Activation of prolyl hydroxylase-2 for stabilization of mitochondrial stress along with simultaneous downregulation of HIF-1α/FASN in ER + breast cancer subtype.

The present study was undertaken to inquest the chemical activation of prolyl hydroxylase-2 for the curtailment of hypoxia-inducible factor-1α and fatty acid synthase. It was well documented that hypoxia-inducible factor-1α and fatty acid synthase were overexpressed in mammary gland carcinomas. After screening a battery of compounds, BBAP-2 was retrieved as a potential prolyl hydroxylase-2 activator and validates its activity using ER + MCF-7 cell line and n-methyl-n-nitrosourea-induced rat in vivo model, respectively. BBAP-2 was palpable for the morphological characteristics of apoptosis along with changes in the mitochondrial intergrity as visualized by acridine orange/ethidium bromide and JC-1 staining against ER + MCF-7 cells. BBAP-2 also arrest the cell cycle of ER + MCF-7 cells at G2/M phase. Afterward, BBAP-2 has scrutinized against n-methyl-n-nitrosourea-induced mammary gland carcinoma in albino Wistar rats. BBAP-2 restored the morphological architecture when screened through carmine staining, haematoxylin and eosin staining, and scanning electron microscopy. BBAP-2 also delineated the markers of oxidative stress favourably. The immunoblotting and mRNA expression analysis validated that BBAP-2 has a potentialty activate the prolyl hydroxylase-2 with sequential downregulating effect on hypoxia-inducible factor-1α and its downstream checkpoint. BBAP-2 also fostered apoptosis through mitochondrial-mediated death pathway. The present study elaborates the chemical activation of prolyl hydroxylase-2 by which the increased expression of HIF-1α and FASN can be reduced in mammary gland carcinoma.

Recurrent benign ossifying fibroma of the orbit - clinical, radiological profile and management options in a child.

Ossifying fibroma (OF) is a benign fibro-osseous neoplasm which may be mistaken for other similar lesions due to overlapping clinical and radiological features. We report a 5-year-old male child with recurrent benign OF of the orbit. The child had two episodes of recurrence in a span of 18 months. Computed tomography (CT) of orbit showed a large, lobulated expansile fibro-osseous lesion involving the greater wing of sphenoid and orbital roof without intracranial extension. An excisional biopsy was done though an orbital approach. Histopathology showed fibroblast rich stroma with bony trabeculae. Osteoblastic rimming without any mitotic activity was suggestive of juvenile OF. The child developed a recurrence 6 months following the initial excision, and surgical excision was done by a neurosurgeon using a bicoronal approach. The patient had another recurrence after 1 year requiring further surgery. At 2-year follow up there was no recurrence. Juvenile OF is the most aggressive variant that commonly occurs in children, the other benign fibro-osseous lesions being fibrous dysplasias (FDs), osseous dysplasias, and familial gigantiform cementomas.

Implementation of the Treat All Policy Among Persons with HIV Infection Enrolled in Care But Not on Antiretroviral Therapy - India, May 2017-June 2018.

Since September 2015, the World Health Organization has recommended antiretroviral therapy (ART) for all persons with human immunodeficiency virus (HIV) infection, regardless of clinical stage or CD4 count (1). This Treat All policy was based on evidence that ART initiation early in HIV infection as opposed to waiting for the CD4 count to decline to certain levels (e.g., <500 cells/mm3, per previous guidelines), was associated with reduced morbidity, mortality, and HIV transmission (2-4). Further, approximately half of persons enrolled in non-ART care that included monitoring for HIV disease progression (i.e., in pre-ART care) were lost to follow-up before becoming ART-eligible (5). India, the country with the third largest number of persons with HIV infection in the world (2.1 million), adopted the Treat All policy on April 28, 2017. This report describes implementation of Treat All during May 2017-June 2018, by India's National AIDS Control Organization (NACO) and partners, by facilitating ART initiation among persons previously in pre-ART care at 46 ART centers supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR)* in six districts in the states of Maharashtra and Andhra Pradesh. Partners supported these 46 ART centers in identifying and attempting to contact persons who were enrolled in pre-ART care during January 2014-April 2017, and educating those reached about Treat All. ART center-based records were used to monitor implementation indicators, including ART initiation. A total of 9,898 (39.6%) of 25,007 persons previously enrolled in pre-ART care initiated ART; among these 9,898 persons, 6,315 (63.8%) initiated ART after being reached during May 2017-June 2018, including 1,635 (16.5%) who had been lost to follow-up before ART initiation. NACO scaled up efforts nationwide to build ART centers' capacity to implement Treat All. Active tracking and tracing of persons with HIV infection enrolled in care but not on ART, combined with education about the benefits of early HIV treatment, can facilitate ART initiation.

Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats.

The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test. Significant correlation was observed between social behavioral domains (nociception, anxiety and motor coordination) and pro-inflammatory load in the pups when treated with MMR/LPS along with PCM. A significant change in pro and anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 ± 0.000, 15,488 ± 0.000***, 9661.1 ± 157.29***a, 15,312 ± 249.29***, 10,471 ± 0.00***a, 16,789 ± 273.34*** and 12,882 ± 0.00***a). Pups were also scrutinized for the markers of oxidative stress, inflammation and histopathologically. All the treatment groups showed significant alteration in the behavioral changes, oxidative markers (TBARS-in control-4.33 ± 0.02, PCM-9.42 ± 0.18***, MMR-5.27 ± 0.15***, MMR + PCM-8.57 ± 0.18*** a, LPS-6.84 ± 0.10***, LPS + PCM-4.51 ± 0.30***a, DPT-5.68 ± 0.12***, DPT + PCM-7.26 ± 0.18***a) and inflammatory markers without following any specific treatment. These observation could be accorded to variable phenotypes of autistic spectrum disorders (ASDs).

Revisiting the systemic lipopolysaccharide mediated neuroinflammation: Appraising the effect of l-cysteine mediated hydrogen sulphide on it.

The present research was ventured to examine the effect of l-cysteine on neuro-inflammation persuaded by peripheral lipopolysaccharides (LPS, 125 µg/kg, i.p.) administration. No behavioral, biochemical, and inflammatory abnormality was perceived in the brain tissues of experimental animals after LPS administration. l-cysteine precipitated marginal symptoms of toxicity in the brain tissue. Similar pattern of wholesome effect of LPS were perceived when evaluated through the brain tissue fatty acid profile, histopathologically and NF-ĸBP65 protein expression. LPS was unsuccessful to alter the levels of hydrogen sulphide (H2S), cyclooxygenase (COX) and lipoxygenase (LOX) enzyme in brain tissue. LPS afforded significant peripheral toxicity, when figured out through inflammatory markers (COX, LOX), gaseous signaling molecules nitric oxide (NO), H2S, liver toxicity (SGOT, SGPT), and inflammatory transcription factor (NF-ĸBP65) and l-cysteine also provided a momentous protection against the same as well. The study inculcated two major finding, firstly LPS (i.p.) cannot impart inflammatory changes to brain and secondly, l-cysteine can afford peripheral protection against deleterious effect of LPS (i.p.).

Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study.

Cancer-Associated Fibroblasts (CAFs) are crucial in genesis and progression of tumors; however, cervical CAFs (C-CAFs) are not well characterized. Estradiol (E2) has been implicated as a cofactor in human papillomavirus (HPV)-mediated cervical cancer (CxCa), both in animal models and in women using oral contraceptives; however, the exact role of the hormone is unclear. Human C-CAFs have recently been shown to express estrogen receptor alpha (ER-α). We investigated gene expression patterns in ex vivo cultured early and late stage C-CAFs in the context of E2. CAFs were isolated from four patients with early and two patients with late stage CxCa. ER-α expression in CxCa tissues was localized to stromal fibroblast-like cells and confirmed in ex vivo cultured C-CAFs. Two ER antagonists (ICI 182,780 and Methyl Piperidino Pyrazole) were used to unravel ER signaling in CAFs. Microarray technology was used for expression profiling and validated by quantitative reverse transcription PCR. The transcriptomes of C-CAFs across stages indicated their activated state. C-CAFs had gene expression patterns associated with both pro-tumorigenic and pro-inflammatory signaling. Late-stage C-CAFs compared to those of early stage appeared to be more actively metabolizing and cycling but expressed fewer genes related to immune function. We report differential expression profiles between C-CAFs: early vs. late stage and in the presence of ER antagonists. Both ER antagonists seemed to modulate C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression. This study characterized C-CAFs from early and late stage disease, and experiments with ER inhibitors emphasized the probable importance of canonical ER-α signaling. Interfering with paracrine signaling through fibroblast ER-α is worth exploiting as a targeted therapy in CxCa management.

