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Glycolysis, a central metabolic pathway, harbors evolutionary conserved enzymes that modulate and potentially shift the cellular metabolism on requirement. Pyruvate kinase, which catalyzes the last but rate-limiting step of glycolysis, is expressed in four isozymic forms, depending on the tissue requirement. M2 isoform (PKM2) is exclusively expressed in embryonic and adult dividing/tumor cells. This tetrameric allosterically regulated isoform is intrinsically designed to downregulate its activity by subunit dissociation (into dimer), which results in partial inhibition of glycolysis at the last step. This accumulates all upstream glycolytic intermediates as an anabolic feed for synthesis of lipids and nucleic acids, whereas reassociation of PKM2 into active tetramer replenishes the normal catabolism as a feedback after cell division. In addition, involvement of this enzyme in a variety of pathways, protein–protein interactions, and nuclear transport suggests its potential to perform multiple nonglycolytic functions with diverse implications, although multidimensional role of this protein is as yet not fully explored. This review aims to provide an overview of the involvement of PKM2 in various physiological pathways with possible functional implications.

Mitochondrial DNA alterations in recent years have been suggested as modifier events, providing a possible proliferative advantage to the tumor cells. In order to provide further insight into the process of tumorigenesis, a study of whole mitochondria genome was conducted in 134 tissue samples obtained from 2 unrelated cancers (tumor and adjacent normal tissues from 36 breast cancer and 31 esophageal squamous cell carcinoma (ESCC) patients) with known p53 somatic mutation background. Fifteen of 36 (41.66%) breast and 12 of 31 (38.71%) ESCC tumors were found to contain at least 1 mtDNA somatic mutation, which correlated significantly with the concomitant presence of somatic mutation in DNA binding domain of the p53 gene (Breast cancer, p = 0.006; ESCC, p = 0.002). Interestingly, mutations in the non D-loop region of the mtDNA contributed significantly (Breast cancer, p = 0.004; ESCC, p = 0.032) in comparison to the hotspot-D-Loop-region. The concomitant presence of mutations in p53 and mtDNA were also predominant in breast cancer tumors with poor prognosis, that is, with the advanced stage, grade and the ER/PR negativity. Also, the observation made was apparently well explained in 10398A bearing N haplogroup genetic background with increased presence of novel and pathogenic germline mutation in mtDNA. Our study suggests that the concomitant presence of somatic alteration in mtDNA and the DNA binding domain of the p53 gene facilitates cell survival and tumorigenesis, requiring specialized therapeutic intervention because of a possible resistance to conventional chemotherapy.

In this report a family is described where cerebellar ataxia occurred along with total albinism. A possibility of syntenic condition of the two genes responsible for the traits could explain the occurrence of the two conditions. The presence of two traits singly in the sibs reflects a recombinant event and suggests that the linkage is not absolute. Chromosomal study did not show any structural or numerical anomalies except in 1/50 metaphase plates scored in the proband (with cerebellar ataxia) where in chromosome No. 14 proximal intense band (21) seemed to be shifted, inv. (14) (q13q23?). The affected sibs with ataxia and albinism or ataxia alone depicted relatively a lower sister chromatid exchange (SCE) rate than their parents and age matched controls.

Genotypic status of the signal peptide region of transforming growth factor beta1 (TGF-beta1) showed a significant difference in C/C-genotype frequency at +29 position (codon 10) between a range of viral hepatitis patients and controls (P = 0.009, OR = 3.15, CI = 1.29-7.678), contributed by those who were infected with hepatitis B virus (HBV) alone or HBV + hepatitis delta virus (HDV) (P = 0.003, OR = 5.0, CI = 1.78-13.97).

Transforming growth factor beta (TGF-beta) is an example for a large and still-growing family of growth factors. TGF-beta1 is known to act both as a tumour suppressor and as a stimulator of tumour progression. This study examines the relationship amongst putative enhancer, promoter, 5'-untranslated-region (UTR) and exon-1 polymorphisms of the TGF-beta1 gene (region I from -1881 to -1613; region II from -1410 to -1123, and region III from -55 to +176, as per human genome organisation (HUGO) nomenclature) in 26 breast cancer patients and 97 healthy control subjects. The germline and somatic status of the four known polymorphisms was ascertained, and a significant difference was observed for the germline C/T and T/T genotype distribution between patients and controls in comparison to C/C genotypes at position -1349 (chi2 = 6.193; P = 0.009). In addition to the somatic variations observed for some of the regions studied, in 10/26 (38%) sporadic breast cancer cases, a novel somatic mutation in codon 47 of exon 1 (GenBank accession number AY059373) was also detected in tumour samples. The risk of cancer was found to be significant (OR = 4.525) for the -1349 C/T and T/T genotype background, suggesting that this genetic background may act as a risk factor for sporadic breast cancer.

Summary Two new single nucleotide mutations were observed within the promoter region of human interleukin-6 gene (IL-6) in the tumour sample of a patient with sporadic breast cancer, which was a somatic change. Both mutations, one at −125 (C > G) and the other at position −173 (G > T) from the translation start site, were transversions observed at new positions, not reported earlier. In addition to these two novel mutations in this patient, a known somatic polymorphism was also observed at position −174 (G > C) (from the transcription initiation site, redesignated as −236 from the translational initiation site as per the HUGO nomenclature). Further, a preliminary comparative analysis of the studied promoter region by the ‘ConsInspector 3.0’ program, where the mutated sequence (AF362378) was compared with the sequence existing in the database (Y00081), depicted the presence of the variations in putative binding sites for transcription factors such as glucocorticoid response element (GRE) and nuclear factor kappa-B (NFκ-B), which could lead to differential expression of this gene.

The present study evaluates the potential of arecoline alkaloid on chlorophyllin (CHL) modulated levels of hepatic biotransformation system enzymes in suckling neonate and lactating mice. CHL [50, 100, or 200 mg/kg body weight (b.w.)/day] induced significant increases in the hepatic levels of glutathione S-transferase (GST) and sulfhydryl (-SH) in lactating dams and suckling pups of 14 or 21 days. The depleted level of hepatic Cytochrome (Cyt.) P-450 was observed only in lactating dams given 200 mg/kg b.w. CHL. Arecoline (20 mg/kg b.w.) could depress the CHL-induced levels of hepatic GST and -SH, while Cyt. P-450 and Cyt. b5 levels remained unaltered by arecoline alone or arecoline plus CHL treatment. In lactating dams the modulated levels of hepatic biotransformation system enzymes potentially could affect the detoxication efficacy of administered chemicals besides influencing the rate and extent of passage of metabolites to suckling neonate.