Methanol extraction revealed anticancer compounds Quinic Acid, 2(5H)­Furanone and Phytol in Andrographis paniculata.

Andrographis paniculata (Ap) has been a part of traditional medicine for its anti-inflammatory effects, treatment of snake bites and liver abnormalities. Several investigations have revealed its bioactive components to be andrographolides. The methanolic extracts of leaves from Ap were characterized, the non-andrographolides were identified and screened for anti-proliferative activity. The extracts showed significant toxicity against numerous cancer cells including HeLa, MCF7, BT549, 293 and A549 cells. Anti-proliferative activity and effect on cancer cell invasion (metastatic potential) and cell migration were examined. The extracts revealed significant inhibition of the ability of HeLa cells in repairing the gap created by a vertical wound made on a confluent cell monolayer. Similarly, a 40% reduction in cell migration was observed in presence of the extracts. Significant anti-angiogenic activity in terms of reduced blood capillary formation was observed on the Chorioallantoic membranes of embryonated hen eggs co-inoculated with HeLa cells and the extracts. Analysis of HeLa cells treated with the extracts using flow cytometry indicated the arrest of cell cycle progression at the G2/M phase. Variation in the Bax/Bcl-2 ratio and elevated caspase-3 levels by immunoblotting confirmed cell death induction via the apoptotic pathway. Investigation of the extracts by gas chromatography-mass spectrometry displayed the predominant components to be 2(5H)-Furanone (14.73%), Quinic acid (17.32%), and Phytol (11.43%). These components have been previously known to have anticancer activity, while being studied individually in other plants. This is the first study, to the best of our knowledge, on the anti-proliferative and anti-angiogenic activity of the non-andrographolide components from Ap.

The Histopathology of Oral Cancer Pain in a Mouse Model and a Human Cohort.

Oral cancer patients often have severe, chronic, and mechanically induced pain at the site of the primary cancer. Oral cancer pain is initiated and maintained in the cancer microenvironment and attributed to release of mediators that sensitize primary sensory nerves. This study was designed to investigate the histopathology associated with painful oral cancers in a preclinical model. The relationship of pain scores with pathologic variables was also investigated in a cohort of 72 oral cancer patients. Wild-type mice were exposed to the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Nociceptive (pain) behavior was measured with the dolognawmeter, an operant device and assay for measuring functional and mechanical allodynia. Lesions developed on the tongues and esophagi of the 4NQO-treated animals and included hyperkeratoses, papillomas, dysplasias, and cancers. Papillomas included lesions with benign and dysplastic pathological features. Two histologic subtypes of squamous cell carcinomas (SCCs) were identified-SCCs with exophytic and invasive components associated with papillary lesions (pSCCs) and invasive SCCs without exophytic histology (iSCCs). Only the pSCC subtype of tongue cancer was associated with nociceptive behavior. Increased tumor size was associated with greater nociceptive behavior in the mouse model and more pain experienced by oral cancer patients. In addition, depth of invasion was associated with patient-reported pain. The pSCC histology identifies 4NQO-induced tongue cancers that are expected to be enriched for expression and release of nociceptive mediators.

The silver lining: towards the responsible and limited usage of silver.

Silver has attracted a lot of attention as a powerful, broad spectrum and natural antimicrobial agent since the ancient times because of its nontoxic nature to the human body at low concentrations. It has been used in treatment of various infections and ulcers, storage of water and prevention of bacterial growth on the surfaces and within materials. However, there are numerous medical and health benefits of colloidal or nanosilver apart from its microbicidal ability which as yet has not been fully embraced by the medical community. These include antiplatelet activity, antioxidant effect, anticancer activity, wound healing and bone regeneration, enhancement of immunity, and increase in antibiotic efficiency. Additionally silver also provides protection against alcohol toxicity, upper respiratory tract infections and stomach ailments. Although nanosilver has been proposed for various topical applications, its usage by ingestion and inhalation remains controversial due to the lack of detailed and precise toxicity information. These beneficial properties of silver can be utilized by using silver at very low concentrations which are not harmful to the human body and environment. The following review discusses the diverse medical applications of silver and further recommends human clinical studies for its in vivo usage.

