Intraoperative Facial Nerve Involvement in Parotid Tumours - A Retrospective Analysis in a Tertiary Care Centre.

Purpose: The study aims to provide a comprehensive overview of the various malignant and benign parotid tumours and evaluate the predictive factors for intraoperative nerve involvement leading to facial palsy (FP). Methods: It is a single-centre retrospective analysis for reviewing the involvement of facial nerve in post- parotidectomy patients. The clinical database from January 2012 to December 2020 was included in the study with a follow-up period of a minimum of 2 years. To maintain homogeneity, all squamous cell carcinomas of level 2 nodes involving parotid or residual/recurrent disease of the oral cavity requiring parotid dissection were excluded. Results: A total of 248 patients (171 benign; 77 malignant) were evaluated with a mean age of 46.48 ± 10.76 years. The presence of malignancy increases the risk of FP (p = 0.027). 37 (14.92%) patients with FP were detected which included 34 with partial [32.35% in malignant; 62.16% in recurrent pleomorphic adenoma (RPA)] and 3 with total paralysis (66.67% in malignant; 33.33% in RPA). The recurrence of pleomorphic adenoma increases FP. While old age, larger size, hard fixed swelling with masseteric space (MS) infiltration appeared as risk factors for FP in malignant tumours (p = 0.047; p = 0.004; p < 0.00001 respectively). Conclusion: Tumour size, malignancy, hard fixed mass, masseteric space infiltration, recurrence, and age > 45yrs have been statistically significant predictive factors for intraoperative facial nerve involvement leading to FP. The study also revealed that FP occurred more commonly when there was concurrent involvement of both superficial and deep lobes but was not statistically significant.

Squamous Cell Carcinoma of Scalp: Our Experience in a Single Tertiary Care Centre.

Cutaneous cancer is a rare entity accounting for less than 1% of all diagnosed cancers in India. In contrast to the West, squamous cell carcinoma is the commonest skin cancer in India, often affecting the scalp. However, due to their rarity, not much is known regarding their biological behavior and prognosis. The present study is a retrospective cohort study undertaken in a tertiary cancer centre on 19 consecutive cases of squamous cell carcinoma of the scalp over a period of 5 years. Patients with non-sqamous histology and those associated with xeroderma pigmentosum were excluded. Nineteen patients were evaluated with a mean age of 52.7 years. Majority presented with a swelling (11 patients; 57.9%) in the parieto-occipital region (13 patients; 68.4%). All patients underwent wide excision with or without excision of underlying bone or dura, depending on involvement. Only 4 (21%) required major reconstruction. On histopathology, 8 (42.1%) were poorly differentiated, while 3 (15.8%) had presence of perineural invasion (PNI). The mean duration of follow-up was 38.14 months. Three of the 4 (75%) and 2 of 3 (66.67%) patients with poorly differentiated histology and PNI respectively developed recurrence, while only 1 of the 6 (16.67%) with close or positive base margin developed recurrence. Hence, to conclude, poorly differentiated histology and PNI are poor prognostic indicators, while in the event the mucoperiosteum is clinically uninvolved, the underlying bone may be preserved in select cases, even if the base margin is close.

Mucormycosis in COVID-19 pandemic and its neurovascular spread.

PURPOSE: Rhinocerebral mucormycosis is a rapidly progressive angioinvasive fungal infection commonly seen in diabetics. In the COVID-19 pandemic we have witnessed a sudden surge in these cases. We aimed to evaluate the disease presentation, patterns of spread, and any association with the COVID-19 virus. METHODS: This prospective study was conducted on mucormycosis patients operated between March and July 2021. The diagnosis was confirmed either on KOH staining, fungal culture or histopathological examination. RESULTS: Thirty one cases (21 males, 10 females) with a mean age of 53.3 years were included, of which 9 (29.1%) were COVID positive on presentation, 17 (54.8%) were post-COVID, while 5 (16.1%) had radiological evidence of COVID sequelae. Most common symptoms were cheek numbness (87.1%), headache (83.9%), visual disturbances (77.4%), and palate involvement (58.1%). Blackening of turbinates was uncommon (22.6%). Ethmoid sinus was involved in all patients. Pterygopalatine fossa involvement was present in 77.4%, and was accurately diagnosed on contrast enhanced MRI scan. There were 8 (25.8%) deaths, while the remaining are discharged or under treatment. CONCLUSION: An increase in the incidence of mucormycosis in the COVID-19 pandemic is probably due to a compromise in host immunity along with a synergistic effect in thrombotic microangiopathy. Spread of infection to the soft tissues of the infratemporal fossa, orbit or palate occur via neurovascular structures rather than by bone erosion. The pterygopalatine fossa is involved in most individuals.

