Synergistic and additive interactions of Shewanella sp., Pseudomonas sp. and Thauera sp. with chlorantraniliprole and emamectin benzoate for controlling Spodoptera litura (Fabricius).

The imprudent use of insecticides causes the development of resistance in insect pest populations, contamination of the environment, biological imbalance and human intoxication. The use of microbial pathogens combined with insecticides has been proposed as an alternative strategy for insect pest management. This IPM approach may offer effective ways to control pests, in addition to lowering the risk of chemical residues in the environment. Spodoptera litura (Fabricius) is a major pest of many crops like cotton, maize, tobacco, cauliflower, cabbage, and fodder crops globally. Here, we evaluated the combined effects of new chemistry insecticides (chlorantraniliprole and emamectin benzoate) and entomopathogenic bacterial strains, Shewanella sp. (SS4), Thauera sp. (M9) and Pseudomonas sp. (EN4) against S. litura larvae inducing additive and synergistic interactions under laboratory conditions. Both insecticides produced higher larval mortality when applied in combination with bacterial isolates having maximum mortality of 98 and 96% with LC50 of chlorantraniliprole and emamectin benzoate in combination with LC50 of Pseudomonas sp. (EN4) respectively. The lower concentration (LC20) of both insecticides also induced synergism when combined with the above bacterial isolates providing a valuable approach for the management of insect pests. The genotoxic effect of both the insecticides was also evaluated by conducting comet assays. The insecticide treatments induced significant DNA damage in larval hemocytes that further increased in combination treatments. Our results indicated that combined treatments could be a successful approach for managing S. litura while reducing the inappropriate overuse of insecticides.

Radiobiological modelling of radiation-induced acute skin toxicity (dermatitis): A single institutional study of breast carcinoma.

Purpose: The purpose of the study was to estimate the fitting parameters of the sigmoidal dose response (SDR) curve of radiation-induced acute dermatitis in breast cancer patients treated with intensity-modulated radiation therapy for calculation of normal tissue complication probability (NTCP). Materials and Methods: Twenty-five breast cancer patients were enrolled to model the SDR curve for acute dermatitis. The acute radiation-induced (ARI) dermatitis toxicity was assessed weekly for all the patients, and their scores were determined using the common terminology criterion adverse events version 5.0. The radiobiological parameters n, m, TD50, and γ50 were derived using the fitted SDR curve obtained from breast cancer Patient's clinical data. Results: ARI dermatitis toxicity in carcinoma of breast patients was calculated for the end point of acute dermatitis. The n, m, TD50, and γ50 parameters from the SDR curve of Grade-1 dermatitis are found to be 0.03, 0.04, 28.65 ± 1.43 (confidence interval [CI] 95%) and 1.02 and for Grade-2 dermatitis are found to be 0.026, 0.028, 38.65 ± 1.93 (CI. 95%) and 1.01 respectively. Conclusion: This research presents the fitting parameters for NTCP calculation of Grade-1 and Grade-2 acute radiation-induced skin toxicity in breast cancer for the dermatitis end point. The presented nomograms of volume versus complication probability and dose versus complication probability assist radiation oncologists in establishing the limiting dose to reduce acute toxicities for different grades of acute dermatitis in breast cancer patients.

Larvicidal, growth inhibitory and biochemical effects of soil bacterium, Pseudomonas sp. EN4 against Spodoptera litura (Fab.) (Lepidoptera: Noctuidae).

