Lipid-Based Nanocarrier by Targeting with LHRH Peptide: A Promising Approach for Prostate Cancer Radio-Imaging and Therapy.

Prostate cancer is a prevalently detected malignancy with a dismal prognosis. Luteinizing-hormone-releasing-hormone (LHRH) receptors are overexpressed in such cancer cells, to which the LHRH-decapeptide can specifically bind. A lipid-polyethylene glycol-conjugated new LHRH-decapeptide analogue (D-P-HLH) was synthesized and characterized. D-P-HLH-coated and anticancer drug doxorubicin (DX)-loaded solid lipid nanoparticles (F-DX-SLN) were formulated by the cold homogenization technique and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, differential scanning calorimetry, dynamic light scattering, electron microscopy, entrapment efficiency, and drug-release profile studies. F-DX-SLN allows site-specific DX delivery by reducing the side effects of chemotherapy. Cancer cells could precisely take up F-DX-SLN by targeting specific receptors, boosting the cytotoxicity at the tumor site. The efficacy of F-DX-SLN on PC3/SKBR3 cells by the MTT assay revealed that F-DX-SLN was more cytotoxic than DX and/or DX-SLN. Flow cytometry and confocal microscopic studies further support F-DX-SLNs' increased intracellular absorption capability in targeting LHRH overexpressed cancer cells. F-DX-SLN ensured high apoptotic potential, noticeably larger mitochondrial transmembrane depolarization action, as well as the activation of caspases, a longer half-life, and greater plasma concentration. F-DX-SLN/DX-SLN was radiolabeled with technetium-99m; scintigraphic imaging studies established its tumor selectivity in PC3 tumor-bearing nude mice. The efficacy of the formulations in cancer treatment, in vivo therapeutic efficacy tests, and histopathological studies were also conducted. Results clearly indicate that F-DX-SLN exhibits sustained and superior targeted administration of anticancer drugs, thus opening up the possibility of a drug delivery system with precise control and targeting effects. F-DX-SLN could also provide a nanotheranostic approach with improved efficacy for prostate cancer therapy.

High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight.

High-grade serous ovarian carcinoma (HGSOC), the deadliest ovarian cancer, alone accounts for 90% of all its subtypes. Characterized by hallmark mutation of TP53, HGSOC show diverse molecular etiology. HGSOC can arise from both ovarian epithelium as well as the fimbrial epithelium of the fallopian tube. Ovulation induced reactive oxygen species, follicular fluid associated growth factor induced stemness, deregulation of hormone receptors like ER, FSHR, AR and hormones like FSH, LH, prolonged ovulation cycle, use of oral contraceptives are agonists of HGSOC while parity, breastfeeding provide protective effect from HGSOC development. Apart from a generic TP53 mutation, mutation of BRCA1/2, RAD51, BRIP1, PALB2, CHEK2, RAD50 etc., were reportedly associated with development of HGSOC. Epigenetic events like methylation of RASSF1A of RAS signaling pathway,OR51L1, OR51I1, OR51F1 etc. has been reported in HGSOC. Micro-RNAs like miR-1290, miR 27-a-3p miR23a, miR205 were reportedly upregulated in HGSOC. Amongst its cognate subtypes viz. differentiated, immunoreactive, mesenchymal, and proliferative, mesenchymal, and proliferative show worst prognosis. A system biology approach showed five major altered pathways in HGSOC, namely, RB, PI3K/RAS, NOTCH, HRR and FOXM1 signaling. For chemonaive patients, drugs that helps in efflux of reduced glutathione or prevent the redox coupling of GSH-GSSG, like Cisplatin, could be considered as the best therapeutic choice for HGSOC. For patients with BRCA1/2 mutations, PARP inhibitors alone or with Bevacizumab can be effective. Immune checkpoint inhibitors could be effective against immunoreactive subtypes. Identification of genes deregulated in chemoresistance could provide better insights in dealing with the disease.

Synthesis, Characterization, and Biological Evaluation of Radiolabeled Glutamine Conjugated Polymeric Nanoparticles: A Simple Approach for Tumor Imaging.

