Polymorphism at codon 72 of p53, human papillomavirus, and cervical cancer in South India.

Purpose: It has been suggested that host genetic factors play a role in human papillomavirus (HPV)-associated tumorigenesis, although the issue continues to be a focus of much debate. Previous studies have reported that a common polymorphism of the wild type p53 gene at codon 72 of exon 4 (Arg/Arg) is associated with a sevenfold increased risk of HPV-associated cancer compared to Arg/Pro and Pro/Pro polymorphisms. In vitro studies also suggested that the Arg/Arg polymorphism was much more susceptible to HPV 16 E6-mediated degradation as compared to other allelic forms.

Evaluation of 90Y-DTPA and 90Y-DOTA for potential application in intra-vascular radionuclide therapy.

90Y-1,4,7,10-tetraazacyclododecane tetraacetic acid (90Y-DOTA) and 90Y-diethylene triamine pentaacetic acid (90Y-DTPA) complexes were studied for possible use in intra-vascular radionuclide therapy (IVRNT). 90Y was obtained from a 90Sr-90Y generator based on supported liquid membrane technique. The 90Y-DOTA and 90Y-DTPA complexes were prepared under optimised conditions.

Feasibility study for production of 175Yb: a promising therapeutic radionuclide.

Owing to its favourable decay characteristics 175Yb (T1/2 = 4.2 d, E beta(max) = 480 keV) can be regarded as a potential radionuclide for therapeutic applications. Production of 175Yb using (174Yb(n, gamma)175Yb) reaction by thermal neutron bombardment on natural ytterbium target is described.

177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation.

177Lu (T 1/2 = 6.71 d, Ebeta(max) = 497 keV) has radionuclidic properties suitable for use in palliative therapy of bone pain due to metastasis. 177Lu was produced in high-specific activity (3-4TBq/g) and excellent radionuclidic purity (100%) by thermal neutron bombardment of natural Lu target.

Apoptosis in epithelial ovarian tumors.

It is now recognized that apoptosis plays an important role in the pathogenesis of tumors. This study evaluated the extent of apoptosis in different grades of ovarian tumors and correlated it with the expression of apoptosis regulatory genes, p53 and bcl-2 and with the total proliferative compartment of the tumor defined by the expression of the proliferating cell nuclear antigen (PCNA). Apoptosis was evaluated by the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay.

Preparation and evaluation of 90 Y skin patches for therapy of superficial tumours in mice.

90Y, a beta emitting radionuclide, was immobilized in a bandage patch for possible application for the therapy of superficial maladies such as tumours and skin cancers. The aim was to prepare a radiation source that could deliver uniform dose within a short duration and avoid the inconveniences faced with the gamma sources used in teletherapy and brachytherapy. 90Y-ferric hydroxide macroaggregates were prepared, filtered and immobilized between two layers of gauze.

Cellular manifestations of human papillomavirus infection in laryngeal tissues.

Background And Objectives: Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53.

Methods: Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA.

Preparation and bioevaluation of 166Ho labelled hydroxyapatite (HA) particles for radiosynovectomy.

The preparation of 166Ho labeled hydroxy apatite (HA) particles for radiosynovectomy applications is described in this paper. 166Ho was prepared by the irradiation of Ho2O3 at a flux of 1.8 x 10(13) neutrons/cm2/s for about 7 days.

177Lu labelled polyaminophosphonates as potential agents for bone pain palliation.

Polyphosphonate ligands labelled with radioisotopes decaying by moderate energy beta emission have shown utility as palliative agents for painful bone metastasis. 177Lu (T(1/2)=6.71 d, Ebetamax=497 keV) has radionuclidic properties suitable for use in palliative therapy of bone metastasis.

Evolution of Tc-99m in diagnostic radiopharmaceuticals.

The progress in diagnostic nuclear medicine over the years since the discovery of 99mTc is indeed phenomenal. Over 80% of the radiopharmaceuticals currently being used make use of this short-lived, metastable radionuclide, which has reigned as the workhorse of diagnostic nuclear medicine. The preeminence of 99mTc is attributable to its optimal nuclear properties of a short half-life and a gamma photon emission of 140 keV, which is suitable for high-efficiency detection and which results in low radiation exposure to the patient.

A novel [186/188Re]-labelled porphyrin for targeted radiotherapy.

The concept of labelling a porphyrin, a tumour-avid agent, with a radionuclide to evaluate its potential as a therapeutic modality is reported. A novel water-soluble porphyrin, namely meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin, with suitable dicarboxylic acid groups as aromatic substituents in the periphery, was synthesized and characterized. The labelling of this porphyrin with 186/188Re, a beta(-) emitter, was optimized by varying the reaction conditions.

Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer.

Oral cancer ranks first among all cancers in males and is the third most common among females in India. Tobacco-derived carcinogens are involved in the development of oral cancer. Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens.

Preparation and studies with 90Y-labelled particles for use in radiation synovectomy.

90Y-FHMA (Ferric hydroxide macroaggregates) and 90Y-HA (hydroxyapatite) were prepared in >95% yield using 90Y from an in-house 90Sr-90Y generator. Most of the particles ranged from 5 to 20 microm in diameter and retained radiochemical purity > 95% in human serum for at least 7 days at 37 degrees C. Gamma camera imaging of normal rabbits after intraarticulation of the particles showed complete retention of activity within the knee cavity with no measurable radioactivity leaching out of the joints over a 96 hour period.