Peritonsillar Ropivacaine Infiltration in Paediatric Tonsillectomy: A Randomised Control Trial.

INTRODUCTION: Various efforts have been made to reduce post tonsillectomy pain in children. The present study was undertaken to evaluate the efficacy and safety of Ropivacaine in post-operative pain management in these children. MATERIALS AND METHODS: This study is a Randomized control study on 140 patients between 4 - 12 years of age, in whom tonsillectomy was performed in a tertiary care centre between January 2017 to November 2018 using standard dissection and snare surgical technique. Postoperatively, patients were randomized into 2 groups of 70 patients each, receiving tonsillar fossa infiltration with 0.2% Ropivacaine or 0.9% normal saline respectively. Patients were assessed as per Wong Baker's Faces Scoring System at 2 hours, 4 hours, 8 hours, 18 hours, 24 hours, and 48 hours postoperatively. All the results were analyzed by SPSS software. Chi- square test and Mann-Whitney test were used for assessment of level of significance, with P- value of less than 0.05 taken as significant. RESULTS: Both the groups were comparable with respect to age and sex. At 48 hours, in study group, maximum number of patients 35 (50%) had Wong Baker score 0, while in control group, maximum number of patients 52 (74.3%) had Wong Baker score 4 (P< 0.01). The difference in the mean Deglutition time between both groups was significant (P< 0.01). CONCLUSION: Ropivacaine infiltration is a effective modality for post-tonsillectomy pain management in children, with minimal side-effects.

Relation of Musculoskeletal Strength and Function to Postural Stability in Ambulatory Adults With Cerebral Palsy.

OBJECTIVE: To understand the relation of musculoskeletal strength and function to postural stability in ambulatory adults with cerebral palsy (CP) who have already developed muscle atrophy and osteoporosis. DESIGN: Two independent group comparison of adults with CP and those without it. SETTING: Laboratory study. PARTICIPANTS: Thirteen adults with CP with sex (9 women: 4 men), age (21-62y), and Gross Motor Function Classification System I-III, and 13 sex-, age-, and body-weight-matched control participants completed our study (N=26). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Bone mineral density (BMD), structural or geometrical deformities (at the proximal region of the femur at the hip joint), and maximal muscular strength (forearm and thigh) were measured. The primary outcome measure was postural stability (balance measured using an automated balance system and a Berg Balance Test). RESULTS: Femoral BMD was significantly lower in the CP group compared to the control group, whereas BMD at lumbar and forearm regions was similar between groups. Geometrical angles, lengths, and diameters at the proximal femur were significantly lower in the CP group. There was a direct relation between BMD in the femoral neck and knee extension peak torque in the control group with no relation in the CP group. Although the control group did not show a relation between muscular strength and balance test, the CP group showed a significant linear relation among improving postural stability with greater levels of muscular strength. CONCLUSION: There were structural differences at the proximal femur and muscular weakness in adults with CP. In adults with CP, balance appears to be more influenced by structural alterations at the femur than muscular strength compared to the control group.

The use of freeze-dried retronasal stimuli to assess olfactory function.