Application of nanoradiopharmaceuticals for molecular imaging has gained worldwide importance for their multifaceted potentials focusing on providing a safe and cost-effective approach. Biodistribution studies on such species are capable of bringing nanomedicine to patients. Current therapeutically available labeling strategies suffer from different limitations, including off-target cytotoxicity and radiolabel release over time. Poly(lactic-co-glycolic acid)(PLGA) nanoparticles are biodegradable carriers for a variety of contrast agents that can be employed in medicine with high loading capacity for multimodal imaging agents. Here, glutamine-conjugated PLGA polymers were used to construct polymeric nanoparticles (G-PNP) similar to unconjugated PLGA nanoparticles (PNP)s formulated for ex vivo cell labeling and in vivo tumor scintigraphy studies. G-PNP/PNP, characterized by Fourier-transform infrared, atomic-force-microscopy, particle-size, and zeta-potential studies, were biocompatible as evaluated by MTT assay. G-PNPs were radiolabeled with 99mtechnetium (99mTc) by borohydrite reduction. G-PNPs demonstrated higher cellular uptake than PNPs, with no major cytotoxicity. Radiochemical purity indicated that 99mTc labeled G-PNP (99mTc-G-PNP) can form a stable complex with substantial stability in serum with respect to time. Imaging studies showed that 99mTc-G-PNP significantly accumulated at the C6 glioma cell induced tumor-site in rats. Thus, 99mTc-G-PNP demonstrated favorable characteristics and imaging potential which may make it a promising tumor imaging nanoprobe as a nanoradiopharmaceutical.

Kaempferol with Verapamil impeded panoramic chemoevasion pathways in breast cancer through ROS overproduction and disruption of lysosomal biogenesis.

BACKGROUND: Reactive oxygen species (ROS) at low level promotes cell survival through lysosome induced autophagy induction. Glucose stress induced acidosis, hypoxia, ROS, upregulates markers related to cancer stemness and multidrug resistance. Also, lysosomal upregulation is proposed to be one of the important indicators of cell survival under ROS induced stress. Studies supported that, stimulation of Lysosome-TFEB-Ca2+ cascade has important role in induction of chemoresistance and survival of cancerous cells. PURPOSE: To observe the effect of synergistic drug combination, Kaempferol and Verapamil on markers regulating chemoevasion, tumor stemness & acidosis as well as lysosome upregulation pathways, under low as well as high glucose conditions. HYPOTHESIS: Based on our earlier observation as well as previous reports, we hypothesized, our drug combination Kaempferol with Verapamil could attenuate markers related to chemoevasion, tumor stemness & acidosis as well as lysosome-TFEB-Ca2+ pathway, all of which have indispensable association and role in chemoresistance. METHODS: RNA and protein expression of candidate genes, along with ROS production and Ca2+ concentrations were measured in ex vivo models in altered glucose conditions upon treatment with KV. Also, computational approaches were utilized to hypothesize the mechanism of action of the drug combination. PCR, IHC, western blotting and molecular docking approaches were used in this study. RESULTS: The overproduction of ROS by our candidate drugs KV, downregulated the chemoresistance and tumor acidosis markers along with ATP1B1 and resulted in lysosomal disruption with reduction of Ca2+ release, diminishing TFEB expression under low glucose condition. An anomalous outcome was observed in high glucose conditions. We also observed KV promoted the overproduction of ROS levels thereby inducing autophagy-mediated cell death through the upregulation of LC3-II and p62 in low glucose conditions. The ex vivo studies also corroborate with in silico study that exhibited the parallel outcome. CONCLUSION: Our ex-vivo and in-silico studies revealed that our candidate drug combination KV, could effectively target several pathways regulating chemoresistance, that were not hitherto studied in the same experimental setup and thus may be endorsed for therapeutic purposes.

Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer.

Gall bladder cancer (GBC) is becoming a very devastating form of hepatobiliary cancer in India. Every year new cases of GBC are quite high in India. Despite recent advanced multimodality treatment options, the survival of GBC patients is very low. If the disease is diagnosed at the advanced stage (with local nodal metastasis or distant metastasis) or surgical resection is inoperable, the prognosis of those patients is very poor. So, perspectives of targeted therapy are being taken. Targeted therapy includes hormone therapy, proteasome inhibitors, signal transduction and apoptosis inhibitors, angiogenesis inhibitors, and immunotherapeutic agents. One such signal transduction inhibitor is the specific short interfering RNA (siRNA) or short hairpin RNA (shRNA). For developing siRNA-mediated therapy shRNA, although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells, many more clinical trials are required. To date, many such genes have been identified. This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.