Effect of ß-sitosterol against methyl nitrosourea-induced mammary gland carcinoma in albino rats.

BACKGROUND: The present study was in quested to study the effects of ß-sitosterol on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. METHODS: Animals were randomized and divided into four groups of eight animals each. Group I (sham control 1 % CMC in normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v); Group III (MNU 47 mg/kg, i.v + ß-sitosterol, 10 mg/kg, p.o); Group IV (MNU 47 mg/kg, i.v + ß-sitosterol, 20 mg/kg, p.o). Toxicity was induced by single i.v. injection of MNU followed by ß-sitosterol supplementation therapy for 115 days at the dose mentioned above. RESULTS: Treatment with ß-sitosterol evidenced decrease in the alveolar bud and lobule score in the whole mount of the mammary gland. ß-sitosterol exhibited diminishing effect on oxidative stress through synchronizing lipid and enzymatic antioxidant defense. A significant decrease in the saturated and unsaturated fatty acid was evident with the MNU treatment and ß-sitosterol demonstrated a marked effect on it. Pgp 9.5 expression was dose dependently upregulated by ß-sitosterol treatment in comparison to MNU treatment. On the contrary, downregulated NF-kB expression was perceived, when ß-sitosterol was concomitantly administered with MNU. CONCLUSION: ß-sitosterol afforded significant protection against the deleterious effects of MNU.

α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats.

This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.

Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating the role of hydrogen sulphide through metformin intervention.

OBJECTIVE: The present study was aimed to enumerate the role of metformin-associated H2S release against lipopolysaccharide (LPS) induced neuroinflammation. MATERIALS AND METHODS: Five groups of animals were subjected to treatment as control (normal saline), toxic control (LPS, 125 µg/kg, i.p.), and three separate groups treated with 6.25, 12.5, and 25 mg/kg of metformin along with LPS for a period of 28 days. LPS was administered on 1st, 2nd, 3rd, 4th, 23rd, 24th, 25th and 26th day. The animals were evaluated for behavioral (elevated plus maze, rotarod and actophotometer); biochemical (plasma and tissue H2S, COX, LOX and NO), antioxidant (TBARS, SOD, catalase, protein carbonyl and GSH) and liver toxicity (SGOT and SGPT) markers. The brain tissues were further evaluated histopathologically, free fatty acid profile and NF-κB expression. RESULT: The LPS could not hasten any significant behavioral, biochemical, antioxidant and histopathological changes in the brain tissue. LPS also failed to modify the free fatty acid profile and NF-κB expression in the brain tissue. The LPS demarcated a well-defined peripheral inflammation as perceived through the plasma H2S, NO, SGOT and SGPT. Metformin administration demonstrated a marked effect on the peripheral inflammation induced by LPS. CONCLUSION: The LPS (i.p.) administration is devoid of any neuroinflammatory effects; however, precipitates peripheral inflammatory reactions and the same can could be attributed to the fact that LPS is devoid of/confined by very minimal permeability across the blood brain barrier. Metformin demonstrated a significant effect on peripheral inflammatory reactions precipitated through LPS.

Refractory Gestational Trophoblastic Neoplasia: A Novel Drug Combination With Paclitaxel and Carboplatin Produces Durable Complete Remission.

OBJECTIVE: The aim of this study was to evaluate the results with novel drug combination consisting of paclitaxel and carboplatin (PC) for salvage of refractory high-risk gestational trophoblastic neoplasia (GTN) previously treated with EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine) and EMA-EP (etoposide, methotrexate, actinomycin, and cisplatin) regimens. STUDY DESIGN: This was a prospective study conducted at a regional cancer institute from 2008 to 2012. The study group received the combination of paclitaxel (175 mg/m) and carboplatin (area under the curve, 6) intravenously every 3 weeks. After undetectable ß-subunit of human chorionic gonadotropin values are achieved, 2 courses of additional chemotherapy were administered to reduce the risk of relapse. They were followed up and assessed by clinical examination, monthly ß-subunit of human chorionic gonadotropin for a minimum of 24 months. The event-free survival and overall survival were calculated for all patients using Kaplan-Meier curve (SPSS version 19; SPSS Inc). RESULTS: A total of 65 persistent GTN patients were treated during the study period. Eight (12.3%) of 65 patients having refractory GTN were treated with PC regimen. The initial International Federation of Gynecology and Obstetrics staging in the study group was stage I disease in 1 (12.5%), stage III in 4 (50%), and stage IV in 3 (37.5%) patients. According to the World Health Organization prognostic risk scores, 1 patient was in the low-risk group (12.5%), and 7 patients were in the high-risk group (87.5%). The study group received a total 35 courses of the combination PC. The median number of courses for each patient was 4.4. The complications include mucositis in 3 patients and thrombocytopenia, febrile neutropenia, and transient hepatic dysfunction in other patients. Six (75%) of 8 patients had good response, whereas 2 patients had progression. Five patients (62.5%) are in remission at median 30 months' follow-up, and 3 (37.5%) of 8 patients have died. CONCLUSION: The combination of paclitaxel and carboplatin (PC) regimen produces durable complete remission and manageable side effect profile in patients with refractory GTN previously treated extensively with frontline chemotherapies.