Impact of the United Kingdom national bowel cancer awareness campaigns 2012 on colorectal cancer services and patient survival.

AIM: The UK national bowel cancer awareness campaigns in 2012 were intended to improve survival of patients with colorectal cancer (CRC) by raising public awareness and prompting symptomatic individuals to seek medical attention early. The aim of the present study was to compare the number of CRCs diagnosed, tumour stage at diagnosis, survival and number of investigations performed during the campaigns compared with a similar time period in 2011. METHOD: A retrospective study was carried out of 1439 consecutive referrals through the 2-week wait pathway (2WW) to our colorectal unit during the February and September 2012 campaigns. Patient demographics, number of referrals, investigations performed and newly diagnosed cases of CRC with their respective staging were determined and compared with a group in 2011. Two-year survival was evaluated by Kaplan-Meier statistics. RESULTS: Referrals through the 2WW increased by 55-60% and endoscopic and the number of radiological investigations performed increased by over 70% during the awareness campaigns. Although new diagnoses of CRC nearly doubled, the increase in the patients referred meant the diagnostic yield remained low at 6%. The bowel cancer awareness campaigns did not alter the tumour stage at presentation, as over 50% of patients were diagnosed with Stage 3 and 4 CRC and there was no significant difference in 2-year survival. CONCLUSION: The UK bowel cancer awareness campaigns appear to have improved public awareness of CRC and encouraged symptomatic individuals to seek urgent medical attention. The increase in 2WW referrals has not translated into better survival for symptomatic patients, partly due to the proportion presenting with advanced disease.

Estimation and correlation of salivary thiocyanate levels in healthy and different forms of tobacco users having chronic periodontitis: A cross-sectional biochemical study.

BACKGROUND: Periodontitis is a common inflammatory disease with complex and multi-factorial origin. Tobacco usage has shown its adverse effect on periodontal health. Various components within saliva not only protect the integrity of oral tissues, but also provide clues to local and systemic diseases and conditions. Salivary thiocyanate (SCN) has been shown to be a chemical indicator in smokers and smokeless tobacco users. Noninvasive nature of salivary testing has made it an attractive and effective alternative to blood and urine testing. Limited studies are there comparing and correlating the salivary SCN levels in smokers with chronic periodontitis (CP). However, no studies show correlation of salivary SCN among gutka chewers with CP. AIMS AND OBJECTIVES: The objective of the following study is to estimate, compare, and correlate the SCN levels in periodontally healthy, CP, smokers with CP and gutka chewers with CP subjects. MATERIALS AND METHODS: Study includes 120 subjects with age 18-55 years, categorized as periodonally healthy (n = 30), CP (n = 30), smokers (n = 30), and gutka chewers (n = 30) with CP. Required clinical parameters such as gingival index, probing depth and clinical attachment loss were recorded and salivary SCN levels were estimated through ultraviolet-spectrophotometer. RESULTS: Mean salivary SCN level were shown to be higher among smokers and gutka chewers with CP as compared to healthy and CP alone. CONCLUSION: The present study exhibited the significant increase in salivary SCN levels among smokers and gutka chewers when compared to others, concluding that the analysis of salivary SCN levels could be used as an adjunctive means of diagnosis.

First Report of Tobacco streak virus Infecting Pigeon Pea (Cajanus cajan) in India.