Interplay of gut microbiome, fatty acids, and the endocannabinoid system in regulating development, progression, immunomodulation, and chemoresistance of cancer.

The roles of gut microorganisms in cancer are diverse. Studies on metagenomics and bioinformatics have documented diverse microbial etiology in different tumors. Evidence supports that a commensal microbiome could provide a promising strategy to treat and prevent cancer through interference in several biologic processes, such as host cell survival and death, host immune function, inflammation, oncogenic signaling, and several hormone receptor signaling and detoxification pathways. The cumulative evidence recommends that metabolites of commensal gut microorganisms (e.g., short-chain fatty acids, omega-3 and -6 fatty acids) play an important role in cancer prevention, with a robust antiproliferative effect of omega-3 fatty acids. Intriguingly, the endocannabinoid system (omega-3 and -6 fatty acid-derived neurotransmitter of the body) shows diverse effects on cancer prevention and oncogenesis depending on the context of the tumor microenvironment. Thus, an interplay of gut microorganisms with their fatty acid metabolites and the endocannabinoid system play an important role in the development, progression, immunomodulation, and chemoresistance of cancer. In this review, we highlight aspects of the current knowledge of and interactions between the microbiome with fatty acids and the host endocannabinoid system. We also document their effect on host immunomodulation and chemoresistance, and discuss how these insights might translate into future development of microbiome-targeted therapeutic interventions.

Kaempferol attenuates viability of ex-vivo cultured post-NACT breast tumor explants through downregulation of p53 induced stemness, inflammation and apoptosis evasion pathways.

Early onset of chemotherapy evasion is a therapeutic challenge. Chemotherapy-induced upregulation of stem cell markers imparts invasiveness and metastatic property to the resident tumor. The efficacy of Kaempferol in attenuating epithelial to mesenchymal transition has earlier been established in the breast cancer cell. In our study population, progression-free survival was observed to be statistically more significant in post-NACT low-grade tumors than the high-grade tumors. Further, in post-NACT TNBCs, high-grade tumors showed a preponderance of strong nuclear p53 expression and very low expression of Caspase 3, indicating that, altered p53 expression predisposes these tumors to apoptosis escape and up-regulation of stemness markers. Herein, we report the robust efficacy of Kaempferol on ex-vivo grown breast tumors, derived from post-NACT TNBC patients, through downregulation of nuclear p53, CD44, ALDH1, NANOG, MDR1, Ki67, BCL2 and upregulation of Caspase 3. Such tumors also showed concurrent deregulated RNA and protein expression of CD44, NANOG, ALDH1 and MDR1 with upregulation of Caspase 3 and cleaved Caspase 3, upon Kaempferol treatment. Validation of efficacy of the treatment dosage of Kaempferol through immunophenotyping on MDA-MB-231, suggested that Kaempferol at its IC-50 dosage was effective against CD44 and CD326 positive breast cancer through deregulating their expression. Protein-protein interaction network through STRING pathway analysis and co-expression study of candidate proteins showed the highest degree of co-expression of p53 and KI-67, CD44, NF- kappaB, ALDH1, NANOG, MDR1, and BCL2. Thus, potentially targetable oncogenic protein markers, that are susceptible to downregulation by Kaempferol, provides insight into biomarker-driven therapeutic approaches with it.

Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil.

Chemoresistance is an imminent therapeutic challenge for breast cancer. Previous evidence suggests that breast cancer stem cells (BCSC) develop resistance through upregulation of stemness and chemo-evasion markers viz. SOX2, OCT4, NANOG, MDR1 and CD44, following anticancer chemotherapeutic treatments. Early studies suggest an inhibitory role of Kaempferol in BCSC propagation through downregulation of epithelial to mesenchymal transition. We hypothesized that the pathway involved in chemoresistance could be effectively addressed through Kaempferol (K), alone or in combination with Verapamil (V), which is an inhibitor of MDR1. We used K in combination with V, in multiple assays to determine if there was an inhibitory effect on BCSC. Both K and KV attenuated pH-dependent mammosphere formation in primary BCSC and MDA-MB-231 cells. RNA and protein (immunocytochemistry, western blot) expression of candidate markers viz. SOX2, OCT4, NANOG, MDR1 and CD44 were carried out in the presence or absence of candidate drugs in ex-vivo grown primary BCSC and MDA-MB-231 cell line. Immunoprecipitation assay, cell cycle analysis was carried out in MDA-MB-231. Our candidate drugs were not only anti-proliferative, but also downregulated candidate genes expression at RNA and protein level in both settings, with more robust efficacy in KV treatment than K; induced G2/M dependent cell cycle arrest, and interrupted physical association of CD44 with NANOG as well as MDR1 in MDA-MB-231. In primary tumor explant but not in adjacent normal tissue, our candidate drugs K and KV induced robust γH2AX expression. Thus, our candidate drugs are effective in attenuating BCSC survival.