BACKGROUND: Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) also known as tobacco caterpillar, is one of the most serious polyphagous pests that cause economic losses to a variety of commercially important agricultural crops. Over the past few years, many conventional insecticides have been used to control this pest. However, the indiscriminate use of these chemicals has led to development of insecticide resistant populations of S. litura in addition to harmful effects on environment. Due to these ill effects, the emphasis is being laid on alternative eco-friendly control measures. Microbial control is one of the important components of integrated pest management. Thus, in search for novel biocontrol agents, the current work was carried out with the aim to evaluate the insecticidal potential of soil bacteria against S. litura. RESULTS: Among the tested soil bacterial isolates (EN1, EN2, AA5, EN4 and R1), maximum mortality (74%) was exhibited by Pseudomonas sp. (EN4). The larval mortality rate increased in a dose-dependent manner. Bacterial infection also significantly delayed the larval development, reduced adult emergence, and induced morphological deformities in adults of S. litura. Adverse effects were also detected on various nutritional parameters. The infected larvae showed a significant decrease in relative growth and consumption rate as well as efficiency of conversion of ingested and digested food to biomass. Histopathological studies indicated damage to the midgut epithelial layer of larvae due to the consumption of bacteria treated diet. The infected larvae also showed a significantly decreased level of various digestive enzymes. Furthermore, exposure to Pseudomonas sp. also caused DNA damage in the hemocytes of S. litura larvae. CONCLUSION: Adverse effects of Pseudomonas sp. EN4 on various biological parameters of S. litura indicate that this soil bacterial strain may be used as an effective biocontrol agent against insect pests.

Primary Bone Lymphoma: An Experience of a Regional Cancer Center from India.

Background Primary bone lymphoma (PBL) is a rare disease, representing <5% of all extranodal non-Hodgkin's lymphomas (NHLs). The optimal treatment strategy is still unclear. Here, we report our institutional outcome analysis of patients diagnosed with PBL. Materials and Methods From 2007 to 2014, the medical records of 22 patients with PBL were reviewed. Analysis was done for symptom-, patient-, disease-, and treatment-related characteristics. All patients were treated with chemotherapy with or without radiotherapy. Treatment response and impact of different prognostic factors on clinical outcome were analyzed. Results The median age of presentation was 44 years (range: 18-70 years). A total of 19 (86.4%) patients were ≤60 years of age and 3 (13.6%) patients were >60 years. Out of all, 18 were males and 4 were females. Ann Arbor clinical staging at diagnosis was Stage I in 13 (59.1%), Stage II in 3 (13.6%), Stage III in 2 (9.1%), and Stage IV in 4 (18.2%) patients. Spine was the most common site of involvement seen in 12 (54.5%) patients. Diffuse large B cell lymphoma histology was seen in 8 (36.4%) patients and 8 (36.4%) had high-grade NHL. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone was given to 20 (90.9%) patients, whereas 2 (9.1%) patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab. Radiotherapy (30-40 Gy) was delivered to 19 (86.4%) patients. The median follow-up period was 40 months (range: 8-105 months). The overall response rate was 86.3% with complete response (CR) in 15 (68.1%) and partial response in 4 (18.2%) patients. Relapses were seen in three (13.5%) patients: two nodal, and one in the bone. Disease-free survival (DFS) and overall survival (OS) at 5 years were 56.6 and 72.7%, respectively. CR after initial treatment was associated with a significant better OS, 80 and 25%, respectively ( p < 0.0001). Age, sex, stage, International Prognostic Index, histologic subtype, and number of sites had no significant influence on OS. Combining radiation therapy with chemotherapy (with or without rituximab) also did not improve the OS or DFS of patients. Conclusion In spite of small number of patients reported in this study, conventional chemotherapy remains an effective treatment option for patients with PBL. OS was found to be affected by the initial response to treatment.

Toxicity and clinical outcomes with definitive three-dimensional conformal radiotherapy (3DCRT) and concurrent cisplatin chemotherapy in locally advanced cervical carcinoma.

