmium (Cd), arsenic (As) and mercury (Hg) in different vegetables grown in Sindh province of Pakistan during 2007-2008. Two hundred ten samples of twenty one vegetables were collected from farmers' field of Sindh and exporters at Karachi. These samples were grouped into four categories viz., leafy, root and tuberous, cucurbits and fruity. The samples in duplicate were digested with nitric and perchloric acid mixture with 3:1 ratio. Cadmium and Pb were analyzed with Graphite Furnace Atomic Absorption Spectrophotometer and As and Hg on Atomic Absorption using Vapor and Hydride Generation Assembly. Average concentration of Cd, Pb, As and Hg in leafy vegetables was found 0.083 μgg-1, 0.05 μgg-1, 0.042 μgg-1 and 0.008 μgg-1 respectively, in roots and tuberous vegetables was 0.057 μgg-1, 0.03 μgg-1, 0.045 μgg-1 & 0.004 μgg-1 respectively, in cucurbit vegetables was 0.021 μgg-1, 0.051 μgg-1, 0.056 μgg-1 and 0.0089 μgg-1 respectively and in fruity vegetables was 0.035 μgg-1, 0.067 μgg-1, 0.054 μgg-1 and 0.007 μgg-1 respectively. In leafy vegetables, the concentration of cadmium, lead and mercury were found comparatively higher than other three groups of vegetables. However, concentration of heavy metals found in the samples of all four categories of vegetables, was within the permissible limits and safe to consume. Keywords: Atomic Absorption Spectroscopy; Heavy Metals; Vegetables; Graphite Furnace; Vapor Generation; Hydride GenerationDOI: 10.3126/kuset.v6i2.4013Kathmandu University Journal of Science, Engineering and Technology Vol.6. No II, November, 2010, pp.60-65

As an FDA-approved drug, glycylcycline tigecycline has been used to treat complicated microbial infections. However, recent studies in multiple hematologic and malignant solid tumors reveal that tigecycline treatment induces cell cycle arrest, apoptosis, autophagy and oxidative stress. In addition, tigecycline also inhibits mitochondrial oxidative phosphorylation, cell proliferation, migration, invasion and angiogenesis. Importantly, combinations of tigecycline with chemotherapeutic or targeted drugs such as venetoclax, doxorubicin, vincristine, paclitaxel, cisplatin, and imatinib, have shown to be promising strategies for cancer treatment. Mechanism of action studies reveal that tigecycline leads to the inhibition of mitochondrial translation possibly through interacting with mitochondrial ribosome. Meanwhile, this drug also interferes with several other cell pathways/targets including MYC, HIFs, PI3K/AKT or AMPK-mediated mTOR, cytoplasmic p21 CIP1/Waf1, and Wnt/β-catenin signaling. These evidences indicate that antibiotic tigecycline is a promising drug for cancer treatment alone or in combination with other anticancer drugs. This review summarizes the biological function of tigecycline in the treatment of tumors and comprehensively discusses its mode of action.

TRANSLATIONAL RELEVANCEOMTX705 is a novel, potent, antibody-drug conjugate that targets FAP positive CAFs, a critical component of the cancer stroma. The agent exerts preclinical antitumor activity as single agent, in combination with chemotherapy and in tumors resistant to PD-1 inhibitors. These data support the clinical development of this drug for cancer treatment.Research.

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Glioma is the most common primary tumor of the nervous system, and approximately 50% of patients exhibit the most aggressive form of the cancer, glioblastoma. The biological function of epidermal growth factor receptor (EGFR) in tumorigenesis and progression has been established in various types of cancers, since it is overexpressed, mutated, or dysregulated. Its overexpression has been shown to be associated with enhanced metastatic potential in glioblastoma, with EGFR at the top of a downstream signaling cascade that controls basic functional properties of glioblastoma cells such as survival, cell proliferation, and migration. Thus, EGFR is considered as an important therapeutic target in glioblastoma. Many anti-EGFR therapies have been investigated both in vivo and in vitro, making their way to clinical studies. However, in clinical trials, the potential efficacy of anti-EGFR therapies is low, primarily because of chemoresistance. Currently, a range of epigenetic drugs including histone deacetylase (HDAC) inhibitors, DNA methylation and histone inhibitors, microRNA, and different types of EGFR inhibitor molecules are being actively investigated in glioblastoma patients as therapeutic strategies. Here, we describe recent knowledge on the signaling pathways mediated by EGFR/EGFR variant III (EGFRvIII) with regard to current therapeutic strategies to target EGFR/EGFRvIII amplified glioblastoma.

The complete mitochondrial genome (mitogenome) of Leucoma salicis (Lepidoptera: Lymantriidae) was sequenced and annotated. It is a circular molecule of 15,334 bp, containing the 37 genes usually present in insect mitogenomes. All protein-coding genes (PCGs) are initiated by ATN codons, other than cox1, which is initiated by CGA. Three of the 13 PCGs had an incomplete termination codon, T or TA, while the others terminated with TAA. The relative synonymous codon usage of the 13 protein-coding genes (PCGs) was consistent with those of published lepidopteran sequences. All tRNA genes had typical clover-leaf secondary structures, except for the tRNASer (AGN), in which the dihydrouridine (DHU) arm could not form a stable stem-loop structure. The A + T-rich region of 325 bp had several distinctive features, including the motif ‘ATAGA’ followed by an 18 bp poly-T stretch, a microsatellite-like (AT)7 element, and an 11-bp poly-A present immediately upstream of tRNAMet. Relationships among 32 insect species were determined using Maximum Likelihood (ML), Neighbor Joining (NJ) and Bayesian Inference (BI) phylogenetic methods. These analyses confirm that L. salicis belongs to the Lymantriidae; and that Lymantriidae is a member of Noctuoidea, and is a sister taxon to Erebidae, Nolidae and Noctuidae, most closely related to Erebidae.