Pigeon pea is an important pulse crop grown in diversified cropping systems in India. In the rainy season of August 2011 and September 2012, pigeon pea cv. LRG 30 plants with leaf necrosis having wrinkled margin on one side were observed in Kadiri mandal of the Anantapuram district of Andhra Pradesh (A.P.), India. Symptoms included necrotic spots on young leaves followed by wilting of leaves, petiole and branch/axillary shoot proliferation, with small leaves having mosaic symptoms. Symptomatic leaves were sap-inoculated onto 10 seedlings of cowpea (cv. Pusa Komal) using 0.01 M phosphate buffer (pH 7.0). Localized necrotic lesions developed in all the inoculated plants after 2 days post inoculation. Field symptoms were reproduced on healthy pigeon pea upon back inoculation using single lesions of infected cowpea leaves. In direct antigen coating (DAC)-ELISA, all the infected pigeon pea and cowpea leaf samples were positive to a polyclonal antiserum specific to Tobacco streak virus (TSV) supplied by ICRISAT, India. Total RNA was extracted using infected pigeon pea and healthy leaf samples by TRI Reagent (Sigma). Reverse transcription (RT)-PCR was carried out using primers specific to the coat protein (CP) gene of TSV (1). A product of the 700-bp DNA fragment was obtained in field-infected pigeon pea samples but not in healthy controls. The amplicon was cloned into PTZ57R/T using the Ins TA clone PCR kit (Fermentas). Recombinant clone was sequenced in both directions and the CP gene sequence obtained was deposited in GenBank (KF220492). Sequence analysis of the CP gene of TSV from pigeon pea shared 98 to 100% identity with Indian TSV isolates originating from different hosts including groundnut (FJ355948), mung bean (FJ749259), and sunflower (DQ864448), and 88 to 92% similarity with TSV type isolate (white clover: X00435) both at nucleotide and amino acid levels. TSV belongs to the genus Ilarvirus of family Bromoviride and has a wide host range. TSV is pollen borne, assisted by thrips causing mechanical injury (2). To our knowledge, this is the first report of TSV on pigeon pea in India and was widespread in Anantapuram, Kadapa, Kurnool, and Mahbubnagar districts of A.P. Yield loss depends on the stage of infection as early infection resulted in complete failure of the crop. TSV was prevalent on many legume crops such as black gram, green gram, and groundnut in A.P, Tamil Nadu, Karnataka, and Maharashtra states (3). TSV infection of pigeon pea may pose a serious implication for pulse production. References: (1). A. I. Bhat et al. Arch. Virol. 147:651, 2002. (2). M. Sharman et al. Australian Plant Dis. 6:54, 2011. (3). K. Vemana and R. K. Jain. Indian J. Virol. 21:117, 2010.

The role of CT and staging laparoscopy in the staging of gastric cancer.

AIM: To assess the relative roles of computed tomography (CT) and diagnostic laparoscopy in the staging process of patients with potentially curable gastric cancer. MATERIALS AND METHODS: Fifty-two patients underwent laparoscopy and CT as part of staging; 36 patients underwent surgery without laparoscopy. Pathological findings at laparoscopy or surgery were compared with initial CT reports, and analysis of the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) was performed. RESULTS: Of the patients who underwent laparoscopy and CT, six were staged as positive for peritoneal disease (PD), of which five (83%) were positive for PD at laparoscopy. Forty-six patients were reported at CT as negative for PD, of which 40 (87%) were negative at laparoscopy. Of 36 patients with no advanced disease at CT, who had surgery without diagnostic laparoscopy, nine (25%) were positive at surgery for PD. The overall sensitivity of CT for PD was therefore 25%, the specificity was 99%, the PPV was 86%, and the NPV was 83%. CONCLUSION: CT is not sufficiently sensitive to detect or exclude PD in patients with gastric cancer, although is highly specific. Staging laparoscopy is an essential adjunct to imaging in all patients being considered for curative surgery for gastric cancer.

Constitutional, organopathic and combined homeopathic treatment of benign prostatic hypertrophy: a clinical trial.