Inhibitory role of a smart nano-trifattyglyceride of Moringa oleifera root in epithelial ovarian cancer, through attenuation of FSHR - c-Myc axis.

BACKGROUND AND AIM: Epithelial ovarian cancer has the deadliest prognosis amongst gynaecological cancers, warranting an unmet need for newer drug targets. Based on its anticancer as well as abortifacient potential, Moringa oleifera Lam. root was hypothesized to have some implications in follicle stimulating hormone receptor (FSHR) dependent cancers like epithelial ovarian cancer. EXPERIMENTAL PROCEDURE: Effect of Moringa oleifera Lam. root extract (MRE) was studied in epithelial ovarian cancer cell line through in vitro studies viz. MTT assay, clonogenic assay, cell cycle analysis, flow cytometry, western blot analysis, immunocytochemical analysis of FSHRand c-Myc expression and in vivo studies viz. effect of MRE in mice model of ovarian carcinoma. The structure of the active compound of MRE was elucidated following solvent extraction, purification through column chromatography, preparative TLC and bioactivity guided structural identification through 1H-NMR, 13C-NMR, DEPT-135, ESIMS,FT-IR spectrophotometry, UV-vis-NIR spectrophotometry and DFT study. RESULTS AND CONCLUSION: Crude MRE displayed cytotoxic activity, induced apoptosis, and attenuated expression of FSHR and c-Myc in ovarian cancer cell line OAW42. MRE also attenuated expression of CD31, FSHR, and c-Myc in tumour xenograft mouse model. Finally, the active compound purified from ethyl acetate-n-hexane subfraction ofMRE, that attenuated viability of ovarian carcinoma cell lines and reduced FSHR and c-Myc expression, was identified as a naturally hydrated-trifattyglyceride, showing aDFT-optimized folded amphipathic structure for easy transportation through hydrophilic and hydrophobic regions in a biological system, indicating its immense therapeutic relevance in epithelial ovarian carcinoma.

Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia.

BACKGROUND: Philadelphia chromosome, a hallmark of chronic myeloid leukemia (CML), plays a key role in disease pathogenesis. It reflects a balanced reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL fusion gene is necessary for the diagnosis and monitoring of CML. Previously, many technologies, most of which are laborious and time consuming, have been developed to detect BCR-ABL chimeric gene or chromosome. METHODS: A new flow cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and applicability, sensitivity, reliability, efficacy and rapidity of this method was evaluated. RESULTS: From February 2009 to January 2014, a total 648 CML patients were investigated for the status of BCR-ABL1 protein. Among them, 83 patients were enrolled for comparative study of BCR-ABL1 positivity by three routinely used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well as immunobead flow cytometry assay. BCR-ABL protein analysis was found consistent, more sensitive (17% greater sensitivity) and reliable than the conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT-PCR. CONCLUSION: BCR-ABL fusion protein assay using a new flow cytometric immunobead might be useful in the diagnosis and monitoring CML patients.

Mugineic acid, active ingredient of wheat grass: an oral novel hexadentate iron chelator in iron overloaded diseases.