OBJECTIVES: To evaluate a test of olfactory perception that uses freeze-dried stimuli developed to rapidly release aromas capable of migrating to the olfactory mucosa retronasally. DESIGN: Validation study. SETTING: Psychology and Chemistry Departments. PARTICIPANTS: First, 15 participants provided data for psychometric functions. Second, 70 participants made perceptual judgments of retronasal stimuli. Inclusion criterion included informed consent and a satisfactory Nasal Obstruction Symptom Evaluation result. MAIN OUTCOME MEASURES: First, psychometric functions were generated for two types of freeze-dried stimuli (coffee and orange) using the Single-Interval Adjustment Matrix method. Second, participants provided ratings of pleasantness, intensity, and familiarity and performed a standardised identification test using seven retronasally presented aromas alongside the previously validated Sniffin' Sticks orthonasal olfactory test. RESULTS: Psychometric functions indicated a dose-response relationship between aroma concentration and probability of detection. Test-retest reliability of the retronasal stimuli was acceptable (r70  = 0.72, P < 0.001), and identification scores were not dependent on testing method (ie, retronasal vs Sniffin' Sticks). Stimuli delivered using the Sniffin' Sticks test were rated more pleasant than their retronasal counterparts. CONCLUSIONS: Freeze-dried retronasal stimuli offer an easy-to-use and rapid means to test olfaction function and are arguably well suited for clinical practice, but require further development and trialing prior to the adoption in the clinical context.

Bone Metastases in Follicular Carcinoma of Thyroid.

Though the association between follicular carcinoma and bone metastasis is well established, the site-wise distribution is not known. One hundred seventy-three patients of follicular carcinoma presenting between 2003 and 2011 were selected from 1093 patients of follicular lesions presenting at a single institution. Of these, 59 (34%) with bone metastasis were included in the study. Fifty of the 59 patients (84.7%) had metastasis at presentation, while 9 developed bone metastasis during follow-up. Sixty-one percent had solitary metastasis, 15 (25.4%) had multiple bone involvement, while 8 patients (13.6%) had synchronous lung metastasis. Overall, the spine was the commonest site of bone metastases, seen in 20 patients (33.9%), followed by the pelvis, skull, long bones and sternum. Bone metastasis is a known phenomenon in follicular carcinoma. The spine is the commonest site followed by the pelvis.

Unusual parapharyngeal lipoma.

Lipomas of the parapharyngeal space (PPS) are extremely rare. CT scan and MRI are indispensable tools to investigate these hard to access tumors. PPS lipomas are confined to either the prestyloid or post styloid compartments. We report an unusual parapharyngeal lipoma involving both the compartments of the PPS.

Prospective study of 583 neck dissections in oral cancers: implications for clinical practice.

BACKGROUND: Determining the level of nodal metastases may help decrease the extent of neck dissections and reduce morbidity. METHODS: A prospective study of neck dissections in patients with oral cancer was conducted. Each nodal level was delineated, sent for histopathology, and reported level-wise. Incidence of overall and isolated metastatic nodes at different levels was calculated. Logistic regression was used to find factors predicting metastases to levels IIB and V. RESULTS: Five hundred eighty-three neck dissections were prospectively evaluated. A total of 95.7% metastases occurred at levels I to IV. Overall incidence of metastases to levels IIB and V was 3.8% and 3.3%, respectively. Multivariate analysis revealed IIA positivity as an independent predictive factor for metastases to both IIB and V. CONCLUSION: This study of lymph node mapping in patients with oral cancer showed a predictable pattern of lymph node metastasis according to primary site. Selective neck dissection (levels I-IV) in patients with oral cancers may be adequate. Determining status of level IIA is important to guide dissection of levels IIB and V.

Dural involvement in skull base tumors--accuracy of preoperative radiological evaluation and intraoperative assessment.

BACKGROUND: Dural involvement is an important consideration in assessment of cranial base tumors dictating resectability and prognosis. Preoperative as well as intraoperative clues are valuable but not always correct. We evaluated a consecutive series of craniofacial resections at our center to correlate radiologically suspected dural involvement vis-à-vis intraoperative assessment and eventual pathology. METHODS: We conducted a retrospective analysis of cases of skull base tumors where potential dural involvement was considered. We recorded the preoperative radiological impression (contrast-enhanced magnetic resonance imaging) regarding dural involvement (normal, extradural, intradural, parenchymal disease), intraoperative impression (normal, adherent, subdural, parenchymal disease), and final histology (normal, reactive, tumor). We also recorded instances where the dura was resected and/or inadvertently breached and the incidence of postoperative cerebrospinal fluid leak and meningitis. RESULTS: One hundred twenty-seven cases were evaluated. Transcranial approaches were performed in 68 cases. Nineteen percent (24 cases) were endoscopic procedures. Dural resection was performed in 38 cases (30 being proven pathologically). The incidence of cerebrospinal fluid leak was 4.7%. The sensitivity, specificity, positive predictive value, and negative predictive value of magnetic resonance assessment were 34.5%, 97.9%, 83.3%, and 83.2%, respectively, providing an overall accuracy of 84%, and those for intraoperative dural adherence were 84.6%, 85.6%, 44%, 97.6%, and 85.5.%, respectively. CONCLUSIONS: Preoperative magnetic resonance imaging, although a good modality for imaging the disease extent, may not always identify the extent of dural involvement. Intraoperative assessment therefore becomes very important especially when it is unequivocally normal. Both should be used to ensure accurate treatment strategies and tailor the need for dural resection.