BACKGROUND: Benign Prostatic Hypertrophy (BPH) is common in older men. This study compared homeopathic treatment strategies using constitutional medicines (CM) or organopathic medicines (OM) alone or in combination (BCOM) in patients suffering from BPH. METHODS: 220 men aged 30-90 years were recruited in Odisha, India. Patients presenting symptoms of prostatism, with or without evidence of bladder outflow obstruction were included in the study. Patients with serum prostate specific antigen (PSA)> 4 nmol/mL, malignancy, complete urine retention, stone formation and gross bilateral hydronephrosis were excluded. Patients were sequentially allocated to OM, CM or BCOM. The main outcome measure was the International Prostate Symptom Score (IPSS). RESULTS: 73, 70 and 77 patients respectively were sequentially allocated to OM, CM or BCOM. 180 patients (60 per group) completed treatment and were included in the final analysis. Overall 85% of patients showed improvement of subjective symptoms such as frequency, urgency, hesitancy, intermittent flow, unsatisfactory urination, feeble stream, diminution of residual urine volume but there was no reduction in prostate size. Treatment response was highest with BCOM (38.24%) compared to OM (31.62%) and CM (30.15%). Effect sizes were highest for the decrease in IPSS, residual urine volume and urinary flow rate.

Impact of the introduction of integrated PET-CT into the preoperative staging pathway of patients with potentially operable oesophageal carcinoma.

AIM: To retrospectively evaluate the role of integrated positron emission tomography computed tomography (PET-CT) in oesophageal carcinoma staging, in predicting prognosis and its influence on surgical management. MATERIALS AND METHODS: Twenty-five consecutive patients with potentially operable, biopsy-proven oesophageal malignancy who undergoing PET-CT from September 2004 to April 2007 were included in this study. Chi-square and Fisher's exact tests were used to compare the accuracy of N staging with PET-CT and CT/endoscopic ultrasound (EUS) using postoperative loco-regional nodal histology as the reference standard. The prognostic value of primary tumour maximum standardized uptake value (SUVmax) was derived using logistic regression. RESULTS: Seventeen men and eight women with a mean age of 62 years were studied. All tumours showed abnormal 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake. Fifteen patients underwent surgical resection. There was high concordance between N staging at CT/EUS (14/15) and final histology. PET-CT N staging was discordant with final nodal histology in over half of the patients (8/15). PET-CT detected occult metastases in three patients (12%) that were not identified on CT and new synchronous tumours in two patients (8%). Patient management was altered in 10 patients (40%) as a direct result of PET-CT. No statistically significant association was observed between SUVmax and clinical outcome (p=0.65). CONCLUSION: Integrated PET-CT has a significant incremental value over conventional staging investigations mainly in the detection of distant metastases and synchronous tumours and frequently impacts on patient management.

Plasmacytoma of bronchus treated by radical radiotherapy--a rare case with four and a half years follow up.

Plasmacytoma of the bronchus is a very rare plasma cell neoplasm affecting the bronchus. Here we report a case of plasmacytoma of the bronchus treated by radical radiotherapy in July 2002. The tumor responded very well to treatment and showed a slow but sustained regression in the size over two years. Presently, he has completed four and a half years of follow-up and is free of disease.

A study on contralateral breast surface dose for various tangential field techniques and the impact of set-up error on this dose.

The risk of inducing contralateral breast (CLB) cancer in patients undergoing tangential field irradiation for the treatment of breast cancer is a serious concern in radiation oncology. A bilateral breast phantom made of wax attached onto the Alderson Rando phantom was used for studying the CLB dose for techniques using physical wedges, EDWs, IMRT and open fields. The skin dose to the CLB was measured at four different points (3 cm from the medial border of the tangential field (P1), nipple (P3), axilla (P4), midpoint between P3 and P1 (P2)). The highest measured dose occurred at P1 with the 60 degrees physical wedges; it was 15.3% of the dose at isocentre. Similarly, the dose measured at P3 (nipple) with 60 degrees physical wedges was 1.90 times higher than the dose with 60 degrees EDWs. The dose at P1 for IMRT (7.8%) was almost the same as that for the open field (8.7%). The skin dose measured at the nipple was 2.1 - 10.9 % of the isocentre dose. The highest CLB doses were contributed by medial wedged fields. The dose to the CLB can be reduced by using IMRT or avoiding wedging the medial tangential fields. A set-up error in the longitudinal direction has little impact on the CLB dose. Set-up errors > 1 cm in the vertical and lateral directions have significant impact on the CLB dose.

Primary lymphoma of CNS, mycophenolate mofetil and lupus.