Iron chelation therapies are required for the treatment of iron overloaded patients; nonetheless, their side effects are also well known. We have evaluated iron-chelating activity of wheat grass extract (WHE) and its purified compound, mugineic acid in murine model with phenylhydrazine (PHZ) and dextran induced acute and chronic iron overload conditions. PHZ and dextran treatment induced acute and chronic iron overload condition in mice, respectively, as indicated by increased serum and tissue iron in both cases. Iron overload was also accompanied with haemosiderosis in tissues (liver and spleen). These PHZ and dextran -: treated mice were orally treated with either crude WHE or purified mugineic acid. The efficacy of mugineic acid and WHE was compared with the potent oral iron chelator ICL670 (Exjade). PHZ and dextran treatment followed by oral administration of WHE or mugineic acid significantly checked the rise of serum/plasma levels of iron as well as tissue iron and also, haemosiderosis in tissues. The results are highly comparable with known iron chelator ICL670. WHE and purified mugineic acid, both seem to have significant prospect to be the cheap, non-toxic, hexadentate and oral therapeutic agents to prevent or alleviate toxic iron overload in patients.

Antioxidative and anticarcinogenic activities of methylpheophorbide a, isolated from wheat grass (Triticum aestivum Linn.).

Methylphophorbide a (MPa) has been isolated from the ethanol extract of the wheat grass plant. Its antioxidative efficacy is evaluated by hydroxyl radical scavenging activities and reducing capacity which are significantly up regulated in comparison with aqueous extract of the plant. The compound shows iron-binding capacity where the Fe(2+) binds with MPa by two types of binding patterns with dissociation constants 157.17 and 27.89. It has antioxidative and cytotoxic effects on HeLa and Hep G2 cells. The cancerous cell survivability decreases with increasing concentration of MPa. These findings have provided evidence for the traditional use of the wheat grass plant in the treatment of cancers, oxidative stress and iron overloaded disorders.

Acute toxicity test of a natural iron chelator and an antioxidant, extracted from Triticum aestivum Linn. (wheat grass).

Triticum aestivum (wheat grass) is widely used in traditional medicine to treat various diseases. Previously the purified compounds and crude extract of T. aestivum were established to have iron chelation potency and antioxidant activity. So it is necessary to evaluate the toxic properties of any compound isolated from plant extract to prevent any untoward side effects. The aim of this study was to determine the acute oral toxicity level of our purified compounds, i.e. mugineic acids and methylpheophorbide a., and crude extract of T. aestivum, on Swiss albino mice at dosage of 2000 mg/kg for a period of 14 days using the organisation for economic co-operation and development guidelines 423. There was no mortality. No change in behavioural pattern, clinical signs, body weight and blood biochemistry profile were observed. Kidney and liver showed normal histo-pathological architecture. Hence, the oral administration of compounds and extract of T. aestivum did not produce any significant toxic effect on mice. Thus we may conclude that the extract can be utilised for pharmaceutical formulations as iron chelator and antioxidant agent for various diseases.

Role of HLA class II loci polymorphism in the manifestation of type 1 diabetes in a Bengali Indian patient population.

To assess the contribution of the HLA class II region for susceptibility to type 1 diabetes mellitus (T1DM), we investigated the association of HLA class II alleles-DP, DQ, and DRB1. Here, we present an extensive molecular typing for HLA class II alleles and their haplotypes in a Bengali-speaking Indian population of T1DM patients (n=151) and controls (n=151) from West Bengal. HLA typing was done by DNA sequencing using a 3730 DNA Analyzer. The individual analysis of each gene gave the following alleles to be higher in cases than in controls, thus making them susceptible alleles-DPA1*020103, DPB1*020102, DQA1*050101, DQA1*0201, and DQB1*020101G. Similarly, the following alleles are protective alleles in our study-DPA1*010602, DPB1*040101, DQA1*010201, DQA1*0103, and DRB1*15. Our result confidently establishes that HLA-DP allelic, and its haplotypic, diversity contributes significantly to the risk for T1DM. The DQA1*0103 allele is a novel allele with a significant association with the protection from T1DM. Among the various haplotypes tested, the DQA1*0201:DQB1*020101G, DQA1*050101:DQB1*020101G, and DQA1*0201:DQB1*030101G were the most frequently found in T1DM patients. In India, very few investigations have been undertaken to study the impact of the genetic background on the risk to develop T1DM in its population, where the annual average incidence is 10.5/100,000/year. In conclusion, the present study highlights the genetic effect of HLA haplotypes that contributes to the susceptibility to T1DM.

Frequency of 5382insC mutation of BRCA1 gene among breast cancer patients: an experience from Eastern India.

