Duvuru Prathiba

Comparative evaluation of antiproliferative, antiangiogenic and apoptosis inducing potential of black tea polyphenols in the hamster buccal pouch carcinogenesis model.

Background To evaluate the relative chemopreventive efficacy of two black tea polyphenols, Polyphenon-B [P-B] and BTF-35 on 7,12-dimethylbenz [a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Methods Hamsters were divided into 6 groups. The right buccal pouches of animals in groups 1–3 were painted with 0.5% of DMBA three times a week for 14 weeks. While hamsters in group 1 received no further treatment, animals in groups 2 and 3 received diet containing 0.05% P-B and BTF-35 respectively, four weeks before DMBA painting that was continued until the end of the experiments. Animals in groups 4 and 5 were given P-B and BTF-35 alone respectively as in groups 2 and 3. Group 6 animals served as the untreated control. All the animals were sacrificed after 18 weeks. The expression of p21, cyclin D1, glutathione S-transferase pi (GST-P), nuclear factor kappa B (NF-κB), Bcl-2, Bax, cytochrome C, caspase-3, caspase-9, poly(ADP-ribose) polymerase (PARP), cytokeratins and vascular endothelial growth factor (VEGF) was analysed by RT-PCR, immunohistochemical and Western blot analyses. Results DMBA treated animals developed buccal pouch carcinomas that displayed increased expression of p21, cyclin D1, GST-P, NF-κB, cytokeratins, VEGF and Bcl-2 with decreased expression of Bax, cytochrome C, caspase-3, caspase-9, and PARP. Dietary administration of both P-B and BTF-35 reduced the incidence of DMBA-induced HBP carcinomas by modulating markers of cell proliferation, cell survival, tumour infiltration, angiogenesis, and apoptosis. Conclusion The results of the present study provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. The greater efficacy of BTF-35 in inhibiting HBP carcinogenesis and modulating multiple molecular targets may have a potential role in the prevention of oral cancer.

Modulatory effects of black tea polyphenols on oxidant–antioxidant profile and expression of proliferation, apoptosis, and angiogenesis-associated proteins in the rat forestomach carcinogenesis model

BackgroundChemoprevention by dietary constituents has emerged as a novel approach to control stomach cancer incidence. We therefore evaluated the chemopreventive effects of black tea polyphenols (Polyphenon-B) on oxidant–antioxidant status, cell proliferation, apoptosis, and angiogenesis during N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis.MethodsMale Wistar rats were divided into four groups. Rats in group 1 and 2 were given MNNG (150 mg/kg body weight) by intragastric intubation three times at 2 week intervals and followed for 26 weeks. Rats in group 2 received in addition a basal diet containing 0.05% Polyphenon-B. Group 3 animals were given 0.05% Polyphenon-B alone. Group 4 animals served as controls. The status of lipid peroxidation and antioxidants and the expression of the lipid peroxidation marker 4-hydroxy nonenal (4-HNE), proliferating cell nuclear antigen (PCNA), glutathiones-transferase (GST)-π, Bcl-2, Bax, cytochrome C, caspase 3, cytokeratins, and vascular endothelial growth factor (VEGF) were used as biomarkers.ResultsIntragastric administration of MNNG induced well-differentiated squamous cell carcinomas that showed diminished lipid and protein oxidation and an increase in antioxidant status. This was associated with increased cell proliferation, angiogenesis, and invasive potential coupled with apoptosis evasion as revealed by upregulation of PCNA, GST-π, Bcl-2, cytokeratins, and VEGF and downregulation of Bax, cytochrome C, and caspase 3 protein expression. Dietary administration of Polyphenon-B effectively suppressed MNNG-induced gastric carcinogenesis, as evidenced by modulation of oxidant–antioxidant status, inhibition of cell proliferation and infiltration, and angiogenesis associated with apoptosis induction.ConclusionsThe present study provides evidence that Polyphenon-B exerts multifunctional inhibitory effects on MNNG-induced gastric carcinogenesis and suggests that it can be developed as a potential chemopreventive agent.

Dietary chlorophyllin inhibits the canonical NF-κB signaling pathway and induces intrinsic apoptosis in a hamster model of oral oncogenesis.

Chlorophyllin, a water-soluble, semi-synthetic derivative of the ubiquitous green pigment chlorophyll is shown to exert potent anticarcinogenic effects. In the present study, we investigated the chemopreventive effects of chlorophyllin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis by analyzing the expression of NF-κB family members and markers of intrinsic apoptosis. Dietary administration of chlorophyllin (4 mg/kg bw) suppressed the development of HBP carcinomas by inhibiting the canonical NF-κB signaling pathway by downregulating IKKβ, preventing the phosphorylation of IκB-α, and reducing the expression of nuclear NF-κB. Inactivation of NF-κB signaling by chlorophyllin was associated with the induction of intrinsic apoptosis as evidenced by modulation of Bcl-2 family proteins, enforced nuclear localization of survivin, upregulation of apoptogenic molecules, activation of caspases, and cleavage of PARP. The results of the present study demonstrate that chlorophyllin inhibits the development of DMBA-induced HBP carcinogenesis by targeting NF-κB and the intrinsic apoptotic pathway. Thus, dietary agents such as chlorophyllin that simultaneously target divergent pathways of cell survival and cell death are novel candidates for cancer chemoprevention.

Coronary atherosclerosis in sudden cardiac death: an autopsy study.