Lymphoproliferative disorders are known to complicate immunosuppressive therapy and two cases of primary lymphoma of CNS (PCNSL) have previously been described in association with mycophenolate mofetil (MMF) treatment. We report the third case of PCNSL in a patient with lupus nephropathy while on MMF treatment. PCNSL may be seen more frequently considering the increased use of MMF in immunosuppressant responsive conditions.

Evaluation of Tc99m-glucoheptonate for SPECT functional imaging of medulloblastoma.

OBJECTIVES: Functional imaging of medulloblastoma using SPECT has been a difficult problem as this tumour does not concentrate conventional brain tumour imaging radiopharmaceuticals. This study aimed to evaluate Tc99m-glucoheptonate as a "brain tumour-seeking" radiopharmaceutical for functional imaging of medulloblastoma. METHODS: Tc99m-glucoheptonate brain SPECT was performed in 27 patients with medulloblastoma after radiation therapy and with clinical suspicion of tumour recurrence. Histological verification was obtained within 7 days in patients with a SPECT diagnosis of tumour recurrence. Patients with a SPECT diagnosis of post-radiation gliosis were clinically observed for a minimum period of one year after the SPECT study. RESULTS: Fourteen patients had increased radiotracer uptake in the primary tumour bed, suggesting tumour recurrence. Histopathology confirmed viable medulloblastoma in all cases. Thirteen patients had no increased tracer uptake in the primary tumour bed, suggesting post-radiation gliosis. They all had a clinical course consistent with post-radiation gliosis. CONCLUSION: Tc99m-glucoheptonate is an ideal SPECT tracer for functional evaluation of medulloblastoma. SPECT utilising Tc99m-glucoheptonate is a reliable diagnostic modality to differentiate tumour recurrence from post-radiation gliosis in patients with medulloblastoma.

Role of Tc-glucoheptonic acid brain single photon emission computed tomography in differentiation of recurrent brain tumour and post-radiation gliosis.

Blood-brain barrier imaging of brain tumours is fast attracting interest now that it has been demonstrated that disruption of the blood-brain barrier is essential for uptake of all tumour-seeking agents. The aim of the present study was to differentiate recurrent tumour from post-radiation gliosis using (99m)technetium-glucoheptonate ((99m)Tc-GHA) as a tumour-seeking agent. Brain single photon emission computed tomography (SPECT) with (99m)Tc-GHA was performed in 73 patients with primary malignant brain tumours after radiotherapy, and the results were correlated with the clinical behaviour of the disease on follow up. The SPECT was suggestive of recurrent tumour in 55 patients. The clinical course was consistent with recurrence in 51 of the 55 patients. The clinical course was consistent with radiation necrosis in the remaining 21 patients, which included 17 patients with a negative SPECT and four patients with a positive SPECT study. Mean GHA index in recurrent tumour and post-radiation gliosis was 7.04 +/- 4.35 and 1.88 +/- 1.70, respectively (P = 0.0001). Mean GHA index in high-grade and low-grade glioma was 7.78 +/- 4.73 and 3.15 +/- 2.44, respectively (P = 0.001). (99m)Technetium-glucoheptonate brain SPECT is a sensitive and reliable diagnostic modality to differentiate recurrent tumour from post-radiation gliosis.

Carcinoma of the vulva: a retrospective review of 37 cases at a regional cancer centre in South India.