186Re-1,4,8,11-tetraaza cyclotetradecyl-1,4,8,11-tetramethylene phosphonic acid: a novel agent for possible use in metastatic bone-pain palliation.

In connection with our work on the development of 186Re-tetra-phosphonates with optimum properties for use in bone pain palliation, a novel cyclic tetraphosphonate derivative, has been synthesized, complexed with 186Re and evaluated with promising results. The ligand, which consists of a cyclic array of tetra-aminomethylphosphonate groups, was synthesized using orthophosphorus acid, 1,4,8,11-tetraazacyclotetradecane and formaldehyde. The labeling conditions with 186Re have been standardized under varying reaction conditions to give maximum yield.

Potential (166)Ho radiopharmaceuticals for intravascular radiation therapy (IVRT)-I: [(166)Ho] holmium labeled ethylene dicysteine.

The use of beta(-) emitting radionuclides in the control of restenosis in post angioplasty patients is currently under intense investigation at many leading cardiovascular research centers. (32)P coated metallic stents, (192)Ir wire source and balloons filled with an appropriate radionuclide solution such as of (188)Re, attached to catheter are being studied. (166)Ho has comparable radionuclidic properties to that of (188)Re, can be more easily produced and hence is an attractive alternative to (188)Re.

Tc-99m and Re-186 complexes of tetraphosphonate ligands and their biodistribution pattern in animal models.

The syntheses of four alpha-aminomethyl phosphonates and their complexation studies with (99m)Tc and (186/188)Re are reported. Complexation conditions were standardized to give maximum yields, which ranged from 90-97%. The yields of complexation were estimated by paper chromatography.

Apoptosis, angiogenesis and proliferation: trifunctional measure of tumour response to radiotherapy for oral cancer.

Local recurrence is a significant problem following radiotherapy in oral carcinoma and hence there is a paramount need for predictive markers. This study therefore analysed the predictive value of pre-treatment status of angiogenesis, apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation in relation to tumour response to radiotherapy. Sixty-nine histologically defined invasive carcinoma lesions were included in the study.

Telomerase, p53 and human papillomavirus infection in the uterine cervix.

Human papillomavirus infection is postulated to be a major risk factor for cervical cancer, while more recent data have stressed the clinical significance of telomerase expression during tumorigenesis. This study therefore looked for any relationship between telomerase expression, presence of human papillomavirus (HPV) and expression of the high-risk HPV E6 protein at various phases of tumor progression in the uterine cervix. In addition, accumulation of the p53 protein and total tissue proliferative fraction were also studied.

188Re-ethylene dicysteine: a novel agent for possible use in endovascular radiation therapy.

Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously.

Development of a condemned mucosa syndrome and pathogenesis of human papillomavirus-associated upper aerodigestive tract and uterine cervical tumors.

High-risk human papillomaviruses (HPVs) have been shown to be involved in the pathogenesis of many squamous carcinomas, particularly those of the uterine cervix. A number of random studies have also reported association of high-risk HPV subtypes with cancers of the oral cavity, larynx, hypopharynx, and esophagus. The roles of other molecular factors involved during HPV infection in these tumors still remain unclear.

Transforming Growth Factor Beta Related to Extent of Tumor Angiogenesis but Not Apoptosis or Proliferation in Breast Carcinoma.

BACKGROUND: Recent investigations have demonstrated the clinical significance of intralesional mean vessel density (ILVD), as a marker of tumor angiogenesis.The role of growth factors in mediating angiogenesis has also been well documented. Transforming growth factor beta (TGFbeta) belongs to a family of polypeptideswith diverse biological functions.

Apoptosis: future directions in cancer therapy.

Cancer as a multifactorial disease results in gain of immortality due to defective apoptosis. The primary mode of cell death by apoptosis induced by various modes of treatment often fail in vivo. The in vitro environment is less complex while the in vivo environment is influenced by various external regulatory signals besides the existence of multiple, parallel and independent apoptotic pathways.

[(186/188)Re] rhenium-ethylene dicysteine (Re-Ec): preparation and evaluation for possible use in endovascular brachytherapy.

188ReO(4)(-), (188)Re-MAG(3), and (188)Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Because (99m)Tc-labeled ethylene dicysteine (EC) is a well-established agent for renal tubular function imaging, the use of [(188)Re] rhenium-labeled EC as a potential agent for prevention of restenosis after angioplasty is worth evaluation. In this article, the preparation and pharmacological behavior of [(188/186)Re]Re complex of EC are reported.

In situ apoptosis in the thyroid.

Recent evidence has emphasized the importance of programmed cell death, or apoptosis, in the maintenance of tissue homeostasis and pathogenesis of tumors. This study analyzed the significance of apoptosis in relation to the expression of p53 and bcl-2 proteins, tissue proliferation defined by Ki-67 expression, and tissue histology in thyroid tissue. Extent of apoptosis was defined by morphological criteria and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate (dUTP) biotin nick end labeling (TUNEL) assay.

Syntheses and radiolabeling of cysteine-oximes and pharmacological behaviour of their 99mTc complexes.

Synthesis of two novel ligands using 2-oximino-butan-3-one and L-ethyl cysteinate is described. The synthetic procedure involved the formation of Schiffs base by the condensation of the amino group of L-ethyl cysteinate with the carbonyl group of 2-oximino-butan-3-one to provide the ligand I, N'(butan-2-enyl-3-oximino)ethyl cysteinate, followed by reduction of the Schiffs base with sodium borohydride to ligand II, N'(3-oximinobutyl)ethyl cysteinate. The ligands were characterised by NMR spectroscopy.