E3 ubiquitin ligase Fbw7 negatively regulates granulocytic differentiation by targeting G-CSFR for degradation.

Tight control between activation and attenuation of granulocyte colony stimulating factor receptor (G-CSFR) signaling is essential to regulate survival, proliferation and differentiation of myeloid progenitor cells. Previous studies demonstrated negative regulation of G-CSFR through endosomal-lysosomal routing and ubiquitin-proteasome mediated degradation. However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin-proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation. Our data shows that Fbw7 also interacts with and degrades G-CSFR-T718 (a truncated mutant of G-CSFR found in severe congenital neutropenia/acute myeloid leukemia (SCN/AML patients)) though at a quite slower rate compared to G-CSFR. We further show that glycogen synthase kinase 3 beta (GSK3ß), like Fbw7 also targets G-CSFR and G-CSFR-T718 for degradation; however, Fbw7 and GSK3ß are interdependent in targeting G-CSFR/G-CSFR-T718 for degradation because they are unable to degrade G-CSFR individually when either of them is knocked down. We further show that Fbw7 mediated downregulation of G-CSFR inhibits signal transducer and activator of transcription 3 (STAT3) phosphorylation which is required for G-CSF dependent granulocytic differentiation. In addition, our data also shows that inhibition of Fbw7 restores G-CSFR signaling leading to enhanced STAT3 activity resulting in massive granulocytic differentiation. These data indicate that Fbw7 together with GSK3ß negatively regulates G-CSFR expression and its downstream signaling.

E3 ubiquitin ligase E6AP negatively regulates adipogenesis by downregulating proadipogenic factor C/EBPalpha.

CCAAT/Enhancer Binding Protein Alpha (C/EBPα) is a key transcription factor involved in the adipocyte differentiation. Here for the first time we demonstrate that E6AP, an E3 ubiquitin ligase inhibits adipocyte differentiation in 3T3-L1 cells as revealed by reduced lipid staining with oil red. Knock down of E6AP in mouse 3T3L1 preadipocytes is sufficient to convert them to adipocytes independent of external hormonal induction. C/EBPα protein level is drastically increased in E6AP deficient 3T3L1 preadipocytes while inverse is observed when wild type E6AP is over expressed. We show that transient transfection of wild type E6AP downregulates C/EBPα protein expression in a dose dependent manner while catalytically inactive E6AP-C843A rather stabilizes it. In addition, wild type E6AP inhibits expression of proadipogenic genes while E6AP-C843A enhances them. More importantly, overexpression of E6AP-C843A in mesenchymal progenitor cells promotes accumulation of lipid droplets while there is drastically reduced lipid droplet formation when E6AP is over expressed. Taken together, our finding suggests that E6AP may negatively control adipogenesis by inhibiting C/EBPα expression by targeting it to ubiquitin-proteasome pathway for degradation.

Proteomic identification of Profilin1 as a corepressor of estrogen receptor alpha in MCF7 breast cancer cells.

Nuclear receptor coregulators play an important role in the transcriptional regulation of nuclear receptors. In the present study, we aimed to identify estrogen receptor α (ERα) interacting proteins in Tamoxifen treated MCF7 cells. Using in vitro GST-pull down assay with ERα ligand-binding domain (ERα-LBD) and MS-based proteomics approach we identified Profilin1 as a novel ERα interacting protein. Profilin1 contains I/LXX/L/H/I amino acid signature motif required for corepressor interaction with ERα. We show that these two proteins physically interact with each other both in vitro as well as in vivo by GST-pull down and coimmunoprecipitation, respectively. We further show that these two proteins also colocalize together in the nucleus. Previous studies have reported reduced expression of Profilin1 in breast cancer; and here we found that Tamoxifen increases Profilin1 expression in MCF7 cells. Our data demonstrate that over expression of Profilin1 inhibits ERα-mediated transcriptional activation as well as its downstream target genes in ERα positive breast cancer cells MCF7. In addition, Profilin1 overexpression in MCF7 cells leads to inhibition of cell proliferation that apparently is due to enhanced apoptosis. In nutshell, these data indicate that MS-based proteomics approach identifies a novel ERα interacting protein Profilin1 that serves as a putative corepressor of ERα functions.