Dual inhibition of arachidonic acid pathway by mulberry leaf extract.

The present work investigates the anti-inflammatory, analgesic and antipyretic activity of methanolic extract of mulberry leaves of variety S-1, S-13 and S-146. The S-146 extract was further evaluated for its efficacy against adjuvant arthritis in albino rats followed by inhibitory potential for COX 1, COX 2 and 5 LOX. The HPLC analysis enumerated the presence of morin, reversterol, scopoletin and 7-hydroxy coumarin as the major constituents. The anti-inflammatory, antipyretic and analgesic activity observed in the present experiment could be accredited to the dual inhibition in the AA pathway. The inhibition of COX and LOX enzymes could be imparted to the presence of resveraterol, morin, scopoletin and 7-hydroxy coumarin.

Primary carcinoma of the fallopian tube: a review of a single institution experience of 8 cases.

AIMS AND OBJECTIVES: To evaluate the clinicopathologic features, response to cytoreductive surgery and adjuvant platinum-based chemotherapy with or without paclitaxel. MATERIALS AND METHODS: A retrospective observational study of 8 women with a histopathologic diagnosis of primary fallopian tube carcinoma (PFTC) from January 2000 to February 2013. RESULTS: 4/8 (50%) of the women were in the early stage and an intraoperative frozen section was 100% effective in identifying fallopian tube carcinoma and then a staging laparotomy was performed. All 4/8 cases in the early stage had received and responded to single agent carboplatin and all are alive without clinical, radiological, or biochemical evidence of recurrence at the end of 2 years and the longest survivor has completed 13 years. Primary optimal cytoreductive surgery was achievable in 3/4 (75%) in advanced disease. All showed response to adjuvant paclitaxel and carboplatin (T+C), but all had succumbed to the disease following recurrence with mean progression-free survival of 19 months (range 15-21 months) and mean overall survival of 27 months (range 22-36 months). CONCLUSION: The pivotal role played by a frozen section in diagnosing PFTC which is rare needs to be reemphasized, therefore justifying a primary staging laparotomy in an early stage. Prolonged survival observed in this group following an optimum tailored adjuvant single agent carboplatin is worth noting.

Treatment of high-risk gestational trophoblastic neoplasia with weekly high-dose methotrexate-etoposide.

OBJECTIVE: To assess toxicity and efficacy of weekly high-dose methotrexate-etoposide (HD MTX-ETO) in high-risk gestational trophoblastic neoplasia (GTN). METHODS: Retrospective chart review of high-risk GTN patients treated with HD MTX-ETO (methotrexate 1000 mg/m² day 1, etoposide 100 mg/m² days 1 and 2, q 1 wk). RESULTS: 134 cycles of HD MTX-ETO were administered to twelve patients; median number of cycles was 8 (range 2-39 cycles). Median follow up was 25.5 months (range 11-69). 7 of these patients switched due to ototoxicity from EP-EMA (etoposide 150 mg/m², cisplatin 75 mg/m² i.v. day 1; etoposide 100 mg/m², methotrexate 300 mg/m², dactinomycin 0.5 mg i.v. day 8, q 14 d) to HD MTX-ETO, after an average of 7 cycles of EP-EMA. Six achieved complete remission without disease recurrence. One patient with a placental site trophoblastic tumour died due to progressive disease. Five patients received HD MTX-ETO primarily; 1 patient with choriocarcinoma presenting with metastases to the brain and liver (WHO score 19) was switched to EP-EMA and died due to complications under EP-EMA. The other 4 achieved complete remission without disease recurrence. HD MTX-ETO was well tolerated; non-haematological toxicity was low except for alopecia and fatigue. Nine patients had grade 2-4 anaemia and received packed cells. Eight patients had grade 3-4 neutropenia and received G-CSF. Two patients developed febrile neutropenia without sepsis. CONCLUSIONS: These preliminary results show a better toxicity profile with HD MTX-ETO than EP-EMA and encouraging efficacy. HD MTX-ETO might be a treatment option for some patients with high-risk GTN and needs further investigation.