OBJECTIVE(S): This study aimed to retrospectively evaluate the toxicity and clinical outcomes in patients of locally advanced cervical cancer treated with three-dimensional conformal radiotherapy (3DCRT) and concurrent chemotherapy. MATERIAL AND METHODS: Two hundred and ten newly diagnosed patients of locally advanced cervical cancer of FIGO 2009 Stage II-III treated with 3DCRT (46 Gy/23 fractions/4½ weeks) and weekly concurrent Cisplatin (40 mg/m2), from January 2013 to 2015 were analyzed. A planning computed tomography was performed and contouring was done according to published guidelines. External radiotherapy was followed by Intracavitary brachytherapy delivered to a dose of 9 Gy HDR in 2-fractions, given one week apart. The endpoints were treatment related toxicities and clinical outcomes. Local control (LC), overall survival (OS) and disease free survival (DFS) were evaluated and toxicities were documented using the common terminology criteria for adverse events (v3.0) (CTCAE). RESULTS: The median follow up time was 37 (range, 19-54) months. The 3 year OS, DFS and LC were 84.2%, 80.6% and 81% respectively. Grade ≥3 acute skin, upper and lower gastrointestinal (GI) and genitourinary (GU) toxicity was observed in 3 (1.4%), 11 (5.2%), 12 (5.7%) and 0 (0%) patients, respectively. Grade ≤2 hematological toxicity was observed in 154 (73.3%) patients. Grade ≥3 late GI and GU toxicity was seen in 9 (4.2%) patients and 2 (0.9%) patients, respectively. CONCLUSION: 3DCRT with concurrent chemotherapy results in good loco-regional control with acceptable normal tissue toxicity. In the background of indeterminate evidence regarding routine practice of intensity modulated radiotherapy in carcinoma of the cervix, 3DCRT may be considered as the treatment of choice.

A cytomegalovirus DNA vaccine induces antibodies that block viral entry into fibroblasts and epithelial cells.

A vaccine to prevent congenital cytomegalovirus (CMV) infections is a national priority. Investigational vaccines have targeted the viral glycoprotein B (gB) as an inducer of neutralizing antibodies and phosphoprotein 65 (pp65) as an inducer of cytotoxic T cells. Antibodies to gB neutralize CMV entry into all cell types but their potency is low compared to antibodies that block epithelial cell entry through targeting the pentameric complex (gH/gL/UL128/UL130/UL131). Hence, more potent overall neutralizing responses may result from a vaccine that combines gB with pentameric complex-derived antigens. To assess the ability of pentameric complex subunits to generate epithelial entry neutralizing antibodies, DNA vaccines encoding UL128, UL130, and/or UL131 were formulated with Vaxfectin(®), an adjuvant that enhances antibody responses to DNA vaccines. Mice were immunized with individual DNA vaccines or with pair-wise or trivalent combinations. Only the UL130 vaccine induced epithelial entry neutralizing antibodies and no synergy was observed from bi- or trivalent combinations. In rabbits the UL130 vaccine again induced epithelial entry neutralizing antibodies while UL128 or UL131 vaccines did not. To evaluate compatibility of the UL130 vaccine with DNA vaccines encoding gB or pp65, mono-, bi-, or trivalent combinations were evaluated. Fibroblast and epithelial entry neutralizing titers did not differ between rabbits immunized with gB alone vs. gB/UL130, gB/pp65, or gB/UL130/pp65 combinations, indicating a lack of antagonism from coadministration of DNA vaccines. Importantly, gB-induced epithelial entry neutralizing titers were substantially higher than activities induced by UL130, and both fibroblast and epithelial entry neutralizing titers induced by gB alone as well as gB/pp65 or gB/UL130/pp65 combinations were comparable to those observed in sera from humans with naturally-acquired CMV infections. These findings support further development of Vaxfectin(®)-formulated gB-expressing DNA vaccine for prevention of congenital CMV infections.

Hypofractionated radiotherapy in carcinoma breast: What we have achieved?