The incidence of breast cancer in India is on the rise and is rapidly becoming the number one cancer in females pushing the cervical cancer to the second position. The mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, are frequently associated with familial breast cancer. The main objective of the study was to determine the frequency of the mutation 5382insC in BRCA1 of eastern Indian breast cancer patients and also study the hormonal receptor status and histopathology of the patients. Altogether 92 patients affected with breast cancer were included in this study. ARMS-PCR based amplification was used to detect the presence of mutation. The mutations were considered only after pedigree analysis. Out of 92 patients (age range: 20-77 years) with family history (57 individuals) and without family history (35 individuals) were screened. Fifty controls have been systematically investigated. Seven patients and two family members were found to be carriers of 5382insC mutation in BRCA1 gene. We have found 42.64 % ER(-)/PR(-) cancer and 20.58 % triple negative cancer. Invasive ductal carcinoma is the most common histology among the investigated individuals. The presented data confirm a noticeable contribution of BRCA1 5382insC mutation in BC development in Eastern India, which may justify an extended BRCA1 5382insC testing within this patient population. We found HER-2/neu negativity and BRCA1 positivity associated with familial breast cancer. From the hospital's patient history, it was revealed that the age of menarche plays an important role in development of breast cancer.

Incidence of the Hb E [ß26(B8)Glu→Lys, GAG>AAG] variant in Totos, one of the smallest primitive tribes in the world.

Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as ß-thalassemia (ß-thal). We have studied 443 Totos to define their Hb E [ß26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the ß-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ - - - - -] (HincII 5'ϵ, HindIII (G)γ, HindIII (A)γ, HincII 5'ψß, HincII 3'ψß and HinfI 3'ß). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future.

Surveillance and expected outcome of acute lymphoblastic leukemia in children and adolescents: An experience from Eastern India.

OBJECTIVE: Research in Eastern India especially among children and adolescents for acute lymphoblastic leukemia (ALL) have not been well documented until recently when it was conducted at a cancer institute of tertiary care with primary objectives of examining and correlating different cell surface markers involved with respect to disease surveillance thereby highlighting it as a strong prognostic marker for future diagnosis and treatment. MATERIALS AND METHODS: A total of 500 consecutively selected ALL patients were diagnosed and treated according to National Cancer Institute protocol (MCP 841) for a period of 24-88 months during this hospital-based study. RESULTS: Of the total, 50.4% had a higher incidence of T-ALL and 47.6% had pro-B, B-cell precursor ALL. Disease free survival and event free survival were remarkably higher in B-ALL adolescent patients as compared to T-ALL, who had significantly lower overall survival ratio. Prevalence of T-ALL was also observed in relapse cases for adolescent patients. CONCLUSIONS: We conclude that there is an increased prevalence of T-ALL among adolescents in Eastern India. Immunophenotypic analysis might help in proper evaluation and prediction of treatment outcomes with an increased thrust on studying age-specific incident rates enabling well planned future treatments for improved and better outcome.

Multiple-injection thoracic paravertebral block as an alternative to general anaesthesia for elective breast surgeries: A randomised controlled trial.

BACKGROUND: General anaesthesia is currently the conventional technique used for surgical treatment of breast lump. Paravertebral block (PVB) has been used for unilateral procedures such as thoracotomy, breast surgery, chest wall trauma, hernia repair or renal surgery. METHODS: We compared unilateral thoracic PVB with general anaesthesia (GA) in 60 consenting ASA physical status I and II female patients of 18-65 years age, scheduled for unilateral breast surgery. Patients were randomly assigned into two groups, P (n=30) or G (n=30), to receive either PVB or GA, respectively. RESULTS: The average time to first post-operative analgesic requirement at visual analogue scale score≥4 (primary endpoint) was significantly longer in group P (303.97±76.08 min) than in group G (131.33±21.36 min), P<0.001. Total rescue analgesic (Inj. Tramadol) requirements in the first 24 h were 105.17±20.46 mg in group P as compared with 176.67±52.08 mg in group G (P<0.001). Significant post-operative nausea and vomiting requiring treatment occurred in three (10.34%) patients of the PVB group and eight (26.67%) patients in the GA group. CONCLUSION: The present study concludes that unilateral PVB is more efficacious in terms of prolonging post-operative analgesia and reducing morbidities in patients undergoing elective unilateral breast surgery.