EP-EMA regimen (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia.

OBJECTIVE: Evaluation of toxicity and outcome of high-risk gestational trophoblastic neoplasia when treated with EP-EMA (etoposide, 150 mg/m; cisplatin, 75 mg/m, intravenous, day 1; etoposide, 100 mg/m; methotrexate, 300 mg/m; dactinomycin, 0.5 mg, intravenous, day 8, every two weeks). MATERIALS AND METHODS: We conducted a retrospective chart review of the period 2004-2010. The first-line chemotherapy regimen for high-risk gestational tropholdastic neoplasia was EP-EMA. RESULTS: Eighteen patients were treated with EP-EMA, either as first-line chemotherapy for high-risk gestational trophoblastic neoplasia (n = 6), placental site trophoblastic tumor (n = 1), or as salvage chemotherapy for gestational trophoblastic neoplasia after single-agent methotrexate (methotrexate, 1 mg/kg, on days 1, 3, 5, and 7 every two weeks) (n = 10) or high-dose methotrexate-etoposide: methotrexate, 1000 mg/m, on day 1; etoposide, 100 mg/m, on days 1 to 2, every week) (n = 1). Median number of cycles of EP-EMA was 8 (range, 3-11). Median follow-up was 19 months (range, 7-77 months). Concerning response rate, 16 patients (89%) achieved complete remission without disease recurrence.Two patients (11%) died: One patient with placental site trophoblastic tumor died of progressive disease; the second patient presented with choriocarcinoma, primarily metastasized to liver, lung, skin, kidney, and brain. She died of sepsis and endocarditis after adding intrathecal methotrexate and switching cisplatin to carboplatin in the EP-EMA regimen. Toxicity was significant. Eight treatment changes were made owing to grade 2 to grade 3 ototoxicity: 7 to high-dose methotrexate-etoposide, 1 change of cisplatin to carboplatin. Fifteen patients (83%) experienced grade 3/4 neutropenia.

Impact of Optimal Therapy and Prognostic Factors in Malignant Germ Cell Tumors of Ovary: 20 Years' Institutional Experience.

The objective of this study is to analyze the impact of clinicopathological and treatment-related factors on survival in patients with malignant ovarian germ cell tumor. A total of 253 patients of ovarian germ cell malignancy were retrospectively reviewed during 2000-2019. Out of these, 111 had primary treatment at our institute, which is a dedicated regional cancer center. The remaining 142 were operated elsewhere and were referred to us for adjuvant chemotherapy or with recurrent disease. The clinicopathological and treatment-related characteristics were analyzed for association with tumor persistence/recurrence or death. Among them, 107 were dysgerminomas; 60 had endodermal sinus tumor, 53 mixed germ cell tumors, and 31 immature teratoma; and one each had embryoma and primitive germ cell tumor. The median follow-up period was 19 months (range 0-214). Median time to recurrence or progression was 5 months. Forty-nine patients (19.4%) had a recurrence and there were 16 (6.3%) deaths. Five-year disease-free-survival was 71.3% and 5-year overall survival rate was 88.1%, for the entire cohort. Disease-free-survival was 90.4% and overall survival was 92.1% for patients entirely treated at the reporting institute. Sub-group analysis based on treatment adequacy showed that survival rate was 91.0% in patients who had timely and complete initial treatment versus 78.3% in patients where treatment was incomplete or delayed (p = 0.032). Factors affecting relapse were tumor histology, absence of surgical staging, presence of residual disease, inadequate response to chemotherapy, treatment outside reporting institute, and incomplete/delayed chemotherapy. Significant factors adversely affecting survival were presence of post-operative residual disease, tumor histology, incomplete response to chemotherapy, and inadequate/delayed treatment at primary setting. There was no statistically significant difference based on disease stage and whether fertility-sparing surgery or non-fertility-sparing surgery was performed. Prognosis of ovarian germ cell malignancies is excellent with timely, optimal treatment. The outcome improves significantly if managed adequately in the primary setting, involving dedicated gynecologic oncologists.

Plasma protein oxidation in patients with brain tumors.