Healthy breast tissue is sensitive to radiation fraction size, such that small changes in fraction size can lead to larger changes in radiation effects on these tissues. Conventional breast and/or chest wall irradiation uses 2 Gy daily fractions, for 5-6 weeks. Such a long treatment schedule has major implications on both patient quality of life and burden of radiotherapy (RT) departments. Some investigators have hypothesized that breast cancer is as sensitive as normal breast tissue to fraction size. According to the hypothesis, small fraction sizes of 2.0 Gy or less offer no therapeutic advantage, and a more effective strategy would be to deliver fewer, larger fractions that result in a lower total radiation dose. This short (hypofractionated) RT schedule would be more convenient for patients (especially those coming from remote areas to RT facilities) and for healthcare providers, as it would increase the turnover in RT departments. This thought has prompted us to write a systematic review on role of hypofractionated RT in breast cancer in a developing country like ours where patient burden is an alarming problem.

Prospective randomized trial to compare accelerated (six fractions a week) radiotherapy against concurrent chemoradiotherapy (using conventional fractionation) in locally advanced head and neck cancers.

BACKGROUND: Concurrent chemoradiation (CCRT) is currently considered to be the standard of care in locally advanced head and neck cancer. The optimum radiotherapy schedule for best local control and acceptable toxicity is not yet clear. We aimed at shortening of treatment time by using accelerated radiation, thereby comparing the disease response, loco-regional tumor control and tolerability of accelerated radiation (six fractions per week) against CCRT in locally advanced head and neck cancer. MATERIALS AND METHODS: We conducted the prospective randomized study for a period of 2 years from June 2011 to May 2013 in 133 untreated patients of histologically confirmed squamous cell carcinoma of head and neck. Study group (66 patients) received accelerated radiotherapy with 6 fractions per week (66Gy/33#/5½ weeks). Control group (67 patients) received CCRT with 5 fractions per week radiation (66 Gy/33#/6½ weeks) along with intravenous cisplatin 30 mg/m(2) weekly. Tumor control, survival, acute and late toxicities were assessed. RESULTS: Median overall treatment time was 38 days and 45 days in the accelerated radiotherapy and concurrent chemoradiation arm, respectively. At a median follow up of 12 months, 41 patients (62.1%) in the accelerated radiotherapy arm and 47 patients (70.1%) in the CCRT arm were disease free (P = 0.402). Local disease control was comparable in both the arms. Acute toxicities were significantly higher in the CCRT arm as compared with accelerated radiotherapy arm. There was no difference in late toxicities between the two arms. CONCLUSION: We can achieve, same or near to the same local control, with lower toxicities with accelerated six fractions per week radiation compared with CCRT especially for Indian population.

Prospective randomized trial to compare the outcome and tolerability of delivering the same total dose of radiation in 61/2 weeks versus 51/2 weeks time in head and neck cancers.

BACKGROUND: Concurrent chemoradiation is currently considered to be the standard of care in the treatment of head and neck cancer. In developing countries like ours, a good number of patients cannot tolerate chemoradiation because of the poor general condition and financial constraints. Those patients are treated with radiation alone. The optimum radiotherapy (RT) schedule for best local control and acceptable toxicity is not yet clear. We aimed to find out whether shortening of treatment time using six instead of five RT fractions per week improves the locoregional control in squamous cell carcinoma of head and neck. MATERIALS AND METHODS: We conducted a prospective randomized study for a period of 2 years from September 2007 to August 2009 in 109 untreated patients of squamous cell carcinoma of head and neck with histologically confirmed diagnosis and no evidence of distant metastasis. Study group (55 patients) received accelerated RT with 6 fractions per week (66 Gy/33#/51/2 weeks). Control group (54 patients) received conventional RT with 5 fractions per week (66 Gy/33#/61/2 weeks). Tumor control, survival, acute and late toxicities were assessed. RESULTS: At a median follow-up of 43 months, 29 patients (52.7%) in the 6 fractions group and 24 patients (44.4%) in the 5 fractions group were disease-free (P = 0.852). The benefit of shortening was higher for advanced disease control though it was not statistically significant. Grade 3 and 4 skin toxicity was significantly higher in the accelerated RT (70.9%) arm as compared to conventional (35.1%) arm (P = 0.04). Grade 3 mucositis was significantly higher in the accelerated RT arm (32.7% vs. 16.6%; P = 0.041). Those acute toxicities were managed conservatively. There was no difference in late toxicities between the two arms. CONCLUSION: Use of 6 fractions per week instead of 5 fractions per week is feasible, tolerable, and results in a better outcome in the patients of head and neck cancers.