BACKGROUND The incidence of ischemic heart disease (IHD) has markedly increased in India over the past few years. Considering the variations in racial, dietary and lifestyle patterns in our population, it is essential to study the biology of coronary atherosclerosis in our patients. Vulnerable plaques have a large number of foam cells, extracellular lipid, thin fibrous caps and clusters of inflammatory cells and are more prone to rupture. These plaques are nourished by the microvessels arising from the vasa vasorum of the blood vessels and by lumen-derived microvessels through the fibrous cap. This autopsy study was designed to analyse the coronary arterial tree in cases of sudden cardiac death, classify coronary atherosclerotic plaques and to assess the factors contributing to vulnerability of the plaques including inflammation, calcification and microvascular density. MATERIALS AND METHODS Seven cases of sudden cardiac death were included in the study. The hearts were perfusion-fixed and the coronary arteries along with their main branches were dissected and studied. The location of the plaques, type of plaques, presence of inflammation and calcification were assessed. The cap thickness and microvessel density per 1000 um 2 were assessed. The statistical significance was estimated. RESULTS AND CONCLUSIONS Extensive high-grade coronary atherosclerotic disease was seen in all sudden cardiac death cases. Majority of the plaques were vulnerable. High-grade inflammation was seen in most of the vulnerable and ruptured plaques. All the ruptured plaques were uncalcified indicating that calcification probably stabilizes the plaques and protects against rupture. Increased microvessel density was noted in ruptured plaques compared to vulnerable plaques. However, it was not statistically significant.

Malignant proliferating trichilemmal tumour presenting early in life: An uncommon feature

Malignant proliferating trichilemmal tumour is a rare cutaneous malignant neoplasm usually occurring in elderly women. We present a case of malignant trichilemmal tumour in a young lady of 26 years of age with a previous history of proliferating trichilemmal tumour at the same site.

Papillary lesions of breast - An introspect of cytomorphological features

Background: True papillary lesions of the breast have a significantly high error rate on fine needle aspiration cytology (FNAC), as many other nonpapillary breast lesions exhibit overlapping features on cytosmears. Aim: To evaluate the utility of individual morphological features in offering a more precise cytodiagnosis in papillary lesions of the breast. Materials and Methods: Cytology smears reported as papillary lesions on nipple discharge / FNAC and histopathology over a period of two years were studied and correlated. A subjective assessment of morphological features, namely, the cellular yield, presence of three-dimensional papillary clusters, stromal bare nuclei, presence of cyst macrophages and cellular atypia was carried out on cytosmears. Results: Fourteen cases of papillary lesions were identified. Thirty-six per cent of the cases were found to be true positive, 43% false negative and 21% false positive with a sensitivity of 42% for papillary lesions. Eight of nine papillary lesions showed cyst macrophages. Stromal bare nuclei were seen in three of four malignant papillary lesions. However, the number of stromal bare nuclei was less compared to benign lesions. None of the malignant nonpapillary lesions showed stromal bare nuclei. Conclusions: Cytomorphological features alone are inadequate for the precise diagnosis of papillary lesions of the breast.

Granular cell tumor in inguinal region: A case of mistaken identity on cytology.

A 63-year-old male presented with sudden increase in size of a right inguinal swelling which was present for the past 10 years. Clinical diagnosis of inguinal soft tissue mass/lymph node enlargement was made and patient was investigated further for a conclusive diagnosis. Ultrasound examination suggested it to be a lymph node and guided fine needle aspiration cytology was performed. Cytology was suggestive of a reactive lymph node. Subsequently, an excision biopsy was performed that revealed a granular cell tumor with many lymphoid aggregates. On reviewing the cytosmears, we realised that the granular neoplastic cells were mistaken for histiocytes; and the lymphoid background and bare nuclei mislead us to consider it a reactive lymph node. Since granular cell tumor can occur almost anywhere, a careful examination of cytosmears and knowledge of its distinctive cyto-morphological features would be helpful in providing an accurate diagnosis on cytology.

Solid variant of papillary carcinoma of nipple: An under recognized entity

Papillary lesions of the breast represent a heterogeneous group with differing biological behavior. Solid papillary carcinomas are uncommon tumors composed of circumscribed large cellular nodules separated by bands of fibrosis. Correct diagnosis is crucial but may be difficult, as many other benign and malignant lesions have similar histological appearances. Immunohistochemistry plays a useful role in their differentiation. We describe one such case of a solid variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had no other palpable mass in rest of the breast tissue. The case is documented for the rarity of its occurrence and significance of recognition of this lesion.

Cytologic features of pulmonary blastoma.

Pulmonary blastomas are rare lung neoplasms constituting 0.5% of all lung tumors. This tumor has an aggressive course and needs to be recognized on cytology. A preoperative diagnosis of pulmonary blastoma is difficult to obtain by cytopathologic methods. A diagnosis of biphasic pulmonary blastoma should be considered when there is a dimorphic population of cells on cytology. A 30-year-old male presented with gradually progressing breathlessness and left-sided chest pain for the past one month. Chest radiograph and computed tomography of thorax revealed an anterior mediastinal mass that was subjected to ultrasound-guided fine-needle aspiration cytology. Aspiration cytology showed a highly cellular lesion with a dimorphic population of tumor cells in a necrotic background. The possibility of a non-small cell carcinoma was suggested. Subsequent histopathology revealed the tumor to be a pulmonary blastoma. The importance of recognizing the dimorphic population of cells in cytology is discussed.

An Uncommon Sighting—Lupus Vulgaris of the Foot

Lupus vulgaris (LV)is a progressive form of cutaneous tuberculosis (TB)that may occur in a patient with a moderate or high degree of immunity. The incidence of LV has declined with that in TB; it is relatively uncommon even in developing countries. LV commonly presents in the head and neck regions as flat plaques. Variants of LV form huge, soft, tumor-like forms with deep tissue and cartilage destruction resulting in deformities. The authors report a case of LV in a patient who presented with an ulcero-proliferative growth in the lower extremity, mimicking a malignancy.