OBJECTIVE: Proteins can undergo numerous covalent changes on exposure to oxidants. Oxidative modification of protein in vivo may affect a variety of cellular functions. Protein oxidation in vivo is a natural consequence of aerobic life. Oxygen radicals and other activated oxygen species generated as byproducts of cellular metabolism or from environmental sources cause modifications to the amino acids of proteins that generally result in loss of protein function/enzymatic activity. It is now well known that reactive oxygen species (ROS) play a key role in human cancer development. Moreover, the brain is especially vulnerable to ROS mediated injury. METHOD: Therefore, in the present study, protein oxidation was assessed in the plasma of 17 patients with brain tumors and 16 age and gender-matched controls by measuring protein thiols and protein carbonyls spectrophotometrically. RESULTS: There was a significant decrease in protein thiols and carbonyls in malignant cases of brain tumors when compared with the control group. No significant change in protein thiols was noted in benign cases compared to controls. A comparison of levels in benign and malignant cases for both the parameters also showed no significant difference. DISCUSSION: Thus, free radical toxicity does lead to protein oxidation in patients with brain tumors.

PHD-2 activation: a novel strategy to control HIF-1α and mitochondrial stress to modulate mammary gland pathophysiology in ER+ subtype.

Estrogen receptor-positive mammary gland carcinoma and its involvement in regulation of overexpressed hypoxia-inducible factor-1α and fatty acid synthase level in hypoxia influenced cancer cells are the present molecular crosstalk of this entire study. To test the hypothesis, we have proceed our study through chemical activation of prolyl hydroxylase 2 which leads to inhibition of hypoxia-inducible factor-1α and fatty acid synthase in ER+MCF-7 cancer cell line and n-methyl-n-nitrosourea induced mammary gland carcinoma rat model. ER+MCF-7 cells were evident with array of nuclear changes when stained through acridine orange/ethidium bromide. Afterward, JC-1 staining of the cells was evident in mitochondrial depolarization. The cells were arrested in G2/M phase when analyzed with flow cytometry. The morphological analysis of rat mammary gland tissue revealed decrease in alveolar buds, restoration of histopathological features along with intra-arterial cushion. The western blotting and fold change expressions of the genes validating the anticancer efficacy of BBAPH-1 is mediated through mitochondria-mediated apoptosis pathway. BBAPH-1 also modulates the expression of prolyl hydroxylase-2 with significant curtailment of hypoxia-inducible factor-1α, fatty acid synthase expression, and their respective downstream markers. These finding suggest that the BBAP-1-mediated activation of prolyl hydroxylase-2 significantly decreased the level of hypoxia-inducible factor-1α and fatty acid synthase. BBAPH-1 also activates the mitochondria-mediated death apoptosis pathway.

Susceptibility of peripheral lymphocytes of brain tumour patients to in vitro radiation-induced DNA damage, a preliminary study.

OBJECTIVE: The present investigation aimed to study the susceptibility of lymphocytes collected from brain tumour patients to radiation-induced DNA damage under in vitro conditions. METHODS: The peripheral lymphocytes collected from brain tumour patients were exposed to 2-Gy gamma radiation. Susceptibility of lymphocytes to radiation-induced DNA damage and their repair ability was assessed by alkaline comet assay. RESULTS: Lymphocytes of patients with benign and malignant tumour had a significantly higher (p < 0.001) baseline DNA damage compared to lymphocytes from normal subjects. A significant increase (p < 0.001) in DNA damage was observed immediately after irradiation of lymphocytes from healthy subjects and brain tumour patients. However, at 1 h after irradiation the level of DNA damage dropped significantly (p < 0.001) compared to that of immediately after irradiation of respective groups. DISCUSSION: In conclusion, the lymphocytes of brain tumour patients possess a higher level of basal DNA damage and exhibit a higher susceptibility to a clastogenic agent like radiation.

Ciprofloxacin-induced generalised non-bullous fixed drug eruption.

Ciprofloxacin, a very common antibiotic used in our day-to-day practice can cause adverse cutaneous reactions in 1-2% of patients. Photosensitivity, urticaria and maculopapular rash are the usual skin reactions. Fixed drug eruption (FDE) is an uncommon side effect of ciprofloxacin. Ciprofloxacin-induced generalised bullous FDEs have been very rarely reported in the literature. We report one such case of a young man who developed generalised non-bullous FDEs after treatment with ciprofloxacin.