Role of scintimammography in assessing the response of neoadjuvant chemotherapy in locally advanced breast cancer.

Locally advanced breast cancer (LABC) is a common cancer in the developing countries. Neoadjuvant chemotherapy (NACT) is a very important step in the treatment of such tumors and hence that the disease can be down staged and made amenable for surgery. All the tumors do not respond to the therapy equally. Hence, it becomes very important to predict the response of chemotherapy in such cases. This study evaluated the role of scintimammography in assessing the response to NACT in 23 patients with LABC. Histologically proven 23 patients of LABC were recruited in this study. Prechemotherapy tumor size was measured clinically in all patients and technitium (Tc)-99m sestamibi test was performed before NACT for each patient. Early (10 min) and delayed (2 h) image of the breast were acquired in anterior and lateral views after Tc-99m sestamibi intravenous injections and wash out rate (WOR) was computed. After 3-4 cycles of chemotherapy, surgery in the form of modified radical mastectomy was performed in 20 out of 23 patients (3 patients lost to follow-up) with pathologic evaluation of the residual tumor size. The pretherapy Tc-99m sestamibi WOR ranged from 8.3% to 68% with mean ± SD of 34.5% ±16.5%. The prechemotherapy Tc-99m sestamibi study predicted chemoresistance (WOR >45%) in 6 out of 20 patients and no chemoresistance (WOR <45%) in 14 out of 20 patients. When the WOR cut-off was set at >45%, the predictivity of the test was indicated by sensitivity of 91.7%, specificity of 62.5%, positive predictive value of 78.6%, and negative predictive value of 82.3% with a likelihood ratio of 0.1. Tc-99m sestamibi WOR is a reliable test for predicting tumor response to NACT. WOR >45% is highly predictive of chemoresistance with likelihood ratio of 0.1 than WOR <45% being predictive of chemoresponsiveness.

Ovarian granulosa cell tumor: clinical features, treatment, outcome, and prognostic factors.

BACKGROUND: Granulosa cell tumors are rare neoplasms characterized by long natural history and favorable prognosis. AIMS: The objective of this study was to determine the clinical presentation, treatment, outcome, and prognostic factors for patients of granulosa cell tumors. MATERIALS AND METHODS: A retrospective analysis of 26 patients of granulosa cell tumor of ovary from 2002 to 2011 was carried out. The records of all patients were analyzed to determine clinical presentation, treatment, survival, and prognostic factors. RESULTS: The median age of the patients was 50 years (range, 17-71 years). Abdominal pain was the most common presenting symptom. The median follow-up was 71.4 months (range, 21.6-149.9 months). The estimated 5 and 10 year overall survival (OS) was 84.6 and 72.5%, respectively. Event-free survival (EFS) was 76.5 and 52.9% at 5 and 10 years, respectively. Advanced stage was significant independent poor prognostic indicator for both OS and EFS. CONCLUSION: Majority of the patients with granulosa cell tumors of the ovary present in early stage. Surgery is the primary treatment modality for granulosa cell tumors. Advanced stage and presence of residual disease were associated with inferior survival, but only prospective studies can ascertain their definite role.

In vivo imaging of cellular transplants.

We will talk about the techniques of in vivo imaging currently used in today's research and biomedical field, giving a general view of how each technique works and examples of practical applications of each technique. We will cover fluorescent (BL/CL), PET, SPECT and quantum dot imaging. Afterwards, we will cover how in vivo imaging is used in a biomedical sense; more specifically we will see how researchers studying cancer and neurodegenerative disease employ in vivo imaging.