Dural involvement in skull base tumors-accuracy of preoperative radiological evaluation and intraoperative assessment.

BACKGROUND: Dural involvement is an important consideration in assessment of cranial base tumors dictating resectability and prognosis. Preoperative as well as intraoperative clues are valuable but not always correct. We evaluated a consecutive series of craniofacial resections at our center to correlate radiologically suspected dural involvement vis-à-vis intraoperative assessment and eventual pathology. METHODS: We conducted a retrospective analysis of cases of skull base tumors where potential dural involvement was considered. We recorded the preoperative radiological impression (contrast-enhanced magnetic resonance imaging) regarding dural involvement (normal, extradural, intradural, parenchymal disease), intraoperative impression (normal, adherent, subdural, parenchymal disease), and final histology (normal, reactive, tumor). We also recorded instances where the dura was resected and/or inadvertently breached and the incidence of postoperative cerebrospinal fluid leak and meningitis. RESULTS: One hundred twenty-seven cases were evaluated. Transcranial approaches were performed in 68 cases. Nineteen percent (24 cases) were endoscopic procedures. Dural resection was performed in 38 cases (30 being proven pathologically). The incidence of cerebrospinal fluid leak was 4.7%. The sensitivity, specificity, positive predictive value, and negative predictive value of magnetic resonance assessment were 34.5%, 97.9%, 83.3%, and 83.2%, respectively, providing an overall accuracy of 84%, and those for intraoperative dural adherence were 84.6%, 85.6%, 44%, 97.6%, and 85.5.%, respectively. CONCLUSIONS: Preoperative magnetic resonance imaging, although a good modality for imaging the disease extent, may not always identify the extent of dural involvement. Intraoperative assessment therefore becomes very important especially when it is unequivocally normal. Both should be used to ensure accurate treatment strategies and tailor the need for dural resection.

Proteomic analysis of rosiglitazone and guggulsterone treated 3T3-L1 preadipocytes.

Adipogenesis is the differentiation of preadipocytes to adipocytes which is marked by the accumulation of lipid droplets. Adipogenic differentiation of 3T3-L1 cells is achieved by exposing the cells to Insulin, Dexamethasone and IBMX for 5-7 days. Thiazolidinedione drugs, like rosiglitazone are potent insulin sensitizing agents and have been shown to enhance lipid droplet formation in 3T3-L1 cells, a model cell line for preadipocyte differentiation. Guggulsterone is a natural drug extracted from the gum resin of tree Commiphora mukul. Guggulsterone has been shown to inhibit adipogenesis and induce apoptosis in 3T3-L1 cells. In this study we treated the 3T3-L1 preadipocytes with rosiglitazone and guggulsterone and assessed the protein expression profile using 2D gel electrophoresis-based proteomics to find out differential target proteins of these drugs. The proteins that were identified upon rosiglitazone treatment generally regulate cell proliferation and/or exhibit anti-inflammatory effect which strengthens its differentiation-inducing property. Guggulsterone treatment resulted in the identification of the apoptosis-inducing proteins to be up regulated which rightly is in agreement with the apoptosis-inducing property of guggulsterone in 3T3-L1 cells. Some of the proteins identified in our proteomic screen such as Galectin1, AnnexinA2 & TCTP were further confirmed by Real Time qPCR. Thus, the present study provides a better outlook of proteins being differentially regulated/expressed upon treatment with rosiglitazone and guggulsterone. The detailed study of the differentially expressed proteins identified in this proteomic screen may further provide the better molecular insight into the mode of action of these anti-diabetic drugs rosiglitazone and guggulsterone.

Proteomics approaches for myeloid leukemia drug discovery.