A retrospective review of 37 cases of carcinoma of the vulva presenting between 1996 and 2000 has been carried out. Thirty-three cases were managed with curative intent and four cases with advanced loco-regional disease were managed with palliative intent. The surgical treatment consisted of wide excision in one case, radical vulvectomy (RV) in six cases, radical vulvectomy and bilateral groin node dissection (RV+BGND) in 25 cases and radical vulvectomy and unilateral groin node dissection in one case. Nine of these 33 women also received adjuvant chemotherapy preoperatively in the hope of achieving better tumour-free surgical margins. Eight cases had a partial response and one case achieved complete response; the surgical margins were free in all these patients. One case received neoadjuvant radiotherapy to the vulva and pelvis followed by RV+BGND, which revealed no residual tumour. Overall, 26/33 cases had groin/inguinal node dissection and 23 (88.4%) of them had groin wound dehiscence. Thirteen of these 26 patients (50%) had inguinal node metastases (Stage III, four patients; Stage IV, nine patients). All the patients with negative nodes were free of disease while three of four patients with Stage III and two of nine patients with Stage IV with nodal metastases remained free of disease. The only patient with Stage III disease plus inguinal node metastases who recurred had multiple positive nodes with extracapsular spread. It appears that although bilateral involvement of the inguinal lymph nodes carries a worse prognosis, unilateral involvement with or without vaginal involvement carries an excellent prognosis provided multiple nodes are not involved. The role of neoadjuvant chemotherapy as compared to neoadjuvant radiotherapy, in locally advanced tumours, needs to be explored further.

Is brain SPECT a suitable modality for evaluation of postradiotherapy posterior fossa brain tumours? A comparative evaluation with contrast enhanced computed tomography.

Single photon emission computed tomography (SPECT) of the brain is exquisitely sensitive in detecting viable tumour tissue in the supratentorial region, but its efficacy has not been properly evaluated till date in case of infratentorial posterior fossa tumours. Twenty-four patients with primary posterior fossa brain tumour were included in this study. In each case brain SPECT with 99mTc-glucoheptonate (GHA) was performed for the evaluation of disease status. Contrast enhanced computerised tomography of brain was also performed in all the patients. Brain SPECT was positive in four patients with recurrence of tumour as compared to fifteen cases with computed tomography with a mean GHA retention index 5.26 +/- 1.64. Patients with postradiation gliosis (n=9) showed lower GHA retention index of 1.24 +/- 0.27. This study demonstrates that brain SPECT is not sensitive in detecting recurrence of tumour tissue in infratentorial region, as it is in the supratentorial region, with a sensitivity of 20%, accuracy of 45.83% and negative predictive value of 40% and the chance of any single study coming as false negative is about 80%.

The post-cystectomy pseudotumour sign: MRI appearances of a modified chronic pelvic haematoma due to retained haemostatic gauze.

The magnetic resonance imaging (MRI) findings of five men who had incidental similar pelvic masses identified after radical cystectomy are presented. In all patients the haemostatic agent Kaltostat had been used. In one patient, surgical resection of the mass was performed and histological evaluation showed a foreign body inflammatory reaction within a chronic haematoma. The differentiation between this lesion and other post-operative collections or tumours is discussed.

Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternative-free response receiver operating characteristic analysis.

PURPOSE: To compare the performance of magnetic resonance (MR) imaging after the administration of superparamagnetic iron oxide (SPIO) and dual-phase computed tomography (CT) in the depiction of liver metastases. MATERIALS AND METHODS: Fifty-one hepatic resection candidates with known colorectal metastases were examined. MR imaging comprised fast spin-echo (SE) T2-weighted imaging, T1-weighted gradient-echo (GRE) fast low-angle shot imaging before SPIO enhancement, dual-echo SE imaging, T2-weighted fast low-angle shot imaging, and T1-weighted GRE imaging after SPIO enhancement. CT was performed with 8-mm collimation and 1:1 pitch; imaging commenced 20 seconds and 65-70 seconds after injection of 150 mL of contrast medium. All images were reviewed independently by four blinded observers. The alternative-free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings from surgery, intraoperative ultrasonography, and histopathologic studies in 31 patients and with consensus review together with all other imaging and clinical follow-up in 20 patients. Sensitivities were also calculated. RESULTS: The mean sensitivity of MR was significantly higher than that of CT (p < .02): 79.8% for MR and 75.3% for CT for all lesions, and 80.6% for MR and 73.5% for CT for malignant lesions. The mean areas under the alternative-free response ROC curves were 0.83 for MR and 0.78 for CT (difference not significant). CONCLUSION: SPIO-enhanced MR imaging was more sensitive than dual-phase CT in the depiction of colorectal metastases.