INTRODUCTION: Global protein expression profiling between healthy vs diseased states helps identifying differential expression and post-translational modifications of proteins, thereby providing better insights into the molecular changes of disease diagnosis and prognosis. In addition, analytical separation and identification of proteins from complex mixtures can provide insight into targeted drug therapy and prediction of response to different therapeutics. AREAS COVERED: In the present review the authors summarize the readily available quantitative proteomics tools for the analytical separation and identification of target proteins in myeloid leukemia, AML in particular, and its future perspectives in its diagnostics and therapeutics. Within, the authors highlight some of the proteomics approaches such as gel-based quantitation strategies (2D, 2D-DIGE); MS-based quantitative proteomics tools (metabolic labeling (SILAC), chemical labeling (ITRAQ, ICAT)); MS techniques (MALDI-MS/MS). In addition, some of the target proteins identified using proteomics approaches in myeloid leukemia are also discussed that may encourage cancer biology investigators to undertake proteomics as a vital tool in their study. EXPERT OPINION: With suitable, selective application of diverse set of quantitative proteomics strategies integrated with bioinformatics software and precise statistical analysis in myeloid leukemia holds tremendous promise in deciphering cancer proteome, understanding tumor pathophysiology and development of personalized molecular medicine and therapy.

Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells.

Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer.

2-D gel electrophoresis-based proteomic analysis reveals that ormeloxifen induces G0-G1 growth arrest and ERK-mediated apoptosis in chronic myeloid leukemia cells K562.

Ormeloxifen is a nonsteroidal selective estrogen receptor modulator (SERM) and has been shown to possess anticancer activities in breast and uterine cancer. Here, we show that ormeloxifen induces apoptosis in dose-dependent manner in a variety of leukemia cells, more strikingly in K562. 2-DE-gel electrophoresis of K562 cells induced with ormeloxifen showed that 57 and 30% of proteins belong to apoptosis and cell-cycle pathways, respectively. Our data demonstrate that ormeloxifen-induced apoptosis in K562 cells involves activation of extracellular signal-regulated kinases (ERKs) and subsequent cytochrome c release, leading to mitochondria-mediated caspase-3 activation. Ormeloxifen-induced apoptosis via ERK activation was drastically inhibited by prior treatment of K562 cells with ERK inhibitor PD98059. Ormeloxifen also inhibits proliferation of K562 cells by blocking them in G0-G1 phase by inhibiting c-myc promoter via ormeloxifen-induced MBP-1 (c-myc promoter-binding protein) and upregulation of p21 expression. We further show that ormeloxifen-induced apoptosis in K562 is translatable to mononuclear cells isolated from chronic myeloid leukemia (CML) patients. Thus, ormeloxifen induces apoptosis in K562 cells via phosphorylation of ERK and arrests them in G0-G1 phase by reciprocal regulation of p21 and c-myc. Therefore, inclusion of ormeloxifen in the therapy of chronic myeloid leukemia can be of potential utility.

Proteomic approaches in myeloid leukemia.

After human genome is decoded, the characterization of the proteins is the next challenging task. The study of the complete protein complement of the genome, the 'proteome' referred to as proteomics, is an important tool for the identification of new therapeutic targets. Research efforts are underway to develop the technology necessary to compare the specific protein profiles of diseased versus healthy states. These technologies provide a wealth of information by rapidly generating large quantities of data. These data can be useful for predictive mathematical descriptions of biological systems for rapid identification of novel therapeutic targets and identification of biomarkers in metabolic disorders. In recent years, using proteomics, we and others have identified various interacting as well as target proteins, PTMs and protein markers in myeloid leukemia. This review summarizes the usage of proteomics in recent years as an important technique in defining the proteome of myeloid leukemia, which has helped in elaborate understanding of the disease and has provided new avenues for developing better therapeutics.

Synthesis and cytotoxicity evaluation of (tetrahydro-beta-carboline)-1,3,5-triazine hybrids as anticancer agents.

A series of tetrahydro-beta-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC50 values of 105.8, 664.7 and 122.2 nM, respectively; while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2.5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC50 value of 740 nM, also arrests cell cycle in G1 phase and induces apoptosis in MCF7 and MDA MB231 cell lines.